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.

Antimicrobials are used primarily to treat infectious disease, but they have other effects. Here, we assess anthropometry measurements in children 6–60 months in 24 communities randomized to one or two mass azithromycin distributions over a 1-year period in Niger. We compared the prevalence of wasting, low mid-upper arm circumference, stunting, and underweight in communities in the two treatment arms. We were unable to prove that there was a difference in the prevalence of wasting in the 12 communities that received one mass azithromycin distribution versus the 12 communities that received two mass azithromycin distributions (odds ratio = 0.75, 95% confidence interval = 0.46–1.23). Likewise, we were unable to detect a difference in the two treatment arms for low mid-upper arm circumference, stunting, and underweight. There may not be an association between antibiotic use and improved growth in humans, or this trial was not powerful enough to detect an association if it exists.

Background

Trachoma control programs utilize mass azithromycin distributions to treat ocular Chlamydia trachomatis as part of an effort to eliminate this disease world-wide. But it remains unclear what the community-level risk factors are for infection.

Methods

This cluster-randomized, controlled trial entered 48 randomly selected communities in a 2×2 factorial design evaluating the effect of different treatment frequencies and treatment coverage levels. A pretreatment census and examination established the prevalence of risk factors for clinical trachoma and ocular chlamydia infection including years of education of household head, distance to primary water source, presence of household latrine, and facial cleanliness (ocular discharge, nasal discharge, and presence of facial flies). Univariate and multivariate associations were tested using linear regression and Bayes model averaging.

Findings

There were a total of 24,536 participants (4,484 children aged 0–5 years) in 6,235 households in the study. Before treatment in May to July 2010, the community-level prevalence of active trachoma (TF or TI utilizing the World Health Organization [WHO] grading system) was 26.0% (95% CI: 21.9% to 30.0%) and the mean community-level prevalence of chlamydia infection by Amplicor PCR was 20.7% (95% CI: 16.5% to 24.9%) in children aged 0–5 years. Univariate analysis showed that nasal discharge (0.29, 95% CI: 0.04 to 0.54; P = 0.03), presence of flies on the face (0.40, 95% CI: 0.17 to 0.64; P = 0.001), and years of formal education completed by the head of household (0.07, 95% CI: 0.07 to 0.13; P = 0.03) were independent risk factors for chlamydia infection. In multivariate analysis, facial flies (0.26, 95% CI: 0.02 to 0.49; P = 0.03) and years of formal education completed by the head of household (0.06, 95% CI: 0.008 to 0.11; P = 0.02) were associated risk factors for ocular chlamydial infection.

Interpretation

We have found that the presence of facial flies and years of education of the head of the household are risk factors for chlamydia infection when the analysis is done at the community level.

Trial Registration

ClinicalTrials.gov NCT00792922

Author Summary

Trachoma is one of the most important neglected tropical diseases because it is the leading cause of blindness from an infection in the world. There are about 1.3 million persons blind from the disease and many more at risk of blindness in the future. It is caused by the common bacterium Chlamydia trachomatis and can be treated with mass drug administrations (MDA) of azithromycin. We have begun a clinical trial in Niger, a country with limited resources in Africa, to determine the best treatment strategy. Our study from May to July 2010, which began before MDA's were given, showed that 26% of children aged 0–5 years were infected with the disease. In these children, we found that discharge from the nose, presence of flies on the face, and the number of years of education completed by the head of the household were risk factors for infection in 48 different communities. We hope to use this information about risk factors of infection to help guide future studies for trachoma and also to help with the WHO goal of eliminating the disease worldwide by the year 2020.

Background and aims: Trachoma is a sight-threatening process triggered by the infection of the conjunctiva with Chlamydiae. Blindness associated with trachoma was reported in Sahelian areas of Cameroon. However, data on the prevalence of this neglected infection in the Far North Region are not available. The aim of this study was a) to assess clinical trachoma and b) to detect Chlamydia in the conjunctiva of trachomatous populations living in the Far North Regions of Cameroon.

Methods: A total of 2,423 randomly selected children (1–10 years) and 1,590 women over 14 from randomly selected villages from the Kolofata Health District (115,000 inhabitants) were included in a cross-sectional study in February 2009. Trained staff examined and obtained conjunctival swabs from trachomatous subjects. DNA was extracted and amplified to detect Chlamydia DNA by real-time PCR. The quality of sampling was assessed by quantifying the number of epithelial cells.

Results: Children (2,397 or 98.9% of the predicted number) and women (1,543; 97.0%) were examined. The prevalence of follicular trachoma (TF) in children was 21% (95% CI 17.8–24.5) and of intense inflammatory trachoma (TI) 5.2% (95% CI 3.6–7.3). Among the women, trichiasis (TT) was observed in 3.4% (95% CI 2.4–4.7), corneal opacities (CO) in 1.4% (95% CI 0.8–2.3) and trachoma-related blindness in 0.9% (95% CI 0.4–1.8). Conditions related to income, illiteracy, latrines, water supply and animals wandering close to dwellings were similar in all the villages. PCR was positive in 35% of children with active trachoma and in 6% of adult females presenting TT and/or related corneal opacities.

Conclusion: The prevalence of trachoma and the severe trachoma sequelae found during this survey underline the urgent need to implement efficient blindness prevention interventions to improve the visual future of the people in the Sahelian region.

Background

Following an epidemiological study carried out in 2006 showing a high prevalence of blinding trachoma in the Far North Region of Cameroon, a trachoma elimination programme using the SAFE strategy was initiated: three yearly trachoma mass treatments were to be performed.

Methodology/Principal Findings

The entire district population (120,000 persons) was treated with azithromycin 1.5% eye drops in February 2008 and January 2009. To assess the effect of treatment on the prevalence of active trachoma, three epidemiological studies were conducted on a representative sample of children aged between 1 and 10 years. The first study was performed just prior to the first treatment, the second just prior to the 2nd treatment and the third one, one year later. The prevalence of active forms of trachoma (TF + TI) dropped from 31.5% (95%CI 26.4–37.5) before treatment to 6.3% (95%CI 4.1–9.6) one year after first treatment; a reduction of nearly 80%. One year after the second treatment, the prevalence decreased to 3.1% (95%CI 2.0–4.9), a total reduction of 90%. Furthermore, there were no more TI cases (only TF). There was no report of serious or systemic side effects. Tolerance was excellent.

Conclusions/Significance

Active trachoma mass treatment with azithromycin 1.5% eye drops is feasible, well tolerated, and effective.

Author Summary

Trachoma is the leading cause of infectious blindness worldwide, accounting for 1.3 million cases of blindness. Although it has disappeared in many regions of the world, trachoma is still endemic in Africa, Eastern Mediterranean, Latin America, Asia, and Australia. The WHO has currently set a target of 2020 for controlling trachoma to a low enough level that resulting blindness will not be a major public health concern. Topical tetracycline was for a long time the recommended treatment for active trachoma, but compliance to the regimen is extremely poor. Azithromycin has properties that make it an ideal treatment for Chlamydia trachomatis: high efficacy, intracellular accumulation, and a long tissue half-life. There is now a new mass treatment of trachoma by azithromycin 1.5% eye drops which is as effective as the oral route. In the test health district of Kolofata, Cameroon, the prevalence of trachoma among children dramatically decreased from 31% to less than 5% after 2 treatments. A third treatment was performed in January 2010. An epidemiological surveillance is implemented to see if this removal will be permanent. It also avoids misuse of oral azithromycin and the eye drops are directly treating the site of the infection.