Dataset Information

Annual Versus Biannual Mass Azithromycin Distribution and Malaria Parasitemia During the Peak Transmission Season Among Children in Niger.

ABSTRACT: BACKGROUND:Azithromycin has modest efficacy against malaria, and previous cluster randomized trials have suggested that mass azithromycin distribution for trachoma control may play a role in malaria control. We evaluated the effect of annual versus biannual mass azithromycin distribution over a 3-year period on malaria prevalence during the peak transmission season in a region with seasonal malaria transmission in Niger. METHODS:Twenty-four communities in Matameye, Niger, were randomized to annual mass azithromycin distribution (3 distributions to the entire community during the peak transmission season) or biannual-targeted azithromycin distribution (6 distributions to children <12 years of age, including 3 in the peak transmission season and 3 in the low transmission season). Malaria indices were evaluated at 36 months during the high transmission season. RESULTS:Parasitemia prevalence was 42.6% (95% confidence interval: 31.7%-53.6%) in the biannual distribution arm compared with 50.6% (95% confidence interval: 40.3%-60.8%) in the annual distribution arm (P = 0.29). There was no difference in parasite density or hemoglobin concentration in the 2 treatment arms. CONCLUSIONS:Additional rounds of mass azithromycin distribution during low transmission may not have a significant impact on malaria parasitemia measured during the peak transmission season.

SUBMITTER: Oldenburg CE

PROVIDER: S-EPMC5924654 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Annual Versus Biannual Mass Azithromycin Distribution and Malaria Parasitemia During the Peak Transmission Season Among Children in Niger.

Oldenburg Catherine E CE Amza Abdou A Kadri Boubacar B Nassirou Beido B Cotter Sun Y SY Stoller Nicole E NE West Sheila K SK Bailey Robin L RL Porco Travis C TC Keenan Jeremy D JD Lietman Thomas M TM Gaynor Bruce D BD

The Pediatric infectious disease journal 20180601 6

<h4>Background</h4>Azithromycin has modest efficacy against malaria, and previous cluster randomized trials have suggested that mass azithromycin distribution for trachoma control may play a role in malaria control. We evaluated the effect of annual versus biannual mass azithromycin distribution over a 3-year period on malaria prevalence during the peak transmission season in a region with seasonal malaria transmission in Niger.<h4>Methods</h4>Twenty-four communities in Matameye, Niger, were ran ...[more]

PMID: 29088030

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Project description:BackgroundMass azithromycin distributions have been shown to reduce mortality in preschool children, although the factors mediating this mortality reduction are not clear. This study was performed to determine whether mass distribution of azithromycin, which has modest antimalarial activity, reduces the community burden of malaria.Methods and findingsIn a cluster-randomized trial conducted from 23 November 2014 until 31 July 2017, 30 rural communities in Niger were randomized to 2 years of biannual mass distributions of either azithromycin (20 mg/kg oral suspension) or placebo to children aged 1 to 59 months. Participants, field staff, and investigators were masked to treatment allocation. The primary malaria outcome was the community prevalence of parasitemia on thick blood smear, assessed in a random sample of children from each community at study visits 12 and 24 months after randomization. Analyses were performed in an intention-to-treat fashion. At the baseline visit, a total of 1,695 children were enumerated in the 15 azithromycin communities, and 3,029 children were enumerated in the 15 placebo communities. No communities were lost to follow-up. The mean prevalence of malaria parasitemia at baseline was 8.9% (95% CI 5.1%-15.7%; 52 of 552 children across all communities) in the azithromycin-treated group and 6.7% (95% CI 4.0%-12.6%; 36 of 542 children across all communities) in the placebo-treated group. In the prespecified primary analysis, parasitemia was lower in the azithromycin-treated group at month 12 (mean prevalence 8.8%, 95% CI 5.1%-14.3%; 51 of 551 children across all communities) and month 24 (mean 3.5%, 95% CI 1.9%-5.5%; 21 of 567 children across all communities) than it was in the placebo-treated group at month 12 (mean 15.3%, 95% CI 10.8%-20.6%; 81 of 548 children across all communities) and month 24 (mean 4.8%, 95% CI 3.3%-6.4%; 28 of 592 children across all communities) (P = 0.02). Communities treated with azithromycin had approximately half the odds of parasitemia compared to those treated with placebo (odds ratio [OR] 0.54, 95% CI 0.30 to 0.97). Parasite density was lower in the azithromycin group than the placebo group at 12 and 24 months (square root-transformed outcome; density estimates were 7,540 parasites/μl lower [95% CI -350 to -12,550 parasites/μl; P = 0.02] at a mean parasite density of 17,000, as was observed in the placebo arm). No significant difference in hemoglobin was observed between the 2 treatment groups at 12 and 24 months (mean 0.34 g/dL higher in the azithromycin arm, 95% CI -0.06 to 0.75 g/dL; P = 0.10). No serious adverse events were reported in either group, and among children aged 1 to 5 months, the most commonly reported nonserious adverse events (i.e., diarrhea, vomiting, and rash) were less common in the azithromycin-treated communities. Limitations of the trial include the timing of the treatments and monitoring visits, both of which took place before the peak malaria season, as well as the uncertain generalizability to areas with different malaria transmission dynamics.ConclusionsMass azithromycin distributions were associated with a reduced prevalence of malaria parasitemia in this trial, suggesting one possible mechanism for the mortality benefit observed with this intervention.Trial registrationThe trial was registered on ClinicalTrials.gov (NCT02048007).

