The impact on malaria of biannual treatment with azithromycin in children age less than 5 years: a prospective study

Evan M Bloch, Beatriz Munoz, Zakayo Mrango, Jerusha Weaver, Leonard E G Mboera, Tom M Lietman, David J Sullivan Jr, Sheila K West, Evan M Bloch, Beatriz Munoz, Zakayo Mrango, Jerusha Weaver, Leonard E G Mboera, Tom M Lietman, David J Sullivan Jr, Sheila K West

Abstract

Background: The MORDOR study, a cluster randomized clinical trial, showed that single-dose azithromycin (20 mg/kg) administered biannually for 2 years to preschool children reduced mortality; a study was conducted to determine its effect on clinical symptomatic episodes of malaria as a potential mechanism for mortality benefit.

Methods: A randomized control trial (RCT) was conducted, whereby 30 randomly selected communities in Kilosa District, Tanzania were randomized to receive 6-monthly treatment of children ages 1-59 months with single-dose azithromycin (20 mg/kg) vs. placebo. A prospective cohort study was nested within the RCT: children, aged 1 to 35 months at baseline, were randomly selected in each community and evaluated at 6-monthly intervals for 2 years. At each visit, the children were assessed for recent or ongoing fever and anti-malarial treatment; a rapid diagnostic test (RDT) for malaria was performed. The two major outcomes of interest were prevalence of RDT positivity and clinical malaria. The latter was defined as RDT-positivity with fever at time of evaluation and/or reported fever in the 3 days prior to evaluation. Methods that account for correlations at community level and within individuals over time were used to evaluate associations.

Results: At baseline, the prevalence rates in the children in the azithromycin and placebo arms were 17.6% vs. 15.5% for RDT positivity (p = 0.76) and 6.1% vs. 4.3% (p = 0.56) for clinical malaria. There was a decline in both RDT-positivity and clinical malaria over time in both arms. The difference by treatment assignment was not significant for clinical malaria; it was significant for RDT-positivity with greater odds of decline in the placebo arm (p = 0.01).

Conclusions: Lack of evidence for a significant difference in the prevalence of clinical malaria in children at any visit following treatment suggests that the effect of single-dose azithromycin on malaria is at best transient and limited in scope. Chance overrepresentation of non-seasonal transmission in the communities in the azithromycin arm may account for higher rates of RDT-positivity and less decline over time. Trial registration Clinicaltrials.gov NCT02047981.

Keywords: Azithromycin; Child mortality; Clinical trial; Malaria; Tanzania.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Follow up rates in the cohort over time, by community treatment assignment. Some children missed visits but returned for subsequent visits. The figure reflects those who were also seen in other visits
Fig. 2
Fig. 2
Number of communities with 0 to more than 30% baseline prevalence of RDT positivity in cohort children by treatment arm
Fig. 3
Fig. 3
Map of participating communities by treatment assignment

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