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In group or cluster-randomized trials (GRTs), matching is a technique that can be used to improve covariate balance. When baseline data are available, we suggest a strategy that can be used to achieve the desired balance between treatment and control groups across numerous potential confounding variables. This strategy minimizes the overall within-pair Mahalanobis distance; and involves iteratively: 1) making pairs that minimize the distance between pairs of clusters with respect to potentially confounding variables; 2) visually assessing the potential effects of these pairs and resulting possible randomizations; and 3) reweighting variables of selecting weights to make pairs of clusters. In step 2, we plot the between-arm differences with a parallel-coordinates plot. Investigators can compare plots of different weighting schemes to determine the one that best suits their needs prior to the actual, final, randomization. We demonstrate application of the approach with the Mupirocin-Iodophor Swap Out trial. A webapp is provided.

Carryover, or the effects of treatment after it ceases, has been largely ignored in statistical literature except as a nuisance parameter. When testing for carryover, comparing cumulative incidence rates is biased when diagnosis is based on a noisy measurement crossing a threshold (such as in blood pressure) then followed by open-label treatment. This issue was raised in the context of preventing hypertension by the TROPHY trial. We show that modelling the noisy measurement itself using linear mixed effect models, then computing the expected proportion over the threshold, gives valid tests and consistent estimates. The key insight is that the data made unavailable by open-label treatment after diagnosis are missing at random. We demonstrate the analysis in simulations based on a large set of blood pressure measurements from a New Zealand healthcare organisation and show that properly specified random effects models accurately estimate carryover effects even in the presence of data censored at diagnosis.

Abstract Background The SCOPE trials (SCOPE 1, NeoSCOPE and SCOPE 2) have been the backbone of oesophageal RT trials in the UK. Many changes in oesophageal RT techniques have taken place in this time. The SCOPE trials have, in addition to adopting these new techniques, been influential in aiding centres with their implementation. We discuss the progress made through the SCOPE trials and include details of a questionnaire sent to participating centres. to establish the role that trial participation played in RT changes in their centre. Methods Questionnaires were sent to 47 centres, 27 were returned. Results 100% of centres stated their departmental protocol for TVD was based on the relevant SCOPE trial protocol. 4DCT use has increased from 42 to 71%. Type B planning algorithms, mandated in the NeoSCOPE trial, were used in 79.9% pre NeoSCOPE and now in 83.3%. 12.5% of centres were using a stomach filling protocol pre NeoSCOPE, now risen to 50%. CBCT was mandated for IGRT in the NeoSCOPE trial. 66.7% used this routinely pre NeoSCOPE/SCOPE 2 which has risen to 87.5% in the survey. Conclusion The results of the questionnaires show how participation in national oesophageal RT trials has led to the adoption of newer RT techniques in UK centres, leading to better patient care.

Abstract Background Recently, trials addressing noisy measurements with diagnosis occurring by exceeding thresholds (such as diabetes and hypertension) have been published which attempt to measure carryover - the impact that treatment has on an outcome after cessation. The design of these trials has been criticised and simulations have been conducted which suggest that the parallel-designs used are not adequate to test this hypothesis; two solutions are that either a differing parallel-design or a cross-over design could allow for diagnosis of carryover. Methods We undertook a systematic simulation study to determine the ability of a cross-over or a parallel-group trial design to detect carryover effects on incident hypertension in a population with prehypertension. We simulated blood pressure and focused on varying criteria to diagnose systolic hypertension. Results Using the difference in cumulative incidence hypertension to analyse parallel-group or cross-over trials resulted in none of the designs having acceptable Type I error rate. Under the null hypothesis of no carryover the difference is well above the nominal 5 % error rate. Conclusions When a treatment is effective during the intervention period, reliable testing for a carryover effect is difficult. Neither parallel-group nor cross-over designs using the difference in cumulative incidence appear to be a feasible approach. Future trials should ensure their design and analysis is validated by simulation.

