tropical infection disease _lecture2

7/28/2019 Tropical Infection Disease _lecture2

1/67

TROPICAL INFECTION

DISEASES

Gatot Sugiharto, MD, Internist

Internal Medicine Department

Faculty of Medicine, Wijaya Kusuma UniversitySurabaya

GSH - Tropmed - 2010 1


2/67

LEPTOSPIROSIS






3/67

Introduction

GSH - Tropmed - 2010

3

Leptospirosis is an acute anthropo-zoonotic infection

Occurs in tropical, subtropical and temperate zones.

Synonym : Weil Disease, Hemorrhagic Jaundice, Mud

Fever, Swineherd Disease, Canicola Fever, seven-day

fever (commonly in Japan), Cane cutters disease (in

Australia), Rice field Leptospirosis (in Indonesia) , Fort

Bragg fever in U.S.Andaman haemorrhagic fever(AHF)


4/67

Leptospirosis


4

Caused by spirochete bacteria leptospira, a thin spiral organism It is characterized by very active motility, by rotating

(spinning) and bending. Usually one or both ends of this single-cell organism are bent or hooked

>250 serovars L. Interrogans

L. canicola

L. hardjo

L. pomona

L. icterohaemorrhagiae


5/67

High risk occupations


5

Rice/taro farming

Mining

Sewage/canal work

Cane harvesting

Fish farming


6/67

Route of Transmission


6

Main resevoir : rodents, livestock (cattle, horses,

sheep, goats, swine), canines, and wild mammals

Replicates in renal tubules, excreted in urine

Human infection occurs with direct contact with

infected urine, or indirect exposure to organisms in

wet soil & water, rarely by droplet inhalation

Often results from occupational exposure to rat-infected water


7/67



8/67


8


9/67



10/67

Mechanism of

Disease


10

Systemic vasculitis occurs, facilitating migration

of spirochetes into organsHepatocellular damage with jaundice, inc INR

Acute tubular necrosis of kidney

Increased capillary fragility hemorrhage can

occur in any internal organ (pulmonary hemorrhage)


11/67

Scanning electron microscopy of a renal tubule from

an experimentally infected rat

11



12/67

Clinical Presentation(1)


12

Incubation period: 2-20 days (median 11days)

Two types of leptospirosis:

Anicteric leptospirosis or self-limited illness (85 -90% )

Icteric leptospirosis (5 - 10% )


13/67

Clinical Presentation : early phase (4-7

days)


13

Symptoms: HA, myalgia, chills, back pain, anorexia, sore throat

nausea/vomiting

Hemoptysis, cough, SOB

Signs: Acute febrile illness (40oC)

Conjunctival suffusion

Nontender transient pretibial raised erythematous patches

Hepatomegaly Meningitis

Labs: thrombocytopenia, proteinuria, elevated WBC


14/67

Clinical Presentation: Late Phase


14

Second (Immune) phase: day 7+

Patient develops antibodies to the organism

Meningitis or hepatorenal manifestations more

prominent

Fevers may subside, becomes more jaundiced, can

bleed into skin, mucous membranes, lungs

Oligouric renal failure, shock, myocarditis, arrythmiascan follow


15/67

Weils Disease


15

Severe form of leptospirosis

Described by Weil in 1886 as a clinical syndrome in

4 men with severe jaundice, fever, hemorrhage, and

renal involvement Inada et al identified the causal agent in Japan in

1916

Most severe cases, with hepatorenal involvementand jaundice, can have a mortality rate of 20-40%


16/67

Diagnosis


16

Direct visualization of leptospires in blood (earlyphase) or urine (late phase) by darkfield microscopic

examination

Low sensitivity (40.2%) and specificity (61.5%)

Need special media (Fletcher's, Ellinghausen's, polysorbate )

Takes 2-3 weeks to be positive

IgM antibodies appear in late phase (5-7 days)

Microscopic agglutination test (MAT), ELISA

Titer >1:100 helps, but fourfold rise in titer is diagnostic

(need convalescent sample)


