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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.To determine the efficacy of mass azithromycin distributions to preschool-aged children as a strategy for trachoma elimination in areas with hypoendemic disease.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.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.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.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).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.ClinicalTrials.gov Identifier: NCT02048007.

Recent evidence indicates mass drug administration with azithromycin may reduce child mortality. This study uses verbal autopsy (VA) to investigate the causes of individual deaths during the Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial in Malawi. Cluster randomization was performed as part of MORDOR. Biannual household visits were conducted to distribute azithromycin or placebo to children aged 1–59 months and update the census to identify deaths for VA. MORDOR was not powered to investigate mortality effects at individual sites, but the available evidence is presented here for hypothesis generation regarding the mechanism through which azithromycin may reduce child mortality. Automated VA analysis was performed to infer the likely cause of death using two major analysis programs, InterVA and SmartVA. A total of 334 communities were randomized to azithromycin or placebo, with more than 130,000 person-years of follow-up. During the study, there were 1,184 deaths, of which 1,131 were followed up with VA. Mortality was 9% lower in azithromycin-treated communities than in placebo communities (rate ratio 0.91 [95% CI: 0.79–1.05]; P = 0.20). The intention-to-treat analysis by cause using InterVA suggested fewer HIV/AIDS deaths in azithromycin-treated communities (rate ratio 0.70 [95% CI: 0.50–0.97]; P = 0.03) and fewer pneumonia deaths (rate ratio 0.82 [95% CI: 0.60–1.12]; P = 0.22). The use of the SmartVA algorithm suggested fewer diarrhea deaths (rate ratio 0.71 [95% CI: 0.51–1.00]; P = 0.05) and fewer pneumonia deaths (rate ratio 0.58 [95% CI: 0.33–1.00]; P = 0.05). Although this study is not able to provide strong evidence, the data suggest that the mortality reduction during MORDOR in Malawi may have been due to effects on pneumonia and diarrhea or HIV/AIDS mortality.

The recent Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial reported a reduction in child mortality following biannual azithromycin mass drug administration (MDA). Here, we investigate the financial costs and cost-effectiveness from the health provider perspective of azithromycin MDA at the MORDOR-Malawi study site. During MORDOR, a cluster-randomized trial involving biannual azithromycin MDA or placebo to children aged 1–59 months, fieldwork-related costs were collected, including personnel, transport, consumables, overheads, training, and supervision. Mortality rates in azithromycin- and placebo-treated clusters were calculated overall and for the five health zones of Mangochi district. These were used to estimate the number needed to treat to avert one death and the costs per death and disability-adjusted life year (DALY) averted. The cost per dose of MDA was $0.74 overall, varying between $0.63 and $0.94 in the five zones. Overall, the number needed to treat to avert one death was 1,213 children; the cost per death averted was $898.47, and the cost per DALY averted was $9.98. In the three zones where mortality was lower in azithromycin-treated clusters, the number needed to treat to avert one death, cost per death averted, and cost per DALY averted, respectively, were as follows: 3,070, $2,899.24, and $32.31 in Monkey Bay zone; 1,530, $1,214.42, and $13.49 in Chilipa zone; and 344, $217.98, and $2.42 in Namwera zone. This study is a preliminary cost-effectiveness analysis that indicates azithromycin MDA for reducing child mortality has the potential to be highly cost-effective in some settings in Malawi, but the reasons for geographical variation in effectiveness require further investigation.

Reductions in malaria morbidity have been reported following azithromycin mass drug administration (MDA) for trachoma. The recent Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) trial reported a reduction in child mortality following biannual azithromycin MDA. Here, we investigate the effects of azithromycin MDA on malaria at the MORDOR-Malawi study site. A cluster-randomized double-blind placebo-controlled trial, with 15 clusters per arm, was conducted. House-to-house census was updated biannually, and azithromycin or placebo syrup was distributed to children aged 1–59 months for a total of four biannual distributions. At baseline, 12-month, and 24-month follow-up visits, a random sample of 1,200 children was assessed for malaria with thick and thin blood smears and hemoglobin measurement. In the community-level analysis, there was no difference in the prevalence of parasitemia (1.0% lower in azithromycin-treated communities; 95% CI: −8.2 to 6.1), gametocytemia (0.7% lower in azithromycin-treated communities; 95% CI: −2.8 to 1.5), or anemia (1.7% lower in azithromycin-treated communities; 95% CI: −8.1 to 4.6) between placebo and azithromycin communities. Further interrogation of the data at the individual level, both per-protocol (including only those who received treatment 6 months previously) and by intention-to-treat, did not identify differences in parasitemia between treatment arms. In contrast to several previous reports, this study did not show an effect of azithromycin MDA on malaria parasitemia at the community or individual levels.

Background Gastrointestinal illness is a major cause of morbidity in travellers and is a common reason for presentation to healthcare services on return. Whilst the aetiology of imported gastrointestinal disease is predominantly infectious, outcomes are variable due to a range of phenomena such as post-infectious irritable bowel syndrome, drug resistance and occult pathology (both infectious and non-infectious). Previous studies have focussed on predictors of aetiology of gastrointestinal disease in travellers; we present a retrospective study combining both aetiological and early outcome data in a large cohort of returned travellers. Method We identified 1450 patients who attended our post-travel walk-in clinic with gastrointestinal symptoms between 2010 and 2016. Demographic, travel, clinical and laboratory data was collected through case note review. Logistic regression analysis to examine correlates of aetiology and outcome were performed in R (CRAN Project 2017). Results Of 1450 patients in our cohort 153 reported bloody diarrhoea and 1081 (74.6%) reported non-bloody diarrhoea. A definitive microbiological diagnosis was made in 310 (20.8%) of which 137 (9.4%) had a parasite identified and 111 (7.7%) had a bacterial cause identified. Factors associated with a parasitological diagnosis included history of travel to South Asia (aOR = 2.55; 95%CI 1.75–3.70, p p p p p 5iu/dL (aOR = 4.68; 95%CI 2.91–7.72, p p p p Conclusions In a cohort of returned travellers, we were able to identify multiple factors that are correlated with both aetiology and outcome of imported gastrointestinal syndromes. We predict these data will be valuable in the development of diagnostic and therapeutic pathways for patients with imported gastrointestinal infections.

Background In 2009 Ghana began to design a trachoma pre-validation surveillance plan, based on then-current WHO recommendations. The plan aimed to identify active trachoma resurgence and identify and manage trichiasis cases, through both active and passive surveillance approaches. This paper outlines and reviews the adaptations made by Ghana between 2011 and 2016. The assessment will provide a learning opportunity for a number of countries as they progress towards elimination status. Methods A mixed methods approach was taken, comprising in-depth interviews and documents review. Between January and April 2016, 20 in-depth interviews were conducted with persons involved in the operationalisation of the trachoma surveillance system from across all levels of the health system. A three-tier thematic coding framework was developed using a primarily inductive approach but also allowed for a more iterative approach, which drew on aspects of grounded theory. Results During the operationalisation of the Ghana surveillance plan there were a number of adaptations (as compared to the WHO recommendations), these included: (i) Inclusion of surveillance of active trachoma in the passive surveillance approach, as compared to trichiasis alone. Issues with case identification, challenges in implementation coverage and a non-specific reporting structure hampered effectiveness; (ii) Random selection and increase in number of sites selected for the active surveillance component. This likely lacked the spatiotemporal power to be able to identify recrudescence in a timely manner; (iii) Targeted trichiasis door-to-door case searches, led by ophthalmic nurses. An effective methodology to identify trichiasis cases but resource intensive; (iv) A buddy system between ophthalmic nurses to support technical skills in an elimination setting where it is difficult to attain diagnostic and surgical skills, due to a lack of cases. The strategy did not take into account the loss of proficiency within experienced personnel. Conclusions Ghana developed a comprehensive surveillance system that exceeded the WHO recommendations but issues with sensitivity and specificity likely led to an inefficient use of resources. Improved targeted surveillance strategies for identification of recrudescence and trichiasis case searches, need to be evaluated. Strategies must address the contextual changes that arise because of transmission decline, such as loss of surgical skills. Electronic supplementary material The online version of this article (10.1186/s40249-019-0585-x) contains supplementary material, which is available to authorized users.

