ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั...

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Viral hemorrhagic fever and laboratory diagnosis ศาสตราจารย์ ดร.ไลพันธ์ พุธวัฒนะ ศูนย์ความร่วมมือการวิจัยไข้หวัดใหญ่ ภาควิชาจุลชีววิทยา คณะแพทยศาสตร์ศิริราชพยาบาล มหาวิทยาลัยมหิดล การอบรมเชิงปฏิบัติการ เครือข่ายห้องปฏิบัติการโรคติดเชื ้ออุบัติใหม่ 2558” โรงแรมลองบีช ชะอา 7 กรกฎาคม 2558

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Page 1: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Viral hemorrhagic fever and laboratory diagnosis

ศาสตราจารย ดรพไลพนธ พธวฒนะ

ศนยความรวมมอการวจยไขหวดใหญ ภาควชาจลชววทยา คณะแพทยศาสตรศรราชพยาบาล

มหาวทยาลยมหดล

การอบรมเชงปฏบตการ ldquoเครอขายหองปฏบตการโรคตดเชออบตใหม 2558rdquo โรงแรมลองบช ชะอ า 7 กรกฎาคม 2558

Viruses causing hemorrhagic fever (VHF)

At least 23 viruses from 4 families

bull Filoviridae

bull Arenaviridae

bull Bunyaviridae

bull Flaviviridae

Common characteristics of viruses causing HF

bull Enveloped virus with RNA genome

bull Wide range of natural hosts zoonotic

diseases and some are vector-borne viruses

bull Geographically restrict

Flaviviruses

bull Yellow fever virus- Yellow fever in tropical Africa and South America

bull Dengue viruses- DHF DSS

bull Omsk hemorrhagic fever virus- Omsk HF in Western Siberia

bull Kyasanur Forest disease virus - Kyasanur Forest disease in India

Bunyaviruses

bull Crimean-Congo hemorrhagic fever virus ndash Crimean-Congo HF in the Middle East Southern Europe and western China

bull Rift Valley fever virus- Rift Valley fever in Africa and Arabian Pennisula

bull Genus Hantavirus- hemorrhagic fever with renal syndrome in Eurasia

bull Severe fever with thrombocytopenia syndrome virus in China

Arenaviruses

bull Junin virus- Argentine HF

bull Machupo virus ndash Bolivian HF

bull Guanarito virus ndash Venezuelan HF

bull Sabia virus ndash Brazillian HF

bull Lassa virus ndashLassa HF in West Africa

bull Lujo virus- unnamed disease in Zambia

bull Chapare virus- unnamed disease in Bolivia

Filoviruses

bull Marburg virus ndash emerged in 1967 in Marburg Germany and Yugoslavia

bull Ebolavirus- emerged in 1976 in Zaire (DR Congo) and Sudan

VHF in Africa

bull Flaviviridae Yellow fever virus

bull Arenaviridae Lassa fever virus

bull Filoviridae Marburg virus

Ebola virus

bull Bunyaviridae

Crimean-Congo hemorrhagic fever virus

Rift Valley fever virus

VHF in Thailand

bull Dengue virus types 1-4

bull Hantaan virus

Pathogenic mechnisms of VHF

bull Vascular damage increased vascular permeability and plasma leakage

bull Hemorrhage

bull Hepatocellular necrosis leads to deficiency of coagulation factors

bull Complement activation

bull Disseminated intravascular coagulation

bull Cytokine storm

Re-emergence of Ebola virus disease

bull The EVD outbreak began in December 2013 and reported to WHO on 21 March 2014

13

Ebola signs and symptoms

Classification of Ebola virus

Order Mononegavirales

Family Filoviridae

Genus Marburgvirus

Genus Ebolavirus

Zaire ebolavirus (EBOV) Fatality rate 70-90

Sudan ebolavirus (SUDV) 40-60

Bundibugyo ebolavirus (BDBV) 32

Taiuml Forest ebolavirus (TAFV)

