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Abstract Objectives Bone defects caused by diseases and trauma are usually accompanied by inflammation, and the implantation of biomaterials as a common repair method has also been found to cause inflammatory reactions, which affect bone metabolism and new bone formation. This study investigated whether exosomes from adipose-derived stem cells (ADSC-Exos) plays an immunomodulatory role in traumatic bone defects and elucidated the underlying mechanisms. Methods ADSC-Exos were loaded by a biomaterial named gelatine nanoparticles (GNPs), physical and chemical properties were analysed by zeta potential, surface topography and rheology. A rat model of skull defect was used for our in vivo studies, and micro-CT and histological staining were used to analyse histological changes in the bone defect area. RT-qPCR and western blotting were performed to verify that ADSC-Exos could regulate M1/M2 macrophage polarization. MicroRNA (miRNA) array analysis was conducted to determine the miRNA expression profiles of ADSC-Exos. After macrophages were treated with a miR-451a mimic, miR-451a inhibitor and ISO-1, the relative expression of genes and proteins was measured by RT-qPCR and western blotting. Results In vivo, micro-CT and histological staining showed that exosome-loaded GNPs (GNP-Exos) hydrogel, with good biocompatibility and strong mechanical adaptability, exhibited immunomodulatory effect mainly by regulating macrophage immunity and promoting bone tissue healing. Immunofluorescence further indicated that ADSC-Exos reduced M1 marker (iNOS) expression and increased M2 marker (CD206) expression. Moreover, in vitro studies, western blotting and RT-qPCR showed that ADSC-Exos inhibited M1 macrophage marker expression and upregulated M2 macrophage marker expression. MiR-451a was enriched in ADSC-Exos and targeted macrophage migration inhibitory factor (MIF). Macrophages treated with the miR-451a mimic showed lower expression of M1 markers. In contrast, miR-451a inhibitor treatment upregulated the expression of M1 markers and downregulated the expression of M2 markers, while ISO-1 (a MIF inhibitor) treatment upregulated miR-451a expression and downregulated M1 macrophage marker expression. Conclusion GNP-Exos can effectively regulate bone immune metabolism and further promote bone healing partly through immune regulation of miR-451a, which may provide a therapeutic direction for bone repair.

Abstract Existing bone tissue engineering strategies aim to achieve minimize surgical trauma, stabilize the injured area, and establish a dynamic osteogenic microenvironment. The cutting‐edge bone glue developed in this study satisfies these criteria. Inspired by the excellent adhesive properties of mussels, herein, a super osteogenic glue (L‐DPZ) that integrates poly(vinyl alcohol), L‐dopa amino acid, and zeolitic imidazolate framework‐8 characterized by catechol–metal coordination is used to successfully adhere to hard tissue with a maximum adhesive strength of 10 MPa, which is much higher than those of commercial and previously reported bone glues. The stable hard tissue adhesion also enables it to adhere strongly to luxated or broken teeth, Bio‐Oss (a typical bone graft material), and splice fragments from comminuted fractures of the rabbit femur. Then, it is testified that the L‐DPZ hydrogels exhibit satisfactory biocompatibility, stable degradability, and osteogenic ability in vitro. Moreover, the ability to anchor Bio‐Oss and sustained osteogenesis of L‐DPZ result in satisfactory healing in calvarial bone defect models in rabbits, as observed by increased bone thickness and the ingrowth of new bone tissue. These results are expected to demonstrate solutions to clinical dilemmas such as comminuted bone fracture fixation, bone defect reconstruction, and teeth dislocation replantation.

BackgroundSchneiderian membrane (SM) perforation is a major complication of maxillary sinus elevation with simultaneous bone grafting, yet under this scenario there is no standard biomaterial that maximizes favorable tissue healing and osteogenic effects.PurposeTo compare the effect of advanced platelet-rich fibrin (A-PRF) and collagen membrane (CM) on a perforated SM with simultaneous bone grafting in a maxillary sinus elevation model.Materials and MethodsAfter perforation of the SM was established, 24 animals were randomly divided into two groups: (i) group CM: CM and deproteinized bovine bone mineral (DBBM) (n = 12), (ii) group A-PRF: A-PRF and DBBM (n = 12). Radiographic and histological evaluations were performed at 1 and 4 weeks post-operation.ResultsAt 1 week, an intact SM was found in group A-PRF. At each time point, the number of inflammatory cells at the perforated site was higher in group CM, and the area of new osteoid formation was significantly greater in group A-PRF (p < 0.0001). At 4 weeks, the osteogenic pattern was shown as from the periphery to the center of the sinus cavity in group A-PRF.ConclusionThe higher elasticity, matching degradability, and plentiful growth factors of A-PRF resulted in a fully repaired SM, which later ensured the two osteogenic sources from the SM to generate significant new bone formation. Thus, A-PRF can be considered to be a useful bioactive tissue-healing biomaterial for SM perforation with simultaneous bone grafting.

