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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]

Background: Cryptosporidiosis is an emerging infectious disease of public health significance worldwide. The burden of disease caused by Cryptosporidium varies between and within countries/areas. To have a comprehensive understanding of epidemiological status and characteristics of human Cryptosporidium infection in China since the first report in 1987, a retrospective epidemiological analysis was conducted by presenting differences in the prevalence of Cryptosporidium by province, year, population, living environment and season and possible transmission routes and risk factors as well as genetic characteristics of Cryptosporidium in humans. Methodology/Principal findings: A systematic search was conducted to obtain epidemiological papers of human Cryptosporidium infection/cryptosporidiosis from PubMed and Chinese databases. Finally, 164 papers were included in our analysis. At least 200,054 people from 27 provinces were involved in investigational studies of Cryptosporidium, with an average prevalence of 2.97%. The prevalence changed slightly over time. Variable prevalences were observed: 0.65–11.15% by province, 1.89–47.79% by population, 1.77–12.87% and 0–3.70% in rural and urban areas, respectively. The prevalence peak occurred in summer or autumn. Indirect person-to-person transmission was documented in one outbreak of cryptosporidiosis in a pediatric hospital. 263 Cryptosporidium isolates were obtained, and seven Cryptosporidium species were identified: C. hominis (48.3%), C. andersoni (22.43%), C. parvum (16.7%), C. meleagridis (8.36%), C. felis (3.04%), C. canis (0.76%) and C. suis (0.38%). Conclusions/Significances: This systematic review reflects current epidemiological status and characteristics of Cryptosporidium in humans in China. These data will be helpful to develop efficient control strategies to intervene with and prevent occurrence of human Cryptosporidium infection/cryptosporidiosis in China as well as have a reference effect to other countries. Further studies should focus on addressing a high frequency of C. andersoni in humans and a new challenge with respect to cryptosporidiosis with an increasing population of elderly people and patients with immunosuppressive diseases. Author summary: Cryptosporidium is a major cause of diarrheal disease in humans globally. Due to the lack of effective drug treatment and vaccine prevention against cryptosporidiosis, it is particularly important to develop efficient control strategies to intervene with and prevent Cryptosporidium infection in humans. The present review presented and analyzed epidemiological status and characteristics of Cryptosporidium infection in humans in China since the first report in 1987. To date, epidemiological investigations of Cryptosporidium infecion have been carried out in different populations in 27 provinces, autonomous regions, and municipalities. Average prevalence of Cryptosporidium was 2.97% (5,933/200,054). Like other infectious disease, due to poor sanitation conditions in rural areas, people living in rural areas had a significantly higher prevalence of Cryptosporidium (1.77–12.87%) than those living in urban areas (0–3.70%). Seven Cryptosporidium species were identified, including C. hominis, C. andersoni, C. parvum, C. meleagridis, C. felis, C. canis and C. suis. This retrospective epidemiological analysis indicates wide geographical distribution of human Cryptosporidium infection/cryptosporidiosis in China. [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]

Introduction: Individuals and communities affected by NTDs are often the poorest and most marginalised; ensuring a gender and equity lens is centre stage will be critical for the NTD community to reach elimination goals and inform Universal Health Coverage (UHC). NTDs amenable to preventive chemotherapy have been described as a 'litmus test' for UHC due to the high mass drug administration (MDA) coverage rates needed to be effective and their model of community engagement. However, until now highly aggregated coverage data may have masked inequities in availability, accessibility and acceptability of medicines, slowing down the equitable achievement of elimination goals., Methods: We conducted qualitative programmatic analysis across different country contexts through the novel application of the Tanahashi Coverage Framework enhanced by gendered intersectional theory to interrogate different components of programme coverage: availability, accessibility, acceptability, contact and effective. Drawing on communities and health implementers perspectives (using focus groups, interviews, and participatory methods) from varying levels of the health system, across four African country contexts (Cameroon, Ghana, Liberia and Nigeria), we show who is left behind and provide recommendations for programmes to respond., Findings: We have unmasked inequities in programme delivery that repeatedly leave vulnerable populations underserved in relation to the prevention and treatment of PC NTDs across all components of coverage explored within the Tanahashi framework. Inequities are influenced by health systems challenges and limitations, due to lack of consideration of gender, power and equity issues. Effective treatment for individuals and communities is shaped by individual identities and the intersecting axes of inequity that converge to shape these positions including gender, age, disability, and geography. Health systems are inherently social and gendered thus they become mediators in managing the impact that social and structural processes have on individual health outcomes., Significance: To our knowledge this is the only paper which has combined a comprehensive equity framework with intersectional feminist theory, to establish a fuller understanding of who is left behind and why in MDA across countries and contexts. Ensuring the most vulnerable have continued access to future treatment options will contribute to the progressive realisation of UHC, allowing the NTD community to continue to support their vision of being a true 'litmus test'., Competing Interests: The authors have declared that no competing interests exist.

The Special Programme for Research and Training in Tropical Diseases (TDR) is an independent global programme of scientific collaboration cosponsored by the United Nations Children's Fund, the United Nations Development Program, the World Bank, and the World Health Organization. TDR's strategy is based on stewardship for research on infectious diseases of poverty, empowerment of endemic countries, research on neglected priority needs, and the promotion of scientific collaboration influencing global efforts to combat major tropical diseases. In 2001, in view of the achievements obtained in the reduction of transmission of Chagas disease through the Southern Cone Initiative and the improvement in Chagas disease control activities in some countries of the Andean and the Central American Initiatives, TDR transferred the Chagas Disease Implementation Research Programme (CIRP) to the Communicable Diseases Unit of the Pan American Health Organization (CD/PAHO). This paper presents a scientometric evaluation of the 73 projects from 18 Latin American and European countries that were granted by CIRP/PAHO/TDR between 1997 and 2007. We analyzed all final reports of the funded projects and scientific publications, technical reports, and human resource training activities derived from them. Results about the number of projects funded, countries and institutions involved, gender analysis, number of published papers in indexed scientific journals, main topics funded, patents inscribed, and triatomine species studied are presented and discussed. The results indicate that CIRP/PAHO/TDR initiative has contributed significantly, over the 1997–2007 period, to Chagas disease knowledge as well as to the individual and institutional-building capacity. [ABSTRACT FROM AUTHOR]

The predominant clonal evolution (PCE) model seeks to formulate a common population genetics framework for all micropathogens (namely, parasitic protozoa, fungi and yeasts, bacteria, and viruses). It relies on a definition of clonality that is only based on population structure features (namely, strongly restrained genetic recombination). Its clear-cut properties make it of strong interest for applied and basic research, since it permits the definition of stable, clearly delimited units of analysis below the species level: clonal genotypes and discrete genetic subdivisions (“near-clades”). These units of analysis can be used for clinical and epidemiological studies, vaccine and drug design, species description, and evolutionary studies on natural and experimental populations. In this review, the evolutionary and population genetics background of the model will be only briefly mentioned, while considerable emphasis will be given to its practical significance for the study and control of neglected tropical diseases. The goal of the paper is to make this practical usefulness accessible to a broad audience of readers, including scientists who are not evolution specialists, such as epidemiologists, field scientists, and clinicians. For extensive developments about the evolutionary background of the model, see our previous papers [–]. Citations of these former articles lead to the many references quoted in them, which cannot be listed again here. [ABSTRACT FROM AUTHOR]

