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Cholera: The link between the world's major outbreaks leads to better control strategies

November 13, 2017

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.

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."
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* 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.

About the Institut Pasteur and the Institut Pasteur International Network:

The Institut Pasteur, a private foundation with officially recognized charitable status set up by Louis Pasteur in 1887, is today an internationally renowned center for biomedical research with a network of 33 institutes worldwide. In the pursuit of its mission to prevent and fight against diseases in France and throughout the world, the Institut Pasteur operates in four main areas: scientific and medical research, public health and health monitoring, teaching, and business development and technology transfer. More than 2,500 people work on its Paris campus. The Institut Pasteur is a globally recognized leader in infectious diseases, microbiology, and immunology. Its 130 units also focus their research on certain cancers, genetic and neurodegenerative diseases, genomics and developmental biology. This research aims to expand our knowledge of living organisms in a bid to lay the foundation for new prevention strategies and novel therapeutics. Since its inception, 10 Institut Pasteur scientists have been awarded the Nobel Prize for Medicine, including two in 2008 for the 1983 discovery of the human immunodeficiency virus (HIV) that causes AIDS.

http://www.pasteur.fr/en

The London School of Hygiene & Tropical Medicine:

The London School of Hygiene & Tropical Medicine is a world-leading centre for research and postgraduate education in public and global health, with more than 4,000 students and 1,000 staff working in over 100 countries. The School is one of the highest-rated research institutions in the UK, is among the world's leading schools in public and global health, and was named University of theYear in the Times Higher Education Awards 2016. Our mission is to improve health and health equity in the UK and worldwide; working in partnership to achieve excellence in public and global health research, education and translation of knowledge into policy and practice. http://www.lshtm.ac.uk

The Wellcome Trust Sanger Institute:

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. To celebrate its 25th year in 2018, the Institute is sequencing 25 new genomes of species in the UK. Find out more at http://www.sanger.ac.uk or follow @sangerinstitute

Wellcome:

Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. http://www.wellcome.ac.uk

Institut Pasteur

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