News and Opinions  –  2018

Mass administration of antibiotics does not solve the root cause of child mortality in Africa

2018-05-23

The situation for many children in sub-Saharan Africa is dire: a variety of infectious diseases (such as pneumonia, diarrhea and malaria), malnutrition and inadequate water, sanitation and hygiene infrastructure all take their toll in these most vulnerable. According to UNICEF, the estimated mortality rate in children under 5 years in sub-Saharan Africa in 2016 was 78.4 deaths per 1000 live births. This can be contrasted with the estimated mortality rate in Western Europe being 3.9 deaths per 1000 live births. The difference is immense, and we all share a responsibility to reduce these mortality rates.

A case for azithromycin to reduce child mortality

A paper in the New England Journal of Medicine, researchers studied the effect of offering intermittent single doses of antibiotics to all children between 1 month and 5 years of age in a community on mortality over the course of 2.5 years. The study team conducted censuses in communities in Niger, Malawi and Tanzania, and offered all children in the communities to participate in the study, where the whole community were randomized into treatment or placebo regimens. This mass administration of antibiotics to whole communities of children reduced the measured overall mortality rates from 16.5 to 14.6 per 1000 person-years, a 13.5 % drop. The team also assessed the causes of death in a random sample of 250 deaths per country: 41% were caused by malaria, 18% by diarrhea or dysentery, and 12 were caused by pneumonia.

No assessment of antibiotic resistance

However, the study wasn’t designed to detail how azithromycin contributes to reduced mortality. Certainly, azithromycin can be used against pneumonia and gastrointestinal infections, and to some degree malaria, and the accumulated efficacy shown in the study could support that the pathogen carriage burden in the community can be reduced. Unfortunately no assessment of antibiotic resistance was made in the communities that participated in the trial, albeit the authors acknowledge the problem of resistance to azithromycin caused by mass treatment of trachoma.

Difference between regions and age groups

Efficacy of Azithromycin by Age Group. Shown is the estimated percent lower mortality with twice-yearly distributions of oral azithromycin than with placebo, according to age group at the time of treatment. Younger children had the greatest benefit in all three countries. bars indicate 95% confidence intervals. JD Keenan et al. N Engl J Med 2018;378:1583-1592.

Subgroup analysis showed great differences between regions and over age groups. In children aged 1-5 months, mortality was clearly reduced in all three countries by approximately 25%, but in children older than 6 months, there was no benefit of azithromycin in Malawi and Tanzania in contrast with Niger, where mortality was decreased with approximately 20%.

Benefits need to be assessed regionally

In the situation described in the study, it seems that a universal mass administration campaign is not warranted for children older than 5 months. Rather, the possible benefits need to be assessed regionally – in this case it would be imprudent to mass administer azithromycin in Malawi and Tanzania. Although the researchers did not observe resistance throughout the trial, it was noted that mass nonspecific distribution of antibiotics has potential risks of induction or amplification of resistance, which could curb or reverse any short-term gains in childhood mortality.

Should antibiotics be administered en masse?

Any use of antibiotics, necessary or not, causes selective pressures and contributes to the development and spread of resistance and needs to be carefully considered. The extension of recommending mass distribution of oral azithromycin in the trial requires further assessment of associated costs of increasing selective pressure for resistance. Given the major crisis of antibiotic resistance, measures should be taken to reduce the use of antibiotics globally. While the study didn’t find immediate adverse events to be caused by azithromycin, the unintended consequences, including the risk of resistance development need to be taken seriously.

While we do have a collective global responsibility to reduce childhood mortality, non-specific mass administration of antibiotics is not a solution in the longer perspective. Rather, such ‘quick fix’ could be dangerous if it tends to discourage more systematic and sustainable interventions in tackling the complex, underlying causes of mortality. We need to prevent the infections as far as possible and treat the ones that cannot be prevented more efficiently. The short-term medical gains from antibiotic use should not be an excuse not to strengthen health systems in preventing, diagnosing and documenting infections, especially in resource-limited settings.

Antibiotic mass administration do not solve root problem and there are alternatives

Even though the results in the paper are promising in the short term, using antibiotics do not solve the root problems in these communities. It is important to realize that there are better, more sustainable ways to prevent infections than using antibiotics. The major factor that can control spread of a plethora of infections is improved water, sanitation and hygiene (WASH). This one intervention could break the chain of transmission to a level where antibiotics are rarely needed. Estimates from UNICEF show that 494 million cases of diarrhea are treated with antibiotics each year in Brazil, Indonesia, India and Nigeria alone. Universal access to improved WASH in these four countries could cut this number by 60%. Other factors that also play in are preventing mosquito bites in the case of malaria, improved access to health services and proper diagnostics. Better nutrition also plays a vital part in the proper functioning of the immune system and reduces susceptibility to infections.

Sources

UNICEF Data: Monitoring the Situation of Children and Women.

New England Journal of Medicine: Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa (paywall)

CIDRAP: African study on pre-emptive antibiotics in kids spurs resistance debate.

UNICEF: Pneumonia and diarrhoea: Tackling the deadliest diseases for the world’s poorest children. 

ReAct – Action on Antibiotic Resistance: ReAct Fact sheets

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