Travelers’ Diarrhea Diagnosis and Therapy Study in United States Military Personnel on Short-Term Deployment in Thailand

Title of Dissertation: Travelers’ Diarrhea Diagnosis and Therapy Study in United States Military Personnel on Short-Term Deployment in Thailand Name, degree, year: David R. Tribble, M.D., M.P.H., Doctor of Public Health, 2004 Thesis directed by: Paul Hshieh, Ph.D., Assistant Professor, Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences Campylobacter species are the predominant cause of diarrhea in military travelers to Thailand accounting for approximately 40-50% of evaluated cases. The clinical presentation and subsequent time to resolution for Campylobacter-associated cases differs from other etiologies in this setting evidenced by frequent systemic toxicity, increased diarrhea severity at presentation, delayed recovery, and higher 72-hr clinical failure rates [associated with use of fluoroquinolone (FQ) antibiotics]. These findings were observed during a period of time when the rates of FQ-resistant C. jejuni exceed 85% and the most common therapy prescribed was a FQ antibiotic. Diagnostic tests were evaluated in U.S. soldiers presenting with acute diarrhea during deployment in Thailand. Bedside and field laboratory diagnostic tests were compared to stool microbiology findings in 182 enrolled patients. Clinical findings, inflammatory screening tests [stool hemoccult, fecal leukocytes, fecal lactoferrin (LFLA), plasma C-reactive protein], or Campylobacter-specific peripheral blood antibody-secreting cells failed to increase posttest probability above 90% in this Campylobacter hyperendemic setting. A Campylobacter-specific commercial EIA, and less so a research PCR, were strong positive predictors. Negative predictive value (reducing post-test probability less than 10%) was similarly observed with these Campylobacter-specific stool-based tests as well the fecal LFLA. A randomized, active drug-controlled, double-blinded study definitively demonstrated azithromycin to be the preferred antibiotic for traveler's diarrhea empiric treatment in Thailand. Clinical cure by 72 hours was highest at 96% with single dose azithromycin compared to 85% with 3-day azithromycin and 71% with levofloxacin (P = .002). Microbiologic eradication was significantly better for azithromycin-based regimens, 96-100%, as compared to levofloxacin at 38% (P = .001). Higher rate of posttreatment nausea in the 30 minutes after first dose (14 vs.< 6%, P = 0.06) were observed as a mild self-limited complaint with single dose azithromycin. Single-dose azithromycin is recommended for empiric therapy of travelers’ diarrhea acquired in Thailand and should be further investigated for broader application in areas with more diverse enteropathogens. TRAVELERS’ DIARRHEA DIAGNOSIS AND THERAPY STUDY IN UNITED STATES MILITARY PERSONNEL ON SHORT-TERM DEPLOYMENT IN THAILAND by David R. Tribble, M.D., M.P.H. Thesis submitted to the Faculty of the Department of Preventive Medicine and Biometrics Graduate Program of the Uniformed Services University of the Health Sciences in partial fulfillment of the requirements for the degree of Doctor of Public Health 2004 ACKNOWLEDGEMENT AND DEDICATION Throughout this journey to broaden my medical and infectious diseases training and experience with formal public health education, I have been continuously supported by many people. My friends and colleagues in the military enteric diseases community have been critical to the success of my thesis project. I particularly wish to acknowledge Lou Bourgeois, Shahida Baqar, John Sanders, Dan Scott, Lorrin Pang, and Carl Mason for their efforts. Gary Gackstetter and Paul Hshieh have both provided me with much help throughout the masters and doctoral degree programs. I especially appreciate the helpful guidance and hard work provided by Dave Cruess, Alison O’Brien, Bonnie Smoak, Rich Thomas, and Paul Hshieh as my thesis committee for the past four years. I dedicate this work to my wife, Laura, who always provides me with needed support, and our daughters, Katherine and Caroline. Lastly, I am grateful to the military volunteers who agreed to participate in these studies and for whom this work is designed to assist.