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      Progress and projections in the program to eliminate trachoma

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          Abstract

          The problem of trachoma Trachoma is a progressive and miserable disease. Initiated by frequent and repeated ocular infections with the bacterium Chlamydia trachomatis, scars on the inside of the eyelids contract, disrupting the lid margin and causing the eyelashes to rotate inwards until they rest against the eye. With each excruciating blink, the lashes damage the sensitive cornea leading to corneal opacity and irreversible blindness. Trachoma has been with us for a long time; it is among the conditions catalogued in the oldest medical text—the Ebers Papyrus. Taking into account life expectancies too short to allow many people to develop cataracts, trachoma was likely the leading cause of blindness before the Industrial Revolution and the consequent increase in life expectancy. In our view, the integrated and holistic SAFE strategy to eliminate trachoma—a strategy based on surgical correction of misplaced lashes, the mass distribution of donated antibiotics, and the promotion of water, sanitation, and hygiene (WASH)—makes the program the most compelling of the neglected tropical disease (NTD) elimination programs. SAFE implementation goes far beyond “just” putting trachoma in the crosshairs for elimination as a public problem. Whilst we are used to the concept of collateral damage, the SAFE strategy comes with considerable collateral benefits. Such benefits include the improved quality of life associated with surgery, particularly for patients who are yet to suffer loss of vision [1]. An annual dose of azithromycin increases child survivorship by reducing mortality from common ailments like malaria, bacterial respiratory tract infections, and diarrhea, the three of which remain the primary killers of children living in poverty—children who do not have routine access to antibiotics [2, 3]. Freedom from trachoma does not have to wait for development. Development is the result of freedom from trachoma. Scaling up the donation program When the World Health Assembly adopted the elimination of trachoma in 1998, the geographical distribution of the disease and numbers affected could only be estimated. Without a clear understanding of the scale of the problem, the pharmaceutical company Pfizer Inc. agreed to an initial donation of 10 million doses of its antibiotic azithromycin through the International Trachoma Initiative as a proof of concept after it was demonstrated that a single oral dose was as effective as the current standard treatment of six weeks of topical ophthalmic tetracycline [4]. The first countries to receive donations, including Ghana, Morocco, Nepal, Tanzania, and Vietnam, demonstrated that the donated azithromycin could be managed without mixing it with the general pharmaceutical supply and developed best practices in managing the mass drug administration (MDA). As a result, the donation was quickly increased to 35 million doses. With the incorporation of the International Trachoma Initiative into The Task Force for Global Health in 2009, the donation program moved into a new period of scale-up, serving an average 15 countries with approximately 45 million doses of azithromycin annually. Between 1998 and 2012, just over 1,000 health districts had conducted rigorous epidemiological surveys to assess the prevalence of trachoma. Then came a game changer in trachoma elimination efforts: the Global Trachoma Mapping Project (GTMP). Through the extremely successful implementation of GTMP, over 1,500 additional health districts were surveyed between 2012 and 2016 [5]. With the global prevalence map just about complete, and all the data freely available and updated regularly via the online map (www.trachomaatlas.org), the scale of the task ahead of us could be visualized. The target of eliminating trachoma set in 1998 suddenly felt real and achievable. Now we were not shooting in the dark, new financial resources were made available (largely from the United States and United Kingdom governments and the Queen Elizabeth Diamond Jubilee Trust), and Pfizer Inc. once again doubled the size of its donation to over 100 million doses a year in 2016 (Fig 1). That same year, six implementing organizations (The Carter Center, the Fred Hollows Foundation, Helen Keller International, Orbis, RTI, and Sightsavers) were each scheduled to support the distribution of over 10 million doses within the context of the full SAFE strategy. By 2016, it was clear that the SAFE strategy worked and the global program was fully at scale. 