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Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense and is invariably fatal unless treated. Current therapies present limitations in their application, parasite resistance, or require further clinical investigation for wider use. Our work, informed by previous findings, presents novel 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidine derivatives with promising antitrypanosomal activity. In particular, 32 exhibits an in vitro EC50 value of 0.5 µM against Trypanosoma brucei rhodesiense, and analogues 29, 30 and 33 show antitrypanosomal activities in the

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.

Neglected Tropical Diseases (NTDs) are a public health challenge in Nigeria, especially within the marginalized populations; millions of people are affected. As much as biomedical interventions go a long way in the elimination of NTDs, stigma from these diseases forms a very strong barrier to care. It has profound mental health implications for affected individuals. Much of this stigma results from cultural myths and fear of contagion, leading to late health-seeking behavior, social isolation, and discrimination. These psychosocial factors, linked to an inadequate response from mental health services, seriously hinder effective treatment and control measures, increasing the burden of the disease. This paper discusses the relationship between stigma and mental health in NTDs and outlines gaps in the current health strategy while providing a comprehensive approach to deal with these pertinent issues. Combating NTDs and stigma requires a multifaceted approach, including training healthcare providers on the legal rights of those affected, community-level stigma reduction to improve health-seeking behaviors, and policy reforms. More importantly, by incorporating mental health services, reducing stigma, and improving health-seeking behavior, Nigeria will be advancing her efforts toward the goals of NTD elimination. [ABSTRACT FROM AUTHOR]

Background: Yemen has experienced a dramatic increase in neglected tropical diseases (NTDs) amidst ongoing conflict and humanitarian crises. This systematic review aims to consolidate and analyse the available literature on NTDs in Yemen, focusing on aetiology, geographic distribution, and associated risk factors. Methods: A comprehensive literature search was conducted across five international databases and one national database, resulting in 3,652 identified records. After screening and applying eligibility criteria, 230 articles were included in this review. Data extraction focused on publication year, study design, sample types, diagnostic methods, reported pathogens, and geographic distribution. The aetiology of reported NTDs was categorized into four groups: viruses, bacteria, protozoa, and helminths. Results: Viral NTDs were the most frequently reported, accounting for 39% of the articles, followed by bacterial (26%), helminthic (21%), and protozoal NTDs (15%). Dengue virus, hepatitis B and C viruses were the most prominent viral pathogens, while bacterial NTDs were primarily caused by Escherichia coli, cholera, and Salmonella. Schistosomiasis and ascariasis were the most reported helminth infections, whereas leishmaniasis and malaria were the leading protozoal NTDs. Geographically, over 69% of the reported studies focused on northern Yemen, with the highest concentrations in Sana'a, Al Hudaydah, and Taiz. The review identified multiple risk factors, including poor sanitation, inadequate water quality, and urbanization, exacerbating NTD prevalence. Conclusions: The findings highlight the significant burden and regional disparities of NTDs in Yemen, emphasizing the need for targeted interventions. Prioritizing improvements in sanitation, water quality, and vector control measures, alongside community engagement, is critical. Policymakers must allocate resources effectively to address the root causes of NTDs and strengthen Yemen's healthcare infrastructure. [ABSTRACT FROM AUTHOR]

Background The coendemicity of onchocerciasis with other filariae warrants a better diagnostic tool for elimination efforts that are highly sensitive and specific for use in surveillance and xenomonitoring. Methods Based on next-generation sequencing data, quantitative polymerase chain reaction (qPCR) assays were designed for 15 highly repeated targets from Onchocerca volvulus (Ov) and 11 from Onchocerca ochengi. The 2 most promising repeats Ov15R and Ov16R from Ov and OoR1 and OoR5 from O. ochengi , were selected for further testing. Results The analytic sensitivity of Ov15R and Ov16R was similar, with limits of detection at 1 fg and specificity approaching 100%. Using DNA obtained previously from skin snips of participants infected with Ov , Ov16R identified 17 additional samples as positive for Ov infections when compared with the gold standard O-150. Although Ov16R failed to detect circulating cell-free DNA (ccfDNA) in the plasma of individuals infected with Ov , 1-mL urine samples were variably positive for ccfDNA. Interestingly, plasma levels of ccfDNA were shown to be easily measurable as early as 12 to 24 hours following treatment. To enable processing of larger volumes of urine for better sensitivity, a chitosan-based filter technique was developed that efficiently captured ccfDNA from 1 to 15 mL of urine. Interestingly, Ov15R, Ov16R, and O-150 map to the same region(s) of the Ov genome, prompting a redesign of the standard O-150 qPCR. This resulted in a new O-150 assay that performs on par with Ov15R/Ov16R. Conclusions Each of these assays dramatically improve detection of Ov DNA and can easily be configured to field-friendly isothermal formats. [ABSTRACT FROM AUTHOR]

Neglected tropical diseases (NTDs) represent a group of chronic and debilitating infections that affect more than one billion people, predominantly in low-income communities with limited health infrastructure. This paper analyzes the factors that perpetuate the burden of NTDs, highlighting how poor health infrastructure, unfavorable socioeconomic conditions and lack of therapeutic resources exacerbate their impact. The effectiveness of current interventions, such as mass drug administration (MDA) programs and improved sanitation, in reducing disease prevalence is examined. In addition, the role of climate change, which alters transmission dynamics and expands affected territories, is discussed as an emerging challenge. The analysis suggests that integrated, multisectoral approaches, including health education and infrastructure interventions, are essential to breaking the cycle of poverty and disease. Although international programs have marked significant progress, achieving elimination targets by 2030 requires sustained commitment, innovation, and increased research capacity in endemic countries. [ABSTRACT FROM AUTHOR]

