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Abstract Background Policymakers, who are constantly discussing growing health expenditures, should know whether the health system is efficient. We can provide them with such information through international health system efficiency evaluations. The main objectives of this study are: (a) to evaluate the efficiency of health systems in 28 developed countries by multiple-criteria decision analysis (MCDA) and data envelopment analysis (DEA) and (b) to identify reasonable benchmark countries for the Czech Republic, for which we collect information on the relative importance of health system inputs and outputs. Methods We used MCDA and DEA to evaluate the efficiency of the health systems of 28 developed countries. The models included four health system inputs (health expenditure as a relative share of GDP, the number of physicians, nurses, and hospital beds) and three health system outputs (life expectancy at birth, healthy life expectancy, and infant mortality rate). The sample covers 27 OECD countries and Russia, which is also included in the OECD database. To determine the input and output weights, we used a questionnaire sent to health policy experts in the Czech Republic. Results We obtained subjective information on the relative importance of the health system inputs and outputs from 27 Czech health policy experts. We evaluated health system efficiency using four MCDA and two DEA models. According to the MCDA models, Turkey, Poland, and Israel were found to have efficient health systems. The Czech Republic ranked 16th, 19th, 15th, and 17th. The benchmark countries for the Czech Republic’s health system were Israel, Estonia, Luxembourg, Italy, the UK, Spain, Slovenia, and Canada. The DEA model with the constant returns to scale identified four technically efficient health systems: Turkey, the UK, Canada, and Sweden. The Czech Republic was found to be one of the worst-performing health systems. The DEA model with the variable returns to scale identified 15 technically efficient health systems. We found that efficiency results are quite robust. With two exceptions, the Spearman rank correlations between each pair of models were statistically significant at the 0.05 level. Conclusions During the model formulation, we investigated the pitfalls of efficiency measurement in health care and used several practical solutions. We consider MCDA and DEA, above all, as exploratory methods, not methods providing definitive answers.

Abstract Background An international comparison of health system performance is a popular tool of health policy analysis. However, the efficiency evaluation of health systems is a practical example of an international comparison in which non-homogeneity is expected. The objective of this paper is to evaluate the efficiency of health systems by models in which a degree of non-homogeneity among countries is considered. Methods We study the problem of non-homogeneity of health systems in the theoretical framework of the data envelopment analysis (DEA), which is a popular method of efficiency evaluation with hundreds of applications from various fields. DEA assume the homogeneity of production units and the homogeneity of the environment in which the production units operate. Hence, we compiled a summary of 14 recommendations on how to deal with the non-homogeneity in the DEA models. The analysed sample includes 38 OECD member countries. The data are from the year 2019. Results As an example, we evaluated the health system efficiency of the Czech Republic. We used the DEA models with the neighbourhood measure of distance and the constraint limiting the comparison of countries with different levels of economic development. The health system inputs were the numbers of physicians, nurses, and hospital beds. In the production of the intermediate outputs (doctor consultations, inpatient care discharges), the Czech Republic should look at Poland, Slovakia and Slovenia. In the production of health outcomes (life expectancy), the peer countries are France, Italy and Switzerland. Conclusions The results of the DEA analysis are only indicative because no single analytical method can determine whether a health system is better or worse than others. We need to combine different methods, and DEA is one of them. We consider DEA as an exploratory method, not a method providing definitive answers.

Abstract Background An analysis of the regional distribution of health resources is one of the tools for evaluating equal geographic access to health care. The usual analytical approach to an assessment of regional differences is to evaluate each health resource separately. This is a sensible approach, because there may be systematic reasons for any differences, for example, higher salaries in urban areas. However, a separate evaluation of the regional distribution of health resource capacities may be misleading. We should evaluate all health resource capacities as a whole and consider the substitutability of resources. Objective This study aims to measure regional inequalities in the Czech Republic with the help of alternative approaches to the evaluation of regional inequalities in the case of several substitutable health resources. Methods Five alternative evaluation methods (models) are described and applied: the separate evaluation, expert model, market model, common weights model, and production frontier model. Results The regional distribution of physicians and nurses in the Czech Republic in 2017 was evaluated. In spite of many regulations at the national and regional levels, we have found inequalities in regional resource distribution. The models that consider all health resources and the possibility of a resource substitution show lower inequalities between regional health resource capacities. Conclusion Both researchers and policy-makers should always consider the possibility of resource substitutions in the assessment of regional inequalities.

O artigo trata de análises de atividades esportivas em alunos púberes (12 a 15 anos) na República Tcheca e em alguns países da UE. O objetivo do estudo é analisar, verificar e identificar o status quo do interesse das crianças em atividades de locomotivas nas escolas básicas e sua atitude em relação a essas atividades, incluindo determinantes que moldam a atitude. O estudo é feito com a ajuda de pesquisa kinatropológica. Escolhemos um método baseado em levantamento de questionário e após análises e sínteses de dados obtidos. Esperávamos que mais de 50% dos alunos fizessem regularmente alguma atividade esportiva. Após a avaliação dos resultados, a nossa expectativa foi comprovada porque 93% das crianças dos estados da UE escolhidos fazem alguns esportes regularmente. ABSTRACT Physical activity of pubescent in the Czech Republic and other EU States The paper deals with analyses of sports activities in pubescent (12 – 15 years old) pupils in the Czech Republic and some EU countries. The aim of the study is to analyse, to verify and to identify the status quo of children’s interest in locomotive activities at basic schools and their attitude to these activities including determinants that shape the attitude. The study is done with help of kinatropological research. We chose a method based on questionnaire survey and following analyses and syntheses of gained data. We expected that over 50% of pupils do regularly some sport activity. After the evaluation of the results our expectation was proved true because 93% of children from the chosen EU states do some sports regularly.

