Boy collects water in Yemen

In Yemen, an outbreak of cholera — which spreads through contaminated water — has killed thousands. Can genomics help to trace its spread?Credit: AP/Shutterstock

Cholera is easy to prevent and treat, but continues to take a heavy toll in many developing countries. The aim of the World Health Organization (WHO) is to reduce cholera deaths by 90% by 2030, and to eliminate the disease from 20 of the 48 affected countries. Its road map focuses on controlling the disease at a national level, and a key element is working out how outbreaks begin. Whole-genome sequencing of the bacterium that causes cholera is now providing fresh insight into where strains emerge and then spread around the world. It is time to integrate these developments into public-health measures.

A paper published this month in Nature on the genomics of the ongoing cholera outbreak in Yemen (caused by Vibrio cholerae) demonstrates the power of such an approach for tracing the lineages of strains, how these change over time and space, and the routes of disease spread — known as genomic phylogeography (F.-X. Weill et al. Nature 565, 230–233; 2019). Researchers sequenced the genomes of 116 V. cholerae samples from the Yemen epidemic, and worked out each one’s place in a global phylogenetic tree of more than 1,000 other isolates. They found that the strain originated in south Asia, and caused outbreaks in East Africa before spreading to Yemen. The findings are in line with an emerging picture of cholera in which south Asia serves as a cradle of new strains that lead to waves of cholera outbreaks worldwide.

Existing cholera strains in Africa are often thought to be locally entrenched. In fact, insights from genomics suggest that previous pandemic strains died out in Africa within a relatively short period — the most persistent one hung around for 28 years — and that, without imports of new strains, cholera might eventually vanish from Africa altogether.

Two seminal papers on the genomics of cholera spread were published in November 2017 (a month after the WHO road map). The first traced the genomic history of a cholera pandemic that started in Indonesia in 1961 (F.-X. Weill et al. Science 358, 785–789; 2017). The scientists studied 1,070 whole-genome sequences of samples of V. cholerae collected in 45 African countries over almost 50 years. They discovered that all epidemics on the continent had been caused by a single expanded lineage of cholera from Asia, which had been introduced on at least 11 occasions since 1970.

In the second study, researchers investigated the whole genomes of cholera strains in Central and South America, and reached a similar conclusion: although local strains can cause sporadic cases of cholera, it is new imports of Asian strains that fuel epidemics (D. Domman et al. Science 358, 789–793; 2017).

This altered picture of disease spread revealed by genomics shows that, although the WHO rightly focuses its efforts on controlling cholera in Africa, where most cases occur, it is crucial to tackle cholera at its source in Asia to reduce outbreaks in the long term. Asia is also where most antibiotic-resistant strains of cholera emerge.

The WHO road map appropriately concentrates on the basics of cholera control. The disease, which spreads through faecal contamination of food and water, can easily be prevented by the use of basic systems for sanitation and by providing clean drinking water. Infection can cause severe, acute diarrhoea that can kill within hours, but most cases are mild and can be swiftly treated by prompt administration of an oral hydration solution.

Cholera is often a marker of extreme poverty, and of vulnerable populations afflicted by conflicts or natural disaster. It causes an estimated 1.3 million to 4 million cases every year, and results in 21,000 to 143,000 deaths worldwide. This decade has witnessed major outbreaks in Haiti, Nigeria, the Democratic Republic of the Congo, Ghana, the Horn of Africa and East Africa. The war in Yemen has caused such destruction that more than half of the population has no access to sanitation or clean water, which helps to explain why the nation had more than 1 million cholera cases and more than 2,000 people died from the disease in 2017. These figures make Yemen’s cholera epidemic the largest in recent history.

Genomics can complement conventional methods of surveillance and diagnosis by placing outbreaks in a global context. Given that the costs of sequencing cholera genomes have fallen over the past ten years, the WHO should consider transforming today’s ad hoc genomic surveillance of cholera into a formal arrangement. This would organize sample collection and sequencing, providing information on the global emergence and circulation of cholera strains almost in real time — much as the WHO does now for strains of the influenza virus that infect humans.

Decent cholera surveillance also demands comprehensive reporting of outbreaks, and sharing of biological samples. Yet many cholera-endemic countries do not count or report the number of cases. Some nations in the Horn of Africa, East Africa and elsewhere also often report a major outbreak as ‘acute watery diarrhoea’ without saying which pathogen caused it. Countries often fear the public’s reaction or the negative economic consequences, such as falling tourism, if they declare outbreaks of the stigma-laden disease.

Yet as with many infectious diseases, the sooner control efforts are brought to bear, the easier it will be to prevent the rapid spread of an epidemic. Collecting and sharing more samples during outbreaks gives a fuller epidemiological and geographical picture, too.

A WHO stockpile of cheap and effective oral cholera vaccines is now available to countries that declare an outbreak — something that should give nations an incentive to report cases. And if a country is transparent about its cholera outbreaks, it is more likely to share samples from them. Through genomics, nations have much to gain in terms of improving understanding of cholera and being able to curb it. And that helps to build a more complete picture of the global spread and dynamics of this horrible disease.