An Ensemble Framework for Projecting the Impact of Lymphatic Filariasis Interventions Across Sub-Saharan Africa at a Fine Spatial Scale.

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2030. Although mass treatments have led to huge reductions in LF prevalence, some countries or regions may find it difficult to achieve elimination by 2030 owing to various factors, including local differences in transmission. Subnational projections of intervention impact are a useful tool in understanding these dynamics, but correctly characterizing their uncertainty is challenging. METHODS: We developed a computationally feasible framework for providing subnational projections for LF across 44 sub-Saharan African countries using ensemble models, guided by historical control data, to allow assessment of the role of subnational heterogeneities in global goal achievement. Projected scenarios include ongoing annual treatment from 2018 to 2030, enhanced coverage, and biannual treatment. RESULTS: Our projections suggest that progress is likely to continue well. However, highly endemic locations currently deploying strategies with the lower World Health Organization recommended coverage (65%) and frequency (annual) are expected to have slow decreases in prevalence. Increasing intervention frequency or coverage can accelerate progress by up to 5 or 6 years, respectively. CONCLUSIONS: While projections based on baseline data have limitations, our methodological advancements provide assessments of potential bottlenecks for the global goals for LF arising from subnational heterogeneities. In particular, areas with high baseline prevalence may face challenges in achieving the 2030 goals, extending the "tail" of interventions. Enhancing intervention frequency and/or coverage will accelerate progress. Our approach facilitates preimplementation assessments of the impact of local interventions and is applicable to other regions and neglected tropical diseases.

Subnational Projections of Lymphatic Filariasis Elimination Targets in Ethiopia to Support National Level Policy.

BACKGROUND: Lymphatic filariasis (LF) is a debilitating, poverty-promoting, neglected tropical disease (NTD) targeted for worldwide elimination as a public health problem (EPHP) by 2030. Evaluating progress towards this target for national programmes is challenging, due to differences in disease transmission and interventions at the subnational level. Mathematical models can help address these challenges by capturing spatial heterogeneities and evaluating progress towards LF elimination and how different interventions could be leveraged to achieve elimination by 2030. METHODS: Here we used a novel approach to combine historical geo-spatial disease prevalence maps of LF in Ethiopia with 3 contemporary disease transmission models to project trends in infection under different intervention scenarios at subnational level. RESULTS: Our findings show that local context, particularly the coverage of interventions, is an important determinant for the success of control and elimination programmes. Furthermore, although current strategies seem sufficient to achieve LF elimination by 2030, some areas may benefit from the implementation of alternative strategies, such as using enhanced coverage or increased frequency, to accelerate progress towards the 2030 targets. CONCLUSIONS: The combination of geospatial disease prevalence maps of LF with transmission models and intervention histories enables the projection of trends in infection at the subnational level under different control scenarios in Ethiopia. This approach, which adapts transmission models to local settings, may be useful to inform the design of optimal interventions at the subnational level in other LF endemic regions.

District-Level Forecast of Achieving Trachoma Elimination as a Public Health Problem By 2030: An Ensemble Modelling Approach.

Assessing the feasibility of 2030 as a target date for global elimination of trachoma, and identification of districts that may require enhanced treatment to meet World Health Organization (WHO) elimination criteria by this date are key challenges in operational planning for trachoma programmes. Here we address these challenges by prospectively evaluating forecasting models of trachomatous inflammation-follicular (TF) prevalence, leveraging ensemble-based approaches. Seven candidate probabilistic models were developed to forecast district-wise TF prevalence in 11 760 districts, trained using district-level data on the population prevalence of TF in children aged 1-9 years from 2004 to 2022. Geographical location, history of mass drug administration treatment, and previously measured prevalence data were included in these models as key predictors. The best-performing models were included in an ensemble, using weights derived from their relative likelihood scores. To incorporate the inherent stochasticity of disease transmission and challenges of population-level surveillance, we forecasted probability distributions for the TF prevalence in each geographic district, rather than predicting a single value. Based on our probabilistic forecasts, 1.46% (95% confidence interval [CI]: 1.43-1.48%) of all districts in trachoma-endemic countries, equivalent to 172 districts, will exceed the 5% TF control threshold in 2030 with the current interventions. Global elimination of trachoma as a public health problem by 2030 may require enhanced intervention and/or surveillance of high-risk districts.

