A Virtual Reading Center Model Using Crowdsourcing to Grade Photographs for Trachoma: Validation Study.

BACKGROUND: As trachoma is eliminated, skilled field graders become less adept at correctly identifying active disease (trachomatous inflammation-follicular [TF]). Deciding if trachoma has been eliminated from a district or if treatment strategies need to be continued or reinstated is of critical public health importance. Telemedicine solutions require both connectivity, which can be poor in the resource-limited regions of the world in which trachoma occurs, and accurate grading of the images. OBJECTIVE: Our purpose was to develop and validate a cloud-based "virtual reading center" (VRC) model using crowdsourcing for image interpretation. METHODS: The Amazon Mechanical Turk (AMT) platform was used to recruit lay graders to interpret 2299 gradable images from a prior field trial of a smartphone-based camera system. Each image received 7 grades for US $0.05 per grade in this VRC. The resultant data set was divided into training and test sets to internally validate the VRC. In the training set, crowdsourcing scores were summed, and the optimal raw score cutoff was chosen to optimize kappa agreement and the resulting prevalence of TF. The best method was then applied to the test set, and the sensitivity, specificity, kappa, and TF prevalence were calculated. RESULTS: In this trial, over 16,000 grades were rendered in just over 60 minutes for US $1098 including AMT fees. After choosing an AMT raw score cut point to optimize kappa near the World Health Organization (WHO)-endorsed level of 0.7 (with a simulated 40% prevalence TF), crowdsourcing was 95% sensitive and 87% specific for TF in the training set with a kappa of 0.797. All 196 crowdsourced-positive images received a skilled overread to mimic a tiered reading center and specificity improved to 99%, while sensitivity remained above 78%. Kappa for the entire sample improved from 0.162 to 0.685 with overreads, and the skilled grader burden was reduced by over 80%. This tiered VRC model was then applied to the test set and produced a sensitivity of 99% and a specificity of 76% with a kappa of 0.775 in the entire set. The prevalence estimated by the VRC was 2.70% (95% CI 1.84%-3.80%) compared to the ground truth prevalence of 2.87% (95% CI 1.98%-4.01%). CONCLUSIONS: A VRC model using crowdsourcing as a first pass with skilled grading of positive images was able to identify TF rapidly and accurately in a low prevalence setting. The findings from this study support further validation of a VRC and crowdsourcing for image grading and estimation of trachoma prevalence from field-acquired images, although further prospective field testing is required to determine if diagnostic characteristics are acceptable in real-world surveys with a low prevalence of the disease.

Evaluation of away-from-home excursion patterns after falling among individuals with glaucoma: a longitudinal study.

BACKGROUND: Unintentional falls among older adults are associated with an ensuing decline in physical activity. Our objective is to evaluate the associations between fall status and changes in excursions after a fall. METHODS: Prospective cohort study of older adults with glaucoma or suspected glaucoma who reported falls for 1 year and wore a GPS device for 1-week at the baseline and 1 year later. GPS data were quantified into average: daily excursions, daily time away from home, and time per excursion. Fall status was categorized as fallers, injurious fallers, recurrent fallers, and recurrent injurious fallers. Multivariable negative binomial regression and generalized estimating equations models were employed to evaluate relationship between excursion parameters and fall status. RESULTS: A total of 192 eligible participants were included in the analyses. Approximately half were males (50.5%) with a mean age of 70.1 years and one-fourth were Black (28.1%). There were no significant associations between fall status and end-of-study excursion parameters (p > 0.06 for all), and visual field damage did not modify these relationships (p > 0.07 for all). For instance, patients with multiple falls during a one-year study period did not demonstrate more daily excursions (incident rate ratio [IRR] = 1.16, 95% confidence interval [CI] = 0.85 to 1.57), longer time per excursion (IRR = 0.79, 95% CI =0.59 to 1.06), or more average daily time away (IRR = 1.05, 95% CI = 0.84 to 1.30) conducted at the end-of-the study. Excursion parameters at the final assessment were not significantly different from those at baseline (p > 0.09 for all) and the changes did not vary by fall status (p > 0.23 for all). CONCLUSIONS: Older adults with glaucoma did not modify their travel away from home after experiencing a fall. Additional research is necessary to understand how often maintenance of travel outside the home after a fall reflects proper compensation for greater fall risk or continued activity despite the risk of falling.

Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa.

