The relationship among (i ) the local incidence of cholera, (ii) the prevalence in the aquatic environment of Vibrio cholerae, and (iii) bacterial viruses that attack potentially virulent O1 and O139 serogroup strains of this organism (cholera phages) was studied in Dhaka, Bangladesh. Over nearly a 3-year period, we found that significantly more environmental water samples contained either a phage or a phage-susceptible V. cholerae strain than both (P < 0.00001). The number of cholera patients varied seasonally during this period and frequently coincided with the presence of pathogenic V. cholerae strains in water samples that otherwise lacked detectable cholera phages. Interepidemic periods were characterized by water samples containing cholera phages but no viable bacteria. Our data support the conclusion that cholera phages can influence cholera seasonality and may also play a role in emergence of new V. cholerae pandemic serogroups or clones.bacteriophage ͉ seasonality ͉ epidemiology ͉ emergence ͉ lysogeny E pidemics of cholera caused by toxigenic Vibrio cholerae belonging to the O1 or O139 serogroups are a major public health problem in many developing countries of Asia, Africa, and Latin America (1). Cholera epidemics occur with seasonal regularity in the Ganges delta region of Bangladesh and India. Epidemics usually occur twice during a year, with the highest number of cases just after the monsoon during September to December. A somewhat smaller peak of cholera cases also is observed during the spring, between March and May. Although V. cholerae is a human pathogen, these bacteria constitute part of the normal aquatic flora in estuarine environments, and water is clearly a vehicle for transmission of V. cholerae. Although the seasonality of cholera in Bangladesh and elsewhere has been temporally associated with numerous physical and biological parameters (2), these associations do not directly cause epidemics, nor do they end them. More than a century of public health experience has shown that toxigenic O1 and O139 V. cholerae cells cause cholera epidemics and that the elimination of these cells from drinking water ends cholera epidemics. The parameters that directly modulate the level of viable cells belonging to the pathogenic clones of V. cholerae O1 and O139 in the Ganges delta aquatic environment remain unknown. Furthermore, the fact that pathogenic strains of V. cholerae are clonally distinct from environmental, nonpathogenic V. cholerae strains (1) undermines proposed mechanisms of seasonality and pandemic spread that are based on data from studies measuring the abundance of all Vibrio species in the aquatic environment (2).Bacterial viruses (phages) are known to play a critical role in the evolution of pathogenic bacterial species, and V. cholerae in particular. For example, cholera toxin genes are transferred to nontoxigenic strains by means of a lysogenic filamentous phage, CTX⌽ (3). Here we show that the presence of bacterial viruses acting on V. cholerae O1 or O139 (cholera phages or vibriopha...

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Phage predation of Vibrio cholerae has recently been reported to be a factor that influences seasonal epidemics of cholera in Bangladesh.To understand more about this phenomenon, we studied the dynamics of the V. cholerae-phage interaction during a recent epidemic in Dhaka. Because the outbreak strain causing this epidemic was resistant to multiple antibiotics, including streptomycin, we used a selective medium containing streptomycin to monitor accurately the abundance of this strain in the environment. The changing prevalence in the environment of the epidemic V. cholerae O1 strain and a particular lytic cholera phage (JSF4) to which it was sensitive was measured every 48 -72 h for 17 weeks. We also monitored the incidence of phage excretion in stools of 387 cholera patients during the epidemic. The peak of the epidemic was preceded by high V. cholerae prevalence in the environment and was followed by high JSF4 phage levels as the epidemic ended. The buildup to the phage peak in the environment coincided with increasing excretion of the same phage in the stools of cholera patients. These results suggest that patients toward the end of the epidemic ingested both JSF4 phage and the outbreak V. cholerae strain. Host-mediated phage amplification during the cholera epidemic likely contributed to increased environmental phage abundance, decreased load of environmental V. cholerae and, hence, the collapse of the epidemic. Thus, in vivo phage amplification in patients and subsequent phage predation in the environment may explain the self-limiting nature of seasonal cholera epidemics in Bangladesh.Vibrio cholerae ͉ vibriophage T oxigenic strains of Vibrio cholerae belonging to the O1 and O139 serogroups cause cholera, a devastating diarrhea disease that occurs frequently as epidemics in many developing countries (1). Epidemics of cholera occur regularly in the Ganges Delta region of Bangladesh and India. In Bangladesh, outbreaks usually occur twice during a year, with the highest number of cases just after the monsoon and a somewhat smaller number of cholera cases during the spring. The occurrence of epidemics are known to coincide with increased prevalence of the causative V. cholerae strain in the aquatic environment (2). A variety of physical and biological parameters are likely to influence the survival and abundance of V. cholerae as a species in the environment, but these factors do not exclusively modulate the prevalence of toxigenic V. cholerae O1 and O139 strains. In contrast, bacterial viruses (phage or bacteriophage) in the environment have recently been found to inversely correlate with the abundance of toxigenic V. cholerae in water samples and the incidence rates of cholera (3). These data strongly suggest that phage predation in the environment likely influences the temporal dynamics of cholera epidemics. Phages also play a role in the emergence of pathogenic clones and may also be involved in territorialism between different strains of V. cholerae (3-5). For example, cholera toxin genes are transferred ...