Neglected Tropical Diseases Research Articles

Assessing the Incidence of Snakebites in Rural Gabon-A Community-Based, Cross-Sectional Pilot Survey.

Snakebite envenoming (SBE) is a neglected tropical disease (NTD). Community-based studies from sub-Saharan Africa are urgently required as data on the incidence are scarce. This study aimed to determine the lifetime prevalence of snakebites in rural Gabon by preparing the conduct of a larger regional survey. A cross-sectional community-based epidemiological survey in Sindara, Ngounie province, was conducted. Households were interviewed about the history of snakebites of household members to calculate lifetime prevalence. In addition, the average annual incidence rate per 100,000 over the last 5 years was calculated. A total of 771 inhabitants were enrolled, of which 5 (0.65%; 95% confidence interval (95% CI: 0.2-1.5%)) were victims of snakebites. Over the past 5 years, annual incidence was 77 bites per 100,000 (95% CI: 0-620). This study provides a first rough estimate of the incidence of SBE from rural central Gabon, demonstrating the importance of this NTD. Key Contribution: The estimated annual incidence of snakebites found was 77 per 100,000. Snakebites occurred mainly during agricultural activities.

Evaluation of the anti-trypanosoma activity of alkaloids from Pilocarpus microphyllus by molecular docking: A search for new drugs for Chagas disease

Trypanosoma cruzi and Trypanosoma brucei, respectively, transmit the neglected tropical diseases (NTDs) Chagas disease and sleeping sickness. They cause symptoms that are harmful to public health. Treatment often has adverse effects, including high toxicity and neurosensory disorders. Studies aimed at developing pharmacological technologies are essential. In this study, we performed computational simulations based on in silico predictions. The amino acid sequence of the proteins for both parasites, T. cruzi and T. brucei, and their three-dimensional (3D) structures were obtained and drawn using the UniProt and Swiss model servers, respectively; later, they were used for in silico molecular docking studies. The GaussView software was used to get the two-dimensional (2D) and three-dimensional (3D) ligands of epiisopiloturine, epiisopilosine, pilosine, isopilosine, macaubine, and pilocarpine. To perform the optimization and frequency calculations of the alkaloids, the Gaussian 09w software and the Density Functional Theory (DFT) method were used with the hybrid functional B3LYP and the STO-3G support base. All the output files generated after the calculations were used to create the input files for the bond energy calculations. For the molecular docking studies, we have evaluated the side-ligands protein interactions and antiparasitic activity of the ligands. The anti-Trypanosomatidae potential of alkaloids extracted from Pilocarpus microphyllus “jaborandi” were evaluated by molecular docking. The results of the interactions of the 6 alkaloids: isopilosine, epiisopiloturine, epiisopilosine, pilocarpine, macubine and pilosine, with the proteins trypanothione reductase, sterol 14-alpha demethylase, phosphoinositide phospholipase c, farnesyl pyrophosphate synthase, nitroreductase, from the parasites T. cruzi and T. brucei, demonstrated that for 5 of them, the simulations showed minimums energy to be characterized as reactions that occur in biological systems spontaneously. For trypanothione reductase-epiisopilosine for both parasites, the alkaloid was observed to bind to the amino acid Glu467 through hydrogen bonds. For phosphoinositide phospholipase C-epiisopilosine, parameter values found were -8.2 Kcal.mol-1, only the amino acid Asn262 had interaction through hydrogen bonding. Other hydrophobic interactions were also observed between the proteins and epiisopilosine. Regarding the results of the alignment of amino acid sequences for both parasites, it was found a similarity of 83.30% and 52.38% between the nucleotide sequences of T. cruzi and T. brucei for trypanothione reductase and phosphoinositide phospholipase C, concluding that the best candidate for therapy against Chagas disease and sleeping sickness would be epiisopilosine alkaloid.

