Model of yearly transition to severe trachomatous scarring and trichiasis in a cohort of women in Kongwa Tanzania.

One criterion for validation of trachoma elimination is the management of Trachomatous Trichiasis (TT) after Trachoma inflammation-follicular (TF) is eliminated in children ages 1-9 years at district level. No data exist on how long countries must have dedicated TT programs, as the timeline for progression to TT from trachomatous scarring is unknown. We used eight years of longitudinal data in women in Kongwa Tanzania to model progression from no scarring (S0) through grades of scarring severity (S1-S4) to TT. Markov models were used, with age, community prevalence of TF (CPTF), and household characteristics as co-variates. Adjusted for covariates, the incidence of S1 was estimated at 4∙7% per year, and the risk increased by 26% if the CPTF was between 5-10% and by 48% if greater than 10%. The transition from S4 to TT was estimated at 2∙6% per year. Districts, even after elimination of TF, may have some communities with TF ≥ 5% and increased risk of incident scarring. Once scarring progresses to S2, further progression is not dependent on CPTF. These data suggest that, depending on the district level of scarring and degree of heterogeneity in CPTF at the time of elimination, incident TT will still be an issue for decades.

Severity of Trachomatous Scarring among Adults in Trachoma-Endemic Amhara Region of Ethiopia.

Trachomatous scarring has been shown to progress regardless of active ocular Chlamydia trachomatis infection, indicating that scarring drivers may be unrelated to ongoing transmission. Although scarring prevalence is commonly associated with older age and female sex, less is known about other potential contributors to its development. This study identified and assessed risk factors associated with scarring magnitude in a trachoma-endemic setting, utilizing a five-point photographic scale (S0-S4). During 2017 trachoma surveys of Amhara, Ethiopia, photographers captured left and right conjunctival images of adults (ages 15 years and older) from 10 districts. Subsequently, two graders independently assessed photographs for scarring, with discrepancies adjudicated by an expert grader. Scarring scores for 729 individuals were aggregated from the eye level to the participant level, excluding 17 participants because of poor photograph quality. Among those with scarring, most cases (20.4%) were severe (S4, comprising more than 90% of the tarsal conjunctiva) compared with the prevalence of moderate S3-A/B (11.2%), S2 (8.3%), and mild S1 (19.2%). The youngest group (ages 15-19 years) exhibited all scarring stages. Older participants (60 years and older) experienced a greater burden of severe scarring (S4 prevalence: 32.6%) than their younger (15-19 years) counterparts (6.2%). Multivariate ordinal logistic regression models indicated female sex, increasing age, and district-level trachomatous follicular-inflammation prevalence were significant predictors of scarring severity. Trachomatous scarring and its progression to trichiasis, may prove a barrier to meeting WHO timelines for trachoma elimination and will necessitate ongoing surveillance and interventions after elimination thresholds have been met.

Comparison of two approaches to measuring clean faces as part of the facial cleanliness component of the SAFE trachoma elimination strategy.

BACKGROUND: The Alliance for the Global Elimination of Trachoma (GET) endorses the full SAFE strategy to eliminate trachoma; Surgery (for trichiasis), Antibiotics (to reduce the community pool of infection, Facial cleanliness, and Environmental improvement (to decrease transmission). There is no accepted measure of facial cleanliness. This study compared two possible metrics for facial cleanliness. METHOD/FINDINGS: Metric one: Clean face was defined as observed absence of ocular and nasal discharge on the face. Metric two: observing a grade of dirtiness (scale 10 = lightest to 0 = darkest) on a standard facial wipe. The reliability of grading a child's face or grading a facial wipe was determined in children in Kongwa Tanzania. We also observed both measurements in a cohort of 202 children ages 1 to <7years prior to face cleaning, immediately afterwards, and 4 hours afterwards. Fifty of the children did not have face cleaning and were controls. Intra-and interobserver reliability was similar for both measures, the latter = 0.53 for observing a clean face and 0.52 for grading a facial wipe. There was no correlation between the two. Both measures detected facial cleaning, compared to control children who were not cleaned, immediately after cleaning; control children with 53% clean faces and wipe score of 6.7 compared to cleaned children with 88% clean faces and wipe score of 8 (p = .0001, p = < .0001, respectively). Both measures also detected face washing 4 hours previously compared to controls. CONCLUSIONS: The two metrics were equally reliable, and both measured the behavior of face washing. They measure different aspects of a clean face; one measures the amount of dirt on wiped area and the other measures ocular and nasal discharge. Both measurements appear to capture the behavior of facial cleaning, and the choice of metric would appear to rest on the measurement that captures the stated objective of the behavior, consideration of costs, training, logistics, and implementation.

