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The Effect of Multiple Rounds of Mass Drug Administration on the Association between Ocular Chlamydia trachomatis Infection and Follicular Trachoma in Preschool-Aged Children

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      Abstract

      Purpose

      To examine the relationship between ocular Chlamydia trachomatis infection and follicular trachoma (TF) in children prior to and following multiple rounds of annual mass drug administration (MDA) with azithromycin.

      Methodology/principal findings

      Thirty-two communities with endemic trachoma in Kongwa District, Tanzania, were offered annual MDA as part of a district-wide trachoma control program. Presence of ocular C. trachomatis infection and TF were assessed in 3,200 randomly sampled children aged five years and younger, who were examined prior to each MDA. Infection was detected using the Amplicor CT/NG assay and TF was identified by clinical examination using the World Health Organization (WHO) simplified grading system. The association between chlamydial infection and TF in children was evaluated at baseline prior to any treatment, and 12 months after each of three annual rounds of mass treatment. Factors associated with infection were examined using generalized estimating equation models.

      At baseline, the overall prevalence of chlamydial infection and TF was 22% and 31%, respectively. Among children with clinical signs of TF, the proportion of those with infection was 49% prior to treatment and declined to 30% after three MDAs. The odds of infection positivity among children with clinical signs of TF decreased by 26% (OR 0.74, 95% CI 0.65 to 0.84, p = <0.01) with each MDA, after adjusting for age. For children aged under one year, who did not receive treatment, the relationship was unchanged.

      Conclusions/significance

      The association between ocular C. trachomatis infection and TF weakened in children with each MDA, as both infection and clinical disease prevalence declined. However, there was still a significant proportion of TF cases with infection after three rounds of MDA. New strategies are needed to assess this residual infection for optimal treatment distribution.

      Author Summary

      Trachoma, which is caused by infection by the bacterium Chlamydia trachomatis, is the leading preventable cause of blindness worldwide. Annual mass drug administration with azithromycin is recommended for trachoma control; however, monitoring the impact of azithromycin, which targets C. trachomatis, relies on the clinical assessment of follicular trachoma. If the relationship between chlamydial infection and the presence or absence of follicular trachoma were to remain unchanged with each round of treatment, we would be able to predict the level of residual infection, and the need for additional treatment, from the prevalence of follicular trachoma. In this study, we examined the association between infection and presence or absence of follicular trachoma in children prior to and following multiple rounds of treatment. Findings suggest that with increasing rounds of treatment, the prevalence of infection declines in children both with and without signs of follicular trachoma. Newer strategies, including tests that can rapidly detect infection under field conditions, may be needed to assess residual infection in treated communities.

      Related collections

      Most cited references 23

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      Global data on visual impairment in the year 2002.

      This paper presents estimates of the prevalence of visual impairment and its causes in 2002, based on the best available evidence derived from recent studies. Estimates were determined from data on low vision and blindness as defined in the International statistical classification of diseases, injuries and causes of death, 10th revision. The number of people with visual impairment worldwide in 2002 was in excess of 161 million, of whom about 37 million were blind. The burden of visual impairment is not distributed uniformly throughout the world: the least developed regions carry the largest share. Visual impairment is also unequally distributed across age groups, being largely confined to adults 50 years of age and older. A distribution imbalance is also found with regard to gender throughout the world: females have a significantly higher risk of having visual impairment than males. Notwithstanding the progress in surgical intervention that has been made in many countries over the last few decades, cataract remains the leading cause of visual impairment in all regions of the world, except in the most developed countries. Other major causes of visual impairment are, in order of importance, glaucoma, age-related macular degeneration, diabetic retinopathy and trachoma.
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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: global magnitude of a preventable cause of blindness.

          Trachoma is the leading cause of infectious blindness worldwide. It is known to be highly correlated with poverty, limited access to healthcare services and water. In 2003, the WHO estimated that 84 million people were suffering from active trachoma, and 7.6 million were severely visually impaired or blind as a result of trachoma: this study provides an updated estimate of the global prevalence of trachoma based on the most recent information available. A literature search of recent published and unpublished surveys in the 57 endemic countries was carried out: the result of surveys that used the WHO trachoma grading system and additional information from regional and country experts served as a basis to determine the prevalence of trachoma in each country. Population-based surveys provided recent information for 42 out of 57 endemic countries. 40.6 million people are estimated to be suffering from active trachoma, and 8.2 million are estimated to have trichiasis. The current estimate of prevalence of trachoma is lower than the previous WHO estimates: this can be explained by the success in implementing control strategy, by more accurate data, as well as by socio-economic development in endemic countries.
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            Author and article information

            Affiliations
            [1 ]Dana Center for Preventive Ophthalmology, Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States of America
            [2 ]Kongwa Trachoma Project, Kongwa, Tanzania
            [3 ]Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America
            [4 ]Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
            University of California San Francisco, United States of America
            Author notes

            The authors have declared that no competing interests exist.

            Conceived and designed the experiments: SKW BEM HM. Performed the experiments: HM. Analyzed the data: BEM JSL. Contributed reagents/materials/analysis tools: CAG TCQ. Wrote the paper: JSL SKW BEM.

            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
            April 2014
            10 April 2014
            : 8
            : 4
            24722392 3983082 PNTD-D-13-01152 10.1371/journal.pntd.0002761

            This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

            Counts
            Pages: 6
            Funding
            This study was supported by a grant from the Bill and Melinda Gates Foundation (Grant ID 48027) and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
            Categories
            Research Article
            Medicine and Health Sciences
            Infectious Diseases
            Bacterial Diseases
            Trachoma
            Ophthalmology
            Tropical Diseases
            Neglected Tropical Diseases

            Infectious disease & Microbiology

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