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Additional file 2: Table S1. Larval sampling site description and species found.

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

Background: The Solomon Islands is targeting elimination of malaria by 2030. The dominant vector is the predominantly exophagic, exophilic Anopheles farauti sensu strictu. This biting behaviour limits the efficacy of conventional vector control tools and highlights the need for new strategies. When administered to humans ivermectin has been shown to have a mosquitocidal effect. Mass drug administration (MDA) with ivermectin is an emerging strategy in the control of scabies. In this study we explored any incidental effect of ivermectin MDA conducted for scabies control on mosquitoes. Methods: MDA for scabies was conducted in three villages. We performed human landing catches and measured 5-day mortality amongst Anopheles mosquitoes caught before and after MDA. Cox regression was used to calculate hazard ratios (HR) for mortality between mosquitoes caught before and after MDA. Results: There was a significant increase in 5-day mortality in anopheline mosquitoes caught post-MDA which was highest on the day of MDA itself (HR 4.2 95% CI 1.8 to 10.1, p=0.001) and the following day (HR 4.4 95% CI 1.8 to 10.8, p=0.002) compared to mosquitoes caught before MDA. Conclusions: This study shows a possible mosquitocidal effect of ivermectin MDA conducted for scabies control. Studies with a larger sample size with clinical as well as entomological outcomes should be conducted in this population.

NKG2C is an activating receptor that is preferentially expressed on natural killer (NK) cells. The gene encoding NKG2C (killer cell lectin-like receptor C2, KLRC2) is present at different copy numbers in the genomes of different individuals. Deletion at the NKG2C locus was investigated in a case–control study of 1522 individuals indigenous to East- and West-Africa and the association with the ocular Chlamydiatrachomatis infection and its sequelae was explored. The frequency of homozygous KLRC2 deletion was 13.7 % in Gambians and 4.7 % in Tanzanians. A significantly higher frequency of the deletion allele was found in West-Africans from the Gambia and Guinea-Bissau (36.2 % p = 2.105 × 10−8, 26.8 % p = 0.050; respectively) in comparison to East-African Tanzanians where the frequency of the deletion is comparable to other human populations (20.9 %). We found no evidence for an association between the numbers of KLRC2 gene copies and the clinical manifestations of trachoma (follicular trachoma or conjunctival scarring). A new method for imputation of KLRC2 genotypes from single nucleotide polymorphism (SNP) data in 2621 individuals from the Gambia further confirmed these results. Our data suggest that NKG2C does not play a major role in trachomatous disease. We found that the deletion allele is present at different frequencies in different populations but the reason behind these differences is currently not understood. The new method offers the potential to use SNP arrays from genome wide association studies to study the frequency of KLRC2 deletion in other populations and its association with other diseases. Electronic supplementary material The online version of this article (doi:10.1007/s00439-016-1694-2) contains supplementary material, which is available to authorized users.

Multivariable regression model of the contribution of miR expression to clinical papillary hypertrophy score. Collapsed papillary hypertrophy score (P0, P1 or P2/3, as defined by the WHO 1981 FPC scoring system) was used as an ordinal outcome variable to define trachomatous inflammation in 163 clinical samples. Age, gender, Ct load and inverted ∆CT values (40-∆CT) of miR are included as independent variables. Model AIC (Akaike information criterion) is 227.3725. aOR = Odds ratio, bCI = confidence intervals, cCt load is defined as log-(e) omcB copies/swab. (PDF 59 kb)

Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections, causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis shows that predicting phylogenetic structure using ompA, which is traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks any true relationships present. We show that in many instances, ompA is a chimera that can be exchanged in part or as a whole both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, which is another key diagnostic target. We used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b.

Relative abundance of miR in the conjunctiva of cases of follicular trachoma (TF) and controls (N). MiR with a mean read count in TF cases or controlsâ

Focused list of published roles for miR that are differentially expressed in follicular trachoma that relate to inflammation or fibrosis. (PDF 59Â kb)

A combined treponemal and nontreponemal rapid diagnostic test was found to have good sensitivity and specificity for both syphilis and yaws. The performance of both the treponemal and nontreponemal test components was strongly associated with the rapid plasma reagin titer., Background. The human treponematoses are important causes of disease. Mother-to-child transmission of syphilis remains a major cause of stillbirth and neonatal death. There are also almost 100 000 cases of endemic treponemal disease reported annually, predominantly yaws. Rapid diagnostic tests (RDTs) would improve access to screening for these diseases. Most RDTs cannot distinguish current and previous infection. The Dual Path Platform (DPP) Syphilis Screen & Confirm test includes both a treponemal (T1) and nontreponemal (T2) component and may improve the accuracy of diagnosis. Methods. We conducted a metaanalysis of published and unpublished evaluations of the DPP-RDT for the diagnosis of syphilis and yaws. We calculated the sensitivity, specificity, and overall agreement of the test compared with reference laboratory tests. Results. Nine evaluations, including 7267 tests, were included. Sensitivity was higher in patients with higher titer rapid plasma reagin (≥1:16) for both the T1 (98.2% vs 90.1%, P < .0001) and the T2 component (98.2% vs 80.6%, P < .0001). Overall agreement between the DPP test and reference serology was 85.2% (84.4%–86.1%). Agreement was highest for high-titer active infection and lowest for past infection. Conclusions. The RDT has good sensitivity and specificity of the treponemal and nontreponemal components both in cases of suspected syphilis and yaws, although the sensitivity is decreased at lower antibody titers.

