When the Neighboring Village is Not Treated: Role of Geographic Proximity to Communities Not Receiving Mass Antibiotics for Trachoma.

BACKGROUND: Mass administration of azithromycin is an established strategy for decreasing the prevalence of trachoma in endemic areas. However, nearby untreated communities could serve as a reservoir that may increase the chances of chlamydia reinfection in treated communities. METHODS: As part of a cluster-randomized trial in Ethiopia, 60 communities were randomized to receive mass azithromycin distributions and 12 communities were randomized to no treatments until after the first year. Ocular chlamydia was assessed from a random sample of children per community at baseline and month 12. Distances between treated and untreated communities were assessed from global positioning system coordinates collected for the study. RESULTS: The pretreatment prevalence of ocular chlamydia among 0 to 9 year olds was 43% (95% confidence interval [CI], 39%-47%), which decreased to 11% (95% CI, 9%-14%) at the 12-month visit. The posttreatment prevalence of chlamydia was significantly higher in communities that were closer to an untreated community after adjusting for baseline prevalence and the number of mass treatments during the year (odds ratio, 1.12 [95% CI, 1.03-1.22] for each 1 km closer to an untreated community). CONCLUSIONS: Mass azithromycin distributions to wide, contiguous geographic areas may reduce the likelihood of continued ocular chlamydia infection in the setting of mass antibiotic treatments.

Incidence, prevalence and mortality rates of malaria in Ethiopia from 1990 to 2015: analysis of the global burden of diseases 2015.

BACKGROUND: In Ethiopia there is no complete registration system to measure disease burden and risk factors accurately. In this study, the 2015 global burden of diseases, injuries and risk factors (GBD) data were used to analyse the incidence, prevalence and mortality rates of malaria in Ethiopia over the last 25 years. METHODS: GBD 2015 used verbal autopsy surveys, reports, and published scientific articles to estimate the burden of malaria in Ethiopia. Age and gender-specific causes of death for malaria were estimated using cause of death ensemble modelling. RESULTS: The number of new cases of malaria declined from 2.8 million [95% uncertainty interval (UI) 1.4-4.5 million] in 1990 to 621,345 (95% UI 462,230-797,442) in 2015. Malaria caused an estimated 30,323 deaths (95% UI 11,533.3-61,215.3) in 1990 and 1561 deaths (95% UI 752.8-2660.5) in 2015, a 94.8% reduction over the 25 years. Age-standardized mortality rate of malaria has declined by 96.5% between 1990 and 2015 with an annual rate of change of 13.4%. Age-standardized malaria incidence rate among all ages and gender declined by 88.7% between 1990 and 2015. The number of disability-adjusted life years lost (DALY) due to malaria decreased from 2.2 million (95% UI 0.76-4.7 million) in 1990 to 0.18 million (95% UI 0.12-0.26 million) in 2015, with a total reduction 91.7%. Similarly, age-standardized DALY rate declined by 94.8% during the same period. CONCLUSIONS: Ethiopia has achieved a 50% reduction target of malaria of the millennium development goals. The country should strengthen its malaria control and treatment strategies to achieve the sustainable development goals.

A socio-ecological analysis of barriers to the adoption, sustainablity and consistent use of sanitation facilities in rural Ethiopia.

BACKGROUND: Despite evidence showing that access to and use of improved sanitation is associated with healthier households and communities, barriers influencing the adoption and sustainablity of sanitation facilities remain unclear. We conducted a qualitative case study to explore barriers influencing the adoption, sustainablity and consistent use of sanitation facilities in rural Ethiopia. METHODS: A qualitative study was conducted in the rural district of Becho, in central Ethiopia, from June to August 2016. A socio-ecological model and Integrated Behavioural Model (IBM) for a Water Hygiene and Sanitation (WASH) framework were employed to design the study and analyse data. A total of 10 in-depth interviews (IDI) were conducted with latrine adopters (n = 3), latrine non-adopters (n = 3), health extension workers (n = 3) and the district WASH coordinator (n = 1). Eight Focus Group Discussions (FGD) were undertaken with 75 participants, of which 31 were women. The FGDs and IDIs were tape-recorded, transcribed verbatim and translated into English. The analysis was supported using Nvivo version 10 software. RESULTS: Barriers to sustained adoption and use of sanitation facilities were categorized into 1) individual level factors (e.g., past latrine experience, lack of demand and perceived high cost to improved latrines), 2) household level factors (e.g., unaffordability, lack of space and absence of a physically strong family member), 3) community level factors (e.g., lack of access to public latrines, lack of shared rules against open defecation, lack of financial access for the poor), and 4) societal level factors (e.g., lack of strong local leadership, flooding, soil conditions, lack of appropriate sanitation technology, lack of promotion and demand creation for improved latrines). CONCLUSION: The use of the socio-ecological model and IBM-WASH framework helped to achieve a better understanding of multi-level and multi-dimensional barriers to sustained latrine adoption. The results indicate that there is a need to consider interventions that address multi-level factors concurrently.

