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).

Epilation for trachomatous trichiasis and the risk of corneal opacification.

PURPOSE: Eight million people have trachomatous trichiasis (TT). The World Health Organization (WHO) recommends entropion surgery for TT regardless of severity. However, epilation is widely practiced for treating minor TT (1-5 lashes touching the globe). We report the frequency and effectiveness of patient-initiated epilation and its relationship to corneal opacity. DESIGN: Cross-sectional baseline data of individuals recruited to 2 randomized, clinical trials. PARTICIPANTS: We included 2556 individuals (4310 eyes) with previously unoperated TT in ≥ 1 eye. METHODS: A single ophthalmologist examined all participants for signs of trachoma using WHO grading systems with additional assessment of entropion grading, location and number of trichiatic lashes, and evidence of epilation. A questionnaire enquired about epilation practices. MAIN OUTCOME MEASURES: The association between epilation and degree of corneal opacity. Epilation practices of TT patients. RESULTS: Central corneal scarring was present in 1436 (33%) eyes. Entropion was absent/mild in 2328 (54%) eyes, moderate in 1259 (29.2%), and severe in 723 (16.8%). The median number of lashes touching the eye was 2 (interquartile range, 1-5; range, 0-133). There was clinical evidence of epilation in 3018 (70%) eyes, of which 738 (24%) were successfully epilated (no lashes touching globe). Epilation was performed frequently (at least monthly in 3311 [76.8%] eyes), by someone other than the patient (92.8%), and using locally made forceps (88.9%). Controlling for age and degree of entropion, successful epilation was associated with less corneal opacity (odds ratio [OR], 0.61; 95% confidence interval [CI]. 0.43-0.88; P = 0.007). The association was only significant in patients with severe entropion (OR, 0.07; 95% CI, 0.02-0.25; P<0.005). CONCLUSIONS: We found an association between successful epilation and less central corneal opacity. This indicates the importance of preventing eyelashes from touching the cornea, particularly in individuals with severe entropion. This is a cross-sectional study; therefore, a causative relationship cannot be concluded. However, the results suggest that among patients who decline or are unable to access surgery, and perhaps in minor TT where the management remains controversial, the provision of high-quality forceps and epilation training may be beneficial. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Surgery versus epilation for the treatment of minor trichiasis in Ethiopia: a randomised controlled noninferiority trial.

BACKGROUND: Trachomatous trichiasis can cause corneal damage and visual impairment. WHO recommends surgery for all cases. However, in many regions surgical provision is inadequate and patients frequently decline. Self-epilation is common and was associated with comparable outcomes to surgery in nonrandomised studies for minor trichiasis (

Absorbable versus silk sutures for surgical treatment of trachomatous trichiasis in Ethiopia: a randomised controlled trial.

BACKGROUND: Trachoma causes blindness through an anatomical abnormality called trichiasis (lashes touching the eye). Trichiasis can recur after corrective surgery. We tested the hypothesis that using absorbable sutures instead of silk sutures might reduce the risk of recurrent disease among patients with major trichiasis in a randomised trial. METHODS AND FINDINGS: 1,300 individuals with major trichiasis from rural villages in the Amhara Region of Ethiopia were recruited and assigned (1:1) by computer-generated randomisation sequence to receive trichiasis surgery using either an absorbable suture (polyglactin-910) or silk sutures (removed at 7-10 days) in an otherwise identical surgical technique. Participants were examined every 6 months for 2 years by clinicians masked to allocation. The primary outcome measure was recurrent trichiasis (≥one lash touching the eye) at 1 year. There was no difference in prevalence of recurrent trichiasis at 1 year (114 [18.2%] in the absorbable suture group versus 120 [19.7%] in the silk suture group; odds ratio = 0.90, 95% CI 0.68-1.20). The two groups also did not differ in terms of corneal opacification, visual acuity, conjunctival inflammation, and surgical complications. CONCLUSIONS: There was no evidence that use of absorbable polyglactin-910 sutures was associated with a lower prevalence of trichiasis recurrence at 1 year postsurgery than silk sutures. However, from a programmatic perspective, polyglactin-910 offers the major advantage that patients do not have to be seen soon after surgery for suture removal. The postoperative review after surgery using absorbable polyglactin-910 sutures can be delayed for 3-6 months, which might allow us to better determine whether a patient needs additional surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT00522860.

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.

Risk factors for active trachoma in children and trichiasis in adults: a household survey in Amhara Regional State, Ethiopia.

Identification of risk factors is essential for planning and implementing effective trachoma control programmes. We aimed to investigate risk factors for active trachoma and trichiasis in Amhara Regional State, Ethiopia. A survey was undertaken and eligible participants (children aged 1-9 years and adults aged 15 years and above) examined for trachoma. Risk factors were assessed through interviews and observations. Using ordinal logistic regression, associations between signs of active trachoma in children and potential risk factors were explored. Associations between trichiasis in adults and potential risk factors were investigated using conventional logistic regression. A total of 5427 children from 2845 households and 9098 adults from 4039 households were included in the analysis. Ocular discharge [odds ratio (OR)=5.9; 95% CI 4.8-7.2], nasal discharge (OR=1.6; 95% CI 1.3-1.9), thatch roof in household (OR=1.3; 95% CI 1.0-1.5), no electricity in household (OR=2.4; 95% CI 1.3-4.3) and increasing altitude (Ptrend<0.001) were independently associated with severity of active trachoma. Trichiasis was associated with increasing age (ORper 5 year increase=1.5; 95% CI 1.4-1.7), female gender (OR=4.5; 95% CI 3.5-5.8), increasing prevalence of active trachoma in children (Ptrend=0.003) and increasing altitude (Ptrend=0.015).

