Comparison of annual versus twice-yearly mass azithromycin treatment for hyperendemic trachoma in Ethiopia: a cluster-randomised trial.

BACKGROUND: In trachoma control programmes, azithromycin is distributed to treat the strains of chlamydia that cause ocular disease. We aimed to compare the effect of annual versus twice-yearly distribution of azithromycin on infection with these strains. METHODS: We did a cluster-randomised trial in 24 subdistricts in northern Ethiopia, which we randomly assigned to receive annual or twice-yearly treatment for all residents of all ages. Random assignment was done with the RANDOM and SORT functions of Microsoft Excel. All individuals were offered their assigned treatment of a single, directly observed, oral dose of azithromycin. A 6 week course of topical 1% tetracycline ointment, applied twice daily to both eyes but not directly observed, was offered as an alternative to azithromycin in patients younger than 12 months, and in patients with self-reported pregnancy, with allergy, or who refused azithromycin. Our primary, prespecified outcome was the prevalence of ocular chlamydial infection in a random sample of children aged 0-9 years at baseline and every 6 months for a total of 42 months within sentinel villages. Our analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00322972. FINDINGS: Antibiotic coverage of children aged 1-9 years was greater than 80% (range 80·9 to 93·0) at all study visits. In the groups treated annually, the prevalence of infection in children aged 0-9 years was reduced from a mean 41·9% (95% CI 31·5 to 52·2) at baseline to 1·9% (0·3 to 3·5) at 42 months. In the groups treated twice yearly, the prevalence of infection was reduced from a mean 38·3% (29·0 to 47·6) at baseline to 3·2 % (0·0 to 6·5) at 42 months. The prevalence of ocular chlamydial infection in children aged 0-9 years in groups treated annually was not different from that of the groups treated twice yearly at 18, 30, and 42 months (pooled regression p>0·99, 95 % CI -0·06 to 0·06). The mean elimination time in the twice-yearly treatment group was 7·5 months earlier (2·3 to 17·3) than that of the annual group (p=0·10, Cox proportional hazards model). INTERPRETATION: After 42 months of treatment, the prevalence of ocular infection with chlamydia was similar in the groups treated annually and twice yearly. However, elimination of infection might have been more rapid in the groups of villages that received treatment twice yearly. FUNDING: National Institutes of Health (NEI U10 EY016214).

Ribosomal RNA evidence of ocular Chlamydia trachomatis infection following 3 annual mass azithromycin distributions in communities with highly prevalent trachoma.

Twelve trachoma-hyperendemic communities were treated with 3 annual mass azithromycin distributions. Children aged 0-9 years were monitored 1 year following the third treatment. An RNA-based test detected ocular chlamydial infection in more children than did a DNA-based test (6.9% vs 4.2%), and in a larger number of communities (8 vs 7).

Effect of Azithromycin on the Ocular Surface Microbiome of Children in a High Prevalence Trachoma Area.

PURPOSE: The aim of this study was to evaluate the effect of the 4 times per year mass azithromycin distributions on the ocular surface microbiome of children in a trachoma endemic area. METHODS: In this cluster-randomized controlled trial, children aged 1 to 10 years in rural communities in the Goncha Seso Enesie district of Ethiopia were randomized to either no treatment or treatment with a single dose of oral azithromycin (height-based dosing to approximate 20 mg/kg) every 3 months for 1 year. Post hoc analysis of ocular surface Chlamydia trachomatis load, microbial community diversity, and macrolide resistance determinants was performed to evaluate differences between treatment arms. RESULTS: One thousand two hundred fifty-five children from 24 communities were included in the study. The mean azithromycin coverage in the treated communities was 80% (95% CI: 73%-86%). The average age was 5 years (95% CI: 4-5). Ocular surface C. trachomatis load was reduced in children treated with the 4 times per year azithromycin ( P = 0.0003). Neisseria gonorrhoeae , Neisseria lactamica , and Neisseria meningitidis were more abundant in the no-treatment arm compared with the treated arm. The macrolide resistance gene ermB was not different between arms ( P = 0.63), but mefA / E was increased ( P = 0.04) in the azithromycin-treated arm. CONCLUSIONS: We found a reduction in the load of C. trachomatis and 3 Neisseria species in communities treated with azithromycin. These benefits came at the cost of selection for macrolide resistance.