Efficacy of Single-Dose Azithromycin for Ocular Chlamydial Infection: A Longitudinal Study.

Millions of doses of azithromycin are distributed each year for trachoma, yet the treatment efficacy of a single dose of azithromycin for ocular Chlamydia infection has not been well characterized. In this study, four villages in Niger received a mass azithromycin distribution for trachoma. All 426 children aged 0-5 years residing in the study villages were offered conjunctival swabbing every 6 months to test for ocular Chlamydia trachomatis. Among the children infected with ocular Chlamydia before treatment, 6% (95% CI: 2-15%) tested positive for ocular Chlamydia infection 6 months later, and 15% (95% CI: 7-28%) tested positive 12 months later. The most important predictor of post-treatment ocular Chlamydia infection was pretreatment ocular Chlamydia infection (relative risk: 3.5, 95% CI: 1.3-9.4). Although the 6-monthly monitoring schedule was suboptimal for testing the treatment efficacy of an antibiotic, these findings are nonetheless consistent with high treatment efficacy of a single dose of azithromycin and suggest that additional interventions might be most effective if targeted to those children infected prior to treatment.

Gender differences in trachomatous scarring prevalence in a formerly trachoma hyperendemic district in Tanzania.

BACKGROUND: Trachoma is a chronic conjunctivitis caused by the bacterium Chlamydia trachomatis. Repeated infections lead to trachomatous conjunctival scarring which can progress to potentially blinding trachomatous trichiasis (TT). In trachoma hyperendemic conditions, women compared to men have an increased risk of scarring and TT, which can progress to blinding corneal opacification. This study determined if there were gender differences in scarring prevalence and severity when trachoma prevalence approaches elimination, in a formerly trachoma hyperendemic region. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional prevalence study was conducted amongst adults age 15 years and older in Kongwa district, Tanzania in 2019. 3168 persons over age 15 years agreed to be examined and had at least one eye with a gradable image. Ocular photographs were graded for scarring according to a published four-step severity scale. Overall, about half of all study participants had scarring. However, more females (52.3%) had any scarring compared to males (47.2%), OR = 1.22 (95% CI = 1.05-1.43). For every year increase in age, there was a 6.5% increase in the odds of having more severe scarring (95% CI: 5.8%, 7.2%). Women were more likely than men to have severe scarring, OR 2.36 (95% CI: 1.84-3.02). Residence in a community with TF≥10% was associated with a 1.6-fold increased odds of any scarring. CONCLUSIONS/SIGNIFICANCE: Overall scarring prevalence and more severe scarring prevalence was higher in females compared to males, even adjusting for age and community TF prevalence. The data suggest that processes occur that lead to women preferentially progressing towards more severe scarring compared to men.

Comparing image quality and trachoma detection across three camera types from a survey in Kongwa, Tanzania.

BACKGROUND: There is an increasing demand for photography for trachoma prevalence surveys. In previous studies, digital single lens reflex (DSLR) images were superior to smartphone images, but newer-model smartphones and/or lens attachments may be able to bridge this gap. This study compares the image quality and ability to detect trachomatous inflammation - follicular (TF) of three camera types: a DSLR Nikon camera, an iPhone SE and an iPhone 13 Pro with a cell scope. METHODS: We surveyed 62 children ages 1-7 y from two Tanzanian communities. Upper tarsal conjunctiva images of both eyes were graded for TF by two standardized graders. The McNemar's test and a logistic regression model were used for analyses. RESULTS: The DSLR camera malfunctioned during the study, thus the iPhone SE and iPhone 13 Pro with cell scope were both more likely to take high-quality, gradable photographs (88% and 86%, respectively) compared with the DSLR camera (69%) (p<0.001 and p=0.02, respectively). TF was detected in gradable images from the iPhone SE (8.8%) and iPhone 13 Pro with cell scope (9.0%) at the same rate (p=1.0) as images from the DSLR camera (9.7%). CONCLUSION: Smartphones with high-quality image capture, like the iPhone SE/13 Pro, have the potential for use in trachoma surveys if the proportion of gradable images can be improved.

Expanding a photographic grading system for trachomatous scarring.