The aim of the paper is to explain the specific structure of training (not only in the Czech Republic), its characteristics and its principles. It will also be useful to include some new, hitherto carefully hidden - also to point out and highlight some as-yet unpublished inside information about some specific training concepts of this martial art. An integral part of this training is to develop the internal energy called Qigong and some specific techniques within the different levels of performance in Kung Fu. Qigong is an effective part of alternative and natural medicine (and not only) in Shaolin Kung Fu and contribution highlights the need for the necessary representation of Qigong in Shaolin Kung Fu. Part of the contribution is also an aspect of the philosophy of martial arts Shaolin Kung Fu and its relationship to other martial arts. RESUMO O objetivo do artigo é explicar a estrutura específica de treinamento (não apenas na República Tcheca), suas características e seus princípios. Também será útil incluir alguns novos, até então cuidadosamente escondidos - também para destacar algumas informações ainda não publicadas sobre alguns conceitos específicos de treinamento dessa arte marcial. Uma parte integrante deste treinamento é desenvolver a energia interna chamada Qigong e algumas técnicas específicas dentro dos diferentes níveis de desempenho no Kung Fu. O Qigong é uma parte efetiva da medicina alternativa e natural (e não apenas) no Shaolin Kung Fu e a contribuição destaca a necessidade da representação necessária do Qigong no Shaolin Kung Fu. Parte da contribuição é também um aspecto da filosofia das artes marciais Shaolin Kung Fu e sua relação com outras artes marciais.

Biological systems manifest continuous weak autoluminescence, which is present even in the absence of external stimuli. Since this autoluminescence arises from internal metabolic and physiological processes, several works suggested that it could carry information in the time series of the detected photon counts. However, there is little experimental work which would show any difference of this signal from random Poisson noise and some works were prone to artifacts due to lacking or improper reference signals. Here we apply rigorous statistical methods and advanced reference signals to test the hypothesis whether time series of autoluminescence from germinating mung beans display any intrinsic correlations. Utilizing the fractional Brownian bridge that employs short samples of time series in the method kernel, we suggest that the detected autoluminescence signal from mung beans is not totally random, but it seems to involve a process with a negative memory. Our results contribute to the development of the rigorous methodology of signal analysis of photonic biosignals.

The existence of geographic differences in health resources, health expenditures, the utilization of health services, and health outcomes have been documented by a lot of studies from various countries of the world. In a publicly financed health system, equal access is one of the main objectives of the national health policy. That is why inequalities in the geographic allocation of health resources are an important health policy issue. Measures of inequality express the complexity of variation in the observed variable by a single number, and there is a variety of inequality measures available. The objective of this study is to develop a measure of the geographic inequality in the case of multiple health resources. The measure uses data envelopment analysis (DEA), which is a non-parametric method of production function estimation, to transform multiple resources into a single virtual health resource. The study shows that the DEA originally developed for measuring efficiency can be used successfully to measure inequality. For the illustrative purpose, the inequality measure is calculated for the Czech Republic. The values of separate Robin Hood Indexes (RHIs) are 6.64% for physicians and 3.96% for nurses. In the next step, we use combined RHI for both health resources. Its value 5.06% takes into account that the combinations of two health resources serve regional populations.

Mozambique is making progress towards elimination of trachoma as a public health problem, but in some districts trachomatous inflammation-follicular (TF) prevalence remains above the 5% elimination threshold despite years of various interventions, including antibiotic mass drug administration. To characterize transmission in four districts, we incorporated testing of ocular infection and serology into routine trachoma impact surveys (TIS) in August 2022. We examined residents aged ≥ 1 year for trachoma and collected information on household water, sanitation, and hygiene. Among children aged 1-9 years, we tested conjunctival swabs for Chlamydia trachomatis nucleic acid and dried blood spots for C. trachomatis antibodies. We modeled age-dependent seroprevalence to estimate seroconversion rate (SCR). We examined 4841 children aged 1-9 years. TF prevalence ranged between 1.1 and 6.0% with three districts below the 5% threshold. PCR-confirmed infection prevalence ranged between 1.1 and 4.8%, and Pgp3 seroprevalence ranged between 8.8 and 24.3%. Pgp3 SCR was 1.9 per 100 children per year in the district with the lowest TF prevalence. Two other districts with TF < 5% had SCR of 5.0 and 4.7. The district with TF ≥ 5% had a SCR of 6.0. This enhanced TIS furthered understanding of transmission in these districts and provides information on additional indicators for monitoring trachoma programs., (© 2024. The Author(s).)