Purpose: The prevalence of trichiasis is higher in females and increases markedly with age. Surveys carried out in the daytime, particularly in developing countries, are prone to find older individuals and females at home at the time of the survey. Population-level trichiasis estimates should adjust sample proportions to reflect the demographic breakdown of the population, although the most accurate method of doing this is unclear. Methods: Having obtained data from 162 surveys carried out in Ethiopia as part of the Global Trachoma Mapping Project from 2012 to 2015, we used internal validation with both Brier and Logarithmic forecast scoring to test stratification models to identify those models with the highest predictive accuracy. Selection of partitions was undertaken by both simple random sampling (SRS) and cluster sampling (CS) over 8192 selections. Results: A total of 4529 (1.9%) cases of trichiasis were identified from 241,139 individuals aged ≥15 years from a total of 4210 kebeles and 122,090 households visited. Overall, the binning method using 5-year bands from age 15 to 69 years, with coarser binning in 20-year age-bands above this age, provided the best predictive accuracy, in both SRS and CS methodologies and for both the Brier and Logarithmic scoring rules. Conclusion: The greatest predictive accuracy for trichiasis estimates was found by adjusting for sex and in 5-year age-bands from the age of 15 to 69 years and in 20-year age-bands in those aged 70 years and greater. Trichiasis surveys attempting to make population-level inferences should use this method to optimise surgery backlog estimates.

Background The World Health Organization-recommended strategy for trachoma elimination as a public health problem is known by the acronym “SAFE”, where “F” stands for facial cleanliness to reduce transmission of ocular Chlamydia trachomatis infection. Accurately and reliably measuring facial cleanliness is problematic. Various indicators for measuring an unclean face exist, however, the accuracy and reliability of these indicators is questionable and their relationship to face washing practices is poorly described. Methods Clean face indicator (ocular or nasal discharge, flies on the face, and dirt on the face), trachoma clinical sign, and ocular C. trachomatis infection data were collected for 1613 children aged 0–9 years in 12 Senegalese villages as part of a cross-sectional trachoma prevalence study. Time of examination was recorded to the nearest half hour. A risk factor questionnaire containing Water, Sanitation and Hygiene (WASH) questions was administered to heads of compounds (households that shared a common doorway) and households (those who shared a common cooking pot). Results WASH access and use were high, with 1457/1613 (90.3%) children living in households with access to a primary water source within 30 min. Despite it being reported that 1610/1613 (99.8%) children had their face washed at awakening, > 75% (37/47) of children had at least one unclean face indicator at the first examination time-slot of the day. The proportion of children with facial cleanliness indicators differed depending on the time the child was examined. Dirt on the face was more common, and ocular discharge less common, in children examined after 11:00 h than in children examined at 10:30 h and 11:00 h. Conclusions Given the high reported WASH access and use, the proportion of children with an unclean face indicator should have been low at the beginning of the day. This was not observed, explained either by: the facial indicators not being reliable measures of face washing; eye discharge, nose discharge or dirt rapidly re-accumulated after face washing in children in this population at the time of fieldwork; and/or responder bias to the risk factor questionnaire. A high proportion of children had unclean face indicators throughout the day, with certain indicators varying by time of day. A reliable, standardised, practical measure of face washing is needed, that reflects hygiene behaviour rather than environmental or cultural factors. Graphical Abstract

Summary Background The Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) trial found that biannual mass distribution of azithromycin to children younger than 5 years in Niger reduced the primary outcome of all-cause mortality by 18%. We aimed to determine the causes of mortality among deceased children using verbal autopsy. Methods In this 2-year cluster-randomised controlled trial, 594 community clusters in Niger were randomly allocated (1:1 ratio) to receive biannual mass distributions of either oral azithromycin (approximately 20 mg per kg of bodyweight) or placebo targeted to children aged 1–59 months. Participants, study investigators, and field workers were masked to treatment allocation. Between Nov 23, 2014, and July 31, 2017, 3615 child deaths were recorded by use of biannual house-to-house censuses, and verbal autopsies were done between May 26, 2015, and May 17, 2018, to identify cause of death. Cause-specific mortality, as assessed by verbal autopsy, was a prespecified secondary outcome. This trial is completed and is registered with ClinicalTrials.gov , NCT02047981 . Findings Between Nov 23, 2014, and July 31, 2017, 303 communities (n=40 375 children at baseline) in Niger received mass azithromycin and 291 communities (n=35 747 children at baseline) received placebo. Treatment coverage was 90·3% (SD 10·6) in the azithromycin group and 90·4% (10·1) in the placebo group. No communities were lost to follow-up. In total, 1727 child deaths in the azithromycin group and 1888 child deaths in the placebo group were reported from the population censuses. Of these, the cause of death for 1566 (90·7%) children in the azithromycin group and 1735 (91·9%) children in the placebo group were ascertained by verbal autopsy interviews. In the azithromycin group, 437 (27·9%) deaths were due to malaria, 252 (16·1%) deaths were due to pneumonia, and 234 (14·9%) deaths were due to diarrhoea. In the placebo group, 493 (28·4%) deaths were due to malaria, 275 (15·9%) deaths were due to pneumonia, and 251 (14·5%) deaths were due to diarrhoea. Relative to communities that received placebo, child mortality in communities that received azithromycin was lower for malaria (incidence rate ratio 0·78, 95% CI 0·66–0·92; p=0·0029), dysentery (0·65, 0·44–0·94; p=0·025), meningitis (0·67, 0·46–0·97; p=0·036), and pneumonia (0·83, 0·68–1·00; p=0·051). The distribution of causes of death did not differ significantly between the two study groups (p=0·98). Interpretation Mass azithromycin distribution resulted in approximately a third fewer deaths in children aged 1–59 months due to meningitis and dysentery, and a fifth fewer deaths due to malaria and pneumonia. The lack of difference in the distribution of causes of death between the azithromycin and placebo groups could be attributable to the broad spectrum of azithromycin activity and the study setting, in which most childhood deaths were due to infections. Funding Bill & Melinda Gates Foundation.

BACKGROUND: Mass distributions of azithromycin for trachoma have been associated with secondary benefits, including reductions in child mortality. METHODS: In the Partnership for the Rapid Elimination of Trachoma cluster-randomized trial in Niger, 24 communities were randomized to annual treatment of everyone and 24 communities were randomized to biannual treatment of children under 12 for 3 years (clinicaltrials.gov, NCT00792922). Treatment was a single dose of directly observed oral azithromycin (20 mg/kg up to 1 g in adults). Vital status was assessed during annual census and monitoring visits. In this prespecified secondary analysis, we compared the mortality rate among children 6 months to less than 5 years of age by treatment arm using negative binomial regression. RESULTS: Among children 6 months to less than 5 years of age, 404 deaths occurred during the study period. The mortality rate was 35.6 deaths per 1000 person-years (231 deaths, 95% CI: 30.9-40.9) in the annual arm and 29.0 deaths per 1000 person-years (173 deaths, 95% CI: 24.8-33.8) in the biannual arm. The mortality rate ratio comparing children in the biannual arm to the annual arm was 0.81 (95% CI: 0.66-1.00, P = 0.07; primary outcome). The mortality rate ratio comparing children who died from infectious causes in the biannual arm to the annual arm was 0.73 (95% CI: 0.57-0.94; P = 0.02). No adverse events were reported. CONCLUSIONS: This secondary analysis of a cluster-randomized trial found a nonsignificant 19% decrease in mortality among children 6 months to less than 5 years of age who received biannual azithromycin compared with children who received annual azithromycin. This study was conducted in a high mortality, trachoma-endemic area; thus, results may be specific to this environment only. In addition, the trial was neither designed nor powered to detect a mortality effect, and we cannot rule out the possibility that mortality differences resulted from bias.