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.

Clearing the backlog: trichiasis surgeon retention and productivity in northern Ethiopia.

BACKGROUND: In 2006 there were an estimated 645,000 people in Amhara, Ethiopia, with trachomatous trichiasis (TT) who needed surgery. Despite an extensive integrated eye care worker training programme (IECW) and robust support for TT surgical services, productivity has not reached targets. We investigated why surgeon productivity was below target. METHODOLOGY/PRINCIPAL FINDINGS: Confidential interviews were conducted in person with TT surgeons trained from 24 selected districts in Amhara Region and their supervisors. Determinants of attrition and productivity were investigated. We interviewed 225 people who had received IECW training; 139 (59%) had subsequently changed career/job. Staff retention was associated with good road access to their health centre, mobile telephone network and a shorter time from initial training. Amongst the 94 IECW still working in the programme, the average number of patients operated was 41/year, which was mostly (86%) done through outreach campaigns and only 14% of cases were performed in the static facilities where they routinely worked. Spot checks were made of surgical instruments and consumables: only 3/94 IECW had the minimum instruments and consumables to perform surgery. The main barriers to operating were lack of time, shortage of consumables, lack of patients, lack of support and equipment problems. Very few IECW received ongoing supervision or active management. CONCLUSIONS/SIGNIFICANCE: Surgeon attrition rates are high. Vertical surgery campaigns were effective in treating large numbers of cases, whilst static-site service productivity was low. Good health system management is key to building a well-staffed and well-run service.

Comparison of Parascreen Pan/Pf, Paracheck Pf and light microscopy for detection of malaria among febrile patients, Northwest Ethiopia.

Two malaria rapid diagnostic tests (RDT), Parascreen Pan/Pf and Paracheck Pf, were tested in rural health centres in Ethiopia against independent expert microscopy (the gold standard). Participants (n =1997) presented with presumptive malaria to ten health centers in Amhara Regional State during the 2007 peak malaria season (October to December). By microscopy, 475 (23.8%) suspected malaria cases were positive, of which 57.7% were P. falciparum; 24.6% P. vivax and 17.7% mixed infections. Parascreen and Paracheck were positive for 442 (22.1%) and 277 (13.9%) febrile patients, respectively. For Parascreen, P. falciparum sensitivity was 79.6%, specificity 97.4%, positive predictive value (PPV) 86.9%, and negative predictive value (NPV) 95.6%. For Parascreen, P. vivax sensitivity was 74.4%, specificity 98.6%, PPV 76.3% and NPV 98.4%. For Paracheck, P. falciparum sensitivity was 73.7%, specificity 99.2%, PPV 95.3%, NPV 94.5%. Sensitivity was significantly higher for both tests (P<0.05) when parasite density was >100/microl of blood; in these cases Parascreen was 90.7% and 91.5% sensitive for P. falciparum and P. vivax, respectively, while Paracheck was 87.9% sensitive for P. falciparum. Parascreen thus performed adequately for both P. falciparum and P. vivax compared to expert microscopy and is more useful than Paracheck where microscopy is unavailable.

Integrating an NTD with one of "The big three": combined malaria and trachoma survey in Amhara Region of Ethiopia.

BACKGROUND: Amhara Regional State of Ethiopia has a population of approximately 19.6 million, is prone to unstable and epidemic malaria, and is severely affected by trachoma. An integrated malaria and trachoma control program is being implemented by the Regional Health Bureau. To provide baseline data, a survey was conducted during December 2006 to estimate malaria parasite prevalence, malaria indicators, prevalence of trachoma, and trachoma risk factors in households and people of all ages in each of the ten zones of the state, excluding three urban centers (0.4% of the population). METHODOLOGY/PRINCIPAL FINDINGS: The study was designed to provide prevalence estimates at zone and state levels. Using multi-stage cluster random sampling, 16 clusters of 25 households were randomly selected in each of the ten zones. Household heads were interviewed for malaria indicators and trachoma risk factors (N = 4,101). All people were examined for trachoma signs (N = 17,242), and those in even-numbered households provided blood films for malaria parasite detection (N = 7,745); both thick and thin blood films were read. Zonal malaria parasite prevalence ranged from 2.4% to 6.1%, with the overall state-wide prevalence being 4.6% (95% confidence interval (CI): 3.8%-5.6%). The Plasmodium falciparum: Plasmodium vivax ratio ranged from 0.9-2.1 with an overall regional ratio of 1.2. A total of 14.8% of households reported indoor residual spraying in the past year, 34.7% had at least one mosquito net, and 16.1% had one or more long-lasting insecticidal net. Zonal trachoma prevalence (trachomatous inflammation follicular [WHO grade TF] in children aged 1-9 years) ranged from 12.6% to 60.1%, with the overall state-wide prevalence being 32.7% (95% CI: 29.2%-36.5%). State-wide prevalence of trachomatous trichiasis (TT) in persons aged over fifteen was 6.2% (95% CI: 5.3-7.4), and 0.3% (95% CI: 0.2-0.5) in children aged 0-14 years. Overall, an estimated 643,904 persons (lower bound 419,274, upper bound 975,635) have TT and require immediate corrective surgery. CONCLUSIONS/SIGNIFICANCE: The results provide extensive baseline data to guide planning, implementation, and evaluation of the integrated malaria and trachoma control program in Amhara. The success of the integrated survey is the first step towards demonstration that control of priority neglected tropical diseases can be integrated with one of the "big three" killer diseases.