Trachoma is targeted for elimination as a public health problem worldwide by 2030. In Nigeria, elimination activities are implemented at the local government area (LGA) level. They started in 2002 by conducting baseline population-based prevalence surveys (PBPSs), which continued in a systematic manner with engagement from the Global Trachoma Mapping Project in 2013, and subsequently Tropical Data. The results led to the development of Nigeria's first trachoma action plan and its subsequent revision with additional information. Following 449 baseline PBPSs, 122 LGAs had an active trachoma prevalence above the elimination threshold, requiring interventions, while 231 LGAs required community-based interventions for trichiasis management. By 2021, >34 million antibiotic treatments had been provided in 104 LGAs, with 89 LGAs eliminating active trachoma. Nationally, water and sanitation coverages increased by 3% and 18%, respectively, in 7 y. Systematic trichiasis case finding and management were carried out in 231 LGAs, resulting in the management of 102 527 people. Fifty-four LGAs decreased trichiasis prevalence unknown to the health system to <0.2% in persons ≥15 y of age. Where this elimination prevalence threshold was reached, trichiasis services were transitioned to routine eye/healthcare systems. Such progress relied on strong leadership and coordination from the national trachoma program and tremendous support provided by partners. Attaining elimination of trachoma as a public health problem in Nigeria by 2030 is feasible if funding support is sustained. [ABSTRACT FROM AUTHOR]

Background: Yaws is an infectious, neglected tropical disease that affects the skin of many children and adolescents who live in poor, rural, low-income communities in humid, tropical areas of Africa, Southeast Asia, and the Pacific Islands. Yaws is currently endemic in at least 15 countries, but adequate surveillance data are lacking. In line with the WHO's effort to improve early detection, diagnosis, and proper management leading to the eventual eradication of yaws, this article reviews the existing literature on yaws in Africa to highlight the epidemiological pattern, genetic variability, diagnosis modalities, treatment, and control strategies, the challenges and prospects for yaws eradication. Methods: We searched PubMed and Scopus databases to identify published data in line with the review objectives. Results: One hundred and eighty-eight peer-reviewed articles were identified by PubMed and Scopus, out of which thirty were eligible. The studies covered 11 African countries, with the reported prevalence ranging from 0.50% to 43.0%. Conclusions: There is a great prospect for eradication if countries capitalize on the availability of simple, inexpensive, and well-tolerated oral treatment that has proven effective, validated point-of-care diagnostic tests and new molecular tests. Countries should embark on integrated disease control efforts to increase sustainability and improve the quality of life for people living with this NTD in poor communities. [ABSTRACT FROM AUTHOR]

Background: Following baseline surveys in 2013 and 2014, trachoma elimination interventions, including three rounds of azithromycin mass drug administration (MDA), were implemented in 13 woredas (administrative districts) of Gambella Regional State, Ethiopia. We conducted impact surveys to determine if elimination thresholds have been met or if additional interventions are required. Methods: Cross-sectional population-based surveys were conducted in 13 woredas of Gambella Regional State, combined into five evaluation units (EUs), 6─12 months after their last MDA round. A two-stage systematic (first stage) and random (second stage) sampling technique was used. WHO-recommended protocols were implemented with the support of Tropical Data. Household water, sanitation and hygiene (WASH) access was assessed. Results: The age-adjusted prevalence of trachomatous inflammation – follicular (TF) in 1–9-year-olds in the five EUs ranged from 0.3–19.2%, representing a general decline in TF prevalence compared to baseline estimates. The age- and gender-adjusted prevalence of trachomatous trichiasis (TT) unknown to the health system in those aged ≥ 15 years ranged from 0.47–3.08%. Of households surveyed, 44% had access to an improved drinking water source within a 30-minute return journey of the house, but only 3% had access to an improved latrine. Conclusion: In two EUs, no further MDA should be delivered, and a surveillance survey should be conducted after two years without MDA. In one EU, one further round of MDA should be conducted followed by another impact survey. In two EUs, three further MDA rounds are required. Surgery, facial cleanliness and environmental improvement interventions are needed throughout the region. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to estimate the prevalence of trachomatous inflammation–follicular (TF) in 1–9-year-olds and trachomatous trichiasis (TT) unknown to the health system in ≥15-year-olds in Benishangul Gumuz (BGZ) region, Ethiopia. This will help to assess progress towards the elimination of trachoma as a public health problem and determine the need for future interventions against trachoma in the region. Methods: Cross-sectional population-based trachoma prevalence surveys were conducted in four evaluation units (EUs) of BGZ using World Health Organization-recommended survey methodologies. Individuals were examined for clinical signs of trachoma. Household access to water, sanitation and hygiene facilities (WaSH) was assessed. Results: A total of 11,778 people aged ≥1 year were examined. The prevalence of TF in 1–9-year-olds was <5% in three EUs and ≥5% in one EU. The prevalence of TT unknown to the health system in people aged ≥15-years was ≥0.2% in all four EUs. The proportion of households with an improved drinking water source within a 30-minute round-trip ranged from 27−60%. The proportion of households with an improved latrine ranged from <1−6%. Conclusions: Surgical interventions for TT are required in all EUs in BGZ. One annual round of mass drug administration (MDA) of azithromycin is required in one EU before resurvey to reassess progress in lowering TF prevalence below the WHO elimination threshold of 5% in 1–9-year-olds. MDA should be stopped in the other three EUs and trachoma surveillance surveys should be conducted at least 24 months after the surveys described here. Ongoing strengthening of WaSH infrastructure may help sustain the low prevalence of trachoma. [ABSTRACT FROM AUTHOR]

Loa loa is an arthropod-transmitted filarial nematode, and one of four pathologically prevalent blood microfilaria associated with human infection. This case report describes an instance of a 41-year-old male diagnosed with Loa loa by peripheral blood smear and subsequently also diagnosed with Onchocerca. Here we describe the clinical course, diagnostic evaluation and treatment considerations when managing potential nematode co-infections. This case also highlights laboratory diagnosis strategies, treatment challenges, and emphasizes a differential diagnosis of chronic infections with neglected tropical infectious agents. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to describe the prevalence of lymphatic filariasis (LF), soil‐transmitted helminthiasis (STH) and schistosomiasis (SC) in Indonesia before and after PC implementation through a systematic review and meta‐analysis. Methods: Embase, MEDLINE, PubMed, Scopus, Web of Science and Google Scholar were searched for articles published between 1 January 1992 and 31 December 2022, reporting LF, STH and SC in Indonesia. Using the Ministry of Health lists of districts receiving PC programs, we identified whether data collection was conducted before or after PC implementation in that particular district. A meta‐analysis was performed with a random‐effects model applied to pool pre‐ and post‐PC prevalence of LF, STH and SC. Results: Overall, 195 studies were included. The pooled prevalence of LF was 9.72% (95% CI, 5.56%–13.87%). The pre‐PC pooled prevalence of LF was 11.48% (95% CI, 5.52%–17.45%). The prevalence decreased after PC implementation, and the pooled prevalence was 7.12% (95% CI, 1.79%–12.44%). The overall prevalence of STH was 35.16% (95% CI, 30.36%–39.96%). The pre‐PC prevalence of STH was 36.29% (95% CI, 30.37%–42.20%). The post‐PC prevalence of STH decreased at 31.93% (95% CI, 24.25%–39.62%), although the difference between before and after PC was not significant (p = 0.379). Only nine studies investigated the prevalence of SC; based on the random‐effects model, the pooled prevalence was 21.90% (95% CI, 4.88%–38.92%). Owing to the scarcity of studies, we could not perform the funnel tests for publication bias and moderating variables of the pooled prevalence for SC. Conclusions: The prevalence of LF and STH decreased after PC implementation, although it was not significant. The difference for SC could not be assessed because of limited post‐PC data. The uneven distribution of research and the lack of standardised sampling methods may not fully capture the situation. [ABSTRACT FROM AUTHOR]

