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      Non-Participation during Azithromycin Mass Treatment for Trachoma in The Gambia: Heterogeneity and Risk Factors

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          Abstract

          Background

          There is concern that untreated individuals in mass drug administration (MDA) programs for neglected tropical diseases can reduce the impact of elimination efforts by maintaining a source of transmission and re-infection.

          Methodology/Principal Findings

          Treatment receipt was recorded against the community census during three MDAs with azithromycin for trachoma in The Gambia, a hypo-endemic setting. Predictors of non-participation were investigated in 1–9 year olds using random effects logistic regression of cross-sectional data for each MDA. Two types of non-participators were identified: present during MDA but not treated (PNT) and eligible for treatment but absent during MDA (EBA). PNT and EBA children were compared to treated children separately. Multivariable models were developed using baseline data and validated using year one and two data, with a priori adjustment for previous treatment status. Analyses included approximately 10000 children at baseline and 5000 children subsequently. There was strong evidence of spatial heterogeneity, and persistent non-participation within households and individuals. By year two, non-participation increased significantly to 10.4% overall from 6.2% at baseline, with more, smaller geographical clusters of non-participating households. Multivariable models suggested household level predictors of non-participation (increased time to water and household head non-participation for both PNT and EBA; increased household size for PNT status only; non-inclusion in a previous trachoma examination survey and younger age for EBA only). Enhanced coverage efforts did not decrease non-participation. Few infected children were detected at year three and only one infected child was EBA previously. Infected children were in communities close to untreated endemic areas with higher rates of EBA non-participation during MDA.

          Conclusions/Significance

          In hypo-endemic settings, with good coverage and no association between non-participation and infection, efforts to improve participation during MDA may not be required. Further research could investigate spatial hotspots of infection and non-participation in other low and medium prevalence settings before allocating resources to increase participation.

          Author Summary

          As the target year for Global Elimination of Trachoma (GET2020) approaches, the scale up of mass drug administration (MDA) with azithromycin will lead to more endemic areas becoming low prevalence settings. In such areas, identification of those at highest risk of Chlamydia trachomatis infection and at highest risk of non-participation during MDA could inform control planning, especially if correlation is present. We investigated non-participation in children aged 1–9 years during three annual MDAs in The Gambia, a low prevalence setting. We found evidence that non-participation is associated with household membership and decision-making, as seen in medium and high prevalence settings in East Africa. In addition, we demonstrate geographical heterogeneity (spatial clustering) of non-participation, persistent non-participation behaviour over time and different non-participator types. Between the first and third MDA, non-participation increased significantly overall from 6.2% to 10.4%, whilst spatial clusters became smaller with non-participation more focused in single households or small groups of households. There was no evidence of association between infection and non-participation. In low prevalence settings with no evidence to suggest non-participation as a risk factor for infection, resources to improve participation may not be required. Spatial hotspot analysis could address this research question in areas with more infection.

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          Most cited references25

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          The coverage and frequency of mass drug administration required to eliminate persistent transmission of soil-transmitted helminths

          A combination of methods, including mathematical model construction, demographic plus epidemiological data analysis and parameter estimation, are used to examine whether mass drug administration (MDA) alone can eliminate the transmission of soil-transmitted helminths (STHs). Numerical analyses suggest that in all but low transmission settings (as defined by the magnitude of the basic reproductive number, R 0), the treatment of pre-school-aged children (pre-SAC) and school-aged children (SAC) is unlikely to drive transmission to a level where the parasites cannot persist. High levels of coverage (defined as the fraction of an age group effectively treated) are required in pre-SAC, SAC and adults, if MDA is to drive the parasite below the breakpoint under which transmission is eliminated. Long-term solutions to controlling helminth infections lie in concomitantly improving the quality of the water supply, sanitation and hygiene (WASH). MDA, however, is a very cost-effective tool in long-term control given that most drugs are donated free by the pharmaceutical industry for poor regions of the world. WASH interventions, by lowering the basic reproductive number, can facilitate the ability of MDA to interrupt transmission.
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            Re-emergence of Chlamydia trachomatis infection after mass antibiotic treatment of a trachoma-endemic Gambian community: a longitudinal study.

