Search

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

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

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

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

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

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

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

Mycetoma, a neglected infection of subcutaneous tissues, poses a significant health burden, especially in tropical regions. It is caused by fungal (eumycetoma) and bacterial (actinomycetoma) pathogens, with current treatments often providing unsatisfactory outcomes. This study aims to discover novel broad-spectrum antimicrobial agents to circumvent the lengthy and costly diagnostic procedures. Eight essential oils (EOs) from the roots and aerial parts of Geigeria alata, Lavandula angustifolia, Melaleuca alternifolia, Myristica fragrans, Pimpinella anisum, Syzigum aromaticum, and Thymus vulgaris were prepared using steam distillation. The in vitro antimycetomal activity against Madurella mycetomatis and Actinomadura madurae strains was assessed using resazurin assays. The chemical compositions of the EOs were analyzed using gas chromatography and mass spectrometry (GC–MS). Promising EOs underwent further in vivo toxicity and efficacy testing in Galleria mellonella larvae models. EOs of G. alata roots, M. fragrans, P. anisum, S. aromaticum, and T. vulgaris showed wide-spectrum dual in vitro antimycetomal activity against all tested strains, with minimum inhibitory concentrations (MICs) ranging from 0.004 to 0.125% v/v. G. alata aerial parts and L. angustifolia EOs demonstrated activity predominantly against A. madurae, while M. alternifolia EO did not inhibit any tested strains. M. fragrans and P. anisum EOs significantly enhanced the survival of M. mycetomatis-infected larvae without inducing toxicity in uninfected larvae. Notably, P. anisum EO tended to enhance the survival of A. madurae-infected larvae, ranking it as the most promising EO among those tested. The investigated EOs, particularly P. anisum, exhibited promising broad-spectrum antimycetomal activity against fungal and bacterial pathogens responsible for mycetoma. These findings highlight the potential of essential oils as a basis for developing novel antimycetomal agents, offering hope for improved treatment strategies for this neglected disease. [ABSTRACT FROM AUTHOR]

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

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

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

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

The World Health Organization's (WHO) designation of noma as a neglected tropical disease (NTD) on 15 December 2023 marks a crucial advancement in global health efforts. This move sheds light on a condition predominantly affecting undernourished children in isolated regions of sub-Saharan Africa. Recognized as the 21st NTD, noma, or cancrum oris, is a serious condition leading to orofacial gangrene. The disease largely impacts young children and those with compromised immune systems, including individuals with human immunodeficiency virus or leukaemia. Determining the exact prevalence of noma is complex, hindered by rapid disease progression, societal stigma and a lack of reporting, especially in impoverished areas. The WHO's acknowledgment is a significant step, emphasizing the need for more in-depth research and resources to address this overlooked disease. It highlights the critical role of multifaceted prevention strategies, including economic empowerment, improved nutrition and enhanced vaccination efforts. This recognition is pivotal in guiding international health initiatives towards better outcomes for some of the most at-risk populations globally. [ABSTRACT FROM AUTHOR]

Neglected tropical diseases (NTDs) are a group of illnesses which usually present with a chronic clinical picture. NTDs can lead to permanent disability and are often associated with social stigma. In many developing countries where NTDs are endemic, there are no diagnostic tools for the safe storage and transport of biological samples, and there are no specialist diagnostic centers where the samples could be processed. The transport of biological samples (blood, urine) collected in field conditions and brought to laboratories located in developed countries requires the maintenance of the cold chain during transportation. Ensuring temperature control during transport could be problematic or even impossible to achieve; it is also expensive. A helpful solution to this problem is to use the dried matrix spot (DMS) technique, which seems to be a reliable method for collecting biological samples to be used for screening purposes and conducting epidemiological surveillance of NTDs in developing countries. This article is an overview of how DMSs can be used in the diagnosis of most neglected tropical diseases. [ABSTRACT FROM AUTHOR]

