Activated Peripheral Blood B Cells in Rheumatoid Arthritis and Their Relationship to Anti-Tumor Necrosis Factor Treatment and Response: A Randomized Clinical Trial of the Effects of Anti-Tumor Necrosis Factor on B Cells.

OBJECTIVE: B cells can become activated in germinal center (GC) reactions in secondary lymphoid tissue and in ectopic GCs in rheumatoid arthritis (RA) synovium that may be tumor necrosis factor (TNF) and lymphotoxin (LT) dependent. This study was undertaken to characterize the peripheral B cell compartment longitudinally during anti-TNF therapy in RA. METHODS: Participants were randomized in a 2:1 ratio to receive standard dosing regimens of etanercept (n = 43) or adalimumab (n = 20) for 24 weeks. Eligible participants met the American College of Rheumatology 1987 criteria for RA, had clinically active disease (Disease Activity Score in 28 joints >4.4), and were receiving stable doses of methotrexate. The primary mechanistic end point was the change in switched memory B cell fraction from baseline to week 12 in each treatment group. RESULTS: B cell subsets remained surprisingly stable over the course of the study regardless of treatment group, with no significant change in memory B cells. Blockade of TNF and LT with etanercept compared to blockade of TNF alone with adalimumab did not translate into significant differences in clinical response. The frequencies of multiple activated B cell populations, including CD21- double-negative memory and activated naive B cells, were higher in RA nonresponders at all time points, and CD95+ activated B cell frequencies were increased in patients receiving anti-TNF treatment in the nonresponder group. In contrast, frequencies of transitional B cells-a putative regulatory subset-were lower in the nonresponders. CONCLUSION: Overall, our results support the notion that peripheral blood B cell subsets are remarkably stable in RA and not differentially impacted by dual blockade of TNF and LT with etanercept or single blockade of TNF with adalimumab. Activated B cells do associate with a less robust response.

Infant Temperament and Behavioral Problems: Analysis of High-Risk Infants in Child Welfare.

Researchers have demonstrated the association between difficult temperament in infancy and early childhood behavioral problems, but to date this has not been demonstrated in the child welfare population. This study utilized the National Survey of Child and Adolescent Well-Being (NSCAW), a nationally representative, longitudinal survey of children in the child-welfare system. The sample consisted of 1,084 infants 0-12 months old at baseline who were investigated for suspected child abuse. The researchers used longitudinal, multivariable logistic regression to examine the association between difficult temperament score in infants 0-12 months who had child welfare involvement and clinical-range Child Behavior Checklist (CBCL; Achenbach & Rescorla, 2000) score at 36-months-follow-up. Findings from this study suggest that among children with substantiated maltreatment, difficult temperament in infancy predicts early childhood behavioral problems. This relationship persists after adjusting for other risk factors, such as placement, caregiver depression, and family income. The study also discusses implications for child welfare practices.

Enteric virome of Ethiopian children participating in a clean water intervention trial.

BACKGROUND: The enteric viruses shed by different populations can be influenced by multiple factors including access to clean drinking water. We describe here the eukaryotic viral genomes in the feces of Ethiopian children participating in a clean water intervention trial. METHODOLOGY/PRINCIPAL FINDINGS: Fecal samples from 269 children with a mean age of 2.7 years were collected from 14 villages in the Amhara region of Ethiopia, half of which received a new hand-dug water well. Feces from these villages were then analyzed in 29 sample pools using viral metagenomics. A total of 127 different viruses belonging to 3 RNA and 3 DNA viral families were detected. Picornaviridae family sequence reads were the most commonly found, originating from 14 enterovirus and 6 parechovirus genotypes plus multiple members of four other picornavirus genera (cosaviruses, saliviruses, kobuviruses, and hepatoviruses). Picornaviruses with nearly identical capsid VP1 were detected in different pools reflecting recent spread of these viral strains. Next in read frequencies and positive pools were sequences from the Caliciviridae family including noroviruses GI and GII and sapoviruses. DNA viruses from multiple genera of the Parvoviridae family were detected (bocaviruses 1-4, bufavirus 3, and dependoparvoviruses), together with four species of adenoviruses and common anelloviruses shedding. RNA in the order Picornavirales and CRESS-DNA viral genomes, possibly originating from intestinal parasites or dietary sources, were also characterized. No significant difference was observed between the number of mammalian viruses shed from children from villages with and without a new water well. CONCLUSIONS: We describe an approach to estimate the efficacy of potentially virus transmission-reducing interventions and the first complete (DNA and RNA viruses) description of the enteric viromes of East African children. A wide diversity of human enteric viruses was found in both intervention and control groups. Mammalian enteric virome diversity was not reduced in children from villages with a new water well. This population-based sampling also provides a baseline of the enteric viruses present in Northern Ethiopia against which to compare future viromes.

