•1480 bagian XVII ◆ Penyakit menular

death. The onset is usually abrupt, and the illness tends to follow a biphasic course ( Fig.
Bab 220 220-1 ). After an incubation period of 7-12 days, there is an initial or septicemic phase lasting
2-7 days, during which leptospires can be isolated from the blood, cerebrospinal fluid

Leptospira
(CSF), and other tissues. This phase may be followed by a brief period of well- being
before onset of a second symptomatic immune or leptospiruric phase. This phase is
associated with the appearance of circulating immunoglobulin M antibody,
H. Dele Davies dan Kari A. Simonsen disappearance of organisms from the blood and CSF, and appearance of signs and
symptoms associated with localization of leptospires in the tissues. Despite the
presence of circu- lating antibody, leptospires can persist in the kidney, urine, and
Leptospirosis adalah zoonosis umum dan luas yang disebabkan oleh aerobik, spirochetes aqueous humor. The immune phase can last for several weeks. Symp- tomatic
motil dari genus Leptospira. infection may be anicteric or icteric.

ETIOLOGI
leptospira patogen milik 9 spesies, yang mencakup lebih dari 300 serovars antigen yang
berbeda. Sebuah serovar tunggal dapat menghasilkan berbagai sindrom yang berbeda,
dan manifestasi klinis tunggal dapat disebabkan oleh beberapa serotipe.
EPIDEMIOLOGI
Most human cases of leptospirosis occur in tropical and subtropical countries, but the
distribution is worldwide. Leptospires survive for days to weeks in warm and damp
environmental conditions, including water and moist soil. In the United States, Hawaii
reports approxi- mately 50% of all cases, with Pacific coastal states and Southern
states having higher incidence than the remainder of the country. Leptospires infect
many species of animals, including rats, mice, moles, livestock (such as cattle, goats,
sheep, horses, and pigs), wild mammals like rac- coons or opossums, and domestic
dogs. Infected animals excrete spi- rochetes in their urine for prolonged periods.
Worldwide, most human cases result from occupational exposure to water or soil
contaminated with rat urine; however, the major animal reservoir in the United States
is the dog. Groups at high risk for leptospirosis include persons exposed
occupationally or recreationally to contaminated soil, water, or infected animals,
including agricultural workers, veterinarians, abattoir workers, meat inspectors, rodent
control workers, laboratory workers, and military personnel. Transmission via animal
bites and directly from person to person has been rarely reported.
Anicteric Leptospirosis
The septicemic phase of anicteric leptospirosis has an abrupt onset with flu-like
symptoms of fever, shaking chills, lethargy, severe head- ache, malaise, nausea,
vomiting, and severe debilitating myalgia most prominent in the lower extremities,
lumbosacral spine, and abdomen. Bradycardia and hypotension can occur, but
circulatory collapse is uncommon. Conjunctival suffusion with photophobia and orbital
pain (in the absence of chemosis and purulent exudate), generalized lymph-
adenopathy, and hepatosplenomegaly may also be present. A transient (<24 hr)
erythematous maculopapular, urticarial, petechial, purpuric, or desquamating rash
occurs in 10% of cases. Rarer manifestations include pharyngitis, pneumonitis,
arthritis, carditis, cholecystitis, and orchitis. The second or immune phase can follow a
brief asymptom- atic interlude and is characterized by recurrence of fever and aseptic
meningitis. Although 80% of infected children have abnormal CSF profiles, only 50%
have clinical meningeal manifestations. CSF abnor- malities include a modest elevation
in pressure, pleocytosis with early polymorphonuclear leukocytosis followed by
mononuclear predomi- nance rarely exceeding 500 cells/ µ L, normal or slightly elevated
protein levels, and normal glucose values. Encephalitis, cranial and peripheral
neuropathies, papilledema, and paralysis are uncommon. A self- limited unilateral or
bilateral uveitis can occur during this phase, rarely resulting in permanent visual
impairment. Central nervous system symptoms usually resolve spontaneously within 1
wk, with almost no mortality.

PATHOLOGY AND PATHOGENESIS

Leptospires enter humans through mucous membranes (primarily eyes, nose, and
mouth) or abraded skin or by ingestion of contami- nated water. After penetration, they
circulate in the bloodstream to all body organs, causing endothelial lining damage of
small blood vessels with secondary ischemic damage to end organs.
CLINICAL MANIFESTATIONS
The spectrum of human leptospirosis ranges from asymptomatic infec- tion (most
cases) to severe disease with multiorgan dysfunction and
Icteric Leptospirosis (Weil Syndrome)
Weil syndrome is a rare (<10% of cases) severe form of leptospirosis seen more
commonly in adults (>30 yr) than in children. The initial manifestations are similar to
those described for anicteric leptospirosis. The immune phase, however, is
characterized by jaundice, renal failure, thrombocytopenia, and, in fulminant cases,
hemorrhage and cardio- vascular collapse. Hepatic involvement leads to right upper
quadrant pain, hepatomegaly, direct and indirect hyperbilirubinemia, and

Anicteric Leptospirosis Icteric Leptospirosis (Weil

Syndrome)

First Stage 3-7 Second Stage 0 Second Stage

days days–1 mo 10-30 days
(Septicemic) (Immune) (Immune)

(Septicemic)
Demam

First Stage 3-7 days

failure Myocarditis
Hemorrhage Renal
Myalgia Meningitis Jaundice
Headache Uveitis
Abdominal Rash
pain Fever
penting
Temuan
klinis