17/67

Diagnostic Tests for Leptospirosis



18/67

Differential diagnosis


18

Influenza Meningitis (encephalitis)

Viral hepatitis

Rickettsiosis Typhoid fever

Septicemia

Toxoplasmosis Legionnaires disease

Malaria


19/67

Treatment


19

IV penicillin for severe disease

Oral amoxycillin, erythromycin, doxycycline for mild

illness (10-14 d)

Jarisch-Herxheimer reactions have been reported inpatients treated with penicillin

Prognose

Humans with leptospirosis usually excrete the organism

in the urine for 4-6 weeks and occasionally for as long

as 18 weeks.


20/67

Prevention


20

Rodent control measures

Immunization of animals with killed vaccines short-lived, requires boosters

Protective clothing, footwear Burning canefield prior to harvest (young shoots can

cut hands)

Drink boiled water Doxycycline prophylaxis for high-risk workers


21/67

COMPLICATIONS


21

Azotemia

Oliguria

Hemorrhage

Purpura

Hemolysis

Gastrointestinal bleeding

Hypoprothrombinemia & thrombocytopenia


22/67

Fort Bragg Fever


22 August 1942, an unusual acute

febrile illness (99.8 to 105.6F)occurred in a group of soldiers atFort Bragg, N.C.

Soldiers quartered near a smallstream and its tributaries

40 patients with sudden onsetmalaise, mild aches, lumbar pain,severe headaches

Bilaterally symmetrical rash limitedin to the pretibial areas on thefourth day

Similar outbreaks 1946 and 1947among soldiers quartered in thesame area of the post


23/67

MALARIA






24/67

Introduction


24

The protozoan genus Plasmodiumis responsiblefor malaria

Four important species: Plasmodium falciparum,P. vivax, P. malariaeand P. ovale

Rapidly fatal and is responsible for most malariarelated deaths : P. Falciparum

Mosquito-transmitted malaria is the greatest

public health problem in large parts of the worldwith more than 500 million clinical cases andover 3 million deaths every year


25/67

Epidemiology


25

Occurs in most of the tropics of the world

Prevalence of falciparum and vivax malarias being

about the same in Asia, Oceania and South America

Malaria can be a travelers disease and imported

into any country.

A rural disease due to the presence of the female

Anophelesmosquito vector.


26/67

Tranmission


26

Transmision : by an infected femaleAnopheles biting

Others : blood transfusion or congenitallyfeto-maternal

Malaria-carryingAnophelesbite only near

dusk and dawn.


27/67


27


28/67


28


29/67

Clinical manifestation on life cycle.


29

Plasmodia replicate inside the RBC hemoliysis release of toxic metabolic by products into

the bloodstream.

These symptoms include chills, headache,myalgias and malaise, occurring in cycles.

Also may cause splenomegaly, jaundice andanemia

P falciparummay induce kidney failure, comaand death.


30/67

Chronic & relapse


30

All infected liver cells parasitized with P. falciparumand P.malariaerupture and release merozoites at about thesame time.

In contrast, P. vivaxand P. ovalehave two exoerythrocytic

forms. The primary type develops, causes liver cellrupture, and releases merozoites. The other form, whichdevelops concurrently, is known as the hypnozoite.

Sporozoites that enter liver cells differentiate into

nonsexual hypnozoites that remain dormant for weeks, oreven years.

The hypnozoites activate and undergo exoerythrocyticschizogony, forming a wave of merozoites that cause a

relapse.


31/67

Clinical symptoms(1)


31

Cough, fatigue, malaise, arthralgia, myalgia, andparoxysm of shaking chills and sweats

The classic paroxysm : begins with shivering and

chills, (1-2 hours) followed by high fever Paroxyms of varying 48 hours belong to vivax,

ovale and falciparum malaria, whereas 72 hoursbelongs to malariae infections.