10.1371/journal.pntd.0005402.g001 Fig 1 Total doses of Zithromax shipped to trachoma-endemic countries by year (updated 31 December, 2016). Getting to elimination: Scaling down the donation program Endemic districts are considered to warrant MDA with azithromycin until such time as the clinical signs of active disease in children aged one to nine years (TF1-9) fall below 5% and stay below 5% for two years. In calendar years 2014 and 2015, 143 health districts with a total population of 29.7 million people reached this elimination target. In addition, a new country-level validation process has been developed, and Morocco joins Oman in being validated as having eliminated trachoma as a public health problem by the World Health Organization [6]. Of the original countries in the donation program, four are likely to have crossed the finish line. The trachoma community is now working to finalize a forecast model, based on conservative assumptions, that will allow us to determine when the global elimination of trachoma will be achieved. Because a country cannot declare elimination of trachoma until the very last of its endemic districts is demonstrated to reach and remain below 5% TF1-9, countries will be validated relatively slowly. However, this masks the remarkable progress being made in hundreds of districts around the world. By the year 2020, we estimate that at least 70% of the endemic districts will have reached the transmission target of TF1-9 below 5%. This forecast will allow the global program to identify areas where an infusion of additional funding, an alternative treatment strategy, or other creative approaches will be required in order to speed the achievement of our elimination goals. The next 15 years—Maintaining the momentum The astonishing progress shown in the global program demonstrates that trachoma can be eliminated as a public health problem. The targets can be reached. People need no longer live with the prospect of having their corneas scratched out by their own eyelashes. The global trachoma program is public health at its best. The allure of “getting to zero” and freeing humankind from a disease that has plagued it for millennia is inspiring, but considerable challenges remain [7]. Some districts, most notably in northern Ethiopia and central Tanzania, are responding to intervention slower than the rest of the world: ten or more years of intervention with many rounds of MDA are often insufficient to reach the elimination target [8]. Alternative, more aggressive treatment strategies may be needed. For trachoma to be eliminated, every endemic community must be reached. The most marginalized people—indigenous tribes in the Amazon forest and hunter-gatherers in Africa, refugees and internally displaced people, and those living in areas of armed conflict—must be reached, in addition to the settled populations. Sadly, the most marginalized people and those living in war-torn areas are often those most at risk of neglected tropical diseases. The evidence base for the global program has been developed and refined largely on the backs of ongoing national programs: we have been building the ship as we sailed it [9]. Adequate investment in primary research is absolutely essential, and funding for trachoma research to date has not been proportional to the problem. As we get closer to the end, those places in which we have failed to fully understand the transmission dynamics may remain as islands of potential infection, preventing achievement of global elimination. We must learn lessons from other disease elimination or eradication efforts; for example, the unexpected discovery of dogs with Guinea worm disease, suggesting the existence of an unknown paratenic host for the parasite, only came to light after 99.9% of the global burden of Guinea worm disease was eliminated [10]. The global program has made tremendous progress. We have come further than we could possibly have hoped at the launch in 1998; but as strong as the global program is, we are also fragile. Any significant change in philanthropic philosophy, power, and politics can trump public health gains. The global program remains dependent on strong political will to succeed in endemic countries, the active participation of over 200 million people at risk, an unfaltering supply of donated medicine, a continuous pipeline of donor funds, increasing support to operational and basic science research, and access to all endemic areas. Despite the challenges, it is possible to eliminate trachoma as a public health problem. The world deserves our continued efforts and best work now so that future generations will never know the pain and suffering of trachoma. Funding statement No funding was provided for the preparation of this opinion piece. This opinion piece was prepared by PME, PJH and VS in their personal capacity. The views and opinions expressed are the views and opinions of the authors themselves and do not reflect the opinions, views or policy of the Task Force for Global Health, Pfizer Inc. or the International Coalition for Trachoma Control.