Natural variables separate the endemic areas of Clonorchis sinensis and Opisthorchis viverrini along a continuous, straight zone in Southeast Asia

BackgroundClonorchiasis and opisthorchiasis, caused by the liver flukes Clonorchis sinensis and Opisthorchis viverrini respectively, represent significant neglected tropical diseases (NTDs) in Asia. The co-existence of these pathogens in overlapping regions complicates effective disease control strategies. This study aimed to clarify the distribution and interaction of these diseases within Southeast Asia.MethodsWe systematically collated occurrence records of human clonorchiasis (n = 1809) and opisthorchiasis (n = 731) across the Southeast Asia countries. Utilizing species distribution models incorporating environmental and climatic data, coupled machine learning algorithms with boosted regression trees, we predicted and distinguished endemic areas for each fluke species. Machine learning techniques, including geospatial analysis, were employed to delineate the boundaries between these flukes.ResultsOur analysis revealed that the endemic range of C. sinensis and O. viverrini in Southeast Asia primarily spans across part of China, Vietnam, Thailand, Laos, and Cambodia. During the period from 2000 to 2018, we identified C. sinensis infections in 84 distinct locations, predominantly in southern China (Guangxi Zhuang Autonomous Region) and northern Vietnam. In a stark contrast, O. viverrini was more widely distributed, with infections documented in 721 locations across Thailand, Laos, Cambodia, and Vietnam. Critical environmental determinants were quantitatively analyzed, revealing annual mean temperatures ranging between 14 and 20 °C in clonorchiasis-endemic areas and 24–30 °C in opisthorchiasis regions (P < 0.05). The machine learning model effectively mapped a distinct demarcation zone, demonstrating a clear separation between the endemic areas of these two liver flukes with AUC from 0.9 to1. The study in Vietnam delineates the coexistence and geographical boundaries of C. sinensis and O. viverrini, revealing distinct endemic zones and a transitional area where both liver fluke species overlap.ConclusionsOur findings highlight the critical role of specific climatic and environmental factors in influencing the geographical distribution of C. sinensis and O. viverrini. This spatial delineation offers valuable insights for integrated surveillance and control strategies, particularly in regions with sympatric transmission. The results underscore the need for tailored interventions, considering regional epidemiological variations. Future collaborations integrating eco-epidemiology, molecular epidemiology, and parasitology are essential to further elucidate the complex interplay of liver fluke distributions in Asia.

Single-cell transcriptomics of the human parasite Schistosoma mansoni first intra-molluscan stage reveals tentative tegumental and stem-cell regulators

Schistosomiasis is a major Neglected Tropical Disease, caused by the infection with blood flukes in the genus Schistosoma. To complete the life cycle, the parasite undergoes asexual and sexual reproduction within an intermediate snail host and a definitive mammalian host, respectively. The intra-molluscan phase provides a critical amplification step that ensures a successful transmission. However, the cellular and molecular mechanisms underlying the development of the intra-molluscan stages remain poorly understood. Here, single cell suspensions from S. mansoni mother sporocysts were produced and sequenced using the droplet-based 10X Genomics Chromium platform. Six cell clusters comprising two tegument, muscle, neuron, parenchyma and stem/germinal cell clusters were identified and validated by in situ hybridisation. Gene Ontology term analysis predicted key biological processes for each of the clusters, including three stem/germinal sub-clusters. Furthermore, putative transcription factors predicted for stem/germinal and tegument clusters may play key roles during parasite development and interaction with the intermediate host.

Navigating diagnostic and therapeutic challenges in ocular manifestations of Hansen's disease and trachoma: A narrative review.

Neglected tropical diseases (NTDs) encompass a group of approximately 20 diseases prevalent in tropical and subtropical regions, closely associated with poverty, affecting over a billion people in low-income countries. This manuscript aims to explore the ocular manifestations and burden of two significant NTDs, namely Hansen's disease and trachoma while addressing gaps in understanding and management. Hansen's disease, caused by Mycobacterium leprae , has a long history and presents with diverse neurological and ocular manifestations. Despite the availability of treatment, ocular complications persist, leading to significant visual impairment in some cases. The manuscript emphasizes the importance of early diagnosis, regular ophthalmic examinations, and follow-ups to prevent and control ocular complications, reducing the burden of visual impairment and blindness. Trachoma, caused by Chlamydia trachomatis , remains the leading infectious cause of blindness in underdeveloped and remote areas. The manuscript highlights the clinical diagnosis and implementation of the World Health Organization's (WHO's) SAFE (surgery, antibiotics, facial hygiene, and environmental sanitation) strategy to prevent transmission and associated blindness. However, challenges in health surveillance tools and underreporting of trachoma cases are addressed, emphasizing the need for improved strategies to combat the disease effectively. Through a comprehensive review of the ocular manifestations and management of Hansen's disease and trachoma, this manuscript contributes to the existing knowledge base and enhances a deeper understanding of these NTDs. Addressing gaps in understanding and management emphasizes the importance of implementing WHO's strategies and collaborative efforts to achieve the global goal of reducing the burden of NTDs and improving community health and well-being. The manuscript underscores the significance of early intervention, preventive measures, and technological advancements, providing valuable insights for policymakers, healthcare professionals, and researchers working in the field of NTDs.