The 48 hour fever is called tertian (occurs every3rd day) day 1 : fever, day 2 : no fever, day 3

: fever & so on. The 72 hour fever is calledquartan (returns on every 4th day)


32/67


32

30% of non-immune adults infected with P falciparumsuffer acute renal failure, some with seizures.

Blackwater fever : hemoglobinuria with the passage ofdark-colored urine

Non-cardiogenic pulmonary edema :common inpregnant women and results in death in 80% of patients

Profound hypoglycemia : young children and pregnantwomen.

The most prominent symptoms all relate to loss ofRBCs: a) tachycardia, b) anemia, c) fever, d)hypotension and e) splenomegaly.


33/67

Severe malaria


33

1. Cerebral malaria2. Acute renal failure3. ARDS4. Severe anaemia (Hb < 5g%)

5. DIC6. Haemoglobinuria7. Hypotension, Shock8. Hyperparasitemia9. Repeated seizures

10. Hyperpyrexia11. Haemolysis (Sr bil. >3 mg%)


34/67

Cerebral malaria


34

The principal signs : seizures and unconsciousness,preceded by a severe headache.

Neurologic examination : contracted or unequal

pupils, a Babinski sign, and absent or exaggerateddeep tendon reflexes

Cerebrospinal fluid examination : increasedpressure, increased protein, and minimal or no

pleocytosis. High fever, 41 to 42C, with hot, dry skin may

occur.


35/67

ARDS


35

Often fatal, develop rapidly, associatedwith excessive intravenous fluid therapy.

Fast, labored respiration, SOB, a non-productive cough, rales and rhonchi

Chest X-rays : increased bronchovascularmarkings.


36/67

Confirmed Diagnosis of Malaria


36

All clinically suspected malaria cases require

laboratory examination and confirmation.

Only in case where laboratory confirmation is not

possible start treatment immediately. Parasitological confirmation is done by thin-thick

blood smear microscopy examination or by dipstick

(Rapid Diagnostic Test [RDT]) or by serologic test (ICT)


37/67


37


38/67


38


39/67

Figure 1. Morphology of Plasmodium knowlesi in a Giemsa-stained thin blood smear. Infectederythrocytes were not enlarged, lacked Schuffner stippling, and contained much pigment. Shown

are examples of trophozoites (AF), a schizont (G), and a gametocyte (H). Scale bars = 5 m.


39

Malaria Therapy


40/67

Malaria Therapy

Plasmodium

Condition 1st reg Formula 2nd reg Formula 3rd reg/relaps

Formula

Un

known

Nonpregnant

Chloroquin

Primaquin

4-4-2

3

Kina

Primaquin

3x2 (7)

2-3

Pregnant Chloroquin 4-4-2 Kina 3x2 (7)

Falciparum

SensitiveChloroquin

Chloroquin

Primaquin

4-4-2

3

SP

Primaquin

3

2-3

Kina

Primaquin

3x2 (7days)

2-3

ResistenChloroquin< 25%

Chloroquin

SPPrimaquin

4-4-2

33

ResistenChloroquin>25%

Kina

Primaquin

3x2 (7)

3

SP

Tetra/doxy

Primaquin

3

4x2/2x1 (7)

3

Resisten

SP >25%

Chloroquin

Tetra/doxyPrimaquin

4-4-2

4x2/2x1 (7)3

Chloroquin

KinaPrimaquin

4-4-2

3x2 (7)3

Resintenboth SP+C

Kina

Tetra/doxy

Primaquin

3x2 (7)

4x2/2x1 (7)

3


CI for pregnancy, infant : Primaquin, SP


41/67

Plasmodium

Condi

tion

1st reg Formula 2nd reg Formula 3rd reg/relaps

Formula

Vivax/ovale

Chloroquin

Primaquin

4-4-2

1 (14)

Kina

Primaquin

3x2 (7)

1

Chloroquin

Primaquin

4 (8-12 week)

3 (8-12 week)ResistenChloroquin < 25%

Chloroquin

Tetra/doxy

Primaquin

4-4-2

4x2/2x1 (7)