The National Programme to Eliminate Lymphatic Filariasis from Ethiopia.

Lymphatic filariasis (LF) is one of the most debilitating and disfiguring diseases common in Ethiopia and is caused by Wuchereria bancrofti. Mapping for LF has shown that 70 woredas (districts) are endemic and 5.9 million people are estimated to be at risk. The national government's LF elimination programme commenced in 2009 in 5 districts integrated with the onchocerciasis programme. The programme developed gradually and has shown significant progress over the past 6 years, reaching 100% geographical coverage for mass drug administration (MDA) by 2016. To comply with the global LF elimination goals an integrated morbidity management and disability prevention (MMDP) guideline and a burden assessment programme has also been developed; MMDP protocols and a hydrocoele surgical handbook produced for country-wide use. In Ethiopia, almost all LF endemic districts are co-endemic with malaria and vector control aspects of the activities are conducted in the context of malaria programme as the vectors for both diseases are mosquitoes. In order to monitor the elimination, 11 sentinel and spot-check sites have been established and baseline information has been collected. Although significant achievements have been achieved in the scale up of the LF elimination programme, there is still a need to strengthen operational research to generate programme-relevant evidence, to increase access to morbidity management services, and to improve monitoring and evaluation of the LF programme. However, the current status of implementation of the LF national programme indicates that Ethiopia is poised to achieve the 2020 goal of elimination of LF. Nevertheless, to achieve this goal, high and sustained treatment coverage and strong monitoring and evaluation of the programme are essential.

Evidence for clonal expansion after antibiotic selection pressure: pneumococcal multilocus sequence types before and after mass azithromycin treatments.

BACKGROUND: A clinical trial of mass azithromycin distributions for trachoma created a convenient experiment to test the hypothesis that antibiotic use selects for clonal expansion of preexisting resistant bacterial strains. METHODS: Twelve communities in Ethiopia received mass azithromycin distributions every 3 months for 1 year. A random sample of 10 children aged 0-9 years from each community was monitored by means of nasopharyngeal swab sampling before mass azithromycin distribution and after 4 mass treatments. Swab specimens were tested for Streptococcus pneumoniae, and isolates underwent multilocus sequence typing. RESULTS: Of 82 pneumococcal isolates identified before treatment, 4 (5%) exhibited azithromycin resistance, representing 3 different sequence types (STs): 177, 6449, and 6494. The proportion of isolates that were classified as one of these 3 STs and were resistant to azithromycin increased after 4 mass azithromycin treatments (14 of 96 isolates [15%]; P = .04). Using a classification index, we found evidence for a relationship between ST and macrolide resistance after mass treatments (P < .0001). The diversity of STs-as calculated by the unbiased Simpson index-decreased significantly after mass azithromycin treatment (P = .045). CONCLUSIONS: Resistant clones present before mass azithromycin treatments increased in frequency after treatment, consistent with the theory that antibiotic selection pressure results in clonal expansion of existing resistant strains.

Estimation of insecticide persistence, biological activity and mosquito resistance to PermaNet® 2 long-lasting insecticidal nets over three to 32 months of use in Ethiopia.