Reston ebolavirus (RESTV)

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 2: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Viruses causing hemorrhagic fever (VHF)

At least 23 viruses from 4 families

bull Filoviridae

bull Arenaviridae

bull Bunyaviridae

bull Flaviviridae

Common characteristics of viruses causing HF

bull Enveloped virus with RNA genome

bull Wide range of natural hosts zoonotic

diseases and some are vector-borne viruses

bull Geographically restrict

Flaviviruses

bull Yellow fever virus- Yellow fever in tropical Africa and South America

bull Dengue viruses- DHF DSS

bull Omsk hemorrhagic fever virus- Omsk HF in Western Siberia

bull Kyasanur Forest disease virus - Kyasanur Forest disease in India

Bunyaviruses

bull Crimean-Congo hemorrhagic fever virus ndash Crimean-Congo HF in the Middle East Southern Europe and western China

bull Rift Valley fever virus- Rift Valley fever in Africa and Arabian Pennisula

bull Genus Hantavirus- hemorrhagic fever with renal syndrome in Eurasia

bull Severe fever with thrombocytopenia syndrome virus in China

Arenaviruses

bull Junin virus- Argentine HF

bull Machupo virus ndash Bolivian HF

bull Guanarito virus ndash Venezuelan HF

bull Sabia virus ndash Brazillian HF

bull Lassa virus ndashLassa HF in West Africa

bull Lujo virus- unnamed disease in Zambia

bull Chapare virus- unnamed disease in Bolivia

Filoviruses

bull Marburg virus ndash emerged in 1967 in Marburg Germany and Yugoslavia

bull Ebolavirus- emerged in 1976 in Zaire (DR Congo) and Sudan

VHF in Africa

bull Flaviviridae Yellow fever virus

bull Arenaviridae Lassa fever virus

bull Filoviridae Marburg virus

Ebola virus

bull Bunyaviridae

Crimean-Congo hemorrhagic fever virus

Rift Valley fever virus

VHF in Thailand

bull Dengue virus types 1-4

bull Hantaan virus

Pathogenic mechnisms of VHF

bull Vascular damage increased vascular permeability and plasma leakage

bull Hemorrhage

bull Hepatocellular necrosis leads to deficiency of coagulation factors

bull Complement activation

bull Disseminated intravascular coagulation

bull Cytokine storm

Re-emergence of Ebola virus disease

bull The EVD outbreak began in December 2013 and reported to WHO on 21 March 2014

13

Ebola signs and symptoms

Classification of Ebola virus

Order Mononegavirales

Family Filoviridae

Genus Marburgvirus

Genus Ebolavirus

Zaire ebolavirus (EBOV) Fatality rate 70-90

Sudan ebolavirus (SUDV) 40-60

Bundibugyo ebolavirus (BDBV) 32

Taiuml Forest ebolavirus (TAFV)

Reston ebolavirus (RESTV)

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 3: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Common characteristics of viruses causing HF

bull Enveloped virus with RNA genome

bull Wide range of natural hosts zoonotic

diseases and some are vector-borne viruses

bull Geographically restrict

Flaviviruses

bull Yellow fever virus- Yellow fever in tropical Africa and South America

bull Dengue viruses- DHF DSS

bull Omsk hemorrhagic fever virus- Omsk HF in Western Siberia

bull Kyasanur Forest disease virus - Kyasanur Forest disease in India

Bunyaviruses

bull Crimean-Congo hemorrhagic fever virus ndash Crimean-Congo HF in the Middle East Southern Europe and western China

