越境性動物疾病（ TAD）の現状鹿児島大学農学部越境性動物疾病（ TAD）研究センター教授獣医学科病態予防獣医学講座獣医公衆衛生学分野　岡本嘉六

熊本県獣医療職員研修会

Approximately 75% of recently emerging infectious diseases affecting humans are diseases of animal origin; approximately 60% of all human pathogens are zoonotic. Quoted from CDC, USA

SARS2003

palm civet et.al

HPAI H5N11997/2003Water birdBSE

1986/1993Cow

West Nile1999

Bird/Mosquito

H1N1 Pandemic2009

Swine/Bird

Nipah virus1998

Megabat/Swine

Ebola1976

Monkey

HPS1993

Rodentia

Hendra virus1994

Megabat/Horse

Lassa1969

Rodentia BzHF1994

RodentiaVzHF1991

Rodentia

E. Coli O1571982

Cow/Food

Examples of emerging infectious disease(Pathogen, Year, Natural reservoir)

HPS: Hantavirus Pulmonary SyndromeSARS: Severe Acute Respiratory Syndrome

Venezuelan & Brazilian Hemorrhagic Fever

Cyclozoonosis

Metazoonoses

Direct zoonoses

Saprozoonoses

an vertebrate host

Avian influenza, Rabies, Hantavirus, Psittacosis, Bovine tuberculosis, Brucellosis, E. coli O157, Anthrax

an invertebrate host

West Nile fever, Y ｅｌｌｏｗ ｆｅｖｅｒ , Ｒｉｆｔ Ｖａｌｌｅｙ ｆｅｖｅｒ , Plague, Aｎｉｓａｋｉａｓｉｓ

more than one vertebrate host

Echinococcosis, Cｙｓｔｉｃｅｒｃｏｓｉｓ , Toxoplasmosis, Tｒｉｃｈｉｎｉａｓｉｓ

non-animal reservoir

Tetanus, Bｏｔｕｌｉｓｍ , Aｓｐｅｒｇｉｌｌｏｓｉｓ , Hｉｓｔｏｐｌａｓｍｏｓｉｓ , Tｏｘｏｃａｒｉａｓｉｓ , Fascioliasis, Anthrax

Global Framework for Transboundary Animal Diseases (GF-TADs) May 2004

Transboundary Animal Diseases(TADs) may be defined as those epidemic diseases which are highly contagious or transmissible and have the potential for very rapid spread, irrespective of national borders, causing serious socio-economic and possibly public health consequences.

The GF-TADs is a joint initiative of FAO and OIE which combines the strengths of both organisations in the fight against TADs world wide. It is composed of a global component at the OIE and FAO Headquarters level and of regional and sub-regional components. The ultimate aim of the Programme is to control and eradicate the most significant animal diseases including those transmissible to humans.

The GF-TADs programme will be developed along four main thrusts:

(1) A regionally led mechanism, to operationally address and implement action against priority diseases as agreed by relevant stakeholders;

(2) The development of Regional and Global Early Warning Systems for major animal diseases;

(3) The enabling and application of research on TADs causing agents at the molecular and ecological levels for more effective strategic disease management and control; and,

(4) The completion of the Global Rinderpest Eradication Programme set for achieving global declaration of freedom by the year 2010.

Contributing to One World, One HealthA Strategic Framework for

Reducing Risks of Infectious Diseases at the Animal-Human-

Ecosystems Interface14 October 2008

Contents1. Introduction: HPAI and beyond2. Achievements and lessons learned from HPAI and their relevance to Emerging infectious diseases(EID)3. Emerging and existing infectious diseases and their impacts4. The Strategic Framework5. Specific objectives and outputs6. Cross-cutting issues to be addressed7. Institutional issues8. Financing the framework

This principle may be called “OWOH” or “One Health”.

Executive summaryHumanity faces many challenges that require global solutions. One of these challenges is the spread of infectious diseases that emerge (or re-emerge) from the interfaces between animals and humans and the ecosystems in which they live. This is a result of several trends, including the exponential growth in human and livestock populations, rapid urbanization, rapidly changing farming systems, closer integration between livestock and wildlife, forest encroachment, changes in ecosystems and globalization of trade in animal and animal products.