Reemergence of Human African Trypanosomiasis Caused by Trypanosoma brucei rhodesiense, Ethiopia.

We report 4 cases of human African trypanosomiasis that occurred in Ethiopia in 2022, thirty years after the last previously reported case in the country. Two of 4 patients died before medicine became available. We identified the infecting parasite as Trypanosoma brucei rhodesiense. Those cases imply human African trypanosomiasis has reemerged.

The Epidemiology of Ocular Chlamydia trachomatis Infection within Districts Persistently Endemic for Trachoma in Amhara, Ethiopia.

Persistent trachoma is a growing concern to trachoma control programs globally and programs serving Ethiopia specifically. Persistent trachoma is defined as a district with two or more trachoma impact surveys (TISs) at which the prevalence of trachomatous inflammation-follicular (TF) among children ages 1-9 years is ≥5%, the elimination threshold. Because the global target for trachoma elimination as a public health problem is 2030, research is needed to better characterize persistent trachoma. This study described the epidemiology of ocular Chlamydia trachomatis infection, the causative bacteria of trachoma, in seven contiguous districts experiencing persistent trachoma. In 2019, multistage cluster random sampling TISs were conducted in the seven districts after 10 years of interventions. All individuals ages ≥1 year were examined for trachoma clinical signs by certified graders, and conjunctival swabs were collected from children ages 1-5 years to test for C. trachomatis infection. The district TF prevalence ranged from 11.8% (95% CI:7.6-16.0%) to 36.1% (95% CI:27.4-44.3%). The range of district-level C. trachomatis infection prevalence was between 2.7% and 34.4%. Statistically significant spatial clustering of high-infection communities was observed in the study districts, and children with infection were more likely than those without to be found in households with clinical signs of trachoma and those without latrines. These seven districts appear to constitute a persistent hotspot in Amhara, where an additional 3-5 years or more of interventions will be required. The global program will need to strengthen and enhance intervention strategies within persistent districts if elimination by 2030 is to be achieved.

Wait and watch: A trachoma surveillance strategy from Amhara region, Ethiopia.

BACKGROUND: Trachoma recrudescence after elimination as a public health problem has been reached is a concern for control programs globally. Programs typically conduct district-level trachoma surveillance surveys (TSS) ≥ 2 years after the elimination threshold is achieved to determine whether the prevalence of trachomatous inflammation-follicular (TF) among children ages 1 to 9 years remains <5%. Many TSS are resulting in a TF prevalence ≥5%. Once a district returns to TF ≥5%, a program typically restarts costly mass drug administration (MDA) campaigns and surveys at least twice, for impact and another TSS. In Amhara, Ethiopia, most TSS which result in a TF ≥5% have a prevalence close to 5%, making it difficult to determine whether the result is due to true recrudescence or to statistical variability. This study's aim was to monitor recrudescence within Amhara by waiting to restart MDA within 2 districts with a TF prevalence ≥5% at TSS, Metema = 5.2% and Woreta Town = 5.1%. The districts were resurveyed 1 year later using traditional and alternative indicators, such as measures of infection and serology, a "wait and watch" approach. METHODS/PRINCIPAL FINDINGS: These post-surveillance surveys, conducted in 2021, were multi-stage cluster surveys whereby certified graders assessed trachoma signs. Children ages 1 to 9 years provided a dried blood spot and children ages 1 to 5 years provided a conjunctival swab. TF prevalence in Metema and Woreta Town were 3.6% (95% Confidence Interval [CI]:1.4-6.4) and 2.5% (95% CI:0.8-4.5) respectively. Infection prevalence was 1.2% in Woreta Town and 0% in Metema. Seroconversion rates to Pgp3 in Metema and Woreta Town were 0.4 (95% CI:0.2-0.7) seroconversions per 100 child-years and 0.9 (95% CI:0.6-1.5) respectively. CONCLUSIONS/SIGNIFICANCE: Both study districts had a TF prevalence <5% with low levels of Chlamydia trachomatis infection and transmission, and thus MDA interventions are no longer warranted. The wait and watch approach represents a surveillance strategy which could lead to fewer MDA campaigns and surveys and thus cost savings with reduced antibiotic usage.

