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There is a need for novel chemical matter for phenotypic and target-based screens to find starting points for drug discovery programmes in neglected infectious diseases and non-hormonal contraceptives that disproportionately affect Low- and Middle-Income Countries (LMICs). In some disease areas multiple screens of corporate and other libraries have been carried out, giving rise to some valuable starting points and leading to preclinical candidates. Whilst in other disease areas, little screening has been carried out. Much screening against pathogens has been conducted phenotypically as there are few robustly validated protein targets. However, many of the active compound series identified share the same molecular targets. To address the need for new chemical material, in this article we describe the design of a new library, designed for screening in drug discovery programmes for neglected infectious diseases. The compounds have been selected from the Enamine REAL (REadily AccessibLe) library, a virtual library which contains approximately 4.5 billion molecules. The molecules theoretically can be synthesized quickly using commercially available intermediates and building blocks. The vast majority of these have not been prepared before, so this is a source of novel compounds. In this paper we describe the design of a diverse library of 30,000 compounds from this collection (graphical abstract). The new library will be made available to laboratories working in neglected infectious diseases, subject to a review process. The project has been supported by the Bill & Melinda Gates Foundation and the Wellcome Trust (Wellcome). Author summary: Screening of diverse compound libraries is a powerful way to find chemical start points for drug discovery programmes. There is a lack of such chemical libraries available for neglected infectious diseases and other neglected areas such as non-hormonal contraception. In this paper we describe the design of such a library of 30,000 compounds (graphical abstract). The aim was to develop a library of diverse chemical matter unlikely to have been screened in these disease areas. The compounds were selected from the REAL (REadily AccessibLe) Enamine library, a virtual library of 4.5 billion compounds. The methodology for selection of the compounds is described, along with a detailed analysis of the physicochemical properties of the compounds and comparison to other libraries that we have assembled. This shows that the library contains hit/lead-like compounds suitable as chemical start points, and whilst it covers a similar space to some other libraries, the material within the library is mainly different to other libraries. Copies of the library will be made available for screening; the process for gaining access to this library is described. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the diagnostic efficacy of Xpert MTB/RIF assay for rapid diagnosis of Tuberculosis (TB) and detection of rifampicin (RIF) resistance in patients suspected of having EPTB, assessing it against traditional culture and drug susceptibility test (DST) by proportional method, and the ability to predict multidrug resistance TB by Xpert MTB/RIF assay. In this study, the Xpert MTB/RIF assay was applied to 1,614 extrapulmonary specimens. Compared with TB culture and Composite Reference Standard (CRS), the Xpert MTB/RIF assay had a high sensitivity and specificity for detection of EPTB. Depending on the culture method or CRS as the standard, sensitivity of the Xpert MTB/RIF assay for detection of MTB in pleural effusion, cerebrospinal fluid, thoracic drainage fluid and throat swabs specimens were lower than that of other specimens. According to the experimental results, we have reason to believe that Xpert MTB/RIF assay is a rapid and simple technique with high sensitivity and specificity for diagnosing EPTB and detecting drug resistance in variety of specimens. Xpert MTB/RIF assay combined with DST maybe identify more cases of multi-drug resistant tuberculosis (MDR-TB). Author summary: Tuberculosis (TB) is the second most deadly infectious disease after COVID-19. Improving the accessibility of WHO recommended rapid molecular diagnostic tests to achieve earlier and more accurate diagnosis of TB is an important part of strengthening TB laboratory work in the strategy of ending the epidemic of tuberculosis. Extrapulmonary tuberculosis (EPTB) accounts for 15% of all tuberculosis cases. Due to the unique biological samples of different classified EPTB and the occult nature of their onset, their diagnosis is more challenging. Smear microscopy is often insensitive and culture methods are prolonged. With the introduction of Xpert MTB/RIF assay (Cepheid Inc.), this has changed TB diagnostics by providing a rapid accessible platform to diagnose TB and identify rifampicin(RIF) resistance within 2h. Xpert MTB/RIF assay is a suite of semi-nested real-time fluorescent quantitative PCR in vitro diagnostic technologies with good detection efficiency. In recent years, WHO has limited recommended Xpert MTB/RIF assay to detect various types of samples other than sputum for preliminary diagnosis of EPTB. The purpose of this paper is to systematically evaluate the practical application effect of Xpert MTB/RIF assay in the clinical diagnosis of EPTB, and provide scientific guidance for clinicians.ű [ABSTRACT FROM AUTHOR]