Background: Serologic testing for chlamydial antibodies is one potential tool for trachoma monitoring. Understanding the dynamics of seroconversion and seroreversion in low endemic districts is critical for determining the value of using serology., Methodology/principal Findings: We surveyed a random sample of 2536 children aged 1-9 years in Kongwa, Tanzania, over three years; 1719 (67.8%) participants had all three follow-ups. Surveys assessed trachomatous inflammation-follicular (TF), Chlamydia trachomatis infection, and anti-pgp3 antibodies. Mass drug administration occurred immediately after the first and second follow-up surveys. The cohort was classified into trajectories of change in serostatus, and risk factors were evaluated for seroconversion and seroreversion. We found that 86.2% of seropositives remained seropositive throughout the study, whereas 12.1% seroreverted. Seroreverters were younger (Odds Ratio [OR] = 0.88 for every one-year increase in age, 95% CI = 0.79-0.99). 84.5% of seronegatives remained seronegative, and 13.0% seroconverted. Seroconverters were also younger (OR = 0.92, 95% CI = 0.87-0.98). Seroconversion and seroreversion were not explained by indeterminate values for the intensity of antibody response. Less than 1% of the cohort had unstable changes in serostatus, mostly explained by values in the indeterminate range. TF and infection in the cohort declined over time, while seropositivity increased from 31.5% to 36.4%., Conclusions/significance: Antibody status is relatively stable over time. Both seroconversion and seroreversion occurred over the three years in this low endemic district, especially in younger children. Modeling seroreversion is important for accurate determination of seroconversion. The use of serology as a monitoring tool should target the younger aged children as they will most likely capture recent changes in serostatus., Competing Interests: The authors have declared that no competing interests exist.

Background: Suboptimal antiretroviral therapy (ART) adherence and disengagement in care present significant public health challenges because of the increased probability of HIV transmission. In the United States, men who have sex with men (MSM) continue to be disproportionately affected by HIV, highlighting a critical need to engage high-risk MSM living with HIV who are not engaged or retained in care., Objective: The aim of the study was to assess the feasibility of at-home blood self-collection and laboratory quantification of HIV-1 RNA viral load (VL) to report laboratory-based VL outcomes and compare self-reported and laboratory-reported VL., Methods: Between 2016 and 2017, 766 US HIV-positive MSM enrolled in a Web-based behavioral intervention were invited to participate in an at-home dried blood spot (DBS) collection study using HemaSpot-HF kits (Spot On Sciences, Inc, Austin, TX) for laboratory-quantified VL., Results: Of those invited to participate, 72.3% (554/766) enrolled in the DBS study. Most (79.2%, 439/554) men enrolled reported attempting to collect their blood, 75.5% (418/554) of participants mailed a DBS specimen to the research laboratory, and 60.8% (337/554) had an adequate blood sample for VL testing. Of the 337 specimens tested for VL by the laboratory, 52.5% (177/337) had detectable VL (median: 3508 copies/mL; range: 851-1,202,265 copies/mL). Most men (83.9%, 135/161) who returned a DBS specimen with laboratory-quantified detectable VL self-reported an undetectable VL during their last clinical visit., Conclusions: Home collection of DBS samples from HIV-positive MSM is feasible and has the potential to support clinical VL monitoring. Discrepant laboratory HIV-1 RNA values and self-reported VL indicate a need to address perceived VL status, especially in the era of treatment as prevention. Most participants were willing to use an at-home DBS kit in the future, signaling an opportunity to engage high-risk MSM in long-term HIV care activities., (©Sabina Hirshfield, Richard A Teran, Martin J Downing Jr, Mary Ann Chiasson, Hong-Van Tieu, Laura Dize, Charlotte A Gaydos. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 01.11.2018.)

Antibody-based epidemiologic surveillance to determine population-level exposure to sexually transmitted infections could help inform public health fertility preservation strategies. We compared the performance of three platforms to detect antibodies against the Chlamydia trachomatis (CT) antigen Pgp3 - multiplex bead array (MBA), enzyme-linked immunosorbent assay (ELISA), and lateral flow assay (LFA) - on sera from adolescents and young adults (AYAs) with pelvic inflammatory disease (PID). Ninety-five of 118 AYAs diagnosed with PID (80.5%) had positive antibody response to Pgp3 antigen by at least one test, and 78 (66.1%) tested positive by all three tests. Among 27 individuals with infection detected using nucleic acid amplification testing, 92.6% were positive by MBA (25/27), 77.8% (21/27) were positive by ELISA, and 74.1% (20/27) were positive by LFA. These data suggest that the MBA was the most sensitive of the three tests and could be useful in seroepidemiologic studies designed to assess population-level exposure to CT.

