Bloch EM, Munoz B, Mrango Z, et al. - Given the observed reduction in mortality in the MORDOR study, a cluster-randomized clinical trial, following single-dose azithromycin (20 mg/kg) administration biannually for 2 years to preschool children, researchers examined if this mortality benefit could be related to its effect on clinical symptomatic episodes of malaria. An RCT was conducted randomizing 30 randomly selected communities in Kilosa District, Tanzania to receive 6-monthly treatment of children ages 1–59 months with single-dose azithromycin (20 mg/kg) vs placebo was performed. Within the RCT, a prospective cohort study was nested: random selection of children (aged 1 to 35 months at baseline) in each community was made and evaluation of these children at 6-monthly intervals for 2 years was done. Assessment of the children for recent or ongoing fever and anti-malarial treatment was made at each visit; and further, a rapid diagnostic test (RDT) for malaria was performed at each visit. At baseline, the children in the azithromycin and placebo arms had prevalence rates of 17.6% vs 15.5% for RDT positivity and 6.1% vs 4.3% for clinical malaria. Both RDT-positivity and clinical malaria declined over time in both arms. No evidence was identified indicating a significant difference in the prevalence of clinical malaria in children at any visit following treatment. This suggests that the effect of single-dose azithromycin on malaria is at best transient and limited in scope. In the communities in the azithromycin arm, chance overrepresentation of non-seasonal transmission was observed that may account for higher rates of RDT-positivity and less decline over time.