Tropical Infection Diseases Gatot Sugiharto, MD, Internist Internal Medicine Department Faculty of Medicine, Wijaya Kusuma University Surabaya GSH - Tropmed

GSH - Tropmed - 2010 1

Tropical Infection Diseases

Gatot Sugiharto, MD, InternistInternal Medicine Department

Faculty of Medicine, Wijaya Kusuma University Surabaya


LEPTOSPIROSIS




Introduction• Leptospirosis suatu infeksi anthropo-zoonosis

akut• Sering terjadi pada daerah tropis dan subtropis• Nama lain : Weil Disease, Hemorrhagic

Jaundice, Mud Fever, Swineherd Disease, Canicola Fever, seven-day fever (commonly in Japan), Cane cutter’s disease (in Australia), Rice field Leptospirosis (in Indonesia) , Fort Bragg fever in U.S.Andaman haemorrhagic fever (AHF)


Leptospirosis• Penyakit ini disebabkan oleh bakteri leptospira, • suatu organisme berbentuk spriral dan tipis yang memiliki

daya motilitas yang aktif. • >250 serovars

– L. Interrogans– L. canicola– L. hardjo– L. pomona– L. icterohaemorrhagiae


Pekerjaan yang beresiko terkena:

Petani Penambang Pekerja kanal nelayan


Route of Transmission

• 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





Mechanism of Disease

• Systemic vasculitis occurs, facilitating migration of spirochetes into organs – Hepatocellular damage with jaundice, inc INR– Acute tubular necrosis of kidney– Increased capillary fragility hemorrhage can

occur in any internal organ (pulmonary hemorrhage)


Scanning electron microscopy of a renal tubule from an experimentally infected rat


Clinical Presentation(1)

• Incubation period: 2-20 days (median 11 days)• Two types of leptospirosis:

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

– Icteric leptospirosis (5 - 10% )


Clinical Presentation : early phase (4-7 days)• 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


Clinical Presentation: Late Phase• 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,

arrythmias can follow


Weil’s Disease• 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 involvement and jaundice, can have a mortality rate of 20-40%


Diagnosis• Direct visualization of leptospires in blood (early phase)

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)


Diagnostic Tests for Leptospirosis


Differential diagnosis

• Influenza• Meningitis (encephalitis)• Viral hepatitis• Rickettsiosis• Typhoid fever• Septicemia• Toxoplasmosis• Legionnaire’s disease• Malaria


Treatment• IV penicillin for severe disease• Oral amoxycillin, erythromycin, doxycycline for

mild illness (10-14 d)• Jarisch-Herxheimer reactions have been

reported in patients 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.


Prevention• 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


COMPLICATIONS• Azotemia• Oliguria• Hemorrhage• Purpura• Hemolysis• Gastrointestinal bleeding• Hypoprothrombinemia & thrombocytopenia


Fort Bragg Fever • August 1942, an unusual acute febrile illness (99.8° to 105.6°F) occurred in a group of soldiers at Fort Bragg, N.C.

• Soldiers quartered near a small stream and its tributaries

• 40 patients with sudden onset malaise, mild aches, lumbar pain, severe headaches

• Bilaterally symmetrical rash limited in to the pretibial areas on the fourth day

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


MALARIA




Introduction• The protozoan genus Plasmodium is responsible

for malaria• Four important species: Plasmodium

falciparum, P. vivax, P. malariae and P. ovale• Rapidly fatal and is responsible for most

malaria related deaths : P. Falciparum • Mosquito-transmitted malaria is the greatest

public health problem in large parts of the world with more than 500 million clinical cases and over 3 million deaths every year


Epidemiology• 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 traveler’s disease and

imported into any country.

• A rural disease due to the presence of the

female Anopheles mosquito vector.


Tranmission

• Transmision : by an infected female Anopheles biting

• Others : blood transfusion or congenitally feto-maternal

• Malaria-carrying Anopheles bite only near dusk and dawn.




Clinical manifestation on life cycle.

• 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 and anemia

• P falciparum may induce kidney failure, coma and death.


Chronic & relapse• All infected liver cells parasitized with P. falciparum

and P. malariae rupture and release merozoites at about the same time.

• In contrast, P. vivax and P. ovale have two exoerythrocytic forms. The primary type develops, causes liver cell rupture, and releases merozoites. The other form, which develops concurrently, is known as the hypnozoite.

• Sporozoites that enter liver cells differentiate into nonsexual hypnozoites that remain dormant for weeks, or even years.

• The hypnozoites activate and undergo exoerythrocytic schizogony, forming a wave of merozoites that cause a relapse.


Clinical symptoms(1)

• Cough, fatigue, malaise, arthralgia, myalgia, and paroxysm 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 hours belongs to malariae infections.

• The 48 hour fever is called tertian (occurs every 3rd day) day 1 : fever, day 2 : no fever, day 3 : fever & so on. The 72 hour fever is called quartan (returns on every 4th day)


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

• Blackwater fever : hemoglobinuria with the passage of dark-colored urine

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

• Profound hypoglycemia : young children and pregnant women.

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

Clinical symptoms(2)


Severe malaria• 1. Cerebral malaria

2. Acute renal failure 3. ARDS4. Severe anaemia (Hb < 5g%)5. DIC6. Haemoglobinuria7. Hypotension, Shock8. Hyperparasitemia9. Repeated seizures10. Hyperpyrexia11. Haemolysis (Sr bil. >3 mg%)


Cerebral malaria• The principal signs : seizures and

unconsciousness, preceded by a severe headache.

