Scientifically Speaking: The evolving map of Cholera

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Scientifically Speaking: evolving


In 1896, a British scientist named Ernest Hankin was stumped by something he noticed in the water of the Ganga and the Yamuna.

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Cholera has caused seven pandemics in the last two centuries. (Representative file photo)
Cholera has caused seven pandemics in the last two centuries. (Representative file photo)

The rivers received the bodies of cholera victims. Water downstream should have been loaded with the curved bacterium that Robert Koch had identified in the early 1880s as the cause of the disease. There should be widespread outbreaks.

Yet outbreaks faded quickly. Something in the river water seemed to be killing the cholera bacteria because they could cause havoc. Hankin also noted that the effect was stronger in the Ganga than in the Yamuna, and that it was stronger than in well water from nearby towns.

Hankin could not see the killer and found that it was small enough to pass through a porcelain filter designed to hold back bacteria. He guessed it was a chemical agent in the water and published his results.

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Twenty years later, Frederick Twort in England and Félix d’Hérelle in France described tiny viruses that infect and kill bacteria. D’Hérelle gave them the name bacteriophages, which means bacteria eaters. This is the name that has stuck. These viruses that parasitize bacteria are the most predominant biological entities on the planet and they outnumber bacteria by roughly ten to one.

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Looking back, it’s tempting to wonder if Hankin was the first person to find bacteriophages when he noted something in the water. We will never know for sure, but it’s an important question and not just for historical reasons. Cholera is still very much with us, even though we know what causes it and how to prevent it.

Cholera has caused seven pandemics in the last two centuries. The first began in 1817 around Jessore in the Ganga Delta. The seventh began in 1961 in Sulawesi, and we are still in the midst of it. In 2023, the World Health Organization reported around 667,000 cases across five of its six regions. In the spring of 2022, a hospital in Bangladesh treated more than 42,000 patients in Dhaka in a single outbreak.

Bacteria-eating viruses have been with cholera through all those years. In the mid-2000s, researchers showed that as cholera bacteria multiplied in waters during outbreaks, viruses that preyed on them rose in number too, apparently causing the outbreaks to end.

These viruses seem to be making cholera less severe inside the body too. A few years ago, researchers found that cholera patients with high ratios of cholera killing viruses to cholera bacteria in their stool had milder dehydration. On the other hand, patients with low ratios were sicker.

Now two back-to-back papers recently published in Nature add to the complex and forth between these viruses and cholera.

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In one project, researchers watched a new antiviral defense system spread through the cholera population in Bangladesh in real time. Bacteria routinely pick up loose pieces of DNA from their surroundings, from other bacteria, and sometimes even from the viruses that prey on them. Some of those pieces carry instructions for useful survival tools. In a way bacteria have their own “immune systems” and they may be the ancestors of many aspects of our own immunity as well.

In September 2021, cholera bacteria in Bangladesh began carrying a new antiviral tool, one that worked as a shield against bacteria-eating viruses. Within nine months, the shield was found in 91 percent of cholera samples from patients because it was giving them a survival advantage. By the time the 2022 outbreak hit in Bangladesh, the viruses sampled from patient stool could no longer kill the new shielded cholera. Cholera bacteria were on top, at least for a while.

But that advantage didn’t last either. Eleven months later, new virus variants emerged that were good at killing cholera bacteria. Viruses struck back against cholera bacteria.

The whole sequence reads like an espionage novel on a microscot kill them come back with new tools. Bacteria then try to get the upper hand, and the seesaw swings back and forth ad infinitum.

The second project published in Nature is equally interesting because it tells us how cholera has been spreading. Researchers read the full genetic blueprints of cholera samples from Bangladesh and northern India. Every cholera bacterium carries small genetic differences that accumulate as it spreads. Reading those differences and comparing them across thousands of samples lets scientists draw a family tree of the disease, a record of which strains are related to which, and where they come from.

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According to this study, India, more often than Bangladesh, appeared to seed outbreaks elsewhere in the world. Kolkata is not far from Khulna in Bangladesh. Rivers, fish, and birds ignore the international border. What about bacteria and viruses? The new work shows that cholera samples from Kolkata are more closely related to samples from North India, than they are to samples from Bangladesh. In other words, geographically close regions seem to be carrying somewhat different cholera bacteria depending on which country, India or Bangladesh, they originate in.

It’s an intriguing finding, and not just for microbiologists. We’ve known since Koch and Hankin that cholera spreads in dirty water. But new research reinforces something that we should also know about microbes. They follow the movement of people.

Anirban Mahapatra is a scientist and author. His most recent book is When the Drugs Don’t Work. The views expressed are personal.

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