This paper describes a diode-array pulsed spectrometer (DAPS) that performs flash photolysis studies with a time resolution of 10 ns and a spectral resolution of 2.4 nm over a 600-nm wavelength window in the range of 350-1100 nm. It employs a 1024-element photodiode-array detector with high dynamic range and low noise. Laser-pumped fluorescent dye mixtures are used as a novel, stable light source which enable it to record spectra with a photolimited S/N ratio equivalent to 0.001 abs. units in a single shot. The measuring light distribution can be tailored so that a constant S/N ratio across a spectrum is attainable even in regions of high absorbance. Electrical artifacts from the actinic laser or other discharges do not interfere with the measurement and the effects of scattered actinic light and fluorescence from the sample are minimized. The instrument is simple to build, using mainly standard lab equipment, and easy to maintain and operate. [ABSTRACT FROM AUTHOR]

Monitoring trachoma transmission with antibody data requires characterization of decay in IgG to Chlamydia trachomatis antigens. In a 3-year longitudinal cohort in a high-transmission setting, we estimated a median IgG half-life of 3 years and a seroreversion rate of 2.5 per 100 person-years (95% confidence interval, 1.6-3.5). Clinical Trials Registration NCT02754583., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The demand for acute eyecare exponentially outstrips capacity. The public lacks awareness of community eyecare services., Aim: To quantify the burden of acute eyecare on different healthcare service providers in a national population through prescribing and medicines provision by GPs, optometrists, and pharmacists, and provision of care by accident and emergency (A&E) services. A secondary aim was to characterise some of the drivers of this burden., Design and Setting: A retrospective data-linkage study set in Wales, UK., Method: Analysis of datasets was undertaken from the Secure Anonymised Information Linkage Databank (GP and A&E), the Eye Health Examination Wales service (optometry), and the Common Ailments Scheme (pharmacy) during 2017-2018., Results: A total of 173 999 acute eyecare episodes delivered by GPs (168 877 episodes) and A&E services (5122) were identified during the study. This resulted in 65.4 episodes of care per 1000 people per year. GPs prescribed a total of 87 973 653 prescriptions within the general population. Of these, 820 693 were related to acute eyecare, resulting in a prescribing rate of 0.9%. A total of 5122 eye-related and 905 224 general A&E attendances were identified, respectively, resulting in an A&E attendance rate of 0.6%. Optometrists and pharmacists managed 51.8% (116 868) and 0.6% (2635) of all episodes, respectively. Older females and infants of both sexes were more likely to use GP prescribing services, while adolescent and middle-aged males were more likely to visit A&E. GP prescribing burden was driven partially by economic deprivation, access to services, and health score. Season, day of the week, and time of day were predictors of burden in GP and A&E., Conclusion: Acute eyecare continues to place considerable burden on GP and A&E services in Wales, particularly in urban areas with greater economic deprivation and lower overall health. This is likely to increase with a rapidly ageing population. With ongoing pathway development to better utilise optometry and pharmacy, and improved public awareness, there may be scope to change this trajectory., (© The Authors.)