Reclamation

Human living area

Forest with

wildlife

Various pathogens existing among the wildlife could infect livestock and people.

OWOH

Animal influenzas threaten animal health and welfare, agricultural productivity, food security, and the livelihoods of farmers in some of the world’s poorest countries. Both H5N1 HPAI and pandemic H1N1 2009 have also highlighted the potential for animal origin influenza viruses to evolve into global public health threats.

OIE/FAO Network of Expertise on Animal Influenza(OFFLU)

To ensure that the impact and risks for animals and humans are kept at a minimum, it is vital that the animal health sector takes the lead in monitoring influenzas in animals and in sharing this information with the international community.

Humanα2-6α2-6

H1、H2、H3(α2-6α2-6)

Swineα2-3、 α2-6α2-6

H1、H3(α2-3α2-3、 α2-6α2-6)

Poultryα2-3

H5、H7(α2-3α2-3)

Horseα2-3

H3、H7(α2-3α2-3)

Waterbird (Anatidae)α2-3

H type of virus(Affinity to αreceptor)

Animalαreceptor

Shape and thickness of arrows show the frequency of infection.

H1～H16(α2-3α2-3)

Waterbird posess Waterbird posess all typs of H, but all typs of H, but other animals infect other animals infect with difinitive with difinitive types.types.

The flu usually prevalent only within the same species.

H5N1H5N1

α2-6α2-6、 α2-3

α2-α2-3 receptor3 receptorlocalized on localized on alveolar cellalveolar cell

On rare occasions, surpass the “species barrier”

In North America, regional virus repeatedly infect mutually between man and pig.In North America, regional virus repeatedly infect mutually between man and pig.

Emergence of pandemic H1N1 2009SwineSwineH1N1H1N1

PandemicH1N1 2009

HumanHumanH3N2H3N2

EurasiaEurasiaSwine H1N1Swine H1N1

× ⇒

DoubleH3N2

TripleH1N1

97-98

PoultryPoultryH?N?H?N?

TripleH1N2

× ⇒98

TripleH3N2

SwineSwineH1N1H1N1

×

⇒2000 -⇒09

×

PB2PB1PAHANPNAMPNS

PB2PB2PB1PB1PAPAHAHANPNPNANAMPMPNSNS

FAOEMPRES

Novel H1N1 U.S. Deaths, By Age Group

Novel H1N1 Confirmed and Probable Case Rate in the United States, By Age Group

2009 H1N1 Early Outbreak and Characteristics

From April 15 to July 24 From April 15 to July 24 2009, USA reported 43,771 2009, USA reported 43,771 confirmed and probable confirmed and probable cases of novel influenza A cases of novel influenza A (H1N1) infection.(H1N1) infection. Of these Of these cases, 5,011 people were cases, 5,011 people were hospitalized and 302 people hospitalized and 302 people died.died.

The information analyzed by The information analyzed by CDC supports the conclusion CDC supports the conclusion that novel H1N1 flu has that novel H1N1 flu has caused greater disease caused greater disease burden on people younger burden on people younger than 25 years of age than than 25 years of age than older people.older people.

High incidence of young High incidence of young generation and significantly generation and significantly higher fatality rate than higher fatality rate than seasonal influenza seasonal influenza strengthened vigilance strengthened vigilance worldwide.worldwide.

Number of Influenza-Associated Pediatric Deaths by Week of Death

Percentage of Visits for Influenza-like Illness Reported by the U.S. Surveillance Network

FluView USA

On April 28, WHO pulled up flu alert level from "3" to "4", and to "5" on the next day, declaring “Pandemic” on Jun 12.the national

baseline People afraid of the flu pandemic out of season in summer.

Without mutation through the epidemic, the fatality rate is equal or less than those of seasonal flu.

WHO announced that the H1N1 influenza virus has moved into the post-pandemic period. However, localized outbreaks of various magnitudes are likely to continue.

