Dave Goulding, Wellcome Sanger Institute

Cause of 1990s Argentina cholera epidemic uncovered

Work influenced Argentine health policy, where the national alert surveillance system now uses whole-genome sequencing to distinguish between pandemic and non-pandemic bacteria

The evolution of epidemic and endemic strains of the cholera-causing bacterium Vibrio cholerae in Argentina has been mapped in detail by researchers at the Wellcome Sanger Institute, the London School of Hygiene and Tropical Medicine, the University of Cambridge and the INEI-ANLIS “Dr Carlos G. Malbrán”, Argentina. The teams used whole genome sequencing to study the bacteria circulating during the 1991-1998 outbreak of cholera in the country.

The data have influenced health policy in Argentina, where the national alert surveillance system now uses whole-genome sequencing to distinguish between pandemic and non-pandemic lineages of V. cholerae bacteria. The study is published in Nature Communications today (1 October).

Cholera, caused by strains of V. cholerae bacteria, currently affects 47 countries world-wide and claims the lives of nearly 100,000 people a year*. Since the 1800s, there have been seven cholera pandemics around the globe, causing millions of deaths. The current pandemic, which began in the 1960s, is caused by a single lineage of V. cholerae, called 7PET. While South and Central Latin America have largely recovered from the outbreaks that began in Haiti in 2010, the lineage continues to circulate the globe and is the cause of the world’s largest cholera epidemic, ongoing in Yemen, where hundreds of thousands have been infected**, ***.

Josefina Campos, INEI-ANLIS “Dr. Carlos G. Malbrán”
INEI-ANLIS “Dr. Carlos G. Malbrán”
INEI-ANLIS “Dr. Carlos G. Malbrán”

In a new study, the team sequenced the genomes of a unique set of historical V. cholerae samples, held at INEI-ANLIS “Dr. Carlos G. Malbrán”, the national reference laboratory of Argentina. By re-analysing the past, the international team of researchers hope to understand better the future patterns of disease, and to enable rapid alerts for new introductions of pandemic lineages.

Using phylogenetic analysis, they confirmed that the 1992 outbreak of cholera in Argentina was caused by one introduction of 7PET V. cholerae bacteria, originally introduced into Peru. The bacteria then evolved very little during the six years of the epidemic. This was in contrast to the diverse, multiple endemic strains of V. cholerae circulating at the same time. Previous work by the team has shown that while endemic strains can make people ill, they seem to lack the potential to spread quickly and cause an epidemic****.

“When a 7PET pandemic strain enters into Latin America from elsewhere, it can cause massive epidemics, such as those seen in Peru in the 1990s and Haiti in 2010. If we are to control cholera epidemics efficiently, it is vital that we are able to distinguish and understand the differences between the local, endemic V. cholerae that co-exist alongside 7PET during a cholera epidemic. Our study elaborated the genomic evolutionary history of these two types together in a single country, during a decade where there were major cholera outbreaks in this region.”

Matthew Dorman, first author on the study from the Wellcome Sanger Institute

The findings have been used by public health authorities in Argentina, where the national alert system has now been changed to distinguish between pandemic 7PET lineage and local V. cholerae lineages using whole-genome sequencing.

“Thanks to a comprehensive surveillance and reporting system, the reference laboratory in Argentina contains a snapshot of an entire epidemic. This gave us a unique opportunity to understand the detailed evolution of V. cholerae bacteria in our country. We will be able to use these data and this experience to inform how we monitor and respond to any future cholera outbreaks – bacteria that cause epidemics pose a very different risk to those that do not; this is simple information that is critical for disease control. We are the first national reporting system in the world to use genomic data to monitor cholera like this.”

Dr Josefina Campos, senior author from INEI-ANLIS “Dr. Carlos G. Malbrán”, Buenos Aires, Argentina

“Detailed studies like this contribute to our growing understanding of how cholera is moving across the globe: evidence to inform improved control strategies as well as identify areas for further research. Our challenge is to better understand why such a simple bacterium continues to pose such a threat to human health, with this study we are a little step closer.”