Trachoma is targeted for global elimination as a public health problem by 2030. Measurement of IgG antibodies in children is being considered for surveillance and programmatic decision-making. There are currently no guidelines for applications of serology, which represents a generalizable problem in seroepidemiology and disease elimination. We collated Chlamydia trachomatis Pgp3 and CT694 IgG measurements (63,911 children ages 1-9 years) from 48 serosurveys, including surveys across Africa, Latin America, and the Pacific Islands to estimate population-level seroconversion rates (SCR) along a gradient of trachoma endemicity. We propose a novel, generalizable approach to estimate the probability that population C. trachomatis transmission is below levels requiring ongoing programmatic action, or conversely is above levels that indicate ongoing interventions are needed. We provide possible thresholds for SCR at a specified level of certainty and illustrate how the approach could be used to inform trachoma program decision-making using serology., Competing Interests: KR, PJH, and PME are employees of, and EMHE receives salary support from, the International Trachoma Initiative, which receives an operating budget and research funds from Pfizer Inc., the manufacturers of Zithromax® (azithromycin). The other authors declare no competing interests. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated.

Multiplex-based serological surveillance is a valuable but underutilized tool to understand gaps in population-level exposure, susceptibility, and immunity to infectious diseases. Assays for which blood samples can be tested for antibodies against several pathogens simultaneously, such as multiplex bead immunoassays, can more efficiently integrate public health surveillance in low- and middle-income countries. On March 7-8, 2023 a group of experts representing research institutions, multilateral organizations, private industry, and country partners met to discuss experiences, identify challenges and solutions, and create a community of practice for integrated, multi-pathogen serosurveillance using multiplex bead assay technologies. Participants were divided into six working groups: 1) supply chain; 2) laboratory assays; 3) seroepidemiology; 4) data analytics; 5) sustainable implementation; and 6) use case scenarios. These working groups discussed experiences, challenges, solutions, and research needs to facilitate integrated, multi-pathogen serosurveillance for public health. Several solutions were proposed to address challenges that cut across working groups.

To explore the effects of climate change on malaria and 20 neglected tropical diseases (NTDs), and potential effect amelioration through mitigation and adaptation, we searched for papers published from January 2010 to October 2023. We descriptively synthesised extracted data. We analysed numbers of papers meeting our inclusion criteria by country and national disease burden, healthcare access and quality index (HAQI), as well as by climate vulnerability score. From 42 693 retrieved records, 1543 full-text papers were assessed. Of 511 papers meeting the inclusion criteria, 185 studied malaria, 181 dengue and chikungunya and 53 leishmaniasis; other NTDs were relatively understudied. Mitigation was considered in 174 papers (34%) and adaption strategies in 24 (5%). Amplitude and direction of effects of climate change on malaria and NTDs are likely to vary by disease and location, be non-linear and evolve over time. Available analyses do not allow confident prediction of the overall global impact of climate change on these diseases. For dengue and chikungunya and the group of non-vector-borne NTDs, the literature privileged consideration of current low-burden countries with a high HAQI. No leishmaniasis papers considered outcomes in East Africa. Comprehensive, collaborative and standardised modelling efforts are needed to better understand how climate change will directly and indirectly affect malaria and NTDs., (© World Health Organization, 2024. All rights reserved. The World Health Organization has granted the Publisher permission for the reproduction of this article.)

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.)

Sudan is endemic for multiple neglected tropical diseases, including trachoma, onchocerciasis (OV), lymphatic filariasis (LF), and schistosomiasis (SCH). In 2019, dried blood spot samples were collected for a baseline trachoma serosurvey in three localities (El Seraif, Kotom, and Saraf Omrah) in North Darfur State. None were classified previously as OV- or LF-endemic, although low levels of SCH had been identified in all three. Approximately 30 households from 25 communities in each locality were selected by multistage cluster random sampling. Collections of DBSs were analyzed by multiplex bead assay for antibodies to multiple pathogens. This paper presents data on OV (Ov16), LF (Wb123, Bm14, Bm33), and SCH (soluble egg antigen [SEA], Sm25) antibodies among 8,322 individuals from 2,119 households. The survey-adjusted seroprevalence estimates for Ov16 were <0.3% in all localities. Lymphatic filariasis-antigen seroprevalences were discordant. Seroprevalence estimates ranged from 4.6-6.0% (Wb123), 0.99-1.4% (Bm14), and 29.2-33.3% (Bm33). Schistosomiasis seroprevalence estimates among school-aged children ranged from 2.7-8.0% (SEA) and 10.9-15.6% (Sm25). Ov16 seropositivity was low and supported the localities' classification as nonendemic. The results suggested LF exposure, but discordance between antigens, challenges defining seropositivity thresholds, and the absence of programmatic guidance based on antibody serology alone for Wuchereria bancrofti indicate a need for remapping surveys to confirm transmission. Schistosomiasis antibody levels were high enough to warrant further mapping to guide treatment decisions. The lack of gold standards limited interpretation of results, particularly for LF, but in resource-challenged areas, integrated serological surveillance offers the possibility of efficient monitoring of exposure to multiple diseases.

