The rise and fall of Vibrio cholerae O139

Cholera is a serious disease that causes watery diarrhoea and is transmitted by the Vibrio cholerae bacterium, which can contaminate food or water. Only two serogroups of V. cholerae—O1 and O139—cause epidemics, while non-O1/O139 V. cholerae usually cause mild infections with similar symptoms and are linked to food poisoning. ¹ V. cholerae O1 is responsible for all recent epidemics. V. cholerae O139 was first detected in Bangladesh in 1992 and caused some epidemics but has since been uncommon. It has not been found outside Asia. The two serogroups produce the same symptoms. ² There have been seven cholera pandemics heretofore. Cholera became a global threat after a deadly outbreak in Jessore, Bangladesh (formerly part of British India), in 1817. The second cholera pandemic affected Europe and the Americas in 1929. The third and most fatal is believed to have originated in India in 1852. The fourth and fifth were less severe, but some countries such as Italy, Spain, and Russia experienced very high mortality rates. The sixth killed many people in Arabia, India, and the North African coast between 1899 and 1923. The seventh, known as El Tor (after the strain), started on the Indonesian island of Celebes in the 1960s and spread across Asia. ³

A new type of non-O1 V. cholerae emerged in the early 1990s causing a disease very similar to O1 El Tor. This type was first found in Chennai (Tamil Nadu, India), and none of the 138 existing somatic antisera could agglutinate it. It was given a new serogroup name, O139, which was later confirmed. This serogroup is also called the ‘Bengal’ serogroup as it appeared near the Bay of Bengal. Unlike other non-O1 V. cholerae serogroups, which usually do not make cholera toxin (CT), the O139 V. cholerae strains had the genes for CT (CtxAB), sometimes in multiple copies.^4,5

The O139 V. cholerae replaced the El Tor vibrios in the first wave of cases in Bangladesh, India, and nearby countries in 1992–1993. ¹ The O139 vibrios only affected the south coast regions from 1994 to mid-1995, while the remaining regions in India presented a new type of V. cholerae O1 of the El Tor biotype (later studies showed that the O139 genomes had much genetic variation ¹ ). O139 cases appeared in many parts of Bangladesh in late 1995 and early 1996. ⁵ In 1996, Kolkata (West Bengal, India) had more O139 cholera strains than Dhaka (Bangladesh). In 1998 and the first half of 2002, there was a large outbreak of O139 in Dhaka and surrounding areas. ⁶

The origin of the new O139 strain in the early 1990s was a mystery. It is more similar to the El Tor biotype than to the classical strains. Unlike other non-O1 vibrios, it has a capsule. ⁷ The O139 strain soon replaced the El Tor biotype and caused large outbreaks in India, southern Bangladesh, and other parts of Asia until the mid-2000s. It was feared that it might start an eighth pandemic. Because of this, cholera vaccines were changed to include protection for the O139 serogroup. Although we now have much information about Vibrio cholerae O139, the genetic reasons for its appearance, spread, and sudden disappearance are still unknown. ¹

Two major changes in the genes of O139 may have led to its decline after three waves (A-C) of outbreaks, which happened at the same time but were genetically different. First, there was a change from one type of toxin gene (ctxB3) in wave A to five different types of toxin genes (ctxB4, ctxB5, and three new variants) in waves B and C. Second, there was a gradual loss of resistance to antibiotics as the waves progressed. These two changes may have contributed to the end of the epidemic. ¹ O139 changed its genes rapidly and so became more diverse in wave A, then changed more slowly in waves B and C. ¹

Whilst the O139 V. cholera strains that caused the first outbreak in 1992–1993 came from an El Tor O1 strain, later studies showed that the O139 genomes had many genetic differences, including different numbers of the CTX prophage, which carries the toxin gene. ³ An O139 strain found in India in 1993 had a new genetic element (ICE) that gave it resistance to SXT, a combination of two antibiotics. Before this, O139 strains were resistant to SXT and streptomycin but not to tetracycline. The O139 strains found in 1996 lost some of their DNA and became sensitive to SXT. Later tests showed that they were still sensitive to streptomycin and chloramphenicol but more resistant to ampicillin and neomycin. This sudden change in the resistance pattern is due to mobile genetic elements, which can move between bacteria. This is also happening to V. cholerae O1 around the world. ⁸

Conclusion

O139 is no longer a major cause of cholera outbreaks, but there is a chance that O139 or another type could come from O1, with only a few changes in their DNA. Keeping track of O1 and its toxin and resistance genes, as well as its serogroup distribution, is therefore important. Efficacious vaccines require studying their serogroup change and how the new variants spread, to preserve cholera control.