Childhood mortality in a cohort treated with mass azithromycin for trachoma.

BACKGROUND: Mass azithromycin distributions are used to clear ocular strains of chlamydia that cause trachoma, but treatments may also affect respiratory infections, diarrhea, and malaria. Here, we monitor a large cohort in which almost 90% of individuals received azithromycin. We assess whether receiving treatment is associated with reduced all-cause and infectious childhood mortality. METHODS: As part of a clinical trial for trachoma, a census was conducted in 24 communities in rural Ethiopia. All individuals ≥1 year of age were eligible for single-dose oral azithromycin, although antibiotic coverage was not universal. A follow-up census was performed 26 months after treatment to estimate all-cause mortality among children 1-5 years of age, and verbal autopsies were performed to identify infectious mortality. RESULTS: The cohort included 35,052 individuals ≥1 year of age and 5507 children 1-5 years of age, of whom 4914 received a dose of azithromycin. All-cause mortality was significantly lower among those 1-5-year-old children who received azithromycin (odds ratio [OR]=0.35 [95% confidence interval {CI}, 0.17-0.74]), as was infectious mortality (OR=0.20 [95% CI, 0.07-0.58]). When individuals were compared only with members of the same household, azithromycin treatment was still associated with reduced all-cause mortality in children 1-5 years of age (OR=0.40 [95% CI, 0.16-0.96]), although this relationship was not statistically significant for infectious mortality (OR=0.35 [95% CI, 0.10-1.28]). CONCLUSIONS: This study demonstrated an association between mass oral azithromycin treatment and reduced all-cause and infectious childhood mortality. This relationship could not be attributed to bias at the level of the household. Mass azithromycin distributions may have benefits unrelated to trachoma.

Antibiotic selection pressure and macrolide resistance in nasopharyngeal Streptococcus pneumoniae: a cluster-randomized clinical trial.

BACKGROUND: It is widely thought that widespread antibiotic use selects for community antibiotic resistance, though this has been difficult to prove in the setting of a community-randomized clinical trial. In this study, we used a randomized clinical trial design to assess whether macrolide resistance was higher in communities treated with mass azithromycin for trachoma, compared to untreated control communities. METHODS AND FINDINGS: In a cluster-randomized trial for trachoma control in Ethiopia, 12 communities were randomized to receive mass azithromycin treatment of children aged 1-10 years at months 0, 3, 6, and 9. Twelve control communities were randomized to receive no antibiotic treatments until the conclusion of the study. Nasopharyngeal swabs were collected from randomly selected children in the treated group at baseline and month 12, and in the control group at month 12. Antibiotic susceptibility testing was performed on Streptococcus pneumoniae isolated from the swabs using Etest strips. In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%-8.9%) at baseline, to 46.9% (37.5%-57.5%) at month 12 (p = 0.003). In control communities, azithromycin resistance was 9.2% (95% CI 6.7%-13.3%) at month 12, significantly lower than the treated group (p < 0.0001). Penicillin resistance was identified in 0.8% (95% CI 0%-4.2%) of isolates in the control group at 1 year, and in no isolates in the children-treated group at baseline or 1 year. CONCLUSIONS: This cluster-randomized clinical trial demonstrated that compared to untreated control communities, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to intensive azithromycin treatment. Mass azithromycin distributions were given more frequently than currently recommended by the World Health Organization's trachoma program. Azithromycin use in this setting did not select for resistance to penicillins, which remain the drug of choice for pneumococcal infections. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00322972. Please see later in the article for the Editors' Summary.

