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Researchers looking for a simple and inexpensive way to dramatically reduce child deaths in sub-Saharan Africa have published promising new findings today, but it is unclear whether their approach would risk further children in the fight against serious diseases.
The story begins in 2009, when a group of ophthalmologists from the University of California at San Francisco released the startling results of a study they had conducted in Ethiopia on trachoma, an eye infection that is the leading cause of preventable blindness in the world. Ophthalmologists knew that azithromycin, an antibiotic, was effective in controlling the disease and had given it to tens of thousands of children aged 1 to 9 years. They also wanted to know if the drug appeared to have other health benefits. the health of children.
What they have found is remarkable: the mbad treatment with azithromycin, administered twice a year, seems to have an almost miraculous ability to reduce the number of child deaths. In Ethiopia, 58 babies per 1,000 births do not survive before the age of five. This is less than the average for Sub-Saharan Africa (76) but remains well above that of Europe or the United States (where the rate is around 6 per 1,000). But in groups of children treated with azithromycin, the mortality rate was half that of untreated groups.
"It seemed almost unbelievable," says Jeremy Keenan, an ophthalmologist from UCSF who was not involved in the study but who had watched it with interest. Over the next few years, Keenan joined the research team after securing funding from the Gates Foundation (which also supports this blog) and endeavored to replicate the results elsewhere, with the addition of the following: azithromycin donated by the pharmaceutical giant Pfizer, which manufactures it. This effort, in which the antibiotic was administered to nearly 200,000 children in Tanzania, Malawi and Niger, released its first results last year. Even though they were not as shocking as in Ethiopia, they were still impressive: 14% mortality reduction in Tanzania and Malawi and 18% in Niger.
The study does not address the exact cause of this reduction, although researchers suspect that the antibiotic is a general defense against the myriad of gastrointestinal and respiratory microbes that typically affect young children in developing countries and can sometimes be fatal. untreated.
Despite its apparent success, the study raised concerns of global health experts: could such widespread use of an antibiotic in healthy children increase the likelihood of infectious bacteria developing antibiotic resistance? , making germs more difficult to overcome when children inevitably fall ill? In other words, could this seemingly miraculous solution actually trigger an evolutionary arms race that would eventually leave more children less able to defend themselves?
Keenan and his colleagues presented a mixed response to this question today, with the publication of a second set of conclusions in the New England Journal of Medicine. They found that "in Niger, even after three years of bi-annual treatment with azithromycin, the reduction in infant mortality remained about the same, suggesting that the antibiotic was still continuing." be effective and not lose effectiveness over time against resistant insects.
But a separate study by the same team tested participants in the pneumococcal study, a bacterium responsible for pneumonia and sinus infections. In the treated group, they found evidence of significantly higher levels of macrolide-resistant pneumococci (the clbad of antibiotics including azithromycin) compared to the group receiving a placebo. In other words, signs of antibiotic resistance were already starting to appear in the group treated with azithromycin.
The increase in the number of macrolide-resistant bacteria was expected, Keenan said, and was not as pronounced as in other areas where azithromycin has been widely spread to fight the trachoma. On the whole, the results are encouraging, he said. They offer further evidence that azithromycin can be a powerful weapon against infant mortality and that the increase in antibiotic resistance does not seem to be enough to change that.
"Our group really thinks that antimicrobial resistance is still a big problem," he said. "But it is true that there is more resistance and that the benefit of mortality disappears over time, we should be able to see it."
Other public health experts remain skeptical.
"This does not really dispel my worries about the potential for antibiotic resistance," says Nicola Low, an epidemiologist at the Institute of Social and Preventive Medicine at the University of Bern in Switzerland.
Low says she's been following the work of the UCSF team for years and that she's been impressed by the "remarkable" reductions in infant mortality. But she fears that the lawsuit does not go far enough to really measure the side effects of the mbadive distribution of azithromycin. On purpose, the researchers tracked only the deaths of children and not other cases of non-fatal infection (the reason being that, if they continuously monitored their study group for diseases, they would be forced to treat them, which could blur the measures of fatality). So other impacts may be hiding in the shadows, Low says.
"Most infections that children contract are not life-threatening," she says. "So, even if there is a resistance going around, you have to have a huge impact on death so that it is measurable."
In any case, monitoring the signs of antibiotic resistance within the study group itself is only part of the equation, says Marc Lipsitch, epidemiologist at T.H. at Harvard. Chan School of Public Health. Children in the study group could easily transmit antibiotic-resistant insects to their older siblings, parents, or others. And these people could have problems if azithromycin or another macrolide is the usual treatment for this virus, he says, "so you have to sample more people to see the effects."
Azithromycin is not commonly used in Niger for routine infections and, until now, Keenan and his colleagues have not found any signs of resistance from the group. Study with penicillin or other more common antibiotics. Even if they did, said Lipsitch, that would not necessarily be a reason to give up treatment. Antibiotics may be worth the risk in a country like Niger, where one of the highest infant mortality rates in the world is struggling to implement improvements such as food supply infrastructure. drinking water and primary care in rural areas that would help save the lives of children.
"I find nothing better to do with antibiotics than to save lives, and there are very few cases in which one can clearly see in a randomized trial that it saves lives," he said. "So the real question is whether the consequences for human health [of antibiotic resistance] are very serious and, if so, are they serious enough to compete with the impressive benefits of treatment. "
At the same time, says Keenan, "antibiotics are always a complement – they can never replace vaccines, clean water, or primary care, but with an antibiotic, you get what you pay for."
Ahmed Arzika, a Nigerian public health researcher at the US non-profit Carter Center, said Ahmed Arzika, who coordinated the field work for UCSF researchers. Of hundreds of villages that had initially been invited to participate, only one declined the invitation, he said. Several others, left out of the random selection, later contacted him to ask him to be included.
"We shared the results with the local authorities, they appreciated what was going on and wanted to continue to help us," he said. "Because of what it does for children, they are very happy with it."
The research is not over yet: Keenan and her colleagues hope to extend testing to infants under one month, for whom deaths from infections are even more common.
Aaron Milstone, an epidemiologist at the Bloomberg School of Public Health's Johns Hopkins, says it will still take many years to badess how much antibiotic resistance could become a problem for communities participating in the program. ;trial.
"They are not completely rebadured about long-term safety.Low antibiotic exposure in early childhood raises a lot of concerns, and how could this prepare you for other diseases more late in life, "he said. "But if I lived there and had to take the risk, now rather than later in life, I would take azithromycin."
Tim McDonnell is a journalist specializing in environment, conflict and related issues in sub-Saharan Africa. Follow on Twitter and Instagram.
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