During the West African Ebola Virus Disease (EVD) epidemic from 2014 to 2016, a variety of technologies travelled considering the context of the emergency: a highly contagious fast-killing disease outbreak with no known remedy and a rapidly increasing number of cases. The Ebola-Tx clinical trial tested the efficacy of Convalescent Plasma (CP) as a treatment for EVD in Guinea. This paper is based on ethnographic research in the Ebola-Tx trial and focuses on the introduction of a mobile plasma collection centre, referred to as the 'Plasma Mobile', equipped with plasmapheresis and pathogen inactivation technologies, as well as how the transfer itself of this technology entailed complex effects on CP donors as trial participants (i.e. providers of the therapeutic product), directly involved staff and more broadly on the trial implementation as a whole. The transfer led to the emergence of a dimension of hope as CP donors hoped that the plasma would cure and, as providers of the therapeutic, hoped it would decrease their stigmatization and the economic impact of the disease. We conclude that, in light of the intricate effects that the transfer of such health technology can entail–in the localization to the specific context, as well as in the consequences they can have on actors involved in the implementation of such technologies–global health technologies should be put at the services of next epidemic and pandemic (preparedness) on condition that they are accompanied by an understanding of the technologies' own cultural meanings and social understandings. Author summary: The Ebola-Tx trial tested the efficacy of Convalescent Plasma (CP) as a treatment for Ebola Virus Disease (EVD) in Guinea during the 2014–2016 West African outbreak. As part of the trial, a bus equipped with plasmapheresis and pathogen inactivation technologies, referred to as the 'Plasma Mobile', was used to collect plasma from Ebola survivors, hence recruited as CP donors. Previous studies on clinical trials during the EVD outbreak in West Africa showed positive impact triggered by the introduction of technologies such as improvements in work conditions and care. In our ethnographic research on the Plasma Mobile as transferred technology, we show that technologies contributed to bringing less stress and mistrust in the (highly sensitive issue of the) use of blood products. The organization of the technology in the Plasma Mobile aimed at avoiding mistakes and improving staff performance. In sum, we describe the effects of technologies in staff and CP donors, including the hope for new and improved futures for donors and EVD patients. These results may shed light upon epidemic preparedness, for instance on the need for providing cultural meaning and social understandings to the transfer of technologies. [ABSTRACT FROM AUTHOR]

Background: There is no point of care diagnostic test for infection with M. Leprae or for leprosy, although ELISA anti PGL-1 has been considered and sometimes used as a means to identify infection. Methods: A systematic review of all cohort studies, which classified healthy leprosy contacts, at entry, according to anti-PGL1 positivity, and had at least one year follow up. The outcome was clinical diagnosis of leprosy by an experienced physician. The meta-analysis used a fixed model to estimated OR for the association of PGL-1 positivity and clinical leprosy. A fixed model also estimated the sensibility of PGL-1 positivity and positive predictive value. Results: Contacts who were anti PGL-1 positive at baseline were 3 times as likely to develop leprosy; the proportion of cases of leprosy that were PGL-1 positive at baseline varied but was always under 50%. Conclusions: Although there is a clear and consistent association between positivity to anti PGL-1 and development of leprosy in healthy contacts, selection of contacts for prophylaxis based on anti PGL1 response would miss more than half future leprosy cases. Should chemoprophylaxis of controls be incorporated into leprosy control programmes, PGL1 appears not to be a useful test in the decision of which contacts should receive chemoprophylaxis. [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]

Introduction: Assessment of attitude of health care professionals is important as negative attitude could constitute a major deterrent to care-seeking by persons affected by neglected tropical diseases (NTDs) such as leprosy. Leprosy continues to pose a major disease burden in India with an annual new case detection rate of 10.17 per 100,000 population. This paper reports on the development and validation of a culturally appropriate scale to measure attitude of health care providers (HCPs) towards persons affected by leprosy in Tamil Nadu, India. Methodology/Principal findings: The Affective, Behavioural and Cognitive (ABC) model of attitudes guided the development of the scale. Steps in scale development included qualitative interviews and focus group discussions with medical officers and paramedical staffs selected from high prevalence districts in Tamil Nadu, India which informed the development of the draft scale. Reviews of existing attitude questionnaires in related areas further contributed to scale development and together helped to generate a large pool of items which was then subjected to Thurston’s scaling method for selection of items from this pool. Face and content validity were obtained, following which internal consistency and test, re-test reliability were assessed. Scaling exercise resulted in 11 items being discarded from an initial pool of 38, owing to the poor agreement among experts regarding relevance. Face and content validity were good with experts endorsing relevance and applicability of items. The intra-class correlation coefficient (ICC) for test re-test reliability of the 27 item scale was 0.6 (95% CI: 0.20–0.78) indicating marginal intra-class correlation. The overall Cronbach’s alpha was 0.85 while the alphas for each of the affective and behavioural components was good at 0.78 and 0.69 respectively indicating a good degree of consistency and homogeneity between items but the alpha for the cognitive component was low at 0.53. Conclusions: The ABC model of attitudes guided the development of the scale, ensured a mix of 27 items tapping into the three domains of Affect, Behaviour and Cognition which best explained the attitude construct. With good validity and alphas for each of the affective, behavioural components and overall alpha estimates, this scale can be a valuable tool to provide accurate estimates of the true attitudes held by HCPs. This, in turn, would be useful to obtain insights for appropriate intervention programmes that would help change negative attitudes of HCPs towards persons affected by leprosy. With some adaptations, the scales can be validated for other NTDs as well. [ABSTRACT FROM AUTHOR]

Infectious diseases attributable to unsafe water supply, sanitation and hygiene (e.g. Cholera, Leptospirosis, Giardiasis) remain an important cause of morbidity and mortality, especially in low-income countries. Climate and weather factors are known to affect the transmission and distribution of infectious diseases and statistical and mathematical modelling are continuously developing to investigate the impact of weather and climate on water-associated diseases. There have been little critical analyses of the methodological approaches. Our objective is to review and summarize statistical and modelling methods used to investigate the effects of weather and climate on infectious diseases associated with water, in order to identify limitations and knowledge gaps in developing of new methods. We conducted a systematic review of English-language papers published from 2000 to 2015. Search terms included concepts related to water-associated diseases, weather and climate, statistical, epidemiological and modelling methods. We found 102 full text papers that met our criteria and were included in the analysis. The most commonly used methods were grouped in two clusters: process-based models (PBM) and time series and spatial epidemiology (TS-SE). In general, PBM methods were employed when the bio-physical mechanism of the pathogen under study was relatively well known (e.g. Vibrio cholerae); TS-SE tended to be used when the specific environmental mechanisms were unclear (e.g. Campylobacter). Important data and methodological challenges emerged, with implications for surveillance and control of water-associated infections. The most common limitations comprised: non-inclusion of key factors (e.g. biological mechanism, demographic heterogeneity, human behavior), reporting bias, poor data quality, and collinearity in exposures. Furthermore, the methods often did not distinguish among the multiple sources of time-lags (e.g. patient physiology, reporting bias, healthcare access) between environmental drivers/exposures and disease detection. Key areas of future research include: disentangling the complex effects of weather/climate on each exposure-health outcome pathway (e.g. person-to-person vs environment-to-person), and linking weather data to individual cases longitudinally.

