G. Balakrish Nair on the Microbiology of Cholera

Special Topic of Cholera Interview, March 2011

G. Balakrish NairCholera is an infection of the human small intestine caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting which, if left untreated, leads to dehydration and rapidly to death. Historically, it was greatly feared in London and New York City, both of which were hit by pandemics in the 1830s. In developed countries that have good sanitation and few urban slums the disease is now virtually unknown. But in parts of the world with extreme poverty or where there have been natural disasters, such as Haiti, it affects millions of people and is responsible for about 100,000 deaths annually.

Our Special Topics analysis of cholera research published from 2000–2010 has identified Dr. G. Balakrish Nair as a highly cited author in the field of cholera. He has contributed to 137 papers that have received 2,197 citations in the past decade, which ranks him at #1 by number of papers and #3 by total cites. He is also in the top 1% of scientists in the field of Microbiology in Essential Science IndicatorsSM from Thomson Reuters.

Nair is the Director of the National Institute of Cholera & Enteric Diseases (NICED) in Kolkata (formerly Calcutta), India. He also sits on the Editorial/Advisory Boards of several journals, including the Indian Journal of Medical Research; Epidemiology and Infection; Microbes and Environments; and the Journal of Health, Population and Nutrition.

ScienceWatch.com correspondent Simon Mitton interviewed him by phone about his work on cholera.

SW: A notable feature of your highly cited papers is that almost without exception they feature laboratory work on Vibrio cholerae. The citation analysis shows that you are a world expert on the pathogenic strains of this organism. What sparked your interest?

My first degree is in zoology from the University of Madras, following which I studied at Annamalai University for a master's in marine biology, specializing in marine microbiology. At that time I developed an interest in seafood-borne pathogens that cause diarrhea. My doctorate likewise was in marine microbiology, carried out at the Centre of Advanced Study in Marine Biology in Porto Novo in south India, where I was investigating the ecology and taxonomy of Vibrio parahaemolyticus, which is an organism that causes gastroenteritis and is transmitted by contaminated seafood.

At that point I became familiar with Vibrio cholerae, and I became very interested in it. By good fortune, towards the end of my doctoral work, the then-director of the National Institute of Cholera Diseases, Dr. S.C. Pal, visited our center in south India, and offered me a position.

SW: Having got a junior position, how did your interest in the microbiology of cholera develop?

I started at this institute in Kolkata, where I am now the director, in August 1981. Then I did a couple of short stints in the laboratories of Rita Colwell at the University of Maryland, and at Ottawa, at the Laboratory Center for Disease Control (which no longer exists). I then went to Japan for a longer postdoc assignment at the National Children's' Medical Research Centre and with Yoshifumi Takeda at Tokyo University.

I was here at NICED until 2000, when I moved to Dhaka, the capital of Bangladesh, to the International Centre for Diarrhoeal Diseases Research. I came back to NICED in 2007 because I thought it would be great to head a team of very good scientists and to give a research direction to this Institute.

SW: Can you give me a snapshot of how your papers have contributed to our understanding of cholera as a disease?

"...cholera overwhelms the public health system."

I have been trained as an environmental microbiologist, so I am basically a laboratory person. Over the past 30 years of working on cholera we have written a substantial number of papers on the laboratory aspects, which evolved from conventional techniques to more modern molecular methods including analysis of the genome of this elusive pathogen. Most of the papers in the past decade continue the story of laboratory research as applied to understanding the molecular epidemiology of the pathogen.

SW: You spent seven years in Dhaka. Did that influence the direction of your research?

It certainly did. At the hospital in Dhaka I saw that the number of cholera patients did not seem to decline: sometimes they spilled over into the balconies or into the lounge, the courtyard, and even the parking garage! It struck me that I had done a lot of lab work but I had not made a difference to patient outcomes. That reflection changed my perspective: I wanted to look at the disease from an epidemiological point of view, and that characterizes the more recent papers.

I recently conducted a search of papers about cholera published in the past 30 years. Naturally there has been a steep increase in publications. It struck me that as the number of research papers increased, so the global burden of cholera seemed to be on the rise. To a statistician it would have seemed that the more knowledge we had, the greater the burden!

Obviously that's too simplistic but it set me thinking: henceforth I wanted to spend my research time on developing a tangible understanding of how to reduce burden of disease and develop prevention and control strategies.

SW: Can vaccines make a difference, or is it more complicated than that?

Much more complicated! Look, when I came back to Kolkata the Institute was in the midst of a large field trial of a cholera vaccine in collaboration with Dr. John Clemens and his team at the International Vaccine Institute (IVI, Seoul, South Korea). I joined them. That trial, and the collaboration with IVI, has led to a new generation of heat-killed cholera vaccine which from December 2009 is licensed in India.

In a series of lectures given throughout India we told clinicians, particularly those in pediatrics, that we now have a cholera vaccine. But I got a huge surprise: after my first lecture pediatricians asked why we require a vaccine for a disease that does not exist!

