Linear growth in preschool children treated with mass azithromycin distributions for trachoma: A cluster-randomized trial.

BackgroundMass azithromycin distributions have been shown to reduce mortality among pre-school children in sub-Saharan Africa. It is unclear what mediates this mortality reduction, but one possibility is that antibiotics function as growth promoters for young children.Methods and findings24 rural Ethiopian communities that had received biannual mass azithromycin distributions over the previous four years were enrolled in a parallel-group, cluster-randomized trial. Communities were randomized in a 1:1 ratio to either continuation of biannual oral azithromycin (20mg/kg for children, 1 g for adults) or to no programmatic antibiotics over the 36 months of the study period. All community members 6 months and older were eligible for the intervention. The primary outcome was ocular chlamydia; height and weight were measured as secondary outcomes on children less than 60 months of age at months 12 and 36. Study participants were not masked; anthropometrists were not informed of the treatment allocation. Anthropometric measurements were collected for 282 children aged 0-36 months at the month 12 assessment and 455 children aged 0-59 months at the month 36 assessment, including 207 children who had measurements at both time points. After adjusting for age and sex, children were slightly but not significantly taller in the biannually treated communities (84.0 cm, 95%CI 83.2-84.8, in the azithromycin-treated communities vs. 83.7 cm, 95%CI 82.9-84.5, in the untreated communities; mean difference 0.31 cm, 95%CI -0.85 to 1.47, P = 0.60). No adverse events were reported.ConclusionsPeriodic mass azithromycin distributions for trachoma did not demonstrate a strong impact on childhood growth.Trial registrationThe TANA II trial was registered on clinicaltrials.gov #NCT01202331

Physical activity and osteoarthritis:A consensus study to harmonise self-reporting methods of physical activity across international cohorts

Physical activity (PA) is increasingly recognised as an important factor within studies of osteoarthritis (OA). However, subjective methods used to assess PA are highly variable and have not been developed for use within studies of OA, which creates difficulties when comparing and interpreting PA data in OA research. The aim of this study was, therefore, to gain expert agreement on the appropriate methods to harmonise PA data among existing population cohorts to enable the investigation of the association of PA and OA. The definition of PA in an OA context and methods of harmonization were established via an international expert consensus meeting and modified Delphi exercise using a geographically diverse committee selected on the basis of individual expertise in physical activity, exercise medicine, and OA. Agreement was met for all aims of study: (1) The use of Metabolic Equivalent of Task (MET) minutes per week (MET-min/week) as a method for harmonising PA variables among cohorts; (2) The determination of methods for treating missing components of MET-min/week calculation; a value will be produced from comparable activities within a representative cohort; (3) Exclusion of the domain of occupation from total MET-min/week; (4) The need for a specific measure of joint loading of an activity in addition to intensity and time, in studies of diseases, such as OA. This study has developed a systematic method to classify and harmonise PA in existing OA cohorts. It also provides minimum requirements for future studies intending to include subjective PA measures

Development and Validation of a Smartphone-based Contrast Sensitivity Test.

PURPOSE: Contrast sensitivity (CS) testing is an important measure of visual function reflecting variations in everyday visual experience in different conditions and helps to identify more subtle vision loss. However, it is only infrequently used. To make this more accessible, we have developed and validated a smartphone-based CS test. METHODS: A new tumbling-E smartphone-based CS test was developed, Peek Contrast Sensitivity (PeekCS). This was field tested and refined through several iterations. Reference standard was a tumbling-E Pelli-Robson CS test (PRCS). The validation study was conducted in community clinics in Ethiopia. Test-retest variability was measured for both PRCS and PeekCS. PRCS and PeekCS were then compared. Correlation coefficients and 95% confidence intervals (CIs) were calculated; 95% limits of agreement were calculated and displayed on Bland-Altman plots. RESULTS: PeekCS showed strong repeatability (correlation coefficient: 0.93; 95% CI: 0.91-0.95), which was comparable with PRCS (correlation coefficient: 0.96; 95% CI: 0.95-0.97). The 95% limit of agreement for test-retest variability of PRCS and PeekCS were -0.20 to 0.21 and -0.31 to 0.29, respectively. PRCS and PeekCS were highly correlated: 0.94 (95% CI: 0.93-0.95); 95% limits of agreement -0.27 to 0.29; and mean difference 0.010 (95% CI: -0.001 to 0.022). PeekCS had a faster testing time (44.6 seconds) than PRCS (48.6 seconds): mean difference -3.98 (95% CI: -5.38 to -2.58); P < 0.001. CONCLUSIONS: The smartphone-based PeekCS is a repeatable and rapid test, providing results that are highly comparable with the commonly used PRCS test. TRANSLATIONAL RELEVANCE: PeekCS provides an accessible and easy to perform alternative for CS testing, particularly in the community setting