Assessment of herd protection against trachoma due to repeated mass antibiotic distributions: a cluster-randomised trial.

BACKGROUND: Trachoma-control programmes distribute oral azithromycin to treat the ocular strains of chlamydia that cause the disease and to control infection. Theoretically, elimination of infection is feasible if untreated individuals receive an indirect protective effect from living in repeatedly treated communities, which is similar to herd protection in vaccine programmes. We assessed indirect protection against trachoma with mass azithromycin distributions. METHODS: In a cluster randomised trial, 24 subkebeles (government-defined units) in Amhara, Ethiopia, were randomised, with use of a simple random sample, to distribution four times per year of single-dose oral azithromycin to children aged 1-10 years (12 subkebeles, 4764 children), or to delayed treatment until after the study (control; 12 subkebeles, 6014 children). We compared the prevalence of ocular chlamydial infection in untreated individuals 11 years and older between baseline and 12 months in the treated subkebeles, and at 12 months between the treated and control subkebeles. Health-care and laboratory personnel were blinded to study group. Analysis was intention to treat. The study is registered with clinicaltrials.gov, number NCT00322972. FINDINGS: At 12 months, 637 children aged 1-10 years and 561 adults and children aged 11 years and older were analysed in the children-treated group, and 618 and 550, respectively, in the control group. The mean prevalence of infection in children decreased from 48.4% (95% CI 42.9-53.9) to 3.6% (0.8-6.4) after four mass treatments. At 12 months, the mean prevalence of infection in the untreated age group (>/=11 years) was 47% (95% CI 33-57) less than baseline (p=0.002), and 35% (95% CI 1-57) less than that in untreated communities (p=0.04). INTERPRETATION: Frequent treatment of children, who are a core group for transmission of trachoma, could eventually eliminate infection from the entire community. Herd protection is offered by repeated mass antibiotic treatments, providing a strategy for elimination of a bacterial disease when an effective vaccine is unavailable. FUNDING: National Institutes of Health.

Effect of a community intervention with pit latrines in five districts of Amhara, Ethiopia.

OBJECTIVE: To evaluate the change in household latrine coverage and investigated predictors of latrine uptake after 3 years of implementation of trachoma control interventions in Dera, Ebinat, Estie, Enebsie Sarmedir and Huleteju Enese districts of Amhara, Ethiopia. METHODS: Before and after study, baseline surveys were conducted prior to programme implementation and an evaluation after 3 years of interventions. Multi-stage cluster random sampling was used in both surveys. RESULTS: A total of 1096 and 1117 households were sampled and assessed for the presence of household latrines at baseline and evaluation, respectively. The proportion of households with a pit latrine increased by 32.3% overall (95% confidence interval [CI]: 27.9-38.0), ranging from 8.0% (95% CI: 5.1-10.8) in Ebinat to 58.9% (95% CI: 51.9-66.8) in Enebsie Sarmedir. Logistic regression analysis of associations between household latrine ownership and potential factors showed that increasing household size (OR(per additional person) = 1.2[95% CI: 1.1-1.3]), higher socio-economic status (tin roof) (OR = 1.8[95% CI: 1.2-2.9]) and participation in health education (OR = 1.6[95% CI: 1.1-2.5]) were independent predictors of latrine ownership. CONCLUSION: Our study documented heterogeneous increase in household latrine coverage after 3 years of latrine promotion; two of five districts had achieved Millennium Development Goal 7.9 and halved the proportion of households without latrine access. We attribute the striking increase in household latrines to increased political commitment of the local government and intensive community mobilisation under the trachoma control programme in Amhara region.

Frequency of Mass Azithromycin Distribution for Ocular Chlamydia in a Trachoma Endemic Region of Ethiopia: A Cluster Randomized Trial.