What is a diagnostic test for? We might assume the answer to this question is straightforward. A good test would help identify what disease someone suffers from, assist health providers to determine the correct course of treatment and/or enable public health authorities to know and intervene in health at the level of the population. In this article, we show that what a specific diagnostic test is for, the value it holds for different actors, and what makes it good, or not, is often far from settled. We tell the story of the development and design of a rapid antibody test for onchocerciasis, or river blindness, tracking multiple iterations of the device through three configurational moments in the framing of onchocerciasis disease and reshaping of the global health innovation ecosystem. Efforts to build that ecosystem for diagnostics are often premised on the notion that public health needs for diagnostics are pre-given and stable; the challenge is seen to be how to incentivize investment and find a customer base for diagnostics in under-resourced settings. By contrast, we show that for any disease, diagnostic needs are both multiple and constantly in flux, and are unlikely to be met by a single, stand-alone product. In the case of the onchocerciasis Ov-16 rapid test, the failure to recognize and address the multiplicity and instability of diagnostic needs in the innovation process resulted in the development of a rapid point of care test that might be manufactured, procured and used, but is unloved by public health experts and commercial manufacturers alike. The equivocal value of the onchocerciasis rapid test, we suggest, reveals the inadequacy of the current global health innovation ecosystem for developing diagnostic 'goods'. [ABSTRACT FROM AUTHOR]

Scabies, caused by the Sarcoptes scabiei var hominis mite burrowing into the skin, is a highly contagious disease characterized by intense nocturnal itching. Its global impact is considerable, affecting more than 200 million individuals annually and posing significant challenges to healthcare systems worldwide. Transmission occurs primarily through direct skin‐to‐skin contact, contributing to its widespread prevalence and emergence as a substantial public health concern affecting large populations. This review presents consensus‐based clinical practice guidelines for diagnosing and managing scabies, developed through the fuzzy Delphi method by dermatology, parasitology, pediatrics, pharmacology, and public health experts. The presence of burrows containing adult female mites, their eggs, and excreta is the diagnostic hallmark of scabies. Definitive diagnosis typically involves direct microscopic examination of skin scrapings obtained from these burrows, although dermoscopy has become a diagnostic tool in clinical practice. Treatment modalities encompass topical agents, such as permethrin, balsam of Peru, precipitated sulfur, and benzyl benzoate. In cases where topical therapy proves inadequate or in instances of crusted scabies, oral ivermectin is recommended as a systemic treatment option. This comprehensive approach addresses the diagnostic and therapeutic challenges associated with scabies, optimizing patient care, and management outcomes. [ABSTRACT FROM AUTHOR]

Background Podoconiosis is a neglected debilitating yet preventable disease. Despite its public health significance, podoconiosis is often misdiagnosed and confused with lymphatic filariasis. No appropriate diagnostic tests exist, contributing to underestimation and the absence of control interventions. Methods A population-based cross-sectional survey was conducted in seven districts with suspected or reported cases of podoconiosis or an altitude of 1200 m above sea level. Conducted from 30 January to 19 March 2023, the survey employed multilevel stratified sampling to reach eligible household members. Results Of the 10 023 participants sampled, 187 (confidence interval 1.25 to 2.78) had clinical features of podoconiosis. The highest prevalence was recorded in Nakapiripirit (7.2% [58/809]) and Sironko (2.8 [44/1564]) and the lowest in Kasese (0.3% [5/1537]), but ranged from 1.1 to 1.8% in Zombo, Rukungiri, Gomba and Hoima districts. The duration of podoconiosis was reported to range from 1 to 57 y. Factors associated with podoconiosis occurrence included advanced age, tungiasis, household cleanliness and personal hygiene. Sleeping on a bed, bathing daily, use of soap and use of footwear in at least moderate condition were protective against podoconiosis. Conclusions Podoconiosis occurred in all the sampled districts and was linked to personal hygiene. Long-standing cases suggest an absence of treatment. There is potential for early intervention using a holistic care model in managing this condition. Urgent action and stakeholder engagement are essential for effective podoconiosis management. [ABSTRACT FROM AUTHOR]

Abstract Neglected Tropical Diseases (NTDs) are a public health challenge in Nigeria, especially within the marginalized populations; millions of people are affected. As much as biomedical interventions go a long way in the elimination of NTDs, stigma from these diseases forms a very strong barrier to care. It has profound mental health implications for affected individuals. Much of this stigma results from cultural myths and fear of contagion, leading to late health-seeking behavior, social isolation, and discrimination. These psychosocial factors, linked to an inadequate response from mental health services, seriously hinder effective treatment and control measures, increasing the burden of the disease. This paper discusses the relationship between stigma and mental health in NTDs and outlines gaps in the current health strategy while providing a comprehensive approach to deal with these pertinent issues. Combating NTDs and stigma requires a multifaceted approach, including training healthcare providers on the legal rights of those affected, community-level stigma reduction to improve health-seeking behaviors, and policy reforms. More importantly, by incorporating mental health services, reducing stigma, and improving health-seeking behavior, Nigeria will be advancing her efforts toward the goals of NTD elimination.

