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Genomic surveillance of cholera in South America

Article discussing the importance of global pathogen surveillance

The COVID-19 pandemic has brought pathogen genomics into sharp relief, and the language of “variants”, “lineages”, and “mutations” has entered common parlance. The public is now very much aware of the power of genome sequencing to track pathogen spread and evolution, to identify lineages of potential concern, and to monitor changing dynamics of micro-organisms. Genomics has substantially refined our understanding of the current global cholera pandemic and of Vibrio cholerae (the organism which causes this diarrhoeal disease). This is an excellent example of how genomics is entering the context of global health, not least because modern epidemiology has its roots in historical studies of cholera, as exemplified by the seminal work of John Snow to map and control a cholera outbreak in London in the 1850s.

Genomic data have recently shown that the ongoing seventh cholera pandemic has been caused by a specific lineage of serogroup O1 V. cholerae, now dubbed “7PET” (the sixth pandemic, and possibly other historical pandemics, were caused by “Classical” lineage V. cholerae. The 7PET lineage has been transmitted around the world in several waves and has been repeatedly introduced into Africa and Latin America over recent years. Importantly from a global health perspective, genomics can be used to distinguish between 7PET and other “non-7PET” lineages of V. cholerae. The importance of these distinctions is illustrated by a comparison of the cholera epidemics in Latin America.

Prior to 1991, Latin America had been cholera-free for nearly 100 years. However, in early 1991, a large cholera epidemic began in Peru and spread rapidly across the region. Cholera outbreaks and epidemics continued to be reported across Latin America and the Caribbean, until subsiding in the late 1990s, before resurging in Haiti during 2010. Genomic analyses have shown that two independent introductions of 7PET into Latin America occurred in the early 1990s; one sub-lineage was introduced into Peru, and a second discrete sub-lineage was introduced into Mexico. Both sub-lineages were toxigenic and associated with cholera cases, but their origins were distinct. The Haiti outbreak in 2010 was caused by a third independently-introduced sub-lineage of 7PET, rather than being caused by a “resurgence” of either of the previous introductions.

As well as the substantial disease burden caused by 7PET, other “non-7PET” V. cholerae have been identified. These bacteria were often isolated from clinical cases of diarrhoea and were members of the V. cholerae species, and could be toxigenic. However, they were not members of the 7PET lineage and – crucially – did not have the same burden of disease as 7PET. Multiple patterns of disease associated with different lineages of V. cholerae have been described, and just like how SARS-CoV-2 variants and lineages can behave differently, it is clear that different V. cholerae lineages have different abilities to cause outbreaks, epidemics, and pandemics. These observations could be made in Latin America because the enhanced surveillance for cholera in the region increased the number of non-pandemic V. cholerae, samples of which were isolated, stored, and available for sequencing (Figure 1).

200 cases recorded in the 1990s. Non-O1 lineages meanwhile presented fewer cases, and they are spread mostly through Argentina”>

Click to enlarge the image

Figure 1 – During the cholera epidemic of the 1990s, both O1 (“pandemic”) and non-O1 (“non-pandemic”) *V. cholerae* isolates were collected from the same places, at the same times, in Argentina. Such collections of isolates, obtained from the same places and times, are required to enable the comparison of dynamics between different lineages. Source: Nature Communications.

Cholera presents a major threat to public health, and its incidence is on the rise, with outbreaks reported in 29 countries in 2021. It has been estimated that there are ~2.9 million cases of cholera per annum, but these figures are believed to be an underestimate. From a global health perspective, understanding the dynamics of V. cholerae lineages can provide useful information. For instance, Argentina now uses genomic definitions in its declaration of a cholera alert if V. cholerae is isolated from a patient. This is done by using whole-genome sequencing to examine whether or not a V. cholerae isolate is a member of a pandemic lineage. Continued genomic study of V. cholerae will be important in the future, both for continuing to research current pandemic and non-pandemic lineages, and for monitoring for potential new lineages which might display a different pattern of disease.

Further reading

Comparative genomics reveals mechanism for short-term and long-term clonal transitions in pandemic Vibrio cholerae

Genomic Epidemiology of the Haitian Cholera Outbreak: a Single Introduction Followed by Rapid, Extensive, and Continued Spread Characterized the Onset of the Epidemic

Population Genetics of Vibrio cholerae from Nepal in 2010: Evidence on the Origin of the Haitian Outbreak

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Pathogen Genomics: A New Era in Global Health Surveillance and Strategy

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