Background: Conducting clinical trials to assess experimental treatments for potentially pandemic infectious diseases is challenging. Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty. Outbreaks are sudden and unpredictable and so it is essential that as much planning as possible takes place in advance. Statistical aspects of such trial designs should be evaluated and discussed in readiness for implementation., Methodology/principal Findings: This paper proposes a generic ordinal sequential trial design (GOST) for a randomised clinical trial comparing an experimental treatment for an emerging infectious disease with standard care. The design is intended as an off-the-shelf, ready-to-use robust and flexible option. The primary endpoint is a categorisation of patient outcome according to an ordinal scale. A sequential approach is adopted, stopping as soon as it is clear that the experimental treatment has an advantage or that sufficient advantage is unlikely to be detected. The properties of the design are evaluated using large-sample theory and verified for moderate sized samples using simulation. The trial is powered to detect a generic clinically relevant difference: namely an odds ratio of 2 for better rather than worse outcomes. Total sample sizes (across both treatments) of between 150 and 300 patients prove to be adequate in many cases, but the precise value depends on both the magnitude of the treatment advantage and the nature of the ordinal scale. An advantage of the approach is that any erroneous assumptions made at the design stage about the proportion of patients falling into each outcome category have little effect on the error probabilities of the study, although they can lead to inaccurate forecasts of sample size., Conclusions/significance: It is important and feasible to pre-determine many of the statistical aspects of an efficient trial design in advance of a disease outbreak. The design can then be tailored to the specific disease under study once its nature is better understood.

Eumycetoma is a chronic infectious disease characterized by a large subcutaneous mass, often caused by the fungus Madurella mycetomatis. A combination of surgery and prolonged medication is needed to treat this infection with a success rate of only 30%. There is, therefore, an urgent need to find more effective drugs for the treatment of this disease. In this study, we screened 800 diverse drug-like molecules and identified 215 molecules that were active in vitro. Minimal inhibitory concentrations were determined for the 13 most active compounds. One of the most potent compounds, a fenarimol analogue for which a large analogue library is available, led to the screening of an additional 35 compounds for their in vitro activity against M. mycetomatis hyphae, rendering four further hit compounds. To assess the in vivo potency of these hit compounds, a Galleria mellonella larvae model infected with M. mycetomatis was used. Several of the compounds identified in vitro demonstrated promising efficacy in vivo in terms of prolonged larval survival and/or reduced fungal burden. The results presented in this paper are the starting point of an Open Source Mycetoma (MycetOS) approach in which members of the global scientific community are invited to participate and contribute as equal partners. We hope that this initiative, coupled with the promising new hits we have reported, will lead to progress in drug discovery for this most neglected of neglected tropical diseases. [ABSTRACT FROM AUTHOR]

Background: Leprosy is a condition that has long been associated with stigma and discrimination, even when infected persons have been cured. This paper describes stigma and discrimination as viewed by caregivers who are associated with people affected by leprosy in Ghana. Methods: A qualitative interview with semi-structured interviews were conducted for twenty caregivers. Results: Findings indicated that caregivers were of the view that people affected by leprosy in Ghana are stigmatized and discriminated against by the larger society thus making their movements and interactions restricted to the Leprosarium. Besides, employments opportunities are unavailable to them thus making them exposed to financial challenges. The livelihood Empowerment Against poverty (LEAP) money given them is not sufficient for their daily upkeep. Conclusion: People affected by leprosy in Ghana are stigmatized and therefore find it difficult to interact freely with the public. The associated physical deformities with the disease also tend to impede their ability to relate to the general public. The LEAP cash given to people affected by leprosy is helpful however, it could be enhanced to keep pace with prevailing economic conditions in the country. [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]

This year PLOS Neglected Tropical Diseases (PLOS NTDs) celebrates its tenth anniversary following the publication of the first issue in 2007 []. When PLOS NTDs was founded, the framework of the neglected tropical diseases (NTDs) as an alternative to “other diseases” (as they were then referred to in the Millennium Development Goals) was just getting started—especially for Africa [, ]. In the decade since, PLOS NTDs has overseen enormous successes in NTD control and elimination. Here, we want to briefly review the ten year progress made towards the control or elimination of the diseases now identified by the WHO as NTDs. Many of the details are highlighted in PLOS NTDs papers cited here, but the summary information is based on the recently released Global Burden of Disease (GBD) Study 2015 (also launched with Gates Foundation support) that summarized past-decade changes in disease prevalence, mortality, or disability rates (from the years 2005 to 2015) [–], as well as the GBD Study 2013 that summarizes disease prevalence changes over a longer time horizon from 1990 to 2013 []. [ABSTRACT FROM AUTHOR]

Background: The monitoring and evaluation of lymphatic filariasis (LF) has largely relied on the detection of antigenemia and antibodies in human populations. Molecular xenomonitoring (MX), the detection of parasite DNA/RNA in mosquitoes, may be an effective complementary method, particularly for detecting signals in low-level prevalence areas where Culex is the primary mosquito vector. This paper investigated the application of a household-based sampling method for MX in Tamil Nadu, India. Methods: MX surveys were conducted in 2010 in two evaluation units (EUs): 1) a hotspot area, defined as sites with community microfilaria prevalence ≥1%, and 2) a larger area that also encompassed the hotspots. Households were systematically selected using a sampling interval proportional to the number of households in the EU. Mosquito pools were collected and analyzed by real-time polymerase chain reaction (qPCR). Two independent samples were taken in each EU to assess reproducibility of results. Follow-up surveys were conducted in 2012. Results: In 2010, the proportion of positive pools in the hotspot EU was 49.3% compared to 23.4% in the overall EU. In 2012, pool positivity was significantly reduced to 24.3% and 6.5%, respectively (p<0.0001). Pool positivity based on independent samples taken from each EU in 2010 and 2012 were not significantly different except for the hotspot EU in 2012 (p = 0.009). The estimated prevalence of infection in mosquitoes, measured by PoolScreen, declined from 2.2–2.7% in 2010 to 0.6–1.2% in 2012 in the hotspot area and from 0.9–1.1% to 0.2–0.3% in the larger area. Conclusions: The household-based sampling strategy for MX led to mostly reproducible results and supported the observed LF infection trends found in humans. MX has the potential to be a cost-effective, non-invasive monitoring and evaluation tool with sensitive detection of infection signals in low prevalence settings. Further investigation and application of this sampling strategy for MX are recommended to support its adoption as a standardized method for global LF elimination programs. [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: As Bangladesh, India and Nepal progress towards visceral leishmaniasis (VL) elimination, it is important to understand the role of asymptomatic Leishmania infection (ALI), VL treatment relapse and post kala-azar dermal leishmaniasis (PKDL) in transmission. Methodology/ Principal Finding: We reviewed evidence systematically on ALI, relapse and PKDL. We searched multiple databases to include studies on burden, risk factors, biomarkers, natural history, and infectiveness of ALI, PKDL and relapse. After screening 292 papers, 98 were included covering the years 1942 through 2016. ALI, PKDL and relapse studies lacked a reference standard and appropriate biomarker. The prevalence of ALI was 4–17-fold that of VL. The risk of ALI was higher in VL case contacts. Most infections remained asymptomatic or resolved spontaneously. The proportion of ALI that progressed to VL disease within a year was 1.5–23%, and was higher amongst those with high antibody titres. The natural history of PKDL showed variability; 3.8–28.6% had no past history of VL treatment. The infectiveness of PKDL was 32–53%. The risk of VL relapse was higher with HIV co-infection. Modelling studies predicted a range of scenarios. One model predicted VL elimination was unlikely in the long term with early diagnosis. Another model estimated that ALI contributed to 82% of the overall transmission, VL to 10% and PKDL to 8%. Another model predicted that VL cases were the main driver for transmission. Different models predicted VL elimination if the sandfly density was reduced by 67% by killing the sandfly or by 79% by reducing their breeding sites, or with 4–6y of optimal IRS or 10y of sub-optimal IRS and only in low endemic setting. Conclusion/ Significance: There is a need for xenodiagnostic and longitudinal studies to understand the potential of ALI and PKDL as reservoirs of infection. [ABSTRACT FROM AUTHOR]

