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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 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.

45
40
35
30

Severe leptospirosis cases admitted to


Dr. Kariadi Hospital during 10 years
39
35

33
27

28

25

25
20

30

29

88

89

21

19

15
10
5
0

1981

82

83

84

85

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

86

87

1990

HIGHEST INCIDENCE 2000


Country

Region

India
Thailand
India
France

Andaman

India
USA
Brazil
Uruguay
Indonesia

Chennai
Ile de la
Reunion
Kerala
Hawaii
Sao Paulo
Semarang

Incidence
Per 100.000
50.0
23.1
10.5
6.0

Mortality
(%)
21.0
2.5
-

5.6
4.0
1.9
1.6
1.2

10.1
0
12.3
100
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
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%

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.
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

Clinical progression: two stages (biphasic)


Icteric Leptospirosis
(Weil's Syndrome)

Anicteric Leptospirosis
First Stage
3-7 days
(SEPTICEMIC)

Second Stage
0 days - 1 month
(IMMUNE)

First Stage
3-7 days
(SEPTICEMIC)

Second Stage
10-30 days
(IMMUNE)

Fever

Important
Clinical
Findings

Leptospires
Present

Myalgia
Headache
Abdominal
pain
Vomiting
Conjunctival
suffusion

Meningitis
Uveitis
Rash

Blood

Blood

CSF

CSF
Urine

Feigin et al. 1975

Jaundice
Hemorrhage
Renal failure
Myocarditis

Urine

Clinical presentation
Clinical features
Jaundice

Icteric
(Weil`s Disease)

Anicteric

+++

++

Leucocytosis

+++

Hemorrhage

++

Renal failure

++

Aseptic meningitis

++

Disturbance of
consciousness #

Death

Conjunctival suffusion

absent, rare , + can occur , ++ frequent, + + + characteristic

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
infections etc

other viral / bacterial

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: 515% (3050%) 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

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

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:
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

PROGNOSI
S
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