Characterizing trachoma elimination using serology.

Trachoma is targeted for global elimination as a public health problem by 2030. Measurement of IgG antibodies in children is being considered for surveillance and programmatic decision-making. There are currently no guidelines for applications of serology, which represents a generalizable problem in seroepidemiology and disease elimination. We collated Chlamydia trachomatis Pgp3 and CT694 IgG measurements (63,911 children ages 1-9 years) from 48 serosurveys, including surveys across Africa, Latin America, and the Pacific Islands to estimate population-level seroconversion rates (SCR) along a gradient of trachoma endemicity. We propose a novel, generalizable approach to estimate the probability that population C. trachomatis transmission is below levels requiring ongoing programmatic action, or conversely is above levels that indicate ongoing interventions are needed. We provide possible thresholds for SCR at a specified level of certainty and illustrate how the approach could be used to inform trachoma program decision-making using serology.

Subcutaneous mycoses: Endemic but neglected among the Neglected Tropical Diseases in Ethiopia.

BACKGROUND: Subcutaneous (deep) mycoses are a chronic infectious disease of the skin and underlying structures endemic in tropical countries. The disease has serious medical and socioeconomic consequences for patients, communities and health services in endemic areas. The inclusion of mycetoma and other subcutaneous mycoses in the list of Neglected Tropical Diseases by WHO highlights the need to assess the burden of these diseases and establish control programs where necessary. In Ethiopia no strategies can be devised because of a lack of epidemiologic information. To address this evidence gap, we performed a national rapid assessment of the geographic distribution of subcutaneous mycoses. METHODOLOGY: We conducted a rapid retrospective assessment using hospital records to identify all suspected and confirmed cases of subcutaneous mycoses in 13 referral hospitals across the country between 2015 and 2022. In each hospital the logbooks were reviewed for diagnoses of subcutaneous mycosess, as diagnosed per routine practice. Descriptive analysis was done. RESULT: From 13 hospitals we extracted 143 cases of subcutaneous mycoses, registered from July 2018 to September 2022. 118 (82.5%) patients were diagnosed as mycetoma, 21 (14.7%) as chromoblastomycosis and the remaining 4 (2.8%) as sporotrichosis. The mean age of patients was 35.8 years (SD = 14.5). 101 (70.6%) patients were male and 96 (67.1%) patients were farmers. 64 (44.8%) cases were from the Tigray regional state. 56 (65.9%) patients had information on diagnostic microscopic evaluation: for mycetoma histopathologic evaluation and fine needle aspiration cytology had a higher positivity rate while for chromoblastomycosis potassium hydroxide (KOH) staining had a better yield. The main clinical presentations were nodules, sinuses and infiltrative plaques on the skin. Radiologic findings of bone involvement was present in some. CONCLUSIONS: Mycetoma and other subcutaneous mycoses are endemic in Ethiopia, with cases reported from almost all regions with the highest cases numbers reported from the northern part of the country. A routine program and systems should be developed to identify and document the burden of subcutaneous fungal infections in the country. Diagnosis and treatment guidelines should be developed.

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.

Prevalence of Ocular Chlamydia trachomatis Infection in Amhara Region, Ethiopia, after 8 Years of Trachoma Control Interventions.

