The FLuorometholone as Adjunctive MEdical Therapy for Trachomatous Trichiasis Surgery (FLAME) Trial: Study Design.

Purpose: To report the design of FL uorometholone as A djunctive ME dical Therapy for TT Surgery (FLAME) Trial. Design: Parallel design, double-masked, placebo-controlled clinical trial with 1:1 randomization to fluorometholone 0.1% eyedrops twice daily or placebo twice daily for four weeks in eyes undergoing trachomatous trichiasis (TT) surgery; assessing the efficacy, safety, and cost-effectiveness of fluorometholone 0.1% in preventing recurrent postoperative trichiasis. Methods: Up to 2500 eligible persons with trachomatous trichiasis (TT) undergoing lid rotation surgery will be enrolled in Jimma zone, Ethiopia. Participants, surgeons, study field staff, and study supervisors leading operational aspects of the trial are masked to treatment assignment. Randomization is stratified by surgeon, which simultaneously stratifies by the district. The study visits are at baseline/enrollment, at four-week post-enrollment, six months, and one year (study exit). The primary outcome is cumulative one-year postoperative TT (PTT) incidence, defined as: ≥1 lashes touching the globe, evidence of epilation, and/or repeat TT surgery. Secondary postoperative outcomes include number of trichiatic lashes, location thereof (touching the cornea or not), evidence of post-operative epilation, entropion, changes in corneal opacity, IOP elevation, need for cataract surgery, visual acuity change from baseline, eyelid contour abnormality, granuloma, eyelid closure defect, and occurrence of adverse events. Health economic analyses center on calculating the incremental cost per case of PTT avoided by fluorometholone treatment. Conclusion: The FLAME Trial is designed to provide evidence of the efficacy, safety, and cost-effectiveness of adjunctive topical peri-/postoperative fluorometholone 0.1% therapy with trichiasis surgery, which is hypothesized to reduce the risk of recurrent trichiasis while being acceptably safe. Trial Registration: ClinicalTrials.gov # NCT04149210.

SARS-CoV-2 Serosurvey in Addis Ababa, Ethiopia.

In a serosurvey of asymptomatic people from the general population recruited from a clinical laboratory in May 2020 in Addis Ababa, Ethiopia, three of 99 persons tested positive for SARS-CoV-2 IgG (3.0%, 95% binomial exact confidence interval: 0.6-8.6%). Taking into account pretest probability and the sampling scheme, the range of plausible population prevalence values was approximately 1.0-8.4%. These results suggest that a larger number of people have been infected than the counts detected by surveillance to date; nevertheless, the results suggest the large majority of the general population in Addis Ababa currently is susceptible to COVID-19.

Fluorometholone 0.1% as Ancillary Therapy for Trachomatous Trichiasis Surgery: Randomized Clinical Trial.

PURPOSE: To assess the hypothesis that fluorometholone 0.1% eye drops are safe and effective as adjunctive therapy for trachomatous trichiasis (TT) surgery; determining the most promising dose. DESIGN: Randomized, placebo-controlled, double-masked parallel dose-ranging clinical trial. METHODS: Patients undergoing upper lid TT surgery at a rural Ethiopian hospital were randomized to fluorometholone 0.1% twice daily for 4 weeks, 4 times daily for 4 weeks, 4 times daily for 8 weeks, or matching frequency placebo in a 3:1:3:1:3:1 ratio for 1 eye. Randomization was stratified by TT severity (1-4 vs ≥5 lashes touching the globe). Safety outcomes (intraocular pressure [IOP] elevation, cataract, and other dose-limiting toxicities) and postoperative TT incidence were assessed over 1 year. RESULTS: Subjects randomized were 39:13:39:13:38:13 in the respective groups, and 1 subject in the 8-weeks fluorometholone group was withdrawn. Of 154 subjects, 148 (96.1%) completed 1 year's follow-up. Among 76 eyes receiving fluorometholone 4 times daily, 1 developed IOP elevation ≥ 30 mm Hg (to 37 mm Hg) and 1 had an allergic reaction attributed to the study drug; each resolved upon drug cessation without sequelae. No cataract or other dose-limiting toxicity events occurred. Postoperative TT within 1 year occurred in 29.3% of placebo eyes vs 17.7%, 19.6%, and 23.2% among the respective fluorometholone groups (P = .29 comparing placebo vs all active treatments combined). CONCLUSIONS: The results suggest fluorometholone 0.1% is likely to be safe and efficacious to reduce postoperative TT following TT surgery, and 1 drop twice daily for 4 weeks is the most promising dose. Confirmation in a full-scale clinical trial is needed before programmatic implementation.

Prevalence of Trachoma in Gambella Region, Ethiopia: Results of Three Population-Based Prevalence Surveys Conducted with the Global Trachoma Mapping Project.