Mass azithromycin distribution for hyperendemic trachoma following a cluster-randomized trial: A continuation study of randomly reassigned subclusters (TANA II).

BACKGROUND: The World Health Organization recommends annual mass azithromycin administration in communities with at least 10% prevalence of trachomatous inflammation-follicular (TF) in children, with further treatment depending on reassessment after 3-5 years. However, the effect of stopping mass azithromycin distribution after multiple rounds of treatment is not well understood. Here, we report the results of a cluster-randomized trial where communities that had received 4 years of treatments were then randomized to continuation or discontinuation of treatment. METHODS AND FINDINGS: In all, 48 communities with 3,938 children aged 0-9 years at baseline in northern Ethiopia had received 4 years of annual or twice yearly mass azithromycin distribution as part of the TANA I trial. We randomized these communities to either continuation or discontinuation of treatment. Individuals in the communities in the continuation arm were offered either annual or twice yearly distribution of a single directly observed dose of oral azithromycin. The primary outcome was community prevalence of ocular chlamydial infection in a random sample of children aged 0-9 years, 36 months after baseline. We also assessed the change from baseline to 36 months in ocular chlamydia prevalence within each arm. We compared 36-month ocular chlamydia prevalence in communities randomized to continuation versus discontinuation in a model adjusting for baseline ocular chlamydia prevalence. A secondary prespecified analysis assessed the rate of change over time in ocular chlamydia prevalence between arms. In the continuation arm, mean antibiotic coverage was greater than 90% at all time points. In the discontinuation arm, the mean prevalence of infection in children aged 0-9 years increased from 8.3% (95% CI 4.2% to 12.4%) at 0 months to 14.7% (95% CI 8.7% to 20.8%, P = 0.04) at 36 months. Ocular chlamydia prevalence in communities where mass azithromycin distribution was continued was 7.2% (95% CI 3.3% to 11.0%) at baseline and 6.6% (95% CI 1.1% to 12.0%, P = 0.64) at 36 months. The 36-month prevalence of ocular chlamydia was significantly lower in communities continuing treatment compared with those discontinuing treatment (P = 0.03). Limitations of the study include uncertain generalizability outside of trachoma hyperendemic regions. CONCLUSIONS: In this study, ocular chlamydia infection rebounded after 4 years of periodic mass azithromycin distribution. Continued distributions did not completely eliminate infection in all communities or meet WHO control goals, although they did prevent resurgence. TRIAL REGISTRATION: This study was prospectively registered at clinicaltrials.gov (clinicaltrials.gov NCT01202331).

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.

Impact of trichiasis surgery on daily living: A longitudinal study in Ethiopia.

