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Tropical Infection Diseases
Gatot Sugiharto, MD, InternistInternal Medicine Department
Faculty of Medicine, Wijaya Kusuma University Surabaya
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LEPTOSPIROSIS
Gatot Sugiharto, MD, InternistInternal Medicine Department
Faculty of Medicine, Wijaya Kusuma University Surabaya
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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)
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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
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Pekerjaan yang beresiko terkena:
Petani Penambang Pekerja kanal nelayan
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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
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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)
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Scanning electron microscopy of a renal tubule from an experimentally infected rat
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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% )
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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
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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
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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%
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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)
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Diagnostic Tests for Leptospirosis
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Differential diagnosis
• Influenza• Meningitis (encephalitis)• Viral hepatitis• Rickettsiosis• Typhoid fever• Septicemia• Toxoplasmosis• Legionnaire’s disease• Malaria
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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.
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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
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COMPLICATIONS• Azotemia• Oliguria• Hemorrhage• Purpura• Hemolysis• Gastrointestinal bleeding• Hypoprothrombinemia & thrombocytopenia
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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
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MALARIA
Gatot Sugiharto, MD, InternistInternal Medicine Department
Faculty of Medicine, Wijaya Kusuma University Surabaya
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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
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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.
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Tranmission
• Transmision : by an infected female Anopheles biting
• Others : blood transfusion or congenitally feto-maternal
• Malaria-carrying Anopheles bite only near dusk and dawn.
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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.
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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.
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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)
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• 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)
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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%)
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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.
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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.
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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)
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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.
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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
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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
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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
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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
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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.
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Coartem® Dosage Schedule
Source: WHO, 2007
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TOXOPLASMOSIS
Gatot Sugiharto, MD, InternistInternal Medicine Department
Faculty of Medicine, Wijaya Kusuma University Surabaya
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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
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Toxoplasma - organelles
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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.
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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
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Human/Congenital Transfer
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Toxoplasma gondii – Life cycle
Oocyst
Tachyzoite
Bradyzoite
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T. gondii – life cycle (cont.)
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Toxoplasmosis Cycle
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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.
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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.
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Toxoplasmosis Diseases
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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.
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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)
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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
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Toxoplasmosis - Diagnosis
Antibody testing
Antibody testing may be Followed by prenatal PCR or by CT or MRI scans
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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)
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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)
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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
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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
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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.
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