Typhoid fever: a massive, single-point source, multidrug-resistant outbreak in Nepal.

Abstract

In the summer of 2002, a total of 5963 cases of typhoid fever were recorded in Bharatpur, Nepal (population, 92,214) during a 7-week period. A team from the Armed Forces Research Institute of Medical Sciences in Bangkok, Thailand, and the CIWEC Travel Medicine Clinic (Kathmandu, Nepal) assisted the Nepal National Public Health Laboratory (Kathmandu, Nepal) in the further investigation of this large, explosive febrile disease outbreak. Investigators conducted a thorough epidemiologic and laboratory investigation to assess the size and scope of the outbreak. In addition to subculturing of previously collected samples, blood samples were obtained from 100 febrile patients, and culture and susceptibility testing were done by standard laboratory methods. Pulsed field gel electrophoresis (PFGE) and plasmid analysis were done. The majority of the isolates, including 1 from the municipal water supply, were multidrug resistant. The minimum inhibitory concentrations (MICs) of ciprofloxacin ranged from 0.19 microg/mL to 0.125 microg/mL. With use of PFGE, all isolates, including isolates from the water supply, showed an analytical similarity of 96%-100%. Multidrug-resistant isolates had a plasmid encoding for resistance, and those with resistance to nalidixic acid had a single-point mutation. To the best of our knowledge, this outbreak is the largest single-point source outbreak of multidrug-resistant typhoid fever yet reported, and it was molecularly traced to the city's single municipal water supply. Isolates were uniformly resistant to nalidixic acid, there was a decrease in their susceptibility as measured by MIC of fluoroquinolones, and 90% of isolates obtained were resistant to >1 antibiotic.