1 (14)

ResistenChloroqui

n >25%

Kina

Tetra/doxy

Primaquin

3x2 (7)

4x2/2x1 (7)

1 (14)

Aim Regimen Dose Condition Duration

Prophylaxis Chloroquin 2 tabs/week Temporary visitation 1 week before

4 week after visitation

Permanent visitation Max for 3 months

Doxycycline 1.5 mg/kg/day Only for Chloroquinresistan Falciparum

Max for 3 months



42/67


Late Tx failure

Late clinical failure

In 4th-28th shows sign of severe

malaria

Sexual parasite still (+) or temp

>37.5

Late parasitologic failure

Sexual parasite still (+) in 7th,

14th, 21st, 28th day or temp >37.5

Early Tx failure

H1-3 show sign of severe

malaria

H2 parasite count > H0 H3 parasite count > 25% H0

H3 sexual parasite still (+) or

temp >37.5

Monitoring Malaria Treatment


43/67

Artemicin based combined therapy (ACTs) for

uncomplicated falciparum malaria


43

The following ACTs are recommended:

artemether-lumefantrine

artesunate - amodiaquine

artesunate + mefloquine

artesunate + sulfadoxine-pyrimethamine

dihydroartemisinin piperaquine

The artemisinin derivatives (oral formulations) and

partner medicines of ACTs should not be used asmonotherapy in the treatment of uncomplicated malaria

*Update in 2009 WHO Revised Guidelines


44/67

Uncomplicated malaria treatment


44

P. falciparum malaria

The treatment of uncomplicated P. falciparummalaria is undertaken after diagnosis of malaria by

light microscopy or Dipstick. Patients with positive think-thick blood smears or

dipstick for P. falciparum malaria is treated byblisters of Coartem (artemether

20mg/lumefantrine 120mg). See Table 1 fordetails of prescription.


45/67

Coartem Dosage Schedule


45

Source: WHO, 2007

GSH T d 2010 46


46/67

TOXOPLASMOSIS


Gatot Sugiharto, MD, InternistInternal Medicine Department



47/67

Definition


47

Toxoplasmosis is a zoonotic infection caused by a microscopicparasite Toxoplasma gondi.

These microscopic parasites live inside the cells of humans and

animals

Domestic cat and other Felidae are the definitive host

Vertebrates are the intermediate host

Amphibians, fish, reptiles, All warm-blooded animals

including man


48/67


Toxoplasma - organelles


49/67

Epidemiology


49

Toxoplasmosis is one of the most common infections in the

world.

About 60 million people in the United States get it.

400 to 4000 babies are born with congenital toxoplasmosis

each year.

90% of the babies born with it have no symptoms in infancy.

1 in 10 babies show symptoms when born

85% of babies show symptoms months to years later.


50/67

Transmision


50

By touching or coming into contact with infected cat feces.

By eating contaminated raw or undercooked meat.

By eating contaminated unwashed fruits or vegetables.

By passing it to your unborn baby.

By organ transplant or blood transfusion


51/67

Human/Congenital Transfer


51


52/67


Toxoplasma gondii Life cycle

Oocyst

Tachyzoite

Bradyzoite

T dii lif l ( )


53/67


T. gondii life cycle (cont.)


54/67

Toxoplasmosis Cycle


54


55/67



56/67

Toxoplasmosis in Humans


56

Majority of cases are asymptomatic

Mild fever, sore muscles swollen glands and lymph nodes, similar to

mononucleosis

Immunocompromized individuals are at greater risk. HIV patients, Organ

transplant patients, people on chemotherapy

Pregnant womens fetus are at risk if the mother acquires the infection

during gestation.

CDC estimates 400-4000 cases of congenital toxoplasmosis per year.

Blindness, Hydrocephalus, seizures and mental retardation are common

750 human deaths per year make it the 3rd most common lethal foodpoisoning.