After years of programmatic inaccessibility, in 2019-2020 the Sudan Federal Ministry of Health Trachoma Control Program conducted population-based trachoma surveys in three localities (districts) in North Darfur state, Sudan. These baseline surveys were to determine the prevalence of trachomatous inflammation-follicular (TF) among children aged 1-9 years and to further use serological markers to understand the historical trachoma burden within this mass drug administration (MDA)-naive area. Trained and certified graders collected trachoma clinical data, and trained nurses collected dried blood spot (DBS) samples. The DBSs were assayed on a multiplex bead array for antibody responses to the Chlamydia trachomatis antigens Pgp3 and CT694. Across the three localities, 3,613 individuals aged 1-9 years and 3,542 individuals aged ≥15 years were examined for clinical signs, and 8,322 DBSs were collected. The prevalence of TF among children aged 1-9 years was endemic (≥5%) in two localities (El Seraif, 15.6%, and Saraf Omrah, 11.0%) and below the TF elimination threshold (<5%) in the third (Kotom, 1.4%). The Pgp3 seroprevalence among children aged 1-9 years was 34.1% in El Seraif, 35.0% in Saraf Omrah, and 11.0% in Kotom. Locality prevalence results were similar for Pgp3 and CT694. Seroprevalence increased with age in all three localities. Serological data collected within these surveys demonstrate that all three localities have had a long history of exposure to Chlamydia trachomatis and that two of the three localities require MDA to reach elimination as a public health problem threshold.

Background: Relapse rates of 47 % have been reported in patients with neuromyelitis optica (NMOSD) using Azathioprine (AZA) and mycophenolate mofetil (MMF). Prediction of non-responders could help determine which patients are most likely to benefit from newer monoclonal antibody treatments from the outset., Objectives: To identify predictors of AZA and MMF treatment response in NMOSD., Methods: Multicenter cohort study of NMOSD patients from Brazil and the United Kingdom, treated with AZA and MMF. An unsatisfactory response was defined as one severe or two non-severe attacks in a year. Cox regression was used to identify predictive factors of unsatisfactory response to AZA and MMF., Results: 103 NMOSD patients, mean age 38 years, 83% female, and 65% of Black ethnic group were included. An unsatisfactory IS response was observed in 42% of patients over 2.5 years (IQR 1.0-8.8) years. A severe preceding attack was more common in non-responders (31.1% x 76.7%, p = <0.001). In multivariable analysis, severe attack (RR 3.13; 95 % CI 1.37-7.18, p = 0.007) or higher annualized relapse rate (RR 4.84; 95 % CI 2.01-11.65, p = < 0.001) predicted an unsatisfactory response. Interestingly, Black NMOSD patients had a lower risk of poor response (RR 0.39, 95 % CI 0.17-0.85, p = 0.019)., Conclusion: Severe attack and a higher annualized relapse rate before AZA or MMF initiation were associated with an unsatisfactory IS response. In patients with these characteristics, treatment with higher-efficacy drugs should be considered from the outset., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: Trachoma recrudescence after elimination as a public health problem has been reached is a concern for control programs globally. Programs typically conduct district-level trachoma surveillance surveys (TSS) ≥ 2 years after the elimination threshold is achieved to determine whether the prevalence of trachomatous inflammation-follicular (TF) among children ages 1 to 9 years remains <5%. Many TSS are resulting in a TF prevalence ≥5%. Once a district returns to TF ≥5%, a program typically restarts costly mass drug administration (MDA) campaigns and surveys at least twice, for impact and another TSS. In Amhara, Ethiopia, most TSS which result in a TF ≥5% have a prevalence close to 5%, making it difficult to determine whether the result is due to true recrudescence or to statistical variability. This study's aim was to monitor recrudescence within Amhara by waiting to restart MDA within 2 districts with a TF prevalence ≥5% at TSS, Metema = 5.2% and Woreta Town = 5.1%. The districts were resurveyed 1 year later using traditional and alternative indicators, such as measures of infection and serology, a "wait and watch" approach., Methods/principal Findings: These post-surveillance surveys, conducted in 2021, were multi-stage cluster surveys whereby certified graders assessed trachoma signs. Children ages 1 to 9 years provided a dried blood spot and children ages 1 to 5 years provided a conjunctival swab. TF prevalence in Metema and Woreta Town were 3.6% (95% Confidence Interval [CI]:1.4-6.4) and 2.5% (95% CI:0.8-4.5) respectively. Infection prevalence was 1.2% in Woreta Town and 0% in Metema. Seroconversion rates to Pgp3 in Metema and Woreta Town were 0.4 (95% CI:0.2-0.7) seroconversions per 100 child-years and 0.9 (95% CI:0.6-1.5) respectively., Conclusions/significance: Both study districts had a TF prevalence <5% with low levels of Chlamydia trachomatis infection and transmission, and thus MDA interventions are no longer warranted. The wait and watch approach represents a surveillance strategy which could lead to fewer MDA campaigns and surveys and thus cost savings with reduced antibiotic usage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

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.)

Purpose: Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys., Methods: Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported., Results: Between 29 th February 2016 and 24 th April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma., Conclusion: This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets.

