Transcript Leptospira
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 importantshorten 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