Avian influenza viruses do not normally infect humans. However, there have been instances of certain highly pathogenic strains causing severe respiratory disease in humans. In most cases, the people infected had been in close contact with infected poultry or with objects contaminated by their faeces.

Nevertheless, there is concern that the virus could mutate to become more easily transmissible between humans, raising the possibility of an influenza pandemic.

Another threat of flu

H5N1 (Hong Kong, 1997)Highly pathogenic H5N1 poultry outbreaks

18 confirmed human cases, 6 deaths• Median age: 9.5 years (range 1 1-60 yrs.); 11 pneumonia cases• Case-control study: Risk factor: exposure to live poultry the week before illness (OR = 4.5, p = 0.045)• 10% H5N1 antibody seroprevalence in poultry workers• No evidence for efficient human-to to-human transmission: No Pandemic• 1.5 million poultry culled, markets disinfected• Poultry imports temporarily stopped from China• Surveillance: farms, markets, border• Poultry segregated, monthly market “rest days”

Dead birds

Wet Market: Live bird market

Number of Patients with Avian H5N1

Death

Alive

Fatality rate

A fatal human case of avian influenza H5N1 infection occurred in China in Nov 2003, and the disease expanded to South East Asia, in 2005 to world wide. Since then, 552 persons have

been infected and 322 died(Fatality rate is about 60%).

: Viet Nam: Indonesia: Egypt: China

Number of death in major epidemic countries

HPAI H5Ni first attacked Viet Num, followed Indonesia. In 2006, 45 out of 55 patients died. Although the vaccines already had been developed, Indonesia did not available them.

Indonesia government rejected the entrance of supporting parties to obtain new strain of flu virus in 2006. Developed countries stocked huge amount of H5NI vaccine, but many developing countries could never perchase them.

Alveolar cell

Bronchioli respiratorii

Nasal mucosa

Why the spread of H5N1 viruses among humans is limited?

Influenza virus receptors in human.

Virus, 56, 85-90, 2006.

The epithelial cells in the upper respiratory tract of humans mainly possess sialic acid linked to galactose by α 2,6 linkages (SA α 2,6Gal).

No sneeze !

However, many cells in the respiratory bronchioles

and alveoli possess SA α 2,3Gal, which is preferentially recognized by avian viruses. These facts are consistent

with the observation that H5N1 viruses can be directly transmitted from birds to humans and cause serious lower respiratory tract damage in humans.

Most human cases of H5N1 avian influenza have occurred in rural or periurban areas where many households keep small domestic poultry flocks.

However, defeathering or butchering of dead wild birds, especially waterfowl, is particularly hazardous in areas where Avian influenza A/H5N1 virus has been reported or is likely to occur, such as along migratory routes. The public should be advised to report, and avoid contact with, wild birds found dead.

FAO developed a wet market communication pilot project.

Wet Market

Avian Influenza Surveillance of Wild Birds

Wild aquatic birds are considered the natural reservoir of all low pathogenic viruses(LPAI). Wild birds have probably carried influenza viruses, with no apparent harm, for centuries. A considerable circumstantial evidence suggests that migratory birds can introduce low pathogenic H5 and H7 viruses to poultry flocks. In some cases these viruses may then mutate in poultry to the highly pathogenic form. Unfortunately, the role of migratory birds in the spread of high pathogenic virus (HPAI) was not fully understood.

Apr 2005, wild birds began dying at Qinghai Lake in China, wherenumerous migratory birds congregated. Altogether, 6,345 birds from different species died in the coming weeks. This was the first reported instance of any HPAI causing mass deaths in wild birds. This event triggered world-wide spreading of H5N1.

WHO strategic action plan for pandemic influenza

Strategic action1 Reduce human exposure to the H5N1 virus2 Strengthen the early warning system3 Intensify rapid containment operations4 Build capacity to cope with a pandemic5 Coordinate global scientific research and development

The plan aims to achieve two over-arching objectives:1. to exploit all feasible opportunities to prevent the H5N1 virus from

developing the ability to ignite a pandemic and, should this effort fail,2. to ensure that measures are in place to mitigate the high levels of

morbidity and mortality and social and economic disruption that can be expected during the next pandemic.