Relative abundance of miR in the conjunctiva of cases of follicular trachoma (TF) and controls (N). MiR with a mean read count in TF cases or controlsâ

Purpose: Trachoma control programs are underway in endemic regions worldwide. They are based on the SAFE strategy (Surgery for trichiasis, Antibiotic distribution, Facial cleanliness, and Environmental improvement). Although much is known about the effect of community-wide treatment with antibiotics on the prevalence of Chlamydia trachomatis, the impact of the SAFE strategy on severe ocular disease sequelae (the main focus of the Global Elimination of blinding Trachoma by 2020 program) remains largely unknown. Methods: We use a mathematical model to explore the impact of each of the components of the SAFE strategy, individually and together, on disease sequelae, arising from repeat infection and subsequent conjunctival scarring. We ask whether two elimination goals, to reduce the prevalence of trachomatous trichiasis to 1 per 1000 persons, and the incidence of corneal opacity to 1 per 10,000 persons per annum, are achievable, and which combinations of interventions have the greatest impact on these indicators. Results: In high prevalence communities (here, >20% infection of children aged 1–9 years), a combination of efforts is needed to bring down sustainably the prevalence and incidence of ocular disease sequelae. Conclusion: The mass delivery of antibiotics is highly beneficial for the clearance of infection, inflammation and prevention of subsequent scarring, but needs to be supplemented with sustained reductions in transmission and surgery to consider realistically the elimination of blindness by the year 2020.

Chlamydial infection of HEp-2 and HCjE cell lines with three ocular Ct strains. HEp-2 cell monolayers infected with Ct strains A2497 (A), A2497P- (B) and A/HAR-13 (C), and HCjE cell monolayers infected with Ct strains A2497 (D), A2497P- (E) and A/HAR-13 (F) at 48 hpi. Cell nuclei are stained with DAPI (blue) and Ct inclusions are stained with anti-C. trachomatis MOMP antibody (FITC (green)). Cells were infected with an MOI of 1 and viewed at 40X magnification. Representative photographs were taken from one of three replicates for each condition. (PDF 770Â kb)

Focused list of published roles for miR that are differentially expressed in follicular trachoma that relate to inflammation or fibrosis. (PDF 59Â kb)

Chlamydial infection of HEp-2 and HCjE cell lines with three ocular Ct strains. HEp-2 cell monolayers infected with Ct strains A2497 (A), A2497P- (B) and A/HAR-13 (C), and HCjE cell monolayers infected with Ct strains A2497 (D), A2497P- (E) and A/HAR-13 (F) at 48 hpi. Cell nuclei are stained with DAPI (blue) and Ct inclusions are stained with anti-C. trachomatis MOMP antibody (FITC (green)). Cells were infected with an MOI of 1 and viewed at 40X magnification. Representative photographs were taken from one of three replicates for each condition. (PDF 770Â kb)

Purpose: Trachoma control programs are underway in endemic regions worldwide. They are based on the SAFE strategy (Surgery for trichiasis, Antibiotic distribution, Facial cleanliness, and Environmental improvement). Although much is known about the effect of community-wide treatment with antibiotics on the prevalence of Chlamydia trachomatis, the impact of the SAFE strategy on severe ocular disease sequelae (the main focus of the Global Elimination of blinding Trachoma by 2020 program) remains largely unknown. Methods: We use a mathematical model to explore the impact of each of the components of the SAFE strategy, individually and together, on disease sequelae, arising from repeat infection and subsequent conjunctival scarring. We ask whether two elimination goals, to reduce the prevalence of trachomatous trichiasis to 1 per 1000 persons, and the incidence of corneal opacity to 1 per 10,000 persons per annum, are achievable, and which combinations of interventions have the greatest impact on these indicators. Results: In high prevalence communities (here, >20% infection of children aged 1–9 years), a combination of efforts is needed to bring down sustainably the prevalence and incidence of ocular disease sequelae. Conclusion: The mass delivery of antibiotics is highly beneficial for the clearance of infection, inflammation and prevention of subsequent scarring, but needs to be supplemented with sustained reductions in transmission and surgery to consider realistically the elimination of blindness by the year 2020.