A study reveals why a highly infectious variant of the cholera virus, which caused major disease outbreaks in the early 1990s, did not cause the eighth cholera pandemic as feared, but instead disappeared unexpectedly.
The work, published in Nature Communications, analyzed samples of O139 Vibrio cholerae, a variant of the bacterium that causes cholera, and discovered significant changes in its genome over time that led to its unexpected decline.
These genetic changes led to a gradual loss of antimicrobial resistance (AMR) and a change in the types of toxins produced by the cholera virus. In combination, these changes likely explain the failure of O139 to seed the eighth cholera pandemic.
Currently, cholera is not subject to regular monitoring. Scientists say that continuous monitoring of genes underlying AMR and toxin production is essential to stay ahead of the evolution of cholera. In particular, this will help plan changes in vaccines and appropriate public health responses to prevent future cholera outbreaks.
The O139 variant of Vibrio cholerae was first detected in India in 1992. It quickly became dominant over the existing O1 variant and caused major 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, and cholera vaccines were modified as a result. But for some reason, that pandemic never happened: by 2015 the variant had largely declined and the O1 variant was once again established as a dominant strain. Until now, scientists have not understood why.
The rapid spread of O139 across Asia surprised scientists, who feared it would cause the eighth cholera pandemic, and cholera vaccines were modified as a result.
“There is a real possibility that another variant of cholera will emerge with the potential to cause large outbreaks, potentially leading to the eighth cholera pandemic. Continuous surveillance of circulating variants is our best chance of preventing massive outbreaks,” said Ankur Mutreja, from the Institute of Therapeutic Immunology and Infectious Diseases at the University of Cambridge, lead author of the study.
Cholera is a life-threatening infectious disease, usually contracted by eating or drinking contaminated food or water. It only causes large outbreaks in places where hygiene and sanitation are poor, so it is mostly confined to the developing world..
Cholera can also arise when water and sewage systems are interrupted due to war or natural disaster. Recent reports have warned that the Ukrainian city of MariupolNearly destroyed by weeks of Russian bombardment, it is now at risk of a major cholera outbreak.
Cholera is a life-threatening infectious disease, usually contracted by eating or drinking contaminated food or water
In the last 200 years, seven cholera pandemics have killed millions of people worldwide.; the seventh is still ongoing with large outbreaks in Yemen and Somalia. The dominant variant of Vibrio cholerae, the bacterium that causes cholera outbreaks today, is called O1 and emerged in the 1960s, replacing all pre-existing variants.
The new study analyzed 330 samples of the O139 cholera variant, taken between 1992 and 2015, to reveal two key changes in its genome that may have been the cause of its decline in three overlapping waves of disease transmission.
Before the O139 variant appeared, cholera was sensitive to many antibiotics. But O139 was resistant to these, which is probably why it became the dominant variant very quickly.
The study found that O139 had started with several genes that gave it resistance to antibiotics. But over time he gradually lost these genes. Collectively, the O1 variant gained antibiotic resistance.
“When it first emerged, the O139 cholera variant had antimicrobial resistance. But over time, this resistance was lost, while the pre-existing O1 variant gained resistance and re-established itself,” Mutreja concludes.