Transcript Tropical Infection Diseases

Tropical Infection Diseases
Gatot Sugiharto, MD, Internist
Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma
University Surabaya
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LEPTOSPIROSIS
Gatot Sugiharto, MD, Internist
Internal 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:
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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 ratinfected 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,
elevated WBC
GSHproteinuria,
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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
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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
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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, Internist
Internal 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 fetomaternal
• 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.
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Severe malaria
• 1. Cerebral malaria
2. Acute renal failure
3. ARDS
4. Severe anaemia (Hb < 5g%)
5. DIC
6. Haemoglobinuria
7. Hypotension, Shock
8. Hyperparasitemia
9. Repeated seizures
10. Hyperpyrexia
11. 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 nonproductive 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
Plasmo
dium
Un
known
Falci
parum
Condition
1st reg
Formula
2nd reg
Formula
Non
pregnant
Chloroquin
Primaquin
4-4-2
3
Kina
Primaquin
3x2 (7)
2-3
Pregnant
Chloroquin
4-4-2
Kina
3x2 (7)
Sensitive
Chloroquin
Chloroquin
Primaquin
4-4-2
3
SP
Primaquin
3
2-3
Resisten
Chloroquin
< 25%
Chloroquin
SP
Primaquin
4-4-2
3
3
Resisten
Chloroquin
>25%
Kina
Primaquin
3x2 (7)
3
SP
Tetra/doxy
Primaquin
3
4x2/2x1 (7)
3
Resisten
SP >25%
Chloroquin
Tetra/doxy
Primaquin
4-4-2
4x2/2x1 (7)
3
Chloroquin
Kina
Primaquin
4-4-2
3x2 (7)
3
Resinten
both SP+C
Kina
Tetra/doxy
Primaquin
3x2 (7)
4x2/2x1 (7)
3
3rd reg/
relaps
Formula
Kina
Primaquin
3x2 (7days)
2-3
CI for pregnancy, infant : Primaquin, SP
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Plasmo
dium
Condi
tion
Vivax/
ovale
1st reg
Formula
2nd reg
Chloroquin
Primaquin
4-4-2
1 (14)
Resisten
Chloroqui
n < 25%
Chloroquin
Tetra/doxy
Primaquin
4-4-2
4x2/2x1 (7)
1 (14)
Resisten
Chloroqui
n >25%
Kina
Tetra/doxy
Primaquin
3x2 (7)
4x2/2x1 (7)
1 (14)
Aim
Prophylaxis
Regimen
Chloroquin
Doxycycline
Kina
Primaquin
Dose
Formula
3rd reg/
relaps
Formula
3x2 (7)
1
Chloroquin
Primaquin
4 (8-12 week)
3 (8-12 week)
Condition
2 tabs/week
1.5 mg/kg/day
Duration
Temporary visitation
1 week before –
4 week after visitation
Permanent visitation
Max for 3 months
Only for Chloroquin
resistan Falciparum
Max for 3 months
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Monitoring Malaria Treatment
Early Tx failure
Late 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
• 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
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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
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Uncomplicated malaria treatment
P. 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, Internist
Internal 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
Bradyzoite
Tachyzoite
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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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•
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•
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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 may be
Followed by prenatal PCR
or by CT or MRI scans
Antibody testing
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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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