Background: Increasing volumes of data and computational capacity afford unprecedented opportunities to scale up infectious disease (ID) mapping for public health uses. Whilst a large number of IDs show global spatial variation, comprehensive knowledge of these geographic patterns is poor. Here we use an objective method to prioritise mapping efforts to begin to address the large deficit in global disease maps currently available. Methodology/Principal Findings: Automation of ID mapping requires bespoke methodological adjustments tailored to the epidemiological characteristics of different types of diseases. Diseases were therefore grouped into 33 clusters based upon taxonomic divisions and shared epidemiological characteristics. Disability-adjusted life years, derived from the Global Burden of Disease 2013 study, were used as a globally consistent metric of disease burden. A review of global health stakeholders, existing literature and national health priorities was undertaken to assess relative interest in the diseases. The clusters were ranked by combining both metrics, which identified 44 diseases of main concern within 15 principle clusters. Whilst malaria, HIV and tuberculosis were the highest priority due to their considerable burden, the high priority clusters were dominated by neglected tropical diseases and vector-borne parasites. Conclusions/Significance: A quantitative, easily-updated and flexible framework for prioritising diseases is presented here. The study identifies a possible future strategy for those diseases where significant knowledge gaps remain, as well as recognising those where global mapping programs have already made significant progress. For many conditions, potential shared epidemiological information has yet to be exploited. Author Summary: Maps have long been used to not only visualise, but also to inform infectious disease control efforts, identify and predict areas of greatest risk of specific diseases, and better understand the epidemiology of disease over various spatial scales. In spite of the utilities of such outputs, globally comprehensive maps have been produced for only a handful of infectious diseases. Due to limited resources, it is necessary to define a framework to prioritise which diseases to consider mapping globally. This paper outlines a framework which compares each disease's global burden with its associated interest from the policy community in a data-driven manner which can be used to determine the relative priority of each condition. Malaria, HIV and TB are, unsurprisingly, ranked highest due to their considerable health burden, while the other priority diseases are dominated by neglected tropical diseases and vector-borne diseases. For some conditions, global mapping efforts are already in place, however, for many neglected conditions there still remains a need for high resolution spatial surveys. [ABSTRACT FROM AUTHOR]

This paper scrutinises pipelines for Neglected Diseases (NDs), through freely accessible and at-least-weekly updated trials databases. It updates to 2012 data provided by recent publications, and integrates these analyses with information on location of trials coordinators and patients recruitment status. Additionally, it provides (i) disease-specific information to better understand the rational of investments in NDs, (ii) yearly data, to understand the investment trends. The search identified 650 clinical studies. Leishmaniasis, Arbovirus infection, and Dengue are the top three diseases by number of clinical studies. Disease diffusion risk seems to be the most important driver of the clinical trials target choice, whereas the role played by disease prevalence and unmet need is controversial. Number of trials is stable between 2005 and 2010, with an increase in the last two years. Patient recruitment was completed for most studies (57.6%), and Phases II and III account for 35% and 28% of trials, respectively. The primary purpose of clinical investigations is prevention (49.3%), especially for infectious diseases with mosquitoes and sand flies as the vector, and treatment (43.2%), which is the primary target for parasitic diseases Research centres and public organisations are the most important clinical studies sponsors (58.9%), followed by the pharmaceutical industry (24.1%), foundations and non-governmental organisations (9.3%). Many coordinator centres are located in less affluent countries (43.7%), whereas OECD countries and BRICS account for 34.7% and 17.5% of trials, respectively. Information was partially missing for some parameters. Notwithstanding, and despite its descriptive nature, this research has enhanced the evidence of the literature on pipelines for NDs. Future contributions may further investigate whether trials metrics are consistent with the characteristics of the interested countries and the explicative variables of trials location, target (disease) choice, and the object of the trials. [ABSTRACT FROM AUTHOR]

Background: Although trachoma causes more cases of preventable blindness than any other infectious disease, a combination of strategies is reducing its global prevalence. As a district moves toward eliminating trachoma as a public health problem, national programs conduct trachoma impact surveys (TIS) to assess whether to stop preventative interventions and trachoma surveillance surveys (TSS) to determine whether the prevalence of active trachoma has rebounded after interventions have halted. In some contexts, programs also conduct trachomatous trichiasis (TT)-only surveys. A few costing studies of trachoma prevalence surveys exist, but none examine TIS, TSS, or TT-only surveys. Methodology/Principal findings: We assessed the incremental financial cost to the national program of TIS, TSS, and TT-only surveys, which are standardized cluster-sampled prevalence surveys. We conducted a retrospective review of expenditures and grant disbursements for TIS and TSS in 322 evaluation units in 11 countries between 2011 and 2018. We also assessed the costs of three pilot and five standard TT-only surveys in four countries between 2017 and 2018. The median cost of TIS and TSS was $8,298 per evaluation unit [interquartile range (IQR): $6,532–$10,111, 2017 USD]. Based on a linear regression with bootstrapped confidence intervals, after controlling for country, costs per survey did not change significantly over time but did decline by $83 per survey implemented in a single round (95% CI: -$108 –-$63). Of total costs, 80% went to survey fieldwork; of that, 58% went towards per diems and 38% towards travel. TT-only surveys cost a median of $9,707 (IQR: $8,537–$11,635); within a given country, they cost slightly more (106% [IQR: 94%–136%]) than TIS and TSS. Conclusions/Significance: The World Health Organization requires trachoma prevalence estimates for validating the elimination of trachoma as a public health problem. This study will help programs improve their planning as they assemble resources for that effort. [ABSTRACT FROM AUTHOR]

Reliable, comparable information about the main causes of disease and injury in populations, and how these are changing, is a critical input for debates about priorities in the health sector. Traditional sources of information about the descriptive epidemiology of diseases, injuries, and risk factors are generally incomplete, fragmented, and of uncertain reliability and comparability. The Global Burden of Disease (GBD) study has provided a conceptual and methodological framework to quantify and compare the health of populations using a summary measure of both mortality and disability, the disability-adjusted life year (DALY).This paper describes key features of the Global Burden of Disease analytic approach, which provides a standardized measurement framework to permit comparisons across diseases and injuries, as well as risk factors, and a systematic approach to the evaluation of data. The paper describes the evolution of the GBD, starting from the first study for the year 1990, summarizes the methodological improvements incorporated into GBD revisions for the years 2000-2004 carried out by the World Health Organization, and examines priorities and issues for the next major GBD study, funded by the Bill & Melinda Gates Foundation, and commencing in 2007.The paper presents an overview of summary results from the Global Burden of Disease study 2002, with a particular focus on the neglected tropical diseases, and also an overview of the comparative risk assessment for 26 global risk factors. Taken together, trypanosomiasis, Chagas disease, schistosomiasis, leishmaniasis, lymphatic filariasis, onchocerciasis, intestinal nematode infections, Japanese encephalitis, dengue, and leprosy accounted for an estimated 177,000 deaths worldwide in 2002, mostly in sub-Saharan Africa, and about 20 million DALYs, or 1.3% of the global burden of disease and injuries. Further research is currently underway to revise and update these estimates.

