Malaria positivity following a single oral dose of azithromycin among children in Burkina Faso: a randomized controlled trial

Jessica Brogdon, Clarisse Dah, Ali Sié, Mamadou Bountogo, Boubacar Coulibaly, Idrissa Kouanda, Mamadou Ouattara, Guillaume Compaoré, Eric Nebie, Mariam Seynou, Elodie Lebas, Fanice Nyatigo, Huiyu Hu, Benjamin F Arnold, Thomas M Lietman, Catherine E Oldenburg, Jessica Brogdon, Clarisse Dah, Ali Sié, Mamadou Bountogo, Boubacar Coulibaly, Idrissa Kouanda, Mamadou Ouattara, Guillaume Compaoré, Eric Nebie, Mariam Seynou, Elodie Lebas, Fanice Nyatigo, Huiyu Hu, Benjamin F Arnold, Thomas M Lietman, Catherine E Oldenburg

Abstract

Background: Azithromycin is a broad-spectrum antibiotic that has moderate antimalarial activity and has been shown to reduce all-cause mortality when biannually administered to children under five in high mortality settings in sub-Saharan Africa. One potential mechanism for this observed reduction in mortality is via a reduction in malaria transmission.

Methods: We evaluated whether a single oral dose of azithromycin reduces malaria positivity by rapid diagnostic test (RDT). We conducted an individually randomized placebo-controlled trial in Burkina Faso during the high malaria transmission season in August 2020. Children aged 8 days to 59 months old were randomized to a single oral dose of azithromycin (20 mg/kg) or matching placebo. At baseline and 14 days following treatment, we administered a rapid diagnostic test (RDT) to detect Plasmodium falciparum and measured tympanic temperature for all children. Caregiver-reported adverse events and clinic visits were recorded at the day 14 visit.

Results: We enrolled 449 children with 221 randomized to azithromycin and 228 to placebo. The median age was 32 months and 48% were female. A total of 8% of children had a positive RDT for malaria at baseline and 11% had a fever (tympanic temperature ≥ 37.5 °C). In the azithromycin arm, 8% of children had a positive RDT for malaria at 14 days compared to 7% in the placebo arm (P = 0.65). Fifteen percent of children in the azithromycin arm had a fever ≥ 37.5 °C compared to 21% in the placebo arm (P = 0.12). Caregivers of children in the azithromycin group had lower odds of reporting fever as an adverse event compared to children in the placebo group (OR 0.41, 95% CI 0.18-0.96, P = 0.04). Caregiver-reported clinic visits were uncommon, and there were no observed differences between arms (P = 0.32).

Conclusions: We did not find evidence that a single oral dose of azithromycin reduced malaria positivity during the high transmission season. Caregiver-reported fever occurred less often in children receiving azithromycin compared to placebo, indicating that azithromycin may have some effect on non-malarial infections. Trial registration Clinicaltrials.gov NCT04315272, registered 19/03/2020.

Keywords: Azithromycin; Malaria; Randomized controlled trial; Sahel.

Conflict of interest statement

No conflicts of interest are reported. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Map of the study area
Fig. 2
Fig. 2
CONSORT flow diagram of study participants

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