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Transcript
TAKING A CLOSER
LOOK AT
LEPTOSPIROSIS
Lilen C. Sarol, PhD
College of Public Health
University of the Philippines Manila
Leptospirosis in the world
Incidence of severe cases 300,000-500,000 per year
NUMBER OF LEPTOSPIROSIS CASES AND
DEATHS ACCORDING TO REGION
NUMBER OF CLINICALLY CONFIRMED
LEPTO CASES ACCORDING TO REGION
(Jan. 1 – Aug. 14, 2010)
Discovery of Pathogen
in 1915
Ryoukichi Inada
(1874-1950)
Causative Agent
 highly
motile
 flexible
 helical or coiled
 aerobic bacteria
 with bent or
hooked ends

Spirochaeta icterohaemorrhagiae
Yasuda et al. Deoxiribonucleic acid relatedness between
seogroups and serovars in the family Leptospiraceae. Int J
Sys Bacteriol 1987; 407-415
Sensitivity

killed at 500C in 10 mins or 600C in 10
seconds

susceptible to dessication,
hypochlorite disinfectants and pH
outside of 6.2 to 8.0

acid urine, non-aerated sewage and
polluted water
PHENOTYPIC CLASSIFICATION OF LEPTOSPIRES
GENOTYPIC CLASSIFICATION OF LEPTOSPIRES
TRANSMISSION CYCLE OF LEPTOSPIROSIS
DIRECT CONTACT
• thru tissue or urine of
infected animals
• ingestion of contam food
• droplet aerosol inhalation
• contact with moist
soil or vegetation
contaminated with
urine of infected animals
INDIRECT CONTACT
• swimming or wading in
floodwaters
• accidental immersion
• occupational abrasion
Icteric Leptospirosis
Weil's Syndrome
Anicteric Leptospirosis
Second stage
0-1 month
First stage
3-7 days
Second stage
10-30 days
Septicemic
Immune
Septicemic
Immune
Myalgia/
Myositis
Abdominal
pain
Conjunctival
suffusion
Meningitis
Uveitis
Rash
Fever
Lepto
present
Important
Clinical findings
fever
First stage
3-7 days
Blood
Jaundice
Hemorrhage
Renal failure
Myocarditis
Meningitis
Pulmonary
hemorrhage
Respiratory
failure
Blood
CSF
CSF
urine
urine
Signs and Symptoms of Leptospirosis
Icterus and hemorrhage
Acute renal failure
Differential Diagnosis
 Dengue
 Rickettsial
disease : Scrub typhus,
murine typhus
 Acute viral hepatitis
 Sepsis
 Influenza
 Aseptic Meningitis
DIFFERENT STAGES OF
LEPTOSPIROSIS
LEVEL AND DURATION OF IgM ANTIBODIES
AT DIFFERENT TIME INTERVALS
LEVEL AND DURATION OF MICROSCOPIC
AGGLUTINATING ANTIBODIES AT
DIFFERENT TIME INTERVALS
IMMUNOFLOURESCENCE
POSITIVE AND NEGATIVE RESULTS IN MCAT

principle of passive
agglutination
 employs carrier
micro-capsule
particles on the
surface of which
ultrasonicated
leptospiral antigens
are absorbed
LEPTO LATERAL FLOW
based on the binding
of specific IgM
antibodies to the
broadly reactive
heat extracted
antigen prepared
from nonpathogenic
Patoc 1 strain
LEPTO LATEX AGGLUTINATION TEST
(LAT)
agglutination immuno assay for the
detection of leptopsira specific
antibodies
MICROSCOPIC AGGLUTINATION TEST (MAT)
Problem with diagnosis
Low success rate of isolation
 Unreliability of direct demonstration
of leptospires in clinical samples
using dark field microscopy
 Inaccessibility of molecular
techniques to most peripheral
hospitals and clinics
 Serological tests have low sensitivity
during acute stage

Treatment
Early anti-microbial therapy is
importantshorten the course and
prevent carrier state
 Choice : Penicillin G, Ampicillin
 May cause “ Jarish-Huxheimer type
reaction”
 Mild cases oral Doxycycline or
Amoxicillin

Prevention
 Vaccination
of domestic animals
 Rodent control
 Protective gloves and boots
 Avoid swimming in contaminated
waters
 Vaccination in endemic region
TARGETS FOR CONTROL STRATEGIES
Difficulties in Leptospirosis Control
Bacteriology
Laborious culture
Slow colony formation
Delay in genetic research
Actual condition of
Leptospirosis is unclear
Epidemiology
Variety of maintenance animals
Distribution of Leptospires
unknown
More than 250 of serovars
Clinical research
Lack of rapid diagnostic kit
Difficulties in clinical
diagnosis
Neglected
Infectious
Disease
Present
condition
Small research
funds
few researchers
Lack of rapid
diagnostic kits
and vaccine
34
Application to the SATREPS program in 2008
MEXT・JST
Collaboration
MOFA・JICA
Prevention and Control of Leptospirosis in
the Philippines
Kyushu University
Chiba Inst. Science
Research
Partnership
MEXT: Ministry of Education, Culture, Sports, Science and Technology
JST: Japan Science and Technology Agency
College of Public
Health
UP Manila
MOFA: Ministry of Foreign Affairs
JICA: Japan International Cooperation Agency
PO/PDM と Working group との関係図
Plan of Operation (PO)
Project Design Matrix (PDM)
Working Groups in the Philippines
0. Laboratory Renovation
Group A: Microbiology
1) Bacterial surveillance
Yoshida/ Gloriani
2) Diagnostic kit
Masuzawa
3) DNA vaccine
Yoshida
1. Epidemiology
1) Bacteriological surveillance
2) Burden of disease
3) Environmental risk factors
Group B: Burden of disease
Yoshida, Yabe/ Borja
2. Diagnostic kit
Group C: Environmental risk factors
Yanagihara/ Cavinta
3. DNA vaccine
4. Advocacy
Group D: Advocacy
Fujii/ Guevarra
Output of the LEPCON
Advocacy
Burden of Disease by Bacteriological study
Center for LEPCON
Development of Diagnostic kits and DNA vaccines
Epidemiology and Economic burden