Genomics of Ocular Chlamydia trachomatis After 5 Years of SAFE Interventions for Trachoma in Amhara, Ethiopia.

BACKGROUND: To eliminate trachoma as a public health problem, the World Health Organization recommends the SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. As part of the SAFE strategy in the Amhara Region, Ethiopia, the Trachoma Control Program distributed >124 million doses of antibiotics between 2007 and 2015. Despite this, trachoma remained hyperendemic in many districts and a considerable level of Chlamydia trachomatis (Ct) infection was evident. METHODS: We utilized residual material from Abbott m2000 Ct diagnostic tests to sequence 99 ocular Ct samples from Amhara and investigated the role of Ct genomic variation in continued transmission of Ct. RESULTS: Sequences were typical of ocular Ct at the whole-genome level and in tissue tropism-associated genes. There was no evidence of macrolide resistance in this population. Polymorphism around the ompA gene was associated with village-level trachomatous inflammation-follicular prevalence. Greater ompA diversity at the district level was associated with increased Ct infection prevalence. CONCLUSIONS: We found no evidence for Ct genomic variation contributing to continued transmission of Ct after treatment, adding to evidence that azithromycin does not drive acquisition of macrolide resistance in Ct. Increased Ct infection in areas with more ompA variants requires longitudinal investigation to understand what impact this may have on treatment success and host immunity

Epilation for minor trachomatous trichiasis: four-year results of a randomised controlled trial.

BACKGROUND: Trachomatous trichiasis (TT) needs to be managed to reduce the risk of vision loss. The long-term impact of epilation (a common traditional practice of repeated plucking of lashes touching the eye) in preventing visual impairment and corneal opacity from TT is unknown. We conducted a randomized controlled trial of epilation versus surgery for the management of minor TT (fewer than six lashes touching the eye) in Ethiopia. Here we report the four-year outcome and the effect on vision and corneal opacity. METHODOLOGY/ PRINCIPAL FINDINGS: 1300 individuals with minor TT were recruited and randomly assigned to quality trichiasis surgery or repeated epilation using high quality epilation forceps by a trained person with good near vision. Participants were examined six-monthly for two-years, and then at four-years after randomisation. At two-years all epilation arm participants were offered free surgery. At four-years 1151 (88.5%) were re-examined: 572 (88%) and 579 (89%) from epilation and surgery arms, respectively. At that time, 21.1% of the surgery arm participants had recurrent TT; 189/572 (33%) of the epilation arm had received surgery, while 383 (67%) declined surgery and had continued epilating ("epilation-only"). Among the epilation-only group, 207 (54.1%) fully controlled their TT, 166 (43.3%) had minor TT and 10 (2.6%) had major TT (&gt;5 lashes). There were no differences between participants in the epilation-only, epilation-to-surgery and surgery arm participants in changes in visual acuity and corneal opacity between baseline and four-years. CONCLUSIONS/ SIGNIFICANCE: Most minor TT participants randomised to the epilation arm continued epilating and controlled their TT. Change in vision and corneal opacity was comparable between surgery and epilation-only participants. This suggests that good quality epilation with regular follow-up is a reasonable second-line alternative to surgery for minor TT for individuals who either decline surgery or do not have immediate access to surgical treatment

Posterior lamellar versus bilamellar tarsal rotation surgery for trachomatous trichiasis: Long-term outcomes from a randomised controlled trial.

