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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.

Leishmaniases comprise a set of neglected diseases, afflicting over one million people worldwide and frequently leading to fatal outcomes, mainly in their visceral form. The current treatment often comes with severe side effects and limitations regarding its effectiveness. It is imperative to explore novel therapeutic avenues that are more potent and less toxic. In this study, we successfully synthesized α-acyloxycarboxamides (also known as depsipeptides). These compounds underwent rigorous evaluation through a combination of molecular docking, molecular dynamics (MD) simulations, and in vitro assessments against both promastigote and amastigote forms of Leishmania amazonensis. Notably, most of the α-acyloxycarboxamides showed substantially low cytotoxicity in peritoneal macrophages with a CC50 above 400 μM, whereas amphotericin B (positive control) showed a CC50 value greater than 50 μM. This effect is reflected in the selectivity index (SI), where compounds 7a1 and 7db1 showed more favorable results (SI >14.66 and 10.44) when compared to the positive control (SI > 10.36). In vitro experiments demonstrated that the α-acyloxycarboxamides effectively inhibited the growth of axenic promastigote forms of L. amazonensis. Particularly, compounds 7a1 (IC50 = 31.83 μM) and 7db1 (IC50 = 33.88 μM) stood out, displaying significant activity in reducing intracellular parasites as well (IC50 = 27.28 and 38.31 μM, respectively). To gain insights into the potential pathway of activity for compound 7a1, we conducted in silico studies targeting predictive pharmacokinetic parameters and the application of reverse molecular docking utilizing critical biological targets, followed by molecular dynamics (MD) simulations. Among 59 Leishmania targets, the reverse approach suggested that compound 7a1 targets the N-myristoyltransferase enzyme by establishing only hydrophobic interactions with four amino acid residues at the binding site, with an affinity energy of −8.98 kcal mol−1. Subsequently, MD simulations were performed to obtain further information on its binding modes and complex stability under physiological conditions, in which it was observed that the macromolecule presented great stability in the presence of compound 7a1 (<1.0 Å), suggesting a stable ligand–target complex formation. Regarding ADMET studies, a-acyloxycarboxamides demonstrated promising properties, with no violations of the Lipinski rule. This study underscores the promise of α-acyloxycarboxamides as potential therapeutic candidates targeting leishmaniasis. Developing these compounds could lead to more effective and less toxic treatments, addressing a critical need in the fight against this neglected disease. [ABSTRACT FROM AUTHOR]

Buruli ulcer (BU) is a neglected tropical disease of skin and subcutaneous tissues caused by Mycobacterium ulcerans. BU-endemic areas are highly focal, and M. ulcerans transmission dynamics vary by setting. In Victoria, Australia, BU is an endemic vector-borne zoonosis, with mosquitoes and native possums implicated in transmission, and humans incidental hosts. Despite the importance of possums as wildlife reservoirs of M. ulcerans, knowledge of BU in these animals is limited. Opportunistic necropsy-based and active trap-and-release surveillance studies were conducted across Melbourne and Geelong, Victoria, to investigate BU in possums. Demographic data and biological samples were collected, and cutaneous lesions suggestive of BU were mapped. Samples were tested for the presence of M. ulcerans DNA by IS2404 qPCR. The final dataset included 26 possums: 20 necropsied; 6 trapped and released. Most possums (77%) were common ringtails from inner Melbourne. Nine had ulcers, ranging from single and mild, to multiple and severe, exposing bones and tendons in three cases. M. ulcerans was confirmed in 73% (19/26) of examined possums: 8 with lesions and 11 without. Oral swabs were most frequently indicative of M. ulcerans infection status. Severely ulcerated possums had widespread systemic internal bacterial dissemination and were shedding M. ulcerans in faeces. The anatomical distribution of ulcers and PCR positivity of biological samples suggests possums may contract BU from bites of M. ulcerans-harbouring mosquitoes, traumatic skin wounds, ingestion of an unknown environmental source, and/or during early development in the pouch. Ringtail possums appear highly susceptible to infection with M. ulcerans and are important bacterial reservoirs in Victoria. Oral swabs should be considered for diagnosis or surveillance of infected possums. A One Health approach is needed to design and implement integrated interventions that reduce M. ulcerans transmission in Victoria, thereby protecting wildlife and humans from this emerging zoonotic disease. Author summary: Buruli ulcer (BU), a neglected tropical skin disease, is emerging as a public health concern in the temperate Australian state of Victoria. Here, BU is spread by mosquitoes, and native possums are wildlife reservoirs of the causative bacterium, Mycobacterium ulcerans. Possums can be infected by BU, but knowledge of infection and disease in these animals is limited. We conducted surveillance studies in the two largest cities of Victoria, examining live and deceased possums. We found skin lesions in a third of examined possums and confirmed presence of M. ulcerans in almost three-quarters of the animals. Mouth swabs were positive for the bacteria in nearly two thirds of possums, as were pouch swabs of almost half the females. We also conducted mapping of the bodily distribution of skin lesions and found that paws and the undersides of abdomens and tails were the most affected areas. Our findings add support to the concept that possums, particularly ringtails, are M. ulcerans reservoirs in Victoria, and suggest several possible routes of infection for free-living possums that warrant further research. Improved understanding of BU in possums may allow development of targeted interventions that reduce disease transmission and protect both animal and human health. [ABSTRACT FROM AUTHOR]

Children and their families living in leprosarium areas may have a lower quality of life than the general population. However, there is limited evidence on health-related quality of life and its associated factors among children living in previous leprosarium settlement areas. Hence, this study aimed to compare the health-related quality of life among children living in previous leprosarium and non-leprosarium settlement areas in eastern Ethiopia. A community-based comparative cross-sectional study was conducted among 515 randomly selected children aged 8 to 18 years living in the Amir Nur and Babile districts from January to February 30, 2024. Data were collected through interviews with children and parents using the Pediatric Quality of Life Inventory Version 4. The data were analyzed using STATA version 14. Simple and multiple linear regression was employed to identify associations between independent and outcome variables. The overall mean health-related quality of life scores were 73.98 ± 18.47 and 77.67 ± 14.72 in the child self-reports (P = 0.01) and 55.78 ± 12.03 and 55.61 ± 8.50 (P = 0.85) in the parent proxy reports in the previous leprosarium and nonleprosarium settlement areas, respectively. In multiple linear regression, child education (β = 14.69; 95% CI: 8.69, 20.69), the absence of neglected and tropical diseases (β = 4.02; 95% CI: 0.66, 7.37), and child face washing habits (β = 5.54, 95% CI: 2.14, 8.95) increase health-related quality of life. However, a previous history of neglected and tropical diseases (β = -8.54; 95% CI: -12.93, -4.15) and the absence of hand washing facilities (β = -8.57; 95% CI, -15.22, -1.92) decrease the mean health-related quality of life. Based on child self-reports, one in four children from previous leprosarium areas had poor health-related quality of life compared to children living in none leprosarium areas. Children's educational status, their daily habits of washing their face, not having neglected, and tropical diseases had improved health-related quality of life. To improve health-related quality of life, stakeholders should pay attention to and work on the early detection and treatment of neglected and tropical diseases, child education, and proper sanitation practices in the leprosarium community. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis, a chronic parasitic disease, remains a public health issue in tropical and subtropical regions, especially in low and moderate-income countries lacking assured access to safe water and proper sanitation. A national prevalence survey carried out by the Brazilian Ministry of Health from 2011 to 2015 found a decrease in human infection rates to 1%, with 19 out of 26 states still classified as endemic areas. There is a risk of schistosomiasis reemerging as a public health concern in low-endemic regions. This study proposes an integrated landscape-based approach to aid surveillance and control strategies for schistosomiasis in low-endemic areas. Methodology/Principal findings: In the Middle Paranapanema river basin, specific landscapes linked to schistosomiasis were identified using a comprehensive methodology. This approach merged remote sensing, environmental, socioeconomic, epidemiological, and malacological data. A team of experts identified ten distinct landscape categories associated with varying levels of schistosomiasis transmission potential. These categories were used to train a supervised classification machine learning algorithm, resulting in a 92.5% overall accuracy and a 6.5% classification error. Evaluation revealed that 74.6% of collected snails from water collections in five key municipalities within the basin belonged to landscape types with higher potential for S. mansoni infection. Landscape connectivity metrics were also analysed. Conclusions/Significance: This study highlights the role of integrated landscape-based analyses in informing strategies for eliminating schistosomiasis. The methodology has produced new schistosomiasis risk maps covering the entire basin. The region's low endemicity can be partly explained by the limited connectivity among grouped landscape-units more prone to triggering schistosomiasis transmission. Nevertheless, changes in social, economic, and environmental landscapes, especially those linked to the rising pace of incomplete urbanization processes in the region, have the potential to increase risk of schistosomiasis transmission. This study will help target interventions to bring the region closer to schistosomiasis elimination. Author summary: Schistosomiasis is a Neglected Tropical Disease whose transmission in Brazil is related to human contact with water contaminated by the trematode parasite Schistosoma mansoni. The national prevalence survey from 2011–2015 revealed a decline in schistosomiasis positivity rates to 1%, marking areas in the Middle Paranapanema river basin in SP-Brazil (MP) as low endemic. However, control programs face additional challenges due to the new dynamics connected with the social, environmental, and economic developments fueled by an urban-industrial urbanization model in the MP region. To address this, our study proposes a landscape-based methodological approach that categorizes and assesses schistosomiasis transmission potential in different regional landscape patterns. By combining remote sensing, environmental, socioeconomic, epidemiological, and malacological data, a multidisciplinary team identified ten distinct landscape-unit types associated with varying levels of schistosomiasis transmission potential. Using a decision-tree based machine learning classification method, we mapped schistosomiasis risk across the basin at a landscape scale. The identification of landscape features associated with schistosomiasis transmission risk will help to fine tune suitable surveillance and control strategies at both local and regional levels. Our findings indicate that landscape-units with higher transmission potentials are less interconnected across the basin. Low connectivity at the landscape scale, in part, explains the MP low endemic areas, contributing to the low endemicity in the Middle Paranapanema region. This approach offers promise for local and regional schistosomiasis management efforts aimed at eradicating the disease. [ABSTRACT FROM AUTHOR]