bull Rift Valley fever virus- Rift Valley fever in Africa and Arabian Pennisula

bull Genus Hantavirus- hemorrhagic fever with renal syndrome in Eurasia

bull Severe fever with thrombocytopenia syndrome virus in China

Arenaviruses

bull Junin virus- Argentine HF

bull Machupo virus ndash Bolivian HF

bull Guanarito virus ndash Venezuelan HF

bull Sabia virus ndash Brazillian HF

bull Lassa virus ndashLassa HF in West Africa

bull Lujo virus- unnamed disease in Zambia

bull Chapare virus- unnamed disease in Bolivia

Filoviruses

bull Marburg virus ndash emerged in 1967 in Marburg Germany and Yugoslavia

bull Ebolavirus- emerged in 1976 in Zaire (DR Congo) and Sudan

VHF in Africa

bull Flaviviridae Yellow fever virus

bull Arenaviridae Lassa fever virus

bull Filoviridae Marburg virus

Ebola virus

bull Bunyaviridae

Crimean-Congo hemorrhagic fever virus

Rift Valley fever virus

VHF in Thailand

bull Dengue virus types 1-4

bull Hantaan virus

Pathogenic mechnisms of VHF

bull Vascular damage increased vascular permeability and plasma leakage

bull Hemorrhage

bull Hepatocellular necrosis leads to deficiency of coagulation factors

bull Complement activation

bull Disseminated intravascular coagulation

bull Cytokine storm

Re-emergence of Ebola virus disease

bull The EVD outbreak began in December 2013 and reported to WHO on 21 March 2014

13

Ebola signs and symptoms

Classification of Ebola virus

Order Mononegavirales

Family Filoviridae

Genus Marburgvirus

Genus Ebolavirus

Zaire ebolavirus (EBOV) Fatality rate 70-90

Sudan ebolavirus (SUDV) 40-60

Bundibugyo ebolavirus (BDBV) 32

Taiuml Forest ebolavirus (TAFV)

Reston ebolavirus (RESTV)

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 4: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Flaviviruses

bull Yellow fever virus- Yellow fever in tropical Africa and South America

bull Dengue viruses- DHF DSS

bull Omsk hemorrhagic fever virus- Omsk HF in Western Siberia

bull Kyasanur Forest disease virus - Kyasanur Forest disease in India

Bunyaviruses

bull Crimean-Congo hemorrhagic fever virus ndash Crimean-Congo HF in the Middle East Southern Europe and western China

bull Rift Valley fever virus- Rift Valley fever in Africa and Arabian Pennisula

bull Genus Hantavirus- hemorrhagic fever with renal syndrome in Eurasia

bull Severe fever with thrombocytopenia syndrome virus in China

Arenaviruses

bull Junin virus- Argentine HF

bull Machupo virus ndash Bolivian HF

bull Guanarito virus ndash Venezuelan HF

bull Sabia virus ndash Brazillian HF

bull Lassa virus ndashLassa HF in West Africa

bull Lujo virus- unnamed disease in Zambia

bull Chapare virus- unnamed disease in Bolivia

Filoviruses

bull Marburg virus ndash emerged in 1967 in Marburg Germany and Yugoslavia

bull Ebolavirus- emerged in 1976 in Zaire (DR Congo) and Sudan

VHF in Africa

bull Flaviviridae Yellow fever virus

bull Arenaviridae Lassa fever virus

bull Filoviridae Marburg virus

Ebola virus

bull Bunyaviridae

Crimean-Congo hemorrhagic fever virus

Rift Valley fever virus

VHF in Thailand

bull Dengue virus types 1-4

bull Hantaan virus

Pathogenic mechnisms of VHF

bull Vascular damage increased vascular permeability and plasma leakage

bull Hemorrhage

bull Hepatocellular necrosis leads to deficiency of coagulation factors

bull Complement activation

bull Disseminated intravascular coagulation

bull Cytokine storm

Re-emergence of Ebola virus disease

bull The EVD outbreak began in December 2013 and reported to WHO on 21 March 2014