Screening for sexually transmitted infections (STIs) outside of traditional health-care facilities is limited by the privacy needed for sample collection. We explored the acceptability of privacy shelters for the self-collection of genital swabs and tested the use of privacy shelters during mobile STI screening. Attendees ≥14 years old at two outdoor community events completed a questionnaire that assessed participant characteristics, health-care access, and rating of acceptability of self-collecting penile or vaginal swabs in a privacy shelter and four other private spaces: portable restroom, health van, home, and doctor's office. A privacy shelter was used during mobile STI screening. The majority (65%) of the 95 participants reported that using a privacy shelter was somewhat or very acceptable. No participant characteristics or health-care access factors were associated with the acceptability of privacy shelters. Women rated a privacy shelter more acceptable than a portable restroom or health van. Men rated a privacy shelter more acceptable than a portable restroom. During mobile STI screening, all 13 men and women who requested STI testing used the privacy shelter for self-sampling. Rating of acceptability before and after privacy shelter use was the same. Privacy shelters may enable STI screening without using a building or vehicle for sample collection.

Purpose: Serological testing for antibodies to Chlamydia trachomatis pgp3 is being evaluated as a tool to use for trachoma surveillance. There are limited data on the reproducibility of the test results using a multiplex platform., Methods: We tested the reproducibility of a serologic test for C. trachomatis pgp3 in 6 dried blood spots collected from a random sample of 45 children from a trachoma endemic area. The spots were tested on a multiplex bead array platform, using one bead set twice, using another bead set at the same time as the first, and using the same bead set twice on different days separated by several months. Seropositivity was defined using ROC analyses from the same external controls for both bead sets. We compared the mean fluorescent intensity unit minus background (MFI-BG) results using the intraclass correlation coefficient (ICC), and analyzed the concordance of seropositivity designation using the kappa statistic., Results: The tests using the same bead set were highly correlated, ICC = 0.997 (0.995-1.00). Even tested months apart, the slight loss of signal was not statistically significant (p = 0.06). The test of the two different bead sets showed high correlation, but the differences in MFI-BG was statistically significant. However, the serostatus of the children was unchanged comparing the seropositivity using one bead set compared to a second bead set., Conclusion: The reproducibility of the multiplex bead array for serological testing of antibodies to Chlamydia trachomatis pgp3 is high when the same bead set is used for testing., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A serologic test for antibodies to chlamydial antigen pgp3 may be a useful tool for trachoma surveillance. However, little is known about the stability of antibody status over time, or factors associated with seroreversion/conversion. A cohort of 2,111 children ages 1-9 years in Tanzania were followed for one year in the absence of mass azithromycin. At baseline and follow-up, they were evaluated for trachoma, chlamydial infection, and antibodies to chlamydial antigen pgp3. At baseline, 31% of children were seropositive for pgp3 antibodies and 6.4% seroreverted to negative over one year. Of those seronegative, 9.8% seroconverted over the year. The seroreverters had lower baseline mean fluorescence intensity (MFI-BG) values compared to the seropositives who remained positive (Odds Ratio = 0.04 for every unit increase in log 10 MFI-BG, 95% CI = 0.02-0.09), and were more likely to live in communities with trachoma <5% (p < 0.008). While seroconversion was expected, seroreversion was unexpected. The low seroprevalence rate reported from low endemic areas may be due to seroreversion as well as lack of exposure.

Self-collected rectal-swabs were tested for CT and NG on GeneXpert CT/NG as compared to APTIMA Combo2. Of 448 rectal-swabs, 22 were positive for CT; 7 for NG on both assays; two were discordant. Sensitivity and specificity of GeneXpert was 95.5% and 99.7% for chlamydia, respectively; for gonorrhea both were 100%., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Our previous pilot study during 2010-2013, based on the IWantTheKit (IWTK) home self-collection program for sexually transmitted infections (STIs), showed that voluntary risk score tool predicted STIs well in female volunteers compared to their male counterparts. Risk score became a required part of the IWTK program in August 2013. We investigated association of IWTK risk score and presence of STI in 592 male participants living in Maryland and Washington DC from August 2013 to April 2015. The risk score quiz includes questions on demographic and sexual risk behavior. Data were analyzed using the Cochran-Armitage test for trend to determine if prevalence of STIs (Chlamydia, gonorrhea, or trichomoniasis) increased with the higher risk score category. Overall, 57% of participants were aged < 30 years (mean: 30.1 ± 9.3 years); 42% white, 42% black, and 16% other races. The majority (67%) of participants had medium risk scores of 3-6, followed by high scores of 7-10 (22%), and 0-2 (11%). The overall prevalence of STIs was 10.5% (62/592). The prevalence of STIs was 3.1% for users with risk scores of 0-2, 10.4% for those with scores 3-6, and 14.3% for those with scores 7-10 (trend test: p = 0.019). Medium and high IWTK risk scores successfully predicted the probability of STIs in male participants after elimination of potential selection biases.