Leprosy, or Hansen's disease, is one of the oldest infectious diseases in the world. It has long been associated with stigma and discrimination, but only in recent years has this aspect been formally recognized by the international community as a human rights issue. The UN Human Rights Council first adopted a resolution on leprosy in 2008, and this was later followed by a UN General Assembly resolution in 2010. Nonbinding principle and guidelines on elimination of discrimination against persons affected by leprosy and their family members accompanied the 2010 resolution, but these have yet to be fully implemented. In 2017, the Human Rights Council appointed a Special Rapporteur on leprosy to investigate the extent to which the principles and guidelines have been implemented, and her term was extended for a further 3 years in 2020. Considering the proper implementation of the principles and guidelines to be key to eliminating the discrimination that persons affected by leprosy and their families face in various parts of the world, this paper looks at the contribution the Special Rapporteur can make. Based on an assessment of her activities to date, it concludes that the Special Rapporteur has actively worked to build networks with persons affected by leprosy and related organizations and gain their trust, but has faced challenges in organizing official country visits. It goes on to analyze what sort of legacy the Special Rapporteur should aim to leave behind after completing her second term and how she can go about doing so in the time remaining. To this end, it makes 5 suggestions: (1) gather information systematically on the actual situation of discrimination; (2) compile a collection of success stories; (3) ensure that there is consistency between legally binding international covenants and treaties and the principles and guidelines; (4) present proposals for concrete actions that can be taken after the Special Rapporteur's second term ends; and (5) initiate a feasibility study on creating an "index" and "indicators" to measure the current status of stigma and discrimination and the extent to which the principles and guidelines have been implemented. [ABSTRACT FROM AUTHOR]

Background: Leprosy elimination primarily targets transmission of Mycobacterium leprae which is not restricted to patients' households. As interruption of transmission is imminent in many countries, a test to detect infected asymptomatic individuals who can perpetuate transmission is required. Antibodies directed against M. leprae antigens are indicative of M. leprae infection but cannot discriminate between active and past infection. Seroprevalence in young children, however, reflects recent M. leprae infection and may thus be used to monitor transmission in an area. Therefore, this literature review aimed to evaluate what has been reported on serological tests measuring anti-M. leprae antibodies in children without leprosy below the age of 15 in leprosy-endemic areas. Methods and findings: A literature search was performed in the databases Pubmed, Infolep, Web of Science and The Virtual Health Library. From the 724 articles identified through the search criteria, 28 full-text articles fulfilled all inclusion criteria. Two additional papers were identified through snowballing, resulting in a total of 30 articles reporting data from ten countries. All serological tests measured antibodies against phenolic glycolipid-I or synthetic derivatives thereof, either quantitatively (ELISA or UCP-LFA) or qualitatively (ML-flow or NDO-LID rapid test). The median seroprevalence in children in endemic areas was 14.9% and was stable over time if disease incidence remained unchanged. Importantly, seroprevalence decreased with age, indicating that children are a suitable group for sensitive assessment of recent M. leprae infection. However, direct comparison between areas, solely based on the data reported in these studies, was impeded by the use of different tests and variable cut-off levels. Conclusions: Quantitative anti-PGL-I serology in young children holds promise as a screening test to assess M. leprae infection and may be applied as a proxy for transmission and thereby as a means to monitor the effect of (prophylactic) interventions on the route to leprosy elimination. Author summary: Leprosy, a chronic infectious disease caused by Mycobacterium leprae (M. leprae), targets the skin and nerves and often results in irreversible disabilities as well as social exclusion. Though the disease can be efficiently treated, leprosy elimination is hampered by ongoing transmission of M. leprae. Currently, elimination is monitored by the number of new cases. Since only a small percentage of individuals infected with M. leprae develops disease, this does not accommodate monitoring of transmission. Previous studies have shown that antibody levels against M. leprae in blood correspond to the bacterial load in an individual and can be used as a proxy for infection, although antibodies cannot distinguish between past and present infection. In young children, infection is recent by definition, which allows assessment of more current state of transmission in an area. Thus, this literature review investigated studies on leprosy serology in children without leprosy. Our findings underscore that young children are a fitting group for up-to-date monitoring of M. leprae transmission in an area as seropositivity is inversely related with age. Importantly, a standardized, field-friendly test quantitatively measuring anti-M. leprae antibodies should be applied for population screening to monitor the status of transmission and thereby elimination in an area. [ABSTRACT FROM AUTHOR]