BACKGROUND: Information is needed on the expected durability of insecticidal nets under operational conditions. The persistence of insecticidal efficacy is important to estimate the median serviceable life of nets under field conditions and to plan for net replacement. METHODS: Deltamethrin residue levels were evaluated by the proxy method of X-ray fluorescence spectrometry on 189 nets used for three to six months from nine sites, 220 nets used for 14-20 months from 11 sites, and 200 nets used for 26-32 months from ten sites in Ethiopia. A random sample of 16.5-20% of nets from each time period (total 112 of 609 nets) were tested by bioassay with susceptible mosquitoes, and nets used for 14-20 months and 26-32 months were also tested with wild caught mosquitoes. RESULTS: Mean insecticide levels estimated by X-ray fluorescence declined by 25.9% from baseline of 66.2 (SD 14.6) mg/m2 at three to six months to 44.1 (SD 21.2) mg/m2 at 14-20 months and by 30.8% to 41.1 (SD 18.9) mg/m2 at 26-32 months. More than 95% of nets retained greater than 10 mg/m2 of deltamethrin and over 79% had at least 25 mg/m2 at all time periods. By bioassay with susceptible Anopheles, mortality averaged 89.0% on 28 nets tested at three to six months, 93.3% on 44 nets at 14-20 months and 94.1% on 40 nets at 26-32 months. With wild caught mosquitoes, mortality averaged 85.4% (range 79.1 to 91.7%) at 14-20 months but had dropped significantly to 47.2% (39.8 to 54.7%) at 26-32 months. CONCLUSIONS: Insecticide residue level, as estimated by X-ray fluorescence, declined by about one third between three and six months and 14-20 months, but remained relatively stable and above minimum requirements thereafter up to 26-32 months. The insecticidal activity of PermaNet® 2.0 long-lasting insecticidal nets in the specified study area may be considered effective to susceptible mosquitoes at least for the duration indicated in this study (32 months). However, results indicated that resistance in the wild population is already rendering nets with optimum insecticide concentrations less effective in practice.

Setting research priorities for global pandemic preparedness: An international consensus and comparison with ChatGPT's output.

Background: In this priority-setting exercise, we sought to identify leading research priorities needed for strengthening future pandemic preparedness and response across countries. Methods: The International Society of Global Health (ISoGH) used the Child Health and Nutrition Research Initiative (CHNRI) method to identify research priorities for future pandemic preparedness. Eighty experts in global health, translational and clinical research identified 163 research ideas, of which 42 experts then scored based on five pre-defined criteria. We calculated intermediate criterion-specific scores and overall research priority scores from the mean of individual scores for each research idea. We used a bootstrap (n = 1000) to compute the 95% confidence intervals. Results: Key priorities included strengthening health systems, rapid vaccine and treatment production, improving international cooperation, and enhancing surveillance efficiency. Other priorities included learning from the coronavirus disease 2019 (COVID-19) pandemic, managing supply chains, identifying planning gaps, and promoting equitable interventions. We compared this CHNRI-based outcome with the 14 research priorities generated and ranked by ChatGPT, encountering both striking similarities and clear differences. Conclusions: Priority setting processes based on human crowdsourcing - such as the CHNRI method - and the output provided by ChatGPT are both valuable, as they complement and strengthen each other. The priorities identified by ChatGPT were more grounded in theory, while those identified by CHNRI were guided by recent practical experiences. Addressing these priorities, along with improvements in health planning, equitable community-based interventions, and the capacity of primary health care, is vital for better pandemic preparedness and response in many settings.

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).

Physical durability of PermaNet 2.0 long-lasting insecticidal nets over three to 32 months of use in Ethiopia.