Capacity building in health research generally, and helminthiasis research particularly, is pivotal to the implementation of the research and development agenda for the control and elimination of human helminthiases that has been proposed thematically in the preceding reviews of this collection. Since helminth infections affect human populations particularly in marginalised and lowincome regions of the world, they belong to the group of poverty-related infectious diseases, and their alleviation through research, policy, and practice is a sine qua non condition for the achievement of the United Nations Millennium Development Goals. Current efforts supporting research capacity building specifically for the control of helminthiases have been devised and funded, almost in their entirety, by international donor agencies, major funding bodies, and academic institutions from the developed world, contributing to the creation of (not always equitable) North-South "partnerships". There is an urgent need to shift this paradigm in disease-endemic countries (DECs) by refocusing political will, and harnessing unshakeable commitment by the countries' governments, towards health research and capacity building policies to ensure long-term investment in combating and sustaining the control and eventual elimination of infectious diseases of poverty. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. This paper discusses the challenges confronting capacity building for parasitic disease research in DECs, describes current capacity building strategies with particular reference to neglected tropical diseases and human helminthiases, and outlines recommendations to redress the balance of alliances and partnerships for health research between the developed countries of the "North" and the developing countries of the "South". We argue that investing in South-South collaborative research policies and capacity is as important as their North-South counterparts and is essential for scaled-up and improved control of helminthic diseases and ultimately for regional elimination. [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]

Lagochilascariasis is a parasitic disease caused by a helminth of the order Ascaroidea, genus Lagochilascaris that comprises 6 species, among which only Lagochilascaris minor Leiper, 1909, is implicated in the human form of the disease. It is remarkable that the majority of cases of human lagochilascariasis in the Americas have been reported in Brazil. The natural definitive hosts of this parasite seem to be wild felines and canines. Lagochilascariasis is mostly a chronic human disease that can persist for several years, in which the parasite burrows into the subcutaneous tissues of the neck, paranasal sinuses, and mastoid. L. minor exhibits remarkable ability to migrate through the tissues of its hosts, destroying even bone tissue. Fatal cases have been described in which the parasite was found in the lungs or central nervous system. Treatment is often palliative, with recurrence of lesions. This paper summarizes the main features of the disease and its etiologic agent, including prevalence, life cycle, clinical course, and treatment. [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]

Background: Stigma plays in an important role in the lives of persons affected by neglected tropical diseases, and assessment of stigma is important to document this. The aim of this study is to test the cross-cultural validity of the Community Stigma Scale (EMIC-CSS) and the Social Distance Scale (SDS) in the field of leprosy in Cirebon District, Indonesia. Methodology/principle findings: Cultural equivalence was tested by assessing the conceptual, item, semantic, operational and measurement equivalence of these instruments. A qualitative exploratory study was conducted to increase our understanding of the concept of stigma in Cirebon District. A process of translation, discussions, trainings and a pilot study followed. A sample of 259 community members was selected through convenience sampling and 67 repeated measures were obtained to assess the psychometric measurement properties. The aspects and items in the SDS and EMIC-CSS seem equally relevant and important in the target culture. The response scales were adapted to ensure that meaning is transferred accurately and no changes to the scale format (e.g. lay out, statements or questions) of both scales were made. A positive correlation was found between the EMIC-CSS and the SDS total scores (r = 0.41). Cronbach's alphas of 0.83 and 0.87 were found for the EMIC-CSS and SDS. The exploratory factor analysis indicated for both scales an adequate fit as unidimensional scale. A standard error of measurement of 2.38 was found in the EMIC-CSS and of 1.78 in the SDS. The test-retest reliability coefficient was respectively, 0.84 and 0.75. No floor or ceiling effects were found. Conclusions/significance: According to current international standards, our findings indicate that the EMIC-CSS and the SDS have adequate cultural validity to assess social stigma in leprosy in the Bahasa Indonesia-speaking population of Cirebon District. We believe the scales can be further improved, for instance, by adding, changing and rephrasing certain items. Finally, we provide suggestions for use with other neglected tropical diseases. [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]

Successful mass drug administration (MDA) campaigns have brought several countries near the point of Lymphatic Filariasis (LF) elimination. A diagnostic tool is needed to determine when the prevalence levels have decreased to a point that MDA campaigns can be discontinued without the threat of recrudescence. A six-country study was conducted assessing the performance of seven diagnostic tests, including tests for microfilariae (blood smear, PCR), parasite antigen (ICT, Og4C3) and antifilarial antibody (Bm14, PanLF, Urine SXP). One community survey and one school survey were performed in each country. A total of 8,513 people from the six countries participated in the study, 6,443 through community surveys and 2,070 through school surveys. Specimens from these participants were used to conduct 49,585 diagnostic tests. Each test was seen to have both positive and negative attributes, but overall, the ICT test was found to be 76% sensitive at detecting microfilaremia and 93% specific at identifying individuals negative for both microfilariae and antifilarial antibody; the Og4C3 test was 87% sensitive and 95% specific. We conclude, however, that the ICT should be the primary tool recommended for decision-making about stopping MDAs. As a point-of-care diagnostic, the ICT is relatively inexpensive, requires no laboratory equipment, has satisfactory sensitivity and specificity and can be processed in 10 minutes-qualities consistent with programmatic use. Og4C3 provides a satisfactory laboratory-based diagnostic alternative. [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]