Importance: To verify districts for elimination of blinding trachoma, the World Health Organization requires a population-based surveillance survey for follicular trachoma (TF) and trachomatous trichiasis (TT) 2 years after mass drug administration (MDA) activities have ceased. However, it is unknown if 2 years provides enough time to discover reemergence., Objective: To determine the prevalence of trachoma from surveys among 4 districts in Nepal (Dailekh, Dang, Surkhet, and Kanchanpur) that had surveillance intervals of 2, 4, 8, and 10 years, respectively, after cessation of MDA., Design, Setting, and Participants: Cross-sectional surveys were carried out in 2015 and 2016. Data analyses were done from March to September 2016. Among 20 clusters randomly selected from each district, 15 were randomly selected for infection and antibody testing: TF and TT were assessed, conjunctival swabs were tested for chlamydial infection, and blood spots were collected on filter paper to test for antibodies to Chlamydia trachomatis pgp3 using a multiplex bead assay. The study setting was 4 districts previously endemic for trachoma in Nepal. Participants were randomly selected and included 50 children aged 1 to 9 years and 100 adolescents and adults 15 years and older from each of the 20 clusters; this investigation reports on the children., Main Outcomes and Measures: Length of time since the last round of MDA and the prevalence of TF among children aged 1 to 9 years and the prevalence of TT among adolescents and adults 15 years and older., Results: Of 3024 children surveyed in the clusters, 48.0% (n = 1452) were female. The mean (SD) age of the children was 5.4 (2.6) years. Eleven cases of TF were found, with a TF prevalence less than 1% in all 4 districts. Three cases of infection were found. Seropositivity for pgp3 antibody varied from 1.4% (95% CI, 0.7-2.6) in the district with a 10-year surveillance interval to 2.5% (95% CI, 1.3-4.5) in the district with a 4-year surveillance interval. Seropositivity increased slightly with age in only one district. The TT prevalence was less than 1 case per 1000 among the total population in all 4 districts after accounting for cases known to the health system and cases with no scarred conjunctiva., Conclusions and Relevance: This study found no evidence of reemergence of trachoma up to 10 years after cessation of MDA in 4 districts in children in Nepal. The recommendation for a surveillance survey at 2 years, as proposed by the World Health Organization, is supported by these data. Determining if individuals with TT had scarring or are known to the health system was critical for meeting elimination criteria of blinding trachoma.

Trial Design: Trachoma is targeted for global elimination. Infection rates with Chlamydia trachomatis are higher in new arrivals to a community and in travelers who leave for extended periods, suggesting they are sources of re-infection. This community-randomized, clinical trial was designed to determine if a surveillance program that targeted newcomers and travelers, identified weekly, would result in more communities achieving levels of infection of ≤1%., Methods: 52 communities were randomly allocated 1:1 to the control (annual MDA alone if warranted) or intervention arm (annual MDA if warranted, plus a surveillance program to identify and treat newcomers and travelers). In each community, surveys were completed every six months on a random sample of 100 children ages 1-9 years for trachoma and infection. The primary outcome was the proportion of communities in the intervention arm, compared to the control arm, which had a prevalence of infection at ≤1% by 24 months. Registered: clinicaltrials.gov(NCT01767506)., Results: Intervention communities experienced an average of 110 surveillance events per month. At 24 months, 7 (27%) of 26 intervention communities achieved a prevalence of infection ≤1% compared to 4 (15%) of the 26 control communities (odds ratio = 2·6, 95%CI = 0·56-11·9). At 24 months, the average infection prevalence in the intervention communities was 4·8, compared to 6·9 in the control communities (p = ·06)., Conclusion: Despite surveillance programs for community newcomers and travelers, the proportion of intervention communities with a level of infection ≤1% was lower than expected and not significantly different from control communities.