Background Buruli ulcer disease (BUD) is a neglected tropical disease of the skin, subcutaneous tissue and bone caused by Mycobacterium ulcerans , with various disabling and stigmatising sequelae. Patients face a range of adverse impacts owing to the disease as most are unable to relate effectively with their communities, battling stigma and fear of discrimination. This study aimed to explore the stigma associated with the lived experiences of BUD in patients in Nigeria. Methods This was a cross-sectional qualitative study that employed a focus group discussion (FGD) and key informant interviews in Enugu State, Nigeria. A random sampling of communities was followed by a purposive selection of FGD participants and key informants. A total of six key informants and eight FGD participants took part in the study. Data were collected over 6 wk from December 2022 to February 2023. The NVivo application was used to analyse transcripts and compute themes of quotes. Results Patients experienced stigma owing to the condition. The most reported experiences by participants were shame and culpability, isolation and social exclusion, including maltreatment from family members. Conclusions Identifying the stigma experienced by patients owing to BUD helps in the provision of psychosocial management services and support for patients. [ABSTRACT FROM AUTHOR]

We report acute Oropouche virus infections in 2 previously healthy women from a nonendemic region of Brazil outside the Amazon Basin. Infections rapidly progressed to hemorrhagic manifestations and fatal outcomes in 4-5 days. These cases highlight the critical need for enhanced surveillance to clarify epidemiology of this neglected disease. [ABSTRACT FROM AUTHOR]

Snakebite envenomation is a serious health concern in tropical regions, resulting in high mortality. The World Health Organization (WHO) has declared it a neglected tropical disease and is working on strategies to reduce mortality. Russell's viper (Daboia russelii) is one of the most abundant venomous snakes found across Southeast Asia. Proteomic analysis of Russell's viper venom has demonstrated variation, with phospholipase A2 (PLA2) being the most abundant toxin across geographic boundaries. PLA2, a major constituent of the low-molecular-weight fraction of snake venom, hydrolyses phospholipids at the sn-2 position, releasing arachidonic acid and lysophospholipids. They are reported to cause various pharmacological effects, including hemolysis, anticoagulation, neurotoxicity, myotoxicity, and oedema. Though administration of antivenoms (ASV) is the primary treatment for envenomation, it has many drawbacks. Besides causing hypersensitivity reactions and life-threatening anaphylaxis, treatment with ASV is further complicated due to its inability to neutralize low-molecular-weight toxins. Thus, there is a greater need to produce next-generation antivenoms that can target specific toxins in the venom. In this review, we explored the classification of Russell's viper and the variation in its proteomic profile across Southeast Asia to date. In addition, we have also summarized the mechanism of action of PLA2 and discussed various isoforms of PLA2 found across different regions with their respective pharmacological effects. Finally, the drawbacks of commercially available antivenoms and the molecules investigated for inhibiting the low-molecular-weight toxin, PLA2 are discussed. [ABSTRACT FROM AUTHOR]

Background Visceral leishmaniasis (VL) is a neglected tropical disease that mostly affects the working class and impoverished segments of society, having a significant negative effect on the economic development of the affected nation. While anti-leishmanial medications lower mortality among VL patients, patients may still die or require more time to recover while receiving treatment. In this regard, there are limited studies in Ethiopia. This study aims to determine the time to recovery and its associated predictors among adult VL patients at Metema Hospital, Metema, Ethiopia. Methods A hospital-based cross-sectional study was employed and the data were collected from patient's charts from September 2017 to September 2021. Data were entered and analysed using EpiData version 3.1, Stata version 14.2 and R version 3.4.0 statistical software. Kaplan–Meier survival curves and logrank tests were used to compare the survival time. The Cox proportional hazards model assumption and model fitness were checked and used to identify statistical association predictors in VL patients. Results The Cox proportional hazards model was fitted. The overall medium recovery time was 7 d (minimum 4, maximum 14). The variables of nasal bleeding (adjusted hazard ratio [aHR] 0.44 [95% confidence interval {CI} 0.19 to 0.89]), no comorbidity (aHR 2.29 [95% CI 1.27 to 4.11]), relapse of VL (aHR 0.33 [95% CI 0.15 to 0.75]), low parasite load (aHR 2.58 [95% CI 1.48 to 4.51]) and ambulatory (aHR 3.26 [95% CI 2.45 to 6.53]) were significantly associated with time to recovery in VL patients. Conclusions Patients with comorbidities, nasal bleeding, relapse of VL, bedridden and high parasite load should be treated and monitored carefully to recover quickly from their illness. [ABSTRACT FROM AUTHOR]

Therapies that modulate and appropriately direct the immune response are promising candidates for the treatment of infectious diseases. One such candidate therapeutic is DZ13, a short, synthetic, single-stranded DNA molecule. This molecule has enzymatic activity and can modulate the immune response by binding to and degrading the mRNA encoding a key immunoregulatory molecule. Originally developed and entering clinical trials as an anticancer agent, DZ13 has also been evaluated as a treatment for viral infections, and has been shown to provide protection against infection with influenza virus in a mouse model of infection. In this work, we evaluated whether the immunomodulatory properties of DZ13 could provide protection against the potential biothreat pathogen Burkholderia pseudomallei which causes the neglected tropical disease melioidosis. Treatment of mice infected with B. pseudomallei demonstrated that DZ13 did indeed provide excellent protection after only two post-exposure treatments. However, our data indicated that the enzymatic activity contained in DZ13 was not required for protection, with control oligonucleotide treatments lacking activity against the target mRNA equally as protective against B. pseudomallei. We have designed new sequences to study the mechanism of protection further. These novel sequences offer enhanced protection against infection, but are not directly anti-microbial and do not appear to be stimulating the immune system via TLR9 or other key innate immune sensors, despite containing CpG motifs. The molecular mechanism of these novel sequences remains to be elucidated, but the data highlights that these oligonucleotide-sensing pathways are attractive and relevant targets to modulate during bacterial and viral infections. [ABSTRACT FROM AUTHOR]

Human rabies is a prevalent issue in China, posing a significant public health concern in the country. This study fitted the Bayesian model of separable in spatial and temporal variation and inseparable spatiotemporal variation in disease risk respectively based on Integrated Nested Laplace Approximation (INLA) to investigate the spatiotemporal characteristics of human rabies across 31 provinces in China from 2004 to 2020. It also investigated the influence of natural and socio-environmental factors on the incidence of the disease. Within the study period, a total of 26,807 cases of human rabies were reported, with the highest risk of incidence occurring in 2007, followed by a steady annual decline to the lowest risk in 2020. Guangxi Province exhibited the highest risk, while Jilin Province had the lowest, with the southern, central, and eastern regions reporting higher risks than the northern and western areas. By 2020, most provinces such as Guangxi and Guizhou had significantly reduced their relative risk (RR) of human rabies from historical highs. However, some provinces like Hunan, Henan, and Jiangsu experienced an increase in RR compared to previous years. As the annual average temperature increases, the risk of human rabies incidence in China correspondingly rises. Conversely, with increases in the annual average daily sunshine duration, per capita disposable income of urban residents, and local government healthcare expenditures, the risk of human rabies incidence declines. We conclude that the risk of human rabies in China initially increased and then decreased annually from 2004 to 2020. Future efforts should continuously increase financial investments in rabies prevention and control, focusing particularly on Hunan, Henan, Jiangsu, and provinces characterized by higher temperatures, shorter sunshine durations, and lower economic levels. Author summary: Rabies is a Neglected Tropical Disease (NTD), predominantly prevalent in Africa and Asia, with a nearly 100% fatality rate upon onset. China is striving to achieve the WHO's global goal of zero deaths from dog-mediated human rabies by 2030. Therefore, exploring the spatial and temporal evolution of human rabies in China and the possible influencing factors can provide a scientific basis for the development of more effective human rabies prevention and control programs in China. The results of the study showed that from 2004 to 2020, the overall relative risk of human rabies incidence in China showed an increasing and then decreasing trend. The relative risk of most provinces, such as Guangxi and Guizhou, declined significantly, but there were still some provinces, such as Hunan and Henan, where the relative risk showed a rising trend year by year. The results of the analysis of influencing factors indicate that lower per capita disposable income of urban residents, local government healthcare expenditures and sunshine hours, higher temperatures are associated with a higher risk of human rabies. [ABSTRACT FROM AUTHOR]

Introduction: Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi that is transmitted mainly by the feces of infected Triatomines. In Ecuador the main vector is Rhodnius ecuadoriensis which is distributed in several provinces of the country. More than 40% of these insects in the wild have T. cruzi as part of their intestinal microbiota. For this reason, the objective of this research was to characterize the intestinal bacterial microbiota of R. ecuadoriensis. Methods: The methodology used was based on the DNA extraction of the intestinal contents from the wild collected insects (adults and nymphs V), as well as the insects maintained at the insectary of the CISeAL. Finally, the samples were analyzed by metagenomics extensions based on the dierent selected criteria. Results: The intestinal microbiota of R. ecuadoriensis presented a marked divergence between laboratory-raised and wild collected insects. This dierence was observed in all stages and was similar between insects from Loja and Manabí. A large loss of microbial symbionts was observed in laboratory-raised insects. Discussion: This study is a crucial first step in investigating microbiota interactions and advancing new methodologie. [ABSTRACT FROM AUTHOR]