Background: The Gran Chaco ecoregion is a well-known hotspot of several neglected tropical diseases (NTDs) including Chagas disease, soil-transmitted helminthiasis and multiparasitic infections. Interspecific interactions between parasite species can modify host susceptibility, pathogenesis and transmissibility through immunomodulation. Our objective was to test the association between human co-infection with intestinal parasites and host parasitaemia, infectiousness to the vector and immunological profiles in Trypanosoma cruzi-seropositive individuals residing in an endemic region of the Argentine Chaco. Methods: We conducted a cross-sectional serological survey for T. cruzi infection along with an intestinal parasite survey in two adjacent rural villages. Each participant was tested for T. cruzi and Strongyloides stercoralis infection by serodiagnosis, and by coprological tests for intestinal parasite detection. Trypanosoma cruzi bloodstream parasite load was determined by quantitative PCR (qPCR), host infectiousness by artificial xenodiagnosis and serum human cytokine levels by flow cytometry. Results: The seroprevalence for T. cruzi was 16.1% and for S. stercoralis 11.5% (n = 87). We found 25.3% of patients with Enterobius vermicularis. The most frequent protozoan parasites were Blastocystis spp. (39.1%), Giardia lamblia (6.9%) and Cryptosporidium spp. (3.4%). Multiparasitism occurred in 36.8% of the examined patients. Co-infection ranged from 6.9% to 8.1% for T. cruzi-seropositive humans simultaneously infected with at least one protozoan or helminth species, respectively. The relative odds of being positive by qPCR or xenodiagnosis (i.e. infectious) of 28 T. cruzi-seropositive patients was eight times higher in people co-infected with at least one helminth species than in patients with no such co-infection. Trypanosoma cruzi parasite load and host infectiousness were positively associated with helminth co-infection in a multiple regression analysis. Interferon-gamma (IFN-γ) response, measured in relation to interleukin (IL)-4 among humans infected with T. cruzi only, was 1.5-fold higher than for T. cruzi-seropositive patients co-infected with helminths. The median concentration of IL-4 was significantly higher in T. cruzi-seropositive patients with a positive qPCR test than in qPCR-negative patients. Conclusions: Our results show a high level of multiparasitism and suggest that co-infection with intestinal helminths increased T. cruzi parasitaemia and upregulated the Th2-type response in the study patients. [ABSTRACT FROM AUTHOR]

The development of new treatments for neglected tropical diseases (NTDs) remains a major challenge in the 21st century. In most cases, the available drugs are obsolete and have limitations in terms of efficacy and safety. The situation becomes even more complex when considering the low number of new chemical entities (NCEs) currently in use in advanced clinical trials for most of these diseases. Natural products (NPs) are valuable sources of hits and lead compounds with privileged scaffolds for the discovery of new bioactive molecules. Considering the relevance of biodiversity for drug discovery, a chemoinformatics analysis was conducted on a compound dataset of NPs with anti-trypanosomatid activity reported in 497 research articles from 2019 to 2024. Structures corresponding to different metabolic classes were identified, including terpenoids, benzoic acids, benzenoids, steroids, alkaloids, phenylpropanoids, peptides, flavonoids, polyketides, lignans, cytochalasins, and naphthoquinones. This unique collection of NPs occupies regions of the chemical space with drug-like properties that are relevant to anti-trypanosomatid drug discovery. The gathered information greatly enhanced our understanding of biologically relevant chemical classes, structural features, and physicochemical properties. These results can be useful in guiding future medicinal chemistry efforts for the development of NP-inspired NCEs to treat NTDs caused by trypanosomatid parasites. [ABSTRACT FROM AUTHOR]

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. It bears a significant global health burden with limited treatment options, thus calling for the development of new and effective drugs. Certain trypanosomal metabolic enzymes have been suggested to be druggable and valid for subsequent inhibition. In this study, the crystal structure of glycerol kinase from T. cruzi, a key enzyme in glycerol metabolism in this parasite, is presented. Structural analysis allowed a detailed description of the glycerol binding pocket, while comparative assessment pinpointed a potential regulatory site which may serve as a target for selective inhibition. These findings advance the understanding of glycerol metabolism in eukaryotes and provide a solid basis for the future treatment of Chagas disease. [ABSTRACT FROM AUTHOR]

Purpose: Leishmaniasis, caused by the parasite of the genus Leishmania, is a neglected tropical disease which is endemic in more than 60 countries. In South-East Asia, Brazil, and East Africa, it mainly occurs as kala-azar (visceral leishmaniasis, VL), and subsequently as post kala-azar dermal leishmaniasis (PKDL) in a smaller portion of cases. As stated per WHO roadmap, accessibility to accurate diagnostic methods is an essential step to achieve elimination. This study aimed to test the accuracy of a portable minoo device, a small battery-driven, multi-use fluorimeter operating with isothermal technology for molecular diagnosis of VL and PKDL. Methods: Fluorescence data measured by the device within 20 min are reported back to the mobile application (or app) via Bluetooth and onward via the internet to a backend. This allows anonymous analysis and storage of the test data. The test result is immediately returned to the app displaying it to the user. Results: The limit of detection was 11.2 genome copies (95% CI) as determined by screening a tenfold dilution range of whole Leishmania donovani genomes using isothermal recombinase polymerase amplification (RPA). Pathogens considered for differential diagnosis were tested and no cross-reactivity was observed. For its diagnostic performance, DNA extracted from 170 VL and PKDL cases, comprising peripheral blood samples (VL, n = 96) and skin biopsies (PKDL, n = 74) from India (n = 108) and Bangladesh (n = 62), was screened. Clinical sensitivity and specificity were 88% and 91%, respectively. Conclusion: Minoo devices can offer a convenient, cheaper alternative to other molecular diagnostics. Its easy handling makes it ideal for use in low-resource settings to identify parasite burden. [ABSTRACT FROM AUTHOR]