Purpose: Testing for antibodies to Chlamydia trachomatis has potential as a surveillance tool. Our evaluation compares lateral flow assays (LFAs) during surveillance surveys in Nepal with Multiplex bead array (MBA). Fifty children were randomly sampled from each of 15 random clusters in two districts of Nepal. Finger prick blood samples were collected from 1509 children and tested onsite for anti-Pgp3 antibodies by LFA. The LFA was read at 30min as negative, positive, or invalid. Tests results were also rated as difficult to read ("equivocal"). Blood was processed at Johns Hopkins University using the MBA., Results: The LFA had agreement of 40.0% for MBA-positive samples and 99.3% for MBA-negative samples. Inter-reader reliability was kappa=0.65 (95% CI=0.56-0.74). If the equivocal results (7%) could be decreased, reliability could be improved., Conclusions: Further optimization and testing of the LFA test are needed to improve agreement with MBA and the interpretation of the results., (Copyright © 2017. Published by Elsevier Inc.)

Purpose: Clinical trachoma is the current measure of effectiveness of antibiotic and environmental improvements in trachoma endemic communities. Impact assessments measure only trachomatous inflammation-follicular (TF). Trachomatous inflammation-intense (TI) is not used for decisions on stopping mass drug administration (MDA) or achieving intervention goals. We tested the supposition that TI was not associated with Chlamydia trachomatis when disease prevalence is low., Methods: In 35 communities undergoing MDA as part of a larger project, 110 children ages 1 to 9 years were randomly selected in each community for surveys at baseline, 6, and 12 months. Both eyelids were graded for TF and TI, and a swab for detection of C. trachomatis infection was taken., Results: Overall TF prevalence was 5% at baseline. Cases of TI alone constituted 15% of trachoma; 37% of TI cases had infection. At 6 and 12 months, the proportion of trachoma cases that had TI only was 13% and 20%; infection rates were similar to the rates in cases with TF alone., Conclusions: Despite low prevalence of trachoma, infection rates for TF alone and TI alone were similar at each time point. The exclusion of cases of TI alone when reporting trachoma prevalence discards additional information on infection. Trachomatous inflammation-intense could be considered as part of impact surveys.

Purpose: Immigrants and travelers may be sources of re-emergent infection in trachoma-endemic communities close to trachoma elimination. The primary objective of the A Surveillance and Azithromycin Treatment for Newcomers and Travelers Evaluation (ASANTE) trial was to determine whether a newcomer and traveler surveillance and treatment program in addition to annual mass drug administration (MDA) would reduce Chlamydia trachomatis infection when compared to MDA alone., Methods: ASANTE was a randomized controlled trial in 52 communities in Kongwa, Tanzania. In 26 intervention communities, monitors treated everyone in new households, in-coming children and guardians in existing households, and all persons in households who had traveled between annual MDA events. A total of 26 usual practice communities received MDA only. Surveys of 100 1-9-year-olds from each community were conducted at baseline and every 6 months up to 2 years to assess clinical trachoma and C. trachomatis infection. Data on demographics and environmental factors were also collected., Results: Mean prevalences of trachomatous inflammation - follicular (TF) and C. trachomatis were equivalent between the two arms (5.2% and 3.7% in intervention, and 4.9% and 3.6% in usual practice communities, respectively). Of 318 children with TF, 36.5% tested positive for C. trachomatis. TF prevalence was higher among households without a bicycle (p = 0.03) and lower with increasing child's age (p < 0.001). Infection prevalence was higher among households >30 minutes from water (p = 0.015). TF and infection prevalence decreased with increasing years of education (p = 0.004 and p = 0.002, respectively)., Conclusion: The ASANTE trial will inform guidance on the surveillance and treatment of persons traveling or newly arriving to communities hypo-endemic for trachoma.

Men were enrolled in a study to assess the performance and acceptability of self-collected penile meatal swabs as compared to clinician-collected urethral swabs for sexually transmitted infections (STIs). We expected penile-meatal swabs to perform favorably to urethral swabs for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), and Mycoplasma genitalium (MG) detection by nucleic acid amplification assays (NAATs). Of 203 swab pairs tested; for CT, penile-meatal swab sensitivity was 96.8% and specificity was 98.8%. NG sensitivity and specificity were 100% and 98.9%, respectively. For TV, sensitivity was 85.0% and specificity was 96.7%. For MG sensitivity and specificity were 79.3% and 99.4%, respectively. No significant statistical differences between sample type accuracy (CT: P=0.625; NG: P=0.248; TV: P=0.344; and MG: P=0.070) existed. Most men, 90.1%, reported self-collection of penile-meatal swabs as "Very Easy" or "Easy". Self-collected penile-meatal swabs appeared acceptable for NAAT STI detection and an acceptable collection method by men., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The World Health Organization (WHO) now requires a second surveillance survey for trachoma after an impact assessment has found follicular trachoma (TF) <5% to determine if re-emergence has occurred. Using new WHO guidelines, we undertook surveillance surveys, and determined the prevalence of infection and antibody positivity, in two districts in Nepal., Methods: 20 clusters were randomly selected within each district, 15 were randomly selected for antibody testing. In each cluster, we randomly selected 50 children ages 1-9 years and 100 adults ≥15 years. TF and trachomatous trichiasis (TT) were evaluated. Conjunctival swabs to test for chlamydial infection using GenXpert platform were obtained, and dried blood spots were collected to test for antibodies to Chlamydia Trachomatis pgp3 using the Luminex platform., Findings: 3 cases of TF were found in the two districts, and one case of infection. Pgp3 antibody positivity was 2·4% (95% confidence interval: 1·4%, 3·7%), and did not increase with age (P = 0.24). No clustering of antibody positivity within communities was found. TT prevalence was <1/1,000 population., Interpretation: The surveillance surveys, as proposed by WHO, showed no evidence for re-emergence of trachoma in two districts of Nepal. The low level and no significant increase by age in seroprevalence of antibodies to C trachomatis pgp3 antigen deserve further investigation as a marker of interruption of transmission., Competing Interests: The authors have declared that no competing interests exist.