Background: Neglected Tropical Diseases (NTDs) affect more than one billion people globally. A Public Library of Science (PLOS) journal dedicated to NTDs lists almost forty NTDs, while the WHO prioritises twenty NTDs. A person can be affected by more than one disease at the same time from a range of infectious and non-infectious agents. Many of these diseases are preventable, and could be eliminated with various public health, health promotion and medical interventions. This scoping review aims to determine the extent of the body of literature on NTD interventions and health promotion activities, and to provide an overview of their focus while providing recommendations for best practice going forward. This scoping review includes both the identification of relevant articles through the snowball method and an electronic database using key search terms. A two-phased screening process was used to assess the relevance of studies identified in the search–an initial screening review followed by data characterization using the Critical Appraisal Skills Program (CASP). Studies were eligible for inclusion if they broadly described the characteristics, methods, and approaches of (1) NTD interventions and/or (2) community health promotion. Principal findings: 90 articles met the CASP criteria partially or fully and then underwent a qualitative synthesis to be included in the review. 75 articles specifically focus on NTD interventions and approaches to their control, treatment, and elimination, while 15 focus specifically on health promotion and provide a grounding in health promotion theories and perspectives. 29 of the articles provided a global perspective to control, treatment, or elimination of NTDs through policy briefs or literature reviews. 19 of the articles focused on providing strategies for NTDs more generally while 12 addressed multiple NTDs or their interaction with other infectious diseases. Of the 20 NTDs categorized by the WHO and the expanded NTD list identified by PLOS NTDs, several NTDs did not appear in the database search on NTD interventions and health promotion, including yaws, fascioliasis, and chromoblastomycosis. Conclusions: Based on the literature we have identified the four core components of best practices including programmatic interventions, multi sectoral and multi-level interventions, adopting a social and ecological model and clearly defining 'community.' NTD interventions tend to centre on mass drug administration (MDA), particularly because NTDs were branded as such based on their being amenable to MDA. However, there remains a need for intervention approaches that also include multiple strategies that inform a larger multi-disease and multi-sectoral programme. Many NTD strategies include a focus on WASH and should also incorporate the social and ecological determinants of NTDs, suggesting a preventative and systems approach to health, not just a treatment-based approach. Developing strong communities and incorporating social rehabilitation at the sublocation level (e.g. hospital) could benefit several NTDs and infectious diseases through a multi-disease, multi-sectoral, and multi-lateral approach. Finally, it is important the 'community' is clearly defined in each intervention, and that community members are included in intervention activities and viewed as assets to interventions. Author summary: Neglected Tropical Diseases (NTDs) affect more than one billion people globally. A person can be affected by more than one disease at the same time. Many of these diseases are preventable, and could be eliminated with various public health, health promotion and medical interventions. This scoping review aims to determine the extent of the body of literature on NTD interventions and health promotion activities, and to provide an overview of their focus while providing recommendations for best practice going forward. Through a database search and by identifying appropriate literature 75 articles were identified that specifically focus on NTD interventions and approaches to their control, treatment, and elimination, while 15 focus specifically on health promotion and provide a grounding in health promotion theories and perspectives. Based on the literature we have identified the four core components of best practices including programmatic interventions, multi sectoral and multi-level interventions, adopting a social and ecological model and clearly defining 'community.' [ABSTRACT FROM AUTHOR]

Background: Histoplasmosis is acquired by inhalation of spores of the dimorphic fungus Histoplasma spp. Although this pathogen is distributed worldwide, it is more prevalent in the Americas. However, the real burden of histoplasmosis remains undefined in many endemic regions. Methodology: We conducted a series of 61 autopsies to individuals who died in a hospital in the Brazilian Amazon focused on infectious diseases. We performed a detailed histological and microbiological evaluation with genetic characterization of Histoplasma strains with the aim to evaluate the contribution of histoplasmosis to morbidity and mortality. Additionally, we assessed the clinicopathological correlation. Principal findings: Evidence of Histoplasma infection was detected in 21 patients (34%). Eight cases were disseminated infections, all of them occurred in HIV-positive patients. Six cases were localized histoplasmosis, limited to the lungs. In seven patients Histoplasma DNA was detected by PCR in patients with no histological lesions. Histoplasma infection was detected in 38% of HIV-positive patients and was a major contributor to death in 22% of them. Lungs, liver and spleen were affected in all cases of disseminated histoplasmosis. Phylogenetic analysis of the strains suggested a high diversity of Histoplasma species circulating in the Brazilian Amazon. Histoplasmosis was clinically missed in 75% of the disseminated infections. In conclusion, substantial mortality is associated with disseminated histoplasmosis among HIV-positive patients in the Brazilian Amazon. Conclusions: The high incidence of histoplasmosis, the low index of clinical suspicion, and the severity of the disseminated disease highlight the need of proactively implementing sensitive routine screening methods for this pathogen in endemic areas. Antifungal prophylaxis against Histoplasma should be encouraged in the severely immunocompromised HIV patients in these areas. Author summary: Histoplasmosis is a fungal infection caused by inhalation of spores of the fungus Histoplasma spp. It occurs in specific endemic areas, such as areas of USA, Africa and Latin America. However, the real burden of histoplasmosis remains unknown in many endemic regions. Clinically, histoplasmosis is frequently misdiagnosed as tuberculosis. The current study was carried out to explore the frequency and characteristics of Histoplasma infection in a series of autopsies conducted in the Brazilian Amazon. We found evidence of Histoplasma infection in one-third of the deceased patients. A significant proportion of the cases were disseminated infections, with extensive involvement and severe damage of most organs. All these disseminated infections occurred in HIV-positive patients. Strikingly, histoplasmosis was clinically missed in more than two-thirds of these patients and had an extremely high mortality. In conclusion, the high frequency and mortality of histoplasmosis, together with the frequent misdiagnosis of the disease, highlight the need of implementation of sensitive screening methods for Histoplasma in HIV patients in endemic areas. Additionally, antifungal prophylaxis against Histoplasma should be encouraged in the severely immunocompromised HIV patients in these areas. [ABSTRACT FROM AUTHOR]

Background: Hand, foot, and mouth disease (HFMD) is a global infectious disease; particularly, it has a high disease burden in China. This study was aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics, and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model. Methods: This study included datasets of HFMD cases reported in seven regions in Mainland China. The early warning time (week) was calculated using the LDE model with the key parameters estimated by fitting with the data. Two key time points, "epidemic acceleration week (EAW)" and "recommended warning week (RWW)", were calculated to show the early warning time. Results: The mean annual incidence of HFMD cases per 100,000 per year was 218, 360, 223, 124, and 359 in Hunan Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County across the southern regions, respectively and 60 and 34 in Jilin Province and Longde County across the northern regions, respectively. The LDE model fitted well with the reported data (R2 > 0.65, P < 0.001). Distinct temporal patterns were found across geographical regions: two early warning signals emerged in spring and autumn every year across southern regions while one early warning signals in summer every year across northern regions. Conclusions: The disease burden of HFMD in China is still high, with more cases occurring in the southern regions. The early warning of HFMD across the seven regions is heterogeneous. In the northern regions, it has a high incidence during summer and peaks in June every year; in the southern regions, it has two waves every year with the first wave during spring spreading faster than the second wave during autumn. Our findings can help predict and prepare for active periods of HFMD. Author summary: Hand, foot, and mouth disease (HFMD), a global infectious disease, has a high disease burden in China. This study aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model. Our findings showed that 1) the HFMD disease burden in China remained high and HFMD incidence in the southern region was higher than that in the northern region; and 2) the HFMD early warnings times across China were heterogeneous. One high incidence period occurred in the northern regions during summer, peaking in June every year, while in the southern regions two waves emerged every year. Over the southern regions, the disease appeared to spread faster in the spring wave than in the autumn wave. These results provide important information for public health authorities such as the Centers for Disease Control and Prevention staff to predict and prepare for the onset of the high active periods of HFMD, especially by indicating the heterogeneous warning times of HFMD outbreak across different geographical regions in Mainland China. [ABSTRACT FROM AUTHOR]