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

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

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

Abstract Background The Gran Chaco ecoregion is a well-known hotspot of several neglected tropical diseases (NTDs) including Chagas disease, soil-transmitted helminthiasis and multiparasitic infections. Interspecific interactions between parasite species can modify host susceptibility, pathogenesis and transmissibility through immunomodulation. Our objective was to test the association between human co-infection with intestinal parasites and host parasitaemia, infectiousness to the vector and immunological profiles in Trypanosoma cruzi-seropositive individuals residing in an endemic region of the Argentine Chaco. Methods We conducted a cross-sectional serological survey for T. cruzi infection along with an intestinal parasite survey in two adjacent rural villages. Each participant was tested for T. cruzi and Strongyloides stercoralis infection by serodiagnosis, and by coprological tests for intestinal parasite detection. Trypanosoma cruzi bloodstream parasite load was determined by quantitative PCR (qPCR), host infectiousness by artificial xenodiagnosis and serum human cytokine levels by flow cytometry. Results The seroprevalence for T. cruzi was 16.1% and for S. stercoralis 11.5% (n = 87). We found 25.3% of patients with Enterobius vermicularis. The most frequent protozoan parasites were Blastocystis spp. (39.1%), Giardia lamblia (6.9%) and Cryptosporidium spp. (3.4%). Multiparasitism occurred in 36.8% of the examined patients. Co-infection ranged from 6.9% to 8.1% for T. cruzi-seropositive humans simultaneously infected with at least one protozoan or helminth species, respectively. The relative odds of being positive by qPCR or xenodiagnosis (i.e. infectious) of 28 T. cruzi-seropositive patients was eight times higher in people co-infected with at least one helminth species than in patients with no such co-infection. Trypanosoma cruzi parasite load and host infectiousness were positively associated with helminth co-infection in a multiple regression analysis. Interferon-gamma (IFN-γ) response, measured in relation to interleukin (IL)-4 among humans infected with T. cruzi only, was 1.5-fold higher than for T. cruzi-seropositive patients co-infected with helminths. The median concentration of IL-4 was significantly higher in T. cruzi-seropositive patients with a positive qPCR test than in qPCR-negative patients. Conclusions Our results show a high level of multiparasitism and suggest that co-infection with intestinal helminths increased T. cruzi parasitaemia and upregulated the Th2-type response in the study patients. Graphical Abstract

Abstract Background In recent years, the escalating concern for neglected tropical diseases (NTDs) has been recognized as a pressing global health issue. This concern is acutely manifested in low- and middle-income countries, where there is an escalating prevalence among adolescents and young adults. The burgeoning of these conditions threatens to impair patients' occupational capabilities and overall life quality. Despite the considerable global impact of NTDs, comprehensive studies focusing on their impact in younger populations remain scarce. Our study aims to describe the global prevalence of neglected tropical diseases among people aged 15 to 39 years over the 30-year period from 1990 to 2019, and to project the disease burden of the disease up to 2040. Methods Annual data on incident cases, mortality, and disability-adjusted life years (DALYs) for NTDs were procured from the Global Burden of Disease Study 2019 (GBD 2019). These data were stratified by global and regional distribution, country, social development index (SDI), age, and sex. We computed age-standardized rates (ASRs) and the numbers of incident cases, mortalities, and DALYs from 1990 to 2019. The estimated annual percentage change (EAPC) in the ASRs was calculated to evaluate evolving trends. Results In 2019, it was estimated that there were approximately 552 million NTD cases globally (95% Uncertainty Interval [UI]: 519.9 million to 586.3 million), a 29% decrease since 1990. South Asia reported the highest NTD prevalence, with an estimated 171.7 million cases (95% UI: 150.4 million to 198.6 million). Among the five SDI categories, the prevalence of NTDs was highest in the moderate and low SDI regions in 1990 (approximately 270.5 million cases) and 2019 (approximately 176.5 million cases). Sub-Saharan Africa recorded the most significant decline in NTD cases over the past three decades. Overall, there was a significant inverse correlation between the disease burden of NTDs and SDI. Conclusion NTDs imposed over half a billion incident cases and 10.8 million DALYs lost globally in 2019—exerting an immense toll rivaling major infectious and non-communicable diseases. Encouraging declines in prevalence and disability burdens over the past three decades spotlight the potential to accelerate progress through evidence-based allocation of resources. Such strategic integration could substantially enhance public awareness about risk factors and available treatment options.