BACKGROUND: We re-examined the participants of a clinical trial four years after enrolment to identify which of the two most commonly used eyelid surgery procedures to treat the blinding stage of trachoma (trachomatous trichiasis, TT), the posterior Lamellar Tarsal Rotation (PLTR) and Billamelar Tarsal Rotation (BLTR), gives better results in the long-term. METHODS: A randomised, controlled, single masked clinical trial was done in Ethiopia. At baseline, adults (aged >18 years with upper lid unoperated TT were recruited from a community-based screening. Participants were randomly assigned (1:1), to either BLTR or PLTR surgery, stratified by surgeon. At 4 years an independent assessor masked to allocation examined the trial participants' eyes using the same procedures as for the baseline and earlier follow-ups. The primary outcome was the proportion of individuals who had recurrence (postoperative TT, PTT) at the 4-year examination, or a history of repeat surgery in the 4-year period. The intervention effect was estimated by logistic regression, controlled for surgeon as a fixed effect in the model. The trial is registered with the Pan African Clinical Trials Registry (number PACTR201401000743135). FINDINGS: 1000 participants with TT were enrolled, randomly assigned, and treated (501 in the BLTR group and 499 in the PLTR group) between Feb 13, 2014, and May 31, 2014. At year 4, 943 (94.3%) participants were re-examined (471, PLTR; 472, BLTR) and included in the primary outcome analysis. PTT had developed in 169/943 (17•9%) study eyes, among which 129 (76•3%) had minor trichiasis (≤5 lashes touching the eye). PTT was significantly more frequent at 4-year in the BLTR arm (105/472 [22•2%]) than the PLTR arm (64/471 [13•6%]), adjusted OR 1•82 (95% CI, 1•29-2•56); p = 0•0006, with 8•6% (95%CI 3•8-13•5) risk difference. INTERPRETATION: The PLTR surgical procedure had superior long-term outcomes to the BLTR with significantly lower risk of PTT supporting the current WHO guideline that the PLTR should be the procedure of choice for training new surgeons in the programmatic management of TT

Pre-operative trichiatic eyelash pattern predicts post-operative trachomatous trichiasis

Importance Trichiasis surgery programs globally have faced high rates of poor surgical outcomes. Identifying correctable risk factors for improving long-term outcomes is essential for countries targeting elimination of trachoma as a public health problem. Objective To determine whether the location of trichiatic eyelashes prior to surgery influences development of post-operative trichiasis (PTT) within two years after surgery. Design Secondary data analysis of four randomized clinical trials evaluating methods to improve trichiasis surgery outcomes. These include the Surgery for Trichiasis, Antibiotics for Recurrence (STAR) trial, Partnership for Rapid Elimination of Trachoma (PRET-Surgery), absorbable versus silk sutures trial, and epilation versus surgery for minor trichiasis trial. Setting Primary trials were conducted in rural areas of Ethiopia and Tanzania Interventions or exposures Trichiasis surgery performed with either the bilamellar tarsal rotation procedure or posterior lamellar rotation procedure Main outcomes Prevalence of PTT within two years after surgery, location of trichiatic eyelashes pre-operatively and post-operatively Results 6,747 eyelids that underwent first-time trichiasis surgery were included. PTT rates varied by study, ranging from 10–40%. PTT was less severe (based on number of trichiatic eyelashes) than initial trichiasis for 72% of those developing PTT, and only 2% of eyelids were worse at follow up than pre-operatively. Eyelids with central only-trichiasis pre-operatively had lower rates of PTT than eyelids with peripheral only trichiasis in each of the three trials that included severe TT cases. 10% of eyelids with peripheral trichiasis pre-operatively that develop PTT have central TT post-operatively. Conclusions and relevance Pre-operative central trichiasis is less likely than peripheral trichiasis to be associated with subsequent PTT. Regardless of type of surgery, surgeon skill levels, or pre-operative trichiasis severity, the presence of peripheral trichiasis pre-operatively is associated with higher rates of PTT. Making an incision that extends the length of the eyelid and adequately rotating the nasal and temporal aspects of the eyelid when suturing may help to minimize the chance of developing peripheral PTT