The effect of contextual factors on a health intervention against podoconiosis in Ethiopia

IntroductionUnderstanding contextual factors that influence the implementation and outcome of interventions is crucial to improving them. Outcome and process evaluation studies have to date focused on the successes and limitations of interventions with little consideration of external factors that could either facilitate or impede them. Guided by the Context and Implementation of Complex Intervention (CICI) framework, we evaluated the effect of contextual factors on a health intervention implemented against the neglected tropical disease (NTD) podoconiosis in Ethiopia.MethodWe purposefully selected a health intervention jointly implemented by two NGOs in podoconiosis-endemic districts in Northwestern Ethiopia. We employed an exploratory mixed methods approach, and data were collected between April and July 2022. We first conducted document analysis, observations, 4 focus group discussions, 32 in-depth interviews and 19 key informant interviews. Subsequently, we administered a survey to 369 rural residents, of whom 42 were affected by podoconiosis. The qualitative data were managed with NVivo version 12 software. The quantitative data were analyzed using Stata version 15 software.ResultsMost project activities were implemented as per the initial plan and the intervention reached patients that never had access to treatment services before. Contextual factors (geographical, epidemiological, socio-economic, socio-cultural, ethical, legal and political) and lived experience of patients influenced the implementation and outcome of the intervention. Most of the contextual factors pose constraints on implementation and affected the acceptability and sustainability of project activities. On the other hand, political context such the commitment of the government to rollout national programs and set up NTD structures at district level positively influenced the implementation of the intervention.ConclusionHealth intervention implementors should be aware of the interactive effects of contextual factors wherein interventions are put into practice. Minimizing the constraining effects of these contextual factors while utilizing opportunities presented by them might help implement optimal strategies to improve the lives of individuals affected by podoconiosis and similar NTDs.

Using 5-Nitroimidazole Derivatives against Neglected Tropical Protozoan Diseases: Systematic Review

Neglected tropical diseases (NTDs) are a significant global health problem. Additionally, anti-protozoan treatments are toxic, and their therapeutic regimens require prolonged treatment times and high concentrations of the drugs. Additionally, multi-resistant protozoan strains represent an important global emergency that must be addressed. For these reasons, global efforts are being made to identify new drug candidates that are capable of combating these kinds of diseases. This systematic review shows that 5-nitroimidazole derivatives have been successfully used against neglected tropical protozoan diseases (NTPDs), with a specific focus on three diseases: malaria, leishmaniasis, and human trypanosomiasis. Some nitroimidazole derivatives have been repurposed, and an important group of new drugs is available for the treatment of NTPDs. Finally, we address 5-nitroimidazoles using chemoinformatics and medicinal chemistry tools to describe the most recent and promising 5-nitroimidazole derivatives associated with anti-protozoal activity using their published in vitro and in vivo data. We show that 5-nitroimidazoles offer a broader spectrum of activity against a variety of protozoal pathogens. More importantly, these compounds demonstrate a significantly reduced systemic toxicity compared to other nitroimidazoles. This makes them a more favorable option in the treatment of protozoal infections, particularly in scenarios where the patient’s tolerance to drug side effects is a critical concern.

Towards global elimination of lymphatic filariasis: a systematic review of the application of spatial epidemiological methods to enhance surveillance and support elimination programmes

BackgroundIn recent decades, spatial epidemiology has increasingly been used to study neglected tropical diseases (NTDs). Spatial methods are particularly relevant when transmission is strongly driven by sociodemographic and environmental factors,...