PURPOSE: Annual mass azithromycin distribution significantly reduces the prevalence of ocular Chlamydia trachomatis, the causative organism of trachoma. However, in some areas a decade or more of treatment has not controlled infection. Here, we compared multiple treatment arms from a community-randomized trial to evaluate whether increasing frequency of azithromycin distribution decreases prevalence in the short term. METHODS: Seventy-two communities in Goncha Siso Enesie woreda in the Amhara region of Northern Ethiopia were randomized to 1 of 6 azithromycin distribution strategies: (1) delayed, (2) annual, (3) biannual, (4) quarterly to children only, (5) biennial, or (6) biennial plus latrine promotion. We analyzed data from the 60 communities in the delayed, annual, biannual, quarterly, and biennial distribution arms at the 12-month study visit. Communities in the annual and biennial distribution arm were combined, as they each had a single distribution before any 12-month retreatment. We assessed the effect of increased frequency of azithromycin distribution on ocular chlamydia prevalence. RESULTS: Ocular chlamydia prevalence was significantly different across azithromycin distribution frequency in children (P < .0001) and adults (P < .0001), with lower prevalence associated with higher frequency. Among children, quarterly azithromycin distribution led to a significantly greater reduction in ocular chlamydia prevalence than the World Health Organization-recommended annual treatment prevalence (mean difference -11.4%, 95% confidence interval -19.5 to -3.3%, P = .007). CONCLUSIONS: Increased frequency of azithromycin distribution leads to decreased ocular chlamydia prevalence over a short-term period. In some regions with high levels of ocular chlamydia prevalence, additional azithromycin distributions may help achieve local elimination of infection.

Effect of mass distribution of azithromycin for trachoma control on overall mortality in Ethiopian children: a randomized trial.

CONTEXT: Mass oral azithromycin distribution to affected communities is a cornerstone of the World Health Organization's trachoma elimination program. Antibiotics are provided to target the ocular strains of chlamydia that cause trachoma, but may also be efficacious against respiratory disease, diarrhea, and malaria--frequent causes of childhood mortality in trachoma-endemic areas. OBJECTIVE: To compare mortality rates of participants aged 1 to 9 years in treated communities with those in untreated communities. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cluster-randomized clinical trial of mass azithromycin administration for trachoma control. Forty-eight communities (known as subkebeles) were randomized into 1 of 3 treatment schedules (annual treatment of all residents [15,902 participants], biannual treatment of all residents [17,288 participants], or quarterly treatment of children only [14,716 participants]) or into 1 group for which treatment was delayed by 1 year (control, 18,498 participants). Twelve subkebeles were randomized to each of the 4 schedules with all children in each of the 3 communities being eligible for treatment. The trial was conducted in a field setting in rural Ethiopia, May 2006 to May 2007. INTERVENTIONS: A single dose of oral azithromycin (adults, 1 g; children, 20 mg/kg) was administered for treatment of ocular Chlamydia trachomatis infection. Antibiotic coverage levels for children aged 1 to 9 years exceeded 80% at all visits. MAIN OUTCOME MEASURE: The main outcome measure was the community-specific mortality risk for children aged 1 to 9 years over the course of 1 year. Mortality was measured by enumerative census at baseline and again after 1 year. Comparison of the risk of mortality was a prespecified outcome for the clinical trial. RESULTS: The odds ratio for childhood mortality in the intervention communities was 0.51 (95% confidence interval, 0.29-0.90; P = .02; clustered logistic regression) compared with the control group. In the treated communities, the estimated overall mortality rate during this period for children aged 1 to 9 years in the untreated group was 8.3 per 1000 person-years (95% confidence interval, 5.3-13.1), while among the treated communities, the estimated overall mortality rate was 4.1 per 1000 person-years (95% confidence interval, 3.0-5.7) for children aged 1 to 9 years. CONCLUSION: In a trachoma-endemic area, mass distribution of oral azithromycin was associated with reduced mortality in children. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00322972.

Evaluation of light microscopy and rapid diagnostic test for the detection of malaria under operational field conditions: a household survey in Ethiopia.

