Research Article: Reduction and Return of Infectious Trachoma in Severely Affected Communities in Ethiopia

Date Published: February 10, 2009

Publisher: Public Library of Science

Author(s): Takele Lakew, Jenafir House, Kevin C. Hong, Elizabeth Yi, Wondu Alemayehu, Muluken Melese, Zhaoxia Zhou, Kathryn Ray, Stephanie Chin, Emmanuel Romero, Jeremy Keenan, John P. Whitcher, Bruce D. Gaynor, Thomas M. Lietman, Albert I. Ko

Abstract: BackgroundAntibiotics are a major tool in the WHO’s trachoma control program. Even a single mass distribution reduces the prevalence of the ocular chlamydia that causes trachoma. Unfortunately, infection returns after a single treatment, at least in severely affected areas. Here, we test whether additional scheduled treatments further reduce infection, and whether infection returns after distributions are discontinued.MethodsSixteen communities in Ethiopia were randomly selected. Ocular chlamydial infection in 1- to 5-year-old children was monitored over four biannual azithromycin distributions and for 24 months after the last treatment.FindingsThe average prevalence of infection in 1- to 5-year-old children was reduced from 63.5% pre-treatment to 11.5% six months after the first distribution (P<0.0001). It further decreased to 2.6% six months after the fourth and final treatment (P = 0.0004). In the next 18 months, infection returned to 25.2%, a significant increase from six months after the last treatment (P = 0.008), but still far lower than baseline (P<0.0001). Although the prevalence of infection in any particular village fluctuated, the mean prevalence of the 16 villages steadily decreased with each treatment and steadily returned after treatments were discontinued.ConclusionIn some of the most severely affected communities ever studied, we demonstrate that repeated mass oral azithromycin distributions progressively reduce ocular chlamydial infection in a community, as long as these distributions are given frequently enough and at a high enough coverage. However, infection returns into the communities after the last treatment. Sustainable changes or complete local elimination of infection will be necessary.Trial RegistrationClinicalTrials.gov NCT00221364

Partial Text: Trachoma remains a leading cause of blindness in poor, arid areas such as sub-Saharan Africa[1]. The World Health Organization (WHO) has targeted the disease in a control program, relying in part on repeated mass distributions of oral azithromycin to reduce the prevalence of the ocular chlamydial infection that causes the disease[2]. The program has had remarkable success in areas with moderate levels of infection and in areas where socioeconomic improvements are occurring in concert with the trachoma program. Even a single distribution can dramatically reduce the prevalence of chlamydia[3],[4],[5],[6]. In modestly infected communities, infection may then remain low[5]. In fact, in some areas, infectious trachoma is decreasing even in the absence of treatment[7],[8],[9]. However in severely affected communities, infection clearly returns after a single mass distribution, and repeated treatments will be necessary[10],[11],[12]. It is unknown whether scheduled, repeated distributions will progressively reduce infection, and for how long distributions will need to be given[10],[13]. In a previous study in southern Ethiopia, infection returned in the first 6 months after treatment at a rate that suggested that biannual treatment would be necessary for progressive reduction with each distribution[10],[14]. Here we present longer term results from these same villages, assessing the effect of four biannual distributions, and determining whether or not infection returns after treatments have been discontinued.

From the district record of the Enemore district of the Gurage Zone, southern Ethiopia, a simple random sample was chosen of 16 kebele (a government unit which in this area includes approximately 5 villages). A single random village was selected from each of 16 randomly chosen kebele as previously described[10]. Selected villages were given four biannual, community-wide antibiotic distributions starting in March 2003. At scheduled treatments, those aged 1 year and older were offered a single dose of directly observed, oral azithromycin (1 g in adults or 20 mg/kg in children). Pregnant women and those allergic to macrolides were offered a 6-week course of topical 1% tetracycline ointment (applied twice daily to both eyes and not directly observed).

In the baseline census, the 16 villages contained 5735 individuals in 1348 households. There were 808 1–5 year-old children, 48.6% of whom were girls (95% CI 45.3 to 51.9%). In these children, the mean prevalence of clinical activity (defined as either TF or TI in the WHO simplified grading scale), was 91.6% (95% CI 87.8 to 95.5%). The mean coverage of antibiotic at a village visit was 94.1% relative to the census, ranging from 73.9% to 100% of those eligible for treatment (Table 1). The first treatment reduced infection in all 16 villages, and the next three treatments further reduced the prevalence in 14 of 16 villages. Infection increased in the 24 months after the last treatment in 14 of 16 villages, but remained lower than it had been before the first treatment in all 16 villages. The mean prevalence was reduced from 63.5% at baseline (range 26.3% to 85.7%) to 11.5% six months after the first treatment range (0.0 to 24.4%) as previously described (P<0.0001)[10]. The next three biannual distributions continued to reduce the prevalence to 2.6% (range 0.0% to 7.0%), a significant decrease from after a single treatment (P = 0.0004). From 6 to 24 months after the last treatment (the 24 and 42 month visits), infection had returned to an average of 25.2% (range 2.0% to 70.0%). At 24 months after the last treatment, the mean prevalence of infection was far higher than at 6 months after the last treatment (P = 0.008), but was still only 40% of that at baseline (P<0.0001). It has been well documented that a single mass distribution of oral azithromycin to a trachoma-endemic community can lower the prevalence of ocular chlamydial infection. This has been demonstrated in group-randomized trials in Egypt, Tanzania, the Gambia, and a nearby area of Ethiopia and in observational studies in Tanzania, the Gambia, Nepal, and Vietnam[3],[4],[5],[6],[11],[12],[18]. This is true in even the most severely affected communities such as those followed in this study[10]. However, if infection is not locally eliminated, it returns back into a community after a single mass distribution, at least in severely affected areas, so repeated distributions will be necessary[10],[11],[12]. Source: http://doi.org/10.1371/journal.pntd.0000376

 

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