Elsevier

The Lancet

Volume 362, Issue 9379, 19 July 2003, Pages 198-204
The Lancet

Articles
Strategies for control of trachoma: observational study with quantitative PCR

https://doi.org/10.1016/S0140-6736(03)13909-8Get rights and content

Summary

Background

Antibiotics are an important part of WHO's strategy to eliminate trachoma as a blinding disease by 2020. At present, who needs to be treated is unclear. We aimed to establish the burden of ocular Chlamydia trachomatis in three trachomaendemic communities in Tanzania and The Gambia with real-time quantitative PCR.

Methods

Conjunctival swabs were obtained at examination from 3146 individuals. Swabs were first tested by the qualitative Amplicor PCR, which is known to be highly sensitive. In positive samples, the number of copies of omp1 (a single-copy C trachomatis gene) was measured by quantitative PCR

Findings

Children had the highest ocular loads of C trachomatis, although the amount of pooling in young age groups was less striking at the site with the lowest trachoma frequency. Individuals with intense inflammatory trachoma had higher loads than did those with other conjunctival signs. At the site with the highest prevalence of trachoma, 48 of 93 (52%) individuals with conjunctival scarring but no sign of active disease were positive for ocular chlamydiae.

Interpretation

Children younger than 10 years old, and those with intense inflammatory trachoma, probably represent the major source of ocular C trachomatis infection in endemic communities. Success of antibiotic distribution programmes could depend on these groups receiving effective treatment.

Introduction

Trachoma accounts for 10–15% of global blindness.1 It is caused by ocular infection with Chlamydia trachomatis and mainly affects poor, marginalised, and displaced people living in the hot dry regions of the world. Blindness from trachoma is preventable. In 1998, WHO set a target of global elimination of trachoma as a blinding disease by the year 2020.2 The SAFE strategy–surgery for in-turned eyelashes, antibiotics for active disease, face washing (or promotion of facial cleanliness), and environmental improvement to reduce transmission—is to be used in pursuit of this objective.

The antibiotic of first choice against trachoma is now azithromycin: it is effective,3, 4, 5, 6, 7 well tolerated,3, 4, 5, 6, 7, 8 and— because one oral dose produces high cure rates—is simple to administer.9 Yearly mass treatment of communities in which trachoma is hyperendemic has therefore been recommended.6, 10 However, azithromycin is expensive if it is not donated,11 and mass distribution of the drug could lead to development of macrolide resistance in C trachomasis or other human pathogens.12, 13, 14 Depending on the level of endemicity, researchers have suggested that treatment be given only to children younger than 10 years old,15 to children with active trachoma and their families,15 or to children with active trachoma and household contacts who are children.16 Because data showing the effect of these targeted antibiotic strategies are limited,15 establishment of the population subsets that harbour the greatest load of organism would be helpful to predict the approaches that will probably be most effective and cost effective.

Clinically, the highest prevalence of active disease is noted in young children. However, with the ligase chain reaction, Schachter and colleagues6 reported that 27% of individuals without signs of active trachoma were positive for C trachomatis DNA in Egypt and The Gambia, including a high proportion of adults. In a study in Tanzania, 24% of individuals without signs of active trachoma were reported to be positive for C trachomatis by PCR.17 We do not yet know whether such clinically negative individuals who are positive for C trachomatis harbour infection that is of epidemiological importance. If so, restriction of antibiotic treatment to individuals with clinical signs would have limited benefit for trachoma control. Alternatively, the data might just show that the high sensitivity of DNA amplification assays leads to positive results from individuals with transient self-limiting infections. Such people might be unlikely to act as a source for transmission of infection. Quantification of ocular chlamydial infection could help to answer this question.

The aim of our study was to measure—with real-time quantitative PCR—the amount of C trachomatis DNA present in conjunctival swabs taken from all consenting members of three separate trachoma endemic communities in Tanzania and The Gambia, and to examine the relation between the quantitative burden of infection and age, sex, and clinical trachoma status. We used isolation in tissue culture to validate the relevance of the quantitative PCR results.

Section snippets

Methods

Research was done in accordance with the declaration of Helsinki.18 Ethics approval was obtained from the ethics committee of the London School of Hygiene and Tropical Medicine, UK, the research and ethical clearance committee of the Kilimanjaro Christian Medical Centre, Tanzania, the joint committee on clinical investigation at Johns Hopkins School of Medicine, USA, the National Medical Research Council in Tanzania, and the Gambian Government/Medical Research Council joint ethics committee. We

Results

Of 978 residents of Kahe Mpya in Rombo, 956 (98%) were examined and swabbed (table 1), two were temporarily absent from the village, five explicitly refused, and 15 did not attend for examination. In Kongwa, 874 of 1017 residents (86%) were examined and swabbed, 130 were temporarily absent from the village for agriculture, cattle herding, or other reasons, one refused, and 12 were ineligible because they were younger than 6 months of age. Of the 874, no clinical data were recorded for one

Discussion

We have shown the quantitative distribution of ocular C trachomatis infection in three whole trachoma-endemic communities. We recorded that—in two Tanzanian communities mesoendemic and hyperendemic for active trachoma—most of the C trachomatis organism was found in young children, whereas in a Gambian population with a low prevalence of active disease, the burden of infection was more evenly distributed in individuals of all ages. Our results have major importance for trachoma control

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