BACKGROUND: The purpose was to assess an expansion of a previously published photographic four-step severity grading scale for trachomatous scarring (TS). METHODS: Images of everted eyelids of adult women in Tanzania were graded for the presence and severity of TS. The previous S3 grade was subdivided into two categories: S3A, one-third to <50% of the upper eyelid conjunctiva scarred; and S3B, 50% to <90%. The reliability and ease of use were evaluated. This new categorisation was then applied to images taken of the same women 5 y prior to evaluate whether it could help detect previously undetected progression. RESULTS: In total, 142 eyes at baseline and 418 eyes at follow-up after 5 y were graded as S3. Interobserver agreement using the expanded scarring grading scale was a kappa of 0.86. At baseline, 51 (35.9%) eyes were S3A and 91 (64.1%) were S3B. At follow-up after 5 y, 36.6% of the eyes that were previously documented as not having progressed were now detected as having progressed from S3A to S3B. S3B images were more likely to progress to S4 compared with S3A (OR 4.6, 95% CI 2.1 to 9.9). CONCLUSIONS: Adding S3A and S3B is reliable and detects more scarring progression. It will be beneficial for future studies analysing TS in photographs.

Relationship Between Intraocular Pressure and Age: A Population-Based Study in Nepal.

PRCIS: Intraocular pressure (IOP) decreased with age in a population-based study in Nepal, from a mean of 14.1 mm Hg among those 60-64 years old to 13.0 mm Hg among those 80 years old or older. PURPOSE: Few studies have assessed the distribution of IOP from the Indian subcontinent, despite its large population and high burden of glaucoma. The objective of this study was to assess the distribution of IOP measurements from adults living in a lowland region of Nepal. METHODS: In a population-based cross-sectional study, all individuals aged 60 years and older from an area of lowland Nepal were invited for an IOP assessment with a rebound tonometer. RESULTS: Of 160 communities (28,672 people aged ≥60 y) enrolled, 79 (13,808 people aged ≥60 y) were randomly selected for IOP testing. Of those eligible, 10,017 (72.5%) individuals underwent tonometry. Mean IOP decreased monotonically over 5-year age groups, from 14.1 mm Hg (SD: 3.6) among those aged 60-64 years to 13.0 mm Hg (SD: 4.2) among those 80 years or older. The 97.5th percentile IOP measurement was 21.0 mm Hg for all age groups. In adjusted analyses, younger age, self-reported diabetes, and higher population density were each associated with higher IOP, and self-reported cataract surgery was associated with lower IOP. CONCLUSIONS: Mean IOP was lower among older individuals in Nepal, consistent with many studies from East Asia and in contrast to many studies from western populations. These results suggest that ethnic background might be a consideration when diagnosing ocular hypertension.

The Association Between the Severity of Trachomatous Scarring and Trachomatous Trichiasis Severity in Surgical Patients in Tanzania.

PURPOSE: To determine the association between the severity of trachomatous conjunctival scarring (TS) of the upper eyelid conjunctiva and trachomatous trichiasis (TT) severity in TT surgical patients. METHODS: A cross-sectional study was conducted amongst adults with TT who were referred to surgical camps in Bahi District, Tanzania, for TT surgery. Participants underwent ocular examination. The presence and severity of TS was evaluated in photographs of the everted upper eyelid. TT severity was assessed at the time of the ocular exam based on the number of lashes touching the globe and/or evidence and extent of epilation. Ordinal logistic models were used to examine the association between the severity of TS and TT severity. RESULTS: A total of 627 eyes of 388 participants were included. Mean age was 65 years (ranging from 21-98), 81% were females, and 62% had bilateral TT. 93% of eyes with any TT had at least moderate TS; 62% of eyes had severe TS. An increase in TS severity was associated with an increase in the severity of TT. Using as a reference eyes with none to mild TS, in eyes with moderate TS the odds of increased severity of TT was 1.30 (95% CI 0.67-2.51), in eyes with severe TS the odds was 4.20 (95% CI 2.23-7.92). CONCLUSION: In cases of trachomatous trichiasis presenting for surgery, the severity of TT was significantly associated with the severity of TS with almost all cases of TT having moderate or severe scarring.

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.

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.

Association of Optic Nerve Head and Macular Optical Coherence Tomography Measures With Glaucoma-Related Disability.