Background: Trachomatous trichiasis (TT) may lead to disability, impeding productive activities, resulting in loss of income. This study was conducted to determine if trichiasis surgery improves participation in productive and leisure activities, and ability to perform activities without difficulty or assistance. Methods: We recruited 1000 adults with trichiasis (cases) and 200 comparison participants, matched to every fifth trichiasis case on age (+/- two years), sex and location. The 'Stylised Activity List' tool, developed for the World Bank Living Standard Measurement Survey, was adapted to collect data on activity in the last week (participation in activity, difficulty with activity, requirement of assistance for activity), at baseline and 12 months later. All trichiasis cases received trichiasis surgery at baseline. Random effect logistic regression was used to compare cases and comparison participants. Results: There was strong evidence that trichiasis surgery substantially improves the ability of trichiasis cases to perform all the productive and leisure activities investigated without difficulty, with large increases in processing agricultural products, 21.1% to 87.0% (p<0.0001), farming, 19.1% to 82.4% (p<0.0001), and fetching wood, 25.3% to 86.0% (p<0.0001). Similarly, there was a significant increase in the proportion of cases who could perform activities without assistance, with the largest increases in animal rearing 54.2% to 92.0% (p<0.0001) and farming 73.2% to 96.4% (p<0.0001). There was no change in the proportion of comparison participants performing activities without difficulty or assistance. The change in most of the activities in cases was independent of visual acuity improvement and recurrent TT at 12 months. One year after trichiasis surgery, the proportion of cases reporting ocular pain reduced from 98.9% to 33.7% (p<0.0001). Conclusions: Eyelid surgery for TT improves functional capabilities regardless of vision gains. These data lend strong support to the view that TT surgery improves function and contributes to improved household income and wealth.

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.

Predictors of Trachomatous Trichiasis Surgery Outcome.

PURPOSE: Unfavorable outcomes after trachomatous trichiasis (TT) surgery are undermining the global trachoma elimination effort. This analysis investigates predictors of postoperative TT (PTT), eyelid contour abnormalities (ECAs), and granuloma in the 2 most common TT surgery procedures: posterior lamellar tarsal rotation (PLTR) and bilamellar tarsal rotation (BLTR). DESIGN: Secondary data analysis from a randomized, controlled, single-masked clinical trial. PARTICIPANTS: A total of 1000 patients with TT, with lashes touching the eye or evidence of epilation, in association with tarsal conjunctival scarring. METHODS: Participants were randomly allocated and received BLTR (n = 501) or PLTR (n = 499) surgery. Disease severity at baseline, surgical incisions, sutures, and corrections were graded during and immediately after surgery. Participants were examined at 6 and 12 months by assessors masked to allocation. MAIN OUTCOME MEASURES: Predictors of PTT, ECA, and granuloma. RESULTS: Data were available for 992 (99.2%) trial participants (496 in each arm). There was strong evidence that performing more peripheral dissection with scissors in PLTR (odd ratio [OR], 0.70; 95% confidence interval [CI], 0.54-0.91; P = 0.008) and BLTR (OR, 0.83; 95% CI, 0.72-0.96; P = 0.01) independently protected against PTT. Baseline major trichiasis and mixed location lashes and immediate postoperative central undercorrection independently predicted PTT in both surgical procedures. Peripheral lashes in PLTR (OR, 5.91; 95% CI, 1.48-23.5; P = 0.01) and external central incision height ≥4 mm in BLTR (OR, 2.89; 95% CI, 1.55-5.41; P = 0.001) were independently associated with PTT. Suture interval asymmetry of >2 mm (OR, 3.18; 95% CI, 1.31-7.70; P = 0.01) in PLTR and baseline conjunctival scarring in BLTR (OR, 1.72; 95% CI, 1.06-2.81; P = 0.03) were independently associated with ECA. Older age was independently associated with ECA in both PLTR (P value for trend < 0.0001) and BLTR (P value for trend = 0.03). There was substantial intersurgeon variability in ECA rates for both PLTR (range, 19.0%-36.2%) and BLTR (range, 6.1%-28.7%) procedures. In PLTR surgery, irregular posterior lamellar incision at the center of the eyelid (OR, 6.72; 95% CI, 1.55-29.04; P = 0.01) and ECA (OR, 3.08; 95% CI, 1.37-6.94; P = 0.007) resulted in granuloma formation. CONCLUSIONS: Poor postoperative outcomes in TT surgery were associated with inadequate peripheral dissection, irregular incision, asymmetric suture position and tension, inadequate correction, and lash location. Addressing these will improve TT surgical outcomes.

Epidemiology of Soil-Transmitted Helminth and Intestinal Protozoan Infections in Preschool-Aged Children in the Amhara Region of Ethiopia.

