Abstract
.Recent evidence indicates mass drug administration with azithromycin may reduce child mortality. This study uses verbal autopsy (VA) to investigate the causes of individual deaths during the Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial in Malawi. Cluster randomization was performed as part of MORDOR. Biannual household visits were conducted to distribute azithromycin or placebo to children aged 1–59 months and update the census to identify deaths for VA. MORDOR was not powered to investigate mortality effects at individual sites, but the available evidence is presented here for hypothesis generation regarding the mechanism through which azithromycin may reduce child mortality. Automated VA analysis was performed to infer the likely cause of death using two major analysis programs, InterVA and SmartVA. A total of 334 communities were randomized to azithromycin or placebo, with more than 130,000 person-years of follow-up. During the study, there were 1,184 deaths, of which 1,131 were followed up with VA. Mortality was 9% lower in azithromycin-treated communities than in placebo communities (rate ratio 0.91 [95% CI: 0.79–1.05]; P = 0.20). The intention-to-treat analysis by cause using InterVA suggested fewer HIV/AIDS deaths in azithromycin-treated communities (rate ratio 0.70 [95% CI: 0.50–0.97]; P = 0.03) and fewer pneumonia deaths (rate ratio 0.82 [95% CI: 0.60–1.12]; P = 0.22). The use of the SmartVA algorithm suggested fewer diarrhea deaths (rate ratio 0.71 [95% CI: 0.51–1.00]; P = 0.05) and fewer pneumonia deaths (rate ratio 0.58 [95% CI: 0.33–1.00]; P = 0.05). Although this study is not able to provide strong evidence, the data suggest that the mortality reduction during MORDOR in Malawi may have been due to effects on pneumonia and diarrhea or HIV/AIDS mortality.
Highlights
Mass drug administration (MDA) with azithromycin is widely used by trachoma control programs as part of efforts to eliminate trachoma, the leading infectious cause of blindness globally.[1]
As an independent analysis to the verbal autopsy (VA) algorithm outputs, the proportion of individuals with open response terms and positive responses to VA questions related to the major causes of child mortality were assessed, the open response terms “malaria,” “pneumonia,” and “diarrhea” and VA items “maternal test positive for HIV,” “frequent loose/liquid stool continuing until death,” “very severe cough,” and “severe fever”
This study investigated the effect of azithromycin MDA on each of the major causes of child mortality in Mangochi District, Malawi, during the MORDOR trial
Summary
Mass drug administration (MDA) with azithromycin is widely used by trachoma control programs as part of efforts to eliminate trachoma, the leading infectious cause of blindness globally.[1] During interventions principally aimed at eliminating trachoma, evidence emerged of reductions in a number of infectious diseases following azithromycin MDA, including diarrhea,[2] pneumonia,[3] and malaria.[4,5,6] A study from Ethiopia reported a large reduction in child mortality following azithromycin MDA.[7] Expert opinion suggested that a reduction in mortality was likely but to a lesser extent than estimated in this single available trial.[8] MORDOR was a large multicenter trial that recently tested the hypothesis that biannual azithromycin MDA to children aged 1–59 months would reduce childhood mortality, reporting a 14% overall reduction in mortality in those assigned to azithromycin versus placebo.[9] There is limited literature related to the mechanism through which azithromycin MDA may reduce child mortality. Azithromycin may reduce opportunistic infections in HIV-positive individuals, including Mycobacterium avium complex, and investigation is underway regarding its effect on HIV-associated chronic lung disease.[10,11]
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