Background: Neglected tropical diseases (NTDs) significantly impact the physical and mental well-being of affected individuals, particularly in Nigeria. This study aims to evaluate the effectiveness of integrating mental health services with self-care practices for individuals suffering from leprosy, Buruli ulcer (BU), and lymphatic filariasis (LF). The role of trained Healthcare Workers (HCWs) and NTD champions (NTD-Cs) will be explored to enhance health outcomes in this population. Methods: A cluster-randomized controlled trial was conducted in four local government areas (clusters) with the highest incidence of leprosy, BU, or LF. Clusters were purposively selected and randomized into intervention and control groups: three clusters received interventions, while one served as a control. The intervention arms include (a) Mental health and self-care interventions by NTD-Cs. (b) Mental health and self-care interventions by HCWs. (c) Self-care interventions only by HCWs. d) Control group receiving standard care. Data were collected at baseline and postintervention using validated questionnaires, including the Patient Health Questionnaire and World Health Organization Quality of Life (QOL-BREF), among others. The intervention will last for 8 months, with monthly self-help group meetings providing support and resources. Results: The study aims to provide evidence on the effectiveness of integrated mental health and self-care interventions for NTD patients by evaluating outcomes such as mental health status, quality of life (QOL), and socioeconomic factors. Conclusion: This trial aims to inform policy and practice by demonstrating the potential benefits of integrating mental health services within the care framework for individuals affected by NTDs in Nigeria. If successful, the findings will contribute to the enhancement of healthcare delivery and may be incorporated into the National Tuberculosis and Leprosy Control Program for broader implementation across the country. Trial registration: PACTR Registration number: PACTR202404852537141. https://pactr.samrc.ac.za/Default.aspx?Logout=True Retrospectively registered.

Abstract Background Rare infectious diseases of poverty (rIDPs) involve more than hundreds of tropical diseases, which dominantly affect people living in impoverished and marginalized regions and fail to be prioritized in the global health agenda. The neglect of rIDPs could impede the progress toward sustainable development. This study aimed to estimate the disease burden of rIDPs in 2021, which would be pivotal for setting intervention priorities and mobilizing resources globally. Methods Leveraging data from the Global Burden of Disease Study 2021, the study reported both numbers and age-standardized rates of prevalence, mortality, disability-adjusted life-years (DALYs), years lived with disability, and years of life lost of rIDPs with corresponding 95% uncertainty intervals (UIs) at global, regional, and national levels. The temporal trends between 1990 and 2021 were assessed by the joinpoint regression analysis. A Bayesian age-period-cohort model was used to project the disease burden for 2050. Results In 2021, there were 103.76 million (95% UI: 102.13, 105.44 million) global population suffered from rIDPs with an age-standardized DALY rate of 58.44 per 100,000 population (95% UI: 42.92, 77.26 per 100,000 population). From 1990 to 2021, the age-standardized DALY rates showed an average annual percentage change of − 0.16% (95% confidence interval: − 0.22, − 0.11%). Higher age-standardized DALY rates were dominated in sub-Saharan Africa (126.35 per 100,000 population, 95% UI: 91.04, 161.73 per 100,000 population), South Asia (80.80 per 100,000 population, 95% UI: 57.31, 114.10 per 100,000 population), and countries with a low socio-demographic index. There was age heterogeneity in the DALY rates of rIDPs, with the population aged under 15 years being the most predominant. Females aged 15–49 years had four-times higher age-standardized DALY rates of rIDPs than males in the same age. The projections indicated a slight reduction in the disease burden of rIDPs by 2050. Conclusions There has been a slight reduction in the disease burden of rIDPs over the past three decades. Given that rIDPs mainly affect populations in impoverished regions, targeted health strategies and resource allocation are in great demand for these populations to further control rIDPs and end poverty in all its forms everywhere. Graphical Abstract

Abstract Background Globally, community health worker (CHW) programmes are critical to addressing health worker shortages and have been recognised as critical pillars within the drive towards universal health coverage (UHC). In 2016, the Liberian Ministry of Health launched the National Community Health Services Policy 2016–2021, which included significant CHW programme reform to address ongoing health workforce capacity gaps in the country. However, little consideration was given to the impact of such reforms on ongoing health interventions that rely heavily on the use of CHW cadres. Our study explores how CHW programme reform in Liberia influenced performance of CHWs involved in the delivery of Neglected Tropical Disease (NTD) programmes to elucidate how health systems reform can impact the delivery of routine health interventions and vice versa. Methods We used a qualitative case study approach conducted between March 2017 and August 2018. Our instrumental case study approach uses qualitative methods, including document review of five CHW and NTD program-related policy documents; 25 key informant interviews with facility, county, and national level decision-makers; and 42 life and job histories with CHWs in Liberia. Data were analysed using a thematic framework approach, guided by Kok et al. framework of CHW performance. Data were coded in QRS NVIVO 11 Pro. Results Our findings show that CHW programme reform provides opportunities and challenges for supporting enhanced CHW performance. In relation to health system hardware, we found that CHW programme reform provides better opportunities for: formal recognition of CHWs; strengthening capacity for effective healthcare delivery at the community level through improved and formalised training; a more formal supervision structure; and provision of monthly incentives of 70 US dollars. Efficiency gaps in routine intervention delivery can be mitigated through the strengthening of these hardware components. Conversely, supervision deficits in routine CHW functioning can be supported through health interventions. In relation to systems software, we emphasise the ongoing importance of community engagement in CHW selection that is responsive to gendered power hierarchies and accompanied by gendered transformative approaches to improving literacy. Conclusions This study shows how CHW programme reform provides opportunities and challenges for health system strengthening that can both positively and negatively impact the functioning of routine health interventions. By working together, CHW programmes and routine health interventions have the opportunity to leverage mutually beneficial support for CHWs, which can enhance overall systems functioning by enhancing CHW performance.