BACKGROUND: Ethiopia scaled up net distribution markedly starting in 2006. Information on expected net life under field conditions (physical durability and persistence of insecticidal activity) is needed to improve planning for net replacement. Standardization of physical durability assessment methods is lacking. METHODS: Permanet®2.0 long-lasting insecticidal bed nets (LLINs), available for distribution in early 2007, were collected from households at three time intervals. The number, size and location of holes were recorded for 189 nets used for three to six months from nine sites (2007) and 220 nets used for 14 to 20 months from 11 sites (2008). In 2009, a "finger/fist" sizing method classified holes in 200 nets used for 26 to 32 months from ten sites into small (<2 cm), medium (> = 2 to < =10 cm) and large (>10 cm) sizes. A proportionate hole index based on both hole number and area was derived from these size classifications. RESULTS: After three to six months, 54.5% (95% CI 47.1-61.7%) of 189 LLINs had at least one hole 0.5 cm (in the longest axis) or larger; mean holes per net was 4.4 (SD 8.4), median was 1.0 (Inter Quartile Range [IQR] 0-5) and median size was 1 cm (IQR 1-2). At 14 to 20 months, 85.5% (95% CI 80.1-89.8%) of 220 nets had at least one hole with mean 29.1 (SD 50.1) and median 12 (IQR 3-36.5) holes per net, and median size of 1 cm (IQR 1-2). At 26 to 32 months, 92.5% of 200 nets had at least one hole with a mean of 62.2 (SD 205.4) and median of 23 (IQR 6-55.5) holes per net. The mean hole index was 24.3, 169.1 and 352.8 at the three time periods respectively. Repairs were rarely observed. The majority of holes were in the lower half of the net walls. The proportion of nets in 'poor' condition (hole index >300) increased from 0% at three to six months to 30% at 26 to 32 months. CONCLUSIONS: Net damage began quickly: more than half the nets had holes by three to six months of use, with 40% of holes being larger than 2 cm. Holes continued to accumulate until 92.5% of nets had holes by 26 to 32 months of use. An almost complete lack of repairs shows the need for promoting proper use of nets and repairs, to increase LLIN longevity. Using the hole index, almost one third of the nets were classed as unusable and ineffective after two and a half years of potential use.

Pharmacokinetics, feasibility and safety of co-administering azithromycin, albendazole, and ivermectin during mass drug administration: A review.

INTRODUCTION: Traditionally, health ministries implement mass drug administration programmes for each neglected tropical disease (NTD) as separate and distinct campaigns. Many NTDs have overlapping endemicity suggesting co-administration might improve programme reach and efficiency, helping accelerate progress towards 2030 targets. Safety data are required to support a recommendation to undertake co-administration. METHODOLOGY: We aimed to compile and summarize existing data on co-administration of ivermectin, albendazole and azithromycin, including both data on pharmacokinetic interactions and data from previous experimental and observational studies conducted in NTD-endemic populations. We searched PubMed, Google Scholar, research and conference abstracts, gray literature, and national policy documents. We limited the publication language to English and used a search period from January 1st, 1995 through October 1st, 2022. Search terms were: azithromycin and ivermectin and albendazole, mass drug administration co-administration trials, integrated mass drug administration, mass drug administration safety, pharmacokinetic dynamics, and azithromycin and ivermectin and albendazole. We excluded papers if they did not include data on co-administration of azithromycin and both albendazole and ivermectin, or azithromycin with either albendazole or ivermectin alone. RESULTS: We identified a total of 58 potentially relevant studies. Of these we identified 7 studies relevant to the research question and which met our inclusion criteria. Three papers analyzed pharmacokinetic and pharmacodynamic interactions. No study found evidence of clinically significant drug-drug interactions likely to impact safety or efficacy. Two papers and a conference presentation reported data on the safety of combinations of at least two of the drugs. A field study in Mali suggested the rates of adverse events were similar with combined or separate administration, but was underpowered. A further field study in Papua New Guinea used all three drugs as part of a four-drug regimen also including diethylcarbamazine; in this setting, co-administration appeared safe but there were issues with the consistency in how adverse events were recorded. CONCLUSION: There are relatively limited data on the safety profile of co-administering ivermectin, albendazole and azithromycin as an integrated regimen for NTDs. Despite the limited amount of data, available evidence suggests that such a strategy is safe with an absence of clinically important drug-drug interactions, no serious adverse events reported and little evidence for an increase in mild adverse events. Integrated MDA may be a viable strategy for national NTD programmes.

Safety of integrated mass drug administration of azithromycin, albendazole and ivermectin versus standard treatment regimens: a cluster-randomised trial in Ethiopia.

