Viral species richness and composition in young children with loose or watery stool in Ethiopia.

BACKGROUND: Stool consistency is an important diagnostic criterion in both research and clinical medicine and is often used to define diarrheal disease. METHODS: We examine the pediatric enteric virome across stool consistencies to evaluate differences in richness and community composition using fecal samples collected from children aged 0 to 5 years participating in a clinical trial in the Amhara region of Ethiopia. The consistency of each sample was graded according to the modified Bristol Stool Form Scale for children (mBSFS-C) before a portion of stool was preserved for viral metagenomic analysis. Stool samples were grouped into 29 pools according to stool consistency type. Differential abundance was determined using negative-binomial modeling. RESULTS: Of 446 censused children who were eligible to participate, 317 presented for the study visit examination and 269 provided stool samples. The median age of children with stool samples was 36 months. Species richness was highest in watery-consistency stool and decreased as stool consistency became firmer (Spearman's r = - 0.45, p = 0.013). The greatest differential abundance comparing loose or watery to formed stool was for norovirus GII (7.64, 95% CI 5.8, 9.5) followed by aichivirus A (5.93, 95% CI 4.0, 7.89) and adeno-associated virus 2 (5.81, 95%CI 3.9, 7.7). CONCLUSIONS: In conclusion, we documented a difference in pediatric enteric viromes according to mBSFS-C stool consistency category, both in species richness and composition.

Reproducibility of 5 Methods of Ocular Tonometry.

PURPOSE: To evaluate the agreement between Goldmann applanation tonometry (GAT; Haag-Streit, Bern, Switzerland) and several portable tonometers that could be used for glaucoma screening programs. DESIGN: Evaluation of a diagnostic test. PARTICIPANTS: Three hundred twenty-one eyes of 168 participants seeking treatment at the glaucoma clinic of a tertiary eye hospital in India. METHODS: Participants underwent intraocular pressure (IOP) measurement with GAT and 4 index tests: the Icare TA01i rebound tonometer (Icare USA, Raleigh, NC), a noncontact tonometer (NCT; Topcon CT-80; Topcon; Tokyo, Japan), a pneumatonometer (Model 30; Reichert Technologies; Depew, NY), and the Tono-Pen AVIA (Reichert Technologies). MAIN OUTCOME MEASURES: Estimates of reproducibility of IOP measurements between each index test and GAT, including the intraclass correlation coefficient (ICC) and the Bland-Altman 95% limits of agreement. RESULTS: The Icare showed the greatest agreement with GAT (ICC, 0.69; 95% confidence interval, 0.61-0.74), followed by the NCT (ICC, 0.65; 95% confidence interval, 0.58-0.71), the Tono-Pen (ICC, 0.51; 95% confidence interval, 0.43-0.59), and the pneumatonometer (ICC, 0.36; 95% confidence interval, 0.27-0.44). The pneumatonometer and Tono-Pen tended to overestimate IOP relative to GAT, with a mean difference of 3.4 mmHg (95% limits of agreement [LOA], -7.3 to 14.1 mmHg) for the pneumatonometer and 3.2 mmHg (95% LOA, -6.1 to 12.6 mmHg) for the Tono-Pen. In contrast, measurements from the Icare and NCT were on average within 1 point of those for GAT (mean difference, -0.4 mmHg [95% LOA, -8.4 to 7.6 mmHg] and -0.5 mmHg [95% LOA, -8.7 to 7.6 mmHg], respectively). CONCLUSIONS: The Icare and NCT both demonstrated good agreement with GAT across a wide range of IOPs and could be considered for glaucoma screening programs.

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.

Defining Diarrhea: A Population-Based Validation Study of Caregiver-Reported Stool Consistency in the Amhara Region of Ethiopia.

Diarrhea is a leading cause of death among children aged less than five years globally. Most studies of pediatric diarrhea rely on caregiver-reported stool consistency and frequency to define the disease. Research on the validity of caregiver-reported diarrhea is sparse. We collected stool samples from 2,398 children participating in two clinical trials in the Amhara region of Ethiopia. The consistency of each stool sample was graded by the child's caregiver and two trained laboratory technicians according to an illustrated stool consistency scale. We assessed the reliability of graded stool consistency among the technicians, and then compared the caregiver's grade with the technician's grade. We also tested if the illustrated stool consistency scale could improve the validity of caregiver's report. The weighted kappa measuring the agreement between the two laboratory technicians reached 0.90 after 500 stool samples were graded. The sensitivity of caregiver-reported loose or watery stool was 15.5% (95% confidence interval [CI]: 9.7, 24.2) and the specificity was 98.4% (95% CI 97.1, 99.1). With the illustrated scale, the sensitivity was 68.5% (95% CI: 58.5, 77.1) and the specificity was 86.1% (95% CI: 79.3, 90.9). The results indicate that caregiver-reported stool consistency using the terms "loose or watery" does not accurately describe stool consistency as graded by trained laboratory technicians. Given the predominance of using caregiver-reported stool consistency to define diarrheal disease, the low sensitivity identified in this study suggests that the burden of diarrheal disease may be underestimated and intervention effects could be biased. The illustrated scale is a potential low-lost tool to improve the validity of caregiver-reported stool consistency.

Trachomatous Scar Ranking: A Novel Outcome for Trachoma Studies.

AbstractWe evaluated a new trachoma scarring ranking system with potential use in clinical research. The upper right tarsal conjunctivas of 427 individuals from Ethiopian villages with hyperendemic trachoma were photographed. An expert grader first assigned a scar grade to each photograph using the 1981 World Health Organization (WHO) grading system. Then, all photographs were ranked from least (rank = 1) to most scarring (rank = 427). Photographic grading found 79 (18.5%) conjunctivae without scarring (C0), 191 (44.7%) with minimal scarring (C1), 105 (24.6%) with moderate scarring (C2), and 52 (12.2%) with severe scarring (C3). The ranking method demonstrated good internal validity, exhibiting a monotonic increase in the median rank across the levels of the 1981 WHO grading system. Intrarater repeatability was better for the ranking method (intraclass correlation coefficient = 0.84, 95% CI = 0.74-0.94). Exhibiting better internal and external validity, this ranking method may be useful for evaluating the difference in scarring between groups of individuals.