            Community-wide mass antibiotic treatment is a central component of trachoma control. The optimum frequency and duration of treatment are unknown. We measured the effect of mass treatment on the conjunctival burden of Chlamydia trachomatis in a Gambian community with low to medium trachoma prevalence and investigated the rate, route, and determinants of re-emergent infection. 14 trachoma-endemic villages in rural Gambia were examined and conjunctival swabs obtained at baseline, 2, 6, 12, and 17 months. Mass antibiotic treatment with azithromycin was given to the community at baseline. C trachomatis was detected by qualitative PCR and individual infection load then estimated by real-time quantitative PCR. C trachomatis was detected in 95 (7%) of 1319 individuals at baseline. Treatment coverage was 83% of the population (1328 of 1595 people). The effect of mass treatment was heterogeneous. In 12 villages all baseline infections (34 [3%] of 1062 individuals) resolved, and prevalence (three [0.3%]) and infection load remained low throughout the study. Two villages (baseline infection: 61 [24%] of 257 individuals) had increased infection 2 months after treatment (74 [30%]), after extensive contact with other untreated communities. Subsequently, this value reduced to less than half of that before treatment (25 [11%]). Mass antibiotic treatment generally results in effective, longlasting control of C trachomatis in this environment. For low prevalence regions, one treatment episode might be sufficient. Infection can be reintroduced through contact with untreated populations. Communities need to be monitored for treatment failure and control measures implemented over wide geographical areas.
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              Childhood mortality in a cohort treated with mass azithromycin for trachoma.

              Mass azithromycin distributions are used to clear ocular strains of chlamydia that cause trachoma, but treatments may also affect respiratory infections, diarrhea, and malaria. Here, we monitor a large cohort in which almost 90% of individuals received azithromycin. We assess whether receiving treatment is associated with reduced all-cause and infectious childhood mortality. As part of a clinical trial for trachoma, a census was conducted in 24 communities in rural Ethiopia. All individuals ≥1 year of age were eligible for single-dose oral azithromycin, although antibiotic coverage was not universal. A follow-up census was performed 26 months after treatment to estimate all-cause mortality among children 1-5 years of age, and verbal autopsies were performed to identify infectious mortality. The cohort included 35,052 individuals ≥1 year of age and 5507 children 1-5 years of age, of whom 4914 received a dose of azithromycin. All-cause mortality was significantly lower among those 1-5-year-old children who received azithromycin (odds ratio [OR]=0.35 [95% confidence interval {CI}, 0.17-0.74]), as was infectious mortality (OR=0.20 [95% CI, 0.07-0.58]). When individuals were compared only with members of the same household, azithromycin treatment was still associated with reduced all-cause mortality in children 1-5 years of age (OR=0.40 [95% CI, 0.16-0.96]), although this relationship was not statistically significant for infectious mortality (OR=0.35 [95% CI, 0.10-1.28]). This study demonstrated an association between mass oral azithromycin treatment and reduced all-cause and infectious childhood mortality. This relationship could not be attributed to bias at the level of the household. Mass azithromycin distributions may have benefits unrelated to trachoma. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                August 2014
                28 August 2014
                : 8
                : 8
                : e3098
                Affiliations
                [1 ]MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom
                [2 ]Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom
                [3 ]Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom
                [4 ]Disease Control and Elimination Theme, Medical Research Council Unit (MRC), Fajara, Banjul, The Gambia
                [5 ]National Eye Health Programme, Ministry of Health and Social Welfare, Kanifing, The Gambia
                [6 ]Dana Center for Preventive Ophthalmology, Johns Hopkins University, Baltimore, Maryland, United States of America
                University of California San Diego School of Medicine, United States of America
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: TE RB EA. Performed the experiments: TE. Analyzed the data: TE. Contributed to the writing of the manuscript: TE RB EA. Collected the data: EMHE JH SEB AS MJH. Designed the original trial and obtained funding: RB DM SKW MJH.

                Article
                PNTD-D-14-00455
                10.1371/journal.pntd.0003098
                4148234
                25165994
                ecd40a9e-1727-4bae-882d-a27c0a3a3cce
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 March 2014
                : 20 June 2014
                Page count
                Pages: 11
                Funding
                The original PRET trial ( www.clinicaltrials.gov: NCT00792922) was funded by the Bill and Melinda Gates Foundation (grant number 48027). MJH receives salary funding from the Wellcome Trust (grant number 079246/Z/06/Z). TE receives salary support from MRC and DFID (grant MR/K012126/1).
                Categories
                Research Article
                Medicine and Health Sciences
                Custom metadata
                The authors confirm that, for approved reasons, some access restrictions apply to the data underlying the findings. Requests for data should be made to the Data Access Committee of the PRET study, which can be accessed through Dr. Thomas Quinn ( tquinn@ 123456jhmi.edu ).

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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