A One Health approach toward the control and elimination of soil-transmitted helminthic infections in endemic areas

Soil-transmitted helminths (STHs) pose significant health challenges, particularly in developing countries. Over 2 billion people are estimated to have been infected with at least one STH species. These parasites rely on the soil for part of their life cycle and are transmitted to humans through ova ingestion or skin penetration. Key risk factors include poor water, sanitation, hygiene practices, limited healthcare access, and poverty. Globally, STHs are primarily controlled through chemo-preventive deworming of high-risk groups in moderate (where prevalence of STHs is between 20 % and 50 %) to highly endemic areas (prevalence >50 %). Despite the use of deworming to control the STHs in endemic areas, infections still occur. The aim of this article is to explore the potential for enhancing STH control and elimination as Neglected Tropical Diseases (NTDs) in endemic areas through an integrated approach—the One Health approach. The current control program has a single strategy of chemoprophylaxis; in the integrated approach to control of STHs, the parasite control strategies besides being based on the epidemiology of the parasite (endemicity), also include strategies based on the biology (transmission cycle) of the parasites and human behavior patterns in endemic areas. Through the involvement of local communities, healthcare authorities, and stakeholders, participatory approaches foster collaborative efforts to devise and implement control measures. By integrating this integrated approach into existing healthcare and educational initiatives, more effective results can be achieved. The promotion of health education, clean water access, improved sanitation, and hygiene awareness can further enhance control strategies and reduce STH prevalence sustainably. Here, we highlight the benefits of adopting an integrated (One Health) approach to tackle STHs in endemic areas. Through community empowerment and multi-sectorial collaboration, we can strengthen our collective efforts to combat STHs and alleviate the burden of these NTDs.

Computational investigation of turmeric phytochemicals targeting PTR1 enzyme of Leishmania species

In this study, we used in silico techniques to identify available parasite treatments, representing a promising therapeutic avenue. Building upon our computational initiatives aimed at discovering natural inhibitors for various target enzymes from parasites causing neglected tropical diseases (NTDs), we present novel findings on three turmeric-derived phytochemicals as inhibitors of Leishmania pteridine reductase I (PTR1) through in silico methodologies. PTR1, a crucial enzyme in the unique folate metabolism of trypanosomatid parasites, holds established therapeutic significance. Employing MOE software, a molecular docking analysis assesses the efficacy of turmeric phytochemicals against Leishmania PTR1. Validation of the docking protocol is confirmed with an RMSD value of 2. Post-docking, compounds displaying notable interactions with critical residues and binding affinities ranging between −6 and −8 kcal/mol are selected for interaction pattern exploration. Testing twelve turmeric phytochemicals, including curcumin, zingiberene, curcumol, curcumenol, eugenol, bisdemethoxycurcumin, tetrahydrocurcumin, tryethylcurcumin, turmerones, turmerin, demethoxycurcumin, and turmeronols, revealed binding affinities ranging from −5.5 to −8 kcal/mol. Notably, curcumin, demethoxycurcumin, and bisdemethoxycurcumin exhibit binding affinities within −6.5 to −8 kcal/mol and establish substantial interactions with catalytic residues. These phytochemicals hold promise as lead structures for rational drug design targeting Leishmania spp. PTR in future applications. This work underscores the potential of these identified phytochemicals in the development of more effective inhibitors, demonstrating their relevance in addressing neglected tropical diseases caused by parasites.

Prevalence and associated risk factors of neglected tropical diseases in the Amhara region, Ethiopia

This systematic review analyzed the prevalence of neglected tropical diseases (NTDs) and associated risk factors in the Amhara region. Thirty-one articles from 2012 to 2022 were examined, and data analysis was conducted using STATA version 17. The overall NTD prevalence in Amhara was 29.9% (95% CI: 23.32–36.47). The highest prevalences were observed for soil-transmitted helminths (STHs) at 37.86% (95% CI=27.57–48.15), Schistosoma at 37.77% (95% CI=16.90–58.61), scabies at 24.28% (95% CI=6.42-42.15), and trachoma at 19.55% (95% CI=13.38–25.72). Prevalence varied across zones, ranging from 6.10% (95% CI=4.33–7.87) in Awi to 46.40% (95% CI=42.90–48.80) in Bahir Dar. Factors associated with NTDs included illiteracy and raw vegetable consumption for STHs; male gender, river swimming, and contact with river water for Schistosoma; ocular discharge and fly-eye contact for trachoma; and family size &gt;6, clothes sharing, and sleeping with scabies-infected individuals for scabies. Improved sanitation, health education, and personal hygiene are vital for controlling NTDs in the study region.

