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

Malar J. 2019 Aug 23;18(1):284. doi: 10.1186/s12936-019-2914-8.


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 NCT02047981.

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

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antimalarials / administration & dosage*
  • Azithromycin / administration & dosage*
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Malaria / epidemiology
  • Malaria / prevention & control*
  • Male
  • Prevalence
  • Prospective Studies
  • Tanzania / epidemiology
  • Time Factors


  • Antimalarials
  • Azithromycin

Associated data