• Neurologic examination : contracted or unequal pupils, a Babinski sign, and absent or exaggerated deep tendon reflexes

• Cerebrospinal fluid examination : increased pressure, increased protein, and minimal or no pleocytosis.

• High fever, 41° to 42°C, with hot, dry skin may occur.


ARDS• Often fatal, develop rapidly,

associated with excessive intravenous fluid therapy.

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

• Chest X-rays : increased bronchovascular markings.


Confirmed Diagnosis of Malaria• 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)




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

much pigment. Shown are examples of trophozoites (A–F), a schizont (G), and a gametocyte (H). Scale bars = 5 μm.


Malaria Therapy

Plasmodium

Condition

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

Formula

Unknown

Non pregnant

ChloroquinPrimaquin

4-4-23

KinaPrimaquin

3x2 (7)2-3

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

Falci parum

Sensitive Chloroquin

ChloroquinPrimaquin

4-4-23

SPPrimaquin

32-3

KinaPrimaquin

3x2 (7days)2-3

Resisten Chloroquin < 25%

ChloroquinSPPrimaquin

4-4-233

Resisten Chloroquin >25%

KinaPrimaquin

3x2 (7)3

SPTetra/doxyPrimaquin

34x2/2x1 (7)3

Resisten SP >25%

ChloroquinTetra/doxyPrimaquin

4-4-24x2/2x1 (7)3

ChloroquinKinaPrimaquin

4-4-23x2 (7)3

Resinten both SP+C

KinaTetra/doxyPrimaquin

3x2 (7)4x2/2x1 (7)3

CI for pregnancy, infant : Primaquin, SP


Plasmodium

Condition

1st reg Formula 2nd reg Formula

3rd reg/ relaps

Formula

Vivax/ ovale

ChloroquinPrimaquin

4-4-21 (14)

KinaPrimaquin

3x2 (7)1

ChloroquinPrimaquin

4 (8-12 week)3 (8-12 week)

Resisten Chloroquin < 25%

ChloroquinTetra/doxyPrimaquin

4-4-24x2/2x1 (7)1 (14)

Resisten Chloroquin >25%

KinaTetra/doxyPrimaquin

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 Chloroquin resistan Falciparum

Max for 3 months


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


Artemicin based combined therapy (ACTs) for uncomplicated falciparum malaria

• 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 as monotherapy in the treatment of uncomplicated malaria

*Update in 2009 WHO Revised Guidelines*Update in 2009 WHO Revised Guidelines


Uncomplicated malaria treatmentP. falciparum malaria• The treatment of uncomplicated P. falciparum

malaria 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 by blisters of Coartem® (artemether 20mg/lumefantrine 120mg). See Table 1 for details of prescription.


Coartem® Dosage Schedule

Source: WHO, 2007


TOXOPLASMOSIS




Definition• Toxoplasmosis is a zoonotic infection caused by a

microscopic parasite 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


Toxoplasma - organelles


Epidemiology

• 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.


Transmision• 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


Human/Congenital Transfer


Toxoplasma gondii – Life cycle

Oocyst

Tachyzoite

Bradyzoite


T. gondii – life cycle (cont.)


Toxoplasmosis Cycle



Toxoplasmosis in Humans• 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 women’s 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

food poisoning.


SYMPTOMS OF TOXMOPLASMOSIS IN CHILDREN

• 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.


Toxoplasmosis Diseases


CONGENTIAL TOXOPLASMOSIS

• 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.


DURATION

• 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 person’s body for life, but will remain inactive causing no harm. (life long immune protection)

• If the person’s immune system is not working correctly due to HIV or cancer therapy, toxoplasmosis can be reactivated and cause serious harm. (nervous system)


Diagnosing Toxoplasmosis• Detecting oocysts in the stool• Serological Testing—ELISA tests• IGg and IGm• Titers of IgG can last for years• Titers of IgM usually persist for only 12 weeks


Toxoplasmosis - Diagnosis

Antibody testing

Antibody testing may be Followed by prenatal PCR or by CT or MRI scans


DIAGNOSIS DURING PREGNANCY

• Ultra sounds can be done to diagnose congenital toxoplasmosis (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 the genes that have toxoplasmosis parasites. (these help detect congenital toxoplasmosis in the fetus)


TREATMENT DURING PREGNANCY

• Early diagnosis and prevention can greatly decrease the chances 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 active and she is in her first trimester of pregnancy : spiramycin. (Studies show that using spiramycin can reduce the chance of the fetus getting infected by 60%)

• If the fetus is infected, and the mother is 18 weeks gestation or more : pyrimethamine and sulfadiazine. (to reduce the newborn’s symptoms)


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 with Pyrimethamine if blood counts are lowered


TREATMENT FOR INFECTED NEWBORNS

• 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


PREVENTION OF TOXOPLASMOSIS

• 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 cat’s litter boxes (if you

do use gloves and wash hands after cleaning it)• Try to keep your cats indoors to stop them from

eating any animal that has been infected with parasites.

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

Documents

Tropical Infection Diseases Gatot Sugiharto, MD, Internist Internal Medicine Department Faculty of Medicine, Wijaya Kusuma University Surabaya GSH - Tropmed