Introduction: The burden of acute febrile illness remains underestimated in many low- and middle-income countries. The rationale of this study revolves around the gaps in diagnostics for acute febrile illnesses in these regions. Aim: To highlight the seroprevalence and co-infections of different infectious aetiologies in blood culture negative febrile patients. Materials and Methods: This cross-sectional study was conducted at Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India from October 2021 to July 2022, involving 153 serum samples from patients presenting with fever for less than two weeks duration during outpatient and emergency visits. The blood culture negative samples were further tested for other aetiologies such as Leptospirosis, Dengue NS1 antigen, Dengue IgM antibody, Chikungunya, Scrub typhus IgM, and Widal, respectively. Convalescent sera were also tested for all positive Widal results. All statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) statistical software (IBM SPSS version 26.0, Armonk, N.Y.). Results: Out of the 153 patients enrolled, 120 patients were tested for a panel of serological tests. The majority 52 (43.3%) were aged between 21 and 40 years. Fifty-five patients (45.8%) exhibited positivity, among which Scrub typhus was the most common aetiology with 21 (17.5%) case, followed by Leptospirosis 19 (15.8%), Dengue 10 (8.3%), Chikungunya 3 (2.5%), and Enteric fever 2 (1.7%), with no cases of malaria reported. Overall, co-infections reported in present study included 7 (5.8%) cases, of which scrub typhus and Leptospirosis were the most prevalent in 5 (4.16%) cases. Two patients (1.6%) presented with a co-infection of dengue and chikungunya. Conclusion: The diverse aetiologies causing acute febrile illness necessitate a syndrome-based disease surveillance approach, accompanied by strong clinical acumen, for the betterment of patient outcomes.

The shortage of treatment options for leishmaniasis, especially those easy to administer and viable for deployment in the world's poorest regions, highlights the importance of employing these strategies to cost-effectively investigate repurposing candidates. This scoping review aims to map the studies using in silico methodologies for drug repurposing against leishmaniasis. This study followed JBI recommendations for scoping reviews. Articles were searched on PubMed, Scopus, and Web of Science databases using keywords related to leishmaniasis and in silico methods for drug discovery, without publication date restrictions. The selection was based on primary studies involving computational methods for antileishmanial drug repurposing. Information about methodologies, obtained data, and outcomes were extracted. After the full-text appraisal, 34 studies were included in this review. Molecular docking was the preferred method for evaluating repurposing candidates (n=25). Studies reported 154 unique ligands and 72 different targets, sterol 14-alpha demethylase and trypanothione reductase being the most frequently reported. In silico screening was able to correctly pinpoint some known active pharmaceutical classes and propose previously untested drugs. Fifteen drugs investigated in silico exhibited low micromolar inhibition (IC50 < 10 µM) of Leishmania spp. in vitro. In conclusion, several in silico repurposing candidates are yet to be investigated in vitro and in vivo. Future research could expand the number of targets screened and employ advanced methods to optimize drug selection, offering new starting points for treatment development.

Abstract Background Out of the 21 neglected tropical diseases (NTDs) listed by the World Health Organization, 15 affect the People’s Republic of China. Despite significant achievements in controlling NTDs, comprehensive assessments of the disease burden based on actual case data and detailed information on spatial and temporal dynamics are still lacking. This study aims to assess the disease burden and spatial–temporal distribution of NTDs in China from 2005 to 2020, to provide a reference for the formulation of national health agendas in line with the global health agenda, and guide resource allocation. Methods The number of cases and deaths of major NTDs in China from 2005 to 2020 were downloaded from the China Public Health Science Data Center ( https://www.phsciencedata.cn/Share/index.jsp ) of the Chinese Center for Disease Control and Prevention and relevant literatures. Simplified formulas for disability-adjusted life years (DALYs) helped estimate the years of life lost (YLLs), years lived with disability (YLDs), and total DALYs. Spatial autocorrelation analysis of the average NTDs burden data for the years 2005 to 2020 was evaluated using Moran's I statistic. Results China's overall NTDs burden decreased significantly, from 245,444.53 DALYs in 2005 to 18,984.34 DALYs in 2020, marking a reduction of 92.27%. In 2005, the DALYs caused by schistosomiasis and rabies represent a substantial proportion of the total disease burden, accounting for 65.37% and 34.43% respectively. In 2015, Hunan and Sichuan provinces had the highest diversity of NTDs, with 9 and 8 number of different NTDs reported respectively. And the highest disease burden was observed in Sichuan (242,683.46 DALYs), Xizang Zizhiqu (178,318.99 DALYs) and Guangdong (154,228.31 DALYs). The “high-high” clustering areas of NTDs were mainly in China's central and southern regions, as identified by spatial autocorrelation analysis. Conclusions China has made unremitting efforts in the prevention and control of NTDs, and the disease burden of major NTDs in China has decreased significantly. Using the One Health concept to guide disease prevention and control in the field to effectively save medical resources and achieve precise intervention. Graphical abstract

Abstract Background Parasitic neglected tropical diseases (NTDs) or ‘infectious diseases of poverty’ continue to affect the poorest communities in the world, including in the Philippines. Socio-economic conditions contribute to persisting endemicity of these infectious diseases. As such, examining these underlying factors may help identify gaps in implementation of control programs. This study aimed to determine the prevalence of schistosomiasis and soil-transmitted helminthiasis (STH) and investigate the role of socio-economic and risk factors in the persistence of these diseases in endemic communities in the Philippines. Methods This cross-sectional study involving a total of 1,152 individuals from 386 randomly-selected households was conducted in eight municipalities in Mindanao, the Philippines. Participants were asked to submit fecal samples which were processed using the Kato-Katz technique to check for intestinal helminthiases. Moreover, each household head participated in a questionnaire survey investigating household conditions and knowledge, attitude, and practices related to intestinal helminthiases. Associations between questionnaire responses and intestinal helminth infection were assessed. Results Results demonstrated an overall schistosomiasis prevalence of 5.7% and soil-transmitted helminthiasis prevalence of 18.8% in the study population. Further, the household questionnaire revealed high awareness of intestinal helminthiases, but lower understanding of routes of transmission. Potentially risky behaviors such as walking outside barefoot and bathing in rivers were common. There was a strong association between municipality and prevalence of helminth infection. Educational attainment and higher “practice” scores (relating to practices which are effective in controlling intestinal helminths) were inversely associated with soil-transmitted helminth infection. Conclusion Results of the study showed remaining high endemicity of intestinal helminthiases in the area despite ongoing control programs. Poor socio-economic conditions and low awareness about how intestinal helminthiases are transmitted may be among the factors hindering success of intestinal helminth control programs in the provinces of Agusan del Sur and Surigao del Norte. Addressing these sustainability gaps could contribute to the success of alleviating the burden of intestinal helminthiases in endemic areas.