We offered a point-of-care test for Trichomonas vaginalis to women via the Internet to determine if it was acceptable to women to perform the test at home. Most of the 102 participants felt that it was easy to collect the specimen, follow the instructions, and read and interpret the results for the trichomonas self-testing assay.

Background: The AmpliVue Trichomonas Assay (Quidel) is a new Federal Drug Administration-cleared rapid test for qualitative detection of Trichomonas vaginalis (TV) DNA in female vaginal specimens. The assay is based on BioHelix's helicase-dependent amplification isothermal technology in conjunction with a disposable lateral-flow detection device, with a total turnaround time of approximately 45 minutes., Objective: The objective of this study was to compare the performance of this new assay to wet preparation and culture as well as to another Federal Drug Administration-cleared nucleic acid amplification assay., Methods: Four clinician collected vaginal swabs were obtained from women attending sexually transmitted disease, family planning, and OB/GYN clinics and tested by AmpliVue Trichomonas Assay and comparator tests: saline microscopy, TV culture (InPouch), and Aptima TV. AmpliVue Trichomonas Assay results were compared with a composite positive comparator (CPC) as determined by the results from culture and/or wet mount microscopic examination. At least one of either the wet preparation or culture reference test results was required to be positive to establish CPC., Results: A total of 992 patients, 342 symptomatic and 650 asymptomatic patients, were included in the study. Results for AmpliVue for all women combined compared with saline microscopy and culture as a CPC yielded a sensitivity of 100%. Specificity for all women was 98.2%. Overall percent agreement versus Aptima TV was 97.8%. Sensitivity for AmpliVue compared with Aptima was 90.7% %, whereas specificity was 98.9%., Conclusions: The rapid AmpliVue Trichomonas Assay performed as well as microscopy and culture, and had comparable sensitivity and specificity to another nucleic acid amplification test for the detection of TV. This study provided evidence of new diagnostic options and indicated very good performance of amplified testing for detection of TV in symptomatic and asymptomatic women.

Background: Individuals who are sexually active may want to make a decision as to whether they are at risk for having a sexually transmitted infection (STI) such as Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis. Our goal was to develop and evaluate a simple self-taken sexual risk quiz for participants, ordering an online STI self-collection test kit to determine whether the score predicted infection status., Methods: As part of the IWantTheKit programme for home sample self-collection for STIs, 2010-2013, the programme asked male and female users to voluntarily take a risk quiz. The six-question quiz was about risk behaviour and included an age question. Data analyses were stratified by gender as determined a priori. Scores 0-10 were stratified into risk groups for each gender based on similar risk score-specific STI prevalence. Retrospective analyses were performed to assess whether risk group predicted aggregate STI positivity. Urogenital/rectal mailed samples were tested by nucleic acid amplification tests., Results: More females (N=836) than males (N=558) provided voluntary risk scores. The percentage of eligible participants who submitted scores was 43.9% for both females and males. There was a higher STI infection rate in females (14.0%) than in males (7.0%) for having any STI (p<0.001). Multivariate logistic analysis for females, which controlled for age and race, demonstrated that a higher risk score group independently predicted risk for having an STI (OR of 2.2 for risk scores 5-7 and 4.2 OR for scores of 8-10). For males, the multivariate model, which controlled for race, indicated that no risk score group was associated having an STI., Conclusions: Results of a participant's own sexual risk quiz score independently predicted STI positivity for women, but not for men. Further study of this simple risk quiz is required., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Trachoma is targeted for elimination by 2020. World Health Organization advises districts to undertake surveillance when follicular trachoma (TF) <5% in children 1-9 years and mass antibiotic administration has ceased. There is a question if other tools could be used for surveillance as well. We report data from a test for antibodies to C. trachomatis antigen pgp3 as a possible tool., Methodology: We randomly sampled 30 hamlets in Kilosa district, Tanzania, and randomly selected 50 children ages 1-9 per hamlet. The tarsal conjunctivae were graded for trachoma (TF), tested for C. trachomatis infection (Aptima Combo2 assay: Hologic, San Diego, CA), and a dried blood spot processed for antibodies to C. trachomatis pgp3 using a multiplex bead assay on a Luminex 100 platform., Principal Findings: The prevalence of trachoma (TF) was 0.4%, well below the <5% indicator for re-starting a program. Infection was also low, 1.1%. Of the 30 hamlets, 22 had neither infection nor TF. Antibody positivity overall was low, 7.5% and increased with age from 5.2% in 1-3 year olds, to 9.3% in 7-9 year olds (p = 0.015). In 16 of the 30 hamlets, no children ages 1-3 years had antibodies to pgp3., Conclusions: The antibody status of the 1-3 year olds indicates low cumulative exposure to infection during the surveillance period. Four years post MDA, there is no evidence for re-emergence of follicular trachoma.

