Leptospirosis

LEPTOSPIROSIS
zoonosis
ubiquitos distribution
caused by pathogenic species of leptospira
extremely wide spectrum
(subclinical infectionmultiorgan infection high mortality)

Characteristics

Tightly coiled aerobic spirochete

the cell have pointed ends, bent into a hook
obtain energy by -oxidation of fatty acids
can be grown in medium with rabbit serum
(Fletchers medium)

Leptospira
Spirochaeta
Famili

leptospiraeae
Genus leptospira
Spesies:
1. L. interrogans (patogen)
20 serogroup, 200 serovars
2. L. biflexa (free-living, saprophyt)

Transmission source

Rodent (rats)
pig
cow
goat
horse
dog
cat
insect
bird

Cara penularan
kontak

dengan bahan terkontaminasi air

seni hewan penderita leptospirosis
air, tanah, lumpur, tanaman
Invasi
mukosa mata, hidung, kulit lecet, saluran
cerna (makanan terkontaminasi)

 Human

rare
Why ?

to human transmission is very

Pathology
Vasculitis
Endothelial

damage
Inflammatory infiltrates
(monocytic cels, plasma cells,
histiocytes, netrophils)
Histopathology most marked in
liver , kidneys, heart, lungs

Pathology, continued

Liver: may be intrahepatic cholestasis

Kidneys: interstitial nephritis
Heart: interstitial myocarditis, petechial
hemorrhages (particularly epicardium),
mononuclear infiltration in epicardium,
pericardial effusion, coronary arteritis
Lungs: pulmonary congestion and hemorrhage
Skeletal muscles (particularly of legs): focal
necrosis, infiltration of cells
Brain: perivascular cuffing

PATHOGENESIS
Toxin

production
Attachment
Immune mechanism
Surface proteins
immunity

Toxin production
Endotoxic

activity
Hemolysin (several serovars)
Cytotoxic activity

Attachment
To

epitelial cells
Phagocytosed by macrophages
(presence of specific antibody)
Are not killed by neutrophils
LPS stimulates adherence of neutrophils
to endothelial cells and platelets
aggregation thrombocytopenia

Immune Mechanisms
2nd

stage : immune phase

Disappearance of microorganism from
bloodstream, appearance of antibody
Clinical severity : out of proportion of PA
findings.
Immune mediated disease: influence
severity
Immune complex: inflammation

Pathophysiology

Kidney: interstitial nephritis, tubuler necrosis,

impaired capillary permeability
Liver: centrilobuler necrosis, Kupffer cell
proliferation, hepatocelluler dysfunction
Pulmonary: secondary to alveolar and
interstitial vascular damage hemorrhage
Skeletal muscle: secondary to edema,
myofibril vacuolization, and damage to vessels
Damage to vascular system can result in
capillary leakage, hypovolemia, and shock

Manifestasi klinis

Periode inkubasi : 2-20 hari (kisaran 10 hari)

Perjalanan penyakit dengan gambaran bifasik:
Fase septikemia (4-7 hari)
leptospira di darah, CSF, dan sebagian besar
jaringan (vaskulitis ekstensif)
Fase Imun (10-30 hari)
leptospira hilang dari darah dan CSF
menetap intermiten pada urin dan
humor aqueos (manifestasi multisistem)

Anicteric leptospirosis (90% cases)

Septic phase (3-7 days)

abrupt onset, high fever and chills
muscle aches, commonly involving muscle of calf
headache (retrobulbar pain) and prostration
abdominal pain, nausea, vomitus, diarrhea
conjunctival suffusion
Immune phase (0-30 days), may or may not occur
aseptic meningitis
conjunctival hemorrhage
rash
cough, blood-stained sputum, pulmonary infiltrates
acalculous cholecystitis (commonly in children)

Icteric leptospirosis (5-10% cases)

Septic phase (3-7 days)

similar to anicteric form
Immune phase (7-30 days)
reddish jaundice (jaundice+conjunctival+cutaneous
vasculites)
renal failure: oliguria or anuria
increased BUN & creatinine
normal/decreased potassium
hemorragic manifestation
epistaxis, petechial rash, g i/pulmonary hem.
hepatomagaly (splenomegaly is rare)

Leptospirosis ikterik &

anikterik
Sindroma,
Fase
Gambaran klinik

Laboratorium

Leptospirosis anikterik
Fase leptospiremia (3-7 hari)

Demam tinggi, nyeri

kepala, mialgia, nyeri
perut, mual, muntah,
conjunctival suffusion

Darah, LCS

Fase imun (3-30 hari)

Demam ringan, nyeri

kepala, muntah,
meningitis aseptik

Urin

Demam, nyeri kepala,

mialgia, ikterik, gagal
ginjal, hipotensi,
manifestasi perdarahan,
pneumonitis hemoragik,
lekositosis

Darah, LCS (mgg I),

urin (mgg II)

Leptospirosis ikterik
Fase leptospiremia dan fase
imun (sering overlapping)

Antara fase leptospiremia dengan fase imun terdapat periode asimtomatik (1-3 hr). Dimodifikasi
dari Farr RW, 1995

Stages of icteric and anicteric leptospirosis.

