Continuous mass distribution of azithromycin in northern Ethiopia, where the childhood eye infection trachoma is a major cause of blindness, is effective in preventing recurrence of trachoma but does not eliminate the infection entirely, according to a study by Jeremy Keenan and colleagues from the University of California – San Francisco, and the Carter Centre in Addis Ababa and Georgia in the US.
Antibiotic prophylaxis has been used to limit mass outbreaks of bacterial infections, such as meningococcal meningitis and ocular chlamydia infection, known as trachoma, when vaccines or other prophylactic measures are not widely available.
In the current cluster-randomised study (TANA II), a subset of communities in northern Ethiopia that had participated in a 4-year long trachoma prevention trial (TANA I) of either annual or semi-annual azithromycin treatment, were newly assigned to receive either continued annual or semi-annual azithromycin treatment, or cessation of treatment. Participants were observed for another 3-5 years and assessed for ocular chlamydia prevalence compared to baseline within each intervention group.
Between November 2010 and May 2013, 48 communities, including 3,938 children aged 0-9 years at baseline, were included in the trial. In the communities assigned to continue azithromycin, mean antibiotic coverage was greater than 90%. In the discontinuation groups, the mean prevalence of infection increased from 8.3% (95% confidence interval 4.2% to 12.4%) at baseline to 14.7% (95% CI 8.7% to 20.8%, P=0.04) at 36 months. Ocular chlamydia prevalence in communities where mass azithromycin distribution was continued was 7.2% (95% CI 3.3 to 11.0%) at baseline and 6.6% (95% CI 1.1 to 12.0%, P=0.64) at 36 months, showing that despite a total of 7 years of mass azithromycin distribution, infection was not eliminated. Nonetheless, the 36-month prevalence of ocular chlamydia was significantly lower in communities continuing antibiotic treatment compared with those discontinuing treatment (P=0.03)
One limitation of the study is that the results may not apply to regions with lower prevalence of trachoma.
The authors conclude that “stopping mass azithromycin treatment in some
severely affected areas is not realistic,” and that “alternative strategies for trachoma elimination may be required for the most severely affected areas.”
Abstract
Background: The World Health Organization recommends annual mass azithromycin administration in communities with at least 10% prevalence of trachomatous inflammation–follicular (TF) in children, with further treatment depending on reassessment after 3–5 years. However, the effect of stopping mass azithromycin distribution after multiple rounds of treatment is not well understood. Here, we report the results of a cluster-randomized trial where communities that had received 4 years of treatments were then randomized to continuation or discontinuation of treatment.
Methods and findings: In all, 48 communities with 3,938 children aged 0–9 years at baseline in northern Ethiopia had received 4 years of annual or twice yearly mass azithromycin distribution as part of the TANA I trial. We randomized these communities to either continuation or discontinuation of treatment. Individuals in the communities in the continuation arm were offered either annual or twice yearly distribution of a single directly observed dose of oral azithromycin. The primary outcome was community prevalence of ocular chlamydial infection in a random sample of children aged 0–9 years, 36 months after baseline. We also assessed the change from baseline to 36 months in ocular chlamydia prevalence within each arm. We compared 36-month ocular chlamydia prevalence in communities randomized to continuation versus discontinuation in a model adjusting for baseline ocular chlamydia prevalence. A secondary prespecified analysis assessed the rate of change over time in ocular chlamydia prevalence between arms. In the continuation arm, mean antibiotic coverage was greater than 90% at all time points. In the discontinuation arm, the mean prevalence of infection in children aged 0–9 years increased from 8.3% (95% CI 4.2% to 12.4%) at 0 months to 14.7% (95% CI 8.7% to 20.8%, P = 0.04) at 36 months. Ocular chlamydia prevalence in communities where mass azithromycin distribution was continued was 7.2% (95% CI 3.3% to 11.0%) at baseline and 6.6% (95% CI 1.1% to 12.0%, P = 0.64) at 36 months. The 36-month prevalence of ocular chlamydia was significantly lower in communities continuing treatment compared with those discontinuing treatment (P = 0.03). Limitations of the study include uncertain generalizability outside of trachoma hyperendemic regions.
Conclusions: In this study, ocular chlamydia infection rebounded after 4 years of periodic mass azithromycin distribution. Continued distributions did not completely eliminate infection in all communities or meet WHO control goals, although they did prevent resurgence.
Authors
Jeremy D Keenan, Zerihun Tadesse, Sintayehu Gebresillasie, Ayalew Shiferaw, Mulat Zerihun, Paul M Emerson, Kelly Callahan, Sun Y Cotter, Nicole E Stoller, Travis C Porco, Catherine E Oldenburg, Thomas M Lietman
[link url="http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002633"]PLOS One abstract[/link]