Oleh Bagian Ilmu Penyakit DalamFK Universitas Islam Sultang Agung

Semarang2006

LeptospirosisLeptospirosis•

acute febrile illness occurring in humans & animals the most widespread zoonosis in the world one of the emerging infectious diseases an often overlooked disease Caused by multiple species of leptospira

Leptospirosis outbreaks after the big flood

of Jakarta (Feb.- March 2002) Nine (33%) of 27 cases died.

Living areas of severe lLiving areas of severe leptospirosis cases eptospirosis cases in Semarang in Semarang mmunicipality 1990unicipality 1990 & 1991 & 1991

• 1990 1991

Banjirkanal-Barat River`s flood (January, 1990) killed >100 people. 12 adults (black spots) who were living along the river banks admitted to Dr.Kariadi hospital due to severe leptospirosis

BacteriologyBacteriologyCausative organism: Leptospira

Aerobic, coiled, motile spirochete with hooked ends

Size Ø 0,1 um, length 6 – 20 um.

Pathogenic for numerous wild & domestic animals: rats, cattle and dogs

Genus Leptospira: 2 species

Leptospira interrogans (pathogenic)Leptospira biflexa (saprophytic)

24 serogroups & > 240 serovars

Leptospira serovars / strainsLeptospira serovars / strains

More than 240 serovars have been identified in the world

Some serovars / strains has been named with common Indonesian name (people or cities) such as:

sarmin, salinem, paidjan, sentot

hardjoprajitno, rachmat, djasiman

medanensis, samaranga, bataviae,

javanica, bindjei, bangkinang etc.

Severe leptospirosis cases admitted to Dr. Kariadi Hospital during 10 years

27

33

25

19

39

21

28

3530 29

051015202530354045

Soeharyo Hadisaputro, Wahana Medik 1991; 11:4-11

1981 82 83 84 85 86 87 88 89 1990

HIGHEST INCIDENCE 2000HIGHEST INCIDENCE 2000

Country Region IncidencePer 100.000

Mortality(%)

India Andaman 50.0 21.0Thailand 23.1 2.5India Chennai 10.5 -France Ile de la

Reunion6.0 -

India Kerala 5.6 10.1USA Hawaii 4.0 0Brazil Sao Paulo 1.9 12.3Uruguay 1.6 100Indonesia Semarang 1.2 16.7

EPIDEMIOLOGY: transmission & risk EPIDEMIOLOGY: transmission & risk factors factors

Risk factors for transmission of leptospirosis

Walking in flooded streets or stagnant water Living in flood prone areas Personal hygiene, wounds Large rat population Recreational exposures (water sports, triathlon) Occupational risk factors

EPIDEMIOLOGY: EPIDEMIOLOGY: Occupational risk factorsOccupational risk factors

Clinical and epidemiological studies of Leptospirosis in Semarang Phase I : Oct. 2002-March 2004

Environmental & socio-economic risk factors

Frequency (%)

High population of rats 95%Living in coastal part of Semarang 79%Bad flow of water in the gutters of the house

68%

Living in slum districts with bad housing

65%

Living in flood prone areas 56%Walking through stagnant water 56%Unemployed person 34%Low level labours 14%

Possible risk factors for Leptospirosis

Note: Risk factors mostly overlapped

Penetration through skin, conjunctiva or mucous membranes

Multiplication of organisms and dissemination via the bloodstream

Damage to endothelium of small blood vessels, vasculitis, and inflammatory infiltrates Haemorrhage Muscle Subcutaneous tissue

Pathological changes in body organs / tissues Liver Changes are nonspecific, but if severe, may include slight centrilobular necrosis. Hypertrophy & hyperplasia of Kupffer cells.

Intralobular biliary stasis may occur Kidney Renal lessions include tubular necrosis, cortical ischaemia and medullary congestion Renal changes may resemble interstitial nephritis

Lungs Pulmonary congestion may accompany pulmonary haemorrhage

Pathology/pathogenesis

Anicteric Leptospirosis

First Stage 3-7 days

(SEPTICEMIC)

Fever

Second Stage 0 days - 1 month

(IMMUNE)

Myalgia Headache

Abdominal pain

Vomiting Conjunctival

suffusion

Meningitis Uveitis Rash

Jaundice Hemorrhage Renal failure Myocarditis

Important Clinical Findings

Leptospires Present

Blood

CSF

Urine

Blood

CSF

Urine

Icteric Leptospirosis (Weil's Syndrome)

First Stage 3-7 days

(SEPTICEMIC)

Second Stage 10-30 days (IMMUNE)

Clinical progression: two stages (biphasic)

Feigin et al. 1975

Clinical features Icteric

(Weil`s Disease) Anicteric

Jaundice + + + –Conjunctival suffusion + + + Leucocytosis + + + ± Hemorrhage + + ± Renal failure + + ± Aseptic meningitis ± + +Disturbance of consciousness #

+ +

Death + –

Clinical presentation

– absent, ± rare , + can occur , ++ frequent, + + + characteristic # due to uremia in severe, or meningoencephalitis in mild case

Case classification

Clinical case description

Acute febrile illness Headache Prostration / chills Muscle pain & tenderness (calves & thighs!!) Conjunctival suffusion Meningeal irritation Oliguria / anuria Jaundice Haemorrhages (hematemesis, hemoptysis) Cardiac arrhythmia

PLUS A history of exposure to infected animal and / or environment contaminated with animal urine

RISK FACTORS FOR TRANSMISSION OF LEPTOSPIROSIS

Case classification

Laboratory criteria for diagnosis

Isolation of Leptospira from a clinical specimen Blood / LCS : 1-7 days of illness Urine: > 10 days of illness

