PURPOSE Conjunctival infection with non-chlamydial bacteria may play an important role in the progression of trachoma, especially with regard to the development of corneal opacity and blindness. To further characterize the microbiological profile of bacterial conjunctival infections in cicatricial trachoma, a conjunctival swabbing of adults in rural Ethiopia was performed. METHODS In a cross-sectional study conducted in nine Ethiopian villages with hyperendemic trachoma, persons 40 years of age or older with signs or symptoms consistent with trichiasis were recruited and conjunctival swabbing for bacterial pathogens was performed. RESULTS Conjunctival examination and swabbing on 112 females and 36 males were performed. Of the 148 study participants, 101 (68.2%) were confirmed to have trichiasis, and 118 (80%) had conjunctival swabs positive for bacteria. In multivariate analyses, growth of pathogenic conjunctival bacteria was independently associated with trichiasis (odds ratio [OR] 6.93; 95% confidence interval [CI] 2.71-17.7) and female sex (OR 5.90; 95% CI 2.09-16.7). Females were more likely to have swabs positive for Streptococcus pneumoniae or Haemophilus influenzae than were males (OR 9.09; 95% CI 1.17-70.8). CONCLUSIONS In a region of Ethiopia with endemic trachoma, conjunctival bacterial growth was more common in females than that in males. S. pneumoniae and H. influenzae, both of which frequently colonize the nasopharynx of children, were more common in females, suggesting that the preponderance of infection in females may be attributable to close contact with children. This finding is consistent with the theory that childcare activities may preferentially expose females to ocular chlamydial infection. (ClinicalTrials.gov number, NCT00221364.).

It is unclear how the prevalence of clinically active trachoma correlates with the prevalence of ocular chlamydial infection at the community level. In 24 villages from a cluster-randomized clinical trial of mass azithromycin distributions in Ethiopia, the correlation between the prevalence of clinical activity (on examination) and chlamydial infection (by polymerase chain reaction) was moderately strong before mass antibiotic treatments (Pearson's correlation coefficient r = 0.75, 95% confidence interval [CI] = 0.52-0.87), but decreased at each time point during four biannual treatments (at 24 months, r = 0.15, 95% CI = -0.14-0.41). One year after the final treatment, the correlation coefficient had increased, but not to the pre-treatment level (r = 0.55, 95% CI = 0.30-0.73). In a region with hyperendemic trachoma, conjunctival examination was a useful indicator of the prevalence of chlamydial infection before treatments, less useful during mass treatments, but regained utility by one year after treatments had stopped.

BACKGROUND:Antibiotics 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.METHODS:Sixteen 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.FINDINGS:The 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.CONCLUSION:In 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 REGISTRATION:ClinicalTrials.gov NCT00221364.

The purpose of this study was to examine potential differences in the predictors of expressive vocabulary development between children with Down syndrome and typically developing children to support preparation for intervention development. An age cohort of 43 children with Down syndrome and 57 typically developing children with similar nonverbal mental age levels were assessed at three time points. Linear mixed models were used to investigate the predictors of expressive vocabulary over time. Both groups achieved progress in expressive vocabulary. The typically developing children had steeper growth than the children with Down syndrome (1.38 SD vs. 0.8 SD, p < 0.001). In both groups, receptive vocabulary, auditory memory, and the home literacy environment were significant predictors of development. In the children with Down syndrome, the phonological awareness and oral motor skills were also significant. Group comparisons showed that receptive vocabulary, auditory memory and oral motor skills were stronger predictors in the children with Down syndrome than in the typically developing children. These results indicate that children with Down syndrome are more vulnerable when it comes to risk factors that are known to influence expressive vocabulary than typically developing children. Children with Down syndrome therefore require early broad-based expressive vocabulary interventions.