Project description:BackgroundBiannual distribution of azithromycin to children 1-59 months old reduced mortality by 14% in a cluster-randomized trial. The World Health Organization has proposed targeting this intervention to the subgroup of children 1-11 months old to reduce selection for antimicrobial resistance. Here, we describe a trial designed to determine the impact of age-based targeting of biannual azithromycin on mortality and antimicrobial resistance.MethodsAVENIR is a cluster-randomized, placebo-controlled, double-masked, response-adaptive large simple trial in Niger. During the 2.5-year study period, 3350 communities are targeted for enrollment. In the first year, communities in the Dosso region will be randomized 1:1:1 to 1) azithromycin 1-11: biannual azithromycin to children 1-11 months old with placebo to children 12-59 months old, 2) azithromycin 1-59: biannual azithromycin to children 1-59 months old, or 3) placebo: biannual placebo to children 1-59 months old. Regions enrolled after the first year will be randomized with an updated allocation based on the probability of mortality in children 1-59 months in each arm during the preceding study period. A biannual door-to-door census will be conducted to enumerate the population, distribute azithromycin and placebo, and monitor vital status. Primary mortality outcomes are defined as all-cause mortality rate (deaths per 1000 person-years) after 2.5 years from the first enrollment in 1) children 1-59 months old comparing the azithromycin 1-59 and placebo arms, 2) children 1-11 months old comparing the azithromycin 1-11 and placebo arm, and 3) children 12-59 months in the azithromycin 1-11 and azithromycin 1-59 arms. In the Dosso region, 50 communities from each arm will be followed to monitor antimicrobial resistance. Primary resistance outcomes will be assessed after 2 years of distributions and include 1) prevalence of genetic determinants of macrolide resistance in nasopharyngeal samples from children 1-59 months old, and 2) load of genetic determinants of macrolide resistance in rectal samples from children 1-59 months old.DiscussionAs high-mortality settings consider this intervention, the results of this trial will provide evidence to support programmatic and policy decision-making on age-based strategies for azithromycin distribution to promote child survival.Trial registrationThis trial was registered on January 13, 2020 (clinicaltrials.gov: NCT04224987 ).