AbstractIntestinal parasites are important contributors to global morbidity and mortality and are the second most common cause of outpatient morbidity in Ethiopia. This cross-sectional survey describes the prevalence of soil-transmitted helminths and intestinal protozoa in preschool children 0-5 years of age in seven communities in the Amhara region of Ethiopia, and investigates associations between infection, household water and sanitation characteristics, and child growth. Stool samples were collected from children 0-5 years of age, 1 g of sample was preserved in sodium acetate-acetic acid-formalin, and examined for intestinal helminth eggs and protozoa cysts ether-concentration method. A total of 212 samples were collected from 255 randomly selected children. The prevalence of Ascaris lumbricoides, Trichuris trichiura, and hookworm were 10.8% (95% confidence interval [CI] 6.6-15.1), 1.4% (95% CI = 0-3.0), and 0% (95% CI = 0-1.7), respectively. The prevalence of the pathogenic intestinal protozoa Giardia lamblia and Entamoeba histolytica/dispar were 10.4% (95% CI = 6.2-14.6) and 3.3% (95% CI = 0.09-5.7), respectively. Children with A. lumbricoides infections had lower height-for-age z-scores compared with those without, but were not more likely to have stunting. Compared with those without G. lamblia, children with G. lamblia infections had lower weight-for-age and weight-for-height z-scores and were more than five times as likely to meet the z-score definition for wasting (prevalence ratio = 5.42, 95% CI = 2.97-9.89). This article adds to a growing body of research on child growth and intestinal parasitic infections and has implications for their treatment and prevention in preschool-aged children.

Is Using a Latrine "A Strange Thing To Do"? A Mixed-Methods Study of Sanitation Preference and Behaviors in Rural Ethiopia.

Latrines are the most basic form of improved sanitation and are a common public health intervention. Understanding motivations for building and using latrines can help develop effective, sustainable latrine promotion programs. We conducted a mixed-methods study of latrine use in the Amhara region of Ethiopia. We held 15 focus group discussions and surveyed 278 households in five communities. We used the Integrated Behavioral Model for Water, Sanitation, and Hygiene interventions to guide our qualitative analysis. Seventy-one percent of households had a latrine, but coverage varied greatly across communities. Higher household income was not associated with latrine use (odds ratio [OR] = 1.9; 95% confidence interval [CI] = 0.5, 7.7); similarly, cost and availability of materials were not discussed as barriers to latrine use in the focus groups. Male-headed households were more likely to use latrines than households with female heads (OR = 3.5; 95% CI = 1.6, 7.7), and households with children in school were more likely to use latrines than households without children in school (OR = 2.3; 95% CI = 1.6, 3.3). These quantitative findings were confirmed in focus groups, where participants discussed how children relay health messages from school. Participants discussed how women prefer not to use latrines, often finding them strange or even scary. These findings are useful for public health implementation; they imply that community-level drivers are important predictors of household latrine use and that cost is not a significant barrier. These findings confirm that school-aged children may be effective conduits of health messages and suggest that latrines can be better marketed and designed for women.

'If an Eye Is Washed Properly, It Means It Would See Clearly': A Mixed Methods Study of Face Washing Knowledge, Attitudes, and Behaviors in Rural Ethiopia.

BACKGROUND: Face cleanliness is a core component of the SAFE (Surgery, Antibiotics, Facial cleanliness, and Environmental improvements) strategy for trachoma control. Understanding knowledge, attitudes, and behaviors related to face washing may be helpful for designing effective interventions for improving facial cleanliness. METHODS: In April 2014, a mixed methods study including focus groups and a quantitative cross-sectional study was conducted in the East Gojjam zone of the Amhara region of Ethiopia. Participants were asked about face washing practices, motivations for face washing, use of soap (which may reduce bacterial load), and fly control strategies. RESULTS: Overall, both knowledge and reported practice of face washing was high. Participants reported they knew that washing their own face and their children's faces daily was important for hygiene and infection control. Although participants reported high knowledge of the importance of soap for face washing, quantitative data revealed strong variations by community in the use of soap for face washing, ranging from 4.4% to 82.2% of households reporting using soap for face washing. Cost and forgetfulness were cited as barriers to the use of soap for face washing. Keeping flies from landing on children was a commonly cited motivator for regular face washing, as was trachoma prevention. CONCLUSIONS: Interventions aiming to improve facial cleanliness for trachoma prevention should focus on habit formation (to address forgetfulness) and address barriers to the use of soap, such as reducing cost. Interventions that focus solely on improving knowledge may not be effective for changing face-washing behaviors.