CONTEXT:Treatment recommendations assume that repeated mass antibiotic distributions can control, but not eradicate or even locally eliminate, the ocular strains of chlamydia that cause trachoma. Elimination may be an important end point because of concern that infection will return to communities that have lost immunity to chlamydia after antibiotics are discontinued.OBJECTIVE:To determine whether biannual treatment can eliminate ocular chlamydial infection from preschool children and to compare results with the World Health Organization-recommended annual treatment.DESIGN, SETTING, AND PARTICIPANTS:A cluster-randomized clinical trial of biannual vs annual mass azithromycin administrations to all residents of 16 rural villages in the Gurage Zone, Ethiopia, from March 2003 to April 2005.INTERVENTIONS:At scheduled treatments, all individuals aged 1 year or older were offered a single dose of oral azithromycin either annually or biannually.MAIN OUTCOME MEASURE:Village prevalence of ocular chlamydial infection and presence of elimination at 24 months in preschool children determined by polymerase chain reaction, correcting for baseline prevalence. Antibiotic treatments were performed after sample collections.RESULTS:Overall, 14,897 of 16,403 eligible individuals (90.8%) received their scheduled treatment. In the villages in which residents were treated annually, the prevalence of infection in preschool children was reduced from a mean of 42.6% (range, 14.7%-56.4%) to 6.8% (range, 0.0%-22.0%) at 24 months. In the villages in which residents were treated biannually, infection was reduced from 31.6% pretreatment (range, 6.1%-48.6%) to 0.9% (range, 0.0%-4.8%) at 24 months. Biannual treatment was associated with a lower prevalence at 24 months (P = .03, adjusting for baseline prevalence). At 24 months, no infection could be identified in 6 of 8 of those treated biannually and in 1 of 8 of those treated annually (P = .049, adjusting for baseline prevalence).CONCLUSION:Local elimination of ocular chlamydial infection appears feasible even in the most severely affected areas, although it may require biannual mass antibiotic distributions at a high coverage level.TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00221364.

There are various approaches to control trachoma. These include the elimination of the ocular strains of Chlamydia trachomatis that cause the disease and to decrease the spread of infection by other measures such as fly control. Here, we examined how these two are related (i.e., how treating children with antibiotics affects carriage of Chlamydia by flies). Flies were collected in villages that had received mass oral azithromycin distribution and were compared with flies in untreated villages. Polymerase chain reaction (PCR) was performed to detect chlamydial DNA on the flies. Conjunctival swabs were also taken to assay for chlamydial prevalence in the children. Chlamydia was found on 23% of the flies in the untreated villages but only 0.3% in treated villages. Prevalence of trachoma in children proved to be an excellent predictor of the prevalence on flies (correlation coefficient, 0.89). Thus, treating children with antibiotics may drastically reduce the role of flies as a vector.

Background: The World Health Organization recommends periodic mass antibiotic distributions to reduce the ocular strains of chlamydia that cause trachoma, the world's leading cause of infectious blindness. Their stated goal is to control infection, not to completely eliminate it. A single mass distribution can dramatically reduce the prevalence of infection. However, if infection is not eliminated in every individual in the community, it may gradually return back into the community, so often repeated treatments are necessary. Since public health groups are reluctant to distribute antibiotics indefinitely, we are still in need of a proven long-term rationale. Here we use mathematical models to demonstrate that repeated antibiotic distributions can eliminate infection in a reasonable time period.Methods: We fit parameters of a stochastic epidemiological transmission model to data collected before and 6 months after a mass antibiotic distribution in a region of Ethiopia that is one of the most severely affected areas in the world. We validate the model by comparing our predicted results to Ethiopian data which was collected biannually for two years past the initial mass antibiotic distribution. We use the model to simulate the effect of different treatment programs in terms of local elimination of infection.Results: Simulations show that the average prevalence of infection across all villages progressively decreases after each treatment, as long as the frequency and coverage of antibiotics are high enough. Infection can be eliminated in more villages with each round of treatment. However, in the communities where infection is not eliminated, it returns to the same average level, forming the same stationary distribution. This phenomenon is also seen in subsequent epidemiological data from Ethiopia. Simulations suggest that a biannual treatment plan implemented for 5 years will lead to elimination in 95% of all villages.Conclusion: Local elimination from a community is theoretically possible, even in the most severely infected communities. However, elimination from larger areas may require repeated biannual treatments and prevention of re-introduction from outside to treated areas.