13

Ebola signs and symptoms

Classification of Ebola virus

Order Mononegavirales

Family Filoviridae

Genus Marburgvirus

Genus Ebolavirus

Zaire ebolavirus (EBOV) Fatality rate 70-90

Sudan ebolavirus (SUDV) 40-60

Bundibugyo ebolavirus (BDBV) 32

Taiuml Forest ebolavirus (TAFV)

Reston ebolavirus (RESTV)

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 5: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Bunyaviruses

bull Crimean-Congo hemorrhagic fever virus ndash Crimean-Congo HF in the Middle East Southern Europe and western China

bull Rift Valley fever virus- Rift Valley fever in Africa and Arabian Pennisula

bull Genus Hantavirus- hemorrhagic fever with renal syndrome in Eurasia

bull Severe fever with thrombocytopenia syndrome virus in China

Arenaviruses

bull Junin virus- Argentine HF

bull Machupo virus ndash Bolivian HF

bull Guanarito virus ndash Venezuelan HF

bull Sabia virus ndash Brazillian HF

bull Lassa virus ndashLassa HF in West Africa

bull Lujo virus- unnamed disease in Zambia

bull Chapare virus- unnamed disease in Bolivia

Filoviruses

bull Marburg virus ndash emerged in 1967 in Marburg Germany and Yugoslavia

bull Ebolavirus- emerged in 1976 in Zaire (DR Congo) and Sudan

VHF in Africa

bull Flaviviridae Yellow fever virus

bull Arenaviridae Lassa fever virus

bull Filoviridae Marburg virus

Ebola virus

bull Bunyaviridae

Crimean-Congo hemorrhagic fever virus

Rift Valley fever virus

VHF in Thailand

bull Dengue virus types 1-4

bull Hantaan virus

Pathogenic mechnisms of VHF

bull Vascular damage increased vascular permeability and plasma leakage

bull Hemorrhage

bull Hepatocellular necrosis leads to deficiency of coagulation factors

bull Complement activation

bull Disseminated intravascular coagulation

bull Cytokine storm

Re-emergence of Ebola virus disease

bull The EVD outbreak began in December 2013 and reported to WHO on 21 March 2014

13

Ebola signs and symptoms

Classification of Ebola virus

Order Mononegavirales

Family Filoviridae

Genus Marburgvirus

Genus Ebolavirus

Zaire ebolavirus (EBOV) Fatality rate 70-90

Sudan ebolavirus (SUDV) 40-60

Bundibugyo ebolavirus (BDBV) 32

Taiuml Forest ebolavirus (TAFV)

Reston ebolavirus (RESTV)

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 6: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Arenaviruses

bull Junin virus- Argentine HF

bull Machupo virus ndash Bolivian HF

bull Guanarito virus ndash Venezuelan HF

bull Sabia virus ndash Brazillian HF

bull Lassa virus ndashLassa HF in West Africa

bull Lujo virus- unnamed disease in Zambia

bull Chapare virus- unnamed disease in Bolivia

Filoviruses

bull Marburg virus ndash emerged in 1967 in Marburg Germany and Yugoslavia

bull Ebolavirus- emerged in 1976 in Zaire (DR Congo) and Sudan

VHF in Africa

bull Flaviviridae Yellow fever virus

bull Arenaviridae Lassa fever virus

bull Filoviridae Marburg virus

Ebola virus

bull Bunyaviridae

Crimean-Congo hemorrhagic fever virus

Rift Valley fever virus

VHF in Thailand

bull Dengue virus types 1-4

bull Hantaan virus

Pathogenic mechnisms of VHF

bull Vascular damage increased vascular permeability and plasma leakage

bull Hemorrhage

bull Hepatocellular necrosis leads to deficiency of coagulation factors

bull Complement activation

bull Disseminated intravascular coagulation

bull Cytokine storm

Re-emergence of Ebola virus disease

bull The EVD outbreak began in December 2013 and reported to WHO on 21 March 2014