BACKGROUND: We hypothesized that mass distribution of a broad-spectrum antibiotic agent to preschool children would reduce mortality in areas of sub-Saharan Africa that are currently far from meeting the Sustainable Development Goals of the United Nations. METHODS: In this cluster-randomized trial, we assigned communities in Malawi, Niger, and Tanzania to four twice-yearly mass distributions of either oral azithromycin (approximately 20 mg per kilogram of body weight) or placebo. Children 1 to 59 months of age were identified in twice-yearly censuses and were offered participation in the trial. Vital status was determined at subsequent censuses. The primary outcome was aggregate all-cause mortality; country-specific rates were assessed in prespecified subgroup analyses. RESULTS: A total of 1533 communities underwent randomization, 190,238 children were identified in the census at baseline, and 323,302 person-years were monitored. The mean (±SD) azithromycin and placebo coverage over the four twice-yearly distributions was 90.4±10.4%. The overall annual mortality rate was 14.6 deaths per 1000 person-years in communities that received azithromycin (9.1 in Malawi, 22.5 in Niger, and 5.4 in Tanzania) and 16.5 deaths per 1000 person-years in communities that received placebo (9.6 in Malawi, 27.5 in Niger, and 5.5 in Tanzania). Mortality was 13.5% lower overall (95% confidence interval [CI], 6.7 to 19.8) in communities that received azithromycin than in communities that received placebo (P<0.001); the rate was 5.7% lower in Malawi (95% CI, -9.7 to 18.9), 18.1% lower in Niger (95% CI, 10.0 to 25.5), and 3.4% lower in Tanzania (95% CI, -21.2 to 23.0). Children in the age group of 1 to 5 months had the greatest effect from azithromycin (24.9% lower mortality than that with placebo; 95% CI, 10.6 to 37.0). Serious adverse events occurring within a week after administration of the trial drug or placebo were uncommon, and the rate did not differ significantly between the groups. Evaluation of selection for antibiotic resistance is ongoing. CONCLUSIONS: Among postneonatal, preschool children in sub-Saharan Africa, childhood mortality was lower in communities randomly assigned to mass distribution of azithromycin than in those assigned to placebo, with the largest effect seen in Niger. Any implementation of a policy of mass distribution would need to strongly consider the potential effect of such a strategy on antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation; MORDOR ClinicalTrials.gov number, NCT02047981 .).

Patterns of Daily Physical Activity across the Spectrum of Visual Field Damage in Glaucoma Patients.

PURPOSE: To define and quantify patterns of objectively measured daily physical activity by level of visual field (VF) damage in glaucoma patients including: (1) activity fragmentation, a metric of health and physiologic decline, and (2) diurnal patterns of activity, a measure of rest and activity rhythms. DESIGN: Prospective cohort study. PARTICIPANTS: Older adults diagnosed with glaucoma or suspected glaucoma. METHODS: Degree of VF damage was defined by the average VF sensitivity within the integrated VF (IVF). Each participant wore a hip accelerometer for 1 week to measure daily minute-by-minute activity for 7 consecutive days. Activity fragmentation was calculated as the reciprocal of the average activity bout duration in minutes, with higher fragmentation indicating more transient, rather than sustained, activity. Multivariate linear regression was used to test for cross-sectional associations between VF damage and activity fragmentation. Multivariate linear mixed-effects models were used to assess the associations between VF damage and accumulation of activity across 6 3-hour intervals from 5 am to 11 pm. MAIN OUTCOME MEASURES: Activity fragmentation and amount of activity (steps) over the course of the day. RESULTS: Each 5-dB decrement in IVF sensitivity was associated with 16.3 fewer active minutes/day (P < 0.05) and 2% higher activity fragmentation (P < 0.05), but not with the number of active bouts per day (P = 0.30). In time-of-day analyses, lower IVF sensitivity was associated with fewer steps over the 11 am to 2 pm, 2 pm to 5 pm, and 5 pm to 8 pm periods (106.6, 93.1, and 89.2 fewer steps, respectively; P < 0.05 for all), but not over other periods. The activity midpoint (the time at which half of the daily activity is completed) did not vary across level of VF damage. CONCLUSIONS: At worse levels of VF damage, glaucoma patients demonstrate shorter, more fragmented bouts of physical activity throughout the day and lower activity levels during typical waking hours, reflecting low physiologic functioning. Further work is needed to establish the temporality of this association and whether glaucoma patients with such activity patterns are at a greater risk of adverse health outcomes associated with activity fragmentation.

The Impact of Weather and Seasons on Falls and Physical Activity among Older Adults with Glaucoma: A Longitudinal Prospective Cohort Study.