Introduction To date, eleven countries have been validated as having eliminated trachoma as a public health problem, including Ghana in 2018. Surveillance for recrudescence is needed both pre- and post-validation but evidence-based guidance on appropriate strategies is lacking. We explored two potential surveillance strategies in Ghana. Methodology/principal findings Amongst randomly-selected communities enrolled in pre-validation on-going surveillance between 2011 and 2015, eight were identified as having had trachomatous-inflammation follicular (TF) prevalence ≥5% in children aged 1–9 years between 2012 and 2014. These eight were re-visited in 2015 and 2016 and neighbouring communities were also added (“TF trigger” investigations). Resident children aged 1–9 years were then examined for trachoma and had a conjunctival swab to test for Chlamydia trachomatis (Ct) and a dried blood spot (DBS) taken to test for anti-Pgp3 antibodies. These investigations identified at least one community with evidence of probable recent Ct ocular transmission. However, the approach likely lacks sufficient spatio-temporal power to be reliable. A post-validation surveillance strategy was also evaluated, this reviewed the ocular Ct infection and anti-Pgp3 seroprevalence data from the TF trigger investigations and from the pre-validation surveillance surveys in 2015 and 2016. Three communities identified as having ocular Ct infection >0% and anti-Pgp3 seroprevalence ≥15.0% were identified, and along with three linked communities, were followed-up as part of the surveillance strategy. An additional three communities with a seroprevalence ≥25.0% but no Ct infection were also followed up (“antibody and infection trigger” investigations). DBS were taken from all residents aged ≥1 year and ocular swabs from all children aged 1–9 years. There was evidence of transmission in the group of communities visited in one district (Zabzugu-Tatale). There was no or little evidence of continued transmission in other districts, suggesting previous infection identified was transient or potentially not true ocular Ct infection. Conclusions/significance There is evidence of heterogeneity in Ct transmission dynamics in northern Ghana, even 10 years after wide-scale MDA has stopped. There is added value in monitoring Ct infection and anti-Ct antibodies, using these indicators to interrogate past or present surveillance strategies. This can result in a deeper understanding of transmission dynamics and inform new post-validation surveillance strategies. Opportunities should be explored for integrating PCR and serological-based markers into surveys conducted in trachoma elimination settings., Author summary The goal for trachoma programmes is elimination of trachoma as a public health problem. This means that ongoing low-level eye-to-eye transmission of the causative bacterium, Chlamydia trachomatis (Ct), is acceptable. Countries need to implement a suitable surveillance system to identify any return to higher transmission levels. The best methodology for doing this is not known. We first explored the approach used by Ghana in its standard programme, which involved monitoring a limited number of randomly selected communities for evidence of active (inflammatory) trachoma visible in children’s eyes on examination by trained observers. Although this strategy led to identification of at least one community that had probably had recent Ct transmission, the approach is unlikely to consistently identify places where return to higher levels of transmission is a risk. We also explored using information on infection (detected in eye swabs) and antibodies to Ct (detected in the blood) to identify communities at risk. We found evidence of both persistent eye-to-eye Ct transmission and areas where infection was transient and has now gone away. We conclude that the use of infection and antibody data for surveillance of trachoma appears promising.

© 2017 The Author(s). The frequency and duration of Chlamydia trachomatis (Ct) ocular infections decrease with age, suggesting development of partial immunity. However, there is a lack of clear correlates of immunity to Ct infection in humans. We screened sera from a cohort of Gambian children followed for six-months against a Ct-proteome microarray. At genome sequence level, we detected signatures of selection from a population of ocular Ct isolates from Guinea-Bissau. Together these approaches allowed us to highlight the focus of humoral responses and hypothesise new modes of pathogen immune evasion. Children who were susceptible to frequent and/or prolonged Ct infection had a less focussed antibody response, including preferential recognition of forty-two antigens. There was evidence of positive and purifying selection across the genome, but little balancing selection. In contrast, most antigens that were associated with susceptibility were under neutral selection. These data suggest an evasion strategy in which Ct presents a large panel of irrelevant antigens to the immune system to block or misdirect protective responses. Development of a focused immune response, possibly induced through vaccination, may be an effective strategy to promote protection to Ct infection.

Background Helminthic and protozoan infections are common, particularly in low- or middle-income countries. Although an association between parasite carriage and markers of poor growth have been shown in some studies, systematic reviews have suggested only a modest impact of clearing carriage. The prevalence of these pathogens and the effect that they have on growth in preschool children has never been investigated in Malawi. Methods One hundred ninety-three children aged 0–72 months were randomly recruited from rural villages in the Mangochi district of Malawi. Formol-ether concentration was performed on stool and the samples examined with a light microscope. Anthropometric data was taken for each child and the haemoglobin measured with a point of care test. Results The mean age of the children was 2 years 4 months. Overall prevalence of intestinal parasite infection was 37.3%. Protozoa were found in 28.5% of children, while helminths were found in 8.8%. The most commonly found organisms were Giardia lambia (12.4%), Entamoeba coli (10.4%) and Hookworm species (3.6%). Stunting was seen in 47.8% of children, 12.9% were underweight and 5.0% were wasted. No significant association was found between markers of poor growth and infection with any intestinal parasite. Conclusions We found that prevalence of helminth infection was low in preschool children living in the Mangochi district compared to international standards. However a significant proportion of the preschool population are infected with protozoa, particularly Giardia lambia. In this cohort, despite a significant prevalence of stunting, helminth infection was not significantly associated with any markers of poor growth. The significance of protozoal carriage and contribution to growth restriction in this context creates further avenues for future research.

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

The putative vector of trachoma, Musca sorbens, prefers to lay its eggs on human faeces on the ground. This study sought to determine whether M. sorbens females were attracted to volatile odours from human faeces in preference to odours from the faeces of other animals, and to determine whether specific volatile semiochemicals mediate selection of the faeces. Traps baited with the faeces of humans and local domestic animals were used to catch flies at two trachoma-endemic locations in The Gambia and one in Ethiopia. At all locations, traps baited with faeces caught more female M. sorbens than control traps baited with soil, and human faeces was the most successful bait compared with soil (mean rate ratios 44.40, 61.40, 10.50 [P, Author summary Musca sorbens, also known as the Bazaar Fly, visits people’s faces to feed on ocular and nasal discharge. While feeding, M. sorbens can transmit Chlamydia trachomatis, the bacterium that causes the infectious eye disease trachoma. Around 1.9 million people worldwide are visually impaired or blind from this disease. Although it is believed that M. sorbens transmits trachoma, very few studies have looked at ways to control this fly. A large-scale trial has shown that control of fly populations with insecticide reduces active trachoma disease prevalence. Odour-baited traps for the suppression of disease vector populations are an attractive option as there is no widespread spraying of insecticide; however, highly attractive baits are critical to their success. Here, we demonstrate that the preference of these flies for breeding in human faeces is probably mediated by odour cues, and we isolate chemicals in the odour of human faeces that cause a response in the antennae of M. sorbens. These compounds may play a role in the specific attractiveness of human faeces to these flies, perhaps by being present in greater amounts or at favourable ratios. These may be developed into a chemical lure for odour-baited trapping to suppress M. sorbens populations.

Purpose: The clinical sign trachomatous inflammation - follicular (TF) is used to monitor indication for and response to mass azithromycin distribution in trachoma-endemic communities. Here, we assess the relationship between TF, trachomatous inflammation - intense (TI), and infection with ocular Chlamydia trachomatis over time during annual mass azithromycin distribution. Methods: We used data from a cluster-randomized trial of mass azithromycin distribution for trachoma control in a mesoendemic region of Niger. This study includes 24 communities that received 3 years of annual mass azithromycin distribution. TF, TI, and ocular chlamydia infection were monitored among children aged 0-5 years. We assessed the correlation between the prevalence of ocular chlamydia infection and 1) TF and 2) TI prevalence over time. Results: At baseline, ocular chlamydia prevalence was 21.2% (95% CI 14.3-28.1%), TF prevalence was 27.7% (95% CI 21.2-34.2%), and TI prevalence was 8.3% (95% CI 5.2-11.5%). The prevalence of all three measures decreased significantly over time (P < 0.001). At baseline, ocular chlamydia infection prevalence was strongly correlated with both TF (rho = 0.78, P < 0.0001) and TI (rho = 0.76, P < 0.0001). The correlation between ocular chlamydia infection and both TF and TI was weak at months 12 and 24. At 36 months, when TF prevalence had dropped below 10%, ocular chlamydia infection and TF were moderately correlated (rho = 0.70, P= 0.0002). Conclusions: Both TF and TI are good indicators of infection prevalence prior to mass azithromycin distribution. However, this relationship may be affected by repeated rounds of mass azithromycin distribution.

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

Introduction Skin diseases represent a significant public health problem in most low and middle income settings. Nevertheless, there is a relative paucity of high-quality epidemiological data on the prevalence of these conditions. Materials/Methods We conducted two cross-sectional population-based skin-surveys of children (6 months to 9 years old) in the Bijagós Archipelago of Guinea-Bissau during the dry season (February-March 2018) and the wet season (June-July 2018). Following a period of training, a nurse performed a standardised examination for communicable dermatoses for each participant. We calculated the prevalence of each skin condition and investigated demographic associations. Results 1062 children were enrolled in the dry season survey of whom 318 (29.9%) had at least one skin diseases. The most common diagnosis was tinea capitis (154/1062, 14.5% - 95% CI 12.5–16.8%) followed by tinea corporis (84/1062, 7.9% - 95% CI 6.4–9.7%), pyoderma (82/1062, 7.7% - 95% CI 6.2–9.5%) and scabies (56/1062. 5.2% - 95%CI 4.0–6.8%). 320 children were enrolled in the wet season survey of whom 121 (37.8%) had at least one skin problem. Tinea capitis remained the most common diagnosis (79/320, 24.7% - 95% CI 20.1–29.9%), followed by pyoderma (38/320, 11.9% - 95% CI 8.6–16.1%), tinea corporis (23/320, 7.2% - 95% 4.7–10.7%) and scabies (6/320, 1.9% - 95% CI 0.8–4.2%). Conclusions Our study, which utilised robust population-based cluster random sampling methodology, demonstrates the substantial disease burden caused by common communicable dermatoses in this setting. Given these findings, there is a need to consider common dermatoses as part of Universal Health Coverage to deliver ‘skin-health for all’., Author summary Skin conditions are very common in many low and middle income settings but there have been relatively few surveys of skin disease conducted using the best epidemiological approaches. We performed two cross-sectional population-based skin-surveys of children in the Bijagós Archipelago, Guinea-Bissau, using gold-standard sampling methodologies. Skin conditions were extremely common and almost 30% of children had at least one common, infectious skin condition in both surveys. Fungal skin and scalp infections were the most common conditions followed by bacterial skin infections. Our survey demonstrates that common, easily treatable skin conditions are responsible for a high burden of disease in this population. Skin-health should be considered a key component of the Universal Health Coverage agenda.