PRCIS: Optical coherence tomography (OCT) estimated retinal nerve fiber layer (RNFL) thickness associated with glaucoma-related disability independent of the visual field (VF) damage and thus may provide additional patient-relevant disability information beyond what is captured by standard VF testing. PURPOSE: To examine whether OCT metrics [peripapillary RNFL thickness and macular ganglion cell/inner plexiform layer (GCIPL) thickness] are associated with quality of life (QoL) measures and additional disability metrics, and whether these associations are independent of VF damage. METHODS: In this cross-sectional study, 156 patients with glaucoma or suspected glaucoma received VF testing and OCT scans to measure RNFL and GCIPL thickness. QoL was assessed using the Glaucoma Quality-of-Life 15 and additional disability measures including fear of falling, reading speed, and steps per day were assessed. Multivariable regression models adjusting for relevant covariates tested whether RNFL or GCIPL thickness from the less-impaired eye were associated with disability measures and whether associations were independent of VF damage. RESULTS: Greater VF damage is associated with worse QoL (95% CI=0.4-1.4; P <0.001) and slower reading speed (CI=-0.06 to -0.02; P <0.001). Lower RNFL and GCIPL thicknesses were associated with lower QoL scores, but not with QoL scores or other disability metrics after correcting for VF damage. However, post hoc analyses in patients with better eye thicknesses between 55 and 75 µm demonstrated associations between lower RNFL thickness and worse QoL (CI=-2.2 to -0.1; P =0.04) and greater fear of falling (CI=-6.1 to -0.4; P =0.03) even after accounting for VF damage. No such associations were observed for GCIPL thickness. CONCLUSIONS: OCT RNFL, but not GCIPL, thickness is associated with multiple disability measures independent of VF damage severity.

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.

Comparison of Five Camera Systems for Capturing and Grading Trachoma Images.

PURPOSE: As training of trachoma graders using live participants grows increasingly difficult and expensive, alternative ways are needed possibly through replacement of field grading with photography. However, minimum specifications for a camera system capable of capturing high quality images have not been defined. This study compared images captured using four smartphones with those from a Nikon SLR camera for image quality and assessment of trachomatous inflammation - follicular (TF). METHODS: The smartphones - Samsung Galaxy S8 (S8), Techno Camon 17 pro (TC), Infinix Note 10 pro (IN), Huawei p30 pro (HP) - were chosen for their availability and likelihood of good performance based on specifications without external attachments. All smartphones were used in random order for each participant. RESULTS: 129 children in Kongwa, Tanzania were enrolled (32.8% TF prevalence). The SLR camera had the least percent of ungradable images (3.1%), followed by the S8 (14%), HP (23.4%), IN (65.9%), and TC (71.2%). The S8 and the HP were significantly more likely to take ungradable images if they were used toward the end of the camera rotation. Agreement between the SLR and field grade was kappa = 0.73. Agreement between the field grade and gradable images from the S8 (0.68) and HP (0.8) was measured. CONCLUSIONS: Published specifications did not predict the success of using different smartphones for everted eyelid photographs; proprietary post-processing software likely influenced gradeability. Smartphones, though we cannot recommend those tested in this study, may be viable for capturing images for trachoma provided the quality of images from the field are adequate.

The Impact of Neighborhood Factors on Physical Activity in Older Adults With Visual Impairment.

PURPOSE: To investigate the associations of neighborhood-level socioeconomic and environmental characteristics with physical activity in persons with glaucoma. DESIGN: Cross-sectional study (N = 230). METHODS: Home addresses were used to extract neighborhood factors (NFs): Area Deprivation Index, crime rate, and the proportion of racial and ethnic minorities, poverty, college graduates, and park area in their census tract. Participants' average number of daily steps and nonsedentary minutes were collected over 7 days using an accelerometer. Visual field (VF) loss was quantified as integrated VF sensitivity. Multivariable negative binomial regression models and additional models with an interaction term evaluated the effect of NF on physical activity and whether these relationships differed by VF loss severity. RESULTS: Participants were on average 70.6 years of age, 51.7% were male, and 27.8% were black. A higher Area Deprivation Index or poverty share was associated with fewer NSM (incidence rate ratio [IRR] = 0.96 per 1 Area Deprivation Index decile increment, P = .01; IRR = 0.92 per 10% poverty share increment, P = .02), while higher share of college graduates was associated with greater NSM (IRR = 1.03 per 10% increment; P = .03). Stronger associations were noted between both high crime rate and poverty share with NSM in individuals with severe VF damage as opposed to no/mild VF damage (IRR = 0.44, P = .001; IRR = 0.81, P = .02). CONCLUSIONS: Select NFs (poverty share and crime rate) may disproportionately affect physical activity in patients with severe VF loss. Interventions to overcome activity limitations within the context of poverty and high socioeconomic disadvantage are important for addressing glaucoma-related disability, particularly in those with severe VF loss.