Background: Neglected Tropical Disease (NTD) programs require separate and distinct drug regimens for treatment. This has required countries to undertake multiple independent mass drug administration (MDA) programmes, each targeting one or more diseases. The possibility of safely combining different drug regimens together in one MDA may offer several advantages to national programs. We conducted a study to assess the safety of combining ivermectin, albendazole and azithromycin in one integrated MDA. Methods: We conducted an open-label, non-inferiority cluster-randomised trial comparing the frequency of adverse events in communities receiving co-administered ivermectin, albendazole and azithromycin to that in communities given albendazole and ivermectin MDA followed by azithromycin MDA after a two-week interval. The study took place in 58 gares (small administrative units) across two kebeles (sub-districts) in Kofele woreda (district) in the Oromia region of Ethiopia. We randomly assigned 29 gares to the combined treatment arm and 29 gares to the control arm. The study team revisited all individuals within 48 h and actively collected data on the occurrence of adverse events using a dedicated questionnaire and a pre-specified list of adverse events. The study team followed the same process in the control arm for the azithromycin distribution and again after the ivermectin plus albendazole distribution. Following this initial active surveillance, passive surveillance was undertaken for one week after the first visit. The primary outcome was the frequency of adverse events occurring following MDA. The study team determined that the safety of the combined MDA would be non-inferior to that of separate MDAs if the upper limit of the two-sided CI for the difference in rates was equal to or lower than 5%. The trial was registered with ClinicalTrials.gov, NCT03570814. Findings: The study took place from December 2021 to January 2022. The combined MDA arm consisted of 7292 individuals who were eligible to participate, of whom 7068 received all three medications. The separate MDA arm consisted of 6219 eligible individuals of whom 6211 received ivermectin and albendazole and 4611 received azithromycin two weeks later. Overall, adverse events were reported by 197 (1.2%) of individuals. The most commonly reported adverse events included headache, gastrointestinal disturbance and dizziness. There were no serious adverse events in either arm. The cluster-level mean frequency of reported adverse events varied markedly between clusters, ranging from 0.1 to 10.4%. The cluster-level mean frequency of adverse events was 1.4% in the combined MDA arm and 1.2% following ivermectin and albendazole MDA (absolute difference 0.2%, 95% confidence interval [CI] -0.6% to +1.1%). This met the pre-defined 1.5% non-inferiority margin. For the combined MDA comparison to the stand-alone azithromycin MDA the absolute difference was -0.4% (1.4 versus 1.8%, 95% CI -0.8 to +1.5) which also met the pre-specified non-inferiority margin. Interpretation: This study is the largest of its kind to date and demonstrates that the safety of combined MDA of azithromycin, ivermectin and albendazole is non-inferior to the safety of ivermectin-plus-albendazole MDA then azithromycin MDA conducted separately although we may not have been powered to detect very small differences between arms. Co-administration of these three medicines is safe and feasible in this setting and allows national programs to develop new strategies for integrated MDA programs. Funding: Ivermectin (Mectizan) was donated by the Mectizan Donation Program, albendazole was donated by GlaxoSmithKline, and azithromycin (Zithromax®) was donated by Pfizer via the International Trachoma Initiative (ITI). The trial was funded by ITI using operational research funds from the Bill and Melinda Gates Foundation.

Perceptions and acceptability of co-administered albendazole, ivermectin and azithromycin mass drug administration, among the health workforce and recipient communities in Ethiopia.

Several neglected tropical diseases (NTDs) employ mass drug administration (MDA) as part of their control or elimination strategies. This has historically required multiple distinct campaigns, each targeting one or more NTDs, representing a strain on both the recipient communities and the local health workforce implementing the distribution. We explored perceptions and attitudes surrounding combined MDA among these two groups of stakeholders. Our qualitative study was nested within a cluster randomized non-inferiority safety trial of combined ivermectin, albendazole and azithromycin MDA. Using semi-structured question guides, we conducted 16 key informant interviews with selected individuals involved in implementing MDA within the participating district. To better understand the perceptions of recipient communities, we also conducted four focus group discussions with key community groups. Individuals were selected from both the trial arm (integrated MDA) and the control arm (standard MDA) to provide a means of comparison and discussion. All interviews and focus group discussions were led by fluent Afaan oromo speakers. Interviewers transcribed and later translated all discussions into English. The study team synthesized and analyzed the results via a coding framework and software. Most respondents appreciated the time and effort saved via the co-administered MDA strategy but there were some misgivings amongst community beneficiaries surrounding pill burden. Both the implementing health work force members and beneficiaries reported refusals stemming from lack of understanding around the need for the new drug regimen as well as some mistrust of government officials among the youth. The house-to-house distribution method, adopted as a COVID-19 prevention strategy, was by far preferred by all beneficiaries over central-point MDA, and may have led to greater acceptability of co-administration. Our data demonstrate that a co-administration strategy for NTDs is acceptable to both communities and health staff.