BackgroundTrachoma, a neglected tropical disease, is the leading infectious cause of blindness and visual impairment worldwide. Host responses to ocular chlamydial infection resulting in chronic inflammation and expansion of non-chlamydial bacteria are hypothesised risk factors for development of active trachoma and conjunctival scarringMethodsOcular swabs from trachoma endemic populations in The Gambia were selected from archived samples for 16S sequencing and host conjunctival gene expression. We recruited children with active trachoma and adults with conjunctival scarring, alongside corresponding matched controls.FindingsIn children, active trachoma was not associated with significant changes in the ocular microbiome.Haemophilusenrichment was associated with antimicrobial responses but not linked to active trachoma. Adults with scarring trachoma had a reduced ocular bacterial diversity compared to controls, with increased relative abundance ofCorynebacterium. Increased abundance ofCorynebacteriumin scarring disease was associated with innate immune responses to the microbiota, dominated by altered mucin expression and increased matrix adhesion.InterpretationIn the absence of currentC. trachomatisinfection, changes in the ocular microbiome associate with antimicrobial and inflammatory responses that impair epithelial cell health. In scarring trachoma, expansion of ‘non-pathogenic’ bacteria such asCorynebacteriumand innate responses are coincident, warranting further investigation of this relationship. Comparisons between active and scarring trachoma supported the relative absence of type-1 interferon responses in scarring, whilst highlighting a common suppression of re-epithelialisation with altered epithelial and bacterial adhesion, likely contributing to development of scarring pathology.

IntroductionScabies is highly endemic among impoverished populations and has been recently included in the WHO’s list of neglected tropical diseases (NTDs). Community support and behavioural changes are essential for the success of control interventions. This study aimed to explore beliefs, prevention attitudes and health care-seeking behaviours towards scabies in the Bijagós Archipelago of Guinea-Bissau.MethodsData were collected through two methods. Community key informants (community members, community health workers, healthcare workers and traditional healers) were interviewed using snowball sampling. A questionnaire covering perceptions, attitudes and practices was administered to community members using random cluster sampling. Thematic analysis of qualitative data was applied to identify themes. Descriptive statistics were used for quantitative data analysis.ResultsThere was a satisfactory awareness about scabies, but perceptions about disease causation and transmission were imprecise. Misconceptions about personal hygiene as the primary measure for scabies prevention were recurrent. Some participants recognised the importance of early treatment to interrupt transmission. Treatment of close contacts was not considered important. Costs were the main determining factor for treatment choice between traditional healer and the local health centre. Late presentation and delayed treatment were common and associated with poverty and stigmatisation. Scabies impaired quality of life by affecting social interactions, health, fitness to work and school attendance.ConclusionsThere is a need to improve education, recognition, management and affordable access to treatment. Community education, healthcare workers’ training and skin NTDs integrated control programmes should address the challenges highlighted in this study.Authors SummaryScabies is a common skin infection in low income settings. We conducted a study in Guinea-Bissau to explore the knowledge, attitudes and practices about scabies. We conducted interviews with healthcare workers, traditional healers and community members and additionally used an oral-administered questionnaire with a larger sample of community residents. Most individuals had knowledge of scabies and were aware that person to person transmission occurred. However personal and environmental hygiene were both incorrectly identified as particularly important in the transmission of scabies. Cost played a major role in determining where individuals sought care and both poverty and disease associated stigma resulted in delays seeking care. There is a need to improve community and health care worker education about scabies and improve affordable access to treatment.

The complex relationship between malnutrition and malaria affects morbidity and mortality in children younger than 5 years, particularly in parts of sub-Saharan Africa where these conditions occur together seasonally. Previous research on this relationship has been inconclusive. Here, we examine the association between anthropometric indicators and malaria infection in a population-based sample of children younger than 5 years in Niger. This cross-sectional study is a secondary analysis of a cluster-randomized trial comparing treatment strategies for trachoma in Niger. We included children aged 6-60 months residing in the 48 communities enrolled in the trial who completed anthropometric and malaria infection assessments at the final study visit. We evaluated the association between anthropometric indicators, including height-for-age z-score (HAZ) and weight-for-age z-score (WAZ) and indicators of malaria infection, including malaria parasitemia and clinical malaria. In May 2013, we collected data from 1,649 children. Of these, 780 (47.3%) were positive for malaria parasitemia and 401 (24.3%) had clinical malaria. In models of malaria parasitemia, the adjusted odds ratio (aOR) was 1.05 (95% confidence interval [CI]: 1.00-1.10) for HAZ and 1.07 (95% CI: 0.99, 1.15) for WAZ. In models of clinical malaria, the aOR was 1.07 (95% CI: 1.02-1.11) for HAZ and 1.09 (95% CI: 1.01-1.19) for WAZ. Overall, we did not find evidence of an association between most anthropometric indicators and malaria infection. Greater height may be associated with an increased risk of clinical malaria.

Purpose The purpose of this study was to assess whether non-chlamydial bacterial infection is associated with progression of trachomatous scarring in adults. Methods This was a cohort study involving 800 participants in northern Tanzania who underwent clinical examination, photography, and conjunctival swab collection for microbiology over a 24-month period. Samples for microbiology were inoculated onto blood and chocolate agar, and Chlamydia trachomatis was detected by PCR. Progression was determined by comparison of baseline to 24-month photographs. Results C. trachomatis was detected in only four participants at baseline. At 24 months, 617 participants (77.1%) were followed up. Of those seen at 24 months, 452 could be reliably assessed. Definite scarring progression (progressors) was seen in 345 (55.9%); there was no progression (nonprogressors) in 107 (17.3%). Using combined baseline and 12-month microbiology results, progressors had significantly higher levels of commensal and pathogenic bacterial organisms detected compared with nonprogressors. After adjusting for age, baseline scarring, and ethnicity, there was weak evidence (P = 0.07) that the bacteria category was associated with scarring progression (commensal organisms only: odds ratio [OR] = 1.61; 95% confidence interval [CI]: 0.90 to 2.89; pathogenic organisms either with or without commensal: OR = 2.39; 95% CI: 1.10 to 5.16). Conclusion The findings were consistent with the possibility that trachomatous scarring in adults is associated with the presence of non-chlamydial bacterial organisms, particularly pathogenic organisms. C. trachomatis was detected very infrequently and may not be an important factor in the pathogenesis of scarring progression in adults. This has implications for trachoma control programs, which largely concentrate on reducing C. trachomatis levels and transmission.

We hypothesized that mass distribution of a broad-spectrum antibiotic agent to preschool children would reduce mortality in areas of sub-Saharan Africa that are currently far from meeting the Sustainable Development Goals of the United Nations.In this cluster-randomized trial, we assigned communities in Malawi, Niger, and Tanzania to four twice-yearly mass distributions of either oral azithromycin (approximately 20 mg per kilogram of body weight) or placebo. Children 1 to 59 months of age were identified in twice-yearly censuses and were offered participation in the trial. Vital status was determined at subsequent censuses. The primary outcome was aggregate all-cause mortality; country-specific rates were assessed in prespecified subgroup analyses.A total of 1533 communities underwent randomization, 190,238 children were identified in the census at baseline, and 323,302 person-years were monitored. The mean (±SD) azithromycin and placebo coverage over the four twice-yearly distributions was 90.4±10.4%. The overall annual mortality rate was 14.6 deaths per 1000 person-years in communities that received azithromycin (9.1 in Malawi, 22.5 in Niger, and 5.4 in Tanzania) and 16.5 deaths per 1000 person-years in communities that received placebo (9.6 in Malawi, 27.5 in Niger, and 5.5 in Tanzania). Mortality was 13.5% lower overall (95% confidence interval [CI], 6.7 to 19.8) in communities that received azithromycin than in communities that received placebo (P0.001); the rate was 5.7% lower in Malawi (95% CI, -9.7 to 18.9), 18.1% lower in Niger (95% CI, 10.0 to 25.5), and 3.4% lower in Tanzania (95% CI, -21.2 to 23.0). Children in the age group of 1 to 5 months had the greatest effect from azithromycin (24.9% lower mortality than that with placebo; 95% CI, 10.6 to 37.0). Serious adverse events occurring within a week after administration of the trial drug or placebo were uncommon, and the rate did not differ significantly between the groups. Evaluation of selection for antibiotic resistance is ongoing.Among postneonatal, preschool children in sub-Saharan Africa, childhood mortality was lower in communities randomly assigned to mass distribution of azithromycin than in those assigned to placebo, with the largest effect seen in Niger. Any implementation of a policy of mass distribution would need to strongly consider the potential effect of such a strategy on antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation; MORDOR ClinicalTrials.gov number, NCT02047981 .).

