Agreement between novice and experienced trachoma graders improves after a single day of didactic training.

BACKGROUND/AIMS: Prevalence estimates and treatment decisions for trachoma are based entirely on ocular clinical examination. The aim of the current study is to demonstrate that ophthalmic assistants can be trained and certified to provide trachoma grading within a single day. METHODS: Conjunctival photographs from an area with endemic trachoma were randomised into two sets of 60 cases. Photographs were graded for trachomatous inflammation-follicular (TF) and trachomatous inflammation-intense (TI) by three experienced graders. Inter-rater reliability of eight ophthalmic assistants and three experienced graders were compared before and after training. RESULTS: The mean κ agreement between the ophthalmic assistants and the consensus grades of the experienced graders for TF was 0.38 (95% CI 0.18 to 0.58) before training, and increased to 0.60 (95% CI 0.42 to 0.78) after training (p=0.07). The mean κ agreement for TI was 0.16 (95% CI 0.02 to 0.30) before training, and increased to 0.39 (95% CI 0.20 to 0.58) after training (p=0.02). CONCLUSION: A single day of training improves agreement between prospective and experienced trachoma graders, and provides the basis for certification of workers who are able to accurately grade trachoma and generate reliable prevalence estimates.

Inter-Rater Agreement between Trachoma Graders: Comparison of Grades Given in Field Conditions versus Grades from Photographic Review.

PURPOSE: Trachoma surveillance is most commonly performed by direct observation, usually by non-ophthalmologists using the World Health Organization (WHO) simplified grading system. However, conjunctival photographs may offer several benefits over direct clinical observation, including the potential for greater inter-rater agreement. This study assesses whether inter-rater agreement of trachoma grading differs when trained graders review conjunctival photographs compared to when they perform conjunctival examinations in the field. METHODS: Three trained trachoma graders each performed an independent examination of the everted right tarsal conjunctiva of 269 children aged 0-9 years, and then reviewed photographs of these same conjunctivae in a random order. For each eye, the grader documented the presence or absence of follicular trachoma (TF) and intense trachomatous inflammation (TI) according to the WHO simplified grading system. RESULTS: Inter-rater agreement for the grade of TF was significantly higher in the field (kappa coefficient, κ, 0.73, 95% confidence interval, CI 0.67-0.80) than by photographic review (κ = 0.55, 95% CI 0.49-0.63; difference in κ between field grading and photo grading 0.18, 95% CI 0.09-0.26). When field and photographic grades were each assessed as the consensus grade from the three graders, agreement between in-field and photographic graders was high for TF (κ = 0.75, 95% CI 0.68-0.84). CONCLUSIONS: In an area with hyperendemic trachoma, inter-rater agreement was lower for photographic assessment of trachoma than for in-field assessment. However, the trachoma grade reached by a consensus of photographic graders agreed well with the grade given by a consensus of in-field graders.

Does mass azithromycin distribution impact child growth and nutrition in Niger? A cluster-randomized trial.

BACKGROUND: Antibiotic use on animals demonstrates improved growth regardless of whether or not there is clinical evidence of infectious disease. Antibiotics used for trachoma control may play an unintended benefit of improving child growth. METHODOLOGY: In this sub-study of a larger randomized controlled trial, we assess anthropometry of pre-school children in a community-randomized trial of mass oral azithromycin distributions for trachoma in Niger. We measured height, weight, and mid-upper arm circumference (MUAC) in 12 communities randomized to receive annual mass azithromycin treatment of everyone versus 12 communities randomized to receive biannual mass azithromycin treatments for children, 3 years after the initial mass treatment. We collected measurements in 1,034 children aged 6-60 months of age. PRINCIPAL FINDINGS: We found no difference in the prevalence of wasting among children in the 12 annually treated communities that received three mass azithromycin distributions compared to the 12 biannually treated communities that received six mass azithromycin distributions (odds ratio = 0.88, 95% confidence interval = 0.53 to 1.49). CONCLUSIONS/SIGNIFICANCE: We were unable to demonstrate a statistically significant difference in stunting, underweight, and low MUAC of pre-school children in communities randomized to annual mass azithromycin treatment or biannual mass azithromycin treatment. The role of antibiotics on child growth and nutrition remains unclear, but larger studies and longitudinal trials may help determine any association.

Importance of including borderline cases in trachoma grader certification.