Understanding periods of the year associated with higher risk for falling and less physical activity may guide fall prevention and activity promotion for older adults. We examined the relationship between weather and seasons on falls and physical activity in a three-year cohort of older adults with glaucoma. Participants recorded falls information via monthly calendars and participated in four one-week accelerometer trials (baseline and per study year). Across 240 participants, there were 406 falls recorded over 7569 person-months, of which 163 were injurious (40%). In separate multivariable regression models incorporating generalized estimating equations, temperature, precipitation, and seasons were not significantly associated with the odds of falling, average daily steps, or average daily active minutes. However, every 10 °C increase in average daily temperature was associated with 24% higher odds of a fall being injurious, as opposed to non-injurious (p = 0.04). The odds of an injurious fall occurring outdoors, as opposed to indoors, were greater with higher average temperatures (OR per 10 °C = 1.46, p = 0.03) and with the summer season (OR = 2.69 vs. winter, p = 0.03). Falls and physical activity should be understood as year-round issues for older adults, although the likelihood of injury and the location of fall-related injuries may change with warmer season and temperatures.

Morbidity in a Longitudinal Cohort of Children Residing in Villages Randomized to Biannual Treatment With Azithromycin Versus Placebo.

BACKGROUND: The mechanisms underlying the finding of reduced child mortality in communities with biannual treatment with azithromycin remain unclear. We determined if there was a difference in morbidity in a cohort of children aged 1-36 months, residing in communities randomized to biannual treatment of preschool-aged children with azithromycin or placebo. METHODS: Thirty villages in Kilosa, Tanzania, were randomly assigned to receive biannual treatment of all children aged 1-59 months with either azithromycin (20/mg/kg single dose) or placebo. Children who were aged 1-36 months and participated in the baseline survey were enrolled in this cohort study and followed prospectively for 2 years. Children were monitored every 6 months for signs and symptoms of diarrheal disease, acute respiratory illness, and anemia. Mixed-effects models that include age, time, treatment arm, and the interaction of treatment arm and time as independent predictors were used to evaluate differences between children by treatment assignment over time. RESULTS: There was no difference in rates of diarrhea, fever, or anemia by treatment arm at baseline and at all phases of follow-up. The decline over time in reported cough was statistically significant in the children residing in the azithromycin communities, but not in the placebo communities. Once adjusting for clustering and age, the difference in decline between the 2 treatment arms was not significant (P = .09). CONCLUSIONS: A beneficial effect of azithromycin treatment on morbidity outcomes was not evident at biannual surveys. CLINICAL TRIALS REGISTRATION: NCT02048007.

Biannual azithromycin distribution and child mortality among malnourished children: A subgroup analysis of the MORDOR cluster-randomized trial in Niger.

BACKGROUND: Biannual azithromycin distribution has been shown to reduce child mortality as well as increase antimicrobial resistance. Targeting distributions to vulnerable subgroups such as malnourished children is one approach to reaching those at the highest risk of mortality while limiting selection for resistance. The objective of this analysis was to assess whether the effect of azithromycin on mortality differs by nutritional status. METHODS AND FINDINGS: A large simple trial randomized communities in Niger to receive biannual distributions of azithromycin or placebo to children 1-59 months old over a 2-year timeframe. In exploratory subgroup analyses, the effect of azithromycin distribution on child mortality was assessed for underweight subgroups using weight-for-age Z-score (WAZ) thresholds of -2 and -3. Modification of the effect of azithromycin on mortality by underweight status was examined on the additive and multiplicative scale. Between December 2014 and August 2017, 27,222 children 1-11 months of age from 593 communities had weight measured at their first study visit. Overall, the average age among included children was 4.7 months (interquartile range [IQR] 3-6), 49.5% were female, 23% had a WAZ < -2, and 10% had a WAZ < -3. This analysis included 523 deaths in communities assigned to azithromycin and 661 deaths in communities assigned to placebo. The mortality rate was lower in communities assigned to azithromycin than placebo overall, with larger reductions among children with lower WAZ: -12.6 deaths per 1,000 person-years (95% CI -18.5 to -6.9, P < 0.001) overall, -17.0 (95% CI -28.0 to -7.0, P = 0.001) among children with WAZ < -2, and -25.6 (95% CI -42.6 to -9.6, P = 0.003) among children with WAZ < -3. No statistically significant evidence of effect modification was demonstrated by WAZ subgroup on either the additive or multiplicative scale (WAZ < -2, additive: 95% CI -6.4 to 16.8, P = 0.34; WAZ < -2, multiplicative: 95% CI 0.8 to 1.4, P = 0.50, WAZ < -3, additive: 95% CI -2.2 to 31.1, P = 0.14; WAZ < -3, multiplicative: 95% CI 0.9 to 1.7, P = 0.26). The estimated number of deaths averted with azithromycin was 388 (95% CI 214 to 574) overall, 116 (95% CI 48 to 192) among children with WAZ < -2, and 76 (95% CI 27 to 127) among children with WAZ < -3. Limitations include the availability of a single weight measurement on only the youngest children and the lack of power to detect small effect sizes with this rare outcome. Despite the trial's large size, formal tests for effect modification did not reach statistical significance at the 95% confidence level. CONCLUSIONS: Although mortality rates were higher in the underweight subgroups, this study was unable to demonstrate that nutritional status modified the effect of biannual azithromycin distribution on mortality. Even if the effect were greater among underweight children, a nontargeted intervention would result in the greatest absolute number of deaths averted. TRIAL REGISTRATION: The MORDOR trial is registered at clinicaltrials.gov NCT02047981.