Impact of Trichiasis Surgery on Quality of Life: A Longitudinal Study in Ethiopia.

BACKGROUND: Trachomatous trichiasis significantly reduces vision and health related quality of life (QoL). Although trichiasis surgery is widely performed to treat trichiasis, there is little data on the effect of surgery on QoL. We measured the impact of trichiasis surgery on vision and health related QoL in a longitudinal study from Amhara Region, Ethiopia. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 1000 adult participants with trichiasis (cases) and 200 comparison participants, matched to every fifth trichiasis case on age (+/- two years), sex and location. Vision-related quality of life (VRQoL) and health-related quality of life (HRQoL) were measured using the WHO/PBD-VF20 and WHOQOL-BREF questionnaires respectively, at enrolment and 12 months after enrolment. All trichiasis cases received free standard trichiasis surgery immediately after enrolment. The mean difference in QoL scores between enrolment and follow-up for cases and comparison participants, and the difference-in-differences by baseline trichiasis status was analysed using random effects linear regression, the later adjusted for age, sex and socioeconomic status. At 12-months follow-up, data was collected from 980 (98%) and 198 (98%) trichiasis cases and comparison participants respectively. At this follow-up visit, VRQoL and HRQoL scores of trichiasis cases improved substantially in all subscales and domains by 19.1-42.0 points (p<0.0001) and 4.7-17.2 points (p<0.0001), respectively. In contrast, among the comparison participants, there was no evidence of improvement in VRQoL and HRQoL domain scores during follow-up. The improvement in VRQoL and HRQoL in cases was independent of the presence of visual acuity improvement at 12 months. CONCLUSIONS/SIGNIFICANCE: Trichiasis surgery substantially improves both VRQoL and HRQoL regardless of visual acuity change. Unprecedented effort is needed to scale-up trichiasis surgical programmes not only to prevent the risk of sight loss but also to improve overall wellbeing and health perception of affected individuals.

Posterior lamellar versus bilamellar tarsal rotation surgery for trachomatous trichiasis in Ethiopia: a randomised controlled trial.

BACKGROUND: Eyelid surgery is done to correct trachomatous trichiasis to prevent blindness. However, recurrent trichiasis is frequent. Two procedures are recommended by WHO and are in routine practice: bilamellar tarsal rotation (BLTR) and posterior lamellar tarsal rotation (PLTR). This study was done to identify which procedure gives the better results. METHODS: A randomised, controlled, single masked clinical trial was done in Ethiopia. Participants had upper lid trachomatous trichiasis with one or more eyelashes touching the eye or evidence of epilation, in association with tarsal conjunctival scarring. Exclusion criteria were age less than 18 years, recurrent trichiasis after previous surgery, hypertension, and pregnancy. Participants were randomly assigned (1:1) to either BLTR or PLTR surgery, stratified by surgeon. The sequences were computer-generated by an independent statistician. Surgery was done in a community setting following WHO guidelines. Participants were examined at 6 months and 12 months by assessors masked to allocation. The primary outcome was the cumulative proportion of individuals who developed recurrent trichiasis by 12 months. Primary analyses were by modified intention to treat. The intervention effect was estimated by logistic regression, controlled for surgeon as a fixed effect in the model. The trial is registered with the Pan African Clinical Trials Registry (number PACTR201401000743135). FINDINGS: 1000 participants with trichiasis were recruited, randomly assigned, and treated (501 in the BLTR group and 499 in the PLTR group) between Feb 13, 2014, and May 31, 2014. Eight participants were not seen at either 6 month or 12 month follow-up visits and were excluded from the analysis: three from the PLTR group and five from the BLTR group. The follow-up rate at 12 months was 98%. Cumulative recurrent trichiasis by 12 months was more frequent in the BLTR group than in the PLTR group (110/496 [22%] vs 63/496 [13%]; adjusted odds ratio [OR] 1·96 [95% CI 1·40-2·75]; p=0·0001), with a risk difference of 9·50% (95% CI 4·79-14·16). INTERPRETATION: PLTR surgery was superior to BLTR surgery for management of trachomatous trichiasis, and could be the preferred procedure for the programmatic management of trachomatous trichiasis. FUNDING: The Wellcome Trust.