High mobility group (HMG) proteins are intrinsically disordered nuclear non-histone chromosomal proteins that play an essential role in many biological processes by regulating the expression of numerous genes in eukaryote cells. HMGA proteins contain three DNA binding motifs, the "AT-hooks", that bind preferentially to AT-rich sequences in the minor groove of B-form DNA. Understanding the interactions of AT-hook domains with DNA is very relevant from a medical point of view because HMGA proteins are involved in different conditions including cancer and parasitic diseases. We present here the first crystal structure (1.40 Å resolution) of the HMGA AT-hook 1 domain, bound to the minor groove of AT-rich DNA. In contrast to AT-hook 3 which bends DNA and shows a larger minor groove widening, AT-hook 1 binds neighbouring DNA molecules and displays moderate widening of DNA upon binding. The binding affinity and thermodynamics of binding were studied in solution with surface plasmon resonance (SPR)-biosensor and isothermal titration calorimetry (ITC) experiments. AT-hook 1 forms an entropy-driven 2:1 complex with (TTAA)2-containing DNA with relatively slow kinetics of association/dissociation. We show that N-phenylbenzamide-derived antikinetoplastid compounds (1–3) bind strongly and specifically to the minor groove of AT-DNA and compete with AT-hook 1 for binding. The central core of the molecule is the basis for the observed sequence selectivity of these compounds. These findings provide clues regarding a possible mode of action of DNA minor groove binding compounds that are relevant to major neglected tropical diseases such as leishmaniasis and trypanosomiasis. [ABSTRACT FROM AUTHOR]

Background: The prevalence of intestinal schistosomiasis remains a challenge despite government efforts to eliminate the disease. This study aims to assess the prevalence of intestinal schistosomiasis in school-age children living in the villages surrounding Lake Chamo in southern Rift Valley of Ethiopia. Methodology/Principal findings: A cross-sectional study was conducted from January to July 2023 in Shele Mela Kebele in Gamo Zone, South Ethiopia. Stool samples were collected from 597 school-age children. A singe Kato-Katz for helminths and formalin-ether concentration technique for protozoan parasites were used to process the samples. The intensity of Schistosoma mansoni infection among school-age children was determined by counting the number of eggs per gram of stool. Of the 597 children screened, 52.3% (95% CI: 48.4.4–56.4) were positive for Schistosoma mansoni. These findings showed that 55% of the infections were light, 30.3% were moderate, and 14.7% were heavy. The mean egg count of S. mansoni parasites was 182.1 eggs per gram. The prevalence of other intestinal parasites (Hymenolopis nana, Ascaris lumbricoides, Hookworm, Taenia species, Giardia lamblia and Entamoeba histolytica) was found to be 7.7% (46/597). The overall prevalence of S. mansoni co-infection with other intestinal parasites was 5.0% (30/597). Specifically, the co-infection rates were 1.5% for A. lumbricoides, 1.3% for H. nana, 1.0% for Taenia species, 0.2% for Hookworm, 0.2% for E. histolytica, and 0.2% for G. lamblia. Conclusions/Significances: The study showed a high rate of S. mansoni infection among school-age children. This calls for immediate action, such as school-based deworming, to protect these children from the disease and reduce the burden. Further research is needed to understand the transmission of the infection by the intermediate host. Author summary: Schistosomiasis is a neglected tropical parasitic disease that affects over 220 million people globally. Although there is a deworming mass drug administration (MDA) program for soil-transmitted helminths, the study area still needs to be integrated into the Praziquantel MDA. The study focused on school-age children to better understand the prevalence of the disease and recommend interventions. Hence, we assessed the prevalence and intensity of intestinal schistosomiasis among school-age children living in selected villages near Lake Chamo in the southern Rift Valley of Ethiopia. The results revealed that the prevalence of Schistosoma mansoni was 52.3%. The overall prevalence of other intestinal parasites (Hymenolopis nana, Ascaris lumbricoides, Hookworm, Taenia species, Giardia lamblia, and Entamoeba histolytica) was 7.7%. We documented a 5% S. mansoni co-infection with all other intestinal parasites including A. lumbricoides, H. nana, Taenia species, Hookworm, E. histolytica, and G. lamblia. This implies a high prevalence of intestinal parasites in school-age children, necessitating immediate action to alleviate this burden. Implementing school-based mass drug administration (MDA) for schistosomiasis is advisable in the study villages. [ABSTRACT FROM AUTHOR]

Highly pathogenic Burkholderia pseudomallei is the causative agent of melioidosis, a neglected tropical disease endemic in Southeast Asian tropical region. This bacterium encompasses diverse virulence factors which further undergo dynamic gene-expression flux as it transits through distinct environmental niches within the host which may lead to manifestation of differential clinical symptoms. B. pseudomallei, is classified as a Tier 1 select agent in the United States and regarded as a risk group 3 organism in India with the potential to be used as bioweapon. Considering these facts, it is vital to uncover both physiological and genetic heterogeneity of B. pseudomallei, particularly to identify any novel virulence factors that may contribute to pathogenicity. B. pseudomallei strain CM000113 was isolated from a clinical case in India, characterized it for its physiological, biochemical, and prominently genetic traits through WGS. It has a type 2 morphotype with faster doubling time and high biofilm producing capacity as compared to Pseudomonas aeruginosa. The genome size is 7.3 Mbp and it is phylogenetically close to B. pseudomallei strain Mahidol 1106a and Burkholderia mallei Turkey 2. We observed genetic heterogeneity, as key virulence factors that were identified shows sequence dissimilarity with reference strains. Additionally, presence of genomic islands, harbouring two virulence factors, GmhA and GmhB2, associated with pathogenesis indicates possibility of horizontal gene transfer. These results emphasize the need for an extensive study focusing the genome of B. pseudomallei and its associated heterogeneity, to identify molecular biomarkers aiding to develop point-of-care diagnostic kits for early diagnosis of melioidosis. [ABSTRACT FROM AUTHOR]

Background: Podoconiosis is a stigmatising neglected tropical condition, but the nature of podoconiosis stigma has not been fully explored. There is a growing understanding that the experience of stigma is intersectional, yet no research has been done on this matter in relation to podoconiosis. The aim of this paper is to contribute to the understanding of podoconiosis-related stigma by illustrating how multiple individuals' positionalities intersect to shape the experience of stigma due to podoconiosis. Methods: We used qualitative research to explore the experience of stigma among people affected by podoconiosis. Data were gathered using participant observation, interviews, focus group discussions and participatory methods. A total of 59 participants, including patients, local leaders, community health workers, and family members, were purposively selected to participate in this study. Findings: We identified three features in which stigma related to podoconiosis was grounded. These were bodily deformation, illness contamination and bodily weakness. The experience of stigma was shaped by the convergence of multiple individual positionalities and identities. Social positionalities and identities based on socio-economic, gender, age and illness status intersected to shape podoconiosis stigma. Conclusion: Our study demonstrates that the experience of stigma due to podoconiosis is intersectional, going beyond biological features of podoconiosis. The stigma experienced by affected individuals is complex, and shaped by the convergence of social structures and many individual identities such as socio-economic status, gender, disability and age. This understanding is crucial to analysing stigma related to podoconiosis, or other NTDs, and for designing interventions that address stigma that arise from biological aspects of disease and social factors simultaneously. Such holistic interventions can significantly improve the well-being of those affected by podoconiosis. Author summary: Podoconiosis is a neglected tropical disease that causes swelling of the feet and legs leading to bodily disfigurement. An estimated 4 million people are affected worldwide, while in Rwanda, more than six thousand are affected with the disease. Those affected experience social exclusion and discrimination, which cause profound socio-economic and psychological impacts. The nature of this experience has not yet been fully explored. The aim of this paper is to explore the social nuances of podoconiosis-related stigma to contribute to better understanding of the experience of podoconiosis. We explored the experience of stigma of people affected by podoconiosis. We identified various features of podoconiosis-related stigma, such as bodily deformation, illness contamination and bodily weakness. We also noted that socio-economic status, gender, age and severity of podoconiosis fuelled the experience of stigma. Participants explained how affected people experienced stigma that was influenced by many factors: their living conditions, age, gender and illness status, on which their social acceptance or rejection was judged. The experience of affected people is multi-layered, and varies from individual to individual. Therefore, our understanding and actions should rest on an approach that enables us to analyse and identify intersected social features to reduce podoconiosis-related stigma holistically. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by the protozoan parasite Leishmania. In Ethiopia, CL is mainly caused by Leishmania aethiopica and can present in different clinical forms. The aim of this study was to assess whether these different forms are associated with differences in parasite genetic and host systemic immune signatures. Methods: Here we analysed the whole genome sequence data for 48 clinical parasite isolates and the systemic immune signature from a cohort of CL patients, who were recruited in Nefas Mewcha, Northern Ethiopia, from January 2019 to January 2022. Results: Our results show that parasites from CL cases with different presentations in a single Ethiopian setting are from the same genetic population based on a permutation test of genome-wide similarity. Furthermore, a logistic regression test for genome wide association did not identify any individual genetic variants significantly associated with disease presentation. We also measured plasma chemokine and cytokine levels of 129 CL patients presenting with different forms of CL. None of the chemokine [eotaxin, eotaxin-3, interleukin (IL)-8, interferon (IFN)-γ-induced protein-10 (IP-10), monocyte chemoattractant protein (MCP)-1, MCP-4, macrophage-derived chemokines (MDC), macrophage inflammatory protein (MIP)-1α, MIP-1β and thymus- and activation-regulated chemokine (TARC)] or cytokine (IFN-γ, IL-1β, interleukin-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, tumor necrosis factor-α) levels measured were significantly different between the different clinical presentations of CL, as measured by Kruskal–Wallis test. We also compared those with healthy nonendemic controls: our results show a chemokine (IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β and TARC) but not a cytokine immune signature in patients with CL as compared to healthy nonendemic controls, as measured by Mann-Whitney test. Conclusions: The results of our study did not identify a systemic immune signature or parasite genetic factors associated with different clinical presentation of CL. [ABSTRACT FROM AUTHOR]

Chromoblastomycosis, an implantation mycosis, is a neglected tropical disease that causes decreased quality of life, stigma, and disability. The global burden of disease is unknown and data on disease epidemiology and outcomes are severely limited by a lack of access to needed diagnostic tools and therapeutics. The World Health Organization outlined targets for chromoblastomycosis in the Road Map for Neglected Tropical Diseases 2021–2030, but little progress has been made in initiating and implementing an effective control program globally. This lack of guiding policy and progress led to the recent formation of a Global Chromoblastomycosis Working Group which has developed a global chromoblastomycosis strategy. We describe this strategy, which outlines specific steps needed to improve technical progress, strategy and service delivery, and enablers. Clinicians, researchers, public and government officials, patients, and policy makers can align their time, expertise, and resources to improve the lives of communities affected by chromoblastomycosis through this strategy. [ABSTRACT FROM AUTHOR]