Baseline trachoma surveys in Côte d'Ivoire (2019) identified seven evaluation units (EUs) with a trachomatous inflammation-follicular (TF) prevalence ≥10%, but a trachomatous trichiasis (TT) prevalence in individuals ≥15 y of age below the elimination threshold (0.2%). Two of these EUs, Bondoukou 1 and Bangolo 2, were selected for a follow-up survey to understand the epidemiology of trachoma using additional indicators of Chlamydia trachomatis infection (DNA from conjunctival swabs) and exposure (anti-Pgp3 and Ct694 antibodies from dried blood spots [DBSs]). A two-stage cluster sampling methodology was used to select villages and households. All individuals 1-9 y of age from each selected household were recruited, graded for trachoma and had a conjunctival swab and DBS collected. Conjunctival swabs and DBSs were tested using Cepheid GeneXpert and a multiplex bead assay, respectively. The age-adjusted TF and infection prevalence in 1- to 9-year-olds was <1% and <0.3% in both EUs. Age-adjusted seroprevalence was 5.3% (95% confidence interval [CI] 1.5 to 15.6) in Bondoukou 1 and 8.2% (95% CI 4.3 to 13.7) in Bangolo 2. The seroconversion rate for Pgp3 was low, at 1.23 seroconversions/100 children/year (95% CI 0.78 to 1.75) in Bondoukou 1 and 1.91 (95% CI 1.58 to 2.24) in Bangolo 2. Similar results were seen for CT694. These infection, antibody and clinical data provide strong evidence that trachoma is not a public health problem in either EU., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Systematic studies 1-4 have revealed hundreds of ultra-compact dwarf galaxies (UCDs 5 ) in the nearby Universe. With half-light radii r h of approximately 10-100 parsecs and stellar masses M *  ≈ 10 6 -10 8  solar masses, UCDs are among the densest known stellar systems 6 . Although similar in appearance to massive globular clusters 7 , the detection of extended stellar envelopes 4,8,9 , complex star formation histories 10 , elevated mass-to-light ratio 11,12 and supermassive black holes 13-16 suggest that some UCDs are remnant nuclear star clusters 17 of tidally stripped dwarf galaxies 18,19 , or even ancient compact galaxies 20 . However, only a few objects have been found in the transient stage of tidal stripping 21,22 , and this assumed evolutionary path 19 has never been fully traced by observations. Here we show that 106 galaxies in the Virgo cluster have morphologies that are intermediate between normal, nucleated dwarf galaxies and single-component UCDs, revealing a continuum that fully maps this morphological transition and fills the 'size gap' between star clusters and galaxies. Their spatial distribution and redder colour are also consistent with stripped satellite galaxies on their first few pericentric passages around massive galaxies 23 . The 'ultra-diffuse' tidal features around several of these galaxies directly show how UCDs are forming through tidal stripping and that this evolutionary path can include an early phase as a nucleated ultra-diffuse galaxy 24,25 . These UCDs represent substantial visible fossil remnants of ancient dwarf galaxies in galaxy clusters, and more low-mass remnants probably remain to be found., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Healthcare-associated harm is an international public health issue. Children are particularly vulnerable to this with 15%-35% of hospitalised children experiencing harm during medical care. While many factors increase the risk of adverse events, such as children's dependency on others to recognise illness, children have a unique protective factor in the form of their family, who are often well placed to detect and prevent unsafe care. However, families can also play a key role in the aetiology of unsafe care.We aim to explore the role of families, guardians and parents in paediatric safety incidents, and how this may have changed during the pandemic, to learn how to deliver safer care and codevelop harm prevention strategies across healthcare settings., Methods and Analysis: This will be a retrospective study inclusive of an exploratory data analysis and thematic analysis of incident report data from the Learning from Patient Safety Events service (formerly National Reporting and Learning System), using the established PatIent SAfety classification system. Reports will be identified by using specific search terms, such as *parent* and *mother*, to capture narratives with explicit mention of parental involvement, inclusive of family members with parental and informal caregiver responsibilities.Paediatricians and general practitioners will characterise the reports and inter-rater reliability will be assessed. Exploratory descriptive analysis will allow the identification of types of incidents involving parents, contributing factors, harm outcomes and the specific role of the parents including inadvertent contribution to or mitigation of harm., Ethics and Dissemination: This study was approved by Cardiff University Research Ethics Committee (SMREC 22/32). Findings will be submitted to a peer-reviewed journal, presented at international conferences and presented at stakeholder workshops., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Trachoma, caused by ocular Chlamydia trachomatis infection, is targeted for global elimination as a public health problem by 2030. To provide evidence for use of antibodies to monitor C. trachomatis transmission, we collated IgG responses to Pgp3 antigen, PCR positivity, and clinical observations from 19,811 children aged 1-9 years in 14 populations. We demonstrate that age-seroprevalence curves consistently shift along a gradient of transmission intensity: rising steeply in populations with high levels of infection and active trachoma and becoming flat in populations near elimination. Seroprevalence (range: 0-54%) and seroconversion rates (range: 0-15 per 100 person-years) correlate with PCR prevalence (r: 0.87, 95% CI: 0.57, 0.97). A seroprevalence threshold of 13.5% (seroconversion rate 2.75 per 100 person-years) identifies clusters with any PCR-identified infection at high sensitivity ( >90%) and moderate specificity (69-75%). Antibody responses in young children provide a robust, generalizable approach to monitor population progress toward and beyond trachoma elimination., (© 2023. The Author(s).)