The simplified trachoma grading system, amended.

A simplified grading system for trachoma was published by the World Health Organization (WHO) in 1987. Intended for use by non-specialist personnel working at community level, the system includes five signs, each of which can be present or absent in any eye: (i) trachomatous trichiasis; (ii) corneal opacity; (iii) trachomatous inflammation-follicular; (iv) trachomatous inflammation-intense; and (v) trachomatous scarring. Though neither perfectly sensitive nor perfectly specific for trachoma, these signs have been essential tools for identifying populations that need interventions to eliminate trachoma as a public health problem. In 2018, at WHO's 4th global scientific meeting on trachoma, the definition of one of the signs, trachomatous trichiasis, was amended to exclude trichiasis that affects only the lower eyelid. This paper presents the amended system, updates its presentation, offers notes on its use and identifies areas of ongoing debate.

En 1987, l'Organisation mondiale de la Santé a publié un système de codage simplifié du trachome. Destiné au personnel non qualifié travaillant au sein des communautés, il comporte cinq signes, chacun pouvant être présent ou absent dans l'un ou l'autre œil: (i) le trichiasis trachomateux; (ii) l'opacité cornéenne; (iii) l'inflammation trachomateuse ­ folliculaire; (iv) l'inflammation trachomateuse ­ intense; et enfin, (v) la cicatrice trachomateuse. Bien qu'ils ne soient ni parfaitement précis, ni totalement spécifiques au trachome, ces signes constituent des outils essentiels pour identifier les populations qui nécessitent une intervention afin d'éliminer le trachome en tant que problème de santé publique. En 2018, lors de la quatrième réunion scientifique mondiale sur le trachome, la définition de l'un des signes, le trichiasis trachomateux, a été modifiée pour exclure du système de codage le trichiasis qui n'affecte que la paupière inférieure. Ce document expose le nouveau système, actualise sa présentation, formule des remarques sur son utilisation et identifie les domaines qui font encore l'objet de débats.

En 1987, la Organización Mundial de la Salud (OMS) publicó un sistema de clasificación simplificado para el tracoma. Este sistema fue diseñado para que lo utilice el personal no especializado que trabaja a nivel comunitario e incluye cinco signos, cada uno de los cuales puede estar presente o ausente en los ojos: i) la triquiasis tracomatosa; ii) la opacidad corneal; iii) la inflamación tracomatosa-folicular; iv) la inflamación tracomatosa-intensa; y v) la cicatrización tracomatosa. Si bien no son perfectamente sensibles ni muy específicos del tracoma, estos signos han sido herramientas esenciales para identificar a las poblaciones que requieren intervenciones para eliminar el tracoma como problema de salud pública. En 2018, se modificó la definición de uno de los signos, la triquiasis tracomatosa, en la 4.ª Reunión Científica Mundial sobre el Tracoma de la OMS, para descartar la triquiasis que solo afecta al párpado inferior. En el presente documento se describe el sistema modificado, se actualiza su presentación, se ofrecen observaciones sobre su aplicación y se identifican los ámbitos de debate en curso.

Comparison of anthropometric indicators to predict mortality in a population-based prospective study of children under 5 years in Niger.

OBJECTIVE: In the present study, we aimed to compare anthropometric indicators as predictors of mortality in a community-based setting. DESIGN: We conducted a population-based longitudinal study nested in a cluster-randomized trial. We assessed weight, height and mid-upper arm circumference (MUAC) on children 12 months after the trial began and used the trial's annual census and monitoring visits to assess mortality over 2 years. SETTING: Niger. PARTICIPANTS: Children aged 6-60 months during the study. RESULTS: Of 1023 children included in the study at baseline, height-for-age Z-score, weight-for-age Z-score, weight-for-height Z-score and MUAC classified 777 (76·0 %), 630 (61·6 %), 131 (12·9 %) and eighty (7·8 %) children as moderately to severely malnourished, respectively. Over the 2-year study period, fifty-eight children (5·7 %) died. MUAC had the greatest AUC (0·68, 95 % CI 0·61, 0·75) and had the strongest association with mortality in this sample (hazard ratio = 2·21, 95 % CI 1·26, 3·89, P = 0·006). CONCLUSIONS: MUAC appears to be a better predictor of mortality than other anthropometric indicators in this community-based, high-malnutrition setting in Niger.