Background: Hand foot and mouth disease (HFMD) is becoming one of the common human infectious diseases in China. Previous studies have described HFMD in tropical or coastal areas of Asia-Pacific countries. However, limited studies have thoroughly studied the epidemiology and potential risk factors for HFMD in inland areas with complex environmental conditions. Methodology/Principal findings: Using the data from 2009 to 2018 on reported cases of Xinjiang Uighur Autonomous Region, we characterized the epidemic features of HFMD. Panel negative binomial model was used to identify climate, geographical and demographic determinants for HFMD incidence. A total of 70856 HFMD cases (average annual incidence: 305 per million persons) were reported in Xinjiang during the 10-year study period, of which 10393 (14.7%) were laboratory-confirmed and 98 (0.1%) were severe. HFMD peaked in summer every year during the study period, and incidence in 2012, 2015, 2016 and 2018 had minor peaks in autumn. After adjusting the school or holiday month, multiple factors were found to affect HFMD epidemiology: urban area being major land cover type (incidence risk ratio, IRR 2.08; 95% CI 1.50, 2.89), higher gross domestic product per capita (IRR 1.14; 95% CI 1.11, 1.16), rise in monthly average temperature (IRR 1.65; 95% CI 1.61, 1.69) and monthly accumulative precipitation (IRR 1.20; 95% CI 1.16, 1.24) predicted increase in the incidence of HFMD; farmland being major land cover type (IRR 0.72; 95% CI 0.64, 0.81), an increase of percentage of the minority (IRR 0.91; 95% CI 0.89, 0.93) and population density (IRR 0.98; 95% CI 0.98, 0.99) were related to a decrease in the incidence of HFMD. Conclusions/Significance: In conclusion, the epidemic status of HFMD in Xinjiang is characterized by low morbidity and fatality. Multiple factors have significant influences on the occurrence and transmission of HFMD in Xinjiang. Author summary: Hand foot and mouth disease (HFMD) is one of the common human infectious disease threating Asia-Pacific countries. To explore the epidemiology and environmental risk factors for HFMD in inland China, we utilized 10-year HFMD surveillance data in Xinjiang Uighur Autonomous Region and combined multiple spatial-temporal statistical analyses. We identified spatial-temporal clusters of HFMD incidence and found that multiple factors could affect HFMD incidence: urban area being major land cover type, higher gross domestic product per capita, rise in monthly average temperature and monthly accumulative precipitation predicted increase in the incidence of HFMD; farmland being major land cover type, an increase of percentage of the minority and population density were related to a decrease in the incidence of HFMD. Our findings facilitate the understanding of HFMD epidemiology and risk factors in different geographic regions, which are crucial for conducting prevention and control strategies of HFMD. [ABSTRACT FROM AUTHOR]

Background: Surveillance is an essential component of global programs to eliminate infectious diseases and avert epidemics of (re-)emerging diseases. As the numbers of cases decline, costs of treatment and control diminish but those for surveillance remain high even after the 'last' case. Reducing surveillance may risk missing persistent or (re-)emerging foci of disease. Here, we use a simulation-based approach to determine the minimal number of passive surveillance sites required to ensure maximum coverage of a population at-risk (PAR) of an infectious disease. Methodology and principal findings: For this study, we use Gambian human African trypanosomiasis (g-HAT) in north-western Uganda, a neglected tropical disease (NTD) which has been reduced to historically low levels (<1000 cases/year globally), as an example. To quantify travel time to diagnostic facilities, a proxy for surveillance coverage, we produced a high spatial-resolution resistance surface and performed cost-distance analyses. We simulated travel time for the PAR with different numbers (1–170) and locations (170,000 total placement combinations) of diagnostic facilities, quantifying the percentage of the PAR within 1h and 5h travel of the facilities, as per in-country targets. Our simulations indicate that a 70% reduction (51/170) in diagnostic centres still exceeded minimal targets of coverage even for remote populations, with >95% of a total PAR of ~3million individuals living ≤1h from a diagnostic centre, and we demonstrate an approach to best place these facilities, informing a minimal impact scale back. Conclusions: Our results highlight that surveillance of g-HAT in north-western Uganda can be scaled back without substantially reducing coverage of the PAR. The methodology described can contribute to cost-effective and equable strategies for the surveillance of NTDs and other infectious diseases approaching elimination or (re-)emergence. Author summary: Disease surveillance systems are an essential component of public health practice and are often considered the first line in averting epidemics for (re-)emerging diseases. Regular evaluation of surveillance systems ensures that they remain operating at maximum efficiency; systems that survey diseases of low incidence, such as those within elimination settings, should be simplified to reduce the reporting burden. A lack of guidance on how to optimise disease surveillance in an elimination setting may result in added expense, and/or the underreporting of disease. Here, we propose a framework methodology to determine systematically the optimal number and placement of surveillance sites for the surveillance of infectious diseases approaching elimination. By utilising estimates of geographic accessibility, through the construction of a resistance surface and a simulation approach, we identify that the number of operational diagnostic facilities for Gambian human African trypanosomiasis in north-western Uganda can be reduced by 70% with a minimal reduction in existing coverage, and identify the minimum number of facilities required to meet coverage targets. Our analysis can be used to inform the number and positioning of surveillance sites for diseases within an elimination setting. Passive surveillance becomes increasingly important as cases decline and active surveillance becomes less cost-effective; methods to evaluate how best to engage this passive surveillance capacity given facility capacity and geographic distribution are pertinent for several NTDs where diagnosis is complex. Not only is this a complicated research area for diseases approaching elimination, a well-designed surveillance system is essential for the detection of emerging diseases, with this work being topical in a climate where emerging pathogens are becoming more commonplace. [ABSTRACT FROM AUTHOR]

Introduction: Abdominal ultrasound (US) is increasingly used in the diagnostic work-up of infectious diseases, but studies on its diagnostic value in visceral leishmaniasis (VL) are lacking. US could help to identify complications of spleen aspiration (SA). We aimed to assess the diagnostic value of US and the evolution of findings after VL treatment; the incidence and degree of splenic injury; and the pain perceived during SA. Methodology/result: We conducted a cross-sectional prospective study at the Leishmaniasis Research and Treatment Center, Gondar, Ethiopia between Oct 2017 and Dec 2018. We enrolled VL suspects undergoing tissue aspiration; US were conducted before and after SA, and at the end of VL treatment. Splenic injury was graded using the American association of surgery trauma injury scale (grade 1–4). The pain perceived during SA was graded using a visual analogue scale. Out of 392 VL suspects, 192 (49%) were confirmed VL cases. The median age was 25 years (IQR 21–30). Massive splenomegaly and hepatomegaly were the most common US findings. Splenic nodules were seen in 3.7% of the 190 VL cases and 1.5% of the 197 non-VL cases. Ascites was more common in VL (16.4%) than in non-VL cases (9.1%). The frequency of US abnormalities decreased with treatment. None of the US findings had sufficient sensitivity and specificity to justify its use as a diagnostic test. US detected splenic injury in four of the 318 patients who had post-SA US. All four patients remained clinically stable. Pain was perceived as moderate or severe in 51% of patients. Conclusion: The diagnostic value of abdominal US for VL was low but found useful to detect subclinical splenic injury. SA caries a risk of splenic injury and was perceived painful by most. Further research on less invasive diagnostic tools is needed. Author summary: Diagnostic value of abdominal US for visceral leishmaniasis in Ethiopian setting is limited. US finding of patients decreased in frequency with VL treatment. US detects iatrogenic subclinical splenic injury trough splenic aspiration in VL suspects. Iatrogenic splenic injury occurred in 1.3%of all blinded splenic aspirations done in VL suspected patients. 51% of VL suspects described moderate to severe pain (score ≥ 5 on visual analogue scale) after splenic aspiration. [ABSTRACT FROM AUTHOR]