We assessed trachoma grading agreement among field graders using photographs that included the complete spectrum of disease and compared it with cases where there was consensus among experienced graders. Trained photographers took photographs of children's conjunctiva during a clinical trial in Ethiopia. We calculated κ-agreement statistics using a complete set of 60 cases and then recalculated the κ using a consensus set where cases were limited to those cases with agreement among experienced graders. When the complete set of 60 cases was used, agreement was moderate (κ = 0.61, 95% confidence interval [95% CI] = 0.56-0.67). When the consensus set was used, agreement improved significantly (κ = 0.75, 95% CI = 0.68-0.80). The κ of the consensus set was higher than the complete set by 0.14 (95% CI = 0.12-0.16) (P < 0.001). If testing sets remove difficult-to-grade cases, agreement in trachoma grading may be higher than actually seen in population-based trachoma surveys.

Reliability of trachoma clinical grading--assessing grading of marginal cases.

BACKGROUND: Clinical examination of trachoma is used to justify intervention in trachoma-endemic regions. Currently, field graders are certified by determining their concordance with experienced graders using the kappa statistic. Unfortunately, trachoma grading can be highly variable and there are cases where even expert graders disagree (borderline/marginal cases). Prior work has shown that inclusion of borderline cases tends to reduce apparent agreement, as measured by kappa. Here, we confirm those results and assess performance of trainees on these borderline cases by calculating their reliability error, a measure derived from the decomposition of the Brier score. METHODS AND FINDINGS: We trained 18 field graders using 200 conjunctival photographs from a community-randomized trial in Niger and assessed inter-grader agreement using kappa as well as reliability error. Three experienced graders scored each case for the presence or absence of trachomatous inflammation-follicular (TF) and trachomatous inflammation-intense (TI). A consensus grade for each case was defined as the one given by a majority of experienced graders. We classified cases into a unanimous subset if all 3 experienced graders gave the same grade. For both TF and TI grades, the mean kappa for trainees was higher on the unanimous subset; inclusion of borderline cases reduced apparent agreement by 15.7% for TF and 12.4% for TI. When we assessed the breakdown of the reliability error, we found that our trainees tended to over-call TF grades and under-call TI grades, especially in borderline cases. CONCLUSIONS: The kappa statistic is widely used for certifying trachoma field graders. Exclusion of borderline cases, which even experienced graders disagree on, increases apparent agreement with the kappa statistic. Graders may agree less when exposed to the full spectrum of disease. Reliability error allows for the assessment of these borderline cases and can be used to refine an individual trainee's grading.

Impact of mass azithromycin distribution on malaria parasitemia during the low-transmission season in Niger: a cluster-randomized trial.

We assessed the effect of mass azithromycin treatment on malaria parasitemia in a trachoma trial in Niger. Twenty-four study communities received treatment during the wet, high-transmission season. Twelve of the 24 communities were randomized to receive an additional treatment during the dry, low-transmission season. Outcome measurements were conducted at the community-level in children < 1-72 months of age in May-June 2011. Parasitemia was higher in the 12 once-treated communities (29.8%, 95% confidence interval [CI] = 21.5-40.0%) than in the 12 twice-treated communities (19.5%, 95% CI = 13.0-26.5%, P = 0.03). Parasite density was higher in once-treated communities (354 parasites/µL, 95% CI = 117-528 parasites/µL) than in twice-treated communities (74 parasites/µL, 95% CI = 41-202 parasites/µL, P = 0.03). Mass distribution of azithromycin reduced malaria parasitemia 4-5 months after the intervention. The results suggest that drugs with antimalaria activity can have long-lasting impacts on malaria during periods of low transmission.

The association between latrine use and trachoma: a secondary cohort analysis from a randomized clinical trial.

Latrine use has been promoted as a component of an integrated strategy for trachoma control. As part of a randomized trial in Ethiopia, 12 communities received a mass azithromycin distribution followed by a latrine promotion intervention. A random sample of children ages 0-9 years in each community was monitored longitudinally for ocular chlamydia. After latrine construction ended, those communities with a higher proportion of households using latrines were more likely to experience a reduction in the prevalence of ocular chlamydia. Specifically, for each 10% increase in latrine use, there was a 2.0% decrease (95% confidence interval = 0.2-3.9% decrease) in the community prevalence of ocular chlamydia over the subsequent year (P = 0.04).

The easiest children to reach are most likely to be infected with ocular Chlamydia trachomatis in trachoma endemic areas of Niger.