Although trachoma mass drug administration (MDA) programs target ocular Chlamydia trachomatis, the global trachoma control program does not monitor infection as a measure of impact but instead relies on monitoring clinical indicators. This study aimed to monitor the prevalence of ocular C. trachomatis among a population-based sample of children ages 1-5 years throughout Amhara, Ethiopia, a region that has received approximately 8 years of annual MDA as part of trachoma control. Between 2014 and 2021, trachoma impact surveys and surveillance surveys were conducted in all 156 districts of Amhara using a multistage cluster randomized methodology. Certified graders assessed individuals ages ≥ 1 year for trachomatous inflammation-follicular (TF), and a random subset of children ages 1-5 years also provided a conjunctival swab. Polymerase chain reaction was used to test for C. trachomatis. A total of 28,410 conjunctival swabs were collected from children ages 1-5 years across Amhara. The regional C. trachomatis infection prevalence was 4.7% (95% uncertainty interval: 4.3-5.1%). Infection was detected in all 10 zones of the region and ranged from 0.2% in Awi Zone to 11.9% in Waghemra Zone. Infection was detected in 17 (26%) districts with a TF prevalence < 10% and in 7 (21%) districts with a TF prevalence < 5%. Through programmatic monitoring of C. trachomatis infection, this study demonstrated that considerable infection remained throughout Amhara despite approximately 8 years of trachoma interventions and that enhanced interventions such as more frequent than annual MDA will be needed if elimination thresholds are to be reached.

Integrated Prevalence Assessment of Wuchereria bancrofti and Onchocerca volvulus in Three Co-Endemic Districts of Gambella Region, Ethiopia.

Lymphatic filariasis (LF) and onchocerciasis (OV) are among the neglected tropical diseases (NTD) targeted for elimination in Ethiopia. We used a transmission assessment survey (TAS-1) to evaluate the serological status of OV in three co-endemic districts in Gambella simultaneously. During May and June 2019, blood samples were collected from 6- to 7-year-old children who were randomly selected through standard community-based TAS methodology. Children were tested for both circulating filarial antigen (CFA) for LF via filariasis test strip and for Onchocerca volvulus 16 (Ov16) antibody for OV via laboratory-based ELISA. A total of 3,377 children from 150 villages in the three districts were tested; 1,823 (54.0%) were male. All three districts had CFA results below the critical threshold for stopping LF mass drug administration (MDA). In contrast, 40 children (1.2%) were positive for Ov16 antibody, well above the WHO's OV stop MDA threshold of 0.1%. The integrated assessment indicated two programmatic decisions: stop MDA for LF and continue MDA for OV. Accordingly, albendazole MDA was discontinued in the districts but ivermectin MDA continued. This integrated assessment showed that a random sample for TAS can give important information about OV transmission status in co-endemic areas.

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.].

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.

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.

Monitoring transmission intensity of trachoma with serology.

Trachoma, caused by ocular Chlamydia trachomatis infection, is targeted for global elimination as a public health problem by 2030. To provide evidence for use of antibodies to monitor C. trachomatis transmission, we collated IgG responses to Pgp3 antigen, PCR positivity, and clinical observations from 19,811 children aged 1- 9 years in 14 populations. We demonstrate that age-seroprevalence curves consistently shift along a gradient of transmission intensity: rising steeply in populations with high levels of infection and active trachoma and becoming flat in populations near elimination. Seroprevalence (range: 0-54%) and seroconversion rates (range: 0-15 per 100 person-years) correlate with PCR prevalence (r: 0.87, 95% CI: 0.57, 0.97). A seroprevalence threshold of 13.5% (seroconversion rate 2.75 per 100 person-years) identifies clusters with any PCR-identified infection at high sensitivity (>90%) and moderate specificity (69-75%). Antibody responses in young children provide a robust, generalizable approach to monitor population progress toward and beyond trachoma elimination.

Monitoring transmission intensity of trachoma with serology.

Trachoma, caused by ocular Chlamydia trachomatis infection, is targeted for global elimination as a public health problem by 2030. To provide evidence for use of antibodies to monitor C. trachomatis transmission, we collated IgG responses to Pgp3 antigen, PCR positivity, and clinical observations from 19,811 children aged 1-9 years in 14 populations. We demonstrate that age-seroprevalence curves consistently shift along a gradient of transmission intensity: rising steeply in populations with high levels of infection and active trachoma and becoming flat in populations near elimination. Seroprevalence (range: 0-54%) and seroconversion rates (range: 0-15 per 100 person-years) correlate with PCR prevalence (r: 0.87, 95% CI: 0.57, 0.97). A seroprevalence threshold of 13.5% (seroconversion rate 2.75 per 100 person-years) identifies clusters with any PCR-identified infection at high sensitivity ( >90%) and moderate specificity (69-75%). Antibody responses in young children provide a robust, generalizable approach to monitor population progress toward and beyond trachoma elimination.

