1. Armed Forces Research Institute of Medical Sciences Welcome from AFRIMS “…probably the most sophisticated diagnostic and research laboratory in all of Southeast Asia.” U.S. Institute of Medicine report on DoD-GEIS, 2001 A joint medical research facility of the Royal Thai Army and the United States Army Medical Research and Development Command

2. Armed Forces Research Institute of Medical Sciences Major Research Initiatives at AFRIMS Japanese Vaccine Development in 1990sJapanese Vaccine Development in 1990s Dengue Vaccine Development – currentDengue Vaccine Development – current HIV Vaccine Development – currentHIV Vaccine Development – current Diarrhea Research and Surveillance of Drug ResistanceDiarrhea Research and Surveillance of Drug Resistance Malaria Drug Development (mefloquine, tetracycline, new artemisinins) and Surveillance of Drug ResistanceMalaria Drug Development (mefloquine, tetracycline, new artemisinins) and Surveillance of Drug Resistance Mosquito and other Insect BiologyMosquito and other Insect Biology Emerging Diseases Surveillance and ResponseEmerging Diseases Surveillance and Response

3. Armed Forces Research Institute of Medical Sciences Global Emerging Infectious Diseases Surveillance (GEIS) What is an Emerging Disease? a new disease, not previously described (e.g. SARS) an underestimated disease (e.g. leptospirosis), a re-emerging disease, often with increased drug resistance (MDR-TB or MDR-Pf) The DoD-GEIS program at AFRIMS: Febrile illness surveillance (Sangkhlaburi, Kamphaeng Phet, Nepal) Drug resistant malaria surveillance Drug resistant diarrheal pathogen surveillance Rapid sentinel surveillance at RTA hospitals Outbreak response

4. Armed Forces Research Institute of Medical Sciences Summary of Presentations Fever StudyFever Study OverviewDr. Scott MillerOverviewDr. Scott Miller Specific causes of feverDr. Mark FukudaSpecific causes of feverDr. Mark Fukuda Clinical characterizationsNichapat U-ThaimongkolClinical characterizationsNichapat U-Thaimongkol LeptospirosisDr. Ruth EllisLeptospirosisDr. Ruth Ellis Rickettsial IllnessesDr. Scott MillerRickettsial IllnessesDr. Scott Miller Diarrhea Study Dr. Ladaporn BodhidattaDiarrhea Study Dr. Ladaporn Bodhidatta Malaria Drug Resistance Dr. Scott MillerMalaria Drug Resistance Dr. Scott Miller New Directions Drs. Krisada Jongsakul & Mark FukudaNew Directions Drs. Krisada Jongsakul & Mark Fukuda

5. Armed Forces Research Institute of Medical Sciences Surveillance of Febrile Illnesses of Adults in Sangkhlaburi District 1999-2003 Department of Immunology and Medicine AFRIMS Dr. R. Scott Miller, M.D.

6. Armed Forces Research Institute of Medical Sciences Background AFRIMS started doing surveys for malaria prevalence and drug resistance patterns surveys in the Sangkhlaburi district in 1995AFRIMS started doing surveys for malaria prevalence and drug resistance patterns surveys in the Sangkhlaburi district in 1995 Testing an antibiotic, azithromycin:Testing an antibiotic, azithromycin: for prevention of malaria in 1996;for prevention of malaria in 1996; for treatment of PF with quinine in 2000-2001for treatment of PF with quinine in 2000-2001 Started an relationship with Kwai River Christian HospitalStarted an relationship with Kwai River Christian Hospital What is causing the other 70% of fevers at the hospital?What is causing the other 70% of fevers at the hospital?

7. Armed Forces Research Institute of Medical Sciences Objectives To define the specific cause of undifferentiated febrile illnesses: To identify specific rickettsial, arboviruses and zoonotic pathogens. To identify the patterns of drug resistance of diarrheal pathogens and enteric fevers (typhoid) Evaluate the prevalence of these illnesses by sero-surveys of the local populations To evaluate test kits for rapid diagnosis of undifferentiated febrile illnesses as compared to standard diagnostics. Study approved by Committee on Research in Humans Subjects, MOPH

8. Armed Forces Research Institute of Medical Sciences Fever Study Methods Identify volunteers from those presenting to with a fever or history of feverIdentify volunteers from those presenting to with a fever or history of fever Informed consent obtainedInformed consent obtained Blood drawn for:Blood drawn for: Malaria smear and rapid testingMalaria smear and rapid testing WBC, HCT and platelet countWBC, HCT and platelet count Renal and liver testsRenal and liver tests Serum for acute serology testingSerum for acute serology testing Medical history and physical examMedical history and physical exam Treatment by hospital staff or volunteersTreatment by hospital staff or volunteers

9. Armed Forces Research Institute of Medical Sciences Fever Study Methods Return for follow-up visit at 3-4 weeksReturn for follow-up visit at 3-4 weeks And earlier visits as neededAnd earlier visits as needed Interim medical history and examInterim medical history and exam Additional blood drawn for:Additional blood drawn for: Repeat WBC, HCT and platelet countRepeat WBC, HCT and platelet count Renal and liver tests, if initially abnormalRenal and liver tests, if initially abnormal Serum for paired convalescent serology testingSerum for paired convalescent serology testing Fever syndrome classified by clinical and laboratory featuresFever syndrome classified by clinical and laboratory features

10. Armed Forces Research Institute of Medical Sciences Fever Syndrome Classification a). fever with upper respiratory disease b). fever with lower respiratory disease c). fever with meningitis, encephalitis, or neuropathy d). fever with gastrointestinal disease e). fever with renal disease f). fever with abnormal bleeding g). fever with liver disease h). fever with anemia, leukopenia or thrombocytopenia i). fever with hepatomegaly or splenomegaly (circle) j). fever with lymphadenopathy k). fever with arthritis (mono- or polyarticular) l). fever with rash m). fever with eschar n). fever with shock o). fever with non-specific symptoms p). isolated fever without systemic symptoms q). fever with other symptoms (specified) _______________

11. Armed Forces Research Institute of Medical Sciences Fever Study Village Seroprevalence Study Cross-sectional surveys of adult volunteersCross-sectional surveys of adult volunteers End of dry season and rainy season (every 6 months)End of dry season and rainy season (every 6 months) 1999-2001 (2 monsoon cycles)1999-2001 (2 monsoon cycles) Serum collection and malaria smearSerum collection and malaria smear Volunteers from three villages near KRCH (n=497)Volunteers from three villages near KRCH (n=497) Viakadee (n=182)Viakadee (n=182) Mong Satur (n=175)Mong Satur (n=175) Mong Satur Tai (n=140)Mong Satur Tai (n=140) Tested for exposure to: rickettsia, leptospirosis, and other animal diseasesTested for exposure to: rickettsia, leptospirosis, and other animal diseases