Mathematical models point to broader antibiotic use as a tool against cholera

Mathematical models point to broader antibiotic use as a tool against cholera

Cholera kills thousands of people and infects hundreds of thousands every year - and cases have spiked in recent years, forcing governments to urgently find the best ways to control outbreaks.

Current public health guidelines discourage treating cholera with antibiotics in all but the most serious cases to reduce the risk that the disease will develop resistance to the best treatments we provide.

Recent disease research from research at the University of Utah Health, however, suggests that for some cholera outbreaks, more aggressive prescribing of antibiotics may slow or stop the disease and even reduce the likelihood of antibiotic resistance.

The results are based on mathematical modeling and require further research to confirm. However, they represent a first step toward understanding how antibiotics might alter the spread of cholera.

This may be a missed opportunity for cholera control, where scaling up antibiotic treatment to population levels and to control outbreaks can help control outbreaks. “

Lindsay Keegan, PhD, research associate professor of epidemiology at U of U Health and senior author on the study

The results will be published inBulletin of Mathematical Biology.

Apply brakes to breakouts

The key to the researchers' discovery is the fact that antibiotics make people less contagious. Medication is generally reserved for people who are most severely infected, as moderate cases recover quickly with rest and rehydration. Although antibiotics may not help most people feel better faster, they do shorten the time someone is infectious by a factor of 10.

"If you recover from cholera naturally, you will feel better in a day or two, but you will still shed cholera for up to two weeks," explains the PhD, assistant professor of epidemiology at Emory University's Rollins School of Public Health in the study, which included work as a postdoctoral research investigator in Keeger's laboratory. "But if you take an antibiotic, in about a day you'll still feel better and stop letting cholera into your environment."

This means that treating moderate cases with antibiotics can slow outbreaks or, in some cases, stop them in their tracks. Although a higher percentage of people with cholera would use antibiotics, fewer people would get the disease, so fewer antibiotics would be used overall.

Cumulatively, lower antibiotic use lowers the risk of cholera developing antibiotic resistance—which is "a big problem in the field," says Keegan. "Cholera is exceptionally good at evading antibiotics and developing resistance. It's not just a theoretical problem."

The researchers mathematically modeled the spread of cholera under different conditions to determine which cases might benefit from antibiotic use. The key variable is how likely someone is to spread the disease to other people, which in turn depends on factors such as population density and sanitation infrastructure.

In cases where cholera spreads more quickly in regions with higher population densities or without reliable access to clean drinking water, moderate cholera with antibiotics would not slow the spread enough to offset the risks of antibiotic resistance.

However, if the spread is relatively slow, the researchers noted that using antibiotics for moderate cases could limit the spread to the point where fewer people catch the disease and fewer people are treated with antibiotics. In some cases, they predict, the use of antibiotics could stop the outbreaks entirely.

Cases are rising

Figuring out better plans for managing cholera is particularly urgent as outbreaks have increased. Cases and deaths have risen by about a third over the past year, likely related to mass displacement and natural disasters. “We thought it was good in a few specific places, and now it's come out again,” says Ahmed.

As climate shifts and extreme weather events become more common, infrastructure disruptions could lead to cholera outbreaks in countries that have not yet experienced the disease.

The researchers emphasize that more work is needed before their work could motivate changes to how governments treat cholera. Scientists need to determine whether the results appear in more complex simulations that include factors like cholera vaccines, and they need to figure out the rules of thumb to quickly estimate whether the disease is spreading slowly enough for aggressive antibiotic use to be a good call.

"The takeaway isn't 'OK, let's give people antibiotics,'" Keegan says. “This is a first step in understanding the use of antibiotics as a way to control the outbreak.”

"If the results continue to be so compelling," adds Ahmed, "and we can replicate them in different settings, then we're talking about changing our guidelines for antibiotic treatment of cholera. This is a really good example of using data to continually improve our guidelines and our treatment decisions for even well-established diseases."

These results are published inBulletin of Mathematical Biologyas "a theoretical framework for quantifying the trade-off between individual and population benefits of expanded antibiotic use".

The work was funded by the Centers for Disease Control and Prevention (grant numbers 1U01CK000675 and 1NU38FT000009-01-00) and the Agency for Healthcare Research and Quality (grant number 5K08HS026530-06).

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