Mycetoma, a neglected infection of subcutaneous tissues, poses a significant health burden, especially in tropical regions. It is caused by fungal (eumycetoma) and bacterial (actinomycetoma) pathogens, with current treatments often providing unsatisfactory outcomes. This study aims to discover novel broad-spectrum antimicrobial agents to circumvent the lengthy and costly diagnostic procedures. Eight essential oils (EOs) from the roots and aerial parts of Geigeria alata, Lavandula angustifolia, Melaleuca alternifolia, Myristica fragrans, Pimpinella anisum, Syzigum aromaticum, and Thymus vulgaris were prepared using steam distillation. The in vitro antimycetomal activity against Madurella mycetomatis and Actinomadura madurae strains was assessed using resazurin assays. The chemical compositions of the EOs were analyzed using gas chromatography and mass spectrometry (GC–MS). Promising EOs underwent further in vivo toxicity and efficacy testing in Galleria mellonella larvae models. EOs of G. alata roots, M. fragrans, P. anisum, S. aromaticum, and T. vulgaris showed wide-spectrum dual in vitro antimycetomal activity against all tested strains, with minimum inhibitory concentrations (MICs) ranging from 0.004 to 0.125% v/v. G. alata aerial parts and L. angustifolia EOs demonstrated activity predominantly against A. madurae, while M. alternifolia EO did not inhibit any tested strains. M. fragrans and P. anisum EOs significantly enhanced the survival of M. mycetomatis-infected larvae without inducing toxicity in uninfected larvae. Notably, P. anisum EO tended to enhance the survival of A. madurae-infected larvae, ranking it as the most promising EO among those tested. The investigated EOs, particularly P. anisum, exhibited promising broad-spectrum antimycetomal activity against fungal and bacterial pathogens responsible for mycetoma. These findings highlight the potential of essential oils as a basis for developing novel antimycetomal agents, offering hope for improved treatment strategies for this neglected disease.

Abstract Background This study investigates the impact of the COVID-19 pandemic on the prevalence, management, and control of the neglected tropical diseases (NTDs) highlighting the current or prospective impact of COVID-19 on research and development funding for, and execution of, NTD programmes. This review was conducted to determine if, and how, NTDs were affected by COVID-19, and whether those effects will delay the elimination goals of the Sustainable Development goals. Methods Using open-source available data from policy and documentation from official websites of the relevant stakeholders including but not limited to World Health Organization (WHO) documents and policies, government foreign aid documents, and the Policy Cures G-Finder reports, this scoping review explored ongoing challenges to supporting research and development (R&D) for the NTDs and in maintaining NTD control programs; examined the constraints posed for NTD management by the pandemic from disruptions to healthcare services, reduction of finance and explored the potential long-term implications and consequences for those poorer, neglected populations in low and middle income-countries (LMICs). This was done by a scoping review literature search, publications were subject to an initial practical screening step to ensure the most relevant publications were selected for full screening, with the focus on scoping the designated topic of the impact of COVID-19 on NTDs. We further undertook an evaluation of the socio-economic factors exacerbating the impact of COVID-19 on NTD burden. Results Multiple disruptions and setbacks, likely to affect NTD programmes and progress towards their elimination targets were identified in this study. R&D funding for the NTDs and AIDs and TB has declined since the funding high point of 2019, and for malaria since the high point of 2018. Significant changes in allocation of R&D funding within the NTDs are observed post pandemic, likely because of prioritization among donors. Diseases for which the least R&D investment was reported in place, prior to the pandemic (mycetoma, taeniasis/cysticercosis, trachoma and Buruli ulcer) have been particularly impacted post pandemic. We identified specific NTDs including schistosomiasis, leprosy, and rabies that have been affected by the COVID-19 pandemic and disruptions caused to on ongoing NTD control and elimination programs. Pandemic restrictions disrupted essential medical supply manufacturing and distribution impacting immunization programs and hindered efforts to control the spread of infectious diseases. NTD programmes have experienced numerous setbacks including delays in mass drug administration programs (e.g. for schistosomiasis), cancelled or delayed vaccination programs (e.g. for rabies) and closure of testing facilities has resulted in reduced diagnosis, treatment, and disease elimination for all NTDs. Lockdowns and clinic closures causing disruption to essential healthcare services restricted NTD surveillance and treatment programs. Community fears around contracting COVID-19 exacerbated the constraints to service delivery. Disparities in global vaccine distribution have widened with LMICs facing limited access to vaccines and disruption to immunization programs. Finally, the pandemic has led to increased poverty with poor and marginalized communities, impacting nutrition, healthcare access and education all of which have long term implications for NTD management and control. Conclusions The COVID-19 pandemic profoundly impacted global health research and global health equity. Attention and funding were diverted from all sectors, significantly affecting research and development efforts set out in the World Health Organization’s NTD elimination Roadmaps. Ongoing changes to funding, economic crises, logistics and supply chain disruptions as well as deepening poverty has put a strain on already weak healthcare systems and exacerbated LMIC healthcare challenges. In particular, the delays and constraints to NTD management and elimination programs will have long-reaching consequences highlighting the need for global cooperation and renewed investment to put the NTD roadmap back on track. Targets and milestones are unlikely to be met without significant investment for recovery, in place. Graphical Abstract