BACKGROUND: Control programs for trachoma use mass antibiotic distributions to treat ocular Chlamydia trachomatis in an effort to eliminate this disease worldwide. To determine whether children infected with ocular Chlamydia are more likely to present later for examination than those who are uninfected, we compare the order of presentation for examination of children 0-5 years, and the presence of ocular Chlamydia by PCR in 4 villages in Niger where trachoma is endemic. METHODS: We conducted a cluster-randomized, controlled trial where 48 randomly selected villages in Niger are divided into 4 study arms of different mass treatment strategies. In a substudy of the main trial, we randomly selected 1 village from each of the 4 study arms (4 total villages) and we evaluated the odds of ocular Chlamydia versus the rank order of presentation for examination and laboratory assessment before treatment was offered. FINDINGS: We found the odds of harboring ocular Chlamydia dropped by more than 70% from the first child examined to the last child examined (OR 0.27, 95% CI 0.13-0.59, P = 0.001) in the 4 randomly selected villages. We found the odds of active trachoma dropped by 80% from the first child examined to the last child examined (OR 0.20, 95% CI 0.10-0.4, P<0.0001) in the 48 villages in the main trial. INTERPRETATION: This study demonstrates that even if the WHO recommended 80% treatment coverage is not reached in certain settings, children 0-5 years with the greatest probability of ocular Chlamydia have higher odds of receiving attention because they are the first to present. These results suggest there may be diminishing returns when using scarce resources to track down the last few children in a mass treatment program. TRIAL REGISTRATION: ClinicalTrials.gov NCT00792922.

A cluster-randomized controlled trial evaluating the effects of mass azithromycin treatment on growth and nutrition in Niger.

Antimicrobials are used primarily to treat infectious disease, but they have other effects. Here, we assess anthropometry measurements in children 6-60 months in 24 communities randomized to one or two mass azithromycin distributions over a 1-year period in Niger. We compared the prevalence of wasting, low mid-upper arm circumference, stunting, and underweight in communities in the two treatment arms. We were unable to prove that there was a difference in the prevalence of wasting in the 12 communities that received one mass azithromycin distribution versus the 12 communities that received two mass azithromycin distributions (odds ratio = 0.75, 95% confidence interval = 0.46-1.23). Likewise, we were unable to detect a difference in the two treatment arms for low mid-upper arm circumference, stunting, and underweight. There may not be an association between antibiotic use and improved growth in humans, or this trial was not powerful enough to detect an association if it exists.

Community risk factors for ocular Chlamydia infection in Niger: pre-treatment results from a cluster-randomized trachoma trial.

BACKGROUND: Trachoma control programs utilize mass azithromycin distributions to treat ocular Chlamydia trachomatis as part of an effort to eliminate this disease world-wide. But it remains unclear what the community-level risk factors are for infection. METHODS: This cluster-randomized, controlled trial entered 48 randomly selected communities in a 2×2 factorial design evaluating the effect of different treatment frequencies and treatment coverage levels. A pretreatment census and examination established the prevalence of risk factors for clinical trachoma and ocular chlamydia infection including years of education of household head, distance to primary water source, presence of household latrine, and facial cleanliness (ocular discharge, nasal discharge, and presence of facial flies). Univariate and multivariate associations were tested using linear regression and Bayes model averaging. FINDINGS: There were a total of 24,536 participants (4,484 children aged 0-5 years) in 6,235 households in the study. Before treatment in May to July 2010, the community-level prevalence of active trachoma (TF or TI utilizing the World Health Organization [WHO] grading system) was 26.0% (95% CI: 21.9% to 30.0%) and the mean community-level prevalence of chlamydia infection by Amplicor PCR was 20.7% (95% CI: 16.5% to 24.9%) in children aged 0-5 years. Univariate analysis showed that nasal discharge (0.29, 95% CI: 0.04 to 0.54; P = 0.03), presence of flies on the face (0.40, 95% CI: 0.17 to 0.64; P = 0.001), and years of formal education completed by the head of household (0.07, 95% CI: 0.07 to 0.13; P = 0.03) were independent risk factors for chlamydia infection. In multivariate analysis, facial flies (0.26, 95% CI: 0.02 to 0.49; P = 0.03) and years of formal education completed by the head of household (0.06, 95% CI: 0.008 to 0.11; P = 0.02) were associated risk factors for ocular chlamydial infection. INTERPRETATION: We have found that the presence of facial flies and years of education of the head of the household are risk factors for chlamydia infection when the analysis is done at the community level. TRIAL REGISTRATION: ClinicalTrials.gov NCT00792922.

