Phage attack: antibacterial virus might suppress cholera.

In regions where cholera is endemic, outbreaks often coincide with the rainy seasons. But why this waterborne bacterial disease routinely strikes at such times has been unclear.

Researchers working in Bangladesh now offer evidence that bacteria-attacking viruses hold the cholera microbe in check throughout much of the year. But during the monsoons, these viruses probably become diluted in swollen lakes and rivers, leaving the cholera microbe, Vibrio cholerae, without this natural enemy. When this happens, V. cholerae can bloom, causing an outbreak of disease, the researchers conclude in an upcoming Proceedings of the National Academy of Sciences.

Cholera causes severe diarrhea. When poor sanitation permits feces from a cholera patient to enter a water supply, the bacteria spread to other people.

To assess whether bacteria-attacking viruses, called phages, might explain the seasonality of cholera outbreaks, John J. Mekalanos of Harvard Medical School in Boston and a team of researchers took 221 water samples from two rivers and a lake used as drinking-water sources in Bangladesh. They drew the water at random times over 3 years.

Most of the water samples contained either phages or cholera bacteria, but not both. The samples taken during the rainy seasons tended to have more cholera microbes and fewer phages than did samples taken the rest of the year. The data suggest that the viruses kill more cholera bacteria in rivers and lakes during dry seasons than in wet ones, the team says.

Next, the researchers documented cholera outbreaks among people who tapped those water sources for drinking. To pinpoint the start of an outbreak, the researchers recorded when particularly virulent V. cholerae strains showed up in tests of hospitalized diarrhea patients. This lab work and the number of patients treated indicated that cholera outbreaks typically occurred at times when phage concentrations were low. Then, when phage concentrations rose, cholera cases tailed off.

"I think [phages] are a factor, but I don't think they are the silver bullet that explains the biological cycle of cholera," says Rita Colwell, a molecular biologist at the University of Maryland at College Park and the Johns Hopkins Medical Institutions in Baltimore. Other factors, such as water temperature, salinity, and the presence of tiny organisms that can carry the cholera bacteria also affect V. cholerae concentrations in bodies of water, she says.