Climate drivers of migration and neglected tropical disease burden in Latin American and Caribbean immigrants: A pilot study in Atlanta, Georgia

IntroductionClimate change has negatively impacted the agricultural and socioeconomic infrastructure of Latin American and Caribbean (LAC) countries leading to conditions that promote human migration. It has also led to emergence and reemergence of infectious diseases. This pilot study aimed to identify climate-related drivers of migration and to describe the burden of climate-sensitive neglected tropical diseases (NTD) in immigrants living in Atlanta, Georgia, USA. MethodsFirst generation immigrants from LAC countries living in the Atlanta-metro area were recruited between May and December 2021. Participants completed a survey concerning demographics, socioeconomics, living conditions in their country of origin and living conditions in Atlanta, and motivations for migration. Blood and stool samples were collected to identify Chagas disease and soil-transmitted helminths, and skin exams screened for leprosy and leishmaniasis. Descriptive, univariate, and multivariable analyses of this dataset looked at the association between a climate-driven motivation to migrate and geographic and socioeconomic factors. ResultsFifty-seven individuals were recruited representing 11 LAC countries of origin. Most originated from Central America (n = 32; 56 %) and Mexico (n = 13; 23%). Forty-two participants reported a change in climate or weather in their country of origin prior to moving and direct climate drivers of migration (e.g., floods, drought, etc.) were identified by 12 participants (21.1%). Infectious diseases screening found one definitive case of Chagas (2.5%) out of 40 blood samples screened. Food insecurity was significantly associated with a climate-related factor for migrating: aOR = 6.3 (95 % CI 1.1, 35.5). ConclusionsWhile most participants did not directly identify “climate change” as a reason for migration, our study reveals many factors such as food insecurity, agricultural occupations, and region of origin that may underlie climate-motivated migration. Finding one case of Chagas was also noteworthy and shows the need for improved surveillance for this important NTD.

Involving patients in drug development for Neglected Tropical Diseases (NTDs): A qualitative study exploring and incorporating preferences of patients with cutaneous leishmaniasis into Target Product Profile development.

Target Product Profiles (TPPs) are instrumental to help optimise the design and development of therapeutics, vaccines, and diagnostics - these products, in order to achieve the intended impact, should be aligned with users' preferences and needs. However, patients are rarely involved as key stakeholders in building a TPP. Thirty-three cutaneous leishmaniasis (CL) patients from Brazil, Colombia, and Austria, infected with New-World Leishmania species, were recruited using a maximum variation approach along geographic, sociodemographic and clinical criteria. Semi-structured interviews were conducted in the respective patient's mother tongue. Transcripts, translated into English, were analysed using a framework approach. We matched disease experiences, preferences, and expectations of CL patients to a TPP developed by DNDi (Drug for Neglected Diseases initiative) for CL treatment. Patients' preferences regarding treatments ranged from specific efficacy and safety endpoints to direct and significant indirect costs. Respondents expressed views about trade-offs between efficacy and experienced discomfort/adverse events caused by treatment. Reasons for non-compliance, such as adverse events or geographical and availability barriers, were discussed. Considerations related to accessibility and affordability were relevant from the patients' perspective. NTDs affect disadvantaged populations, often with little access to health systems. Engaging patients in designing adapted therapies could significantly contribute to the suitability of an intervention to a specific context and to compliance, by tailoring the product to the end-users' needs. This exploratory study identified preferences in a broad international patient spectrum. It provides methodological guidance on how patients can be meaningfully involved as stakeholders in the construction of a TPP of therapeutics for NTDs. CL is used as an exemplar, but the approach can be adapted for other NTDs.

Synthesis and Evaluation of (Bis)benzyltetrahydroisoquinoline Alkaloids as Antiparasitic Agents.