Context The World Health Organization recommends mass antibiotic distributions in its strategy to eliminate blinding trachoma as a public health concern. Some hypothesize that a single distribution is sufficient to control the ocular strains of chlamydia that cause trachoma. Others believe infection will inevitably return and periodic treatments or other measures are essential.Objective To determine whether ocular chlamydial infection returns to the community up to 24 months after a single mass antibiotic distribution in a hyperendemic region of Ethiopia.Design, Setting, and Participants Longitudinal cohort study conducted March 2003 to March 2005 in the Gurage Zone of Ethiopia. Eight randomly selected villages were assessed for ocular chlamydial infection. Fifteen untreated villages were randomly chosen at 12 months to allow assessment of a secular trend.Intervention A single dose of oral azithromycin was offered to all residents of the 8 selected villages who were aged 1 year or older.Main Outcome Measure Prevalence of ocular chlamydial infection in all children aged 1 to 5 years from each intervention village prior to treatment and 2, 6, 12, 18, and 24 months after mass antibiotic treatment, and also in untreated villages enrolled at 12 months.Results Five hundred fifteen children were examined for ocular chlamydial infection at baseline. For the follow-up examinations, the mean participation rate was 83%. The mean prevalence of infection in children aged 1 to 5 years decreased from 43.5% (95% confidence interval [CI], 35.0%-52.0%) to 5.1% ( 95% CI, 1.1%-9.2%) after treatment. On average, infection returned gradually over 24 months to 11.3% ( 95% CI, 4.5%-18.1%; P = .001). In 7 of 8 villages, infection was higher at 24 months than at 2 months. In the remaining village, no infection could be identified at any point after treatment. Villages enrolled at 12 months had significantly fewer infections than those enrolled 12 months earlier, suggesting a secular trend ( P < .001).Conclusions Ocular chlamydial infection was not eliminated in children aged 1 to 5 years after a single mass azithromycin distribution; it slowly returned over 24 months, although not to baseline levels. Repeated treatments or other effective measures will be necessary for elimination.

Aim: Face seeking flies have long been thought to transmit Chlamydia trachomatis, the causative agent of trachoma, but this has never been proven. The four criteria proposed by Barnett, previously used to incriminate other arthropods suspected of transmitting disease, were examined. One of these criteria remains unmet: the repeated demonstration of the presence of C trachomatis on flies. The authors used polymerase chain reaction (PCR) to look for the presence of C trachomatis DNA on flies in the Gurage Zone of Ethiopia.Methods: Using sticky paper, one fly was collected from the face of each of 103 children aged 1-10 years. The piece of fly paper to which the fly was attached was cut out, followed by the collection of an empty piece from an arbitrary area of the fly paper, which served as control. Roche Amplicor PCR kits were used to detect C trachomatis DNA.Results: Evidence of C trachomatis by PCR was found on 15 of 103 flies versus 0 of 103 controls (p=0.0001).Conclusion: These results meet the final criterion needed to incriminate flies as a vector of trachoma. However, interventional studies will be needed to show the importance of fly control.

PURPOSE To describe the relationship between the clinical exam for trachoma and the polymerase chain reaction (PCR) for ocular chlamydia.METHODS One hundred children in a trachoma-endemic area of Ethiopia were examined three times and swabbed twice for PCR analysis. The assays were compared, and an analysis of the variance between exam and PCR was performed.RESULTS Inter-examiner agreement was 0.57 (Cohen's K), inter-PCR agreement 0.98, and agreement between examiner and PCR, 0.26-0.34. The positive predictive value of the exam in identifying infection was 66%. Inter-examiner variance accounted for 30% of the total variance between the exam and PCR, with the remainder presumably due to an underlying difference in what the exam and PCR measure.CONCLUSIONS Despite modest inter-grader reliability and correlation with evidence of infection, the clinical exam is widely used due to its convenience and low cost. Efforts to make laboratory tests for ocular Chlamydia trachomatis more affordable would be useful.

Trachoma is disappearing in many parts of the world, even in the absence of specific control programs. Following mass antimicrobial drug treatments for trachoma in western Nepal, the prevalence of trachoma declined far more rapidly than could be attributed to the control program alone. Pharmacy surveys in the same region found that children received more antichlamydial drugs from sources outside the trachoma program than they did from the program itself. We demonstrate that high background antimicrobial drug use may be responsible for much of the observed decline in trachoma and discuss its potential role in eliminating this infectious disease.