Background: Wolbachia incompatible insect technique (IIT) programs have been shown in field trials to be highly effective in suppressing populations of mosquitoes that carry diseases such as dengue, chikungunya, and Zika. However, the frequent and repeated release of Wolbachia-infected male mosquitoes makes such programs resource-intensive. While the need for optimization is recognized, potential strategies to optimize releases and reduce resource utilization have not been fully explored. Results: We developed a process-based model to study the spatio-temporal metapopulation dynamics of mosquitoes in a Wolbachia IIT program, which explicitly incorporates climatic influence in mosquito life-history traits. We then used the model to simulate various scale-down and redistribution strategies to optimize the existing program in Singapore. Specifically, the model was used to study the trade-offs between the intervention efficacy outcomes and resource requirements of various release program strategies, such as the total number of release events and the number of mosquitoes released. We found that scaling down releases in existing sites from twice a week to only once a week yielded small changes in suppression efficacy (from 87 to 80%), while requiring 44% fewer mosquitoes and release events. Additionally, redistributing mosquitoes from already suppressed areas and releasing them in new areas once a week led to a greater total suppressive efficacy (83% compared to 61%) while also yielding a 16% and 14% reduction in the number of mosquitoes and release events required, respectively. Conclusions: Both scale-down and redistribution strategies can be implemented to significantly reduce program resource requirements without compromising the suppressive efficacy of IIT. These findings will inform planners on ways to optimize existing and future IIT programs, potentially allowing for the wider adoption of this method for mosquito-borne disease control. [ABSTRACT FROM AUTHOR]

Tsetse flies are vectors of the parasite trypanosoma that cause the neglected tropical diseases human and animal African trypanosomosis. Semiochemicals play important roles in the biology and ecology of tsetse flies. Previous reviews have focused on olfactory-based attractants of tsetse flies. Here, we present an overview of the identification of repellents and their development into control tools for tsetse flies. Both natural and synthetic repellents have been successfully tested in laboratory and field assays against specific tsetse fly species. Thus, these repellents presented as innovative mobile tools offer opportunities for their use in integrated disease management strategies. [ABSTRACT FROM AUTHOR]

Background: Globally, community health worker (CHW) programmes are critical to addressing health worker shortages and have been recognised as critical pillars within the drive towards universal health coverage (UHC). In 2016, the Liberian Ministry of Health launched the National Community Health Services Policy 2016–2021, which included significant CHW programme reform to address ongoing health workforce capacity gaps in the country. However, little consideration was given to the impact of such reforms on ongoing health interventions that rely heavily on the use of CHW cadres. Our study explores how CHW programme reform in Liberia influenced performance of CHWs involved in the delivery of Neglected Tropical Disease (NTD) programmes to elucidate how health systems reform can impact the delivery of routine health interventions and vice versa. Methods: We used a qualitative case study approach conducted between March 2017 and August 2018. Our instrumental case study approach uses qualitative methods, including document review of five CHW and NTD program-related policy documents; 25 key informant interviews with facility, county, and national level decision-makers; and 42 life and job histories with CHWs in Liberia. Data were analysed using a thematic framework approach, guided by Kok et al. framework of CHW performance. Data were coded in QRS NVIVO 11 Pro. Results: Our findings show that CHW programme reform provides opportunities and challenges for supporting enhanced CHW performance. In relation to health system hardware, we found that CHW programme reform provides better opportunities for: formal recognition of CHWs; strengthening capacity for effective healthcare delivery at the community level through improved and formalised training; a more formal supervision structure; and provision of monthly incentives of 70 US dollars. Efficiency gaps in routine intervention delivery can be mitigated through the strengthening of these hardware components. Conversely, supervision deficits in routine CHW functioning can be supported through health interventions. In relation to systems software, we emphasise the ongoing importance of community engagement in CHW selection that is responsive to gendered power hierarchies and accompanied by gendered transformative approaches to improving literacy. Conclusions: This study shows how CHW programme reform provides opportunities and challenges for health system strengthening that can both positively and negatively impact the functioning of routine health interventions. By working together, CHW programmes and routine health interventions have the opportunity to leverage mutually beneficial support for CHWs, which can enhance overall systems functioning by enhancing CHW performance. [ABSTRACT FROM AUTHOR]

Background Scabies and impetigo cause direct health effects and contribute to severe infectious and immune-mediated complications. Ivermectin-based mass drug administration can reduce scabies and impetigo prevalence in island settings with high prevalence, but the effectiveness in moderate-prevalence settings is not known. Methods We conducted a single-arm, before–after community intervention trial. Mass drug administration was offered to the entire population of 4 villages in Uttarakhand, India. The treatment consisted of 2 doses, given 7 days apart, of oral ivermectin (∼200 μg/kg), or topical 5% permethrin if ivermectin was contraindicated. The primary outcome was the prevalence of scabies at 12 months compared with baseline, as diagnosed using clinical assessment and the 2020 International Alliance for the Control of Scabies criteria. Secondary outcomes included the prevalence of impetigo at each time point. The trial was registered with the Australian and New Zealand Trials Registry (ACTRN12619001712190). Results In January 2020, 1211 participants were enrolled (100% of the estimated village population). Treatment coverage was high—1204 (99.4%) and 1177 (97.2%) received 1 and 2 doses, respectively. Scabies was diagnosed in 91 participants (7.5%) and impetigo in 15 (1.2%). In February 2021, 1190 (98.3% of baseline) participants re-enrolled, and of these 11 had scabies (0.9%; relative risk reduction, 87.7%; 95% CI, 77.1%–93.4%) and 5 had impetigo (0.4%; relative risk reduction, 66.1%; 95% CI, 7.0%–87.6%). Conclusions A single round of ivermectin-based mass drug administration substantially reduced the prevalence of scabies and impetigo in this setting with moderate scabies prevalence in northern India. [ABSTRACT FROM AUTHOR]

Neglected tropical diseases (NTDs) encompass a group of diseases predominantly found in tropical regions, with origins dating back to their inclusion in the United Nations Millennium Development Goals in 2000. This initiative aimed to raise awareness and global funding to combat these diseases, which thrive in areas with limited sanitation, healthcare, and education. NTDs are caused by various pathogens such as bacteria, fungi, parasites, and viruses and affect over two billion individuals in resource-poor communities, leading to preventable deaths and devastating consequences. While the musculoskeletal system is only occasionally affected, the resulting chronic disabilities prevent individuals from working, posing a significant socioeconomic burden in this region of the world. Some NTDs exhibit distinct imaging features, and radiologists need to be aware of these characteristics to facilitate early treatment. In this review, we delve into musculoskeletal NTDs, focusing on clinical features and imaging findings, differential diagnosis, and clinical management. [ABSTRACT FROM AUTHOR]