The Impact of Trachomatous Trichiasis on Quality of Life: A Case Control Study.

BACKGROUND: Trachomatous trichiasis is thought to have a profound effect on quality of life (QoL), however, there is little research in this area. We measured vision and health-related QoL in a case-control study in Amhara Region, Ethiopia. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 1000 adult trichiasis cases and 200 trichiasis-free controls, matched to every fifth trichiasis case on age (+/- two years), sex and location. Vision-related quality of life (VRQoL) and health-related quality of life (HRQoL) were measured using the WHO/PBD-VF20 and WHOQOL-BREF questionnaires. Comparisons were made using linear regression adjusted for age, sex and socioeconomic status. Trichiasis cases had substantially lower VRQoL than controls on all subscales (overall eyesight, visual symptom, general functioning and psychosocial, p<0.0001), even in the sub-group with normal vision (p<0.0001). Lower VRQoL scores in cases were associated with longer trichiasis duration, central corneal opacity, visual impairment and poor contrast sensitivity. Trichiasis cases had lower HRQoL in all domains (Physical-health, Psychological, Social, Environment, p<0.0001), lower overall QoL (mean, 34.5 v 64.6; p<0.0001) and overall health satisfaction (mean, 38.2 v 71.7; p<0.0001). This association persisted in a sub-group analysis of cases and controls with normal vision. Not having a marriage partner (p<0.0001), visual impairment (p = 0.0068), daily labouring (p<0.0001), presence of other health problems (p = 0.0018) and low self-rated wealth (p<0.0001) were independently associated with lower overall QoL scores in cases. Among cases, trichiasis caused 596 (59%) to feel embarrassed, 913 (91.3%) to worry they may lose their remaining eyesight and 681 (68.1%) to have sleep disturbance. CONCLUSIONS/SIGNIFICANCE: Trachomatous trichiasis substantially reduces vision and health related QoL and is disabling, even without visual impairment. Prompt trichiasis intervention is needed both to prevent vision loss and to alleviate physical and psychological suffering, social exclusion and improve overall well-being. Implementation of the full SAFE strategy is needed to prevent the development of trachomatous trichiasis.

Trachoma and Relative Poverty: A Case-Control Study.

BACKGROUND: Trachoma is widely considered a disease of poverty. Although there are many epidemiological studies linking trachoma to factors normally associated with poverty, formal quantitative data linking trachoma to household economic poverty within endemic communities is very limited. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred people with trachomatous trichiasis were recruited through community-based screening in Amhara Region, Ethiopia. These were individually matched by age and gender to 200 controls without trichiasis, selected randomly from the same sub-village as the case. Household economic poverty was measured through (a) A broad set of asset-based wealth indicators and relative household economic poverty determined by principal component analysis (PCA, (b) Self-rated wealth, and (c) Peer-rated wealth. Activity participation data were collected using a modified 'Stylised Activity List' developed for the World Bank's Living Standards Measurement Survey. Trichiasis cases were more likely to belong to poorer households by all measures: asset-based analysis (OR = 2.79; 95%CI: 2.06-3.78; p<0.0001), self-rated wealth (OR, 4.41, 95%CI, 2.75-7.07; p<0.0001) and peer-rated wealth (OR, 8.22, 95% CI, 4.59-14.72; p<0.0001). Cases had less access to latrines (57% v 76.5%, p = <0.0001) and higher person-to-room density (4.0 v 3.31; P = 0.0204) than the controls. Compared to controls, cases were significantly less likely to participate in economically productive activities regardless of visual impairment and other health problems, more likely to report difficulty in performing activities and more likely to receive assistance in performing productive activities. CONCLUSIONS/SIGNIFICANCE: This study demonstrated a strong association between trachomatous trichiasis and relative poverty, suggesting a bidirectional causative relationship possibly may exist between poverty and trachoma. Implementation of the full SAFE strategy in the context of general improvements might lead to a virtuous cycle of improving health and wealth. Trachoma is a good proxy of inequality within communities and it could be used to target and evaluate interventions for health and poverty alleviation.