Background: Rabies is a disease of warm-blooded animals that affects the central nervous system and is almost invariably fatal once clinical signs develop. It is one of the most neglected tropical diseases in several areas of the world, including Ethiopia. Additionally, the burden of the disease is estimated to be high in Ethiopia, and public awareness contributes to prevention. Methods: A community-based cross-sectional study design was conducted from June–August 2023 in the Gomma district, Jimma zone, Oromia regional state, Ethiopia, to assess the knowledge, attitudes, and practices of communities towards rabies and associated risk factors using a structured questionnaire survey. A multi-stage sampling technique was used for the selection of the sampling units and a total of 140 participants were interviewed. The questionnaire parts included socio-demographics information, knowledge, attitudes, and practices of the community's respect for rabies management and control. The data was analyzed by Statistical Package for Social Science (SPSS) Version 20. Descriptive analyses were employed and multivariable logistic regression was used to calculate the association between independent and dependent variables (Knowledge, Attitudes, and Practice scores). Results: About 134 (95.7%) respondents had heard about rabies. Likewise, 75 (53.6%), 55 (39.3%), and 95 (67.9%) of the respondents had good knowledge, favorable attitudes, and good practices, respectively. Christians were more likely to have higher knowledge scores than Muslims (AOR = 6.876, CI = 1.750–27.016, p = 0.006). Respondents who knew someone's exposure had a higher knowledge score than those who did not (AOR = 6.208, CI = 2.750–14.012, p = 0.000). Moreover, Muslims were found to have a more favorable attitudes than Christians (AOR = 5.518, CI = 1.199–25.391, p = 0.028). Those who knew someone's exposure to rabies were found to have a more favorable attitudes than those who did not (AOR = 2.367, CI = 1.157–4.839, p = 0.018). Respondents who had favorable attitudes towards rabies were found to have more good practices than unfavorable attitudes (AOR = 3.267, CI = 1.391, 7.730, p = 0.005). Conclusions: The study revealed a gap in knowledge among communities in the study area. Thus, rabies control activity and community awareness should be implemented with stakeholders. Author summary: In a comprehensive assessment conducted in the Gomma district of Jimma zone, Ethiopia, the community's knowledge, attitudes, and practices related to rabies were assessed. While participants generally acknowledged domestic dogs and wild carnivores as the primary source of rabies and were able to identify various preventive measures such as avoiding dog bites and ensuring dog confinement, significant disparities were evident. Despite possessing a reasonable level of knowledge, attitudes, and practices were found to be inconsistent with effective rabies prevention. Notably, a prevalent belief persisted among participants that rabies could be cured through traditional herbal medicine, indicating a misconception regarding the disease's treatment. Additionally, a troubling trend emerged where animals involved in bite incidents were often killed instead of being quarantined, contrary to established guidelines. Recognizing the urgent need for intervention, the study emphasizes the critical role of enhancing awareness and promoting culturally and gender-sensitive educational programs. These initiatives should aim to rectify misconceptions, improve first aid practices, and foster appropriate healthcare-seeking behaviors among community members and healthcare providers alike. By implementing these multifaceted strategies, communities can work towards achieving a significant reduction in the burden of rabies and safeguarding public health. [ABSTRACT FROM AUTHOR]

Background: Strongyloidiasis a neglected tropical disease is known to cause severe disease among immunosuppressed and has not been studied extensively in Sri Lanka. Parasitological diagnostic approaches based on faecal microscopy and culture often fail to detect low-intensity infections. This study investigates the presence of strongyloidiasis among selected immunocompromised individuals using parasitological, molecular and serological techniques. Methods: Adult patients with immunocompromising conditions admitted to three tertiary care hospitals in Sri Lanka were recruited. A faecal sample and 2 ml of venous blood were collected. The faecal samples were subjected to direct faecal smear and cultures (agar plate, charcoal and Harada-Mori) and polymerase chain reaction (PCR) using species specific primers designed for Strongyloides stercoralis. The presence of Strongyloides IgG antibodies was tested in the collected serum samples using DRG Strongyloides IgG enzyme-linked immunosorbent assay (ELISA) kits. The PCR products of the positive samples were sequenced using Sanger sequencing method. Results: A total of 260 patients were recruited to this study, out of which 160 provided faecal samples and 122 provided blood samples. Out of the 160 faecal samples, none were positive for strongyloidiasis by direct smear, charcoal and Harada-Mori cultures. Only one sample (0.6%) was positive by agar plate culture. Out of the 123 samples subjected to PCR, 14 (11.4%), including the culture positive patient, were positive for S. stercoralis. Sequencing results of the PCR products indicated 100% similarity to S. stercoralis. Out of the 122 serum samples subjected to ELISA, 20 (16.4%), including the culture positive patient, were positive for Strongyloides IgG antibodies. However, sociodemographic, exposure factors, clinical features were not significantly associated with the presence of strongyloidiasis infection. Conclusions: Strongyloidiasis is present among the immunocompromised population in Sri Lanka, even in the absence of a significant relationship with associated factors. It is advisable to screen such patients with highly sensitive tests such as PCR for early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) is an infectious neglected tropical disease caused by mosquito-borne nematodes such as Wuchereria bancrofti, Brugia malayi, and Brugia timori. Globally, LF affects 51 million people, with approximately 863 million at risk in 47 countries. In Kenya, filariasis is endemic along the entire coastal strip, and more recently, at the Kenya–Ugandan border. The World Health Organization (WHO) recommends mass drug administration to reduce disease transmission and morbidity. Monitoring the effectiveness of such interventions relies on robust surveillance, achieved through microscopic examination of microfilariae in nighttime blood, detection of circulating filarial antigens (CFA), and molecular xenomonitoring. We focused on molecular xenomonitoring along the Kenyan coast due to its noninvasive nature and the opportunity to identify new vectors. Methods: In 2022, mosquitoes were collected from Kilifi, Kwale, and Taita-Taveta counties located within the LF endemic region in Kenya. Subsequently, genomic deoxyribonucleic acid (gDNA) was extracted from these mosquitoes for speciation and analysis of Wuchereria bancrofti infection rates. The impact of sociodemographic and household attributes on infection rates was assessed using generalized estimating equations. Results: A total of 18,121 mosquitoes belonging to Culicinae (63.0%, n = 11,414) and Anophelinae (37.0%, n = 6707) subfamilies were collected. Morphological identification revealed that Anopheline mosquitoes were dominated by An. funestus (45.4%, n = 3045) and An. gambiae (42.8%, n = 2873). Wuchereria bancrofti infection rates were highest in Kilifi (35.4%; 95% CI 28.0–43.3%, n = 57/161) and lowest in Taita Taveta (5.3%; 95% CI 3.3–8.0%, n = 22/412). The major vectors incriminated are An. rivulorum, An. funestus sensu stricto, and An. arabiensis. Mosquitoes of the An. funestus complex were significantly associated with LF transmission (OR 18.0; 95% CI 1.80–180; p = 0.014). Additionally, a higher risk of transmission was observed outdoors (OR 1.74; 95% CI 1.08–2.82; p = 0.024) and in homesteads that owned livestock (OR 2.00; 95% CI 1.09–3.66; p = 0.025). Conclusions: In this study, we identified An. funestus s.l. sibling species, An. rivulorum and An. funestus s.s., as the primary vectors of lymphatic filariasis along the Kenyan coast. These findings also highlight that a significant portion of disease transmission potentially occurs outdoors where indoor-based vector control tools, including long-lasting insecticidal nets and indoor residual spray, may not be effective. Therefore, control measures targeting outdoor resting mosquitoes such as zooprophylaxis, larval source management, and attractive sugar baits may have potential for LF transmission reduction. [ABSTRACT FROM AUTHOR]

Although among the six most common parasitic diseases, leishmaniasis is considered a neglected disease, being recognised as a serious public health burden worldwide. This fact impairs technological advancements and investments in innovative therapeutic approaches, so that commonly available drugs are still associated with low therapeutic rates and significant side effects. Pentavalent antimonials, such as Pentostan® and Glucantime®, were established as chemotherapeutic agents since the 1940s, being the first line of treatment for leishmaniasis; however, 60% of cases of leishmaniasis are resistant to pentavalent antimonials. Thus, the search for more effective therapies and new therapeutic agents with potential leishmanicidal activity is still in-demand. In this review, an overview about the disease and its pathophysiology is given, discussing the current state-of-the-art of the standard treatments and new alternatives based on drug delivery approaches, enhancing the need for more effective pharmaceutical treatments. [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: Mycetoma is an uncommon and neglected tropical disease in Uganda. We aimed to assess baseline knowledge and provide community health workers (CHWs) in Northern Uganda with knowledge to identify and refer presumptive mycetoma cases. Methodology: Between March and August 2023, we conducted a concurrent triangulation mixed methods study among CHWs in Gulu and Pader districts on mycetoma. We conducted a 1 day in person training on mycetoma. Quantitative data were collected before (pretest), immediately (immediate posttest) and six months (6-month posttest) after the training and results compared using paired sample t test or one-way ANOVA. Qualitative data were collected using four focused group discussions, audio recorded, and analyzed using thematic content analysis. Principal findings: Forty-five CHWs were enrolled, mostly male (66.7%, n = 30), with a median age of 36 years (IQR 29 43). Out of a total score of 18, the baseline mean knowledge score was 7±2.42, improving to 11±1.99 immediately posttest (p<0.001), and 10±2.35 at 6 months (p<0.001), without additional training. Significant knowledge improvements at 6 months were observed among female participants (p = 0.004), those aged 30 40 years (p = 0.031) or 40+ years (p = 0.035), and those with secondary education (p = 0.007). Over 6 months, CHWs screened 2,773 adults, identifying and referring 30 presumptive mycetoma cases. Qualitative findings revealed challenges and barriers to early identification and referral of mycetoma presumptive cases including limited knowledge, stigma, myths, lack of an indigenous name for mycetoma, delayed decision making, and transportation barriers. Conclusions: This study highlights a significant knowledge gap among CHWs about mycetoma, with substantial improvement following training. The identification of presumptive cases by CHWs reflects their potential in community-based surveillance, emphasizing the need to integrate well-trained CHW to lead efforts for mycetoma surveillance and capacity building to enhance health outcomes in Uganda. Author summary: Mycetoma is a rare neglected tropical disease that affects the skin and the tissues beneath skin, causing severe health issues if not diagnosed and treated early. It disproportionately affects people in rural and impoverished communities in sub-Saharan Africa, including Uganda. Mycetoma often affects mostly young adults in their productive years especially those participating in agricultural activities. In our study, we trained community health workers (CHWs) in Northern Uganda for one day to improve their knowledge and skills in identifying and referring cases of mycetoma. Our results showed that the CHWs had significant knowledge improvement that persisted for at least six months without more training. Furthermore, they were able to identify 30 possible cases of mycetoma after assessing nearly 3,000 people in the communities. Furthermore, we found challenges and barriers to early detection of this disease such as limited initial knowledge, stigma, myths about the disease, and practical issues like transportation difficulties and long distances to health facilities. Therefore, our study shows that by empowering local health workers, we can improve early detection and treatment of mycetoma, ultimately enhancing health in affected regions. [ABSTRACT FROM AUTHOR]