Rocky Mountain spotted fever (RMSF), a severe and extraordinarily lethal infectious disease, has emerged as a widespread public health crisis among predominantly vulnerable populations in several countries of Latin America, particularly evident in northern Mexico. Historically, RMSF has gained less attention than many other tropical infectious diseases, resulting in insufficient allocations of resources and development of capabilities for its prevention and control in endemic regions. We argue that RMSF fulfills accepted criteria for a neglected tropical disease (NTD). The relative neglect of RMSF in most Latin American countries contributes to disparities in morbidity and mortality witnessed in this region. By recognizing RMSF as an NTD, an increased public policy interest, equitable and more appropriate allocation of resources, scientific interest, and social participation can ameliorate the impact of this potentially treatable disease, particularly in vulnerable populations. Author summary: Rocky Mountain spotted fever (RMSF), a severe and extraordinarily lethal infectious disease, affects predominantly vulnerable populations in several countries of Latin America. The pathogen, Rickettsia rickettsii, is transmitted to humans through the bite of infected hard ticks from the family Ixodidae. When RMSF is not diagnosed or treated promptly, it often results in life-threatening disease and can be rapidly fatal in as many as 30% to 60% of patients. Among survivors, RMSF can result in long-term sequelae, including permanent cognitive deficits and amputations resulting from gangrene of extremities and appendages. Hyperendemic levels of RMSF, witnessed currently in multiple states across northern Mexico, arises from a complex interaction of zoonotic, environmental, and social determinants that pose enormous challenges to health systems and public policies. These same determinants also exist in most Latin American countries, which place the region at great risk for devastating levels of disease. Historically, RMSF has gained far less attention than many other tropical infectious diseases of equivalent or lesser magnitude, resulting in insufficient allocation of resources and limited efforts for its prevention and control. The neglect of RMSF in most Latin American countries contributes to broadening disparities in morbidity and mortality across this region that involve predominantly persons living in poverty, children, and to an increasing degree, pregnant women. Formal recognition of RMSF as a neglected tropical disease is an important step toward reducing the public health burden created by this disease, fostering political and scientific interest and increasing financial resources for the implementation of medical and sanitary interventions. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) and COVID-19 co-infection poses a significant global health challenge with increased fatality rates and adverse outcomes. However, the existing evidence on the epidemiology and treatment of TB-COVID co-infection remains limited. Methods: This updated systematic review aimed to investigate the prevalence, fatality rates, and treatment outcomes of TB-COVID co-infection. A comprehensive search across six electronic databases spanning November 1, 2019, to January 24, 2023, was conducted. The Joanna Briggs Institute Critical Appraisal Checklist assessed risk of bias of included studies, and meta-analysis estimated co-infection fatality rates and relative risk. Results: From 5,095 studies screened, 17 were included. TB-COVID co-infection prevalence was reported in 38 countries or regions, spanning both high and low TB prevalence areas. Prevalence estimates were approximately 0.06% in West Cape Province, South Africa, and 0.02% in California, USA. Treatment approaches for TB-COVID co-infection displayed minimal evolution since 2021. Converging findings from diverse studies underscored increased hospitalization risks, extended recovery periods, and accelerated mortality compared to single COVID-19 cases. The pooled fatality rate among co-infected patients was 7.1% (95%CI: 4.0% ~ 10.8%), slightly lower than previous estimates. In-hospital co-infected patients faced a mean fatality rate of 11.4% (95%CI: 5.6% ~ 18.8%). The pooled relative risk of in-hospital fatality was 0.8 (95% CI, 0.18–3.68) for TB-COVID patients versus single COVID patients. Conclusion: TB-COVID co-infection is increasingly prevalent worldwide, with fatality rates gradually declining but remaining higher than COVID-19 alone. This underscores the urgency of continued research to understand and address the challenges posed by TB-COVID co-infection. Author summary: Tuberculosis (TB) and COVID-19, both highly infectious diseases, have posed significant global health challenges, particularly in low/middle-income countries (LMICs) with limited medical resources. Our research highlights that TB-COVID co-infection remains a substantial concern, impacting regions with varying TB burdens. The predominant treatment approach for TB-COVID co-infection has not notably evolved since our earlier study in 2021. It typically involves a combination of the recommended TB regimen and standard COVID-19 treatment. Our analysis consistently shows that individuals with TB-COVID co-infection are at heightened risk of hospitalization, protracted recovery periods, and accelerated mortality compared to those with sole COVID-19 infections. Remarkably, we found limited information on the post-COVID-19 condition of co-infected patients. One study indicated a higher prevalence of anxiety symptoms, highlighting the potential psychological toll of TB-COVID co-infection. Although the fatality rate has gradually decreased, it remains notably higher than that of COVID-19 alone. Our findings underscore the urgent need for global collaboration to address the complex challenges posed by TB-COVID co-infection, particularly in countries with limited medical resources. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) is a neglected tropical disease (NTD) targeted by the World Health Organization for elimination as a public health problem (EPHP). Since 2000, more than 9 billion treatments of antifilarial medicines have been distributed through mass drug administration (MDA) programmes in 72 endemic countries and 17 countries have reached EPHP. Yet in 2021, nearly 900 million people still required MDA with combinations of albendazole, diethylcarbamazine and/or ivermectin. Despite the reliance on these drugs, there remain gaps in understanding of variation in responses to treatment. As demonstrated for other infectious diseases, some urgent questions could be addressed by conducting individual participant data (IPD) meta-analyses. Here, we present the results of a systematic literature review to estimate the abundance of IPD on pre- and post-intervention indicators of infection and/or morbidity and assess the feasibility of building a global data repository. Methodology: We searched literature published between 1st January 2000 and 5th May 2023 in 15 databases to identify prospective studies assessing LF treatment and/or morbidity management and disease prevention (MMDP) approaches. We considered only studies where individual participants were diagnosed with LF infection or disease and were followed up on at least one occasion after receiving an intervention/treatment. Principle findings: We identified 138 eligible studies from 23 countries, having followed up an estimated 29,842 participants after intervention. We estimate 14,800 (49.6%) IPD on pre- and post-intervention infection indicators including microfilaraemia, circulating filarial antigen and/or ultrasound indicators measured before and after intervention using 8 drugs administered in various combinations. We identified 33 studies on MMDP, estimating 6,102 (20.4%) IPD on pre- and post-intervention clinical morbidity indicators only. A further 8,940 IPD cover a mixture of infection and morbidity outcomes measured with other diagnostics, from participants followed for adverse event outcomes only or recruited after initial intervention. Conclusions: The LF treatment study landscape is heterogeneous, but the abundance of studies and related IPD suggest that establishing a global data repository to facilitate IPD meta-analyses would be feasible and useful to address unresolved questions on variation in treatment outcomes across geographies, demographics and in underrepresented groups. New studies using more standardized approaches should be initiated to address the scarcity and inconsistency of data on morbidity management. Author summary: Lymphatic filariasis (LF) is a debilitating parasitic disease that the World Health Organization (WHO) has earmarked for elimination by 2030 through a combination of mass distribution of anti-parasitic medicines and disease management approaches. Great strides have been made towards the elimination of LF as a public health problem, but nearly 900 million people still require treatment every year. In recent years, new combinations of medicines have been shown to improve the treatment of LF, yet there remain substantial gaps in understanding of apparent variability in treatment success and on the best treatment and management approaches to alleviate chronic morbidity. Some of these questions could be addressed through the development of a LF global data platform, which would enable pooled analyses of all available individual participant data. Here, we present the results of a systematic literature review of the LF treatment study landscape. We estimate the abundance of individual data on treatment of infection and morbidity and describe the characteristics of the studies and participants that have generated these data. We argue that collating and curating these data into a data LF platform could help to fill gaps in understanding of the best ways to treat infection and disease and enhance prospects of eliminating LF by 2030. [ABSTRACT FROM AUTHOR]

Background: Active trachoma is a highly contagious ongoing stage of trachoma that predominantly occurs during childhood in an endemic area. This study assessed the prevalence and factors associated with active trachoma among school-aged children. Methodology/Principal findings: A community-based analytical cross-sectional study was done from March 1st to June 30th, 2021, in Southwest Ethiopia's people's regional state. A total of 1292 school-aged children were surveyed. The quantitative data were collected using a pre-tested, structured interview-based questionnaire and observation check list. The World health organization (WHO) simplified trachoma grading system was used to assess stages of trachoma. In this study, the prevalence of active trachoma was 570(44.1%), 95% CI (41.4, 46.9). Also, age group 6–10; being female; flies at household (HH), flies on child's face, improved water source, improved sanitation, presence of ocular discharge, presence of nasal discharge, and unclean faces of the child were significantly associated with active trachoma. Conclusions/Significance: The very high prevalence of active trachoma in the study area is significantly associated with; age group 6–10, female gender, presence of flies in household and on child's face, presence of ocular and nasal discharge, unclean faces, improved water source, improved sanitation in the household. Thus, environmental sanitation and facial cleans trachoma elimination strategy should be intensified in the study area. Author summary: Trachoma is the leading cause of preventable blindness, due to repeated bacterial infection of the eye. The early and contagious stage of the disease, known as active trachoma, predominantly affects children. The impact of the disease includes permanent visual impairment, dependency