The first nationally representative, population-based study of schistosomiasis seroprevalence in Nigeria was conducted using blood samples and risk-factor data collected during the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS). Schistosomiasis seroprevalence was estimated by analyzing samples for reactivity to schistosome soluble egg antigen (SEA) in a multiplex bead assay; NAIIS survey data were assessed to identify potential risk factors for seropositivity. The SEA antibody data were available for 31,459 children aged 0 to 14 years. Overall seroprevalence was 17.2% (95% CI: 16.3-18.1%). Seropositive children were identified in every age group, including children < 5 years, and seroprevalence increased with increasing age (P < 0.0001). Several factors were associated with increased odds of seropositivity, including being a boy (odds ratio [OR] = 1.34, 95% CI: 1.24-1.45), living in a rural area (OR = 2.2, 95% CI: 1.9-2.5), and animal ownership (OR = 1.67, 95% CI: 1.52-1.85). Access to improved sanitation and drinking water sources were associated with decreased odds of seropositivity (OR = 0.52, 95% CI: 0.47-0.58 and OR = 0.53, 95% CI: 0.47-0.60, respectively) regardless of whether the child lived in a rural (sanitation: adjusted odds ratio [aOR] = 0.7, 95% CI: 0.6-0.8; drinking water: aOR = 0.7, 95% CI: 0.6-0.8) or urban area (sanitation: aOR = 0.6, 95% CI: 0.5-0.7; drinking water: aOR = 0.5, 95% CI: 0.4-0.6), highlighting the importance of these factors for schistosomiasis prevention and control. These results identified additional risk populations (children < 5 years) and a new risk factor (animal ownership) and could be used to monitor the impact of control programs.

Baseline mapping in the two major population centers of Kiribati showed that trachoma was a public health problem in need of programmatic interventions. After conducting two annual rounds of antibiotic mass drug administration (MDA), Kiribati undertook trachoma impact surveys in 2019, using standardized two-stage cluster surveys in the evaluation units of Kiritimati Island and Tarawa. In Kiritimati, 516 households were visited and in Tarawa, 772 households were visited. Nearly all households had a drinking water source and access to an improved latrine. The prevalence of trachomatous trichiasis remained above the elimination threshold (0.2% in ≥15-year-olds) and was virtually unchanged from baseline. The prevalence of trachomatous inflammation-follicular (TF) in 1-9-year-olds decreased by approximately 40% from baseline in both evaluation units but remained above the 5% TF prevalence threshold for stopping MDA. TF prevalence at impact survey was 11.5% in Kiritimati and 17.9% in Tarawa. Infection prevalence in 1-9-year-olds by PCR was 0.96% in Kiritimati and 3.3% in Tarawa. Using a multiplex bead assay to measure antibodies to the C. trachomatis antigen Pgp3, seroprevalence in 1-9-year-olds was 30.2% in Kiritimati and 31.4% in Tarawa. The seroconversion rate, in seroconversion events/100 children/year, was 9.0 in Kiritimati and 9.2 in Tarawa. Seroprevalence and seroconversion rates were both assessed by four different assays, with strong agreement between tests. These results show that, despite decreases in indicators associated with infection at impact survey, trachoma remains a public health problem in Kiribati, and provide additional information about changes in serological indicators after MDA., Competing Interests: The authors report no competing interests to declare., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

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).)

In Romania, breast cancer (BC) is the most common malignancy in women. However, there is limited data on the prevalence of predisposing germline mutations in the population in the era of precision medicine, where molecular testing has become an indispensable tool in cancer diagnosis, prognosis, and therapeutics. Therefore, we conducted a retrospective study to determine the prevalence, mutational spectrum, and histopathological prediction factors for hereditary breast cancer (HBC) in Romania. A cohort of 411 women diagnosed with BC selected upon NCCN v.1.2020 guidelines underwent an 84-gene NGS-based panel testing for breast cancer risk assessment during 2018-2022 in the Department of Oncogenetics of the Oncological Institute of Cluj-Napoca, Romania. A total of 135 (33%) patients presented pathogenic mutations in 19 genes. The prevalence of genetic variants was determined, and demographic and clinicopathological characteristics were analyzed. We observed differences among BRCA and non- BRCA carriers regarding family history of cancer, age of onset, and histopathological subtypes. Triple-negative (TN) tumors were more often BRCA1 positive, unlike BRCA2 positive tumors, which were more often the Luminal B subtype. The most frequent non- BRCA mutations were found in CHEK2 , ATM , and PALB2 , and several recurrent variants were identified for each gene. Unlike other European countries, germline testing for HBC is still limited due to the high costs and is not covered by the National Health System (NSH), thus leading to significant discrepancies related to the screening and prophylaxis of cancer.

