Literature

Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published June 5, 2019

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Does the addition of azithromycin to seasonal malaria chemoprevention reduce overall childhood mortality and morbidity? 

The frequent contact between children and health care workers that is needed for seasonal malaria chemoprevention provides an opportunity for the delivery of other health interventions. Chandramohan et al. conducted a randomized, double-blind, placebo-controlled trial to determine whether the addition of azithromycin to the monthly sulfadoxine–pyrimethamine plus amodiaquine used for seasonal malaria chemoprevention would reduce mortality and morbidity among African children living in Burkina Faso and Mali. Read the Original Article here.

Clinical Pearls

Q: What is the approach to seasonal malaria chemoprevention in the Sahel and sub-Sahel regions of Africa?

A: Malaria transmission is concentrated during a few months of the year in much of the Sahel and sub-Sahel regions of Africa. In these areas, seasonal malaria chemoprevention — the administration of sulfadoxine-pyrimethamine plus amodiaquine to children at monthly intervals three or four times during the malaria-transmission season — has been a highly effective approach to malaria control.

Q: Has mass administration of azithromycin for trachoma control reduced the incidence of other types of infections?

A: Mass administration of azithromycin has been a highly effective approach to trachoma control. Reductions in the incidences of skin, gastrointestinal, and respiratory infections have been recorded after mass administration of azithromycin.

Morning Report Questions

Q: Does the addition of azithromycin to seasonal malaria chemoprevention reduce overall childhood mortality and morbidity?

A: In the trial by Chandramohan et al., among children in Burkina Faso and Mali, the addition of azithromycin to the antimalarial agents used for seasonal malaria chemoprevention did not result in a lower incidence of death or hospital admission that was not due to trauma or surgery than antimalarial agents plus placebo. The authors noted that the incidences of clinic visits for gastrointestinal infections, upper respiratory tract infections, and nonmalarial febrile illnesses, without adjustment for multiple comparisons, were lower among children who received antimalarial agents plus azithromycin than among those who received antimalarial agents plus placebo. 

Q: Are the findings of Chandramohan et al. similar to those of the MORDOR (Mortality Reduction after Oral Azithromycin) trial?

A: The findings of the trial by Chandramohan et al. contrast with those of the MORDOR trial conducted in Malawi, Niger, and Tanzania, in which azithromycin was given to children younger than 5 years of age twice a year for 2 years and then was associated with a 13.5% (95% CI, 6.7 to 19.8) lower overall all-cause mortality than placebo, with the effect being most marked in Niger. There are several possible explanations for the different outcomes of these two trials. One possible explanation is that azithromycin, which has antimalarial activity, contributed to decreased mortality in the MORDOR trial partly through its effect on malaria, and this benefit was lost when an additional, effective antimalarial combination was given at the same time as azithromycin. However, the effect of azithromycin on malaria has been inconsistent when azithromycin has been given in mass drug administration programs. In addition, all the children in the trial by Chandramohan et al. received sulfadoxine–pyrimethamine, which has weak antimicrobial properties, and this may have reduced the potential benefit of adding another antimicrobial to the regimen. Finally, coverage with a pneumococcal conjugate vaccine was high among children in the trial by Chandramohan et al., and this may have reduced the potential benefit of azithromycin in lowering mortality from pneumonia.

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