November 2005, a meeting on avian influenza and human pandemic influenza was jointly convened by WHO, FAO, OIE, and the World Bank. The meeting agreed with two general principles and five Strategic actions.

(1) preventing the emergence of a pandemic virus or, should this prove impossible, delaying the initial international spread of a pandemic

(2) preparing all countries to cope with a pandemic in ways that reduce morbidity and mortality and also mitigate economic and social disruption.

The World Bank, December 5, 2005: PROGRAM FRAMEWORK DOCUMENT FOR PROPOSED LOANS/CREDITS/GRANTS IN THE AMOUNT OF US$500 MILLION EQUIVALENT FOR A GLOBAL PROGRAM

FOR AVIAN INFLUENZA CONTROL AND HUMAN PANDEMIC PREPAREDNESS AND RESPONSE

Country-Level Financing and Support Framework

Integrated Country Program

Government ResourcesDomestic Private Resources

Existing External Financing and Technical AssistancePotential Additional Support

Bilateral Financing and Technical

Assistance

PossibleWorld Bank-administeredTrust Fund

Multilateral Assistance(International Bank for

Reconstruction and Development/Infocomm Development Authority)

FAO,OIE, WHO

and their jointprograms

RegionalOrganisation

GrantsGrants Loans,

limited grants

Technical Assistance,

etc

WHO Interim Protocol: Rapid operations to contain the initial emergence of pandemic influenza

The draft of interim protocol to achieve the strategic action plan for pandemic influenza was proposed on May 2006, and updated October 2007.

Containment and Buffer Zones for Rapid Containment

Index Cluster Containment Zone: The geographical area and population which contains the Index Cluster and where extensive interventions are applied

Buffer Zone: The geographical area and population around the Containment Zone where active and complete surveillance is applied.

Avian A/H5N1Fatality rate=60%

Pandemic A/H5N1

Seasonal FluA/H1N1A/H3N2 Reassortment in humans

Efficiently transmissible

human-to-human

Avian Virus

Avian H5N1

Human Virus

Reassortmentin swine

Pandemic A/H5N1

Efficiently transmissible

human-to-human

The epithelial cells in the upper respiratory tract of swine possess SA α2,6Gal and SA α2,3Gal. So, human flu virus and avian flu virus can infect swine. Reassortment of both types in swine may emerge novel pandemic virus with very high fatality rate and transmissibility.

Although the control of these transmissions might be hard, we should win this battle. Pandemic H1N1 2009

extended very rapidly throughout the world, but the lethality was low. Novel Pandemic A/H5N1 could be second coming of the 1919 Spanish Flu.

Viet NamIndonesiaEgyptChinaThailandCambodiaTurkeyAzerbaijan

2005 2006 2007 2008 2009 2010

: There is no information available on this disease : Never reported : Disease not reported during this report period : Disease suspected but not confirmed : Confirmed infection but no clinical disease : Confirmed clinical infection : Confirmed infection but limited to certain zones

OIE Disease timelines: Highly pathogenic avian influenza

Small pox Smallpox is an infectious disease unique to humans(not zoonosis), caused by Variola virus. The fatality rate for flat-type is 90% or greater and nearly 100% is observed in cases of hemorrhagic smallpox.

Smallpox is believed to have emerged in human populations about 10,000 BC. In the early 1950s an estimated 50 million cases of smallpox occurred in the world each year.

To eradicate smallpox, each outbreak had to be stopped from spreading, by isolation of cases and vaccination of everyone who lived

close by. This process is known as "ring vaccination".

The global program on smallpox eradication initiated by WHO in 1958 and intensified since

1967. The global eradication of smallpox was certified by a commission of eminent scientists on December 1979.

Hemorrhagic-type smallpox.

Family: Poxviridae

Subfamily: ChordopoxvirinaeGenus: Orthopoxvirus

Camelpox virusCowpox virusEctromelia virus Monkeypox virusRaccoonpox virusTaterapox virusVaccinia virusVariola virusVolepox virus

Genus: ParapoxvirusBovine papular stomatitis virusOrf virusParapoxvirus of red deer in New ZealandPseudocowpox virus

Virus families not assigned to an order(65 Families)

Orthopoxvirus is a genus of poxviruses that includes many species isolated from mammals. Although Variola virus infects only human, some Orthopoxviruses have the ability to infect non-host species, such as monkeypox virus.