BACKGROUND: In most resource-poor settings, malaria is usually diagnosed based on clinical signs and symptoms and not by detection of parasites in the blood using microscopy or rapid diagnostic tests (RDT). In population-based malaria surveys, accurate diagnosis is important: microscopy provides the gold standard, whilst RDTs allow immediate findings and treatment. The concordance between RDTs and microscopy in low or unstable transmission areas has not been evaluated. OBJECTIVES: This study aimed to estimate the prevalence of malaria parasites in randomly selected malarious areas of Amhara, Oromia, and Southern Nations, Nationalities and Peoples' (SNNP) regions of Ethiopia, using microscopy and RDT, and to investigate the agreement between microscopy and RDT under field conditions. METHODS: A population-based survey was conducted in 224 randomly selected clusters of 25 households each in Amhara, Oromia and SNNP regions, between December 2006 and February 2007. Fingerpick blood samples from all persons living in even-numbered households were tested using two methods: light microscopy of Giemsa-stained blood slides; and RDT (ParaScreen device for Pan/Pf). RESULTS: A total of 13,960 people were eligible for malaria parasite testing of whom 11,504 (82%) were included in the analysis. Overall slide positivity rate was 4.1% (95% confidence interval [CI] 3.4-5.0%) while ParaScreen RDT was positive in 3.3% (95% CI 2.6-4.1%) of those tested. Considering microscopy as the gold standard, ParaScreen RDT exhibited high specificity (98.5%; 95% CI 98.3-98.7) and moderate sensitivity (47.5%; 95% CI 42.8-52.2) with a positive predictive value of 56.8% (95% CI 51.7-61.9) and negative predictive value of 97.6% (95% CI 97.6-98.1%) under field conditions. CONCLUSION: Blood slide microscopy remains the preferred option for population-based prevalence surveys of malaria parasitaemia. The level of agreement between microscopy and RDT warrants further investigation in different transmission settings and in the clinical situation.

The association between latrine use and trachoma: a secondary cohort analysis from a randomized clinical trial.

Latrine use has been promoted as a component of an integrated strategy for trachoma control. As part of a randomized trial in Ethiopia, 12 communities received a mass azithromycin distribution followed by a latrine promotion intervention. A random sample of children ages 0-9 years in each community was monitored longitudinally for ocular chlamydia. After latrine construction ended, those communities with a higher proportion of households using latrines were more likely to experience a reduction in the prevalence of ocular chlamydia. Specifically, for each 10% increase in latrine use, there was a 2.0% decrease (95% confidence interval = 0.2-3.9% decrease) in the community prevalence of ocular chlamydia over the subsequent year (P = 0.04).

Reliability of measurements performed by community-drawn anthropometrists from rural Ethiopia.

BACKGROUND: Undernutrition is an important risk factor for childhood mortality, and remains a major problem facing many developing countries. Millennium Development Goal 1 calls for a reduction in underweight children, implemented through a variety of interventions. To adequately judge the impact of these interventions, it is important to know the reproducibility of the main indicators for undernutrition. In this study, we trained individuals from rural communities in Ethiopia in anthropometry techniques and measured intra- and inter-observer reliability. METHODS AND FINDINGS: We trained 6 individuals without prior anthropometry experience to perform weight, height, and middle upper arm circumference (MUAC) measurements. Two anthropometry teams were dispatched to 18 communities in rural Ethiopia and measurements performed on all consenting pre-school children. Anthropometry teams performed a second independent measurement on a convenience sample of children in order to assess intra-anthropometrist reliability. Both teams measured the same children in 2 villages to assess inter-anthropometrist reliability. We calculated several metrics of measurement reproducibility, including the technical error of measurement (TEM) and relative TEM. In total, anthropometry teams performed measurements on 606 pre-school children, 84 of which had repeat measurements performed by the same team, and 89 of which had measurements performed by both teams. Intra-anthropometrist TEM (and relative TEM) were 0.35 cm (0.35%) for height, 0.05 kg (0.39%) for weight, and 0.18 cm (1.27%) for MUAC. Corresponding values for inter-anthropometrist reliability were 0.67 cm (0.75%) for height, 0.09 kg (0.79%) for weight, and 0.22 kg (1.53%) for MUAC. Inter-anthropometrist measurement error was greater for smaller children than for larger children. CONCLUSION: Measurements of height and weight were more reproducible than measurements of MUAC and measurements of larger children were more reliable than those for smaller children. Community-drawn anthropometrists can provide reliable measurements that could be used to assess the impact of interventions for childhood undernutrition.