Various global health initiatives are currently advocating the elimination of schistosomiasis within the next decade. Schistosomiasis is a highly debilitating tropical infectious disease with severe burden of morbidity and thus operational research accurately evaluating diagnostics that quantify the epidemic status for guiding effective strategies is essential. Latent class models (LCMs) have been generally considered in epidemiology and in particular in recent schistosomiasis diagnostic studies as a flexible tool for evaluating diagnostics because assessing the true infection status (via a gold standard) is not possible. However, within the biostatistics literature, classical LCM have already been criticised for real-life problems under violation of the conditional independence (CI) assumption and when applied to a small number of diagnostics (i.e. most often 3-5 diagnostic tests). Solutions of relaxing the CI assumption and accounting for zero-inflation, as well as collecting partial gold standard information, have been proposed, offering the potential for more robust model estimates. In the current article, we examined such approaches in the context of schistosomiasis via analysis of two real datasets and extensive simulation studies. Our main conclusions highlighted poor model fit in low prevalence settings and the necessity of collecting partial gold standard information in such settings in order to improve the accuracy and reduce bias of sensitivity and specificity estimates. Author summary: Accurate schistosomiasis diagnosis is essential to assess the impact of large scale and repeated mass drug administration to control or even eliminate this disease. However, in schistosomiasis diagnostic studies, several inherent study design issues pose a real challenge for the currently available statistical tools used for diagnostic modelling and associated data analysis and conclusions. More specifically, those study design issues are: 1) the inclusion of small number of diagnostic tests (i.e. most often five), 2) non formal consensus about a schistosomiasis gold standard, 3) the contemporary use of relatively small sample sizes in relevant studies due to lack of research funding, 4) the differing levels of prevalence of the studied disease even within the same area of one endemic country and 5) other real world factors such as: the lack of appropriate equipment, the variability of certain methods due to biological phenomena and training of technicians across the endemic countries because of scarce financial resources contributing to the existing lack of a schistosomiasis gold standard. The current study aims to caution practitioners from blindly applying statistical models with small number of diagnostic tests and sample sizes, proposing design guidelines of future schistosomiasis diagnostic accuracy studies with recommendations for further research. While our study is centred around the diagnosis of schistosomiasis, we feel that the recommendations can be adapted to other major tropical infectious diseases as well. [ABSTRACT FROM AUTHOR]

Background: Several large outbreaks of chikungunya have been reported in the Indian Ocean region in the last decade. In 2017, an outbreak occurred in Dhaka, Bangladesh, one of the largest and densest megacities in the world. Population mobility and fluctuations in population density are important drivers of epidemics. Measuring population mobility during outbreaks is challenging but is a particularly important goal in the context of rapidly growing and highly connected cities in low- and middle-income countries, which can act to amplify and spread local epidemics nationally and internationally. Methods: We first describe the epidemiology of the 2017 chikungunya outbreak in Dhaka and estimate incidence using a mechanistic model of chikungunya transmission parametrized with epidemiological data from a household survey. We combine the modeled dynamics of chikungunya in Dhaka, with mobility estimates derived from mobile phone data for over 4 million subscribers, to understand the role of population mobility on the spatial spread of chikungunya within and outside Dhaka during the 2017 outbreak. Results: We estimate a much higher incidence of chikungunya in Dhaka than suggested by official case counts. Vector abundance, local demographics, and population mobility were associated with spatial heterogeneities in incidence in Dhaka. The peak of the outbreak in Dhaka coincided with the annual Eid holidays, during which large numbers of people traveled from Dhaka to other parts of the country. We show that travel during Eid likely resulted in the spread of the infection to the rest of the country. Conclusions: Our results highlight the impact of large-scale population movements, for example during holidays, on the spread of infectious diseases. These dynamics are difficult to capture using traditional approaches, and we compare our results to a standard diffusion model, to highlight the value of real-time data from mobile phones for outbreak analysis, forecasting, and surveillance. Author summary: Chikungunya is an emerging mosquito-borne disease in many parts of the world, with a high morbidity burden. Fluctuations in human density and mobility are important drivers of epidemics, particularly in the context of large cities in low- and middle-income countries, which can act to amplify and spread local epidemics. Here, we first describe the epidemiology of chikungunya in Dhaka, Bangladesh, one of the largest megacities in the world, during an outbreak in 2017. Using data from a household survey, we estimate a much higher attack rate than suggested by official case counts. We then use estimates of population movement from mobile phone data for over 4 million subscribers, to understand the role of human mobility on the spatial spread of chikungunya. We show that regular population fluxes around Dhaka city played a significant role in determining disease risk, and that travel during the Eid holidays likely spread the infection to the rest of the country. Our results show the impact of large-scale population movements, particularly during holidays, on the spread of infectious diseases, and highlight the value of real-time data from mobile phones for outbreak analysis and forecasting. [ABSTRACT FROM AUTHOR]

Background: The emergence and re-emergence of scrub typhus has been reported in the past decade in many global regions. In this study, we aim to identify potential scrub typhus infection risk zones with high spatial resolution in Qingdao city, in which scrub typhus is endemic, to guide local prevention and control strategies. Methodology/Principal findings: Scrub typhus cases in Qingdao city during 2006–2018 were retrieved from the Chinese National Infectious Diseases Reporting System. We divided Qingdao city into 1,101 gridded squares and classified them into two categories: areas with and without recorded scrub typhus cases. A boosted regression tree model was used to explore environmental and socioeconomic covariates associated with scrub typhus occurrence and predict the risk of scrub typhus infection across the whole area of Qingdao city. A total of 989 scrub typhus cases were reported in Qingdao from 2006–2018, with most cases located in rural and suburban areas. The predicted risk map generated by the boosted regression tree models indicated that the highest infection risk areas were mainly concentrated in the mid-east and northeast regions of Qingdao, with gross domestic product (20.9%±1.8% standard error) and annual cumulative precipitation (20.3%±1.1%) contributing the most to the variation in the models. By using a threshold environmental suitability value of 0.26, we identified 757 squares (68.7% of the total) with a favourable environment for scrub typhus infection; 66.2% (501/757) of the squares had not yet recorded cases. It is estimated that 6.32 million people (72.5% of the total population) reside in areas with a high risk of scrub typhus infection. Conclusions/Significance: Many locations in Qingdao city with no recorded scrub typhus cases were identified as being at risk for scrub typhus occurrence. In these at-risk areas, awareness and capacity for case diagnosis and treatment should be enhanced in the local medical service institutes. Author summary: Scrub typhus is a bacterial zoonosis caused by Orientia tsutsugamushi, which is mostly carried by rodents and chigger mites, and occasionally transmitted to humans by bites of infected larval mites. Scrub typhus is geographically endemic across broad areas of south and southeastern Asia, the Pacific islands and northern Australia. In recent years, an obvious increasing trend of the incidence of this disease has been noticed all around the world. China is one of the most endemic country for this disease, with an approximate 10-fold increase of the annual case number from 2006 to 2013. In this study, by using a prediction model for infectious diseases, we found that the highest infection risk area was located at the mid-east and northeast regions of Qingdao, with gross domestic product and precipitation might developed the greatest impact for the occurrence of scrub typhus. Furthermore, 68.7% of the region in Qingdao might have a suitable environment for the occurrence of scrub typhus, with most of them hadn't reported cases yet. This study highlights the emergency to enhance the awareness of this disease and improve the capacity of diagnosis and treatment among medical institutions in high risk areas in Qingdao. [ABSTRACT FROM AUTHOR]