Professor Nick Thomson, senior author from the Wellcome Sanger Institute and the London School of Hygiene and Tropical Medicine

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Notes to Editors

About Cholera:

Cholera is an acute diarrhoeal disease caused by ingesting food or water contaminated with the bacterium, Vibrio cholerae. Some people develop water diarrhoea with severe dehydration, which can lead to death if left untreated. The disease spreads between people in areas with inadequate access to clean water and sanitation. https://www.who.int/health-topics/cholera

* https://www.who.int/en/news-room/feature-stories/detail/prevention-for-a-cholera-free-world

** https://www.nature.com/articles/s41586-018-0818-3

*** World Health Organisation Weekly epidemiological record: https://www.who.int/wer/2020/wer9537/en/

**** https://science.sciencemag.org/content/358/6364/789

Publication

Matthew Dorman et al. Genomics of the Argentinian cholera epidemic elucidate the contrasting dynamics of epidemic and endemic Vibrio cholerae. Nature Communications 2020 11: 4918. DOI: 10.1038/s41467-020-18647-7

Funding

This work was supported by Wellcome, the Ministry of Health, Argentina, NIH, and BBSRC.

Selected websites

  • INEI-ANLIS “Dr Carlos G Malbrán”

    The National Administration of Laboratories and Institutes of Health / ANLIS, “Dr. Carlos G. Malbrán,” is an agency depending on the National Ministry of Health of Argentina. Our responsibilities are to implement the national strategies for referential diagnosis, epidemiological surveillance, outbreak evaluation, monitoring and control, and the production of strategic supplies for human health.

    ANLIS “Dr. Carlos G. Malbrán” is the only Argentine science and technology agency in charge of implementing programs and actions relevant for public health. We have made some major contributions establishing genomic surveillance for pathogens of public health concern for the country and the region with the Genomic Platform and the National Reference Laboratories. For instance, we are working on establishing and piloting genomic surveillance for tuberculosis, molecular epidemiology and tracking of azithromycin-resistant Neisseria gonorrhoeae clones, and determining the relation between virus subtypes and lesion progression in patients with human papillomavirus.

    We also respond to events that impact on public health, such as outbreaks and alerts in Argentina, and recently tracking the SARS-CoV-2 pandemic. We contribute towards understanding the dynamics and evolution of enteric diseases in a national, regional, and global context. This allows us to help answer questions on how enteric diseases spread and evolve by participating in different regional and global studies.

    http://www.anlis.gob.ar/

  • The Wellcome Sanger Institute

    The Wellcome Sanger Institute is a world leading genomics research centre. We undertake large-scale research that forms the foundations of knowledge in biology and medicine. We are open and collaborative; our data, results, tools and technologies are shared across the globe to advance science. Our ambition is vast – we take on projects that are not possible anywhere else. We use the power of genome sequencing to understand and harness the information in DNA. Funded by Wellcome, we have the freedom and support to push the boundaries of genomics. Our findings are used to improve health and to understand life on Earth. Find out more at www.sanger.ac.uk or follow us on Twitter, Facebook, LinkedIn and on our Blog.

  • About Wellcome

    Wellcome exists to improve health by helping great ideas to thrive. We support researchers, we take on big health challenges, we campaign for better science, and we help everyone get involved with science and health research. We are a politically and financially independent foundation.

    https://wellcome.org/

  • The London School of Hygiene & Tropical Medicine (LSHTM)

    is a world-leading centre for research, postgraduate studies and continuing education in public and global health. LSHTM has a strong international presence with over 3,000 staff and 4,000 students working in the UK and countries around the world, and an annual research income of £180 million.

    LSHTM is one of the highest-rated research institutions in the UK, is partnered with two MRC University Units in The Gambia and Uganda, and was named University of the Year 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.

    https://www.lshtm.ac.uk/