Seroepidemiology, or measuring antibodies to pathogens to estimate population-level exposure, can provide useful public health data. The tests used, however, often lack sufficient validation data due to absence of a gold standard. For many pathogens, serum antibodies can be detected long after resolution of infection, but infection status is often used as a gold standard for antibody positivity. To ensure that recently developed antibody tests for seroepidemiology of Chlamydia trachomatis (Ct), the causative agent of urogenital chlamydia and the blinding eye disease trachoma, have high performance, we generated a chimeric antibody to the immunodominant Ct antigen Pgp3. Two clones were selected to evaluate the test performance of three assays to measure antibodies to Pgp3: multiplex bead assay (MBA), enzyme-linked immunosorbent assay (ELISA), and lateral flow assay (LFA). Overall, each assay demonstrated high accuracy and precision when tested using either clone, and the clones were stable when stored at - 20 °C and 4 °C for almost 2 years. The limit of detection was similar for MBA and LFA, but almost a log-fold higher (i.e. less sensitive) using ELISA. Overall, the chimeric antibodies represent stable control reagents for tests with robust performance and will facilitate deployment of these tests to other laboratories., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Serosurveillance can provide estimates of population-level exposure to infectious pathogens and has been used extensively during the COVID-19 pandemic. Simultaneous, serological testing for multiple pathogens can be done using bead-based immunoassays to add value to disease-specific serosurveys. We conducted a validation of four SARS-CoV-2 antigens-full-length spike protein, two receptor binding domain proteins, and the nucleocapsid protein-on our existing multiplex bead assay (MBA) for enteric diseases, malaria, and vaccine preventable diseases. After determining the optimal conditions for coupling the antigens to microsphere beads, the sensitivity and specificity of the assay were determined on two instruments (Luminex-200 and MAGPIX) when testing singly (monoplex) versus combined (multiplex). Sensitivity was assessed using plasma from 87 real-time reverse transcription polymerase chain reaction (rRT-PCR) positive persons collected in March-May of 2020 and ranged from 94.3% to 96.6% for the different testing conditions. Specificity was assessed using 98 plasma specimens collected prior to December 2019 and plasma from 19 rRT-PCR negative persons and ranged from 97.4% to 100%. The positive percent agreement was 93.8% to 97.9% using 48 specimens collected > 21 days post-symptom onset, while the negative percent agreement was ≥ 99% for all antigens. Test performance was similar using monoplex or multiplex testing. Integrating SARS-CoV-2 serology with other diseases of public health interest could add significant value to public health programs that have suffered severe programmatic setbacks during the COVID-19 pandemic.

Background: The epidemiology of trachoma in several Pacific Islands differs from other endemic settings, in that there is a high prevalence of clinical signs of trachoma, particularly trachomatous inflammation-follicular (TF), but few cases of trichiasis and limited evidence of ocular chlamydial infection. This so-called "Pacific enigma" has led to uncertainty regarding the appropriate public health response. In 2019 alongside Nauru's national trachoma population survey, we performed bacteriological and serological assessments of children to better understand the typology of trachoma and to determine whether there is a need for trachoma interventions., Methods: We used two-stage cluster sampling, examining residents aged ≥1 year and collecting household-level water, sanitation, and hygiene (WASH) variables. Children aged 1-9 years provided conjunctival swabs and finger-prick dried blood spots to investigate the presence of Chlamydia trachomatis nucleic acid and anti-Pgp3 antibodies, respectively., Principal Findings: In 818 participants aged 1-9 years, the age-adjusted TF prevalence was 21.8% (95% CI 15.2-26.2%); ocular C. trachomatis prevalence was 34.5% (95% CI 30.6-38.9), and anti-Pgp3 antibody prevalence was 32.1% (95% CI 28.4%-36.3%). The age- and gender-adjusted prevalence of trichiasis in ≥15-year-olds was 0.3% (95% CI 0.00-0.85), but no individual with trichiasis had trachomatous scarring (TS). Multivariable analysis showed an association between age and both TF (OR per year of age 1.3 [95% CI 1.2-1.4]) and anti-Pgp3 positivity (OR 1.2 [95% CI 1.2-1.3]). There were high rates of access to water and sanitation and no WASH variable was associated with the presence of TF., Conclusions: TF, nucleic acid, and age-specific antibody prevalence collectively indicate that high levels of C. trachomatis transmission among children present a high risk of ocular damage due to trachoma. The absence of trichiasis with trachomatous scarring suggest a relatively recent increase in transmission intensity., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AB is employed by the International Trachoma Initiative at The Task Force for Global Health, which receives an operating budget and research funds from Pfizer Inc., the manufacturers of Zithromax (azithromycin). EMHE receives salary support from the International Trachoma Initiative.

