The impact of migration and antimicrobial resistance on the transmission dynamics of typhoid fever in Kathmandu, Nepal: A mathematical modelling study

Background: A substantial proportion of the global burden of typhoid fever occurs in South Asia. Kathmandu, Nepal experienced a substantial increase in the number of typhoid fever cases (caused by Salmonella Typhi) between 2000 and 2003, which subsequently declined but to a higher endemic level than in 2000. This epidemic of S. Typhi coincided with an increase in organisms with reduced susceptibility against fluoroquinolones, the emergence of S. Typhi H58, and an increase in the migratory population in Kathmandu. Methods: We devised a mathematical model to investigate the potential epidemic drivers of typhoid in Kathmandu and fit this model to weekly data of S. Typhi cases between April 1997 and June 2011 and the age distribution of S. Typhi cases. We used this model to determine if the typhoid epidemic in Kathmandu was driven by heightened migration, the emergence of organisms with reduced susceptibility against fluoroquinolones or a combination of these factors. Results: Models allowing for the migration of susceptible individuals into Kathmandu alone or in combination with the emergence of S. Typhi with reduced susceptibility against fluoroquinolones provided a good fit for the data. The emergence of organisms with reduced susceptibility against fluoroquinolones organisms alone, either through an increase in disease duration or increased transmission, did not fully explain the pattern of S. Typhi infections. Conclusions: Our analysis is consistent with the hypothesis that the increase in typhoid fever in Kathmandu was associated with the migration of susceptible individuals into the city and aided by the emergence of reduced susceptibility against fluoroquinolones. These data support identifying and targeting migrant populations with typhoid immunization programmes to prevent transmission and disease. Author summary: Typhoid fever is endemic in Nepal, with Kathmandu coined “the typhoid capital of the world”. We developed a mathematical model to assess the importance of migration and antimicrobial resistance on the transmission of typhoid fever in Kathmandu, Nepal from April 1997 to June 2011. During this period, the burden of typhoid fever increased markedly from January 2000 to December 2003, after which the epidemic declined, but to a higher endemic level than in 2000. Our findings are consistent with the hypothesis that migration of susceptible individuals into Kathmandu played an important role in the epidemic, and may have been further aided by the emergence of typhoid fever with reduced susceptibility against fluoroquinolones. This study showed that identifying and targeting migrant populations with control efforts could be an important avenue to prevent typhoid transmission and disease.