Background: Leprosy is a chronic infection with high morbidity in Brazil. Primary care physicians' lack of knowledge about the disease may play a significant role in underdiagnosis. This study aimed to assess primary care physicians' ability to identify typical leprosy skin lesions and their knowledge of the subject. Methods: This cross‐sectional study relied on a questionnaire in which participating doctors chose one main diagnostic hypothesis and two differential diagnoses for each skin lesion presented. Five leprosy lesions were included. Questions regarding management, follow‐up, and diagnostic workup for the disease were also included. The questionnaire was sent to primary care physicians working in Curitiba, in the Southern Brazilian state of Paraná, and dermatologists, who constituted the control group. Results: Thirty‐two primary care physicians and 26 dermatologists agreed to participate in the study. Primary care physicians accurately identified a mean of 1.8 ± 1.2 of the five leprosy skin lesions, while dermatologists accurately identified 2.5 ± 0.9 (P = 0.009). The main misdiagnosed leprosy forms were the lepromatous and histoid variants. Among primary care physicians, 56.2% claimed to have little knowledge of the subject and a large share of participants was unaware of recent updates in treating paucibacillary forms, even within the dermatologist subgroup. Conclusions: Primary care physicians in Curitiba have little information regarding the diagnosis, treatment, and follow‐up of leprosy. Even dermatologists had difficulties with treatment and patient management, emphasizing the constant need for education on this subject. [ABSTRACT FROM AUTHOR]

Background: Neglected tropical diseases (NTDs) significantly impact the physical and mental well-being of affected individuals, particularly in Nigeria. This study aims to evaluate the effectiveness of integrating mental health services with self-care practices for individuals suffering from leprosy, Buruli ulcer (BU), and lymphatic filariasis (LF). The role of trained Healthcare Workers (HCWs) and NTD champions (NTD-Cs) will be explored to enhance health outcomes in this population. Methods: A cluster-randomized controlled trial was conducted in four local government areas (clusters) with the highest incidence of leprosy, BU, or LF. Clusters were purposively selected and randomized into intervention and control groups: three clusters received interventions, while one served as a control. The intervention arms include (a) Mental health and self-care interventions by NTD-Cs. (b) Mental health and self-care interventions by HCWs. (c) Self-care interventions only by HCWs. d) Control group receiving standard care. Data were collected at baseline and postintervention using validated questionnaires, including the Patient Health Questionnaire and World Health Organization Quality of Life (QOL-BREF), among others. The intervention will last for 8 months, with monthly self-help group meetings providing support and resources. Results: The study aims to provide evidence on the effectiveness of integrated mental health and self-care interventions for NTD patients by evaluating outcomes such as mental health status, quality of life (QOL), and socioeconomic factors. Conclusion: This trial aims to inform policy and practice by demonstrating the potential benefits of integrating mental health services within the care framework for individuals affected by NTDs in Nigeria. If successful, the findings will contribute to the enhancement of healthcare delivery and may be incorporated into the National Tuberculosis and Leprosy Control Program for broader implementation across the country. Trial registration: PACTR Registration number: PACTR202404852537141. https://pactr.samrc.ac.za/Default.aspx?Logout=True Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Chagas disease (CD), a Neglected Tropical Disease caused by Trypanosoma cruzi, affects millions of people in Latin America and the southern US and spreads worldwide. CD results from close interactions between humans, animals, and vectors, influenced by sociodemographic factors and housing materials. Methods: This study aimed to evaluate how these factors, along with seasonal changes, affect the distribution of CD vectors in an endemic community near Puebla, Mexico, using a cross-sectional survey. A total of 383 people from this area, known for the presence of major vectors such as Triatoma barberi and Triatoma pallidipennis, were surveyed. Results: As a result of the survey, it was found that only 27.4% of respondents knew about CD, and 83.3% owned potential reservoir pets; additionally, the quality of the wall, roof, and floor significantly influenced vector sightings, while the seasonal pattern showed less of an association. Chi-square tests confirmed these associations between vector sightings and housing materials (p < 0.001); vector sightings versus seasonal patterns showed less of an association (p = 0.04), and land use changes did not show an association (p = 0.27). Conclusions: Construction materials play an important role in the sighting of triatomines in homes, so important actions should be taken to improve homes. However, further experimental or longitudinal studies are needed to establish causality. [ABSTRACT FROM AUTHOR]

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Background: Parasitic neglected tropical diseases (NTDs) or 'infectious diseases of poverty' continue to affect the poorest communities in the world, including in the Philippines. Socio-economic conditions contribute to persisting endemicity of these infectious diseases. As such, examining these underlying factors may help identify gaps in implementation of control programs. This study aimed to determine the prevalence of schistosomiasis and soil-transmitted helminthiasis (STH) and investigate the role of socio-economic and risk factors in the persistence of these diseases in endemic communities in the Philippines. Methods: This cross-sectional study involving a total of 1,152 individuals from 386 randomly-selected households was conducted in eight municipalities in Mindanao, the Philippines. Participants were asked to submit fecal samples which were processed using the Kato-Katz technique to check for intestinal helminthiases. Moreover, each household head participated in a questionnaire survey investigating household conditions and knowledge, attitude, and practices related to intestinal helminthiases. Associations between questionnaire responses and intestinal helminth infection were assessed. Results: Results demonstrated an overall schistosomiasis prevalence of 5.7% and soil-transmitted helminthiasis prevalence of 18.8% in the study population. Further, the household questionnaire revealed high awareness of intestinal helminthiases, but lower understanding of routes of transmission. Potentially risky behaviors such as walking outside barefoot and bathing in rivers were common. There was a strong association between municipality and prevalence of helminth infection. Educational attainment and higher "practice" scores (relating to practices which are effective in controlling intestinal helminths) were inversely associated with soil-transmitted helminth infection. Conclusion: Results of the study showed remaining high endemicity of intestinal helminthiases in the area despite ongoing control programs. Poor socio-economic conditions and low awareness about how intestinal helminthiases are transmitted may be among the factors hindering success of intestinal helminth control programs in the provinces of Agusan del Sur and Surigao del Norte. Addressing these sustainability gaps could contribute to the success of alleviating the burden of intestinal helminthiases in endemic areas. [ABSTRACT FROM AUTHOR]