I now offer a few topics related with small pox eradication.

Monkeypox

Monkeypox was first found in 1958 in laboratory monkeys. African squirrels might be the common host for the disease. Rats, mice, and rabbits can get monkeypox, too.

Direct zoonoses

Seven years old girl in Republic of Zaire

Human monkeypox

Monkeypox is an exotic infectious disease caused by the monkeypox virus, and is usually transmitted to humans from rodents, pets, and primates through contact with the animal's blood or through a bite.

Human monkey pox can be difficult to distinguish clinically from smallpox. Case-fatality ratios in Africa have ranged from 1% to 10%.

It is assumed that vaccination against smallpox would provide protection against human monkeypox infection. Since the eradication of smallpox in 1979, human case increase gradually.

Six months later, she healed but many pockmark remained.

Distribution of 52 confirmed cases of human monkeypox.

Endemic Human Monkeypox, Democratic Republic of Congo, 2001–2004Emerg Infect Dis. 2007

Monkeypox positive/No. cases investigated

Age

<45–14

15–2425–34>35

Total

male

8/1212/225/172/91/6

28/66

female

7/219/198/130/81/7

24/68

Age and sex distribution of patients with monkeypox

Among 136 patients, 51 (37.5%) had laboratory-confirmed MPX infection, 61 (44.8%) had laboratory-confirmed chickenpox virus infection, and 1 (0.7%) had coinfection.

Movement of imported African rodents to pet shops and distribution of prairie dogs from a pet shop associated with

human cases of monkeypox, in 2003 USA.

All 35 human cases of monkeypox were associated with prairie dogs.

African rodents were resell to Japan, but 15 already dead before arrival and lived two rodents was not infected.

MMWR 2003Rodents and prairie dogs contacted with each other.

762 rodents

Cowpox and Pseudocowpox virusIn 1796, Dr Edward Jenner used “cowpox

virus” to inoculate a patient to prevent them from contracting smallpox. Discovery of virus is in 1892(tobacco mosaic disease), so it is not as clear what virus he used for vaccine 100 years ago. In fact, milker's nodule is usally caused by a parapox virus(Pseudocowpox), not by cowpox virus.

Milker's nodules

Nowadays, cowpox is a rare disease. It mostly occurs in Great Britain and some European countries. Cows are no longer the main carrier of the virus; instead woodland rodents are the natural hosts of the virus who then pass it on to domestic cats. Feline cowpox virus infection

What is cowpox?

Cowpox Virus Transmission from Pet Rats to Humans

16 years old boy

Germany: Outbreak including 5 patients caused by infected pet rats from the same litter in 2009. Human cowpox infections seem to be increasing. One obvious reason for an increase might be the fading cross-protective immunity to cowpox after the cessation of small pox vaccination.

Human cowpox is a disease of young people, with half of all cases occurring in individuals younger than 18 years, because of their not having been vaccinated for smallpox, which may confer some protection against cowpox.

VARV: Variola virus

VACV: vaccinia virus

CPXV: cowpox virus

VACV species imported to Brazil in 1804, when human vaccine arrived at a port on the arms of slaves returning from Portugal. The species was maintained in this manner(arm to arm) and in 1887 the first animal vaccine was produced in calves. In 1963, Brazilian VACVs(Group 1, 2) was isolated from the blood of a rice rat captured near the edge of Amazon rain forest. Since then, those virus were naturally isolated from a wild rodent. In 1999, exanthematous outbreaks affecting dairy cattle and their handlers were reported.

Brazilian VACVs existed before the beginning of the WHO smallpox eradication vaccination campaigns.

Brazilian Vaccinia Viruses and Their Origins

The virus that Dr. Edward Jenner used for vaccination derived from milker's nodule in 1796 may be Brazilian VACVs.

Voyages of Christopher Columbus(1492-1504)