Objectives: Determining an accurate estimate of SARS-CoV-2 seroprevalence has been challenging in African countries where malaria and other pathogens are endemic. We compared the performance of one single-antigen assay and three multi-antigen SARS-CoV-2 IgG assays in a Nigerian population endemic for malaria., Methods: De-identified plasma specimens from SARS-CoV-2 RT-PCR positive, dried blood spot (DBS) SARS-CoV-2 RT-PCR positive, and pre-pandemic negatives were used to evaluate the performance of the four SARS-CoV-2 assays (Tetracore, SARS2MBA, RightSign, xMAP)., Results: Results showed higher sensitivity with the multi-antigen (81% (Tetracore), 96% (SARS2MBA), 85% (xMAP)) versus the single-antigen (RightSign (64%)) SARS-CoV-2 assay. The overall specificities were 98% (Tetracore), 100% (SARS2MBA and RightSign), and 99% (xMAP). When stratified based on <15 days to ≥15 days post-RT-PCR confirmation, the sensitivities increased from 75% to 88.2% for Tetracore; from 93% to 100% for the SARS2MBA; from 58% to 73% for RightSign; and from 83% to 88% for xMAP. With DBS, there was no positive increase after 15-28 days for the three assays (Tetracore, SARS2MBA, and xMAP)., Conclusion: Multi-antigen assays performed well in Nigeria, even with samples with known malaria reactivity, and might provide more accurate measures of COVID-19 seroprevalence and vaccine efficacy., Competing Interests: The authors have no conflicts of interest to declare.

Climate change is an indisputable threat to human health, especially for societies already confronted with rising social inequality, political and economic uncertainty, and a cascade of concurrent environmental challenges. Archaeological data about past climate and environment provide an important source of evidence about the potential challenges humans face and the long-term outcomes of alternative short-term adaptive strategies. Evidence from well-dated archaeological human skeletons and mummified remains speaks directly to patterns of human health over time through changing circumstances. Here, we describe variation in human epidemiological patterns in the context of past rapid climate change (RCC) events and other periods of past environmental change. Case studies confirm that human communities responded to environmental changes in diverse ways depending on historical, sociocultural, and biological contingencies. Certain factors, such as social inequality and disproportionate access to resources in large, complex societies may influence the probability of major sociopolitical disruptions and reorganizations-commonly known as "collapse." This survey of Holocene human-environmental relations demonstrates how flexibility, variation, and maintenance of Indigenous knowledge can be mitigating factors in the face of environmental challenges. Although contemporary climate change is more rapid and of greater magnitude than the RCC events and other environmental changes we discuss here, these lessons from the past provide clarity about potential priorities for equitable, sustainable development and the constraints of modernity we must address.

Black autistic individuals, regardless of age, have not been centered in autism research. Instead, they often exist on the margins-on the periphery of autism research. In fact, Black autistic adults are largely absent from the literature. Most participants in autism research are majority-white autistic individuals and families. In this conceptual article, we use intersectionality and Dis/ability Studies and Critical Race Theory theories to contextualize Black autistic adults' experiences. Second, we argue that systemic disparities and methodological concerns are two contributors to the scholarly neglect of Black autistic adults in autism research. Third, we provide guidelines to support researchers in moving from neglect to inclusive research with Black autistic adults., Competing Interests: No competing financial interests exist., (Copyright 2022, Mary Ann Liebert, Inc., publishers.)

Background: Yaws is targeted for eradication by 2030, using a strategy based on mass drug administration (MDA) with azithromycin. New diagnostics are needed to aid eradication. Serology is currently the mainstay for yaws diagnosis; however, inaccuracies associated with current serological tests makes it difficult to fully assess the need for and impact of eradication campaigns using these tools. Under the recommendation of the WHO Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases(NTDs), a working group was assembled and tasked with agreeing on priority use cases for developing target product profiles (TPPs) for new diagnostics tools., Methodology and Principal Findings: The working group convened three times and established two use cases: identifying a single case of yaws and detecting azithromycin resistance. One subgroup assessed the current diagnostic landscape for yaws and a second subgroup determined the test requirements for both use cases. Draft TPPs were sent out for input from stakeholders and experts. Both TPPs considered the following parameters: product use, design, performance, configuration, cost, access and equity. To identify a single case of yaws, the test should be able to detect an analyte which confirms an active infection with at least 95% sensitivity and 99.9% specificity. The high specificity was deemed important to avoid a high false positive rate which could result in unnecessary continuation or initiation of MDA campaigns. If used in settings where the number of suspected cases is low, further testing could be considered to compensate for imperfect sensitivity and to improve specificity. The test to detect azithromycin resistance should be able to detect known genetic resistance mutations with a minimum sensitivity and specificity of 95%, with the caveat that all patients with suspected treatment failure should be treated as having resistant yaws and offered alternative treatment., Conclusions: The TPPs developed will provide test developers with guidance to ensure that novel diagnostic tests meet identified public health needs., Competing Interests: The authors have declared that no competing interests exist.

This article presents outcomes from a Workshop entitled "Bioarchaeology: Taking Stock and Moving Forward," which was held at Arizona State University (ASU) on March 6-8, 2020. Funded by the National Science Foundation (NSF), the School of Human Evolution and Social Change (ASU), and the Center for Bioarchaeological Research (CBR, ASU), the Workshop's overall goal was to explore reasons why research proposals submitted by bioarchaeologists, both graduate students and established scholars, fared disproportionately poorly within recent NSF Anthropology Program competitions and to offer advice for increasing success. Therefore, this Workshop comprised 43 international scholars and four advanced graduate students with a history of successful grant acquisition, primarily from the United States. Ultimately, we focused on two related aims: (1) best practices for improving research designs and training and (2) evaluating topics of contemporary significance that reverberate through history and beyond as promising trajectories for bioarchaeological research. Among the former were contextual grounding, research question/hypothesis generation, statistical procedures appropriate for small samples and mixed qualitative/quantitative data, the salience of Bayesian methods, and training program content. Topical foci included ethics, social inequality, identity (including intersectionality), climate change, migration, violence, epidemic disease, adaptability/plasticity, the osteological paradox, and the developmental origins of health and disease. Given the profound changes required globally to address decolonization in the 21st century, this concern also entered many formal and informal discussions., (© 2022 American Association of Biological Anthropologists.)