Visceral leishmaniasis and Chagas disease are neglected tropical diseases (NTDs) that severely impact the developing world. With current therapies suffering from poor efficacy and safety profiles as well as emerging resistance, new drug leads are direly needed. In this work, 26 alkaloids (9 natural and 17 synthetic) belonging to the benzyltetrahydroisoquinoline (BI) family were evaluated against both the pro/trypomastigote and amastigote forms of the parasites Leishmania infantum and Trypanosoma cruzi, the causative agents of these diseases. These alkaloids were synthesized via an efficient and modular enantioselective approach based on Bischler-Napieralski cyclization/Noyori asymmetric transfer hydrogenation to build the tetrahydroisoquinoline core. The bis-benzyltetrahydroisoquinoline (BBI) alkaloids were prepared using an Ullmann coupling of two BI units to form the biaryl ether linkage, which enabled a comprehensive survey of the influence of BI stereochemistry on bioactivity. Preliminary studies into the mechanism of action against Leishmania mexicana demonstrate that these compounds interfere with the cell cycle, potentially through inhibition of kinetoplast division, which may offer opportunities to identify a new target/mechanism of action. Three of the synthesized alkaloids showed promising druglike potential, meeting the Drugs for Neglected Disease initiative (DNDi) criteria for a hit against Chagas disease.

Neglected Tropical Diseases: A Comprehensive Review.

Neglected tropical diseases (NTDs) are a group of diseases caused by diverse organisms, affecting millions of people in tropical and subtropical conditions. NTDs are more prevalent among people who live in poverty, without access to clean water, adequate sanitation, and quality health care. Most NTDs are chronic conditions and are potentially disablers than killers, leaving behind a trail of social consequences. Controlling NTDs has become complicated due to limited resources and are frequently ignored by global funding agencies. India experiences a significant burden of global NTDs. The paradox is that NTDs are preventable and treatable at an affordable cost. It then makes no sense as to why we co-exist with such diseases. The World Health Organization (WHO) has donned the leadership role of eliminating, eradicating, and controlling global NTDs. The WHO published a roadmap delineating a plan of action, which was being reviewed periodically. This led to substantive progress in tackling the NTDs. However, many challenges still exist to controlling and preventing NTDs. India has achieved significant progress towards NTD control and elimination by implementing the WHO strategies and action plans. This was evident by an increase in research and funding in this direction. The number of new drugs, vaccines, and investigative tools available and those in the pipeline is testimony to their efforts. Focusing singly on India's NTD problem would substantially reduce the burden of poverty-related neglected diseases and could dramatically advance the global health agenda. This review highlights the problem of NTDs in the Indian and global perspective.

Review of Leishmaniasis Treatment: Can We See the Forest through the Trees?

There are three known clinical syndromes of leishmaniasis: cutaneous (CL), mucocutaneous (MCL), and visceral disease (VL). In MCL and VL, treatment must be systemic (either oral or intravenous), while CL treatment options vary and include observation-only localized/topical treatment, oral medications, or parenteral drugs. Leishmaniasis treatment is difficult, with several factors to be considered. First, the efficacy of treatments varies among different species of parasites prevalent in different areas on the globe, with each species having a unique clinical presentation and resistance profile. Furthermore, leishmaniasis is a neglected tropical disease (NTD), resulting in a lack of evidence-based knowledge regarding treatment. Therefore, physicians often rely on case reports or case series studies, in the absence of randomized controlled trials (RCT), to assess treatment efficacy. Second, defining cure, especially in CL and MCL, may be difficult, as death of the parasite can be achieved in most cases, while the aesthetic result (e.g., scars) is hard to predict. This is a result of the biological nature of the disease, often diagnosed late in the course of disease (with possible keloid formation, etc.). Third, physicians must consider treatment ease of use and the safety profile of possible treatments. Thus, topical or oral treatments (for CL) are desirable and promote adherence. Fourth, the cost of the treatment is an important consideration. In this review, we aim to describe the diverse treatment options for different clinical manifestations of leishmaniasis. For each currently available treatment, we will discuss the various considerations mentioned above (efficacy, ease of use, safety, and cost).

Exploring the Role of Community Involvement in Reducing the Burden of Schistosomiasis and Other Neglected Tropical Diseases in Malawi: Where are We in the Fight Against Neglected Tropical Diseases?