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          Effect of mass distribution of azithromycin for trachoma control on overall mortality in Ethiopian children: a randomized trial.

          Mass oral azithromycin distribution to affected communities is a cornerstone of the World Health Organization's trachoma elimination program. Antibiotics are provided to target the ocular strains of chlamydia that cause trachoma, but may also be efficacious against respiratory disease, diarrhea, and malaria--frequent causes of childhood mortality in trachoma-endemic areas. To compare mortality rates of participants aged 1 to 9 years in treated communities with those in untreated communities. We conducted a cluster-randomized clinical trial of mass azithromycin administration for trachoma control. Forty-eight communities (known as subkebeles) were randomized into 1 of 3 treatment schedules (annual treatment of all residents [15,902 participants], biannual treatment of all residents [17,288 participants], or quarterly treatment of children only [14,716 participants]) or into 1 group for which treatment was delayed by 1 year (control, 18,498 participants). Twelve subkebeles were randomized to each of the 4 schedules with all children in each of the 3 communities being eligible for treatment. The trial was conducted in a field setting in rural Ethiopia, May 2006 to May 2007. A single dose of oral azithromycin (adults, 1 g; children, 20 mg/kg) was administered for treatment of ocular Chlamydia trachomatis infection. Antibiotic coverage levels for children aged 1 to 9 years exceeded 80% at all visits. The main outcome measure was the community-specific mortality risk for children aged 1 to 9 years over the course of 1 year. Mortality was measured by enumerative census at baseline and again after 1 year. Comparison of the risk of mortality was a prespecified outcome for the clinical trial. The odds ratio for childhood mortality in the intervention communities was 0.51 (95% confidence interval, 0.29-0.90; P = .02; clustered logistic regression) compared with the control group. In the treated communities, the estimated overall mortality rate during this period for children aged 1 to 9 years in the untreated group was 8.3 per 1000 person-years (95% confidence interval, 5.3-13.1), while among the treated communities, the estimated overall mortality rate was 4.1 per 1000 person-years (95% confidence interval, 3.0-5.7) for children aged 1 to 9 years. In a trachoma-endemic area, mass distribution of oral azithromycin was associated with reduced mortality in children. clinicaltrials.gov Identifier: NCT00322972.
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            The SAFE strategy for trachoma control: Using operational research for policy, planning and implementation.

            Trachoma is a neglected disease and also the world's leading infectious cause of blindness. It causes misery, dependency and is a barrier to development. Trachoma is controlled by a WHO-endorsed integrated strategy of surgery for trichiasis, antibiotic therapy, facial cleanliness and environmental improvement, which is known by the acronym SAFE. The strategy is based on evidence from field trials and is continually being refined by operational research that informs national policy and planning; the strategy has affected both programme delivery and implementation. As a result of the findings of operational research, surgery is now frequently conducted by paramedics in communities rather than by ophthalmologists in hospitals; yearly mass distribution of a single oral dose of azithromycin has replaced the use of topical tetracycline; and the promotion of better hygiene, face-washing and the use of latrines are used to reduce transmission. Those who implement programmes have been equal partners in conducting operational research thus reducing the "know-do" gap and minimizing the lag that often exists between the completion of trials and putting their results into practice. Operational research has become a part of practice. Although there are still many questions without answers, national programme coordinators have a reasonable expectation that trachoma control programmes based on SAFE will work.
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              Disease eradication.

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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, CA USA )
                1935-2727
                1935-2735
                20 April 2017
                April 2017
                : 11
                : 4
                : e0005402
                Affiliations
                [1 ]International Trachoma Initiative, Decatur, Georgia, United States of America
                [2 ]International Coalition for Trachoma Control, London, United Kingdom
                Baylor College of Medicine, Texas Children's Hospital, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Article
                PNTD-D-17-00185
                10.1371/journal.pntd.0005402
                5398479
                28426814
                32dfcd36-7a58-4b40-b8cd-744e0b804f89
                © 2017 Emerson et al

                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
                Page count
                Figures: 1, Tables: 0, Pages: 4
                Funding
                No funding was provided for the preparation of this opinion piece. This opinion piece was prepared by PME, PJH, and VS in their personal capacity. The views and opinions expressed are the views and opinions of the authors themselves and do not reflect the opinions, views or policy of the Task Force for Global Health, Pfizer Inc. or the International Coalition for Trachoma Control.
                Categories
                Viewpoints
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Trachoma
                Medicine and Health Sciences
                Ophthalmology
                Eye Diseases
                Trachoma
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Trachoma
                Medicine and Health Sciences
                Public and Occupational Health
                Medicine and Health Sciences
                Public and Occupational Health
                Global Health
                Biology and Life Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Cornea
                Medicine and Health Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Cornea
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antimicrobials
                Antibiotics
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobials
                Antibiotics
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Medicine and Health Sciences
                Ophthalmology
                Visual Impairments
                Blindness
                People and Places
                Demography
                Life Expectancy
                Medicine and Health Sciences
                Public and Occupational Health
                Life Expectancy

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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