Cholera: understanding the link between the world’s major outbreaks paves the way to a better control strategy

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Researchers at the Institut Pasteur and the Wellcome Trust Sanger Institute, in collaboration with several other international institutions, recently published two studies tracing the history of cholera outbreaks in Africa, Latin America and the Caribbean from the last 60 years. Genomic analysis of more than 1,200 strains of Vibrio cholerae revealed for the first time the link between the different outbreaks of cholera since 1961. In particular, the researchers’ results show that the latest cholera pandemic originated in Asia, and that the majority of antibiotic resistant strains come from this continent. These findings, published on November 10, 2017 in Science, help to improve understanding of how the cholera bacterium circulates, and to anticipate the risk of new outbreaks emerging and adapt control strategies accordingly.

Cholera* is an acute infection of the small intestine caused by the bacterium Vibrio cholerae. It is thought of as an ancient disease yet still causes major outbreaks such as those recorded in Haiti in 2010 and the one currently ravaging Yemen. In 2016, cases were reported in 38 countries and almost 100,000 lives are still lost to the disease every year. Since the 1800s, there have been seven cholera pandemics around the globe, resulting in millions of deaths. France was notably hit by “Asian cholera” in 1832 during the second pandemic which claimed the lives of 19,000 people in Paris in just 6 months.

Researchers from the Institut Pasteur, the Institut Pasteur International Network and the Wellcome Trust Sanger Institute (Cambridge, UK), in collaboration with different international institutions, recently shed light on the link between the different cholera outbreaks affecting the African and American continents in the course of the current (7th) pandemic that began in 1961. Their research involved analyzing the genomes of more than 1,200 current and past strains of V. cholerae collected from across the globe over the last few decades.

The researchers focused on African and Latin American isolates, due to the large epidemics that have occurred in those regions. The seventh pandemic of cholera first came to Africa in 1970, and Africa has since become the continent most affected by the disease.

The researchers observed that the cholera bacterium had been introduced at least 11 times into Africa over a period of 44 years, always from Asia, and that human populations were the main vectors for disease dispersal throughout Africa.

Dr. François-Xavier Weill, Head of the Institut Pasteur Enteric Bacterial Pathogens Unit, explained: “These results show that cholera was not only introduced into Africa in 1970 before subsequently taking up residence there, but is repeatedly introduced to the two main regions of West and East Africa, spreading across the continent along similar paths to areas of persistence such as the Lake Chad Basin or the Great Lakes region. These results provide information about the regions of Africa that are most susceptible to the introduction of cholera, and that will need to be targeted to stem the wave of cholera before it sweeps the rest of the continent.”

The scientists also investigated the evolution of antibiotic resistance in the cholera bacterium. They discovered that, in the vast majority of cases, the multidrug resistance that the bacteria developed over time was acquired in South Asia before they were introduced into Africa.

In the second study, the team focused on Latin America where epidemic cholera reemerged in 1991 alongside sporadic cases of low level disease. This allowed the researchers to prove that different strains of V. cholerae can be assigned different risks for causing large outbreaks. The massive epidemics seen in Peru in the 1990s and Haiti in 2010 were caused by the Asian pandemic strain, whereas the sporadic cases in Latin America arose from local strains which do not seem to have epidemic potential. The genomic tools developed during this research will help predict the epidemic potential of given V. cholerae strains and enable the health authorities on the American continent to adapt their public health response strategy.

Dr. Marie-Laure Quilici, a scientist at the Institut Pasteur Enteric Bacterial Pathogens Unit and Head of the National Reference Center for Vibrios and Cholera, explained: “These studies show the added value of whole-genome sequencing of V. cholerae strains for cholera surveillance, prevention and control; they illustrate the benefits of combining epidemiological and laboratory data during investigations of epidemics, and lend weight to the message recently issued by the WHO’s Global Task Force on Cholera Control to public health practitioners, which recommends systematically combining these two approaches to improve epidemic management.”

Professor Nick Thomson of the Wellcome Trust Sanger Institute and London School of Hygiene and Tropical Medicine, said: “We are now getting a real sense of how cholera is moving across the globe. These findings have implications for the control of cholera pandemics, but also help to better understand how a simple bacterium continues to pose such a threat to human health.”

 

* About Cholera:
Cholera is an acute diarrheal disease caused by ingesting food or water contaminated with the bacterium Vibrio cholerae. Some people develop water diarrhea with severe dehydration, which can lead to death if left untreated. The disease spreads between humans in areas with inadequate access to clean water and sanitation.

Funding:
Study 1 – Institut Pasteur and the Institut Pasteur International Network, the Fondation Le Roch-Les Mousquetaires, Santé publique France, French government’s Investissement d’Avenir programme (Laboratoire d’Excellence IBEID), Wellcome Trust.

Study 2 – Wellcome Trust, Institut Pasteur, Santé publique France, French government’s Investissement d’Avenir programme (Laboratoire d’Excellence IBEID).

 



Sources

1 - Genomic history of the seventh pandemic of cholera in Africa, Science, November 10, 2017

François-Xavier Weill, Daryl Domman, Elisabeth Njamkepo, Cheryl Tarr, Jean Rauzier, Nizar Fawal, Karen Keddy, Henrik Salje, Sandra Moore, Asish K. Mukhopadhyay, Raymond Bercion, Francisco J. Luquero, Antoinette Ngandjio, Mireille Dosso, Elena Monakhova, Benoit Garin, Christiane Bouchier, Carlo Pazzani, Ankur Mutreja, Roland Grunow, Fati Sidikou, Laurence Bonte, Sébastien Breurec, Maria Damian, Berthe-Marie Njanpop-Lafourcade, Guillaume Sapriel, Anne-Laure Page, Monzer Hamze, Myriam Henkens, Gautam Chowdhury, Martin Mengel, Jean-Louis Koeck, Jean-Michel Fournier, Gordon Dougan, Patrick A.D. Grimont, Julian Parkhill, Kathryn E. Holt, Renaud Piarroux, Thandavarayan Ramamurthy, Marie-Laure Quilici*, Nicholas R. Thomson*

Science. DOI: 10.1126/science.aad5901

2 - Integrated view of Vibrio cholerae in the Americas, Science, November 10, 2017

Daryl Domman, Marie-Laure Quilici, Matthew J. Dorman, Elisabeth Njamkepo, Ankur Mutreja, Alison E. Mather, Gabriella Delgado, Rosario Morales, Cheryl Tarr, Patrick A.D. Grimont, Marcial Leonardo Lizárraga-Partida, Christiane Bouchier, Pablo Kuri-Morales, Cuitláhuac Ruiz-Matus, Gordon Dougan, Julian Parkhill, Josefina Campos, Alejandro Cravioto, François-Xavier Weill*, Nicholas R. Thomson*

Science. DOI: 10.1126/science.aao2136

 

* co-senior authors

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