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      The Easiest Children to Reach Are Most Likely to Be Infected with Ocular Chlamydia trachomatis in Trachoma Endemic Areas of Niger

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          Abstract

          Background

          Control programs for trachoma use mass antibiotic distributions to treat ocular Chlamydia trachomatis in an effort to eliminate this disease worldwide. To determine whether children infected with ocular Chlamydia are more likely to present later for examination than those who are uninfected, we compare the order of presentation for examination of children 0–5 years, and the presence of ocular Chlamydia by PCR in 4 villages in Niger where trachoma is endemic.

          Methods

          We conducted a cluster-randomized, controlled trial where 48 randomly selected villages in Niger are divided into 4 study arms of different mass treatment strategies. In a substudy of the main trial, we randomly selected 1 village from each of the 4 study arms (4 total villages) and we evaluated the odds of ocular Chlamydia versus the rank order of presentation for examination and laboratory assessment before treatment was offered.

          Findings

          We found the odds of harboring ocular Chlamydia dropped by more than 70% from the first child examined to the last child examined (OR 0.27, 95% CI 0.13–0.59, P = 0.001) in the 4 randomly selected villages. We found the odds of active trachoma dropped by 80% from the first child examined to the last child examined (OR 0.20, 95% CI 0.10–0.4, P<0.0001) in the 48 villages in the main trial.

          Interpretation

          This study demonstrates that even if the WHO recommended 80% treatment coverage is not reached in certain settings, children 0–5 years with the greatest probability of ocular Chlamydia have higher odds of receiving attention because they are the first to present. These results suggest there may be diminishing returns when using scarce resources to track down the last few children in a mass treatment program.

          Trial Registration

          ClinicalTrials.gov NCT00792922

          Author Summary

          Trachoma is the most common cause of blindness from an infection in the world. The bacterium that causes trachoma is called Chlamydia trachomatis and it can be treated with the antibiotic azithromycin. Experts recommend trying to reach at least 80% of children for treatment in a community but it is unknown if this is necessary. We began a clinical trial in Niger in 48 villages in the summer of 2010 with mass drug administration (MDA) of azithromycin. We found that the odds of an eye infection were the highest in the first children to come for an examination. This means the extra time and money needed to reach all of the children in a village may provide diminishing returns because the easiest children to reach have the highest odds of infection. Perhaps it would be better to try to reach more villages for MDA instead of spending a lot of time and money trying to reach every single child in every single village.

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          Most cited references14

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          A simple system for the assessment of trachoma and its complications.

          A simple grading system for trachoma, based on the presence or absence of five selected "key" signs, has been developed. The method was tested in the field and showed good observer agreement, the most critical point being the identification of severe cases of the disease. It is expected that the system will facilitate the assessment of trachoma and its complications by non-specialist health personnel working at the community level.
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            Trachoma.

            Trachoma is a keratoconjunctivitis caused by ocular infection with Chlamydia trachomatis. Repeated or persistent episodes lead to increasingly severe inflammation that can progress to scarring of the upper tarsal conjunctiva. Trichiasis develops when scarring distorts the upper eyelid sufficiently to cause one or more lashes to abrade the cornea, scarring it in turn and causing blindness. Active trachoma affects an estimated 84 million people; another 7.6 million have end-stage disease, of which about 1.3 million are blind. Trachoma should stand on the brink of extinction thanks to a 1998 initiative launched by WHO--the Global Elimination of Trachoma by 2020. This programme advocates control of trachoma at the community level with four inter-related population-health initiatives that form the SAFE strategy: surgery for trichiasis, antibiotics for active trachoma, facial cleanliness, and environmental improvement. Evidence supports the effectiveness of this approach, and if current world efforts continue, blinding trachoma will indeed be eliminated by 2020.
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              Assessment of herd protection against trachoma due to repeated mass antibiotic distributions: a cluster-randomised trial.

              Trachoma-control programmes distribute oral azithromycin to treat the ocular strains of chlamydia that cause the disease and to control infection. Theoretically, elimination of infection is feasible if untreated individuals receive an indirect protective effect from living in repeatedly treated communities, which is similar to herd protection in vaccine programmes. We assessed indirect protection against trachoma with mass azithromycin distributions. In a cluster randomised trial, 24 subkebeles (government-defined units) in Amhara, Ethiopia, were randomised, with use of a simple random sample, to distribution four times per year of single-dose oral azithromycin to children aged 1-10 years (12 subkebeles, 4764 children), or to delayed treatment until after the study (control; 12 subkebeles, 6014 children). We compared the prevalence of ocular chlamydial infection in untreated individuals 11 years and older between baseline and 12 months in the treated subkebeles, and at 12 months between the treated and control subkebeles. Health-care and laboratory personnel were blinded to study group. Analysis was intention to treat. The study is registered with clinicaltrials.gov, number NCT00322972. At 12 months, 637 children aged 1-10 years and 561 adults and children aged 11 years and older were analysed in the children-treated group, and 618 and 550, respectively, in the control group. The mean prevalence of infection in children decreased from 48.4% (95% CI 42.9-53.9) to 3.6% (0.8-6.4) after four mass treatments. At 12 months, the mean prevalence of infection in the untreated age group (>/=11 years) was 47% (95% CI 33-57) less than baseline (p=0.002), and 35% (95% CI 1-57) less than that in untreated communities (p=0.04). Frequent treatment of children, who are a core group for transmission of trachoma, could eventually eliminate infection from the entire community. Herd protection is offered by repeated mass antibiotic treatments, providing a strategy for elimination of a bacterial disease when an effective vaccine is unavailable. National Institutes of Health.
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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
                January 2013
                10 January 2013
                : 7
                : 1
                : e1983
                Affiliations
                [1 ]Programme National de Lutte Contre la Cecité, Niamey, Niger
                [2 ]F.I. Proctor Foundation, University of California San Francisco, San Francisco, California, United States of America
                [3 ]Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California, United States of America
                [4 ]Dana Center for Preventive Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States of America
                [5 ]Clinical Research Unit, Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
                [6 ]Department of Ophthalmology, University of California San Francisco, San Francisco, California, United States of America
                [7 ]Institute for Global Health, University of California San Francisco, San Francisco, California, United States of America
                Yale University, United States of America
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: BDG TML JDK SKW AA. Performed the experiments: BDG TML JDK SJB RLB NES SNY BN BK AA. Analyzed the data: BDG TML CEM ZZ NES SNY AA. Wrote the paper: BDG TML CEM SNY AA.

                Article
                PNTD-D-12-00756
                10.1371/journal.pntd.0001983
                3542188
                23326612
                66ce6568-94e9-445c-9143-44e8861c6057
                Copyright @ 2013

                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
                : 18 June 2012
                : 7 November 2012
                Page count
                Pages: 6
                Funding
                The Bill and Melinda Gates Foundation (grant number 48027) was the main supporter of this trial. This project was also supported by the National Institutes of Health (NIH/NEI K23 EYO19881-01 and NIH/NCRR/OD UCSF-CTSI grant number KL2 RR024130). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Infectious Diseases
                Bacterial Diseases
                Trachoma
                Neglected Tropical Diseases
                Trachoma
                Ophthalmology
                Eye Infections
                Trachoma

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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