Complete Elimination is a Difficult Goal for Trachoma Programs in Severely Affected Communities

Deborah A. Gill 1 2 Takele Lakew 1 3 Wondu Alemayehu 1 3 Muluken Melese 1 3 Zhaoxia Zhou 1 2 Jenafir I. House 1 2 Kevin C. Hong 1 2 Kathryn J. Ray 1 2 Nandini Gandhi 1 2 John P. Whitcher 0 1 2 4 Bruce D. Gaynor 1 2 Thomas M. Lietman () 0 1 2 4 0 Epidemiology and Biostatistics 1 Received 28 June 2007; accepted 25 October 2007; electronically published 14 January 2008. Sciences, University of California , San Francisco, San Francisco, CA 94143-0412 2 F. I. Proctor Foundation, Departments of 3 Orbis International , Addis Ababa, Ethiopia 4 Institute for Global Health, University of California , San Francisco The World Health Organization has distributed millions of doses of azithromycin to control the ocular chlamydial infection that causes trachoma. Theoretically, a loftier goal of elimination is feasible. Here, we demonstrate that, although local elimination of infection in the most severely affected communities is difficult, it is possible with biannual antibiotic distributions. - The World Health Organization (WHO) has recommended repeated, community-wide antibiotic distributions to control ocular chlamydial infection so that blinding trachoma is no longer a major public health concern [1]. The WHO does not anticipate that infection can be eradicated or even locally eliminated from an area. Instead, the WHO relies on other measures, such as hygiene and environmental improvements, to prevent infection from returning after antibiotics are discontinued. Although there are reasons to hope that nonantibiotic measures may be beneficial, there is currently no evidence that any particular intervention prevents infection from returning to a community once antibiotics have been discontinued [2]. Thus, if achievable, local elimination of infection would be an important end point. Mathematical models suggest that local elimination of infection is possible even in severely affected communities if antibiotics are distributed frequently enough and to a large enough portion of the community [3, 4]. In villages with low rates of infection, 1 treatments have come close to eliminating infection [57]. In areas of hyperendemicity, if infection is not eliminated from a community, it can clearly return, even if a decrease to a low rate of infection is achieved [4, 8, 9]. To date, no study has demonstrated that infection can be locally eliminated from all members of a severely affected community. In our study, we surveyed all members of 3 Ethiopian villages where ocular chlamydial infection is hyperendemic that are likely candidates for elimination of the infection. Methods. Twenty-four communities in the Enemore district of the Gurage Zone, Ethiopia, received biannual mass oral azithromycin distributions, as described elsewhere [8]. Briefly, a stratified sample of 24 villages was randomly chosen from a complete list of villages in 3 subdistricts. A census was conducted, and all individuals aged 1 year were offered 4 biannual, single-dose azithromycin treatments (1 g to adults and 20 mg/kg to children) over 24 months. Pregnant women were offered topical tetracycline ointment. Children aged 15 years, the age group most likely to harbor infection, were monitored prior to each mass antibiotic administration and at 6 months after the last antibiotic administration. After verbal consent was obtained from the parent or guardian of each child, an upper conjunctival swab specimen was obtained for PCR testing. At 24 months after the study start, there was no PCR-proven infection in preschool-age children in 8 villages for at least 2 consecutive visits, and these villages were considered as candidates for elimination. Three of these 8 villages were chosen for this study on the basis of their populations (!400 individuals) and the prevalence of infection (130%) in the village before treatment. At the 30-month visit in October 2005, we attempted to examine every individual from these 3 villages. If an individual was not present, we returned to the village on a subsequent day within the same 7-day period. Villages were visited until survey coverage was complete or up to 4 times. The upper right tarsal conjunctiva was everted and swabbed. Swab specimens were placed at 4 C immediately and then at 20 C within 6 h and were transported at 4 C to the University of California, San Francisco, for processing using the Amplicor PCR (Roche Molecular Systems). Posttreatment samples from the same village were randomly pooled into groups of 5 for processing. For samples collected from children aged 15 years at baseline or from the entire community at 30 months, every sample in a positive pool was then processed to determine the infected individual(s). For samples collected from children aged 15 years during the 224 months after treatment, the prevalence of infection in the village was estimated directly from the percentage of positive pools using maximum likelihood estimation, as described elsewhere [4, 8]. Note that this pooling strategy is considerably costeffective. Laboratory control samples were included according to the Roche Amplicor protocol. In addition, 2 sets of field controls were obtained. Before changing gloves for the next patient, a second swab was passed within 1 inch of the conjunctiva (without touching) in 5 random individuals from each village (negative field control group). A duplicate swab specimen was obtained from 5 different randomly chosen individuals from each village (duplicate field control group). All specimens were processed in a masked manner. Results. Antibiotic coverage of the intended population (persons aged 1 year) in the 3 villages ranged from 85% to 100% at each village visit, with a mean coverage of 190% (table 1). The 3 most common reasons for not receiving treatment were temporary absence from the village at the time of treatment, migration, and death. Refusal of treatment was rare, and adherence to treatment when given was essentially 100%, because it was single-dose, observed therapy. The 3 villages chosen for the study had a mean estimated population of 211 persons at 30 months, with a mean baseline prevalence of infection of 43%. At 30 months, 19.8% of the population in the 3 villages was aged 15 years. The 24 villages in the original study had a mean baseline prevalence of PCR-positive infection of 52.9% and a mean baseline population of 250 persons. The 5 villages that had no evidence of infection at 18 and 24 months and were not chosen for this study had a mean baseline prevalence of infection of 26.9% and a mean estimated population of 358 persons. Characteristics of the 3 villages chosen for this study are shown in table 1. The estimated prevalence of ocular chlamydial infection among children aged 15 years from pretreatment to 24 months is shown in figure 1. Note that no infections were found in children aged 15 years at the 18- and 24-month visits. At 30 months, coverage with swabbing was nearly complete in village 1. We were unable to examine an 85-year-o (...truncated)