Leprosy remains a significant neglected tropical disease despite the goal of elimination having been achieved in various endemic nations over the past two decades. Reactional episodes complicate the disease course, resulting in deformities and disability. The main aim of treatment is to kill Mycobacterium leprae and decrease the bacterial load, which could help prevent further bacilli transmission. A major concern in breaking the chain of transmission and possibly for recurrent reactions is the role of drug‐resistant bacilli. Though some data is available on the background prevalence of drug resistance in leprosy, there is a paucity of studies that look for resistance specifically in leprosy reactions. Administration of long‐term steroids or immunosuppressants for chronic and recurrent responses in the presence of drug resistance has the twin effect of perpetuating the multiplication of resistant bacilli and encouraging the dissemination of leprosy. The increasing trend of prescribing second‐line drugs for leprosy or type 2 reactions without prior assessment of drug resistance can potentially precipitate a severe public health problem as this can promote the development of resistance to second‐line drugs as well. A comprehensive multicenter study, including drug resistance surveillance testing in cases of reactions, is necessary, along with the current measures to stop the spread of leprosy. Here, we have detailed the history of drug resistance in leprosy, given pointers on when to suspect drug resistance, described the role of resistance in reactions, methods of resistance testing, and the management of resistant cases with second‐line therapy. [ABSTRACT FROM AUTHOR]

Onchocerciasis is an endemic disease in Enugu State that imposes a debilitating medical and economic burden on crop farmers. This study assessed crop farmers' knowledge of Enugu State. A cross-sectional survey of 372 farmers, selected through a multistage sampling technique, was conducted using the Onchocerciasis Knowledge Questionnaire (OKQ). It elicited responses regarding the causes, signs and symptoms, preventive measures, and treatment/treatment options. The results indicated that farmers had poor knowledge (46.4%). The respondents had good knowledge of causation (68.5%) and treatment options (56.7%) but exhibited poor knowledge of signs and symptoms (30.1%) and preventive measures (33.1%). They also exhibited substantial misconceptions about Onchocerciasis. The study also found that females (77.5%) were more knowledgeable than males (68.7%), that those with only primary education (88.9 %) were more knowledgeable, and that older farmers (75.4%) were more knowledgeable than younger farmers. Independent bivariate logistic regression indicated that a statistically significant association existed between marital status and knowledge and between level of education and knowledge, while the association between gender and knowledge, and age and knowledge was not significant at a significance level of 0.05. It was recommended that health education programmes be mounted by requisite State Ministries and Parastatals to arm residents with the knowledge for personal protection and to contribute effectively to ongoing intervention programmes in Enugu State. [ABSTRACT FROM AUTHOR]

Ivermectin (IVM), diethylcarbamazine (DEC) plus albendazole (ALB) – IDA – should be incorporated on a larger scale and adopted for mass drug administration (MDA) campaigns for filarial infections. Novel macrofilaricidal treatments are urgently needed to eliminate filarial infections. The developmental pipeline for new treatments continues to be limited. Cooperation between academia, pharmaceutical companies, non-governmental organizations (NGOs), and local stakeholders is essential to facilitate the development, production, and distribution of new treatment strategies. Although lymphatic filariasis and onchocerciasis have been targeted for global elimination, these helminth infections are still a major public health problem across the tropics and subtropics. Despite decades of research, treatment options remain limited and drugs that completely clear the infections, and can be used on a large scale, are still unavailable. In the present review we discuss the strengths and weaknesses of currently available treatments and new ones in development. Novel candidates (corallopyronin A, DNDi-6166, emodepside, and oxfendazole) are currently moving through (pre)clinical development, while the development of two candidates (AWZ1066S and ABBV-4083/flubentylosin) was recently halted. The preclinical R&D pipeline for filarial infections continues to be limited, and recent setbacks highlight the importance of continuous drug discovery and testing. [ABSTRACT FROM AUTHOR]

Background There is limited knowledge about the stigma associated with cutaneous leishmaniasis (CL) in Sri Lanka. To ensure that leishmaniasis researchers focus on CL-associated stigma, we provide an evidence-based framework that can be used in future research. Methods We conducted a systematic review on CL-associated stigma using international evidence and carried out a multimethod qualitative study in the Anuradhapura district in Sri Lanka. Based on that, we identified manifestations of stigma, drivers and facilitators that we synthesised to develop a conceptual framework on CL-associated stigma. Results Our framework consists of drivers, facilitators and self-stigma experienced by people with CL. Stigma drivers included fear, misbeliefs and misconceptions about CL; the belief that wounds are disfiguring; the treatment burden and implied blame. Facilitators that reduced stigma included knowledge of the curability of CL and awareness that CL is not contagious. The nature of social interactions in rural communities enhanced stigma formation. We identified various enacted, felt and internalised stigma experiences of people with CL. Conclusions We developed a conceptual framework of the stigma associated with CL that can be used to develop targeted interventions to increase CL awareness, address stigma and improve the quality of life for CL patients. [ABSTRACT FROM AUTHOR]

Leishmania infantum is the vector-borne trypanosomatid parasite causing visceral leishmaniasis in the Mediterranean basin. This neglected tropical disease is treated with a limited number of obsolete drugs that are not exempt from adverse effects and whose overuse has promoted the emergence of resistant pathogens. In the search for novel antitrypanosomatid molecules that help overcome these drawbacks, drug repurposing has emerged as a good strategy. Nitroaromatic compounds have been found in drug discovery campaigns as promising antileishmanial molecules. Fexinidazole (recently introduced for the treatment of stages 1 and 2 of African trypanosomiasis), and pretomanid, which share the nitroimidazole nitroaromatic structure, have provided antileishmanial activity in different studies. In this work, we have tested the in vitro efficacy of these two nitroimidazoles to validate our 384-well high-throughput screening (HTS) platform consisting of L. infantum parasites emitting the near-infrared fluorescent protein (iRFP) as a biomarker of cell viability. These molecules showed good efficacy in both axenic and intramacrophage amastigotes and were poorly cytotoxic in RAW 264.7 and HepG2 cultures. Fexinidazole and pretomanid induced the production of ROS in axenic amastigotes but were not able to inhibit trypanothione reductase (TryR), thus suggesting that these compounds may target thiol metabolism through a different mechanism of action. [ABSTRACT FROM AUTHOR]