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Diagnosing trachoma for elimination

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WHO simplified grading system for trachoma diagnosis. These photographs are reproduced with permission from the WHO Programme for the Prevention of Blindness and Deafness

Trachoma is the leading infectious cause of blindness worldwide, caused by ocular infection with the bacterium Chlamydia trachomatis. Trachoma is targeted for elimination as a public health problem by the year 2020. The treatment and prevention strategy to achieve elimination is known as SAFE, and includes: Surgery for in-turned eyelashes, Antibiotics, given as mass drug administration (or MDA), to treat infection, and Facial cleanliness and Environmental improvement to limit transmission of infection. Trachoma is a community disease, and as such, prevalence estimates and interventions are provided at the district level (normal administrative unit for health care management).

Trachoma is diagnosed using clinical signs, using what is known as the World Health Organization (WHO) simplified grading system. This grading system correlates with the pathogenesis of the disease, with the early signs of trachoma detected by everting the upper eyelid and examining the subtarsal conjunctiva. Ocular infection with chlamydia predominantly occurs in children, and results in a keratoconjunctivitis. Trachomatous inflammation-follicular (TF), where there are characteristic off-white follicles of ≥0.5 mm, is the characteristic sign of active trachoma. Some individuals develop intense inflammatory disease (Trachomatous inflammation-intense [TI]) and after repeated rounds of infection there can trachomatous scarring (TS), which can cause distortion of the lid margin and shortening of the upper eyelid, pulling the eye lashes inwards to scratch against the eyeball (trachomatous trichiasis [TT]), which may then result in corneal opacity and blindness.

To certify as having eliminated trachoma, countries submit a dossier to WHO, including showing that the prevalence of TT unknown to the health system is <2 cases per 1000 population aged ≥15 years, and that the prevalence of TF in 1-9 year-olds has fallen below 5%, and that this has been sustained for at least two years, in each formerly endemic district. However, the presence of clinical signs of active trachoma (TF and TI) is poorly correlated with detection of infection, especially after MDA where clinical signs tend to over-estimate prevalence relative to infection. The result is that: 1.) We may be conducting unnecessary rounds of MDA; and 2.) Countries may have eliminated ocular chlamydial infection, but not be able to certify as having eliminated trachoma.

Studies have shown that tests for infection, including lab-based nucleic acid amplification tests, can be cost-effective, especially when their use results in stopping or not initiating MDA [1]. However, these tests have not been implemented or maintained long-term outside the context of research studies, due to the cost relative to the WHO simplified grading system, and infrastructure, training and quality assurance requirements. A number of companies are developing rapid/point-of-care tests for detection of genital chlamydial infection, but these are targeted primarily for use in high-income countries, and may require optimisation for ocular samples, such as the composition of the sample preparation reagents. There therefore remains a need for a fit-for-purpose (“ASSURED”) diagnostic test that can be conducted in-country after minimal training, in order to provide community level prevalence estimates to guide elimination efforts.

 

Emma Harding-Esch is Associate Professor at the London School of Hygiene & Tropical Medicine. She is also Chief Scientist for Tropical Data, a service supporting national programmes to conduct standardised, epidemiologically robust, prevalence surveys of neglected tropical diseases, allowing interventions for disease elimination to be targeted and prioritised. She has a particular research interest in diagnostics for both trachoma and sexually transmitted infections (STIs). She has evaluated the performance and cost-effectiveness of diagnostics for trachoma in The Gambia and Senegal, and was Principal Scientist in the HIV/STI department at Public Health England, and Epidemiology Lead for the Applied Diagnostic Research & Evaluation Unit (ADREU) at St George’s, University of London, where she conducted several diagnostic evaluations to assess the performance, clinical and public health impacts of novel diagnostic technologies for STIs.

Diagnostic stories follows the emerging world of devices, instruments, protocols and machines that make up the world of global health diagnostics. Through the telling of stories about specific technological artefacts it traces the rise of diagnosis as a global health concern and offers a critical perspective on the device-focused approach of many attempts to improve diagnostic infrastructure in the Global South. The series is edited by Alice Street.

Note

[1] A.M. Ramadhani, T. Derrick, D. Macleod, M.J. Holland, M.J. Burton, PLoS neglected tropical diseases 10(10) (2016) e0005080.


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