13

Ebola signs and symptoms

Classification of Ebola virus

Order Mononegavirales

Family Filoviridae

Genus Marburgvirus

Genus Ebolavirus

Zaire ebolavirus (EBOV) Fatality rate 70-90

Sudan ebolavirus (SUDV) 40-60

Bundibugyo ebolavirus (BDBV) 32

Taiuml Forest ebolavirus (TAFV)

Reston ebolavirus (RESTV)

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 7: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Filoviruses

bull Marburg virus ndash emerged in 1967 in Marburg Germany and Yugoslavia

bull Ebolavirus- emerged in 1976 in Zaire (DR Congo) and Sudan

VHF in Africa

bull Flaviviridae Yellow fever virus

bull Arenaviridae Lassa fever virus

bull Filoviridae Marburg virus

Ebola virus

bull Bunyaviridae

Crimean-Congo hemorrhagic fever virus

Rift Valley fever virus

VHF in Thailand

bull Dengue virus types 1-4

bull Hantaan virus

Pathogenic mechnisms of VHF

bull Vascular damage increased vascular permeability and plasma leakage

bull Hemorrhage

bull Hepatocellular necrosis leads to deficiency of coagulation factors

bull Complement activation

bull Disseminated intravascular coagulation

bull Cytokine storm

Re-emergence of Ebola virus disease

bull The EVD outbreak began in December 2013 and reported to WHO on 21 March 2014

13

Ebola signs and symptoms

Classification of Ebola virus

Order Mononegavirales

Family Filoviridae

Genus Marburgvirus

Genus Ebolavirus

Zaire ebolavirus (EBOV) Fatality rate 70-90

Sudan ebolavirus (SUDV) 40-60

Bundibugyo ebolavirus (BDBV) 32

Taiuml Forest ebolavirus (TAFV)

Reston ebolavirus (RESTV)

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 8: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

VHF in Africa

bull Flaviviridae Yellow fever virus

bull Arenaviridae Lassa fever virus

bull Filoviridae Marburg virus

Ebola virus

bull Bunyaviridae

Crimean-Congo hemorrhagic fever virus

Rift Valley fever virus

VHF in Thailand

bull Dengue virus types 1-4

bull Hantaan virus

Pathogenic mechnisms of VHF

bull Vascular damage increased vascular permeability and plasma leakage

bull Hemorrhage

bull Hepatocellular necrosis leads to deficiency of coagulation factors

bull Complement activation

bull Disseminated intravascular coagulation

bull Cytokine storm

Re-emergence of Ebola virus disease

bull The EVD outbreak began in December 2013 and reported to WHO on 21 March 2014

13

Ebola signs and symptoms

Classification of Ebola virus

Order Mononegavirales

Family Filoviridae

Genus Marburgvirus

Genus Ebolavirus

Zaire ebolavirus (EBOV) Fatality rate 70-90

Sudan ebolavirus (SUDV) 40-60

Bundibugyo ebolavirus (BDBV) 32

Taiuml Forest ebolavirus (TAFV)

Reston ebolavirus (RESTV)

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 9: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

VHF in Thailand

bull Dengue virus types 1-4

bull Hantaan virus

Pathogenic mechnisms of VHF

bull Vascular damage increased vascular permeability and plasma leakage

bull Hemorrhage

bull Hepatocellular necrosis leads to deficiency of coagulation factors

bull Complement activation

bull Disseminated intravascular coagulation

bull Cytokine storm

Re-emergence of Ebola virus disease

bull The EVD outbreak began in December 2013 and reported to WHO on 21 March 2014

13

Ebola signs and symptoms

Classification of Ebola virus

Order Mononegavirales

Family Filoviridae

Genus Marburgvirus

Genus Ebolavirus

Zaire ebolavirus (EBOV) Fatality rate 70-90

Sudan ebolavirus (SUDV) 40-60

Bundibugyo ebolavirus (BDBV) 32

Taiuml Forest ebolavirus (TAFV)

Reston ebolavirus (RESTV)

