Host immunity and climate forcing in cholera dynamics and evolution.

Abstract

Consisting of four articles, this thesis focuses on using time series analyses and theoretical modeling approaches to understand cholera dynamics and evolution in endemic regions. The first article develops a nonlinear statistical model with two related objectives: the reconstruction of immunity patterns from data on disease cases and population sizes and the identification of the respective roles of extrinsic and intrinsic factors in the dynamics. Extrinsic factors here include both seasonality and long-term changes or interannual variability in forcing. Results with simulated data show that this semiparametric method successfully recovers the decay of immunity and identifies the origin of interannual variability. An application to historical cholera mortality data (1891-1940) indicates that temporary immunity is long-lasting and that extrinsic forcing of transmission rates has a strong seasonal component along with a long-term decrease. The three subsequent articles focus more specifically on cholera dynamics and evolution in the endemic region of Matlab, Bangladesh over the years 1966-2003. The data for these analyses were provided by the International Centre for Diarrheal Disease Research, Bangladesh (ICDDR,B). Through a two-strain extension of the developed time series model, one article demonstrates that cholera interannual variability in Matlab results from a combination of host immunity fluctuations and climate forcing, with climate forcing changing the transmission rate of <italic>Vibrio cholerae</italic>. Refractory periods, during which environmental conditions for cholera transmission are favorable but high levels of immunity exist in the population, are evident, showing the critical interplay between intrinsic and extrinsic factors in driving disease dynamics. The following article focuses on a long-term transition in cholera serotypes from Inaba to Ogawa. Through a comparison with a two-serotype mathematical model, the observed change in serotype dominance provides evidence for an extended strain cycle resulting from incomplete cross-immunity between the serotypes. The last article uses a toy model together with an adaptive dynamics approach to explain the recent competitive exclusion of the Classical biotype by the El Tor biotype. Together, these chapters further our understanding of the climate variables responsible for cholera dynamics and evolution and highlight the importance of immunity factors in contributing to these processes.