Reliability of measurements performed by community-drawn anthropometrists from rural Ethiopia.

BACKGROUND: Undernutrition is an important risk factor for childhood mortality, and remains a major problem facing many developing countries. Millennium Development Goal 1 calls for a reduction in underweight children, implemented through a variety of interventions. To adequately judge the impact of these interventions, it is important to know the reproducibility of the main indicators for undernutrition. In this study, we trained individuals from rural communities in Ethiopia in anthropometry techniques and measured intra- and inter-observer reliability. METHODS AND FINDINGS: We trained 6 individuals without prior anthropometry experience to perform weight, height, and middle upper arm circumference (MUAC) measurements. Two anthropometry teams were dispatched to 18 communities in rural Ethiopia and measurements performed on all consenting pre-school children. Anthropometry teams performed a second independent measurement on a convenience sample of children in order to assess intra-anthropometrist reliability. Both teams measured the same children in 2 villages to assess inter-anthropometrist reliability. We calculated several metrics of measurement reproducibility, including the technical error of measurement (TEM) and relative TEM. In total, anthropometry teams performed measurements on 606 pre-school children, 84 of which had repeat measurements performed by the same team, and 89 of which had measurements performed by both teams. Intra-anthropometrist TEM (and relative TEM) were 0.35 cm (0.35%) for height, 0.05 kg (0.39%) for weight, and 0.18 cm (1.27%) for MUAC. Corresponding values for inter-anthropometrist reliability were 0.67 cm (0.75%) for height, 0.09 kg (0.79%) for weight, and 0.22 kg (1.53%) for MUAC. Inter-anthropometrist measurement error was greater for smaller children than for larger children. CONCLUSION: Measurements of height and weight were more reproducible than measurements of MUAC and measurements of larger children were more reliable than those for smaller children. Community-drawn anthropometrists can provide reliable measurements that could be used to assess the impact of interventions for childhood undernutrition.

Comparison of annual versus twice-yearly mass azithromycin treatment for hyperendemic trachoma in Ethiopia: a cluster-randomised trial.

BACKGROUND: In trachoma control programmes, azithromycin is distributed to treat the strains of chlamydia that cause ocular disease. We aimed to compare the effect of annual versus twice-yearly distribution of azithromycin on infection with these strains. METHODS: We did a cluster-randomised trial in 24 subdistricts in northern Ethiopia, which we randomly assigned to receive annual or twice-yearly treatment for all residents of all ages. Random assignment was done with the RANDOM and SORT functions of Microsoft Excel. All individuals were offered their assigned treatment of a single, directly observed, oral dose of azithromycin. A 6 week course of topical 1% tetracycline ointment, applied twice daily to both eyes but not directly observed, was offered as an alternative to azithromycin in patients younger than 12 months, and in patients with self-reported pregnancy, with allergy, or who refused azithromycin. Our primary, prespecified outcome was the prevalence of ocular chlamydial infection in a random sample of children aged 0-9 years at baseline and every 6 months for a total of 42 months within sentinel villages. Our analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00322972. FINDINGS: Antibiotic coverage of children aged 1-9 years was greater than 80% (range 80·9 to 93·0) at all study visits. In the groups treated annually, the prevalence of infection in children aged 0-9 years was reduced from a mean 41·9% (95% CI 31·5 to 52·2) at baseline to 1·9% (0·3 to 3·5) at 42 months. In the groups treated twice yearly, the prevalence of infection was reduced from a mean 38·3% (29·0 to 47·6) at baseline to 3·2 % (0·0 to 6·5) at 42 months. The prevalence of ocular chlamydial infection in children aged 0-9 years in groups treated annually was not different from that of the groups treated twice yearly at 18, 30, and 42 months (pooled regression p>0·99, 95 % CI -0·06 to 0·06). The mean elimination time in the twice-yearly treatment group was 7·5 months earlier (2·3 to 17·3) than that of the annual group (p=0·10, Cox proportional hazards model). INTERPRETATION: After 42 months of treatment, the prevalence of ocular infection with chlamydia was similar in the groups treated annually and twice yearly. However, elimination of infection might have been more rapid in the groups of villages that received treatment twice yearly. FUNDING: National Institutes of Health (NEI U10 EY016214).