Ocular infection with Chlamydia trachomatis can lead to trachoma, a leading infectious cause of blindness. Trachoma is targeted for elimination by 2020. Clinical grading for ocular disease is currently used for evaluating trachoma elimination programs, but serological surveillance can be a sensitive measure of disease transmission and provide a more objective testing strategy than clinical grading. We calculated the basic reproduction number from serological data in settings with high, medium, and low disease transmission based on clinical disease. The data showed a striking relationship between age seroprevalence and clinical data, demonstrating the proof-of-principle that age seroprevalence predicts transmission rates and therefore could be used as an indicator of decreased transmission of ocular trachoma.

The www.iwantthekit.org provides Internet-based, at-home sexually transmitted infection screening. The Web site implemented an automated test result access system. To evaluate potential deleterious effects of the new system, we analyzed demographics, Web site usage, and treatment. The post-Web site design captured more participant information and no decrease in requests, kit return, or treatment adherence.

To demonstrate the feasibility and acceptability of mobile point-of-care and near-patient testing for sexually transmissible infections, we offered services during an annual community event and surveyed event-goers. Forty-two participants were tested. When provided with options, the majority of participants chose point-of-care or near-patient testing. Trichomoniasis, chlamydia and gonorrhea were detected. All but one infected participant were notified and prescribed treatment. Participants responding to a written questionnaire reported sample self-collection and testing in a van as acceptable, although men reported self-collection in a van as less acceptable than a doctor's office. Providing mobile point-of-care and near-patient sexually transmitted infection testing to the general population is feasible and acceptable.

Background: Blinding trachoma, caused by the bacteria Chlamydia trachomatis, is a neglected tropical disease targeted for elimination by 2020. A major component of the elimination strategy is mass drug administration (MDA) with azithromycin. Currently, program decisions are made based on clinical signs of ocular infection, but we have been investigating the use of antibody responses for post-MDA surveillance. In a previous study, IgG responses were detected in children lacking clinical evidence of trachoma, suggesting that IgG responses represented historical infection. To explore the utility of serology for program evaluation, we compared IgG and IgA responses to trachoma antigens and examined changes in IgG and IgA post-drug treatment., Methods: Dried blood spots and ocular swabs were collected with parental consent from 264 1-6 year olds in a single village of Kongwa District, central Tanzania. Each child also received an ocular exam for detection of clinical signs of trachoma. MDA was given, and six months later an additional blood spot was taken from these same children. Ocular swabs were analyzed for C. trachomatis DNA and antibody responses for IgA and total IgG were measured in dried bloods spots., Results: Baseline antibody responses showed an increase in antibody levels with age. By age 6, the percentage positive for IgG (96.0%) was much higher than for IgA (74.2%). Antibody responses to trachoma antigens declined significantly six months after drug treatment for most age groups. The percentage decrease in IgA response was much greater than for IgG. However, no instances of seroreversion were observed., Conclusions: Data presented here suggest that focusing on concordant antibody responses in children will provide the best serological surveillance strategy for evaluation of trachoma control programs.