Introduction: Leprosy is a chronic, slowly developing infectious disease that affects the peripheral nerves, specifically Schwann cells. Individuals with the multibacillary type exhibit a propensity for developing chronic pain and a decrease in sensitivity in the plantar region, which directly interferes with balance maintenance. The evaluation of static balance in this population is made through the measurement of the center of pressure (COP) oscillations. Therefore, there is a need to investigate the association between postural control and COP oscillations using a force platform and finding accelerations of the center of mass (COM) from inertial sensors for reliable and portable balance assessment in leprosy patients. Objective: To validate the application of inertial sensors for patients with leprosy by establishing a correlation with the outcomes obtained from a force platform. Methods: This is an observational study with a case-control design, in which 30 participants with leprosy and 30 healthy participants were recruited to evaluate static balance using an inertial sensor and a force platform. Participants underwent balance assessment under two conditions (Eyes Open: OE and Eyes Closed: CE), and data from the platform and sensor were processed using Matlab computational routines. The data were quantified using four parameters: Total Displacement (TD), Area, Antero-Posterior Displacement (APdisp), and Medio-Lateral Displacement (MLdisp). Results: The evaluated parameters showed significantly different values between the groups, where the Leprosy group exhibited significantly higher values compared to the control group, both in the OE and CE conditions for all four parameters. The sensor corroborated the differences demonstrated by the platform and followed the same trend for medio-lateral displacements and accelerations. It can be observed that the evaluated parameters exhibited a varied correlation ranging from moderate to large between the platform and the sensor. Among the four variables, MLdisp had the lowest correlation. Discussion: The results partially confirmed the first hypothesis of concurrent validation, showing a moderate to large correlation between the force platform and the inertial sensor. The second hypothesis of clinical validation was also partially confirmed, as not all group differences observed in the COP measurements from the force platform were reflected in the COM measurements from the inertial sensor. Specifically, the force platform indicated greater oscillations in participants with multibacillary leprosy compared to controls, a finding statistically confirmed by the sensor for all measures except MLdisp. Conclusion: This research confirmed the concurrent validity of the inertial sensor with the force platform and its clinical validation, demonstrating that this instrument can be applied in clinical settings due to its low cost and ease of use. The findings may contribute to public health by identifying postural control tools for patients with multibacillary leprosy. Author summary: Our study aimed to validate the application of inertial sensors for patients with leprosy by establishing a correlation with the outcomes obtained from a force platform. Due to the disease's impact on sensory perception and chronic pain in the plantar region, maintaining balance becomes challenging for affected individuals. Using a force platform and an inertial sensor, we evaluated balance in 30 leprosy patients and 30 healthy participants under Eyes Open and Eyes Closed conditions. Results revealed significantly higher values in balance parameters for the leprosy group compared to controls, indicating greater instability. The inertial sensor confirmed these differences, particularly in medio-lateral displacements and accelerations. While correlation between the platform and sensor varied, our study validated the sensor's concurrent and clinical efficacy. This research underscores the potential of inertial sensors as reliable, cost-effective tools for assessing balance in clinical settings, especially for patients with multibacillary leprosy. Our findings contribute to enhancing public health efforts by offering practical solutions for monitoring and managing balance deficits in this neglected disease population. [ABSTRACT FROM AUTHOR]

Strongyloidiasis is a neglected tropical disease estimated to affect more than 600 million people worldwide. Recently, the World Health Organization road map on neglected tropical diseases 2021–2030 has put the focus on strongyloidiasis, including this disease within its mass drug administration campaigns. With the use of ivermectin in extensive treatment of all populations at-risk, identifying effective therapeutic alternatives is crucial in case ivermectin resistance arises. The objective of the present study was the development of a larval migration inhibition assay to evaluate the anthelmintic efficacy of commercial drugs and diamine and aminoalcohol derivatives against infective Strongyloides ratti third stage larvae. Through this technique, we successfully screened and estimated the in vitro anthelmintic efficacy of six commercial drugs, seven diamine derivatives and eight aminoalcohol derivatives. Unexpectedly, the half-maximal effective concentration of ivermectin and moxidectin (2.21 and 2.34 μM, respectively) were observed as the highest value obtained among all commercial drugs tested by this in vitro technique. Moreover, some diamine and aminoalcohol derivatives showed superior efficacy inhibiting S. ratti motility compared to ivermectin, with five compounds (AA23, AA34, AO2 AO7 and AO14b) also displaying selectivity indexes on HepG2 and Caco2 higher than 1. These findings underscore the potential of these derivatives as promising alternatives for strongyloidiasis treatment, warranting further investigation and in vivo efficacy assessment. Author summary: Strongyloidiasis, a parasitic infection affecting over 600 million people worldwide, is increasingly recognized in global health initiatives. Caused by the nematode Strongyloides stercoralis, it predominantly occurs in tropical and subtropical regions. Transmission results through contact with soil contaminated by infectious larvae, leading to a spectrum of clinical symptoms from mild gastrointestinal discomfort to potentially life-threatening complications, especially in individuals with weakened immune systems. Despite its designation as a neglected tropical disease, concerns regarding the development of drug resistance highlight the need to explore alternative treatment strategies. In our study, we employed innovative methods to evaluate the in vitro efficacy of various drug candidates against Strongyloides ratti larvae, representing a crucial step in identifying novel therapies for human strongyloidiasis. Our findings revealed that some of the novel compounds tested, showed superior efficacy in inhibiting parasite motility, suggesting potential benefits for patient treatment outcomes. Our study underscores the urgent need for diversified treatment approaches in combating strongyloidiasis. [ABSTRACT FROM AUTHOR]

Background: Integrated approaches to mapping skin Neglected Tropical Diseases (NTDs) may be cost-effective way to guide decisions on resource mobilization. Pilot studies have been carried out, but large-scale data covering multiple countries endemic for skin NTDs are lacking. Within the LAMP4YAWS project, we collected integrated data on the burden of multiple skin NTDs. Methods: From March 2021 to March 2023, integrated case searches for yaws alongside other skin conditions were performed in endemic health districts of yaws in Cameroon, Côte d'Ivoire, and Ghana. Integrated activities included training, social mobilization and active case detection. Initial screening involved a brief clinical examination of participants to determine if any skin conditions were suspected. Cases of skin NTDs were then referred to a health facility for appropriate management. Results: Overall 61,080 individuals screened, 11,387 (18.6%) had skin lesions. The majority of individuals (>90%) examined were children aged 15 years old and under. The proportion of serologically confirmed yaws cases was 8.6% (18/210) in Cameroon, 6.8% (84/1232) in Côte d'Ivoire, and 26.8% (440/1643) in Ghana. Other skin conditions based on clinical examination included: scabies, Buruli ulcer, leprosy, lymphatic filariasis (lymphoedema and hydrocele), tungiasis, and fungal infections. The most common conditions were scabies and superficial fungal infections. In Cameroon, scabies and superficial fungal infections accounted for 5.1% (214/4204) and 88.7% (3730/4204) respectively, 25.2% (1285/5095) and 50.4% (2567/5095) in Côte d'Ivoire. In Ghana, 20% (419/2090) of individuals had scabies but superficial fungal infections were not routinely recorded and were reported in only 1.3% (28/2090). Other skin NTDs were less common across all three countries. Conclusion: This study confirms that integrated screening allows simultaneous detection of multiple skin NTDs, maximising use of scarce resources. Author summary: Many Neglected Tropical Diseases (NTDs) predominantly affect the skin and are referred to as skin NTDs. The World Health Organization (WHO) has developed a number of strategies for the control, eradication and elimination of skin NTDs and recognizes the importance of integrated approaches to mapping skin NTDs. We conducted a study adopting integrated screening for multiple skin NTDs and other skin conditions in Cameroon, Côte d'Ivoire, and Ghana. This ran alongside a study focused on diagnostic tests for one specific skin NTD–yaws. The results showed that integrated screening is a feasible and cost-effective way to detect multiple skin NTDs in a single intervention. Of more than 60,000 individuals screened almost one in five had a skin lesion. Cases of yaws confirmed by blood tests were detected more frequently in Ghana compared to Côte d'Ivoire and Cameroon. The most common skin conditions were scabies and superficial fungal infections. Other skin NTDs such as Buruli ulcer, leprosy, lymphatic filariasis and tungiasis were less common. Integrated screening allowed detection of skin conditions and co-endemicity of skin NTDs and the data can guide decisions on resource mobilization to manage skin NTDs. [ABSTRACT FROM AUTHOR]