Positive serology (MAT) Fourfold or greater increase in Leptospira agglutination titer between acute and convalescent phase serum specimen, obtained 2 weeks apart and examined at the same laboratory

Anicteric LeptospirosisAnicteric Leptospirosisclinical diagnosisclinical diagnosis

Clinical diagnosis is difficult

Mild, atypical, anicteric leptospirosis cases are often confused with other febrile illnesses

misdiagnosis Anicteric leptospirosis should be included in the differential diagnosis of every patient with acute

fever Risk factors associated with leptospirosis should be

identified as high index of suspicion for diagnosis

Anicteric LeptospirosisAnicteric Leptospirosisdifferential diagnosisdifferential diagnosis

Influenza uncomplicated malaria

dengue infection HIV seroconversion

hantavirus infection ricketsiosis

typhoid fever infectious mononucleosis

meningitis other viral / bacterial infections etc

IIcteric cteric LLeptospirosiseptospirosisclinical diagnosisclinical diagnosis

Diagnosis of leptospirosis is more easily suspected, and established only in the more severe cases

Nearly all hospitalized patients with leptospirosis in the tropics are severe icteric leptospirosis cases

The only fatal leptospirosis Mortality rates: 5–15% (30–50%) despite in-hospital treatment

Should be included in the differential diagnosis of other potentially fatal infectious diseases: severe falciparum malaria etc.

• Severe falciparum malaria

• Severe complicated typhoid fever

• Haemorrhagic fevers with renal failure (HFRF)

• (hantavirus type Dobrava infection)

• Other severe viral haemorrhagic fevers

Icteric Leptospirosisdifferential diagnosis

Icteric leptospirosisIcteric leptospirosisOrgans involvements / Organs involvements /

ComplicationsComplications

Gastro-hepatobiliary jaundice, hypoalbuminemia liver dysfunction without necrosis hematemesis, acute pancreatitis acalculous cholecystitis etc.

Renal renal failure (oliguric, non-oliguric), uremic syndrome etc.

Gastrointestinal haematemesis, acute pancreatitis

Pulmonary dyspnea, hemoptysis, ARDS, hemorrhagic pneumonitis

Hematologic hemorrhagic diathesis due to vascular damage, thrombocytopenia, uremic platelet dysfunction. post haemorrhagic anemia etc

Cardiac involvement is common but underestimated myocarditis, pericarditis, endocarditis EKG abnormalities (~60%) from atrium fibrilation, AV block, inverted T, ST elevation, rarely with increasing CK-MB, congestive heart failure

Shock hypovolemic, cardiogenic and may be septic shock Ocular uveitis, visual disturbance, vitreous opacities, retinal haemorrhage, etc

CNS aseptic meningitis (rare), nerve palsy, GB syndrome decrease consciousness, “stroke like” etc

Skeletal rhabdomyolysis, severe myalgia “parapharesis”

Icteric leptospirosisOrgans involvements / Complications

Conjunctivalsuffusion

Laboratory diagnosis: Antigen Laboratory diagnosis: Antigen detectiondetection

• Isolation / culture slow, does not contribute to a quick diagnosis has a low sensitivity (<20%)

• Dark-field microscopy often erroneous (unreliable) low detection threshold protein filaments pseudo-Leptospira

• Molecular techniques (PCR, in situ hybridization) laborious, complicated need trained personnel expensive

Sign and SymptomsSign and SymptomsAnicteric( More Common )

• Septic phase : ( 3 – 7 d ) fever, headeche, myalgias, abdominal pain, nausea, vomiting• Immune phase ( 0 d – 1 Mo ) lower fever, intense headache, aseptic meningitis, conjunctival injection, uveitis, hepatosplenomegali, pulmonary involvement, skin rashes.

Icteric( Less common )

• Septic phases ( 3 – 7 d )•Imune phase : ( 10 – 30 d ) jaundice, renal dysfunction, vasculitis, pulmonary hemorrhage, myocardiis

Laboratory diagnosis: Laboratory diagnosis: SerologySerology

•MAT (microscopic agglutination test) gold standard•IgM-ELISA (enzyme linked immuno sorbent assay)•IFAT (immuno fluorescent antibody test)

•MCAT (microcapsule agglutination test)•MA (macroscopic agglutination test)•RLA (rapid latex agglutination)•IHA (indirect hemagglutination test)

Quick tests

Based on the detection ofLeptospira-specific IgM in human sera

LEPTO dipstick 3 hours

LEPTO lateral flow 10 minutes

LEPTO Dri Dot 1 minute

TreatmenTreatmenttAntibiotics

Penicillins: Penicillin Procain etc.Doxycycline, TetracyclineStreptomycin

SupportiveFluids, water balanceDialysis *) Ventilator support

*) a conservative approach should be firstly considered

Prognostic factors for death in Prognostic factors for death in leptospirosisleptospirosis

Independent risk factors associated with mortality

•Oliguria •Hypotension•Dyspnea•Presence of pulmonary rales•Hyperkalemia•High leucocytes count •Alveolar infiltrates on chest X`ray•Abnormalities of EKGDupont et al Clin Infect Dis 1997Panaphut et al J Infect Dis 2002

PROGNOSIPROGNOSISS

Severe Leptospirosis is a life-threatening disease

CFR (case fatality rates) is high, 5 – 40 %Factors independently associated with mortality:

Dyspnea, oliguria, high leukocytosis, EKG abnormalities

Alveolar infiltrates on chest X-ray Renal failure is associated with high

mortality