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

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.

Repeated oral azithromycin distribution targeted only to children has proven effective in reducing the ocular Chlamydia that causes trachoma. Here, we assess whether an enhanced coverage target of at least 90% of children is superior to the World Health Organization recommendation of at least 80%. Twenty-four trachoma-endemic communities in Matamèye, Niger, were randomized to a single day of azithromycin distribution aiming for at least 80% coverage or up to 4 days of treatment and > 90% coverage of children under age 12. All distributions were biannual. Children < 5 years of age and adults > 15 years were monitored for ocular Chlamydia infection by polymerase chain reaction every 6 months for 36 months in children and at baseline and 36 months in adults. Ocular Chlamydia prevalence in children decreased from 24.9% (95% confidence interval [CI] 15.9–33.8%) to 4.4% (95% CI 0.6–8.2%, P < 0.001) at 36 months in the standard coverage arm and from 15.6% (95% CI 10.0–21.2%) to 3.3% (95% CI 1.0–5.5%; P < 0.001) in the enhanced coverage arm. Enhanced coverage reduced ocular Chlamydia prevalence in children more quickly over time compared with standard (P = 0.04). There was no difference between arms at 36 months in children (2.4% lower with enhanced coverage, 95% CI 7.7–12.5%; P = 0.60). No infection was detected in adults at 36 months. Increasing antibiotic coverage among children from 80% to 90% may yield only short term improvements for trachoma control programs. Targeting treatment to children alone may be sufficient for trachoma control in this setting.

Background Vertical transmission can result in neonatal infection and disease. Reducing the transmission of bacterial pathogens from mother to infant may be an effective means of preventing neonatal infection, including bacterial conjunctivitis. Methods In a double-blind, randomized trial, we assessed the effect of administering a single dose of oral azithromycin to women in labour on bacterial colonization of the neonate. A reduction in purulent neonatal conjunctivitis was a secondary objective of the trial. Ocular samples were collected from the lower fornix of infants presenting with clinical signs of purulent conjunctivitis during the first eight weeks of life. Incidence of purulent conjunctivitis was compared between trial arms. Bacterial infection was assessed using PCR and incidence of purulent conjunctivitis due to bacteria was also compared between arms. Results Forty of 843 infants (4.7%) presented clinical signs of purulent conjunctivitis. No significant difference in incidence of purulent conjunctivitis was seen between azithromycin and placebo arms [4.3% (18/419) versus 5.2% (22/424), OR = 0.82, 95% CI (0.44,1.54), p = 0.628]. S. aureus was the most commonly identified pathogen, detected in 38% of cases. Incidence of purulent-conjunctivitis due to bacterial infection was lower in the azithromycin arm [1.2% (5/419) versus 3.8% (16/424), OR = 0.31, 95% CI (0.12–0.82), p = 0.025)]. The incidence of gram-positive bacteria was also lower in the azithromycin arm [1.0% (4/419) versus 3.3% (14/424), OR = 0.28, 95%CI (0.10–0.82), p = 0.029]. Conclusions Oral azithromycin given to women during labour may have the potential to reduce the incidence of bacterial neonatal conjunctivitis. Trial registration ClinicalTrials.gov, identifier NCT01800942 , registration date 26 Feb 2013.

INTRODUCTION: Azithromycin has modest efficacy against malaria, and previous cluster randomized trials have suggested that mass azithromycin distribution for trachoma control may play a role in malaria control. We evaluated the effect of annual versus biannual mass azithromycin distribution over a three-year period on malaria prevalence during the peak transmission season in a region with seasonal malaria transmission in Niger. METHODS: Twenty-four communities in Matamèye, Niger were randomized to annual mass azithromycin distribution (3 distributions to the entire community during the peak transmission season) or biannual targeted azithromycin distribution (6 distributions to children

Objective An outbreak of acute haemorrhagic conjunctivitis occurred in The Gambia, West Africa in 2011. Affected individuals presented with conjunctival haemorrhages, swelling and ocular discharge. In an effort to identify a causative agent of the disease, ocular swabs were taken from patients during the acute and convalescent phases. Total RNA was extracted from all samples and reverse-transcriptase PCR performed using primers specific for all enteroviruses. Resulting amplicons were sequenced and data compared to known sequences using the BLAST algorithm. Results Forty-eight swabs were included in the analysis. Of these, 21 acute and 9 convalescent swabs (65% of the total) gave positive PCR results. Sequence analysis of the resulting amplicons indicated 99% sequence identity with coxsackievirus A24 variant identified during independent outbreaks of acute haemorrhagic conjunctivitis around the world and suggest the Gambian outbreak was due to this virus. Electronic supplementary material The online version of this article (10.1186/s13104-017-3007-9) contains supplementary material, which is available to authorized users.

Studies designed to determine the effects of mass administration of azithromycin on trachoma have suggested that mass azithromycin distributions may also reduce the prevalence of malaria. These studies have typically examined the impact of a small number of treatments over short durations. In this prespecified substudy of a cluster-randomized trial for trachoma, we compared malaria parasitemia prevalence in 24 communities in Niger randomized to receive either annual or biannual mass azithromycin distributions over 3 years. The 12 communities randomized to annual azithromycin received three treatments during the high-transmission season, and the 12 communities randomized to biannual azithromycin received a total of six treatments: three during the high-transmission season and three during the low-transmission season. Blood samples were taken to assess malariometric indices among children in all study communities at a single time point during the high-transmission season after 3 years of the intervention. No significant differences were identified in malaria parasitemia, parasite density, or hemoglobin concentration between the annual and biannual treatment arms. When compared with annual mass azithromycin alone, additional mass azithromycin distributions given during the low-transmission season did not significantly reduce the subsequent prevalence of malaria parasitemia or parasite density after 3 years, as measured during the high-transmission season.

Trachoma is caused byChlamydia trachomatis(Ct). It is targeted for global elimination as a public health problem. In 2014, a population-based cross-sectional study was performed in two previously trachoma-endemic areas of The Gambia. Participants of all ages from Lower River Region (LRR) (N = 1028) and Upper River Region (URR) (N = 840) underwent examination for trachoma and had blood collected for detection of antibodies against the Ct antigen Pgp3, by ELISA. Overall, 30 (1.6%) individuals had active trachoma; the prevalence in children aged 1–9 years was 3.4% (25/742) with no statistically significant difference in prevalence between the regions. There was a significant difference in overall seroprevalence by region: 26.2% in LRR and 17.1% in URR (p

Background Mass drug administration (MDA) with azithromycin is a corner-stone of trachoma control however it may drive the emergence of antimicrobial resistance. In a cluster-randomized trial (Clinical trial gov NCT00792922), we compared the reduction in the prevalence of active trachoma in communities that received three annual rounds of MDA to that in communities that received a single treatment round. We used the framework of this trial to carry out an opportunistic study to investigate if the increased rounds of treatment resulted in increased prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus. Three cross-sectional surveys were conducted in two villages receiving three annual rounds of MDA (3 × treatment arm). Surveys were conducted immediately before the third round of MDA (CSS-1) and at one (CSS-2) and six (CSS-3) months after MDA. The final survey also included six villages that had received only one round of MDA 30 months previously (1 × treatment arm). Results In the 3 × treatment arm, a short-term increase in prevalence of S. aureus carriage was seen following MDA from 24.6% at CSS-1 to 38.6% at CSS-2 (p