Purpose: Mass drug administration (MDA) is part of the SAFE strategy for trachoma elimination. This study examined the effect of three annual MDAs on prevalence of trachoma among 13 longitudinal cohorts of Tanzanian children., Methods: Children younger than 10 years were assigned to cohorts based on age at baseline and followed annually for 3 years, with newborns assigned to new cohorts over time. Annual MDA consisted of topical tetracycline for children younger than 6 months and oral azithromycin for those 6 months and older. Follicular trachoma (TF) and Chlamydia trachomatis infection status were assessed annually before the next MDA. Prevalence and risk factors for TF and infection at each age were compared across cohorts., Results: At each survey, most age groups and cohorts had MDA coverage of more than 80% and showed decreased TF prevalence after every MDA. One cohort had consistently lower coverage, higher-than-expected TF and infection at ages 6 and 7, and elevated risk of TF at age 7 relative to the preceding cohort in spite of receiving one additional MDA (odds ratio 2.3, 95% confidence interval 1.0-5.2). Cohorts aged 1 or older at baseline generally showed reductions in TF and infection after each MDA, whereas younger cohorts showed decreased infection but increased TF over time. Successive cohorts of never-treated children younger than 1 year showed sequential TF and infection reductions with each MDA (P < 0.001)., Conclusions: Multiple MDAs significantly reduce trachoma prevalence and appear to increasingly protect children born into these communities. The youngest children show declining/stable rates of infection but increasing rates of trachoma, which may reflect longer duration of clinical signs.

Ocular swabs collected in Tanzania were evaluated by Amplicor CT PCR and Aptima Combo2 assays for the detection of Chlamydia trachomatis to determine if pooling could be used to reduce the cost of detection. Pooling would be an accurate method and has thus far resulted in a cost-savings of 62.2%., (© 2013.)

Purpose: To determine the sensitivity, specificity, and field utility of the Cepheid GeneXpert Chlamydia trachomatis (CT) Assay (GeneXpert) for ocular chlamydia infection compared to Roche Amplicor CT assay (Amplicor)., Methods: In a trachoma-endemic community in Kongwa Tanzania, 144 children ages 0 to 9 were surveyed to assess clinical trachoma and had two ocular swabs taken. One swab was processed at Johns Hopkins University, Baltimore MD, using Amplicor, (Roche Molecular Diagnostics) and the other swab was processed at a field station in Kongwa using the GeneXpert Chlamydia trachomatis/Neisseria gonorrhoeae assay (Cepheid). The sensitivity and specificity of GeneXpert was compared to the Amplicor assay., Results: Of the 144 swabs taken the prevalence of follicular trachoma by clinical exam was 43.7%, and by evidence of infection according to Amplicor was 28.5%. A total of 17 specimens (11.8%) could not be processed by GeneXpert in the field due to lack of sample volume, other specimen issues or electricity failure. The sensitivity of GeneXpert when compared to Amplicor was 100% and the specificity was 95%. The GeneXpert test identified more positives in individuals with clinical trachoma than Amplicor, 55% versus 52%., Conclusion: The GeneXpert test for C. trachomatis performed with high sensitivity and specificity and demonstrated excellent promise as a field test for trachoma control.

Background: Self-obtained penile-meatal swabs and urine specimens have been used for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) for outreach screening in men., Objective: To compare the sensitivity of self-collected male penile-meatal swabs and urine for the detection of CT, NG and TV., Methods: Matching penile-meatal swabs and urines were collected at home after recruitment to the study; via the internet programme, http://www.iwantthekit.org. The instructions directed the participant to place the tip of a Copan flocked swab at the meatal opening of the urethra to collect the penile-meatal sample. Two ml of urine was collected after the swab onto a Copan sponge-on-a-shaft collection device. Both swab and urine were placed into individual Aptima transport media tubes and mailed to the laboratory for testing. All specimens were tested for CT and NG using the GenProbe Aptima Combo2 Assay and for TV using GenProbe Aptima Analyte Specific Reagents with TV oligonucleotides., Results: Of 634 men, 86 (13.6%) were positive for CT, 9 (1.4%) were positive for NG and 56 (9.3%) positive for TV. For CT, swab sensitivity was 81/86 (94.2%), and urine sensitivity was 66/86 (76.7%). For NG, swab sensitivity was 9/9 (100%) and urine sensitivity was 8/9 (88.9%). For TV, swab sensitivity was 45/56 (80.4%) and urine sensitivity was 22/56 (39.3%)., Conclusions: Self-obtained penile-meatal swabs provided for the detection of more CT, NG and TV, than urine specimens.

The GeneXpert CT/NG assay (GeneXpert) and the Abbott m2000 RealTime CT (m2000) assay were compared to Amplicor for detecting ocular Chlamydia trachomatis. Discordant specimens were tested by the Aptima CT assay. The m2000 assay sensitivity was 100% (95% confidence interval [CI], 90% to 100%), and specificity was 98.46% (95% CI, 95.2% to 99.2%); GeneXpert sensitivity was 100% (95% CI, 90% to 100%), and specificity was 100% (95% CI, 98.1% to 100%). The m2000 and GeneXpert assays appear to perform as well as the Amplicor assay.