Cholera is caused by infection of the small intestine of man by a gram-
negative toxigenic bacteria called Vibrio cholerae. The illness is
characterized by the sudden onset of watery diarrhea, vomiting,
dehydration often leading to death. The route of entry of the organisms into
the human body is through the mouth. There is ample evidence in the
epidemiologic literature that in most outbreaks, V. cholerae infections have
been traced to drinking of contaminated water. Once the viable organisms
are swallowed, the establishment of a small intestinal infection depends on
several factors related to man, the host, and the parasite.
During cholera pathogenesis, V. cholerae expresses a transcriptional
activator ToxT, which subsequently transactivates expressions of two
crucial virulence factors: toxin-coregulated pilus and cholera toxin (CT).
These factors are responsible for intestinal colonization of V. cholerae and
induction of fluid secretion, respectively. In intestinal epithelial cells, CT
binds to GM1 ganglioside receptors on the apical membrane and
undergoes retrograde vesicular trafficking to endoplasmic reticulum, where
it exploits endoplasmic reticulum-associated protein degradation systems
to release a catalytic A1 subunit of CT (CT A1) into cytoplasm. CT A1, in
turn, catalyzes ADP ribosylation of α subunits of stimulatory G proteins,
leading to a persistent activation of adenylate cyclase and an elevation of
intracellular cAMP. Increased intracellular cAMP in human intestinal
epithelial cells accounts for pathogenesis of profuse diarrhea and severe
fluid loss in cholera.
Countries were classified as cholera endemic, cholera non-endemic, or
cholera-free based on whether a spatial regression model predicted an
incidence rate over a certain threshold in at least three of five years (2008-
2012). The number of annual cholera deaths was calculated using inverse
variance-weighted average case-fatality rate (CFRs) from literature-based
CFR estimates. We found that approximately 1.3 billion people are at risk
for cholera in endemic countries. An estimated 2.86 million cholera cases
(uncertainty range: 1.3m-4.0m) occur annually in endemic countries.
Among these cases, there are an estimated 95,000 deaths (uncertainty
range: 21,000-143,000).