Background Following one to five years of antibiotic mass drug administration (MDA) for the elimination of trachoma as a public health problem, programmes must conduct impact surveys to inform decisions on whether MDA is still needed. These decisions are currently based on the prevalence of trachomatous inflammation—follicular (TF), which, after MDA, correlates poorly with prevalence of ocular Chlamydia trachomatis infection. Methodology/Principal findings Impact surveys in six evaluation units (EUs) of Malawi were used as a platform to explore associations between the prevalence of TF, ocular C. trachomatis infection and anti-Pgp3 antibodies one year after the third annual round of MDA. Participants were examined for trachoma using the World Health Organization simplified grading system. Ocular swabs and dried blood spots (DBS) were collected from children aged 1–9 years. Swabs were tested for C. trachomatis DNA using GeneXpert. DBS were assayed for anti-Pgp3 antibodies using ELISA. EU-level prevalence of TF in children aged 1–9 years ranged from 4.7% (95% CI 3.4–6.3) to 7.2% (95% CI 5.8–8.9). Prevalence of C. trachomatis infection in children ranged from 0.1% (95% CI 0.0–0.6) to 0.7% (95% CI 0.3–1.3) while Pgp3 seroprevalence ranged from 6.9% (95% CI 5.4–8.6) to 12.0% (95% CI 10.1–14.0) and increased with age. Conclusions/Significance Based on current global policy, the prevalence of TF indicates that a further year of antibiotic MDA is warranted in four of six EUs yet the very low levels of infection cast doubt on the universal applicability of TF-based cut-offs for antibiotic MDA. Pgp3 seroprevalence was similar to that reported following MDA in other settings that have reached the elimination target however the predictive value of any particular level of seropositivity with respect to risk of subsequent infection recrudescence is, as yet, unknown., Author summary Trachoma, caused by ocular infection with the bacterium Chlamydia trachomatis, is treated at the population level with mass drug administration (MDA) of azithromycin, a broad-spectrum antibiotic. Decisions to stop MDA are subsequently made following impact surveys designed to determine the prevalence of trachoma in children aged 1–9 years. However, clinical signs of trachoma can persist in treated communities even in the absence of active C. trachomatis infection, potentially leading to continued MDA that may be unnecessary. In this study, we use the platform provided by six impact surveys to compare prevalence of clinical signs of trachoma in children with prevalence of C. trachomatis infection and anti-C. trachomatis antibodies. Based on current policy, prevalence of clinical signs of trachoma in four of six evaluation units surveyed indicated further MDA is warranted. However, tests for C. trachomatis DNA indicate extremely low levels of infection making the need for further MDA unclear. Prevalence of anti-C. trachomatis antibodies were similar to that found in other low prevalence settings, however the significance of such levels, and of levels of current C. trachomatis infection, with regard to the risk of reinfection are, as yet, unknown.

Urban areas are traditionally excluded from trachoma surveillance activities, but due to rapid expansion and population growth, the urban area of Brikama in The Gambia may be developing social problems that are known risk factors for trachoma. It is also a destination for many migrants who may be introducing active trachoma into the area. This study aimed to determine the prevalence and risk factors for follicular trachoma and trichiasis in Brikama.A community-based cross-sectional prevalence survey including 27 randomly selected households in 12 randomly selected enumeration areas (EAs) of Brikama. Selected households were offered eye examinations, and the severity of trachoma was graded according to WHO's simplified grading system. Risk factor data were collected from each household via a questionnaire.The overall prevalence of trachomatous inflammation-follicular (TF) in children aged 1-9 years was 3.8% (95% CI 2.5-5.6), and the overall prevalence of trichiasis in adults aged ≥15 years was 0.46% (95% CI 0.17-1.14). EA prevalence of TF varied from 0% to 8.4%. The major risk factors for TF were dirty faces (P0.01, OR = 9.23, 95% CI 1.97-43.23), nasal discharge (P = 0.039, OR = 5.11, 95% CI 1.08-24.10) and residency in Brikama for1 year (P = 0.047, OR = 7.78, 95% CI 1.03-59.03).Follicular trachoma can be considered to have been eliminated as a public health problem in Brikama according to WHO criteria. However, as the prevalence in some EAs is5%, it may be prudent to include Brikama in surveillance programmes. Trichiasis remains a public health problem (0.1%), and active case finding needs to be undertaken.

AIM: To compare in vivo confocal microscopy (IVCM) with the histopathological examination of tissue and cellular changes in normal and diseased conjunctiva. METHODS: Participants underwent clinical examination and IVCM of the tarsal conjunctiva. A biopsy of the upper tarsal conjunctiva was collected and stained with tinctorial stains and by immunohistochemical staining for CD45 and CD83. Connective tissue scarring, inflammatory cell density and the presence of dendritiform cells were quantitatively assessed in a masked manner by both IVCM and histological assessments for comparative analysis. RESULTS: Thirty-four participants with severe trachomatous conjunctival scarring and 33 participants with healthy conjunctiva were recruited. The IVCM connective tissue scarring score was strongly associated with the histological grading of scarring (p

Tumor necrosis factor (TNF) is thought to be a key mediator of the inflammatory and fibrotic response to Chlamydia trachomatis (Ct) infection. A large matched-pair case-control study investigated putative functional single nucleotide polymorphisms (SNPs) across the major histocompatibility complex (MHC) class III region, including TNF and its immediate neighbors nuclear factor of kappa light polypeptide gene enhancer in B cells (IkappaBL), inhibitor like 1 and lymphotoxin alpha (LTA) in relation to the risk of scarring sequelae of ocular Ct infection. Haplotype and linkage disequilibrium analysis demonstrated two haplotypes, differing at position TNF-308, conferring an increased risk of trichiasis. The TNF-308A allele, and its bearing haplotype, correlated with increased TNF production in lymphocyte cultures stimulated with chlamydial elementary body antigen. Thus TNF-308A may determine directly, or be a marker of a high TNF producer phenotype associated with increased risk of sequelae of chlamydial infection. Multivariate analysis provided evidence for the presence of additional risk-associated variants near the TNF locus.

Melioidosis (. Burkholderia pseudomallei infection) has yet to be demonstrated systematically in Bangladesh. A prospective, cross-sectional serological survey was conducted in 2010 at six Bangladeshi hospitals. Age, gender, occupation and residential address were recorded. Of 1244 patients, 359 (28.9%) were positive for . B. pseudomallei by indirect haemagglutination assay. Farmers had an increased risk of seropositivity (risk ratio. =. 1.4, 95% CI 1.0-1.8; p. =. 0.03). There was no clear geographic clustering of seropositives. Melioidosis should be considered as a possible cause of febrile illness in Bangladesh. Further studies are needed to establish the incidence of clinical disease and distribution of environmental risk. © 2012 Royal Society of Tropical Medicine and Hygiene.

Trachoma, an infectious disease of the conjunctiva caused by Chlamydia trachomatis, causes scarring and blindness in some infected individuals but not others. In an African community where trachoma is endemic, we have previously identified an IL10 haplotype that is associated with increased risk of scarring complications. Here we examine the hypothesis that the risk haplotype (H-RISK) affects levels of IL10 expression in the conjunctiva during active trachoma infection. To overcome potential genetic and environmental confounders we used the method of allele-specific quantification, which involved identifying subjects in the community who had active trachoma and were also heterozygous for the H-RISK. We find that there is allelic variation in cis-regulation of IL10 in the conjunctiva during active trachoma, with the H-RISK generating relatively more IL10 transcripts than other haplotypes in this population (average difference in IL10 allelic transcripts in the conjunctiva of heterozygous individuals infected with C. trachomatis of 23% (95% confidence interval: 14-32%, P < 0.0001). These findings provide a plausible functional explanation for the observed genetic association, and support the hypothesis that an excessive IL10 response to C. trachomatis infection is a risk factor for scarring and blindness.

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, Author Summary We previously reported that Trachomatous Trichiasis (TT) has a profound impact on vision and heath related quality of life (QoL), even when vision is not impaired. The World Health Organization (WHO) recommends corrective eyelid surgery for trichiasis to reduce the risk of vision loss. However, trichiasis surgery may also improve overall wellbeing. There is very limited evidence on the long-term impact of trichiasis surgery on QoL. We measured vision and health-related quality of life of 1000 TT patients before and one year after receiving TT surgery and compared the QoL scores of these with the baseline and 1 year follow-up QoL score of 200 matched individuals who have never had trichiasis or trichiasis surgery. We found strong evidence that surgery substantially improves both vision and heath related QoL of TT case, even when there is no improvement in vision; while there was no evidence of improvement in the QoL of the trichiasis free participants. The results provide clear evidence that the benefit of trichiasis surgery goes beyond preventing the risk of blindness and improves the overall wellbeing and health perception of affected individuals, indicating the need to provide prompt surgical intervention for affected individuals.

