One of the puzzling aspects of devastating cholera outbreaks in areas where the disease is endemic is that they generally appear to fizzle out naturally. In Bangladesh, outbreaks usually occur twice a year, with the highest number of cases just after the summer monsoon and a somewhat smaller number of cases in the spring. It appears that a number of biological and physical factors may affect the survival and abundance of the disease-causing bacteria, Vibrio cholerae. But the disease is only carried by the strains O1 and O139 of the bacteria and researchers have puzzled how environmental factors might affect these strains. Recent work has suggested that predation of V. cholerae O1 by bacteriophages may influence this seasonal pattern of epidemics, as it is known that this disease-causing strain is sensitive to a particular lytic bacteriophage, called JSF4. It has, however, been difficult for researchers to get quantitative, dynamic data on the presence of the toxic strain and bacteriophages both in the environment and in patients during the course of an epidemic. But a team led by Shah Faruque at the International Centre for Diarrhoeal Disease Research in Dhaka, and John Mekalanos at Harvard Medical School in Boston now report a study in the Proceedings of the National Academy of Sciences (published online), describing a quantitative estimate of a pathogenic V. cholerae O1 and the lytic bacteriophage JSF4 in environmental water samples and from faeces of patients through the course of an epidemic in Dhaka last year. The team exploited the fact that the toxigenic V. cholerae O1 causing recent epidemics is resistant to multiple antibiotics, including streptomycin. So the team tested for the presence of this strain in samples by selecting for it on culture plates containing streptomycin which would kill non-resistant strains of the bacteria. The team also used this system to monitor the changing prevalence of this strain in relation to that of the JSF4 lytic bacteriophage during the course of the epidemic. The researchers tested the sensitivity of their assay to detect the pathogenic V. cholerae O1 amongst the many other non-pathogenic V. cholerae bacteria in their samples by comparing cultures on media containing or not containing streptomycin. Selection on streptomycin plates revealed 141 of 339 samples contained V. cholerae O1 whereas only 60 samples were positive for V. cholerae O1 from plates without streptomycin, suggesting a much greater sensitivity in tracking the pathogen than in tests without using the antibiotic. This provided the researchers with greater accuracy in following the pathogen throughout the epidemic. As expected, the researchers found the number of patients suffering from cholera rose throughout the start of the epidemic before cases eventually declined. But they also found that the presence of the toxic bacteria and its lytic bacteriophage also varied considerably too throughout the epidemic. The team found that the peak of the epidemic was preceded by high V. cholerae O1 levels in water samples from the environment to which patients were exposed, which was followed by high JSF4 phage levels as the epidemic ended. The build-up to the peak detection of the JSF4 phage in the environment coincided with increasing excretion of it in the faeces of cholera patients. “These results suggest that patients towards the end of the epidemic ingested both JSF4 phage and the outbreak cholera strain,” the authors say. They suggest that phage amplification in patients infected by the disease at this stage may have contributed to increased phage abundance, decreasing the numbers of environmental V. cholerae O1 and, hence, the collapse of the epidemic. These results “may explain the self-limiting nature of seasonal cholera epidemics in Bangladesh,” the authors report. The authors also believe the evidence that phage may help control a major human bacterial disease could be put to clinical use. The work has “significant implications in devising cholera control measures by possible phage-mediated interventions,” the authors say.