Diagnostic characteristics of tests for ocular Chlamydia after mass azithromycin distributions.

PURPOSE: Although trachoma control programs frequently use the World Health Organization (WHO) simplified grading system for trachoma to monitor the clinical response after repeated mass azithromycin treatments, the programmatic relevance of this evaluation after multiple rounds of antibiotic treatments is unclear. METHODS: Three rounds of annual mass azithromycin were distributed to 12 villages in Ethiopia. Twelve months after the third treatment, children were assessed for follicular trachomatous inflammation (TF) and intense trachomatous inflammation (TI) using the WHO simplified grading system and for ocular chlamydial infection using DNA-based and RNA-based tests. Test characteristics for predicting chlamydial infection were computed assuming a chlamydial RNA-based gold standard. As a secondary analysis, test characteristics were also assessed using a latent class analysis. RESULTS: The prevalence of RNA evidence of ocular chlamydia was 7.1% (95% confidence interval [CI], 2.7-17.4). A DNA-based test and TF had sensitivities of 61.0% (95% CI, 47.1-73.3) and 65.9% (95% CI, 41.6-83.9), specificities of 100% (95% CI, 99.3-100) and 67.5% (95% CI, 61.0-73.5), and positive predictive values of 100% (95% CI, 86.3-100) and 13.4% (95% CI, 5.5-29.3) compared with an RNA-based gold standard. The latent class analysis confirmed that the RNA-based test was a reasonable choice for a gold standard, with a sensitivity of 100% (95% CI, 67.1-100) and specificity of 99.6% (95% CI, 98.1-100). CONCLUSIONS: Basing treatment decisions after mass azithromycin distributions on the WHO simplified grading system will maximize the treatment of infected persons compared with a DNA-based test but will also result in more uninfected persons being treated. The RNA-based test was considerably more sensitive, and almost equivalently specific, compared with a DNA-based test. (ClinicalTrials.gov number, NCT00322972.).

Performance of local light microscopy and the ParaScreen Pan/Pf rapid diagnostic test to detect malaria in health centers in Northwest Ethiopia.

BACKGROUND: Diagnostic tests are recommended for suspected malaria cases before treatment, but comparative performance of microscopy and rapid diagnostic tests (RDTs) at rural health centers has rarely been studied compared to independent expert microscopy. METHODS: Participants (N = 1997) with presumptive malaria were recruited from ten health centers with a range of transmission intensities in Amhara Regional State, Northwest Ethiopia during October to December 2007. Microscopy and ParaScreen Pan/Pf® RDT were done immediately by health center technicians. Blood slides were re-examined later at a central laboratory by independent expert microscopists. RESULTS: Of 1,997 febrile patients, 475 (23.8%) were positive by expert microscopists, with 57.7% P. falciparum, 24.6% P. vivax and 17.7% mixed infections. Sensitivity of health center microscopists for any malaria species was >90% in five health centers (four of which had the highest prevalence), >70% in nine centers and 44% in one site with lowest prevalence. Specificity for health center microscopy was very good (>95%) in all centers. For ParaScreen RDT, sensitivity was ≥90% in three centers, ≥70% in six and <60% in four centers. Specificity was ≥90% in all centers except one where it was 85%. CONCLUSIONS: Health center microscopists performed well in nine of the ten health centers; while for ParaScreen RDT they performed well in only six centers. Overall the accuracy of local microscopy exceeded that of RDT for all outcomes. This study supports the introduction of RDTs only if accompanied by appropriate training, frequent supervision and quality control at all levels. Deficiencies in RDT use at some health centers must be rectified before universal replacement of good routine microscopy with RDTs. Maintenance and strengthening of good quality microscopy remains a priority at health center level.