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 10: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Pathogenic mechnisms of VHF

bull Vascular damage increased vascular permeability and plasma leakage

bull Hemorrhage

bull Hepatocellular necrosis leads to deficiency of coagulation factors

bull Complement activation

bull Disseminated intravascular coagulation

bull Cytokine storm

Re-emergence of Ebola virus disease

bull The EVD outbreak began in December 2013 and reported to WHO on 21 March 2014

13

Ebola signs and symptoms

Classification of Ebola virus

Order Mononegavirales

Family Filoviridae

Genus Marburgvirus

Genus Ebolavirus

Zaire ebolavirus (EBOV) Fatality rate 70-90

Sudan ebolavirus (SUDV) 40-60

Bundibugyo ebolavirus (BDBV) 32

Taiuml Forest ebolavirus (TAFV)

Reston ebolavirus (RESTV)

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 11: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Re-emergence of Ebola virus disease

bull The EVD outbreak began in December 2013 and reported to WHO on 21 March 2014

13

Ebola signs and symptoms

Classification of Ebola virus

Order Mononegavirales

Family Filoviridae

Genus Marburgvirus

Genus Ebolavirus

Zaire ebolavirus (EBOV) Fatality rate 70-90

Sudan ebolavirus (SUDV) 40-60

Bundibugyo ebolavirus (BDBV) 32

Taiuml Forest ebolavirus (TAFV)

Reston ebolavirus (RESTV)

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 12: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

13

Ebola signs and symptoms

Classification of Ebola virus

Order Mononegavirales

Family Filoviridae

Genus Marburgvirus

Genus Ebolavirus

Zaire ebolavirus (EBOV) Fatality rate 70-90

Sudan ebolavirus (SUDV) 40-60

Bundibugyo ebolavirus (BDBV) 32

Taiuml Forest ebolavirus (TAFV)

Reston ebolavirus (RESTV)

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 13: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Classification of Ebola virus

Order Mononegavirales

Family Filoviridae

Genus Marburgvirus

Genus Ebolavirus

Zaire ebolavirus (EBOV) Fatality rate 70-90

Sudan ebolavirus (SUDV) 40-60

Bundibugyo ebolavirus (BDBV) 32

Taiuml Forest ebolavirus (TAFV)

Reston ebolavirus (RESTV)

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 14: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Phylogenetic Analysis of the Ebolavirus Genus Including the EBOV Strains from Guinea

Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report N Engl J Med 2014 Apr 16

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 15: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Confirmed probable and suspected EVD cases worldwide (data up to 31 May 2015)

Source WHO EBOLA SITUATION REPORT

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 16: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Figure 3 Distribution of EVD cases in Guinea and Sierra Leone by week of reporting as of week 262015

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 17: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Current situation

bull As of 27 June 2015 WHO has reported 27 541 cases with 11 235 deaths

bull Guinea

bull Sierra Leone

bull According to the last confirmed case on 27 March 2015 Liberia declared EVD free on 9 May 2015 New case was found on 29 June 2015 and number of cases is rising

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 18: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Overview of EVD outbreaks 1976ndash2014

European CDC as of 27 July 2014

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 19: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Why the 2014-2015 outbreak is more serious than previous ones

bull From 1976 to 2014 Ebolavirus is evolving but no change which leads to functional change

bull Wide spread of 2014 outbreak was due to epidemiological factors

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 20: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Organisation drsquoune ldquoClinique Ebola

Conakry Guinea

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 21: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

22

Mesures preacuteventives Prise encharge

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 22: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Sources of infection

bull Animals

bull Human body fluids

Blood urine feces sweat

nasal secretion sputum breast milk

genital secretion semen

aqueous humor of a uveitis case

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 23: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Hypsignathus monstrosus Hammer-headed fruit bat Big-lipped bat

Myonycteris torquata Epomops franqueti

Ebola outbreaks in DRC in 2007-2008 was associated with massive migration of fruit bats