Milestones in the fight to eliminate trachoma.

PURPOSE: Trachoma, a chronic conjunctivitis that can result in vision loss from trichiasis, is targeted for global elimination by 2020. Several milestones in the long process towards elimination are noteworthy for the impact they have had on changing or accelerating progress. The purpose of this review is to describe the milestones and the impact they have had both for trachoma elimination and beyond. FINDINGS: Eight milestones are presented. They are discovery of the causative agent; development of a clinical grading scheme; establishment of the World Health Organization Alliance for the Global Elimination of Trachoma by 2020; setting targets that define elimination; building an evidence base for trichiasis surgery; azithromycin donation programme; use of the SAFE strategy (Surgery, Antibiotics, Facial cleanliness, and Environmental improvement); and The Global Trachoma Mapping Project. SUMMARY: These milestones have significantly pushed the progress towards elimination. Despite challenges to achieving the goal of elimination by 2020, there is continued commitment into the future to ensure that this preventable cause of blindness is no longer a threat.

Mass Oral Azithromycin for Childhood Mortality: Timing of Death After Distribution in the MORDOR Trial.

In a large community-randomized trial, biannual azithromycin distributions significantly reduced postneonatal childhood mortality in sub-Saharan African sites. Here, we present a prespecified secondary analysis showing that much of the protective effect was in the first 3 months postdistribution. Distributing more frequently than biannually could be considered if logistically feasible. Clinical Trials Registration. NCT02047981.

Biannual mass azithromycin distributions and malaria parasitemia in pre-school children in Niger: A cluster-randomized, placebo-controlled trial.

BACKGROUND: Mass azithromycin distributions have been shown to reduce mortality in preschool children, although the factors mediating this mortality reduction are not clear. This study was performed to determine whether mass distribution of azithromycin, which has modest antimalarial activity, reduces the community burden of malaria. METHODS AND FINDINGS: In a cluster-randomized trial conducted from 23 November 2014 until 31 July 2017, 30 rural communities in Niger were randomized to 2 years of biannual mass distributions of either azithromycin (20 mg/kg oral suspension) or placebo to children aged 1 to 59 months. Participants, field staff, and investigators were masked to treatment allocation. The primary malaria outcome was the community prevalence of parasitemia on thick blood smear, assessed in a random sample of children from each community at study visits 12 and 24 months after randomization. Analyses were performed in an intention-to-treat fashion. At the baseline visit, a total of 1,695 children were enumerated in the 15 azithromycin communities, and 3,029 children were enumerated in the 15 placebo communities. No communities were lost to follow-up. The mean prevalence of malaria parasitemia at baseline was 8.9% (95% CI 5.1%-15.7%; 52 of 552 children across all communities) in the azithromycin-treated group and 6.7% (95% CI 4.0%-12.6%; 36 of 542 children across all communities) in the placebo-treated group. In the prespecified primary analysis, parasitemia was lower in the azithromycin-treated group at month 12 (mean prevalence 8.8%, 95% CI 5.1%-14.3%; 51 of 551 children across all communities) and month 24 (mean 3.5%, 95% CI 1.9%-5.5%; 21 of 567 children across all communities) than it was in the placebo-treated group at month 12 (mean 15.3%, 95% CI 10.8%-20.6%; 81 of 548 children across all communities) and month 24 (mean 4.8%, 95% CI 3.3%-6.4%; 28 of 592 children across all communities) (P = 0.02). Communities treated with azithromycin had approximately half the odds of parasitemia compared to those treated with placebo (odds ratio [OR] 0.54, 95% CI 0.30 to 0.97). Parasite density was lower in the azithromycin group than the placebo group at 12 and 24 months (square root-transformed outcome; density estimates were 7,540 parasites/µl lower [95% CI -350 to -12,550 parasites/µl; P = 0.02] at a mean parasite density of 17,000, as was observed in the placebo arm). No significant difference in hemoglobin was observed between the 2 treatment groups at 12 and 24 months (mean 0.34 g/dL higher in the azithromycin arm, 95% CI -0.06 to 0.75 g/dL; P = 0.10). No serious adverse events were reported in either group, and among children aged 1 to 5 months, the most commonly reported nonserious adverse events (i.e., diarrhea, vomiting, and rash) were less common in the azithromycin-treated communities. Limitations of the trial include the timing of the treatments and monitoring visits, both of which took place before the peak malaria season, as well as the uncertain generalizability to areas with different malaria transmission dynamics. CONCLUSIONS: Mass azithromycin distributions were associated with a reduced prevalence of malaria parasitemia in this trial, suggesting one possible mechanism for the mortality benefit observed with this intervention. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (NCT02048007).