The epidemiological dynamics of infectious trachoma may facilitate elimination.

INTRODUCTION: Trachoma programs use mass distributions of oral azithromycin to treat the ocular strains of Chlamydia trachomatis that cause the disease. There is debate whether infection can be eradicated or only controlled. Mass antibiotic administrations clearly reduce the prevalence of chlamydia in endemic communities. However, perfect coverage is unattainable, and the World Health Organization's goal is to control infection to a level where resulting blindness is not a public health concern. Here, we use mathematical models to assess whether more ambitious goals such as local elimination or even global eradication are possible. METHODS: We fit a class of non-linear, stochastic, susceptible-infectious-susceptible (SIS) models which allow positive or negative feedback, to data from a recent community-randomized trial in Ethiopia, and make predictions using model averaging. RESULTS: The models predict that reintroduced infection may not repopulate the community, or may do so sufficiently slowly that surveillance might be effective. The preferred model exhibits positive feedback, allowing a form of stochastic hysteresis in which infection returns slowly after mass treatment, if it returns at all. Results for regions of different endemicity suggest that elimination may be more feasible than earlier models had predicted. DISCUSSION: If trachoma can be eradicated with repeated mass antibiotic distributions, it would encourage similar strategies against other bacterial diseases whose only host is humans and for which effective vaccines are not available.

Adverse events after mass azithromycin treatments for trachoma in Ethiopia.

During a cluster-randomized clinical trial for trachoma in Ethiopia, two rounds of adverse event surveillance were performed in a random sample of communities after community-wide mass azithromycin treatment. The prevalence of any reported adverse event ranged from 4.9% to 7.0% in children 1-9 years of age and from 17.0% to 18.7% in persons ≥ 10 years of age. Adverse events appeared to cluster by household and perhaps by village. Mass azithromycin distributions were well tolerated in this setting.

Association of community antibiotic consumption with clinically active trachoma in rural Ethiopia.

Community antibiotic utilization and its relationship with trachoma has been poorly characterized in areas with endemic trachoma. A survey of all drug-dispensing facilities in an area of rural Ethiopia was conducted. Antibiotic use was calculated using both retrospective and prospective methodology, and expressed as defined daily doses (DDDs). Overall antibiotic consumption estimates ranged from 2.91 to 3.07 DDDs per 1000 person days. Macrolide antibiotics accounted for 0.01 to 0.02 DDDs per 1000 person days. Each additional DDD of antibiotic use per 1000 person days was associated with a 15.0% (95% CI -19.7 to -10.3) decrease in the prevalence of clinically active trachoma among children under 10 years of age after adjusting for age, gender, altitude and the distance to nearest town. Increased background community antibiotic use may therefore be an aspect of socioeconomic development that can partially explain why trachoma prevalence has decreased in some areas in the absence of a trachoma program. The low volume of macrolide consumption in this area suggests that selection for nasopharyngeal pneumococcal macrolide resistance after mass azithromycin treatments likely has little clinical significance.

Efficacy of latrine promotion on emergence of infection with ocular Chlamydia trachomatis after mass antibiotic treatment: a cluster-randomized trial.

