Oleh Bagian Ilmu Penyakit Dalam

FK Universitas Islam Sultang Agung

Semarang
2006
 Leptospirosis
•
 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 leptospirosis cases
in Semarang municipality 1990 & 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
Bacteriology
Causative 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 / 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
45
39
40 35
35 33
30 29
30 27 28
25
25 21
19
20
15
10
5
0
1981 82 83 84 85 86 87 88 89 1990

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

 HIGHEST INCIDENCE 2000

Country Region Incidence Mortality

Per 100.000 (%)
India Andaman 50.0 21.0
Thailand 23.1 2.5
India Chennai 10.5 -
France Ile de la 6.0 -
Reunion
India Kerala 5.6 10.1
USA Hawaii 4.0 0
Brazil Sao Paulo 1.9 12.3
Uruguay 1.6 100
Indonesia Semarang 1.2 16.7
EPIDEMIOLOGY: transmission & risk
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: Occupational risk factors
Clinical and epidemiological studies of Leptospirosis in Semarang
Phase I : Oct. 2002-March 2004

Possible risk factors for Leptospirosis

Environmental & socio-economic Frequency (%)
risk factors
High population of rats 95%
Living in coastal part of Semarang 79%
Bad flow of water in the gutters of 68%
the house
Living in slum districts with bad 65%
housing
Living in flood prone areas 56%

Walking through stagnant water 56%

Unemployed person 34%

Low level labours 14%
Note: Risk factors mostly overlapped
Pathology/pathogenesis
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.
Kidney  Renal
Intralobular biliary
lessions stasis
include may occur
tubular necrosis, cortical ischaemia
and medullary congestion
 Renal changes may resemble interstitial nephritis
Lungs  Pulmonary congestion may accompany pulmonary
haemorrhage
 Clinical progression: two stages (biphasic)
Icteric Leptospirosis
Anicteric Leptospirosis
(Weil's Syndrome)
First Stage Second Stage
First Stage Second Stage 3-7 days 10-30 days
3-7 days 0 days - 1 month (SEPTICEMIC) (IMMUNE)
(SEPTICEMIC) (IMMUNE)

Fever

Myalgia Meningitis
Headache Uveitis Jaundice
Abdominal Rash Hemorrhage
Important pain Renal failure
Clinical Vomiting Myocarditis
Findings Conjunctival
suffusion

Leptospires
Present
Blood Blood

CSF CSF

Urine Urine

Feigin et al. 1975

 Clinical presentation
Clinical features Icteric Anicteric
(Weil`s Disease)

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

– 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 Leptospirosis
clinical 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 Leptospirosis
differential diagnosis

Influenza uncomplicated malaria

dengue infection HIV seroconversion

hantavirus infection ricketsiosis

typhoid fever infectious mononucleosis

meningitis other viral / bacterial infections etc

 Icteric Leptospirosis
clinical 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.
 Icteric Leptospirosis
differential diagnosis

• Severe falciparum malaria

• Severe complicated typhoid fever

• Haemorrhagic fevers with renal

failure (HFRF)
• (hantavirus type Dobrava infection)

• Other severe viral haemorrhagic

fevers
 Icteric leptospirosis
Organs involvements /
Complications
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
 Icteric leptospirosis
Organs involvements / Complications

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”

Conjunctival
suffusion
 Sign and Symptoms
Anicteric • Septic phase : ( 3 – 7 d ) fever, headeche,
( More Common ) 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 • Septic phases ( 3 – 7 d )
( Less common ) •Imune phase : ( 10 – 30 d ) jaundice, renal
dysfunction, vasculitis, pulmonary
hemorrhage, myocardiis
Laboratory diagnosis: Antigen
detection

• 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
 Laboratory diagnosis:
Serology

•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 of

Leptospira-specific IgM in human sera

LEPTO dipstick 3 hours

LEPTO lateral flow 10 minutes

LEPTO Dri Dot 1 minute

 Treatment
Antibiotics
Penicillins: Penicillin Procain etc.
Doxycycline, Tetracycline
Streptomycin

Supportive
Fluids, water balance
Dialysis *)
Ventilator support

*) a conservative approach should be firstly

considered
Prognostic factors for death in leptospirosis

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 EKG
Dupont et al Clin Infect Dis 1997
Panaphut et al J Infect Dis 2002
 PROGNOSIS

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