Introduction The phenotype and function of immune cells infiltrating the conjunctiva in scarring trachoma have yet to be fully characterized. We assessed tissue morphology and immunophenotype of cellular infiltrates found in trachomatous scarring compared to control participants. Methodology Clinical assessments and conjunctival biopsy samples were obtained from 34 individuals with trachomatous scarring undergoing trichiasis surgery and 33 control subjects undergoing cataract or retinal detachment surgery. Biopsy samples were fixed in buffered formalin and embedded in paraffin wax. Hematoxylin and eosin (H&E) staining was performed for assessment of the inflammatory cell infiltrate. Immunohistochemical staining of single markers on individual sections was performed to identify cells expressing CD3 (T-cells), CD4 (helper T-cells), CD8 (suppressor/cytotoxic T-cells and Natural Killer, NK, cells), NCR1 (NK cells), CD20 (B-cells), CD45 (nucleated hematopoietic cells), CD56 (NK and T-cells), CD68 (macrophages/monocytes) and CD83 (mature dendritic cells). The degree of scarring was assessed histologically using cross-polarized light to visualize collagen fibres. Principle Findings Scarring, regardless of clinical inflammation, was associated with increased inflammatory cell infiltrates on H&E and CD45 staining. Scarring was also associated with increased CD8+ and CD56+ cells, but not CD3+ cells, suggestive of a NK cell infiltrate. This was supported by the presence of NCR1+ cells. There was some increase in CD20+ cells, but no evidence for increased CD4+, CD68+ or CD83+ cells. Numerous CD45 negative cells were also seen in the population of infiltrating inflammatory cells in scarred conjunctiva. Disorganization of the normal collagen architecture was strongly associated with clinical scarring. Conclusions/Significance These data point to the infiltration of immune cells with a phenotype suggestive of NK cells in conjunctival trachomatous scarring. A large proportion of CD45 negative inflammatory cells were also present. Future work should seek to understand the stimuli leading to the recruitment of these cells and their role in progressive scarring., Author Summary Trachoma is initiated by repeated infection of the conjunctiva throughout childhood by the bacterium Chlamydia trachomatis (Ct). Conjunctival inflammation and scarring progress throughout the lives of many adults even in the absence of Ct infection, causing the eyelashes to turn inwards (trichiasis) and damage the cornea, resulting in severe pain and eventually leading to blindness. The factors sustaining the inflammation that drives scarring are not understood and there is no treatment to halt scarring progression. We sought to define the phenotypes of immune cells infiltrating the conjunctiva during trichiasis. Eyelid tissue from 34 individuals with trichiasis and 33 control individuals was stained with dyes or specific antibodies to distinguish immune cell subsets. Increased inflammatory cells were detected in individuals with trichiasis even when clinical signs of inflammation were not apparent. Staining of immune cell types pointed to an increased infiltration of natural killer cells in tissue from individuals with trichiasis. These cells may cause tissue damage through cytokine secretion and cell lysis. Surprisingly, a large number of infiltrating immune cells lacked the classical immune cell marker CD45. The phenotype and function of these CD45 negative cells and their role in scarring trachoma warrants further study.

Trachoma is the most common infectious cause of blindness and a major public health problem in many developing countries. It is caused by recurrent ocular infection with Chlamydia trachomatis in childhood, with conjunctival scarring seen later in life. The pathogenesis of trachomatous scarring, however, is poorly understood, and this study was carried out to investigate the immunofibrogenic correlates of trachomatous conjunctival scarring. A case-control study of 363 cases with conjunctival scarring and 363 control participants was conducted. Investigations included in vivo confocal microscopy (IVCM) assessment, quantitative real-time PCR gene expression, C. trachomatis detection, and nonchlamydial bacterial culture. Trachomatous scarring was found to be strongly associated with a proinflammatory, innate immune response with increased expression of psoriasin, interleukin-1β, tumor necrosis factor alpha, defensin-β4A, chemokine ligand 5, and serum amyloid A1. There was also differential expression of various modifiers of the extracellular matrix, including metalloproteinases 7, 9, 10, and 12, tissue inhibitor of matrix metalloproteinase 1, and secreted protein acidic cystein-rich-like 1. The expression of many of these genes was also significantly associated with the presence of nonchlamydial bacterial infection. These infections had a marked effect on conjunctival immune processes, including an increased inflammatory infiltrate and edema seen with IVCM. This study supports the possibility that the immunofibrogenic response in scarring trachoma is partly stimulated by nonchlamydial bacterial infection, which is characterized by the expression of innate factors.

Purpose Eight million people have trachomatous trichiasis (TT). The World Health Organization (WHO) recommends entropion surgery for TT regardless of severity. However, epilation is widely practiced for treating minor TT (1–5 lashes touching the globe). We report the frequency and effectiveness of patient-initiated epilation and its relationship to corneal opacity. Design Cross-sectional baseline data of individuals recruited to 2 randomized, clinical trials. Participants We included 2556 individuals (4310 eyes) with previously unoperated TT in ≥1 eye. Methods A single ophthalmologist examined all participants for signs of trachoma using WHO grading systems with additional assessment of entropion grading, location and number of trichiatic lashes, and evidence of epilation. A questionnaire enquired about epilation practices. Main Outcome Measures The association between epilation and degree of corneal opacity. Epilation practices of TT patients. Results Central corneal scarring was present in 1436 (33%) eyes. Entropion was absent/mild in 2328 (54%) eyes, moderate in 1259 (29.2%), and severe in 723 (16.8%). The median number of lashes touching the eye was 2 (interquartile range, 1–5; range, 0–133). There was clinical evidence of epilation in 3018 (70%) eyes, of which 738 (24%) were successfully epilated (no lashes touching globe). Epilation was performed frequently (at least monthly in 3311 [76.8%] eyes), by someone other than the patient (92.8%), and using locally made forceps (88.9%). Controlling for age and degree of entropion, successful epilation was associated with less corneal opacity (odds ratio [OR], 0.61; 95% confidence interval [CI]. 0.43–0.88; P = 0.007). The association was only significant in patients with severe entropion (OR, 0.07; 95% CI, 0.02–0.25; P Conclusions We found an association between successful epilation and less central corneal opacity. This indicates the importance of preventing eyelashes from touching the cornea, particularly in individuals with severe entropion. This is a cross-sectional study; therefore, a causative relationship cannot be concluded. However, the results suggest that among patients who decline or are unable to access surgery, and perhaps in minor TT where the management remains controversial, the provision of high-quality forceps and epilation training may be beneficial. Financial Disclosure(s) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

The immunological basis of scarring trachoma is not well understood. It is unclear whether it is driven primarily through cell-mediated adaptive or epithelial-cell-derived innate responses. The purpose of this study was to investigate the expression of the inflammatory and fibrogenic mediators which may be involved. We conducted a cross-sectional survey of children living in an untreated trachoma-endemic community in Tanzania. The children were examined for signs of trachoma, and swabs were collected for bacteriological culture and RNA and DNA isolation. Chlamydia trachomatis was detected by the Amplicor PCR test. The expression of the following genes was measured by quantitative reverse transcription-PCR (RT-PCR): S100A7 , IL1B , IL17A , IL23A , CXCL5 , CCL18 , TLR2 , NLRP3 , KLRD1 , CTGF , and MMP9 . Four hundred seventy children under the age of 10 years were included. Follicular trachoma (TF) was detected in 65 children (14%), C. trachomatis was detected in 25 (5%), and bacterial pathogens were cultured in 161 (34%). TF was associated with significantly increased expression of S100A7 , IL17A , CCL18 , CXCL5 , and CTGF. Expression was increased further in the presence of papillary inflammation. Nonchlamydial bacterial infection was associated with increased expression of IL17A , CXCL5 , CCL18 , and KLRD1 . IL17A expression was associated with increased expression of S100A7 , CXCL5 , CCL18 , KLRD1 , and CTGF. These data are consistent with a role for IL-17A in orchestrating the proinflammatory response in trachoma. Its activity may be promoted either as part of the cell-mediated response or through innate pathways. It may drive a range of proinflammatory factors leading to excessive tissue damage and repair involving fibrosis.