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 24: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Routes of infection

bull Mucous membrane skin abrasion

bull Ingestion of contaminated food

bull Airborne transmission is unlikely Aerosols

bull Human to human transmission

Close contact

Sexual transmission possible ndash recommended 3 mo after onset

Dead ceremony

Incubation period 2-21 days

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 25: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

General properties of Ebola virus

bull RNA genome of negative polarity linear about 18 959 nucleotides long 80 nm wide

bull Envelope

bull Filamentous shape

bull Carry enzyme RNA dependent

RNA polymerase (replicase)

in virion

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 26: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Ebola virus virion

httpviralzoneexpasyorgall_by_species207html

970 nm long 80 nm diameter

IFN antagonist Interfere IFN signalling

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 27: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Target cellsorgans for virus replication

bull Monocytesmacrophages

bull Dendritic cells

bull Endothelial cells

bull Hepatocytes

bull Adrenal cortical cells

bull Parenchymal cells of various organs

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 28: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Ebola virus pathogenesis

Feldmann Lancet 2011 377(9768)849-62

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 29: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Ebolavirus stability

bull Virus inactivation- gamma irradiation

- heating at 60 C for 60 min

- boiling for 5 min

bull Sensitive to sodium hypochlorite (bleach)

bull Survive in liquid or dried materials for many days

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 30: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Ebola virus genome

bull GP- glycoprotein sGP ndash secreted glycoprotein

bull N ndash nucleoprotein VP30 ndash component of nucleocapsid

bull L ndash polymerase enzyme VP35 ndashpolymerase complex protein

bull VP40- major matrix protein VP24- minor matrix protein

bull Nucleocapsid is a complex of NP VP35 VP30 and L

httpviralzoneexpasyorgall_by_species207html httpgooglegooglecomari_fundamentalsofmicrobiology_7_microbialgeneticshtm

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 31: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Laboratory diagnosis of Ebola virus

bull Specimens blood samples tissues specimen handling

bull Genome detection by RT-PCR

bull Antigenantibody detection in sera by ELISA

bull Virus isolation in Vero E6 required BSL 4 facilities

bull Electron microscopy

Low viral load is correlated with survival

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 32: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Differential diagnosis of EVD

bull Malaria

bull Lassa fever

bull Yellow fever

bull Leptospirosis

bull Typhoid

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 33: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Marburg virus

bull First discover in 1967 in Marburg and Frankfurt Germany and in Belgrade Serbia (Yugoslavia)

bull Source of infection African Green monkeys from Uganda

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 34: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Marburg hemorrhagic fever outbreak

bull Germany and Yugoslavia 1967

bull South Africa (origin from Zimbubwe ) 1975

bull Kenya 1980 1987

bull DR Congo 1998-2000

bull Angola 2004-2005

bull Uganda 2007 2012

bull 1990 Lab contamination in Russia

bull 2008 USA and Netherlands ex Uganda

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 35: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Marburg hemorrhagic fever

bull Incubation period 5-10 days

bull High fever severe headache severe malaise severe watery diarrhea abdominal pain and cramping CNS involvement

bull Bleeding- fresh blood in vomitus and feces nose gum and vagina venepuncture site

bull Death between day 8 and 9 and usually precedes by severe blood loss and shock

bull Case fatality rate 23-90

Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

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Transmission

bull Fruit bats Rousettus aegypti of the family Pteropidae are reservoir hosts

bull Transmission from bats to human may occur through contact with bat feces or aerosols

bull Transmission from primates

bull Human to human transmission contact to blood secretions body fluidstissues semen or contaminated equipment (household contact nosocomial infection burial ceremony)

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 37: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Pteropid bats

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 38: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Lassa fever virus

bull First report in the town named Lassa in Nigeria in 1969 in 2 American missionaries who died from the disease

bull It is endemic in West Africa in Sierra Leone Liberia Guinea and Nigeria

bull Cases reported from Ivory coast Mali Ghanahellip

bull Estimated number 100000 to 300000 cases with approximately 5000 deaths per year