Model-based geostatistics enables more precise estimates of neglected tropical-disease prevalence in elimination settings: mapping trachoma prevalence in Ethiopia.

BACKGROUND: As the prevalences of neglected tropical diseases reduce to low levels in some countries, policymakers require precise disease estimates to decide whether the set public health targets have been met. At low prevalence levels, traditional statistical methods produce imprecise estimates. More modern geospatial statistical methods can deliver the required level of precision for accurate decision-making. METHODS: Using spatially referenced data from 3567 cluster locations in Ethiopia in the years 2017, 2018 and 2019, we developed a geostatistical model to estimate the prevalence of trachomatous trichiasis and to calculate the probability that the trachomatous trichiasis component of the elimination of trachoma as a public health problem has already been achieved for each of 482 evaluation units. We also compared the precision of traditional and geostatistical approaches by the ratios of the lengths of their 95% predictive intervals. RESULTS: The elimination threshold of trachomatous trichiasis (prevalence ≤ 0.2% in individuals aged ≥15 years) is met with a probability of 0.9 or more in 8 out of the 482 evaluation units assessed, and with a probability of ≤0.1 in 469 evaluation units. For the remaining five evaluation units, the probability of elimination is between 0.45 and 0.65. Prevalence estimates were, on average, 10 times more precise than estimates obtained using the traditional approach. CONCLUSIONS: By accounting for and exploiting spatial correlation in the prevalence data, we achieved remarkably improved precision of prevalence estimates compared with the traditional approach. The geostatistical approach also delivers predictions for unsampled evaluation units that are geographically close to sampled evaluation units.

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.

Evaluation of the efficacy of insecticide-treated scarves to protect children from the trachoma vector Musca sorbens (Diptera: Muscidae): A phase II randomised controlled trial in Oromia, Ethiopia.

Background: The eye-seeking fly Musca sorbens can act as a vector for ocular Chlamydia trachomatis, causing trachoma, yet there has been very little research on control measures. We investigated whether insect repellent products, specifically insecticide-treated clothing, could provide personal protection to the user from eye-seeking flies. Methods: We first conducted a series of phase I laboratory studies to inform our choice of field intervention. We then conducted a phase II randomised controlled trial testing the efficacy of permethrin-treated scarves (PTS) in reducing fly-face contact in Oromia, Ethiopia. Children aged 4-10 years in full health and with no known adverse reactions to permethrin or other insecticides were allocated to either arm using restricted randomisation. Intervention arm children wore Insect Shield® versatile wraps (as PTS) for 28 days. The primary outcomes, fly-eye, -nose and -mouth contact, were assessed on the first day (0/30/60/180 minutes), on day 7 and on day 28. All participants present per timepoint were included in analyses. This trial was registered with ClinicalTrials.gov (NCT03813069). Findings: Participants were recruited to the field trial between 29/10/2019 and 01/11/2019, 58 were randomised to test or control arm. More fly (-eye, -nose and -mouth) contacts were observed in the PTS arm at baseline. After adjusting for baseline contact rates, across all timepoints there was a 35% decrease in fly-eye contacts in the PTS relative to control arm (rate ratio [RR] 0.65, 95% CI 0.52-0.83). Similar cross-timepoint reductions were seen for fly-nose and fly-mouth contacts (RR 0.69, 95% CI 0.51-0.92 and RR 0.79, 95% CI 0.62-1.01, respectively). All children were included on day 0. Two in the control arm were absent on day 7, one left the study and four were excluded from analysis at day 28. No adverse events occurred in the trial. Interpretation: Musca sorbens flies are sufficiently repelled by PTS to reduce fly-eye contacts for the wearer, thus possibly reducing the risk of trachoma transmission. Permethrin-treated scarves may therefore an alternative to insecticide space spraying for protection from these flies. Funding: Wellcome Trust.