The impact on malaria of biannual treatment with azithromycin in children age less than 5 years: a prospective study.

BACKGROUND: The MORDOR study, a cluster randomized clinical trial, showed that single-dose azithromycin (20 mg/kg) administered biannually for 2 years to preschool children reduced mortality; a study was conducted to determine its effect on clinical symptomatic episodes of malaria as a potential mechanism for mortality benefit. METHODS: A randomized control trial (RCT) was conducted, whereby 30 randomly selected communities in Kilosa District, Tanzania were randomized to receive 6-monthly treatment of children ages 1-59 months with single-dose azithromycin (20 mg/kg) vs. placebo. A prospective cohort study was nested within the RCT: children, aged 1 to 35 months at baseline, were randomly selected in each community and evaluated at 6-monthly intervals for 2 years. At each visit, the children were assessed for recent or ongoing fever and anti-malarial treatment; a rapid diagnostic test (RDT) for malaria was performed. The two major outcomes of interest were prevalence of RDT positivity and clinical malaria. The latter was defined as RDT-positivity with fever at time of evaluation and/or reported fever in the 3 days prior to evaluation. Methods that account for correlations at community level and within individuals over time were used to evaluate associations. RESULTS: At baseline, the prevalence rates in the children in the azithromycin and placebo arms were 17.6% vs. 15.5% for RDT positivity (p = 0.76) and 6.1% vs. 4.3% (p = 0.56) for clinical malaria. There was a decline in both RDT-positivity and clinical malaria over time in both arms. The difference by treatment assignment was not significant for clinical malaria; it was significant for RDT-positivity with greater odds of decline in the placebo arm (p = 0.01). CONCLUSIONS: Lack of evidence for a significant difference in the prevalence of clinical malaria in children at any visit following treatment suggests that the effect of single-dose azithromycin on malaria is at best transient and limited in scope. Chance overrepresentation of non-seasonal transmission in the communities in the azithromycin arm may account for higher rates of RDT-positivity and less decline over time. Trial registration Clinicaltrials.gov NCT02047981.

Biannual versus annual mass azithromycin distribution and malaria seroepidemiology among preschool children in Niger: a sub-study of a cluster randomized trial.

BACKGROUND: Biannual mass azithromycin administration to preschool children reduces all-cause mortality, but the mechanism for the effect is not understood. Azithromycin has activity against malaria parasites, and malaria is a leading cause of child mortality in the Sahel. The effect of biannual versus annual azithromycin distribution for trachoma control on serological response to merozoite surface protein 1 (MSP-119), a surrogate for malaria incidence, was evaluated among children in Niger. METHODS: Markers of malaria exposure were measured in two arms of a factorial randomized controlled trial designed to evaluate targeted biannual azithromycin distribution to children under 12 years of age compared to annual azithromycin to the entire community for trachoma control (N = 12 communities per arm). Communities were treated for 36 months (6 versus 3 distributions). Dried blood spots were collected at 36 months among children ages 1-5 years, and MSP-119 antibody levels were assessed using a bead-based multiplex assay to measure malaria seroprevalence. RESULTS: Antibody results were available for 991 children. MSP-119 seropositivity was 62.7% in the biannual distribution arm compared to 68.7% in the annual arm (prevalence ratio 0.91, 95% CI 0.83 to 1.00). Mean semi-quantitative antibody levels were lower in the biannual distribution arm compared to the annual arm (mean difference - 0.39, 95% CI - 0.05 to - 0.72). CONCLUSIONS: Targeted biannual azithromycin distribution was associated with lower malaria seroprevalence compared to that in a population that received annual distribution. Trial Registration Clinicaltrials.gov NCT00792922.

Trachoma elimination in Latin America: prioritization of municipalities for surveillance activities.