The World Health Organization (WHO) recommends environmental improvements such as latrine construction in the integrated trachoma control strategy, SAFE. We report a cluster-randomized trial assessing the effect of intensive latrine promotion on emergence of infection with ocular Chlamydia trachomatis after mass treatment with antibiotics.Twenty-four communities in Goncha Seso Enesie woreda, Amhara Regional State, Ethiopia, were enumerated, and a random selection of 60 children aged 0- 9 years in each was monitored for clinical signs of trachoma and ocular chlamydial infection at baseline, 12 and 24 months. All community members were offered treatment with a single dose of oral azithromycin or topical tetracycline. After treatment, 12 subkebeles were randomized to receive intensive latrine promotion. Mean cluster ocular infection in the latrine and the non-latrine arms were reduced from 45.5% (95% CI 34.1-56.8%) and 43.0% (95% CI 31.1-54.8%) respectively at baseline to 14.6% (95% CI 7.4-21.8%) and 14.8% (95% CI 8.9-20.8%) respectively at 24 months (P=0.93). Clinical signs fell from 72.0% (95% CI 58.2-85.5%) and 61.3% (95% CI 44.0-78.5%) at baseline to 45.8% (36.0-55.6%) and 48.5% (34.0-62.9%) respectively at 24 months (P=0.69). At 24 months, estimated household latrine coverage and use were 80.8% and 61.7% respectively where there had been intensive latrine promotion and 30.0% and 25.0% respectively in the single treatment only arm. We were unable to detect a difference in the prevalence of ocular chlamydial infection in children due to latrine construction.

Latrine promotion for trachoma: assessment of mortality from a cluster-randomized trial in Ethiopia.

Trachoma control strategies, including latrine construction and antibiotic distribution, are directed at reducing ocular chlamydia, but may have additional benefits. In a cluster-randomized clinical trial, 24 subkebeles (administrative geographic units) in Ethiopia were offered a single mass azithromycin treatment, and half were randomized to receive an intensive latrine promotion. At a follow-up census 26 months after the baseline treatment, 320 persons had died. The mortality rate of children 1-5 years of age was 3.87 (95% confidence interval [CI] = 2.19-6.82) per 1,000 person-years in the latrine promotion arm, and 2.72 (95% CI = 1.37-5.42) per 1,000 person-years in the control arm. In a multi-level mixed effects logistic regression model controlling for age, there was no difference in mortality in persons randomized into the latrine or control arms (odds ratio = 1.18, 95% CI = 0.89-1.58). Latrine promotion provided no additional effect on mortality in the context of an azithromycin distribution program (clinicaltrials.gov, #NCT00322972).

Risk factors for ocular chlamydia after three mass azithromycin distributions.

BACKGROUND: An important component of the World Health Organization's comprehensive trachoma elimination strategy is the provision of repeated annual mass azithromycin distributions, which are directed at reducing the burden of ocular chlamydia. Knowledge of characteristics associated with infection after mass antibiotic treatments could allow trachoma programs to focus resources to those most likely to be infected with ocular chlamydia. METHODOLOGY/PRINCIPAL FINDINGS: We monitored 12 communities in rural Ethiopia that had received 3 annual mass azithromycin treatments as part of a cluster-randomized trial for trachoma. One year after the third treatment, a random sample of children from each village received conjunctival examination for follicular trachomatous inflammation (TF) and intense trachomatous inflammation (TI), conjunctival swabbing for chlamydial RNA and DNA, and a household survey. The primary outcome for this study was RNA evidence of ocular chlamydia, which we detected in 41 of 573 swabbed children (7.2%, 95%CI 2.7-17.8). In multivariate mixed effects logistic regression models, ocular chlamydial RNA was significantly associated with ocular discharge (OR 2.82, 95%CI 1.07-7.42), missing the most recent mass azithromycin treatment (OR 2.49, 95%CI 1.02-6.05), having a sibling with ocular chlamydia (OR 4.44, 95%CI 1.60-12.29), and above-median community population (OR 7.81, 95%CI 1.56-39.09). Ocular chlamydial infection was also independently associated with TF (OR 3.42, 95%CI 1.56-7.49) and TI (OR 5.39, 95%CI 2.43-11.98). CONCLUSIONS/SIGNIFICANCE: In areas with highly prevalent trachoma treated with multiple rounds of mass azithromycin, trachoma programs could consider continuing mass azithromycin treatments in households that have missed prior mass antibiotic treatments, in households with clinically active trachoma, and in larger communities.