Diagnosis
Etiological

diagnosis
Serologic diagnosis
Laboratory findings

Etiological diagnosis
Darkfield

examination
blood or CSF (1st week)
urine (after 1st week)
Cultures
blood or CSF (1st week)
urin (2nd week)

Serologic diagnosis

Microscopic agglutination
2 blood specimen must be serologically
compared in an interval of 2 weeks
initial titer of 1:100 or at least 4 fold rise in
antibody titer confirm the diagnosis
Macroscopic slide agglutination
ELISA, Dot-ELISA
detect leptospiral IgM antibodies

Darkfield microscopy of Leptospira.

Scanning electron micrograph

Leptospira interrogans serotype icterohaemorrhagiae. Silver staining of

organisms grown in culture. Notice the tightly coiled body with hooked ends.

Diagnosis by
CDC of Leptospirosis Report
Definitif
ditemukan leptospira dari spesimen apapun
(darah, jaringan/cairan tubuh)
atau
gx klinik + serologi (+)
Presumtif
kriteria dx WHO 1982
(Faine Salomon)

Laboratory findings

Total WBC count may be slightly elevated with neutrophilia

Increased erythrocyte sedimentation rate (about 60 mm)
Thrombocytopenia
Increased BUN & serum creatinine
Normo/hypo/hyperkalemia
Proteinuria, hematuria, casts
Increased in serum bilirubin levels
ALP moderately elevated, as well as GOT & GPT
Marked elevation in serum CK
MB variant (in case of myocarditis)

Treatment

Mild (flu like symptoms): symptomatic treatment.

More severe anicteric : hospital admission, close
observation.
Severe headache: lumbar puncture.
Azotemia prerenal: rehydration, sometimes need dialysis.
Antibiotic:
penicilline iv 6 MU/day (7 days)
oxytetracycline
doxycycline 2x100 mg (7 days)

Pengobatan & Profilaksis

Leptospirosis
Derajat penyakit
Leptospirosis ringan

Penatalaksanaan
1.
2.
3.
4.

Leptospirosis berat

1.
2.
3.
4.
5.
6.

Chemoprophylaxis

Regimen

Antipiretik
Cairan/nutrisi adekuat
Antibiotika
Penanganan komplikasi

Doxycycline, 100 mg 2x1, atau

Ampicillin, 500-750 mg 4x1, atau
Amoxicillin, 500 mg 4x1

Antipiretik
Nutrisi dan cairan
Antibiotika-antileptospiral
Penanganan gagal ginjal
Penanganan infeksi sekunder
Penanganan khusus

Penicillin G, 1.5 jt unit IV /6 j, atau

Ampicillin, 1 g IV /6 j, atau
Amoxicillin, 1 g IV /6 j, atau
Erythromycin, 500 mg IV /6 j

a.
b.
c.
d.
e.
f.

Hiperkalemia
Asidosis metabolik
Hipertensi
Gagal jantung
Kejang
Perdarahan
Doxycycline, 200 mg 1x seminggu

Antibiotik

Benzyl (cristal) penicillin

efektif bila diberikan pada hari ke-4-5 sakit, sebelum ikterik
muncul
Dosis: 6-8 MU iv (5-7 hari)
Cara lain:
kombinasi Cristalline dan PP 4-5 MU im
(5-6 hari)
Alergi
Tetrasiklin (KI RF)
250 mg/8 jam im/iv
250-500/6 jam po (6 hari)
Erythromycine
250 mg/6 jam (5 hari)

Komplikasi

Ginjal: gagal ginjal kematian

Mata: perdarahan
Hati: ikterik berat
Jantung: aritmia, dilatasi jantung, DC
Paru-paru: pneumonitis hemoragik (batuk darah, nyeri
dada, respiratory distress, cyanosis)
Vascular damage:perdarahan saluran nafas, saluran
cerna, ginjal, genital
Kehamilan abortus, lahir mati, prematur, bayi cacat.

Gagal ginjal
Mekanisme:

invasi langsung
reaksi imunologi
reaksi nonspesifik iskemia
nekrosis GGA

Gagal ginjal (Acute Tubuler

Necrosis)
Histopatologi:

nekrosis dan deskuamasi

Rasio osmolaritas urin dan plasma
Tipe : oliguri dan non oliguri
Px buruk:
tipe oliguri, oliguri lama, respon diuresis
lambat, rasio ur:kr meningkat

Manajemen

Suportif:
hidrasi
monitor elektrolit dan uop/24 jam
diuretik mengubah oliguri mjd poliuri
dopamine
Dialisis
hiperkatabolik
hiperkalemia
asidosis metabolik
perdarahan

Prevention

Antimicrobial prevention
doxycicline 200 mg/week (under risk exposure)
doxycicline 100 mg for 7 days (known exposure)
Vaccination of domestic mammals, but cant avoid the
infection and the shedding of L.interrogans in the urine
and the consequent human infection
Effective rats control
Appropriated occupational wear (boots, gloves)
Desinfection of contaminated work areas reduce
incidence of disease

Immunization
Largely

humoral
Relatively serovar specific
Human vaccine havent been applied
widely.

 Kenapa

terapi penicilline masih diberikan

pada saat penderita sudah masuk fase
imun?