Project description:BackgroundBiannual azithromycin distribution has been shown to reduce child mortality as well as increase antimicrobial resistance. Targeting distributions to vulnerable subgroups such as malnourished children is one approach to reaching those at the highest risk of mortality while limiting selection for resistance. The objective of this analysis was to assess whether the effect of azithromycin on mortality differs by nutritional status.Methods and findingsA large simple trial randomized communities in Niger to receive biannual distributions of azithromycin or placebo to children 1-59 months old over a 2-year timeframe. In exploratory subgroup analyses, the effect of azithromycin distribution on child mortality was assessed for underweight subgroups using weight-for-age Z-score (WAZ) thresholds of -2 and -3. Modification of the effect of azithromycin on mortality by underweight status was examined on the additive and multiplicative scale. Between December 2014 and August 2017, 27,222 children 1-11 months of age from 593 communities had weight measured at their first study visit. Overall, the average age among included children was 4.7 months (interquartile range [IQR] 3-6), 49.5% were female, 23% had a WAZ < -2, and 10% had a WAZ < -3. This analysis included 523 deaths in communities assigned to azithromycin and 661 deaths in communities assigned to placebo. The mortality rate was lower in communities assigned to azithromycin than placebo overall, with larger reductions among children with lower WAZ: -12.6 deaths per 1,000 person-years (95% CI -18.5 to -6.9, P < 0.001) overall, -17.0 (95% CI -28.0 to -7.0, P = 0.001) among children with WAZ < -2, and -25.6 (95% CI -42.6 to -9.6, P = 0.003) among children with WAZ < -3. No statistically significant evidence of effect modification was demonstrated by WAZ subgroup on either the additive or multiplicative scale (WAZ < -2, additive: 95% CI -6.4 to 16.8, P = 0.34; WAZ < -2, multiplicative: 95% CI 0.8 to 1.4, P = 0.50, WAZ < -3, additive: 95% CI -2.2 to 31.1, P = 0.14; WAZ < -3, multiplicative: 95% CI 0.9 to 1.7, P = 0.26). The estimated number of deaths averted with azithromycin was 388 (95% CI 214 to 574) overall, 116 (95% CI 48 to 192) among children with WAZ < -2, and 76 (95% CI 27 to 127) among children with WAZ < -3. Limitations include the availability of a single weight measurement on only the youngest children and the lack of power to detect small effect sizes with this rare outcome. Despite the trial's large size, formal tests for effect modification did not reach statistical significance at the 95% confidence level.ConclusionsAlthough mortality rates were higher in the underweight subgroups, this study was unable to demonstrate that nutritional status modified the effect of biannual azithromycin distribution on mortality. Even if the effect were greater among underweight children, a nontargeted intervention would result in the greatest absolute number of deaths averted.Trial registrationThe MORDOR trial is registered at clinicaltrials.gov NCT02047981.

Project description:Vibrio cholerae is an estuarine bacterium associated with a single peak of cholera (March-May) in coastal villages of Bangladesh. For an unknown reason, however, cholera occurs in a unique dual peak (March-May and September-November) pattern in the city of Dhaka that is bordered by a heavily polluted freshwater river system and flood embankment. In August 2007, extreme flooding was accompanied by an unusually severe diarrhea outbreak in Dhaka that resulted in a record high illness. This study was aimed to understand the unusual outbreak and if it was related to the circulation of a new V. cholerae clone. Nineteen V. cholerae isolated during the peak of the 2007 outbreak were subjected to extensive phenotypic and molecular analyses, including multi-locus genetic screening by polymerase chain reaction (PCR), sequence-typing of the ctxB gene, and pulsed-field gel electrophoresis (PFGE). Factors associated with the unusual incidence of cholera were determined and analysis of the disease severity was done. Overall, microbiological and molecular data confirmed that the hypervirulent V. cholerae was O1 biotype El Tor (ET) that possessed cholera toxin (CT) of the classical biotype. The PFGE (NotI) and dendrogram clustering confirmed that the strains were clonal and related to the pre-2007 variant ET from Dhaka and Matlab and resembled one of two distinct clones of the variant ET confirmed to be present in the estuarine ecosystem of Bangladesh. Results of the analyses of both diarrheal case data for three consecutive years (2006-2008) and regional hydroclimatology over three decades (1980-2009) clearly indicate that the pattern of cholera occurring in Dhaka, and not seen at other endemic sites, was associated with flood waters transmitting the infectious clone circulating via the fecal-oral route during and between the dual seasonal cholera peaks in Dhaka. Circular river systems and flood embankment likely facilitate transmission of infectious V. cholerae throughout the year that leads to both sudden and off-season outbreaks in the densely populated urban ecosystem of Dhaka. Clonal recycling of hybrid El Tor with increasing virulence in a changing climate and in a region with a growing urban population represents a serious public health concern for Bangladesh.

Dataset Information

Annual Versus Biannual Mass Azithromycin Distribution and Malaria Parasitemia During the Peak Transmission Season Among Children in Niger.

Publications

Annual Versus Biannual Mass Azithromycin Distribution and Malaria Parasitemia During the Peak Transmission Season Among Children in Niger.

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