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 39: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Signs and symptoms

bull 80 of Lassa fever virus infection are mild and undiagnosed

bull 20 of the cases progress to severe disease and hemorrhage repeated vomiting facial swelling pain in chest back and abdomen and shock Deafness is the most common complication

bull Death occurs from multi-organ failure

bull Fatality rate 1 or 15-20 of hospitalized cases

Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

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Transmission of Lassa virus

bull Mastomys rodents live in savannas and forest and around home Rodents shed the virus in urine and droppings

bull Man gets infection through ingestion and inhalation

bull Human to human transmission through contact with blood secretions excretion and tissues and also nosocomial infection

bull Incubation period 1-3 weeks

Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

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Reservoir host of Lassa virus is a rodent known as the multimammate rat (Mastomys natalensis)

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 42: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Yellow fever virus

bull The first virus known to cause human infection

bull The first virus known to be transmitted by insect vector

bull The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados

Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

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Panama canal locks

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States in part because of the yellow fever and malaria deaths among the projectrsquos workers

The French Panama Canal Effort 1882ndash1889

Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

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Areas with risk of yellow fever virus transmission

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 45: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Aedes aegypti

Vector for Dengue virus Chikungunya virus Yellow fever virus

Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

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Yellow fever vaccine

Live attenuate vaccine strain 17D was developed by Max Theiler in 1937

Protection begins by the 10th day after vaccination in 95 of people and last for at least 10 yrs

Nobel Prize laureate 1950

Max Theiler

Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

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Lab diagnosis of dengue virus infection

bull Genome detection by RT-PCR

bull Paired blood

- Hemagglutination-inhibition (HI) test

lt 1280 primary infection

gt 2560 secondary infection

- Plaque reduction neutralization test

bull ELISA IgGIgM

bull NS1 AgAb

bull Cross reaction with other flaviviruses

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

2557

Page 48: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

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Mahanty S Bray M Lancet Infect Dis 20044(8)487-98

Vascular leakage Coagulopathy Apoptosis

Inhibition of adaptive responses

Inhibition of innate immune responses

Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

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Chronology of previous Ebola virus disease outbreaks

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

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Page 51: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

bull Crisis of climate and environmental changes do not affect only man but also animals

Global warming flood and smoke from fire destroys animalrsquos habitats

bull Animal migration and movement

Bats will be an important source of novel agents

One world one health

Our future

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

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Page 52: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Family Filoviridae is classified into 2 genera Genus Marburgvirus Genus Ebolavirus

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

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Page 53: ศาสตราจารย์ ดรพิไลพนัธ์พธุวฒั ...nih.dmsc.moph.go.th/data/data/58/6_7_58/4.pdfCommon characteristics of viruses causing HF •Enveloped

Symptoms of VHF

bull Specific signs and symptoms vary by type of VHF but the initial signs and symptoms is nonspecific and difficult to provide differential diagnosis

bull Initial symptoms high fever fatigue loss of strength muscle aches

West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

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West Africa Ebola virus disease epidemic curve

Source httpvirologydownunderblogspotcomau201407ebola-virus-disease-evd-2014-westhtml

Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

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Figure 2 Distribution of confirmed cases of EVD by week of reporting Guinea and Sierra Leone weeks 462014 to 262015

Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

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Zaire ebolavirus ซงมอตราตายสงถงรอยละ 70-90 รองลงมาคอ Sudan ebolavirus มอตราตายรอยละ 40-60 และ Bundibugyo ebolavirus มอตราตายประมาณรอยละ 32 ส าหรบเชอตนเหตของการระบาดทเกดขนในปจจบนคอ Zaire ebolavirus การระบาดเรมขนในประเทศกน ตงแตเดอนมกราคม และไดรายงานตอองคการอนามยโลกในวนท 21 มนาคม พศ

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