Corrigendum to "Safety of integrated mass drug administration of azithromycin, albendazole and ivermectin versus standard treatment regimens: a cluster-randomised trial in Ethiopia".

[This corrects the article DOI: 10.1016/j.eclinm.2023.101984.].

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).

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.

Analysis of malaria surveillance data in Ethiopia: what can be learned from the Integrated Disease Surveillance and Response System?

BACKGROUND: Routine malaria surveillance data is useful for assessing incidence and trends over time, and in stratification for targeting of malaria control. The reporting completeness and potential bias of such data needs assessment. METHODS: Data on 17 malaria indicators were extracted from the Integrated Disease Surveillance and Response System database for July 2004 to June 2009 (Ethiopian calendar reporting years 1997 to 2001). Reporting units were standardized over time with 2007 census populations. The data were analysed to show reporting completeness, variation in risk by reporting unit, and incidence trends for malaria indicators. RESULTS: Reporting completeness, estimated as product of unit-month and health facility reporting, was over 80% until 2009, when it fell to 56% during a period of reorganization in the Ministry of Health. Nationally the average estimated annual incidence of reported total malaria for the calendar years 2005 to 2008 was 23.4 per 1000 persons, and of confirmed malaria was 7.6 per 1,000, with no clear decline in out-patient cases over the time period. Reported malaria in-patient admissions and deaths (averaging 6.4 per 10,000 and 2.3 per 100,000 per year respectively) declined threefold between 2005 and 2009, as did admissions and deaths reported as malaria with severe anaemia. Only 8 of 86 reporting units had average annual estimated incidence of confirmed malaria above 20 per 1,000 persons, while 26 units were consistently below five reported cases per 1,000 persons per year. CONCLUSION: The Integrated Disease Surveillance and Response System functioned well over the time period mid 2004 to the end of 2008. The data suggest that the scale up of interventions has had considerable impact on malaria in-patient cases and mortality, as reported from health centres and hospitals. These trends must be regarded as relative (over space and time) rather than absolute. The data can be used to stratify areas for improved targeting of control efforts to steadily reduce incidence. They also provide a baseline of incidence estimates against which to gauge future progress towards elimination. Inclusion of climate information over this time period and extension of the dataset to more years is needed to clarify the impact of control measures compared to natural cycles on malaria.

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.

An observational assessment of the safety of mass drug administration for trachoma in Ethiopian children.

BACKGROUND: The International Trachoma Initiative (ITI) provides azithromycin for mass drug administration (MDA) to eliminate trachoma as a public health problem. Azithromycin is given as tablets for adults and powder for oral suspension (POS) is recommended for children aged <7 y, children <120 cm in height (regardless of age) or anyone who reports difficulty in swallowing tablets. An observational assessment of MDA for trachoma was conducted to determine the frequency with which children aged 6 mo through 14 y received the recommended dose and form of azithromycin according to current dosing guidelines and to assess risk factors for choking and adverse swallowing events (ASEs). METHODS: MDA was observed in three regions of Ethiopia and data were collected on azithromycin administration and ASEs. RESULTS: A total of 6477 azithromycin administrations were observed; 97.9% of children received the exact recommended dose. Of children aged 6 mo to <7 y or <120 cm in height, 99.6% received POS. One child experienced choking and 132 (2%) experienced ≥1 ASEs. Factors significantly associated with ASEs included age 6-11 mo or 1-6 y, non-calm demeanor and requiring coaxing prior to drug administration. CONCLUSIONS: There is a high level of adherence to the revised azithromycin dosing guidelines and low incidence of choking and ASEs.

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.

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 (