Trachoma is the leading infectious cause of blindness. In 2016, Morocco was validated by WHO as having eliminated trachoma as a public health problem. We evaluated two previously endemic districts in Morocco for trachomatous inflammation-follicular (TF), trachomatous trichiasis (TT), and antibodies against Chlamydia trachomatis, the causative agent of trachoma. Community-based cross-sectional surveys in the districts of Boumalene Dades and Agdez included 4,445 participants for whom both questionnaire and serology data were available; 58% were aged 1-9 years. Participants had eyes examined for TF and blood collected for analysis of antibodies to the C. trachomatis antigen Pgp3 by both a multiplex bead assay (MBA) and lateral flow assay (LFA). Seroconversion rates (SCR) per 100 people per year were used to estimate changes in the force of infection using Bayesian serocatalytic models. In Agdez, TF prevalence in 1-9-year-olds was 0.3%, seroprevalence ranged from 9.4% to 11.4%, and SCR estimates ranged from 2.4 to 3.0. In Boumalene Dades, TF prevalence in 1-9-year-olds was 0.07%, and modeling data from the different assays indicated a decrease in transmission between 20 and 24 years ago. The TF data support an absence of active trachoma in the two districts examined. However, seroprevalence and SCR in younger people were higher in Agdez than Boumalene Dades, showing that there can be differences in serology metrics in areas with similar TF prevalence. Data will be included in multicountry analyses to better understand potential thresholds for serological surveillance in trachoma.

Trachoma is an infectious disease characterized by repeated exposures to Chlamydia trachomatis (Ct) that may ultimately lead to blindness. Efficient identification of communities with high infection burden could help target more intensive control efforts. We hypothesized that IgG seroprevalence in combination with geospatial layers, machine learning, and model-based geostatistics would be able to accurately predict future community-level ocular Ct infections detected by PCR. We used measurements from 40 communities in the hyperendemic Amhara region of Ethiopia to assess this hypothesis. Median Ct infection prevalence among children 0-5 years old increased from 6% at enrollment, in the context of recent mass drug administration (MDA), to 29% by month 36, following three years without MDA. At baseline, correlation between seroprevalence and Ct infection was stronger among children 0-5 years old (ρ = 0.77) than children 6-9 years old (ρ = 0.48), and stronger than the correlation between active trachoma and Ct infection (0-5y ρ = 0.56; 6-9y ρ = 0.40). Seroprevalence was the strongest concurrent predictor of infection prevalence at month 36 among children 0-5 years old (cross-validated R2 = 0.75, 95% CI: 0.58-0.85), though predictive performance declined substantially with increasing temporal lag between predictor and outcome measurements. Geospatial variables, a spatial Gaussian process, and stacked ensemble machine learning did not meaningfully improve predictions. Serological markers among children 0-5 years old may be an objective tool for identifying communities with high levels of ocular Ct infections, but accurate, future prediction in the context of changing transmission remains an open challenge., Competing Interests: The authors have declared that no competing interests exist.

Background: As prevalence decreases in pre-elimination settings, identifying the spatial distribution of remaining infections to target control measures becomes increasingly challenging. By measuring multiple antibody responses indicative of past exposure to different pathogens, integrated serological surveys enable simultaneous characterisation of residual transmission of multiple pathogens., Methodology/principal Findings: Here, we combine integrated serological surveys with geostatistical modelling and remote sensing-derived environmental data to estimate the spatial distribution of exposure to multiple diseases in children in Northern Ghana. The study utilised the trachoma surveillance survey platform (cross-sectional two-stage cluster-sampled surveys) to collect information on additional identified diseases at different stages of elimination with minimal additional cost. Geostatistical modelling of serological data allowed identification of areas with high probabilities of recent exposure to diseases of interest, including areas previously unknown to control programmes. We additionally demonstrate how serological surveys can be used to identify areas with exposure to multiple diseases and to prioritise areas with high uncertainty for future surveys. Modelled estimates of cluster-level prevalence were strongly correlated with more operationally feasible metrics of antibody responses., Conclusions/significance: This study demonstrates the potential of integrated serological surveillance to characterise spatial distributions of exposure to multiple pathogens in low transmission and elimination settings when the probability of detecting infections is low., Competing Interests: The authors have declared that no competing interests exist.