OBJECTIVE: To identify and prioritize municipalities in 22 countries of Latin America for trachoma surveillance activities, to measure the absence or prevalence of trachoma, and to support validation and trachoma elimination efforts in the Region of the Americas. METHODS: A prioritization scale was developed in 2017 to rank each municipality by considering a combination of three characteristics: (a) its trachoma vulnerability index, derived from three socioeconomic factors known to be risks for trachoma-lack of access to improved sanitation, to clean drinking water, and to adequate education, according to housing census data from early 2017; (b) its history of trachoma in countries where the disease was not a known public health problem in 2016; and (c) whether or not it shares a border with a municipality where trachoma was a known public health problem in 2016. Municipalities in 22 countries were classified as either very high, high, medium, or low priority for trachoma surveillance. From the Caribbean, only Trinidad and Tobago met inclusion criteria. RESULTS: The prioritization scale identified 1 053 municipalities in Brazil, Colombia, and Guatemala as very high priority for trachoma surveillance. In Ecuador, El Salvador, Guyana, Paraguay, Peru, Suriname, and Venezuela, 183 municipalities were ranked as high priority, and in Argentina, Belize, Bolivia, Chile, Dominican Republic, Honduras, Nicaragua, Panama, and Uruguay, 677 municipalities were designated a medium priority for trachoma surveillance. CONCLUSIONS: This prioritization scale will be useful to countries in Latin America that still need to ascertain their current trachoma situation. The absence or prevalence of trachoma in countries designated as very high and high priority for trachoma surveillance activities must be studied to determine the extent of the disease in Latin America.

The Effect of Antibiotic Selection Pressure on the Nasopharyngeal Macrolide Resistome: A Cluster-randomized Trial.

Background: Frequent use of antibiotics is thought to create selection pressure by clearing susceptible bacteria and allowing resistant bacteria to spread in a community. A cluster-randomized trial comparing 2 different frequencies of mass azithromycin distributions for trachoma provided a convenient experiment for determining the causal relationship between antibiotic consumption and antibiotic resistance. Methods: Twenty-four communities were randomized to either annual or biannual mass azithromycin distributions for trachoma. Randomization was stratified on health catchment area and trachoma prevalence. Swabs were processed for the genetic macrolide resistance determinants ermB and mefA/E in a masked fashion from a random sample of 120 preschool children before treatment and another 120 children after 2 years of mass antibiotics. Results: Macrolide resistance determinants were similar in the 12 annually and 12 biannually treated communities before treatment, with a median prevalence among preschool children of 20% (interquartile range [IQR], 10%-40%) in each group. By 24 months, macrolide resistance determinants were found more commonly in the biannually treated communities (median, 60% [IQR, 50%-80%]) than the annually treated communities (median, 40% [IQR, 20%-40%]; P < .001). Adjusting for baseline, the 24-month prevalence of macrolide resistance determinants in the biannual group was 29.4% higher than that of the annual group (95% confidence interval, 10.5%-56.7%). Conclusions: This randomized trial used direct genetic methods to confirm the causal relationship of community antibiotic consumption and antibiotic resistance. Communities randomized to less frequent use of antibiotics had a significantly lower prevalence of genetic antibiotic resistance determinants. Clinical Trials Registration: NCT00792922.

A Cluster-Randomized Trial to Assess the Efficacy of Targeting Trachoma Treatment to Children.

Background: The World Health Organization recommends annual treatment of entire trachoma-endemic communities, although children typically have a higher load, longer duration, and greater likelihood of infection. Methods: Forty-eight communities in Matameye, Niger, were randomized to annual oral azithromycin treatment of the entire community or biannual treatment of children aged 0-12 years only. Both children and adults were monitored for ocular chlamydial infection by polymerase chain reaction. Results: The prevalence of childhood infection was reduced in the annually treated arm from 21.2% (95% confidence interval [CI], 15.2%-28.0%) at baseline to 5.8% (95% CI, 3.2%-9.0%) at 36 months (P < .001) and in the biannual arm from 20.2% (95% CI, 15.5%-25.3%) to 3.8% (95% CI, 2.2%-6.0%; P < .001). Adult infection in the annual arm was reduced from 1.7% (95% CI, .9%-2.7%) to 0.3% (95% CI, .0%-.7%) and in the biannual arm from 1.2% (95% CI, .5%-2.2%) to 0.0% (95% CI, .0%-.7%; P = .005). The effect of biannual treatment of children compared with annual treatment of the entire community in both children (95% CI, -.04% to .02%) and adults (95% CI, .9%-2.7%) excluded the prespecified noninferiority threshold of 6% (P = .003 and P < .001, respectively). Conclusions: Periodic distribution of antibiotics to children in trachoma-endemic communities reduces chlamydial infection in both children and untreated adults, suggesting a form of herd protection. Biannual treatment of children was comparable to (specifically, noninferior to) annual treatment of the entire community, and may offer lower antibiotic use and other logistical advantages. Clinical Trials Registration: NCT00792922.

