Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger

Arzika, Ahmed M.; Maliki, Ramatou; Goodhew, E. Brook; Rogier, Eric; Priest, Jeffrey W.; Lebas, Elodie; O’Brien, Kieran; Le, Victoria M.; Oldenburg, Catherine E.; Doan, Thuy; Porco, Travis C.; Keenan, Jeremy D.; Lietman, Thomas M.; Martin, Diana L.; Arnold, Benjamin F.

doi:10.1038/s41467-022-28565-5

Cited by 9 publications

(9 citation statements)

References 53 publications

(63 reference statements)

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“…To rehydrate blood samples from DBS, a 6 mm punch (~10 µL whole blood) was taken from each DBS sample and blood eluted to a 1:40 concentration in blocking buffer (Buffer B: Phosphate Buffered Saline (PBS) pH 7.2, 0.5% Bovine Serum Albumin (BSA), 0.05% Tween 20, 0.02% sodium azide, 0.5% polyvinyl alcohol, 0.8% polyvinylpyrrolidone and 3 µg/mL Escherichia coli extract) 41 . Elutions were stored at 4 °C until testing.…”

Section: Multiplex Bead-based Plasmodium Antigen Detection Assaymentioning

confidence: 99%

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Non-falciparum malaria infection and IgG seroprevalence among children under 15 years in Nigeria, 2018

et al. 2023

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Plasmodium falciparum (Pf) is the dominant malaria parasite in Nigeria though P. vivax (Pv), P. ovale (Po), and P. malariae (Pm) are also endemic. Blood samples (n = 31,234) were collected from children aged 0-14 years during a 2018 nationwide HIV survey and assayed for Plasmodium antigenemia, Plasmodium DNA, and IgG against Plasmodium MSP1-19 antigens. Of all children, 6.6% were estimated to have Pm infection and 1.4% Po infection with no Pv infections detected. The highest household wealth quintile was strongly protective against infection with Pm (aOR: 0.11, 95% CI: 0.05–0.22) or Po (aOR= 0.01, 0.00–0.10). Overall Pm seroprevalence was 34.2% (95% CI: 33.3-35.2) with lower estimates for Po (12.1%, 11.6-12.5) and Pv (6.3%, 6.0-6.7). Pm seropositivity was detected throughout the country with several local government areas showing >50% seroprevalence. Serological and DNA indicators show widespread exposure of Nigerian children to Pm with lower rates to Po and Pv.

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Section: Multiplex Bead-based Plasmodium Antigen Detection Assaymentioning

confidence: 99%

“…The IgG-detecting multiplex bead assay (MBA) was performed as described previously 41 , and included targets for a variety of infectious diseases, as well as vaccine-preventable disease targets. Assay plates were run on same machines utilizing the same software as the antigen detection assay.…”

Section: Multiplex Bead-based Igg Detection Assaymentioning

confidence: 99%

Non-falciparum malaria infection and IgG seroprevalence among children under 15 years in Nigeria, 2018

et al. 2023

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“…Azithromycin is a broad-spectrum antibiotic, and its effectiveness in reducing child mortality in this setting likely has numerous mechanisms. Azithromycin MDA has been associated with reductions in morbidity and mortality related to diarrheal disease, respiratory infections, and malaria . Given the possible mechanisms, several potential explanations exist for the association between azithromycin effectiveness and distance.…”

Section: Discussionmentioning

confidence: 99%

Distance to Health Centers and Effectiveness of Azithromycin Mass Administration for Children in Niger

Chao,

Arzika,

Abdou

et al. 2023

JAMA Netw Open

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ImportanceThe MORDOR (Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance) trial demonstrated that mass azithromycin administration reduced mortality by 18% among children aged 1 to 59 months in Niger. The identification of high-risk subgroups to target with this intervention could reduce the risk of antimicrobial resistance.ObjectiveTo evaluate whether distance to the nearest primary health center modifies the effect of azithromycin administration to children aged 1 to 59 months on child mortality.Design, Setting, and ParticipantsThe MORDOR cluster randomized trial was conducted from December 1, 2014, to July 31, 2017; this post hoc secondary analysis was conducted in 2023 among 594 clusters (communities or grappes) in the Boboye and Loga departments in Niger. All children aged 1 to 59 months in eligible communities were evaluated.InterventionsBiannual (twice-yearly) administration of a single dose of oral azithromycin or matching placebo over 2 years.Main Outcomes and MeasuresA population-based census was used to monitor mortality and person-time at risk (trial primary outcome). Community distance to a primary health center was calculated as kilometers between the center of each community and the nearest health center. Negative binomial regression was used to evaluate the interaction between distance and the effect of azithromycin on the incidence of all-cause mortality among children aged 1 to 59 months.ResultsBetween December 1, 2014, and July 31, 2017, a total of 594 communities were enrolled, with 76 092 children (mean [SD] age, 31 [2] months; 39 022 [51.3%] male) included at baseline, for a mean (SD) of 128 (91) children per community. Median (IQR) distance to the nearest primary health center was 5.0 (3.2-7.1) km. Over 2 years, 145 693 person-years at risk were monitored and 3615 deaths were recorded. Overall, mortality rates were 27.5 deaths (95% CI, 26.2-28.7 deaths) per 1000 person-years at risk in the placebo arm and 22.5 deaths (95% CI, 21.4-23.5 deaths) per 1000 person-years at risk in the azithromycin arm. For each kilometer increase in distance in the placebo arm, mortality increased by 5% (adjusted incidence rate ratio, 1.05; 95% CI, 1.03-1.07; P &lt; .001). The effect of azithromycin on mortality varied significantly by distance (interaction P = .02). Mortality reduction with azithromycin compared with placebo was 0% at 0 km from the health center (95% CI, −19% to 17%), 4% at 1 km (95% CI, −12% to 17%), 16% at 5 km (95% CI, 7% to 23%), and 28% at 10 km (95% CI, 17% to 38%).Conclusions and RelevanceIn this secondary analysis of a cluster randomized trial of mass azithromycin administration for child mortality, children younger than 5 years who lived farthest from health facilities appeared to benefit the most from azithromycin administration. These findings may help guide the allocation of resources to ensure that those with the least access to existing health resources are prioritized in program implementation.Trial RegistrationClinicalTrials.gov Identifier: NCT02047981

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“…Compared to prevalence, acquisition and clearance rates better capture the temporal changes at the exposure level and in immunity development. Over the past two decades, only two studies assessed the FOI of Campylobacter in children of heterogeneous age ranges in LMIC’s settings, and the FOI in both studies was estimated by seroconversion rate at an annual scale based on IgG data ( Arnold et al, 2019 , Arzika et al, 2022 ). Although the incidence proportions/rates of Campylobacter spp.…”

Section: Introductionmentioning

confidence: 99%

Acquisition and clearance dynamics of Campylobacter spp. in children in low- and middle-income countries

Chen,

Havelaar,

Platts-Mills

et al. 2024

Epidemics

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Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger

Cited by 9 publications

References 53 publications

Non-falciparum malaria infection and IgG seroprevalence among children under 15 years in Nigeria, 2018

Non-falciparum malaria infection and IgG seroprevalence among children under 15 years in Nigeria, 2018

Distance to Health Centers and Effectiveness of Azithromycin Mass Administration for Children in Niger

Acquisition and clearance dynamics of Campylobacter spp. in children in low- and middle-income countries

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