and stigma. The WHO targeted to eliminate trachoma by 2030 as a public health concern in each endemic country. Through the implementation of the SAFE strategy (surgery to treat the blinding stage; antibiotics to clear infection; environmental improvement; improving access to water and sanitation). In Ethiopia majority of the districts are still trachoma endemic. Thus, this study assessed the prevalence and factors associated with active trachoma among school-aged children in Southwest Ethiopian Peoples Regional State. The region is highly endemic for several neglected tropical diseases including trachoma. In this study 44.1% of the participant had active trachoma. Also, age groups 6–10, being female, improved water sources, and sanitation, presence of flies in the house and on the child's face, ocular and nasal discharge, unclean faces were factors associated with the occurrence of active trachoma. Intensive scaling up of the facial cleanness and environmental improvement components of the SAFE strategy helps reduce the high prevalence of active trachoma. [ABSTRACT FROM AUTHOR]

Background: In leprosy patients, the most commonly reported non-viral co-infections are Tuberculosis, Leishmaniasis, Chromoblastomycosis and Helminths. The presence of a secondary infection is believed to increase the likelihood of leprosy reactions. The purpose of this review was to describe the clinical and epidemiological characteristics of the most reported bacterial, fungal, and parasitic co-infections in leprosy. Methodology/Principal findings: Following the PRISMA Extension for Scoping Reviews guidelines, a systematic literature search was conducted by two independent reviewers, resulting in the inclusion of 89 studies. For tuberculosis, a total of 211 cases were identified, with a median age of 36 years and male predominance (82%). Leprosy was the initial infection in 89% of cases, 82% of individuals had multibacillary disease, and 17% developed leprosy reactions. For leishmaniasis, 464 cases were identified, with a median age of 44 years and male predominance (83%). Leprosy was the initial infection in 44% of cases, 76% of individuals presented with multibacillary disease, and 18% developed leprosy reactions. Regarding chromoblastomycosis, we identified 19 cases with a median age of 54 years and male predominance (88%). Leprosy was the primary infection in 66% of cases, 70% of individuals had multibacillary disease, and 35% developed leprosy reactions. Additionally, we found 151 cases of co-infection with leprosy and helminths, with a median age of 43 years and male predominance (68%). Leprosy was the primary infection in 66% of cases, and 76% of individuals presented with multibacillary disease, while the occurrence of leprosy reactions varied from 37% to 81% across studies. Conclusion: We observed a male-dominated pattern of co-infections among working-age individuals with multibacillary leprosy. Unlike prior studies reporting increased leprosy reactions in chronic viral co-infections, our findings did not indicate any increase among bacterial, fungal, or parasitic co-infections. Rather, co-infections with tuberculosis and leishmaniasis appeared to reduce leprosy reactions. Author summary: Our review summarizes the clinical and epidemiological characteristics of non-viral co-infections in leprosy patients, including tuberculosis, leishmaniasis, chromoblastomycosis, and helminths. By conducting a systematic literature search, my colleagues and I identified 89 studies and found a male-dominated pattern of co-infections among working-age individuals with multibacillary leprosy. Our findings suggest that co-infections with tuberculosis and leishmaniasis may reduce the occurrence of leprosy reactions, which is in contrast to prior studies reporting increased reactions in chronic viral co-infections. Additionally, we observed that the occurrence of leprosy reactions varied from 37% to 81% across studies, depending on the type of helminth co-infection, which is higher than the general population. Overall, our study highlights the importance of understanding the potential impact of co-infections on leprosy patients, as it may affect their disease outcomes and treatment. This information is relevant not only to researchers and healthcare providers but also to the general public, as leprosy is still a significant public health problem in many parts of the world. Our review adds to the growing body of knowledge in the field of infectious diseases and underscores the need for further research on this topic. [ABSTRACT FROM AUTHOR]

Background: The global spread of infectious diseases is currently a prominent threat to public health, with the accelerating pace of globalization and frequent international personnel intercourse. The present study examined the epidemiological characteristics of overseas imported cases of acute infectious diseases in Guangzhou, China. Methods: We retrospectively investigated the distribution of diseases, demographic characteristics, and temporal and spatial variations of imported cases of acute infectious diseases in Guangzhou based on the surveillance data of notifiable infectious diseases from 2005 to 2019, provided by Guangzhou center for Disease Control and Prevention. The Cochran-Armitage trend test was applied to examine the trend in the number of imported cases over time. Results: A total of 1,025 overseas imported cases of acute infectious diseases were identified during the study period. The top three diseases were dengue (67.12%), malaria (12.39%), and influenza A (H1N1) pdm09 (4.10%). Imported cases were predominantly males, with a sex ratio of 2.6: 1 and 75.22% of the cases were those aged 20–49 years. Businessmen, workers, students and