PURPOSE: In Ethiopia, trachoma is a major public health problem, accounting for 11.5% of all cases of blindness. In Gambella, one of the country's most remote regions, the 2005-2006 National Survey of Blindness, Low Vision and Trachoma estimated a region-level prevalence of active trachoma of 19.1% in those aged 1-9 years. Detailed district or sub-regional level estimates are required to implement interventions. METHODS: Population-based prevalence surveys were carried out following a 2-stage cluster random sampling methodology and Global Trachoma Mapping Project protocols. As the 13 districts (woredas) in Gambella had relatively small populations, they were grouped together to form three evaluation units (EUs) of about 100,000 persons each, and all subsequent survey planning and sampling was carried out at EU-level. RESULTS: Altogether, 558 cases of TF (17.2%) were identified in 3238 children aged 1-9 years across the three EUs. The adjusted TF prevalences in 1-9-year-olds for the three EUs were 11.5%, 12.5% and 19.3%; 14.4% for Gambella overall. A total of 142 cases of trichiasis (3.8%) were identified among 3781 adults aged 15 years or older, with age- and sex-adjusted EU-level trichiasis prevalences in adults being 0.8%, 1.3% and 2.4%; 1.5% overall. CONCLUSION: The high prevalences of TF and trichiasis throughout Gambella indicate a need for rapid scaling up of the World Health Organization SAFE strategy (surgery, antibiotics, facial cleanliness, and environmental improvement) to help meet the 2020 target of global elimination of trachoma as a public health problem.

Prevalence of Trachoma in Benishangul Gumuz Region, Ethiopia: Results of Seven Population-Based Surveys from the Global Trachoma Mapping Project.

PURPOSE: Trachoma is a major cause of blindness in Ethiopia, and targeted for elimination as a public health problem by the year 2020. Prevalence data are needed to plan interventions. We set out to estimate the prevalence of trachoma in each evaluation unit of grouped districts ("woredas") in Benishangul Gumuz region, Ethiopia. METHODS: We conducted seven cross-sectional community-based surveys, covering 20 woredas, between December 2013 and January 2014, as part of the Global Trachoma Mapping Project (GTMP). The standardized GTMP training package and methodologies were used. RESULTS: A total of 5828 households and 21,919 individuals were enumerated in the surveys. 19,583 people (89.3%) were present when survey teams visited. A total of 19,530 (99.7%) consented to examination, 11,063 (56.6%) of whom were female. The region-wide age- and sex-adjusted trichiasis prevalence in adults aged ≥15 years was 1.3%. Two evaluation units covering four woredas (Pawe, Mandura, Bulen and Dibate) with a combined rural population of 166,959 require implementation of the A, F and E components of the SAFE strategy (surgery, antibiotics, facial cleanliness and environmental improvement) for at least three years before re-survey, and intervention planning should begin for these woredas as soon as possible. CONCLUSION: Both active trachoma and trichiasis are public health problems in Benishangul Gumuz, which needs implementation of the full SAFE strategy.

Slower clearance of nevirapine resistant virus in infants failing extended nevirapine prophylaxis for prevention of mother-to-child HIV transmission.

Nevirapine resistance mutations arise commonly following single or extended-dose nevirapine (ED-NVP) prophylaxis to prevent mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV), but decay within 6-12 months of single-dose exposure. Use of ED-NVP prophylaxis in infants is expected to rise, but data on decay of nevirapine resistance mutations in infants in whom ED-NVP failed remain limited. We assessed, in Ethiopian infants participating in the Six-Week Extended Nevirapine (SWEN) Trial, the prevalence and persistence of nevirapine resistance mutations at 6 and 12 months following single-dose or up to 6 weeks of ED-NVP, and correlated their presence with the timing of infection and the type of resistance mutations. Standard population genotyping followed by high-throughput cloning were done on dried blood spot samples collected during the trial. More infants who received ED-NVP had nevirapine resistance detected by standard population genotyping (high frequencies) at age 6 months compared with those who received single-dose nevirapine (SD-NVP) (58% of 24 vs. 26% of 19, respectively; p = 0.06). Moreover, 56% of ED-NVP-exposed infants with nevirapine resistance at age 6 months still had nevirapine resistance mutations present at high frequencies at age 1 year. Infants infected before 6 weeks of age who received either SD- or ED-NVP were more likely to have Y181C or K103N; these mutations were also more likely to persist at high frequencies through 1 year of age. HIV-infected infants in whom ED-NVP prophylaxis fails are likely to experience delayed clearance of nevirapine-resistant virus in the first year of life, which in turn places them at risk for early selection of multidrug-resistant HIV after initial therapy with nonnucleoside reverse transcriptase inhibitor-based regimens.

Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials.

BACKGROUND: UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding. METHODS: HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938. FINDINGS: 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54). INTERPRETATION: Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint-risk of HIV transmission at 6 months-suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high. FUNDING: US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center.