Background: WHO promotes the SAFE strategy for the elimination of trachoma as a public health programme, which promotes surgery for trichiasis (ie, the S component), antibiotics to clear the ocular strains of chlamydia that cause trachoma (the A component), facial cleanliness to prevent transmission of secretions (the F component), and environmental improvements to provide water for washing and sanitation facilities (the E component). However, little evidence is available from randomised trials to support the efficacy of interventions targeting the F and E components of the strategy. We aimed to determine whether an integrated water, sanitation, and hygiene (WASH) intervention prevents the transmission of trachoma., Methods: The WASH Upgrades for Health in Amhara (WUHA) was a two-arm, parallel-group, cluster-randomised trial in 40 rural communities in Wag Hemra Zone (Amhara Region, Ethiopia) that had been treated with 7 years of annual mass azithromycin distributions. The randomisation unit was the school catchment area. All households within a 1·5 km radius of a potential water point within the catchment area (as determined by the investigators) were eligible for inclusion. Clusters were randomly assigned (at a 1:1 ratio) to receive a WASH intervention either immediately (intervention) or delayed until the conclusion of the trial (control), in the absence of concurrent antibiotic distributions. Given the nature of the intervention, participants and field workers could not be masked, but laboratory personnel were masked to treatment allocation. The WASH intervention consisted of both hygiene infrastructure improvements (namely, construction of a community water point) and hygiene promotion by government, school, and community leaders, which were implemented at the household, school, and community levels. Hygiene promotion focused on two simple messages: to use soap and water to wash your or your child's face, and to always use a latrine for defecation. The primary outcome was the cluster-level prevalence of ocular chlamydia, measured annually using conjunctival swabs in a random sample of children aged 0-5 years from each cluster at 12, 24, and 36 month timepoints. Analyses were done in an intention-to-treat manner. This trial is ongoing and is registered at ClinicalTrials.gov, NCT02754583., Findings: Between Nov 9, 2015, and March 5, 2019, 40 of 44 clusters assessed for eligibility were enrolled and randomly allocated to the trial groups (20 clusters each, with 7636 people from 1751 households in the intervention group and 9821 people from 2211 households in the control group at baseline). At baseline, ocular chlamydia prevalence among children aged 0-5 years was 11% (95% CI 6 to 16) in the WASH group and 11% (5 to 18) in the control group. At month 36, ocular chlamydia prevalence had increased in both groups, to 32% (24 to 41) in the WASH group and 31% (21 to 41) in the control group (risk difference across three annual monitoring visits, after adjustment for prevalence at baseline: 3·7 percentage points; 95% CI -4·9 to 12·4; p=0·40). No adverse events were reported in either group., Interpretation: An integrated WASH intervention addressing the F and E components of the SAFE strategy did not prevent an increase in prevalence of ocular chlamydia following cessation of antibiotics in an area with hyperendemic trachoma. The impact of WASH in the presence of annual mass azithromycin distributions is currently being studied in a follow-up trial of the 40 study clusters. Continued antibiotic distributions will probably be important in areas with persistent trachoma., Funding: National Institutes of Health-National Eye Institute., Translation: For the Amharic translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests BA reports financial support to attend global health meetings from the Bill & Melinda Gates Foundation. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Two plasmid gene protein (Pgp3)-based serological assays, the Pgp3-ELISA and multiplex bead assay (Pgp3-MBA), were compared and used to estimate seropositivity of Chlamydia trachomatis (CT) among females 14 to 39 years old participating in the National Health and Nutrition Examination Survey between 2013-2016. Of the 2,201 specimens tested, 502 (29.5%, 95% CI 27.6-31.5) were positive using Pgp3-ELISA and 624 (28.4%, 95% CI 26.5-30.3) were positive using Pgp3-MBA. The overall agreement between the assays was 87.7%. Corresponding nucleic acid amplification test (NAAT) results were available for 1,725 specimens (from women 18-39 years old); of these, 42 (2.4%, 95% CI 1.8-3.3) were CT NAAT-positive. Most of the CT NAAT-positive specimens had corresponding positive serological assay results; 33 (78.6%, 95% CI 62.8-89.2) were Pgp3-ELISA-positive and 36 (85.7%, 95% CI 70.8-94.1) were Pgp3-MBA-positive. Although Pgp3-ELISA and Pgp3-MBA demonstrated equivalent performance in this study, an advantage of the Pgp3-MBA over Pgp3-ELISA is that it is well suited for high sample throughput applications., (Published by Elsevier Inc.)

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., Competing Interests: The authors have declared that no competing interests exist.