Objective To characterize the tissue and cellular changes found in trachomatous scarring (TS) and inflammation using in vivo confocal microscopy (IVCM). Design Two complimentary case-control studies. Participants The first study included 363 cases with TS (without trichiasis), of whom 328 had IVCM assessment, and 363 control subjects, of whom 319 had IVCM assessment. The second study included 34 cases with trachomatous trichiasis (TT), of whom 28 had IVCM assessment, and 33 control subjects, of whom 26 had IVCM assessment. Methods All participants were examined with ×2.5 loupes. The IVCM examination of the upper tarsal conjunctiva was carried out with a Heidelberg Retina Tomograph 3 with the Rostock Cornea Module (Heidelberg Engineering GmbH, Dossenheim, Germany). Main Outcome Measures The IVCM images were graded in a masked manner using a previously published grading system evaluating the inflammatory infiltrate density; the presence or absence of dendritiform cells (DCs), tissue edema, and papillae; and the level of subepithelial connective tissue organization. Results Subjects with clinical scarring had a characteristic appearance on IVCM of well-defined bands and sheets of scar tissue visible. Similar changes were also seen in some clinically normal subjects consistent with subclinical scarring. Scarred subjects had more DCs and an elevated inflammatory infiltrate, even after adjusting for other factors, including the level of clinical inflammation. Cellular activity was usually seen only in or just below the epithelium, rarely being seen deeper than 30 μm from the surface. The presence of tissue edema was strongly associated with the level of clinical inflammation. Conclusions In vivo confocal microscopy can be quantitatively used to study inflammatory and scarring changes in the conjunctiva. Dendritic cells seem to be closely associated with the scarring process in trachoma and are likely to be an important target in antifibrotic therapies or the development of a chlamydial vaccine. The increased number of inflammatory cells seen in scarred subjects is consistent with the immunopathologic nature of the disease. The localization of cellular activity close to the conjunctival surface supports the view that the epithelium plays a central role in the pathogenesis of trachoma. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Trachoma is the commonest infectious cause of blindness. Recurrent episodes of infection with serovars A-C of Chlamydia trachomatis cause conjunctival inflammation in children who go on to develop scarring and blindness as adults. It was estimated that in 2002 at least 1.3 million people were blind from trachoma, and currently 40 million people are thought to have active disease and 8.2 million to have trichiasis. The disease is largely found in poor, rural communities in developing countries, particularly in sub-Saharan Africa. The WHO promotes trachoma control through a multifaceted approach involving surgery, mass antibiotic distribution, encouraging facial cleanliness and environmental improvements. This has been associated with significant reductions in the prevalence of active disease over the past 20 years, but there remain a large number of people with trichiasis who are at risk of blindness.

Chlamydia trachomatis causes both trachoma and sexually transmitted infections. These diseases have similar pathology and potentially similar genetic predisposing factors. We aimed to identify polymorphisms and pathways associated with pathological sequelae of ocular Chlamydia trachomatis infections in The Gambia. We report a discovery phase genome-wide association study (GWAS) of scarring trachoma (1090 cases, 1531 controls) that identified 27 SNPs with strong, but not genome-wide significant, association with disease (5 × 10−6 > P > 5 × 10−8). The most strongly associated SNP (rs111513399, P = 5.38 × 10−7) fell within a gene (PREX2) with homology to factors known to facilitate chlamydial entry to the host cell. Pathway analysis of GWAS data was significantly enriched for mitotic cell cycle processes (P = 0.001), the immune response (P = 0.00001) and for multiple cell surface receptor signalling pathways. New analyses of published transcriptome data sets from Gambia, Tanzania and Ethiopia also revealed that the same cell cycle and immune response pathways were enriched at the transcriptional level in various disease states. Although unconfirmed, the data suggest that genetic associations with chlamydial scarring disease may be focussed on processes relating to the immune response, the host cell cycle and cell surface receptor signalling.

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, Author Summary Trachoma has long been considered a disease of poverty. However, there is surprisingly little direct data that formally quantifies the relationship between trachoma and economic poverty, and none that specifically focuses on trichiasis. We compared 200 people with trachomatous trichiasis (TT) to 200 people (controls) without the condition, who were matched on age and sex, living in the same community, in Amhara Region, Ethiopia. We measured household relative poverty using three measures: household assets, self-rated wealth and peer-rated wealth. We also measured activity participation. We found TT case households were poorer by all relative economic measures. We found cases less likely to participate in economically productive activities regardless of visual impairment and other health problems, more likely to report difficulty and need assistance performing activities. The results suggest that the causative relationship between poverty and trachoma could possibly be bidirectional: poor households are more affected by trachoma and trichiasis reduces productivity even prior to development of visual impairment, which may exacerbate poverty. Implementation of the SAFE strategy in the context of general socioeconomic improvements might lead to a virtuous cycle of improving health and wealth. Trachoma could be used as proxy of inequality and to target and evaluate interventions for health and poverty alleviation.

Background Trachoma, a preventable blinding eye disease, is initiated by ocular infection with Chlamydia trachomatis (Ct). We previously showed that microRNAs (miR) -147b and miR-1285 were up-regulated in inflammatory trachomatous scarring. During the initial stage of disease, follicular trachoma with current Ct infection, the differential expression of miR has not yet been investigated. Methods Conjunctival samples were collected from 163 children aged 1–9 years old living in a trachoma-endemic region of Guinea Bissau, West Africa. Small RNA sequencing (RNAseq) was carried out on samples from five children with follicular trachoma and current Ct infection and five children with healthy conjunctivae and no Ct infection. Small RNAseq was also carried out on human epithelial cell lines infected with ocular Ct strains A2497 and isogenic plasmid-free A2497 in vitro. Results were validated by quantitative PCR (qPCR) in 163 clinical samples. Results Differential expression of RNAseq data identified 12 miR with changes in relative expression during follicular trachoma, of which 9 were confirmed as differentially expressed by qPCR (miR-155, miR-150, miR-142, miR-181b, miR-181a, miR-342, miR-132, miR-4728 and miR-184). MiR-155 and miR-184 expression had a direct relationship with the degree of clinical inflammation. MiR-155 was up-regulated (OR = 2.533 ((95 % CI = 1.291–4.971); P = 0.0069) and miR-184 was down-regulated (OR = 0.416 ((95 % CI = 0.300–0.578); P = 1.61*10−7) as the severity of clinical inflammation increased. Differential miR expression was not detected in HEp-2 or HCjE epithelial cells 48 h post infection with Ct in vitro. HCjE cells, a conjunctival epithelial cell line, had a markedly different miR background expression compared to HEp-2 cells. Conclusions In follicular trachoma, expression of miR-155 and miR-184 is correlated with the severity of inflammation. This likely reflects host regulation of the immune response and a prolonged period of wound healing following the clearance of Ct. Prolonged healing may be associated with subsequent development of scarring trachoma. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1367-8) contains supplementary material, which is available to authorized users.

The objective of this study was to use a modified Lot Quality Assurance Sampling methodology to classify communities according to prevalence of active trachoma and to estimate the prevalence of trachoma and trichiasis in Nioro department, Kaolack Region, Senegal. A survey was conducted using two-stage cluster sampling to select 50 children aged 2-5 years in each of 33 clusters. In total 1,648 children were examined for active trachoma. Information on trachoma risk factors was collected through interviews with the mother or the household head of the child. Adults (40 years) with trichiasis were identified through case finding. Nineteen clusters had a low prevalence of active trachoma in children aged 2-5 years (20%), 11 had medium prevalence (20-40%) and three had high prevalence (40%). The prevalence of active trachoma in children aged 2-5 years was 17.4% (95% CI 12.9-21.8%). Multivariate-adjusted predictors of active trachoma were: age, facial cleanliness, hygiene practices and keeping cattle in the household. The prevalence of trichiasis in adults aged over 40 years was 1.77% (95% CI 1.24-2.51), equating to 985 adults (95% CI 765-1250) with trichiasis in Nioro department. In conclusion, a survey using rapid methodology showed that trachoma is a problem of public significance in Nioro department, Senegal.

Background/aim: Trachomatous trichiasis frequently returns following surgery. Several factors may promote recurrence: preoperative disease severity, surgeon ability, surgical procedure, healing responses, and infection. This study investigates whether enhanced control of infection, both of Chlamydia trachomatis and other bacteria, with azithromycin can improve surgical outcome in a trachoma control programme. Methods: Individuals with trachomatous trichiasis were examined and operated. After surgery patients were randomised to the azithromycin or control group. The azithromycin group and children in their household were given a dose of azithromycin. Antibiotic treatment was repeated at 6 months. All patients were reassessed at 6 months and 12 months. Samples were collected for C trachomatis polymerase chain reaction and general microbiology at each examination. Results: 451 patients were enrolled. 426 (94%) were reassessed at 1 year, of whom 176 (41.3%) had one or more lashes touching the eye and 84 (19.7%) had five or more lashes. There was no difference in trichiasis recurrence between the azithromycin and control group. Recurrent trichiasis was significantly associated with more severe preoperative trichiasis, bacterial infection, and severe conjunctival inflammation at 12 months. Significant variability in outcome was found between surgeons. Visual acuity and symptoms significantly improved following surgery. Conclusion: In this setting, with a low prevalence of active trachoma, azithromycin did not improve the outcome of trichiasis surgery conducted by a trachoma control programme. Audit of trichiasis surgery should be routine.