That appalled me. I think this denial has occurred because cholera has a negative political connotation: "don't use the C word—sweep it under the carpet—call it watery diarrhea, dysentery, gastroenteritis, what you like, but not cholera." This has been going on for 30 years: Bangladesh does not report cholera to the WHO. So what I observe is that people have almost forgotten about cholera and the huge burden it causes because of this denial.

SW: There's also a strong link between poverty and cholera I believe.

"At the hospital in Dhaka I saw that the number of cholera patients did not seem to decline: sometimes they spilled over into the balconies or into the lounge, the courtyard, and even the parking garage!"

Yes: cholera unfortunately is driven by poverty. We need to tell the world that cholera has not gone away. What's happened in Haiti, in Zimbabwe, and in a whole lot of places in Africa and Asia gives us clear indication that there is a lot of cholera and it is going to persist because cholera has an environmental reservoir and the moment there is a drop (or even no improvement) in standards of sanitation and hygiene you can be sure that this disease will prevail to an extent that will cause grave public health consequences.

SW: Your papers demonstrate a strong focus on understanding how specific serogroups, O1 and O139 are implicated in cholera. Could you tell me about that?

When I came to this Institute in 1981 I was intrigued by the distinction of serogroups. Only one serogroup at that point, namely O1, caused cholera and epidemics, while the other 130-odd serotypes, then known as non-O1, were incapable of causing cholera and epidemics, but were occasionally associated with diarrhea.

What struck me was a disparity in thinking because everyone worked on serotype O1 because that was the causative agent. A central question which they asked was: Why does O1 cause cholera and the epidemics? I reframed this question: I asked myself why do non-O1s not have the ability to cause cholera?

I imagined if I were able to answer this question perhaps the understanding of why O1 causes cholera would come to light. Therefore the research questions that I asked were different, and in many ways this interest in the non-O1 V. cholerae led to the first discovery of O139 serogroup in 1993.

In 1993 we discovered in Bengal the new bacterium causing cholera, O139. That was an important turning point. We are always on alert for changing phenotypes, and this interest led us to discover the variant/hybrid El Tor strains in 2002 which is now on a rampage across the world because it seems to have the virulence of both the biotypes, the classical and El Tor.

It fascinates us how this organism makes subtle changes. I still do not know if they are due to pre-existing immunity in endemic populations. But that may explain why V. cholerae comes back in slightly different forms and causes epidemics, spreading so efficiently as compared to other enteric pathogens.

SW: So does the organism have the capacity to produce menacing variants?

It is a fascinating organism! My recent publications have been mostly related to these discoveries of subtle new forms, including the variant which we know has caused the outbreak in Zimbabwe. I'm not too sure about the strain causing the outbreak of cholera in Haiti but that is something we are working on right now.

SW: Thank you for such an engaging and informative conversation. I know I've caught you at a busy time as you prepare to go to Haiti. How do you see the future?

I want to see the crushing burden of cholera decrease. I feel that my experience in the laboratory, field, and hospital gives a feel for what cholera can do and what an epidemic is like. I was involved in the epidemic caused by O139 in 1993. We had one patient arriving every four minutes at the infectious-diseases hospital here where we have 770 beds. Within 24 hours we were totally swamped: cholera overwhelms the public health system.

In reality, studies of the kind I make are not going to help very much on the front line. Cholera has become a social problem that requires issues of poverty to be addressed. We know how to eliminate cholera: there is none in Europe or America. It involves upgrading sanitation to levels where there is no water-borne transmission and also the provision of safe drinking water. In India and other developing countries it's a question of education and advocacy. That's what I am working on right now.End

G. Balakrish Nair, M.Sc., Ph.D.
National Institute of Cholera & Enteric Diseases
Beleghata, Kolkata, India


G. BALAKRISH NAIR'S MOST CURRENT MOST-CITED PAPER IN ESSENTIAL SCIENCE INDICATORS:

Sack DA, et al., "Cholera," Lancet 363(9404): 223-33, 17 January 2004 with 189 cites. Source: Essential Science Indicators from Clarivate Analytics.

KEYWORDS: CHOLERA, VIBRIO CHOLERAE, PATHOGENIC STRAINS, DIARRHEA, VIBRIO PARAHAEMOLYTICUS, GASTROENTERITIS, CONTAMINATED SEAFOOD, LABORATORY RESEARCH, MOLECULAR EPIDEMIOLOGY, PATIENT OUTCOMES, GLOBAL BURDEN, PREVENTION, CONTROL STRATEGIES, VACCINES, POVERTY, POLITICS, ENVIRONMENTAL RESERVOIR, SANITATION, HYGIENE, PUBLIC HEALTH, SEROGROUPS, O139, EL TOR, SAFE DRINKING WATER, EDUCATION, ADVOCACY.

 
 

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