Takele Lakew

Comparison of Annual and Biannual Mass Antibiotic Administration for Elimination of Infectious Trachoma

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.

A rationale for continuing mass antibiotic distributions for trachoma.

BackgroundThe World Health Organization recommends periodic mass antibiotic distributions to reduce the ocular strains of chlamydia that cause trachoma, the worlds 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.MethodsWe 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.ResultsSimulations 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.ConclusionLocal 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.

Reduction and return of infectious trachoma in severely affected communities in Ethiopia.

Background Antibiotics are a major tool in the WHOs 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 Decline of Pneumococcal Resistance after Cessation of Mass Antibiotic Distributions for Trachoma

After 6 biannual mass distributions of oral azithromycin for trachoma in Ethiopian communities, 76.8% (95% confidence interval [CI], 66.3%-85.1%) of nasopharyngeal Streptococcus pneumoniae isolates from children aged 1-5 years were resistant to macrolides. Twelve and 24 months after the last azithromycin treatment, resistance decreased to 30.6% (95% CI, 18.8%-40.4%; P <.001 ) and 20.8% (95% CI, 12.7%-30.7%; P < .001), respectively. Macrolide resistance decreases after antibiotic pressure is removed.

Complete local elimination of infectious trachoma from severely affected communities after six biannual mass azithromycin distributions.

OBJECTIVE To determine whether infectious trachoma can be completely eliminated from severely affected villages. DESIGN Cross-sectional survey of 2 villages previously enrolled and monitored over 42 months as part of a larger, group-randomized clinical trial. PARTICIPANTS A total of 758 individuals residing in 2 villages with high baseline trachoma prevalence, of a total population of 768 (98.7%). METHODS All members of the 2 villages were offered 6 biannual mass treatments with oral azithromycin. At 42 months, each current village member was examined. The right upper tarsal conjunctiva was everted and swabbed. Samples were processed for evidence of Chlamydia trachomatis RNA. MAIN OUTCOME MEASURES Clinical activity by World Health Organization simplified grading scale for trachoma and laboratory evidence of chlamydial RNA. RESULTS Average antibiotic coverage over the study period was 90% and 94% in the 2 villages. Clinical trachoma activity in children aged 1 to 5 years decreased from 78% and 83% in the 2 villages before treatment to 17% and 24% at 42 months. Polymerase chain reaction (PCR) evidence of infection in the same age group decreased from 48% to 0% in both villages at 42 months. When all age groups were examined, there were zero cases with evidence of chlamydial RNA among 758 total villagers tested. CONCLUSIONS Biannual mass distribution of azithromycin can locally eliminate ocular chlamydial infection from severely affected communities.

The fitness cost of antibiotic resistance in Streptococcus pneumoniae: insight from the field.

Background Laboratory studies have suggested that antibiotic resistance may result in decreased fitness in the bacteria that harbor it. Observational studies have supported this, but due to ethical and practical considerations, it is rare to have experimental control over antibiotic prescription rates. Methods and Findings We analyze data from a 54-month longitudinal trial that monitored pneumococcal drug resistance during and after biannual mass distribution of azithromycin for the elimination of the blinding eye disease, trachoma. Prescription of azithromycin and antibiotics that can create cross-resistance to it is rare in this part of the world. As a result, we were able to follow trends in resistance with minimal influence from unmeasured antibiotic use. Using these data, we fit a probabilistic disease transmission model that included two resistant strains, corresponding to the two dominant modes of resistance to macrolide antibiotics. We estimated the relative fitness of these two strains to be 0.86 (95% CI 0.80 to 0.90), and 0.88 (95% CI 0.82 to 0.93), relative to antibiotic-sensitive strains. We then used these estimates to predict that, within 5 years of the last antibiotic treatment, there would be a 95% chance of elimination of macrolide resistance by intra-species competition alone. Conclusions Although it is quite possible that the fitness cost of macrolide resistance is sufficient to ensure its eventual elimination in the absence of antibiotic selection, this process takes time, and prevention is likely the best policy in the fight against resistance.

Clinical Activity and Polymerase Chain Reaction Evidence of Chlamydial Infection after Repeated Mass Antibiotic Treatments for Trachoma

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 (Pearsons 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.

Slow Resolution of Clinically Active Trachoma Following Successful Mass Antibiotic Treatments

Trachoma, caused by infection with ocular strains of chlamydia, is the leading infectious cause of blindness worldwide. The World Health Organization recommends that in districts where the prevalence of clinically active trachoma exceeds 10% in children aged 1 to 9 years, communities should receive 3 annual mass antibiotic distributions followed by clinical reassessment; any communities with persistent trachoma should continue receiving annual mass antibiotic treatments until the prevalence of clinically active trachoma in children aged 1 to 9 years falls below 5% 1. Although trachoma treatment decisions are based on the prevalence of clinically active trachoma, it is unclear how quickly the clinical signs of trachoma resolve once infection has been cleared, especially in areas with severe trachoma. We recently performed a series of cluster-randomized clinical trials for trachoma in an area of Ethiopia with hyperendemic trachoma. In these trials, infection was brought to a low level in 24 villages randomized to receive mass azithromycin treatments every 6 months. This provided an opportunity to determine the rate of resolution of the clinical signs of trachoma given little to no chlamydial reinfection.

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

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.

Travel and Implications for the Elimination of Trachoma in Ethiopia

Purpose: Trachoma is the leading infectious cause of blindness. The World Health Organization has set a goal of reducing the trachoma disease burden to a level where it is no longer a public health concern by the year 2020. Some investigators feel that local elimination of ocular chlamydia infection is possible, but little has been done to study the likelihood of reintroduction of infection from neighboring areas. Mass administration of azithromycin has been shown to dramatically reduce the prevalence of infection in many villages in central Ethiopia. However, after treatment is discontinued, infection returns. Reintroduction of infection could occur from the few remaining infected cases in a treated community or from outside the community. People traveling between villages might be responsible thus complicating the elimination of trachoma. Methods: We conducted a survey to assess the travel pattern of the Gurage zone residents in Ethiopia. Seven hundred and seventeen households with at least one child aged 1–5 years in 48 villages were surveyed to collect the details of travel in 1 month prior to the survey. Results: Seventy-eight percent of the surveyed households had at least one traveler, with the majority being women. Pre-school children, the main reservoir of clinically active infection, rarely traveled. Most travel was to the market or to school, and most for less than 1 day. Conclusions: Travel routinely takes place in these villages. Trachoma control programs in this area might consider treating areas with the same markets and schools in the same period to increase the efficacy of mass treatment.