Quantifying Fall-Related Hazards in the Homes of Persons with Glaucoma.

OBJECTIVE: To characterize fall-related hazards in the homes of persons with suspected or diagnosed glaucoma, and to determine whether those with worse visual field (VF) damage have fewer home hazards. DESIGN: Cross-sectional study using baseline (2013-2015) data from the ongoing Falls in Glaucoma Study (FIGS). PARTICIPANTS: One-hundred seventy-four of 245 (71.0%) FIGS participants agreeing to the home assessment. METHODS: Participants' homes were assessed using the Home Environment Assessment for the Visually Impaired (HEAVI). A single evaluator assessed up to 127 potential hazards in 8 home regions. In the clinic, binocular contrast sensitivity (CS) and better-eye visual acuity (VA) were evaluated, and 24-2 VFs were obtained to calculate average integrated VF (IVF) sensitivity. MAIN OUTCOME MEASURES: Total number of home hazards. RESULTS: No significant visual or demographic differences were noted between participants who did and did not complete the home assessment (P > 0.09 for all measures). Mean age among those completing the home assessment (n = 174) was 71.1 years, and IVF sensitivity ranged from 5.6 to 33.4 dB (mean = 27.2 dB, standard deviation [SD] = 4.0 dB). The mean number of items graded per home was 85.2 (SD = 13.2), and an average of 32.7 (38.3%) were identified as hazards. IVF sensitivity, CS, and VA were not associated with total home hazards or the number of hazards in any given room (P > 0.06 for all visual measures and rooms). The bathroom contained the greatest number of hazards (mean = 7.9; 54.2% of graded items classified as hazardous), and the most common hazards identified in at least 1 room were ambient lighting <300 lux and exposed light bulbs. Only 27.9% of graded rooms had adequate lighting. IVF sensitivity, CS, and VA were not associated with home lighting levels (P > 0.18 for all), but brighter room lighting was noted in the homes of participants with higher median income (P < 0.001). CONCLUSIONS: Multiple home fall hazards were identified in the study population, and hazard numbers were not lower for persons with worse VF damage, suggesting that individuals with more advanced glaucoma do not adapt their homes for safety. Further work should investigate whether addressing home hazards is an effective intervention for preventing falls in this high-risk group.

Visual Acuity Change over 12 Months in the Prospective Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: ProgStar Report Number 6.

PURPOSE: To estimate the yearly rate of change of best-corrected visual acuity (BCVA) and the risk of loss 1 line or more over 1 year and to identify risk factors for BCVA loss in patients with Stargardt disease (STGD1). DESIGN: Multicenter, prospective cohort study. PARTICIPANTS: Two hundred fifty-nine patients (489 eyes) with molecularly confirmed STGD1 enrolled at 9 centers in the United States and Europe. METHODS: Participants were followed up every 6 months, and data at the baseline and 6- and 12-month visits were analyzed. Best-corrected visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Standardized reporting forms were used to collect participants' characteristics and clinical observations. Linear mixed effects models were used to estimate the rate of BCVA loss. Linear models with generalized estimating equations were used to identify risk factors for BCVA loss of 1 line or more over 1 year. MAIN OUTCOME MEASURES: Change in BCVA over 1 year. RESULTS: Cross-sectional analysis at baseline showed that earlier symptom onset and longer duration since onset was associated with worse BCVA. Longitudinal analysis showed no overall significant change of BCVA within 12 months, but the rate of BCVA change was significantly different by baseline BCVA (P < 0.001). The BCVA of eyes with baseline BCVA of 20/25 or better declined at a rate of 2.8 ETDRS letters per year (P = 0.10), eyes with baseline BCVA between 20/25 and 20/70 declined at a rate of 2.3 ETDRS letters per year (P = 0.002), eyes with baseline BCVA between 20/70 and 20/200 declined at a rate of 0.8 ETDRS letters per year (P = 0.08), and eyes with baseline BCVA worse than 20/200 showed a significant improvement of 2.3 ETDRS letters per year (P < 0.001). Overall, 12.9% of eyes lost 1 line or more, and the risk of such BCVA loss was different by baseline BCVA level (P = 0.016). Smoking and vitamin A use was not associated significantly with baseline BCVA, nor with rate of BCVA loss over 1 year. CONCLUSIONS: Change in BCVA in STGD1 patients over a 12-month period was small, but varied depending on baseline BCVA. Given the slow change during 1 year, BCVA is unlikely to be a sensitive outcome measure for STGD1 treatment trials with 1 year's duration.