Background: Tropical diseases inflict many of those living in tropical and subtropical areas each year. These populations because of these diseases suffer considerable financial and human losses. Some of these diseases are known as Neglected Tropical Diseases (NTDs) and they can be highly dangerous. Still, they have not received the attention they need. Given the necessity of eliminating these diseases, the present study is an attempt to examine the reasons for unsuccessful attempts to eliminate diseases like NTDs. Methods: The current study was a systematic analysis of literature on neglected tropical diseases that were found in the databases of the Web of Science, PubMed, Scopus, Science Direct, Pro Quest, Cochrane, and Embase before April 2023. The Critical Appraisal Skills Program (CASP) for articles and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were used to conduct the study. Results: Based on the systematic search, 3193 papers were found and after the elimination of duplicates and irrelevant ones, a total of 28 articles remained to examine the challenges to eradicate neglected tropical diseases. Four themes were found for the challenges of controlling and eliminating neglected tropic diseases including drawbacks of programs for disease management policies, environmental challenges, executive challenges, and research field challenges. Thirty-six subthemes were obtained in this study, which showed cases such as the presence of immigrants and refugees, weaknesses in public health infrastructure and programs, dynamic epidemiological settings, lack of executive prioritization appropriate to endemic countries, and highly customized research infrastructures. Ending neglected tropical diseases requires an innovative roadmap and global cooperation. Conclusions: To achieve important eradication goals, measures such as acceleration in practice are needed to plan, intensify executive and operational approaches, change application models, innovate processes, and promote culture are needed. In addition, to make possible the elimination of neglected tropical diseases, there is an undeniable need for providing financial, human, and research resources. In addition, there is a need for efficient health infrastructure management, paying attention to migrants and refugees, setting explicit targets, prioritizing based on local conditions, and paying more attention to political and social developments. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a neglected tropical disease, caused by protozoan parasites of Leishmania (L.), and is transmitted by bite of phlebotomine sandflies. There are several studies on central nervous system infection to indicate that Leishmania can cross the blood–brain barrier, resulting in neurological manifestations, known as "cerebral leishmaniasis." This study highlighted the notions: (i) polarisation of bone marrow‐derived macrophages (BMDM) incubated following stimulation with lipopolysaccharide (LPS) or soluble Leishmania antigen (SLA), (ii) quantification of parasites within co‐culture of Leishmania‐infected macrophages, and astrocytes, and (iii) effect of interferon‐gamma (IFN‐γ) on the infection rate of co‐culture populations. Accordingly, 83% of overall macrophage population was identified on day 7 for CD11b and F4/80 macrophage markers. Flow cytometry analysis revealed significant increases in CD11b and F4/80 surface markers in LPS and SLA‐stimulated BMDMs at 24 h, compared to untreated cells. TNF‐α levels increased significantly in both LPS and SLA‐treated BMDMs after 48 h. Additionally, SLA treatment induced a more elongated, spindle‐like shape in the cells, indicative of M2 macrophage polarisation over the M1 phenotype. When non‐infected astrocytes with/without stimulation with IFN‐γ before co‐culture, gp63 FITC‐labelled parasite populations (%) in co‐culture decreased to 25% at 72 h, thus indicating a lower infection rate in a time‐dependent manner. IFN‐γ and IL‐6 levels significantly increased to 71.66 ± 3.51 and 184 ± 14.42 pg/mL, resulting in the inflammatory response in the co‐culture system at 48 h (p ≤ 0.0001), when compared to the control (30 ± 2.52 pg/mL for IFN‐γ and 8.66 ± 2.37 pg/mL for IL‐6) at 0 h of the incubation. It is the first study to emphasize the communication between Leishmania‐infected macrophages and astrocytes regarding Leishmania parasite load. The results suggest that astrocytes can lead to the reduction in Leishmania parasites, thereby controlling the incidence of cerebral leishmaniasis. [ABSTRACT FROM AUTHOR]

Background: Neglected tropical diseases (NTDs), including leishmaniasis, trypanosomiasis, and schistosomiasis, impose a significant public health burden, especially in developing countries. Despite control efforts, treatment remains challenging due to drug resistance and lack of effective therapies. Objective: This study aimed to synthesize the current research on the combination therapy and phytochemical-loaded nanosystems, which have emerged as promising strategies to enhance treatment efficacy and safety. Methods/Results: In the present review, we conducted a systematic search of the literature and identified several phytochemicals that have been employed in this way, with the notable efficacy of reducing the parasite load in the liver and spleen in cases of visceral leishmaniasis, as well as lesion size in cutaneous leishmaniasis. Furthermore, they have a synergistic effect against Trypanosoma brucei rhodesiense rhodesain; reduce inflammation, parasitic load in the myocardium, cardiac hypertrophy, and IL-15 production in Chagas disease; and affect both mature and immature stages of Schistosoma mansoni, resulting in improved outcomes compared to the administration of phytochemicals alone or with conventional drugs. Moreover, the majority of the combinations studied demonstrated enhanced solubility, efficacy, and selectivity, as well as increased immune response and reduced cytotoxicity. Conclusions: These formulations appear to offer significant therapeutic benefits, although further research is required to validate their clinical efficacy in humans and their potential to improve treatment outcomes in affected populations. [ABSTRACT FROM AUTHOR]

In Australia, native possums are a major wildlife reservoir for Mycobacterium ulcerans, the causative agent of the neglected tropical skin disease Buruli ulcer (BU). Large-scale possum excreta surveys that use PCR to detect M. ulcerans in 100-1,000 s of excreta specimens are an important tool that can inform geospatial modeling and predict locations of future human BU risk. However, the significant expense of commercial kits used to extract DNA from specimens is a major barrier to routine implementation. Here, we developed a low-cost method for DNA extraction from possum excreta, possum tissue, and pure mycobacterial cultures, using a guanidinium isothiocyanate lysis solution and paramagnetic beads. In a 96-well plate format for high-throughput processing, the paramagnetic bead DNA extraction method was threefold less sensitive but only 1/6 the cost of a commonly used commercial kit. Applied to tissue swabs, the method was fourfold more sensitive and 1/5 the cost of a commercial kit. When used for preparing DNA from pure mycobacterial cultures, the method yielded purified genomic DNA with quality metrics comparable to more lengthy techniques. Our paramagnetic bead method is an economical means to undertake large-scale M. ulcerans environmental surveillance that will directly inform efforts to halt the spread of BU in Victoria, Australia, with potential for applicability in other endemic countries. IMPORTANCE Buruli ulcer (BU) is a neglected tropical skin disease, with an incidence that has dramatically increased in temperate southeastern Australia over the last decade. In southeastern Australia, BU is a zoonosis with native possums the major wildlife reservoir of the causative pathogen, Mycobacterium ulcerans. Infected possums shed M. ulcerans in their excreta, and excreta surveys using PCR to screen for the presence of pathogen DNA are a powerful means to predict future areas of Buruli ulcer risk for humans. However, excreta surveys across large geographic areas require testing of many thousands of samples. The cost of commercial DNA extraction reagents used for preparing samples for PCR testing can thus become prohibitive to effective surveillance. Here, we describe a simple, low-cost method for extracting DNA from possum excreta using paramagnetic beads. The method is versatile and adaptable to a variety of other sample types including swabs collected from possum tissues and pure cultures of mycobacteria. [ABSTRACT FROM AUTHOR]

Mycetoma is currently considered as a neglected tropical disease. The incidence of mycetoma is unknown but most of the worldwide cases are present in the "mycetoma belt" including countries like Mexico, India, Senegal, and others. The treatment of mycetoma depends on the etiological agent responsible for the case. Treatment success reaches 60 to 90%; however, common treatment has been reported to be ineffective in some cases, due in part to resistance to the prescribed antibiotics. Therefore, it is necessary to develop new therapeutic options. In the past two decades, quinoxaline derivatives have shown relevance as antibacterial agents. Therefore, in this work, esters of quinoxaline 1,4-di-N-oxide derivatives were evaluated in vitro against the reference strain CECT-3052 from N. brasiliensis, six clinical isolates, and macrophages J774A.1 to determine their cytotoxicity and security index. Additionally, nine reference drugs were evaluated as controls. The results show that nine esters of quinoxaline 1,4-di-N-oxide derivatives had a minimum inhibitory concentration (MIC) < 1 µg/mL against the reference strain and four of them (N-05, N-09, N-11, and N-13) had an MIC < 1 µg/mL against the clinical isolates. Therefore, the scaffold quinoxaline 1,4-di-N-oxide could be used to develop new and more potent antinocardial agents. [ABSTRACT FROM AUTHOR]

Scientists are increasingly specializing to manage the vast knowledge bases within their domains, making knowledge-sharing strategies essential for scientific progress. Among these strategies, international scientific collaboration has increased markedly. We analyse the role of thematic specialization as one of its drivers in the context of Chagas research, a neglected disease. Since there is a strong research tradition in Latin America on this topic, it is an interesting context to study centre-periphery research dynamics. Using a novel bibliometric database on Chagas research during 1990–2019, we exploit its panel structure in a gravity-type econometric model. The findings show that the degree of specialization and its proximity among partners boost joint publications. Both effects are particularly important for country dyads involving authors from the periphery linked to authors in the centre. This paper is the first empirical study to assess the role of specialization as a driver of international scientific collaboration. [ABSTRACT FROM AUTHOR]

The increasing spread of mosquito vectors has made mosquito-borne arboviral diseases a global threat to public health, leading to the urgent need for effective population control methods. Strategies based in the intracellular bacterium Wolbachia Hertig, 1936 are considered environmentally friendly, safe for humans, and potentially cost-effective for controlling arboviral diseases. To minimize undesirable side effects, it is relevant to assess whether Wolbachia is present in the area and understand the diversity associated with native infections before implementing these strategies. With this purpose, we investigated Wolbachia infection status, diversity, and prevalence in populations of Aedes albifasciatus (Macquart, 1838), Aedes fluviatilis (Lutz, 1904), and hybrids of the Culex pipiens (Linnaeus, 1758) complex from Argentina. Aedes albifasciatus and C. pipiens complex samples were collected in the province of Buenos Aires, and A. fluviatilis in the province of Misiones. Aedes albifasciatus was found to be uninfected, while infections with strains wFlu and wPip were detected in A. fluviatilis and hybrids of the C. pipiens complex, respectively. All strains were fixed or close to fixation and clustered within supergroup B. These finding provides valuable information on Wolbachia strains found in natural mosquito populations in Argentina that might be used in heterologous infections in the future or be considered when designing control strategies based on Wolbachia infection. [ABSTRACT FROM AUTHOR]