Importance: 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., Objective: To determine the efficacy of mass azithromycin distributions to preschool-aged children as a strategy for trachoma elimination in areas with hypoendemic disease., Design, Setting, and Participants: 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., Interventions: 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., Main Outcomes and Measures: 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., Results: 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)., Conclusions and Relevance: 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., Trial Registration: ClinicalTrials.gov Identifier: NCT02048007.

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.

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.

The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1-59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger., (© 2022. The Author(s).)

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.)

Background: Chlamydia trachomatis causes pelvic inflammatory disease (PID) and tubal infertility. Plasmid gene protein 3 antibody (Pgp3Ab) detects prior chlamydial infections. We evaluated for an association of high chlamydial seropositivity with sequelae using a Pgp3Ab multiplex bead array (Pgp3AbMBA)., Methods: We performed chlamydia Pgp3AbMBA on sera from women 18-39 years old participating in the 2013-2016 National Health and Nutrition Examination Survey (NHANES) with urine chlamydia nucleic acid amplification test results. High chlamydial seropositivity was defined as a median fluorescence intensity (MFI ≥ 50 000; low-positive was MFI > 551-<50 000. Weighted US population high-positive, low-positive, and negative Pgp3Ab chlamydia seroprevalence and 95% confidence intervals (CI) were compared for women with chlamydial infection, self-reported PID, and infertility., Results: Of 2339 women aged 18-39 years, 1725 (73.7%) had sera, and 1425 were sexually experienced. Overall, 104 women had high positive Pgp3Ab (5.4% [95% CI 4.0-7.0] of US women); 407 had lowpositive Pgp3Ab (25.1% [95% CI 21.5-29.0]), and 914 had negative Pgp3Ab (69.5% [95% CI 65.5-73.4]). Among women with high Pgp3Ab, infertility prevalence was 2.0 (95% CI 1.1-3.7) times higher than among Pgp3Ab-negative women (19.6% [95% CI 10.5-31.7] versus 9.9% [95% CI 7.7-12.4]). For women with low Pgp3Ab, PID prevalence was 7.9% (95% CI 4.6-12.6) compared to 2.3% (95% CI 1.4-3.6) in negative Pgp3Ab., Conclusions: High chlamydial Pgp3Ab seropositivity was associated with infertility although small sample size limited evaluation of an association of high seropositivity with PID. In infertile women, Pgp3Ab may be a marker of prior chlamydial infection., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

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.

Programs to eliminate trachoma as a public health problem use prevalence of the clinical sign trachomatous inflammation-follicular (TF) in 1- to 9-year-olds in endemic districts to make decisions to begin or end mass drug administration with azithromycin. Trachomatous inflammation-follicular is used as a proxy for transmission of ocular Chlamydia trachomatis infection. Long-term monitoring of previously endemic districts for recrudescence of ocular C. trachomatis infection would benefit from a simple blood test that could be integrated with other public health programs. In this study, we evaluated multiple tests to measure antibodies against the C. trachomatis antigen Pgp3-a multiplex bead assay (MBA), an ELISA, and two versions of a lateral flow assay (LFA)-in four districts of the Amhara region of Ethiopia with varying levels of TF. Seroprevalence and seroconversion rate (SCR) results were proportional to TF prevalence by district for most tests, with the notable exception of the LFA using colloidal gold as the developing reagent. Changing the test developing reagent to black latex improved agreement between serological measures and TF prevalence and in inter-rater agreement. Seroconversion rate estimates using data derived from the LFA-gold assay were inconsistent with the shape of the age-seroprevalence curve, which did not increase in older ages. These data revealed potential complications with using SCR that will need further evaluation. Data from MBA, ELISA, and LFA with the black test line showed good agreement with each other and proportionality to TF estimates, providing further data that serology has potential utility for trachoma surveillance.

Multiplex bead assays (MBAs) for serologic testing have become more prevalent in public health surveys, but few studies have assessed their test performance. As part of a trachoma study conducted in a rural part of Ethiopia in 2016, dried blood spots (DBS) were collected from a random sample of 393 children aged 0 to 9 years, with at least two separate 6-mm DBS collected on a filter card. Samples eluted from DBS were processed using an MBA on the Luminex platform for antibodies against 13 antigens of nine infectious organisms: Chlamydia trachomatis, Vibrio cholera, enterotoxigenic Escherichia coli, Cryptosporidium parvum, Entamoeba histolytica, Camplyobacter jejuni, Salmonella typhimurium Group B, Salmonella enteritidis Group D, and Giardia lamblia. Two separate DBS from each child were processed. The first DBS was run a single time, with the MBA set to read 100 beads per well. The second DBS was run twice, first at 100 beads per well and then at 50 beads per well. Results were expressed as the median fluorescence intensity minus background (MFI-BG), and classified as seropositive or seronegative according to external standards. Agreement between the three runs was high, with intraclass correlation coefficients of > 0.85 for the two Salmonella antibody responses and > 0.95 for the other 11 antibody responses. Agreement was also high for the dichotomous seropositivity indicators, with Cohen's kappa statistics exceeding 0.87 for each antibody assay. These results suggest that serologic testing on the Luminex platform had strong test performance characteristics for analyzing antibodies using DBS.