Vomiting
Conjunctival
suffusion
Fever Figure•220-1 Stages of anicteric and icteric leptospirosis.
Blood Blood Correlation between clinical findings and presence of lepto- spires in body
Menyajikan

fluids. CSF, cerebrospinal fluid. ( Reprinted with permission from Feigin RD,
leptospira

CSF CSF
Anderson DC: Human lep- tospirosis, CRC Crit Rev Clin Lab Sci 5:413–467,
Urine Urine
1975. Copy- right CRC Press, Inc, Boca Raton, FL.)
modestly elevated serum levels of hepatic enzymes. Liver function usually returns to
normal after recovery. All patients have abnormal findings on urinalysis (hematuria,
proteinuria, and casts), and azote- mia is common, often associated with oliguria or
anuria. Acute kidney failure occurs in 16-40% of cases and is the principal cause of
death. Abnormal electrocardiograms are present in 90% of cases, but conges- tive
heart failure is uncommon. Transient thrombocytopenia occurs in
exposure to, or handling of infected urine. Leptospirosis was success- fully prevented
in American soldiers stationed in the tropics by admin- istering prophylactic
doxycycline (200 mg PO once a week). This approach may be similarly effective for
travelers to highly endemic areas for short periods; however, there are no specific
pediatric data to support any prophylaxis regimen.

> 50% of cases. Rarely, hemorrhagic manifestations occur, including epistaxis, Bibliography is available at Expert Consult.
hemoptysis, and pulmonary, gastrointestinal, and adrenal hemorrhage. The mortality
rate is 5-15%.

DIAGNOSIS
Leptospirosis should be considered in the differential diagnosis of acute flu-like
febrile illnesses with a history of direct contact with animals or with soil or water
contaminated with animal urine. This disease may be difficult to distinguish
clinically from dengue or malaria.

The diagnosis is most often confirmed by serologic testing and less often by isolation of
the infecting organism from clinical specimens. The “gold-standard” diagnostic method is
the microscopic agglutina- tion test, assay serogrup-tertentu menggunakan hidup
antigen suspensi serovars leptospiral dan-lapangan gelap mikroskop untuk aglutinasi.
Peningkatan 4 kali lipat atau lebih besar dalam titer paired sera menegaskan diagnosis.
Aglutinin biasanya muncul pada hari ke-12 dari penyakit dan mencapai titer maksimal oleh
wk 3. titer rendah dapat bertahan selama bertahun-tahun. Sekitar 10% dari orang yang
terinfeksi tidak memiliki tinins agglu- terdeteksi, mungkin karena tersedia antisera tidak
mengidentifikasi semua Lepto- spira serotipe. Selain itu, metode immunosorbent assay
enzim-linked, lateks aglutinasi, dan immunochromatography yang com- mercially tersedia,
dan DNA polimerase diagnostik reaksi berantai telah dikembangkan tetapi tidak dalam
penggunaan klinis umum. Sebaliknya Phase- dan darkfield mikroskop tidak peka untuk
spirochete tion detec-, tetapi organisme dapat diidentifikasi dengan menggunakan noda
perak Warthin-Starry atau pewarnaan antibodi fluoresen jaringan atau cairan tubuh. Tidak
seperti spirochetes patogen lainnya, leptospira dapat pulih dari darah atau CSF selama 1
10 hari sakit dan dari urin setelah 2 minggu oleh budaya berulang inokulum kecil (yaitu, 1
tetes darah atau CSF dalam 5 ml medium) di tersedia secara komersial Media selektif.
Namun, inokulum dalam spesimen klinis kecil, dan pertumbuhan dapat berlangsung hingga
13 minggu.

PENGOBATAN
Meskipun sensitivitas in vitro Leptospira terhadap penisilin dan tetrasiklin, efektivitas
antibiotik dalam mengobati leptospirosis manusia tidak jelas karena tingkat pemulihan
spontan alami yang tinggi. Beberapa studi menunjukkan bahwa memulai pengobatan
sebelum hari ke-7 memperpendek perjalanan klinis dan mengurangi keparahan infeksi;
sehingga pengobatan dengan penisilin G, sefotaksim, atau doksisiklin (pada anak-anak

≥ 8 tahun usia) harus dilembagakan awal ketika diagnosis dicurigai. Parenteral

penisilin G (6-8 juta unit / m 2 / day divided every 4 hr IV for 7 days) is recommended,
with doxycycline 2 mg/kg/day divided in 2 doses with maximum of 100 mg twice
daily as an alternative for patients allergic to penicillin. Azithromycin was evaluated
in a ran- domized, nonblinded clinical trial and shown to be as effective as
doxycycline and can be used as an alternative in patients for whom doxycycline is
contraindicated. In severe illness, supportive care with specific attention given to
cardiopulmonary status, renal function, coagulopathy, and fluid and electrolyte
balance is warranted.

PREVENTION
Prevention of human leptospirosis infection is facilitated by instituting rodent control
measures and avoiding contaminated water and soil. Immunization of livestock and
domestic dogs is recommended as a means of reducing animal reservoirs. Attempts at
a human vaccine have been challenging, and the diversity of Leptospira serovars and
their geographic distributions are important considerations in vaccine design.
Protective clothing (i.e., boots, gloves, and goggles) should be worn by persons at risk
for occupational exposure. In hospital settings, standard precautions are
recommended, with contact precautions for
 Chapter•220 ◆ Leptospira •1481.e1

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