Detection of trachoma using machine learning approaches.

BACKGROUND: Though significant progress in disease elimination has been made over the past decades, trachoma is the leading infectious cause of blindness globally. Further efforts in trachoma elimination are paradoxically being limited by the relative rarity of the disease, which makes clinical training for monitoring surveys difficult. In this work, we evaluate the plausibility of an Artificial Intelligence model to augment or replace human image graders in the evaluation/diagnosis of trachomatous inflammation-follicular (TF). METHODS: We utilized a dataset consisting of 2300 images with a 5% positivity rate for TF. We developed classifiers by implementing two state-of-the-art Convolutional Neural Network architectures, ResNet101 and VGG16, and applying a suite of data augmentation/oversampling techniques to the positive images. We then augmented our data set with additional images from independent research groups and evaluated performance. RESULTS: Models performed well in minimizing the number of false negatives, given the constraint of the low numbers of images in which TF was present. The best performing models achieved a sensitivity of 95% and positive predictive value of 50-70% while reducing the number images requiring skilled grading by 66-75%. Basic oversampling and data augmentation techniques were most successful at improving model performance, while techniques that are grounded in clinical experience, such as highlighting follicles, were less successful. DISCUSSION: The developed models perform well and significantly reduce the burden on graders by minimizing the number of false negative identifications. Further improvements in model skill will benefit from data sets with more TF as well as a range in image quality and image capture techniques used. While these models approach/meet the community-accepted standard for skilled field graders (i.e., Cohen's Kappa >0.7), they are insufficient to be deployed independently/clinically at this time; rather, they can be utilized to significantly reduce the burden on skilled image graders.

Effect of Biannual Mass Azithromycin Distributions to Preschool-Aged Children on Trachoma Prevalence in Niger: A Cluster Randomized Clinical Trial.

Importance: Because transmission of ocular strains of Chlamydia trachomatis is greatest among preschool-aged children, limiting azithromycin distributions to this age group may conserve resources and result in less antimicrobial resistance, which is a potential advantage in areas with hypoendemic trachoma and limited resources. Objective: To determine the efficacy of mass azithromycin distributions to preschool-aged children as a strategy for trachoma elimination in areas with hypoendemic disease. Design, Setting, and Participants: In this cluster randomized clinical trial performed from November 23, 2014, until July 31, 2017, thirty rural communities in Niger were randomized at a 1:1 ratio to biannual mass distributions of either azithromycin or placebo to children aged 1 to 59 months. Participants and study personnel were masked to treatment allocation. Data analyses for trachoma outcomes were performed from October 19, 2021, through June 10, 2022. Interventions: Every 6 months, a single dose of either oral azithromycin (20 mg/kg using height-based approximation for children who could stand or weight calculation for small children) or oral placebo was provided to all children aged 1 to 59 months. Main Outcomes and Measures: Trachoma was a prespecified outcome of the trial, assessed as the community-level prevalence of trachomatous inflammation-follicular and trachomatous inflammation-intense through masked grading of conjunctival photographs from a random sample of 40 children per community each year during the 2-year study period. A secondary outcome was the seroprevalence of antibodies to C trachomatis antigens. Results: At baseline, 4726 children in 30 communities were included; 1695 children were enrolled in 15 azithromycin communities and 3031 children were enrolled in 15 placebo communities (mean [SD] proportions of boys, 51.8% [4.7%] vs 52.0% [4.2%]; mean [SD] age, 30.8 [2.8] vs 30.6 [2.6] months). The mean coverage of study drug for the 4 treatments was 79% (95% CI, 75%-83%) in the azithromycin group and 82% (95% CI, 79%-85%) in the placebo group. The mean prevalence of trachomatous inflammation-follicular at baseline was 1.9% (95% CI, 0.5%-3.5%) in the azithromycin group and 0.9% (95% CI, 0-1.9%) in the placebo group. At 24 months, trachomatous inflammation-follicular prevalence was 0.2% (95% CI, 0-0.5%) in the azithromycin group and 0.8% (95% CI, 0.2%-1.6%) in the placebo group (incidence rate ratio adjusted for baseline: 0.18 [95% CI, 0.01-1.20]; permutation P = .07). Conclusions and Relevance: The findings of this trial do not show that biannual mass azithromycin distributions to preschool-aged children were more effective than placebo, although the underlying prevalence of trachoma was low. The sustained absence of trachoma even in the placebo group suggests that trachoma may have been eliminated as a public health problem in this part of Niger. Trial Registration: ClinicalTrials.gov Identifier: NCT02048007.