Background: Serological surveys with multiplex bead assays can be used to assess seroprevalence to multiple pathogens simultaneously. However, multiple methods have been used to generate cut-off values for seropositivity and these may lead to inconsistent interpretation of results. A literature review was conducted to describe the methods used to determine cut-off values for data generated by multiplex bead assays., Methodology/principal Findings: A search was conducted in PubMed that included articles published from January 2010 to January 2020, and 308 relevant articles were identified that included the terms "serology", "cut-offs", and "multiplex bead assays". After application of exclusion of articles not relevant to neglected tropical diseases (NTD), vaccine preventable diseases (VPD), or malaria, 55 articles were examined based on their relevance to NTD or VPD. The most frequently applied approaches to determine seropositivity included the use of presumed unexposed populations, mixture models, receiver operating curves (ROC), and international standards. Other methods included the use of quantiles, pre-exposed endemic cohorts, and visual inflection points., Conclusions/significance: For disease control programmes, seropositivity is a practical and easily interpretable health metric but determining appropriate cut-offs for positivity can be challenging. Considerations for optimal cut-off approaches should include factors such as methods recommended by previous research, transmission dynamics, and the immunological backgrounds of the population. In the absence of international standards for estimating seropositivity in a population, the use of consistent methods that align with individual disease epidemiological data will improve comparability between settings and enable the assessment of changes over time., Competing Interests: The authors have declared that no competing interests exist.

Successful achievement of global targets for elimination of trachoma as a public health problem and eradication of yaws will require control efforts to reach marginalized populations, including refugees. Testing for serologic evidence of transmission of trachoma and yaws in residents of registered camps and a Makeshift Settlement in Cox's Bazar District, Bangladesh, was added to a serosurvey for vaccine-preventable diseases (VPDs) conducted April-May 2018. The survey was primarily designed to estimate remaining immunity gaps for VPDs, including diphtheria, measles, rubella, and polio. Blood specimens from 1- to 14-year-olds from selected households were collected and tested for antibody responses against antigens from Treponema pallidum and Chlamydia trachomatis using a multiplex bead assay to evaluate for serologic evidence of the neglected tropical diseases (NTDs) yaws and trachoma, respectively. The prevalence of antibodies against two C. trachomatis antigens in children ranged from 1.4% to 1.5% for Pgp3 and 2.8% to 7.0% for CT694. The prevalence of antibody responses against both of two treponemal antigens (recombinant protein17 and treponemal membrane protein A) tested was 0% to 0.15% in two camps. The data are suggestive of very low or no transmission of trachoma and yaws, currently or previously, in children resident in these communities. This study illustrates how integrated serologic testing can provide needed data to help NTD programs prioritize limited resources.

WHO and its partners aim to interrupt yaws transmission in countries of endemicity and to certify others as being yaws-free. Transmission can be assessed using rapid plasma reagin (RPR) tests, reflecting current or recent infection, but RPR is operationally impractical. We evaluated changes in antibody levels against two recombinant treponemal antigens, rp17 (also known as Tp17) and TmpA, after antibiotic treatment given as part of a randomized controlled trial for yaws in Ghana and Papua New Guinea. Paired serum samples from children aged 6 to 15 years with confirmed yaws, collected before and after treatment, were tested for antibodies to rp17 and TmpA using a semiquantitative bead-based immunoassay. Of 344 baseline samples, 342 tested positive for anti-rp17 antibodies and 337 tested positive for anti-TmpA antibodies. Six months after treatment, the median decrease in anti-rp17 signal was 3.2%, whereas the median decrease in anti-TmpA was 53.8%. The magnitude of change in the anti-TmpA response increased with increasing RPR titer fold change. These data demonstrate that responses to TmpA decrease markedly within 6 months of treatment whereas (as expected) those to rp17 do not. Incorporating responses to TmpA as a marker of recent infection within an integrated sero-surveillance platform could provide a way to prioritize areas for yaws mapping.

Trachoma, caused by repeated ocular infection with Chlamydia trachomatis (Ct), is targeted for elimination as a public health problem. Serological testing for antibodies is promising for surveillance; determining useful thresholds will require collection of serological data from settings with different prevalence of the indicator trachomatous inflammation-follicular (TF). Dried blood spots were collected during trachoma mapping in two districts each of Togo and Democratic Republic of the Congo. Anti-Ct antibodies were detected by multiplex bead assay (MBA) and three different lateral flow assays (LFA) and seroprevalence and seroconversion rate (SCR) were determined. By most tests, the district with > 5% TF (the elimination threshold) had five-sixfold higher seroprevalence and tenfold higher SCR than districts with < 5% TF. The agreement between LFA and MBA was improved using a black latex developing reagent. These data show optimization of antibody tests against Ct to better differentiate districts above or below trachoma elimination thresholds.