Schistosomiasis has been endemic in Malawi since 1947. Despite the longevity of endemicity of the disease, it still maintains a high burden in Malawi. This could be attributed to insufficient coverage of preventive and therapeutic mass drug administration (MDA) which mainly targets school-aged children, leaving out adults who also bear a high burden of the disease. Additionally, despite well documented impact of community involvement in boosting up the effectiveness of health programmes, there is minimal community involvement in schistosomiasis control and prevention programmes. Therefore, this perspective seeks to discuss the historical background of schistosomiasis in Malawi, gaps in community engagement and participation and suggest ways of enhancing the role of the community in prevention and control programmes. Amongst other challenges, the control programmes are centralised, leading to minimal input at the district and community level as well as low awareness of schistosomiasis control and prevention methods at the community level. It is of utmost significance therefore to provide comprehensive schistosomiasis health education to the communities and devise a thorough outline of the specific roles and responsibilities of all stakeholders including community members in the fight against schistosomiasis and other neglected tropical diseases.

Could natural terpenes be an alternative for the treatment of neglected tropical diseases?

AbstractExisting chemotherapy for neglected tropical diseases (NTDs) can often be toxic and ineffective, highlighting the necessity for new treatments. Terpenes are secondary metabolites with pharmacological potential. This aim of this mini‐review is to explore the most promising natural terpenes with anti‐leishmanicidal, anti‐schistosomicidal, and anti‐echinococcal activity, their mechanisms of action, and their efficacy as combination therapy. The study identified a tetracyclic diterpenoid, a sesquiterpene lactone, and a triterpene with the highest biological activity against leishmaniasis. Additionally, a triterpenoid and a tetraterpene showed potent activity against schistosomiasis and echinococcosis, respectively. Compounds have antiparasitic effects by inducing cell death, inhibiting cell stress‐related proteins, degrading extracellular matrix, and modulating immune and inflammatory responses. The employment of combination therapy and terpene nanotransporters appears to enhance the antiparasitic activity of these compounds. Although identifying specific molecular targets is necessary, the use of terpenes in combination therapy presents a safe and highly promising approach for the rational development of more potent and selective antiparasitic drugs.

Subcellular particles for characterization of host-parasite interactions

Parasitic diseases remain a major global health problem for humans. Parasites employ a variety of strategies to invade and survive within their hosts and to manipulate host defense mechanisms, always in the pathogen's favor. Extracellular vesicles (EVs), membrane-bound nanospheres carrying a variety of bioactive compounds, were shown to be released by the parasites during all stages of the infection, enabling growth and expansion within the host and adaptation to frequently changing environmental stressors. In this review, we discuss how the use of existing nanotechnologies and high-resolution imaging tools assisted in revealing the role of EVs during parasitic infections, enabling the quantitation, visualization, and detailed characterization of EVs. We discuss here the cases of malaria, Chagas disease and leishmaniasis as examples of parasitic neglected tropical diseases (NTDs). Unraveling the EVs' role in the NTD pathogenesis may enormously contribute to their early and reliable diagnostic, effective treatment, and prevention.

Unlocking Opportunities for Mycobacterium leprae and Mycobacterium ulcerans.

In the recent decade, scientific communities have toiled to tackle the emerging burden of drug-resistant tuberculosis (DR-TB) and rapidly growing opportunistic nontuberculous mycobacteria (NTM). Among these, two neglected mycobacteria species of the Acinetobacter family, Mycobacterium leprae and Mycobacterium ulcerans, are the etiological agents of leprosy and Buruli ulcer infections, respectively, and fall under the broad umbrella of neglected tropical diseases (NTDs). Unfortunately, lackluster drug discovery efforts have been made against these pathogenic bacteria in the recent decade, resulting in the discovery of only a few countable hits and majorly repurposing anti-TB drug candidates such as telacebec (Q203), P218, and TB47 for current therapeutic interventions. Major ignorance in drug candidate identification might aggravate the dramatic consequences of rapidly spreading mycobacterial NTDs in the coming days. Therefore, this Review focuses on an up-to-date account of drug discovery efforts targeting selected druggable targets from both bacilli, including the accompanying challenges that have been identified and are responsible for the slow drug discovery. Furthermore, a succinct discussion of the all-new possibilities that could be alternative solutions to mitigate the neglected mycobacterial NTD burden and subsequently accelerate the drug discovery effort is also included. We anticipate that the state-of-the-art strategies discussed here may attract major attention from the scientific community to navigate and expand the roadmap for the discovery of next-generation therapeutics against these NTDs.