Associated factors of the co-occurrence of trachoma and soil-transmitted helminthiases in children 1 to 9 years old in rural communities of the Amazon basin in Loreto Department, Peru: Results from a population-based survey.

BACKGROUND: There is evidence of the occurrence of trachoma in Peru, and studies have shown that soil-transmitted helminthiases (STH) are affecting rural communities in the Amazon basin in Loreto Department. This study was done to estimate trachoma prevalence, STH prevalence, and the associated factors for both diseases in children aged 1-9 years in rural communities of Peru. METHODOLOGY: A population-based cross-sectional survey was carried out in rural communities of Loreto. A standardized survey questionnaire with individual and household risk factors related to both diseases was used. Ocular examination was done for all participants aged one year and above, and eye swab samples were collected from children with follicular trachoma (TF). Anthropometric measurements, stool samples for STH, and blood samples for hemoglobin measurement were taken from children. PRINCIPAL FINDINGS: TF prevalence was 7.74% (95% CI 5.08-11.63%), STH prevalence was 49.49% (95% CI 25.00-52.43%), and prevalence of co-occurrence of both diseases was 5.06% (95% CI 2.80-8.98%) in children aged 1-9 years. Being at age 3-8 years old (AOR = 6.76; 95% CI 1.346-33.947), have an unclean face (AOR = 24.64; 95% CI 6.787-89.444), and having been dewormed in the last six months (AOR = 2.47; 95% CI 1.106-5.514), were risk factors of TF. Being a female (AOR = 0.22; 95% CI 0.103-0.457) was associated with decreased odds of TF. Having been dewormed in the last six months (AOR = 0.30; 95% CI 0.139-0.628) was a preventative factor for STH. Risk factors for children with both diseases mirrored the findings for risk factors for individual diseases. CONCLUSIONS: Neglected tropical diseases and associated risk factors overlap in communities living in vulnerable conditions in the Amazon basin of Peru. These findings support the need to implement integrated interventions, including mass drug administration, water, sanitation, and hygiene for both diseases in the study area.

Risk of seroconversion and seroreversion of antibodies to Chlamydia trachomatis pgp3 in a longitudinal cohort of children in a low trachoma prevalence district in Tanzania.

BACKGROUND: Serologic testing for chlamydial antibodies is one potential tool for trachoma monitoring. Understanding the dynamics of seroconversion and seroreversion in low endemic districts is critical for determining the value of using serology. METHODOLOGY/PRINCIPAL FINDINGS: We surveyed a random sample of 2536 children aged 1-9 years in Kongwa, Tanzania, over three years; 1719 (67.8%) participants had all three follow-ups. Surveys assessed trachomatous inflammation-follicular (TF), Chlamydia trachomatis infection, and anti-pgp3 antibodies. Mass drug administration occurred immediately after the first and second follow-up surveys. The cohort was classified into trajectories of change in serostatus, and risk factors were evaluated for seroconversion and seroreversion. We found that 86.2% of seropositives remained seropositive throughout the study, whereas 12.1% seroreverted. Seroreverters were younger (Odds Ratio [OR] = 0.88 for every one-year increase in age, 95% CI = 0.79-0.99). 84.5% of seronegatives remained seronegative, and 13.0% seroconverted. Seroconverters were also younger (OR = 0.92, 95% CI = 0.87-0.98). Seroconversion and seroreversion were not explained by indeterminate values for the intensity of antibody response. Less than 1% of the cohort had unstable changes in serostatus, mostly explained by values in the indeterminate range. TF and infection in the cohort declined over time, while seropositivity increased from 31.5% to 36.4%. CONCLUSIONS/SIGNIFICANCE: Antibody status is relatively stable over time. Both seroconversion and seroreversion occurred over the three years in this low endemic district, especially in younger children. Modeling seroreversion is important for accurate determination of seroconversion. The use of serology as a monitoring tool should target the younger aged children as they will most likely capture recent changes in serostatus.