Schistosomiasis, a neglected tropical disease caused by flatworms of the Schistosoma genus, can lead to severe health complications such as Hepatosplenomegaly, intestinal cancer, anemia, and heightened susceptibility to other infections like HIV. With limited treatment options, especially given the potential rise of drug resistance to the sole available drug, Praziquantel (PZQ), there is an imperative to discover novel and effective drugs against Schistosomiasis. In regards, a computational molecular modelling strategy was employed, with a specific focus on Schistosoma mansoni Thioredoxin glutathione reductase (SmTGR). Using structure-based drug design, we searched the ChEMBL database for lead compounds, identifying Compound 34 with a remarkable binding score of −167.014 kcal mol−1. Six new potent compounds were designed with enhanced binding (−169.451 to −181.579 kcal mol−1) and predicted activities (6.082–6.765) compared to both the lead compound and the standard drug, PZQ. Rigorous validation through molecular dynamics (MD) simulations confirmed the stability and integrity of the docked complexes. An evaluation of drug-likeness and ADMET characteristics revealed that the newly developed analogues possess favourable pharmacokinetic profiles, adhering to Lipinski's rule of five. In addition, the synergistic insights gained from density functional theory (DFT) analyses further underscore the structural diversity and potential applications of these derivatives. [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]

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Encompassing more than 70% of the Earth's surface, the ocean is an extensive and mostly unexplored repository of biodiversity, containing a remarkable variety of living organisms. Of these, marine species including algae, sponges, fungi, bacteria and invertebrates have attracted scientific attention because of their capacity to synthesize a diverse range of bioactive constituents. Recently, there has been considerable interest in marine natural products for their potential as innovative antiviral agents. The present review examines the latest progress in the identification and advancement of marine-derived chemicals exhibiting antiviral properties. We analyze the processes by which these chemicals exercise their effects, which include the suppression of viral entrance, replication and the adjustment of host immunological responses. In addition, we emphasize the role of these natural compounds in fighting new viral infections like SARS-CoV-2 and other respiratory viruses, as well as their possible application in treating neglected tropical diseases. Notwithstanding the encouraging outcomes, the advancement of antiviral drugs generated from marine sources encounters many obstacles, encompassing concerns pertaining to extraction, sustainability, and growth. Yet, progress in biotechnological methods, such as synthetic biology and nanotechnology, provide fresh possibilities to surmount these obstacles. The potential for the advancement of next-generation antiviral treatments may be found in marine natural compounds, suggesting a fruitful direction for the future of antiviral medication research. [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]

Cutaneous leishmaniasis (CL), caused by protozoan parasites of the Leishmania genus, is prevalent in tropical and subtropical regions, with important morbidity, particularly in low- to middle-income countries. Current systemic treatments, including pentavalent antimonials and miltefosine, are associated with significant toxicity, reduced efficacy, and are frequently ineffective in cases of severe or chronic CL. Immunotherapies leverage the immune system to combat microbial infection and offer a promising adjunct or alternative approach to the current standard of care for CL. However, the heterogeneous clinical presentation of CL, which is dependent on parasite species and host immunity, may require informed clinical intervention with immunotherapies. This review explores the clinical and immunological characteristics of CL, emphasising the current landscape of immunotherapies in in vivo models and clinical studies. Such immune-based interventions aim to modulate immune responses against Leishmania, with additive therapeutic effects enabling the efficacy of lower drug doses and decreasing the associated toxicity. Understanding the mechanisms that underlie immunotherapy for CL provides critical insights into developing safer and more effective treatments for this neglected tropical disease. Identifying suitable therapeutic candidates and establishing their safety and efficacy are essential steps in this process. However, the feasibility and utility of these treatments in resource-limited settings must also be considered, taking into account factors such as cost of production, temperature stability, and overall patient access. [ABSTRACT FROM AUTHOR]

Human schistosomiasis, caused by the Schistosoma trematode, is a neglected parasitic disease affecting over 250 million people worldwide. There is no vaccine, and the single available drug is threatened by drug resistance. This study presents a computational approach to designing multiepitope vaccines (MEVs) targeting the cercarial (CMEV) and schistosomular (SMEV) stages of schistosomes, and identifies potential schistosomicidal compounds from the Medicine for Malaria Ventures (MMV) and SuperNatural Database (SND) libraries. The designed vaccines (CMEV and SMEV) are engineered to provoke robust immune responses by incorporating a blend of T- and B-cell epitopes. Structural and immunoinformatics evaluations predicted robust interactions of CMEV and SMEV with key immune receptors and prolonged immune responses. In addition, molecular docking identified several compounds from the MMV and SND libraries with strong binding affinities to vital Schistosoma cathepsin proteases, indicating their potential as schistosomicidal agents. Our findings contribute to the potential development of effective vaccines and drugs against schistosomiasis. [ABSTRACT FROM AUTHOR]

The protozoan parasite Leishmania causes leishmaniasis, a neglected tropical disease, that disproportionately affects underdeveloped countries. This disease has major health, economic, and social implications, particularly because of the limited treatment options, high cost, the severe side effects associated with available therapeutics, and the high rate of treatment failure caused by the parasites' growing resistance to current medications. In this review, we describe first the common strategies used by pathogens to develop drug resistance and then focus on the arsenal of available drugs to treat leishmaniasis, their modes of action, and the molecular mechanisms contributing to drug resistance in Leishmania spp., including the role of genomic, transcriptional, and translational control. We focus more specifically on our recent discovery of translational reprogramming as a major driver of drug resistance leading to coordinated changes in the translation of transcripts and orchestrating changes in metabolome and lipidome to support drug resistance. A thorough understanding of these mechanisms is essential to identify the key elements needed to combat resistance and improve leishmaniasis treatment methods. [ABSTRACT FROM AUTHOR]

The Orthobunyavirus oropoucheense species encompasses a group of arthropod‐borne zoonotic viruses transmitted by biting midges to animals including humans. Several large‐scale human outbreaks caused by the prototype member of this species, Oropouche virus (OROV) have been documented since the 1970s and were primarily confined to the Amazon basin. However, since 2022, more widespread OROV outbreaks have been unfolding in Brazil and across South America, with cases exported to Cuba, Italy, Spain, USA and Germany. In Brazil, the virus has reached and established communitary transmission in all geographic areas of the country. We isolated, characterized the cytopathic effect and recovered the full genome of two OROV isolates from the 2022–24 outbreak detected in patients from the Pernambuco state. Phylogenetic data supports a direct introduction from the Amazonas state, the epicenter of the epidemics in the country. As case counts accumulate in the state mounting evidence is supporting the establishiment of sustained transmission chains. Continued studies are critical to understand the transmission cycle in this region, including the most important vectors and reservoirs, to appropriately deploy control measures. [ABSTRACT FROM AUTHOR]

Mycetoma is a neglected tropical disease (NTD) with devastating morbidity and stigma. Despite increased awareness and international collaboration, the burden of mycetoma is largely unknown and diagnosis and treatment are difficult. Addressing mycetoma globally aligns with several United Nation's Sustainable Development Goals (SDGs). Little progress has been made since the WHO's NTD roadmap publication in 2020. The Global Mycetoma Working Group proposes an enhanced mycetoma-control roadmap to meet the SDGs, stimulate progress and improve the lives of patients experiencing mycetoma. By aligning mycetoma management with the goals and targets of this enhanced roadmap, it becomes possible to leverage existing resources, infrastructure and partnerships to improve the lives of affected individuals and communities. This updated assessment is designed for the benefit of health workers and providers in mycetoma-endemic areas, NTD government officials, civil society and funding and implementing agencies. [ABSTRACT FROM AUTHOR]

Background: Conventional microscopy of Kato-Katz (KK1.0) thick smears, the primary method for diagnosing soil-transmitted helminth (STH) infections, has limited sensitivity and is error-prone. Artificial intelligence-based digital pathology (AI-DP) may overcome the constraints of traditional microscopy-based diagnostics. This study in Ucayali, a remote Amazonian region of Peru, compares the performance of AI-DP-based Kato-Katz (KK2.0) method to KK1.0 at diagnosing STH infections in school-aged children (SAC). Methods: In this prospective, non-interventional study, 510 stool samples from SAC (aged 5–14 years) were analyzed using KK1.0, KK2.0, and tube spontaneous sedimentation technique (TSET). KK1.0 and KK2.0 slides were evaluated at 30-minute and 24-hour timepoints for detection of Ascaris lumbricoides, Trichuris trichiura, and hookworms (at 30-minute only). Diagnostic performance was assessed by measuring STH eggs per gram of stool (EPG), sensitivity of methods, and agreement between the methods. Results: KK2.0 detected more A. lumbricoides positive samples than KK1.0, with detection rates for T. trichiura and hookworms being comparable. At 30-minutes, 37.6%, 23.0%, and 2.6% of the samples tested positive based on KK1.0 for A. lumbricoides, T. trichiura, and hookworms, while this was 49.8%, 24.4%, and 1.9% for KK2.0. At 24-hours, 37.1% and 27.1% of the samples tested positive based on KK1.0 for A. lumbricoides and T. trichiura, while this was 45.8% and 24.1% for KK2.0. Mean EPG between KK2.0 and KK1.0 were not statistically different across STH species and timepoints, except for T. trichiura at 24-hours (higher mean EPG for KK1.0, p = 0.036). When considering infection intensity levels, KK2.0 identified 10% more of the total population as low-infection intensity samples of A. lumbricoides than KK1.0 (p ≤ 0.001, both timepoints) and similar to KK1.0 for T. trichiura and hookworms. Varying agreement existed between KK1.0 and KK2.0 in detecting STH eggs (A. lumbricoides: moderate; T. trichiura: substantial; hookworms: slight). However, these findings should be interpreted carefully as there are certain limitations that may have impacted the results of this study. Conclusions: This study demonstrates the potential of the AI-DP-based method for STH diagnosis. While similar to KK1.0, the AI-DP-based method outperforms it in certain aspects. These findings underscore the potential of advancing the AI-DP KK2.0 prototype for dependable STH diagnosis and furthering the development of automated digital microscopes in accordance with WHO guidelines for STH diagnosis. Author summary: In tropical and sub-tropical regions with limited access to clean potable water, hygiene, and sanitation, infections with intestinal worms (e.g. giant roundworm, whipworm, and hookworms) are widespread, primarily affecting school-aged children (SAC). These infections lead to malnutrition, anemia, and developmental issues. The World Health Organization (WHO) introduced a strategy in 2020 to control intestinal worm infections, emphasizing the need for accurate diagnostic tests. The current recommended method, Kato-Katz (KK1.0), though cost-effective, has limitations in terms of reproducibility and sensitivity. To address this, an artificial intelligence digital pathology (AI-DP)-based Kato-Katz method (KK2.0) was developed to enhance diagnostic accuracy. This study in Ucayali (Amazonian region of Peru) evaluated KK2.0's performance compared to KK1.0 in detecting intestinal worm infections among SAC. Stool samples from 510 SAC (5–14 years) were collected and analyzed using KK1.0 and KK2.0. KK2.0 demonstrated comparable diagnostic performance to KK1.0, with higher sensitivity for low-intensity giant roundworm infections. Prevalence rates differed between KK2.0 and KK1.0, indicating KK2.0's potential to identify additional infections. Overall, the findings suggest KK2.0's effectiveness in diagnosing STH infections, highlighting its potential to improve surveillance and treatment programs. Further research should address technical issues and assess KK2.0 in diverse settings, advancing its application for neglected tropical disease diagnosis. [ABSTRACT FROM AUTHOR]

