Mystery Surrounding Cholera Variant’s Unexpected Disappearance Solved

Researchers in the United Kingdom have solved a recent epidemiological mystery: why a highly infectious variant of cholera that caused large outbreaks in the early 1990s mysteriously disappeared before sparking a pandemic.

Cholera is a life-threatening disease usually caught by eating or drinking contaminated food or water. It only causes large outbreaks in places where hygiene and sanitation is poor, so is mainly restricted to the developing world or in regions experiencing war or natural disaster.  In the past 200 years, seven cholera pandemics have killed millions of people across the world—the seventh is still ongoing with large outbreaks in Yemen and Somalia.  The dominant variant of Vibrio cholerae, the bacteria that causes cholera outbreaks today, is called O1 and arose in the 1960s, replacing all pre-existing variants.

The O139 variant—the subject of the study—was first detected in India in 1992. It quickly became dominant and caused huge disease outbreaks in India and Southern Bangladesh. The rapid spread of O139 across Asia surprised scientists, who feared it would cause the eighth cholera pandemic. Cholera vaccines were modified accordingly, but the pandemic never materialized. By 2015 the variant had largely declined, and the O1 variant established itself once again as a dominant strain.

A study at University of Cambridge has determined why the O139 variant mysteriously disappeared. After analyzing 330 samples of the variant taken between 1992 and 2015, they found that O139 gradually lost genes that conferred antibiotic resistance. Genetic changes also altered the types of toxin produced by the bug. At the same time, the O1 variant gained antibiotic resistance. When combined, these changes are likely to account for O139’s failure to seed the eighth cholera pandemic.

The cholera bug is not currently monitored on a regular basis. Scientists say continuous monitoring of the genes underlying antimicrobial resistance and toxin production is key to keeping ahead of the cholera bug as it evolves. In particular, this will help to plan changes to vaccines and appropriate public health responses to prevent future cholera outbreaks.

“There’s a real possibility that another cholera variant may emerge with the potential to cause large outbreaks, which could lead to the eighth cholera pandemic. Continuous surveillance of the variants in circulation is our best chance of preventing mass outbreaks,” says Dr. Ankur Mutreja, group leader at the University of Cambridge’s Institute of Therapeutic Immunology and Infectious Disease and senior author of the study, published recently in Nature Communications.

The World Health Organization (WHO) estimates that globally there are 1.3 to 4.0 million cases of cholera, with 21,000 to 143,000 deaths annually.