SYMPTOMS OF TOXMOPLASMOSIS IN


57/67

SYMPTOMS OF TOXMOPLASMOSIS IN

CHILDREN


57

Toxoplasmosis can cause premature birth or stillbirth.

In most cases newborns do no show any noticeable symptoms.

Babies born with severe toxoplasmosis usually have:

eye infections, enlarged liver and spleen, jaundice, and

pneumonia, some may die after birth.

Babies who survive having severe toxoplasmosis can develop:

mental retardation, impaired eyesight, cerebral palsy, seizures,and hearing loss.


58/67


Toxoplasmosis Diseases


59/67

CONGENTIAL TOXOPLASMOSIS


59

When a pregnant woman gets the infection during pregnancy

and passes it on to her fetus.

Women who get toxoplasmosis before conception hardly ever

pass the infection during pregnancy.

Babies that get infected during the first trimester show to have

the most severe symptoms.


60/67

DURATION


60

Toxoplasmosis can multiply and spread within a week as soon

as the person gets infected, but it can take weeks or months

before the person gets the symptoms.

Toxoplasmosis is not curable, it stays in the persons body for

life, but will remain inactive causing no harm. (life longimmune protection)

If the persons immune system is not working correctly due to

HIV or cancer therapy, toxoplasmosis can be reactivated and

cause serious harm. (nervous system)


61/67

Diagnosing Toxoplasmosis


61

Detecting oocysts in the stool

Serological TestingELISA tests

IGg and IGm

Titers of IgG can last for years

Titers of IgM usually persist for only 12 weeks

Toxoplasmosis - Diagnosis


62/67


p g

Antibody testing

Antibody testing may be

Followed by prenatal PCRor by CT or MRI scans


63/67

DIAGNOSIS DURING PREGNANCY


63

Ultra sounds can be done to diagnose congenitaltoxoplasmosis (but are not always 100% accurate)

Get blood samples to measure the level of antibodies, which

are the bodies defenses in the immune system.

They have been new tests that can detect the DNA of thegenes that have toxoplasmosis parasites. (these help detect

congenital toxoplasmosis in the fetus)


64/67

TREATMENT DURING PREGNANCY


64

Early diagnosis and prevention can greatly decrease thechances of the baby getting the infection badly, but will not

reduce the chances of transmitting the infection from mother to

child.

If the pregnant woman is believed to have the infection activeand she is in her first trimester of pregnancy : spiramycin.

(Studies show that using spiramycin can reduce the chance of the fetusgetting infected by 60%)

If the fetus is infected, and the mother is 18 weeks gestation or

more : pyrimethamine and sulfadiazine. (to reduce the

newborns symptoms)


65/67


Toxoplasmosis - Treatment

Sulfadiazine and Pyrimethamine (Fansidar)usually given

AIDS patients on antiretrovirals may modify

depending on CD4 counts

Patients allergic to sulfa drugs may take

Clindamycin, Atovaquone, Clarithromycin,

Azithromycin or Dapsone

Leucovorin (Folinic acid) may be given withPyrimethamine if blood counts are lowered


66/67

TREATMENT FOR INFECTED NEWBORNS


66 Babies that are born with toxoplasmosis are also giving

pyrimethamine and sulfadiazine. (first year of life or

sometimes longer)

72% of infected babies had normal intelligence and motor

function in their adolescence, but showed that eye infections

reappeared

Some babies still developed disabilities even after using the

two medications, because of damages done before birth.

In most cases babies are born without symptoms and therefore

do not receive early treatment and developing severe disorders


67/67

PREVENTION OF TOXOPLASMOSIS

67

Do not eat raw or undercooked meat

Wash hands after handling raw meat

Clean utensils, cutting boards, or other things that have come in

contact with raw meats.

Wash and peel fruits and vegetables

Do not empty or clean cats litter boxes (if you do use gloves and

wash hands after cleaning it)

Try to keep your cats indoors to stop them from eating anyanimal that has been infected with parasites.

Use gloves when gardening (soil may have parasites from cats.

tropical infection disease _lecture2

Documents