unemployed persons accounted for a large proportion of the cases (68.49%) and many of the cases came from Southeast Asia (59.02%). The number of imported cases of acute infectious diseases increased during the study period and hit 318 in 2019. A clear seasonal pattern was observed in the number of imported cases with a peak period between June and November. Imported cases were reported in all of the 11 districts in Guangzhou and the central districts were more seriously affected compared with other districts. Conclusions: The burden of dengue imported from overseas was substantial and increasing in Guangzhou, China, with the peak period from June to November. Dengue was the most common imported disease. Most imported cases were males aged 20–49 years and businessmen. Further efforts, such as strengthening surveillance of imported cases, paying close attention to the epidemics in hotspots, and improving the ability to detect the imported cases from overseas, are warranted to control infectious diseases especially in the center of the city with a higher population density highly affected by imported cases. Author summary: Guangzhou, a city located in the south of China, is heavily affected by imported infectious disease, with frequent trade, personnel movements and unique subtropical monsoon climate which favors transmissions of various infectious diseases. In this study, we examined the epidemiological characteristics of imported cases of acute infectious diseases in Guangzhou, 2005–2019. Our findings highlighted the potential risk of spread of infectious diseases triggered by imported cases. The top three imported acute infectious diseases were dengue, malaria and influenza A (H1N1)pdm09 and most of the imported cases came from Southeast Asian. The burden of dengue imported from overseas was substantial and increasing in Guangzhou, China, with the peak period from June to November. Most imported cases were males aged 20–49 years and businessmen. Further efforts, such as strengthening surveillance of imported cases, paying close attention to the epidemics in hotspots, and improving the ability to detect the imported cases from overseas, are warranted to control infectious diseases especially in the center of the city with a higher population density highly affected by imported cases. [ABSTRACT FROM AUTHOR]

Rabies is one of the most lethal infectious diseases, with those living in Asia and Africa having the highest risk of dying from rabies. We conducted a knowledge, attitudes and practices survey in urban and peri-urban areas of Bangladesh to describe canine bite rates, rabies knowledge, and healthcare seeking behaviors and barriers to human and dog vaccination. A bite risk assessment score (BRAS) and healthcare-seeking behavior score (HSBS) was calculated for each bite victim. Respondents were given two hypothetical situations to assess potential behaviors after a bite and willingness to pay for rabies vaccine and immunoglobulin. In total, 2,447 households participated in the survey and 85 bite victims were identified. The BRAS identified that 31% of bites posed no risk of rabies transmission. Multivariate analyses showed that living in Chittagong (β = 1.4; 95% CI: 0.1, 2.7) was associated with a higher HSBS. Findings presented here provide useful information regarding bite occurrences, healthcare-seeking behaviors, and a need for strategies to increase rabies awareness. Author summary: Rabies is one of the most lethal infectious diseases and those living in Asia and Africa have the highest risk of dying from rabies. Bangladesh has the third highest number of estimated human deaths from rabies of all countries with an estimated 2,000–2,500 deaths annually. In 2018, a knowledge, attitude, and practices (KAP) survey was conducted to better describe the rabies burden in four urban and rural areas. Our manuscript will deepen the understanding of ways to develop cost-effective, risk-based PEP delivery to persons with probable rabies exposures to prevent unnecessary PEP shortages among urban and peri-urban populations. The findings here provide useful information regarding bite occurrences, healthcare-seeking behaviors, and a need for strategies to increase rabies awareness in urban and peri-urban areas. This study confirmed a high human rabies death rate in Bangladesh despite a high rate of PEP usage and completion rates and makes a case for IBCM as cost effective means to rabies control in Bangladesh. [ABSTRACT FROM AUTHOR]

Background: Chagas disease is a long-lasting disease with a prolonged asymptomatic period. Cumulative indices of infection such as prevalence do not shed light on the current epidemiological situation, as they integrate infection over long periods. Instead, metrics such as the Force-of-Infection (FoI) provide information about the rate at which susceptible people become infected and permit sharper inference about temporal changes in infection rates. FoI is estimated by fitting (catalytic) models to available age-stratified serological (ground-truth) data. Predictive FoI modelling frameworks are then used to understand spatial and temporal trends indicative of heterogeneity in transmission and changes effected by control interventions. Ideally, these frameworks should be able to propagate uncertainty and handle spatiotemporal issues. Methodology/principal findings: We compare three methods in their ability to propagate uncertainty and provide reliable estimates of FoI for Chagas disease in Colombia as a case study: two Machine Learning (ML) methods (Boosted Regression Trees (BRT) and Random Forest (RF)), and a Linear Model (LM) framework that we had developed previously. Our analyses show consistent results between the three modelling