Pathogenesis of progressive scarring trachoma in Ethiopia and Tanzania and its implications for disease control: two cohort studies.

BACKGROUND: Trachoma causes blindness through a conjunctival scarring process initiated by ocular Chlamydia trachomatis infection; however, the rates, drivers and pathophysiological determinants are poorly understood. We investigated progressive scarring and its relationship to conjunctival infection, inflammation and transcript levels of cytokines and fibrogenic factors. METHODOLOGY/PRINCIPAL FINDINGS: We recruited two cohorts, one each in Ethiopia and Tanzania, of individuals with established trachomatous conjunctival scarring. They were followed six-monthly for two years, with clinical examinations and conjunctival swab sample collection. Progressive scarring cases were identified by comparing baseline and two-year photographs, and compared to individuals without progression. Samples were tested for C. trachomatis by PCR and transcript levels of S100A7, IL1B, IL13, IL17A, CXCL5, CTGF, SPARCL1, CEACAM5, MMP7, MMP9 and CD83 were estimated by quantitative RT-PCR. Progressive scarring was found in 135/585 (23.1%) of Ethiopian participants and 173/577 (30.0%) of Tanzanian participants. There was a strong relationship between progressive scarring and increasing inflammatory episodes (Ethiopia: OR 5.93, 95%CI 3.31-10.6, p<0.0001. Tanzania: OR 5.76, 95%CI 2.60-12.7, p<0.0001). No episodes of C. trachomatis infection were detected in the Ethiopian cohort and only 5 episodes in the Tanzanian cohort. Clinical inflammation, but not scarring progression, was associated with increased expression of S100A7, IL1B, IL17A, CXCL5, CTGF, CEACAM5, MMP7, CD83 and reduced SPARCL1. CONCLUSIONS/SIGNIFICANCE: Scarring progressed in the absence of detectable C. trachomatis, which raises uncertainty about the primary drivers of late-stage trachoma. Chronic conjunctival inflammation appears to be central and is associated with enriched expression of pro-inflammatory factors and altered expression of extracellular matrix regulators. Host determinants of scarring progression appear more complex and subtle than the features of inflammation. Overall this indicates a potential role for anti-inflammatory interventions to interrupt progression and the need for trichiasis disease surveillance and surgery long after chlamydial infection has been controlled at community level.

The Contributions of Onchocerciasis Control and Elimination Programs toward the Achievement of the Millennium Development Goals.

In 2000, 189 member states of the United Nations (UN) developed a plan for peace and development, which resulted in eight actionable goals known as the Millennium Development Goals (MDGs). Since their inception, the MDGs have been considered the international standard for measuring development progress and have provided a blueprint for global health policy and programming. However, emphasis upon the achievement of priority benchmarks around the "big three" diseases--namely HIV, tuberculosis (TB), and malaria--has influenced global health entities to disproportionately allocate resources. Meanwhile, several tropical diseases that almost exclusively impact the poorest of the poor continue to be neglected, despite the existence of cost-effective and feasible methods of control or elimination. One such Neglected Tropical Disease (NTD), onchocerciasis, more commonly known as river blindness, is a debilitating and stigmatizing disease primarily affecting individuals living in remote and impoverished areas. Onchocerciasis control is considered to be one of the most successful and cost-effective public health campaigns ever launched. In addition to improving the health and well-being of millions of individuals, these programs also lead to improvements in education, agricultural production, and economic development in affected communities. Perhaps most pertinent to the global health community, though, is the demonstrated effectiveness of facilitating community engagement by allowing communities considerable ownership with regard to drug delivery. This paper reviews the contributions that such concentrated efforts to control and eliminate onchocerciasis make to achieving select MDGs. The authors hope to draw the attention of public policymakers and global health funders to the importance of the struggle against onchocerciasis as a model for community-directed interventions to advance health and development, and to advocate for NTDs inclusion in the post 2015 agenda.

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

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