Background: Leptospirosis is a priority zoonotic disease in Kenya, but an in-depth review of its presence in humans, animals and the environment is lacking. Therefore, we conducted this systematic review and meta-analysis to understand the epidemiological situation to date. Methodology: We searched for literature in African journals online, AGRIS, Embase, the Leptospira WOAH reference laboratory library, ProMED-mail, PubMed, Scopus, Web of Science, and the institutional repositories of 33 academic institutions and included 66 publications on leptospirosis in Kenya which spanned from 1951 to 2022. The review was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY). Findings: Most investigations were done in rural and urban areas in western, southern, central, and coastal areas in Kenya and the largely pastoral eastern and northern areas were under-represented. A wide host range of domestic animals and wildlife was revealed, and occupational exposure was an important risk factor for humans. The microscopic agglutination test (MAT) was the most frequent test, particularly common in studies conducted during the 1980s and 1990s. However, varying MAT panels and cut-off titres were observed. The overall seroprevalence in cattle was 28.2% (95% confidence intervals [CI]: 12.0–53.0; heterogeneity: I2 = 96.7%, τ2 = 1.4), and 11.0% in goats (95% CI: 5.4–21.2; heterogeneity: I2 = 78.8%, τ2 = 0.4). Molecular tests were seldom used to determine species and illustrate strain diversity. There was a lack of awareness of leptospirosis among farmers and health practitioners. Conclusion: The widespread presence of leptospires and inadequate diagnostic capacity demonstrate that leptospirosis is a common but underreported disease in Kenya. Raising awareness and boosting the country's diagnostic capacity is crucial to timely detection and disease control. Author summary: Leptospirosis is a prevalent but understudied zoonotic disease in Kenya. A comprehensive review of the presence of the disease in various hosts is therefore needed to catalogue the research efforts and inspire future scientific inquiry on this neglected tropical disease. We therefore undertook this comprehensive review of published literature in leading databases and institutional repositories of relevant Kenyan higher institutions of learning. Literature spanning more than 70 years was identified and study areas showed a regional bias towards central, western, southern and coastal regions. The arid and semi-arid areas in the northern and eastern regions with large animal and wildlife populations that could facilitate leptospiral transmission were under-represented, and the inclusion of these pastoral regions could give a better picture of the country's leptospirosis risk profile. Summary estimates in cattle and goats revealed considerable pooled seroprevalence of leptospirosis and the need for control in animal hosts. A low awareness among farmers, and animal and public health practitioners was found, demonstrating the need for education initiatives that can facilitate at-risk populations such as farmers. Additionally, the country lacks the capacity for MAT testing, and recent efforts to culture for leptospires are non-existent. Understanding the circulating serovars and strain diversity is crucial to the effective control of leptospirosis. Investments in diagnostics for peripheral and central laboratories are vital for public health response. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a neglected tropical disease that affects over 250 million people, predominantly in impoverished communities, including those in Ethiopia. However, there is currently no available national data regarding its prevalence in Ethiopia or its potential association with anemia. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-2020) guideline was followed in our study. A comprehensive search strategy was conducted using international databases (PUB Med, Embase, Scopus, and Science Direct) and websites (Google Scholar and Google) from their date of inception to April 22, 2024. The quality of the retrieved studies was assessed using an adapted version of the Newcastle–Ottawa Scale. Publication bias and statistical heterogeneity were statistically assessed. A random effects model was applied, and all analysis was performed with STATA 17 statistical software. Result: The prevalence of schistosomiasis was assessed in twelve studies with 5747 participants. S. mansoni was studied in 11 research papers, while S. hematobium was assessed in one study. Using a random effect model due to high heterogeneity (I2 = 98.46%; P < 0.001), the overall pooled prevalence of schistosomiasis in Ethiopia was 22% (95% CI: 14.3, 29.6). The prevalence of schistosomiasis was about two and a half times higher in rural settings (23%) (95% CI: 15, 31) than in urban areas (10%) (95% CI: 3, 17). The burden of schistosomiasis was 23% between 2020 and 2024, compared to 16% from 2015–2019, with a higher prevalence among pediatric age groups (22%) versus 14% in mixed pediatric and adult age groups. The magnitude of schistosomiasis for good and very good-quality papers was 22% and 17%, respectively. In all the subgroup analyses, there was considerable statistically significant heterogeneity. No study was found to evaluate the association of schistosomiasis with anemia. Conclusion: The study reveals Ethiopia's higher schistosomiasis prevalence. Rural areas have a high burden of schistosomiasis. No eligible study was found to evaluate the association of schistosomiasis with anemia. Therefore, prevention and control measures should focus on rural settings. Trial registration: The registration number at PROSPERO is CRD42024538522. [ABSTRACT FROM AUTHOR]

Background: Trichinella spiralis (T. spiralis) is a parasitic helminth that causes a globally prevalent neglected zoonotic disease, and worms at different developmental stages (muscle larvae, adult worms, newborn larvae) induce immune attack at different infection sites, causing serious harm to host health. Several innate immune cells release extracellular traps (ETs) to entrap and kill most pathogens that invade the body. In response, some unicellular pathogens have evolved a strategy to escape capture by ETs through the secretion of nucleases, but few related studies have investigated multicellular helminths. Results: In the present study, we observed that ETs from neutrophils capture adult worms of T. spiralis, while ETs from macrophages trap muscle larvae and newborn larvae, and ETs had a killing effect on parasites in vitro. To defend against this immune attack, T. spiralis secretes plancitoxin-1, a DNase II-like protein, to degrade ETs and escape capture, which is essential for the survival of T. spiralis in the host. Conclusions: In summary, these findings demonstrate that T. spiralis escapes ET-mediated capture by secreting deoxyribonuclease as a potential conserved immune evasion mechanism, and plancitoxin-1 could be used as a potential vaccine candidate. [ABSTRACT FROM AUTHOR]

Genomics, transcriptomics, and proteomics have significantly advanced our understanding of obligately host-associated microbes, where interrogation of the biology is often limited by the complexity of the biological system and limited tools. This includes the causative agents of many neglected tropical diseases, including filarial nematodes. Therefore, numerous transcriptomics studies have been undertaken on filarial nematodes. Most of these transcriptomics studies focus on Brugia malayi, which causes lymphatic filariasis and is a laboratory model for human filarial disease. Here, we undertook a meta-analysis of the publicly available B. malayi transcriptomics data enabling the direct cross comparison of samples from almost a dozen studies. This reanalysis highlights the consistency of transcriptomics results across many different studies and experimental designs from across the globe for over a decade of research, across many different generations of a sequencing technology, library preparation protocols, and differential expression tools. Males and microfilariae across samples had similar expression profiles. However, female samples were clustered into two differential expression patterns that were significantly different from one another. Largely, we confirm previous results for all studies reanalyzed including tissue-specific gene expression and anti-Wolbachia doxycycline treatment of microfilaria. However, we did not detect previously reported differential expression upon in vitro or in vivo treatment with ivermectin, albendazole, and DEC, instead identifying a consistent lack of transcriptomic change upon exposure to these anthelminthic drugs. Updated annotation has been provided that denotes poorly supported genes including those overlapping rRNAs. Author summary: Numerous previous studies have measured all of the mRNA in Brugia malayi under a variety of conditions. Here, we collectively analyzed all data from those previous studies to gain new insights, which can be facilitated by the additional comparisons of this type of meta-analysis. Importantly, this meta-analysis demonstrates that worms that are shipped to various locations and handled by different laboratories are largely the same. The exception are adult females, where two profiles are apparent that are vastly different, which could lead to differing results in laboratory experiments. We propose that shipping dates and conditions be provided in manuscripts and that a transcriptome profile be collected in future laboratory studies to benchmark worms. In addition, the inclusion of more worm samples reveals that differences between worm shipments and batches is greater than the difference observed upon treatment with anthelminthic agents (ivermectin, albendazole, and DEC) under the conditions examined in the original studies. During this work, we identified some regions of the genome where genes were misidentified that affect RNA-based analysis and provide an updated annotation file to facilitate their removal in future studies. [ABSTRACT FROM AUTHOR]

The article discusses the challenges of evaluating diagnostic tests for neglected tropical diseases (NTDs) and proposes an interpretive framework using Ascaris lumbricoides as an example. The authors argue that using a single "gold standard" reference test can lead to biased estimates of sensitivity and specificity. They recommend using latent class models (LCMs) to analyze data from multiple imperfect tests and account for correlations between test results. The article emphasizes the importance of considering the purpose of testing and the target population when evaluating diagnostic tests for NTDs. The authors provide a graphical illustration to help researchers interpret the results and suggest that the framework should be considered before data collection to modify the combination of tests and populations if necessary. They also highlight the need for further guidance and standardization in diagnostic test evaluation for NTDs. [Extracted from the article]