methods under scrutiny. The predictors (explanatory variables) selected, as well as the location of the most uncertain FoI values, were coherent across frameworks. RF was faster than BRT and LM, and provided estimates with fewer extreme values when extrapolating to areas where no ground-truth data were available. However, BRT and RF were less efficient at propagating uncertainty. Conclusions/significance: The choice of FoI predictive models will depend on the objectives of the analysis. ML methods will help characterise the mean behaviour of the estimates, while LM will provide insight into the uncertainty surrounding such estimates. Our approach can be extended to the modelling of FoI patterns in other Chagas disease-endemic countries and to other infectious diseases for which serosurveys are regularly conducted for surveillance. Author summary: Metrics such as the per susceptible rate of infection acquisition (Force-of-Infection) are crucial to understand the current epidemiological situation and the impact of control interventions for long-lasting diseases in which the infection event might have occurred many years previously, such as Chagas disease. FoI values are estimated from serological age profiles, often obtained in a few locations. However, when using predictive models to estimate the FoI over time and space (including areas where serosurveys had not been conducted), methods able to handle and propagate uncertainty must be implemented; otherwise, overconfident predictions may be obtained. Although Machine Learning (ML) methods are powerful tools, they may not be able to entirely handle this challenge. Therefore, the use of ML must be considered in relation to the aims of the analyses. ML will be more relevant to characterise the central trends of the estimates while Linear Models will help identify areas where further serosurveys should be conducted to improve the reliability of the predictions. Our approaches can be used to generate FoI predictions in other Chagas disease-endemic countries as well as in other diseases for which serological surveillance data are collected. [ABSTRACT FROM AUTHOR]

Based on findings from focus groups and key informant interviews conducted at five sites in Liberia between 2018 and 2019, we explore some of the key factors that influenced people's motivation to travel during the 2014–2016 Ebola Virus Disease (EVD). We discuss how these factors led to certain mobility patterns and the implications these had for EVD response. The reasons for individual mobility during the epidemic were multiple and diverse. Some movements were related to relocation efforts as people attempted to extricate themselves from stigmatizing situations. Others were motivated by fear, convinced that other communities would be safer, particularly if extended family members resided there. Individuals also felt compelled to travel during the epidemic to meet other needs and obligations, such as attending burial rites. Some expressed concerns about obtaining food and earning a livelihood. Notably, these latter concerns served as an impetus to travel surreptitiously to evade quarantine directives aimed specifically at restricting mobility. Improvements in future infectious disease response could be made by incorporating contextually-based mobility factors, for example: the personalization of public health messaging through the recruitment of family members and trusted local leaders, to convey information that would help allay fear and combat stigmatization; activating existing traditional community surveillance systems in which entry into the community must first be approved by the community chief; and increased involvement of local leaders and community members in the provision of food and care to those quarantined so that the need to travel for these reasons is removed. Author summary: Human mobility is an important element of infectious disease outbreaks, both in terms of its spread and control. Understanding and dealing with the complex issue of human mobility warrants serious consideration in efforts to limit the spread of the disease. For these and other reasons, public health responses to infectious disease outbreaks must first be predicated upon a firm understanding of the contextual issues surrounding human movement and agency, especially those pertaining to the social, cultural and political-economic dimensions involved. Focus groups and key informant interviews conducted at five sites in Liberia in 2018/19 offered insight into the reasons people gave to account for their movements during the 2014/16 EVD outbreaks. Based on the understanding of mobility we gained from this study, we recommend that infectious disease response could be improved through the personalizing of public health messaging through the recruitment of family members and trusted local leaders to convey information that would help allay fear and combat stigmatization; activating existing traditional community surveillance systems in which entry into the community must first be approved by the community chief; and increased involvement of local leaders and community members in the provision of food and care to those quarantined so that the need to travel for these reasons is removed. [ABSTRACT FROM AUTHOR]

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. Author summary: Trachoma, one of the leading infectious causes of blindness globally, is targeted for elimination as a public health problem by 2030. District-level estimates of active trachoma among children 1–9 years old are currently used to guide control programs and assess elimination. However, active trachoma, based on diagnosis of clinical signs, is a subjective indicator. Serological markers present an objective, scalable alternative that could be measured in integrated platforms. In a hyperendemic region, community-level seroprevalence aligned more closely with concurrent infection prevalence than active trachoma. The correlation between seroprevalence and infection prevalence was stronger among 0–5-year-olds compared to 6–9-year-olds and was consistent over a three-year period of increasing transmission. Serosurveillance among children 0–5 years old may be a promising monitoring strategy to identify communities with the highest burdens of ocular chlamydial infection. [ABSTRACT FROM AUTHOR]

Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, the annual new case detection in 2019 was 202,189 globally. Measuring endemicity levels and burden in leprosy lacks a uniform approach. As a result, the assessment of leprosy endemicity or burden are not comparable over time and across countries and regions. This can make program planning and evaluation difficult. This study aims to identify relevant metrics and methods for measuring and classifying leprosy endemicity and burden at (sub)national level. Methods: We used a mixed-method approach combining findings from a systematic literature review and a Delphi survey. The literature search was conducted in seven databases, searching for endemicity, burden and leprosy. We reviewed the available evidence on the usage of indicators, classification levels, and scoring methods to measure and classify endemicity and burden. A two round Delphi survey was conducted to ask experts to rank and weigh indicators, classification levels, and scoring methods. Results: The literature review showed variation of indicators, levels, and cut-off values to measure leprosy endemicity and/or burden. The most used indicators for endemicity include new case detection rate (NCDR), new cases among children and new cases with grade 2 disability. For burden these include NCDR, MB cases, and prevalence. The classification levels 'high' and 'low' were most important. It was considered most relevant to use separate scoring methods for endemicity and burden. The scores would be derived by use of multiple indicators. Conclusion: There is great variation in the existing method for measuring endemicity and burden across countries and regions. Our findings contribute to establishing a standardized uniform approach to measure and classify leprosy endemicity and burden at (sub)national level, which would allow effective communication and planning of intervention strategies. Author summary: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. If left untreated, it could lead to deformity and resultant disabilities. The number of new cases has remained stagnant for the past decade. Additional interventions are required tailored to the level of endemicity and burden of an area. Currently, measuring and classifying endemicity and burden in leprosy lacks a standardized uniform approach, making program planning and evaluation difficult. We did a systematic literature search and Delphi survey, a method to elicit (group) opinion from a panel of experts, to take an inventory of indicators, classification levels and cut-offs that were used to measure and classify endemicity and burden of leprosy. This study highlights the variation in usage of indicators, levels, and cut-off values to determine the endemicity and burden of leprosy across regions and countries. There was agreement that endemicity and burden should be measured separately using multiple indicators, and that the classification levels 'high' and 'low' were most important. Our findings contribute to establishing a standardized uniform approach to measure and classify leprosy endemicity and burden at (sub)national level, which would allow effective communication and planning of intervention strategies. [ABSTRACT FROM AUTHOR]

Background: Trachoma is a worldwide infectious disease causing blindness. Trachoma continued as a public health problem in Ethiopia due to a lack of sanitation and inadequate prevention strategies. This study aimed to identify the impact of water supply and sanitation intervention on preventing active trachoma among children. Methods: Systematic literature searches were performed from 4 international databases. The search involved articles published from January 1995 up to March 2019. The Cochran Q and I2 statistical tests were used to check heterogeneity among the studies. A random-effect meta-analysis was employed to determine the pooled estimates with a 95% confidence interval (CI). Data analysis was performed using the CMA V.3 and RevMan 5 software program, and the result of the systematic review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Findings: Out of 211 studies screened for the analysis, only 29 studies were finally included in this systematic review and meta-analysis. The result revealed factors that are significantly associated with increased odds of active trachoma. Accordingly, households with no access to toilet facilities (odds ratio [OR]: 2.04, 95% CI: 1.75–2.38), no access to improved water (OR: 1.58, 95% CI: 1.27–1.96), and do not practice regular face washing for children (OR: 4.19, 95% CI: 3.02–5.81) have shown increased odds of active trachoma. Besides, the results show a higher prevalence of active trachoma among children who did not wash their faces with soap and frequently. Conclusions: The study found strong evidence that lack of access to water, sanitation, and hygiene (WASH) was associated with increased prevalence of active trachoma among children. Therefore, a comprehensive and partnership-oriented program is needed to tackle the problem, but further study will be required to strengthen its implementation. [ABSTRACT FROM AUTHOR]