Abstract Background The burden of neglected tropical diseases (NTDs), HIV/AIDS, tuberculosis, and malaria pose significant public health challenges in Ethiopia. This study aimed to the explore service availability and readiness for NTD care among Ethiopian health facilities treating tuberculosis (TB), HIV/AIDS, and/or malaria. Methods This study utilized secondary data from the Ethiopian Service Provision Assessment 2021–22 survey. The availability of services was calculated as the percentage of HIV/AIDS, tuberculosis, or malaria facilities providing NTD services. Facilities were considered highly prepared to manage any type of NTD if they scored at least half (> 50%) of the tracer items listed in each of the three domains (staff training and guidelines, equipment, and essential medicines). Descriptive statistics and logistic regression models were employed to present the study findings and analyze factors influencing facility readiness, respectively. Results Out of 403 health facilities providing NTD care nationally, 179, 183, and 197 also offer TB, HIV/AIDS, and malaria services, respectively. The majority of TB (90.1%), HIV/AIDS (89.6%), and malaria (90.9%) facilities offer soil-transmitted helminth services, followed by trachoma (range 87–90%). The percentages of the aforementioned facilities with at least one trained staff member for any type of NTD were 87.2%, 88.4%, and 82.1%, respectively. The percentage of facilities with guidelines for any type of NTD was relatively low (range 3.7–4.1%). Mebendazole was the most widely available essential medicine, ranging from 69 to 70%. The overall readiness analysis indicated that none of the included facilities (TB = 11.9%; HIV/AIDS = 11.6%; and malaria = 10.6%) were ready to offer NTD care. Specifically, a higher level of readiness was observed only in the domain of medicines across these facilities. Hospitals had better readiness to offer NTD care than did health centers and clinics. Furthermore, a significant associations were observed between facility readiness and factors such as facility type, region, presence of routine management meetings, types of NTD services provided, and fixed costs for services. Conclusions Ethiopian health facilities treating TB, HIV/AIDS, and malaria had an unsatisfactory overall service availability and a lack of readiness to provide NTD care. Given the existing epidemiological risks and high burden of TB, HIV/AIDS, malaria, and NTDs in Ethiopia, there is an urgent need to consider preparing and implementing a collaborative infectious disease care plan to integrate NTD services in these facilities.

Abstract Background Currently, European and especially Italian healthcare systems are being challenged with providing medical care to an increasing number of refugees but also to the homeless living on the streets, in reception facilities or cohabitation. In 2022, over 200,000 irregular arrivals of migrants to Europe were recorded, coming from mainly African and also Asian countries and frequently via Mediterranean migration routes. Objectives This study aims to report the results of a social support programme to provide treatment and improve health‐related quality of life (HrQoL) in refugees and homeless people. Methods Observational study during the year 2022, including patients with an immigration background visiting the Clinica dell'Istituto di S. Maria e S. Gallicano di Roma, Italy (IRCCS), or being homeless during this observational study. Results We have seen 210 patients. In 177 cases (84.3%), a definitive diagnosis is known. Most frequent skin conditions were infectious, allergic or due to secondary inflammation. We also saw rare cutaneous conditions like Madelung disease or Darier disease. Conclusions We provided dermatological consultation and treatment to this very vulnerable population, and our experience shows that this social support programme to enable access to dermatological consultation for the poor was able to improve not only the clinical condition but also the HrQoL 4 weeks after consultation and beginning of treatment.

Abstract Cutaneous leishmaniasis (CL), a neglected tropical disease (NTD), is a major public health problem in Yemen with widespread distribution in rural areas. Evaluating the knowledge and understanding of people’s beliefs towards the disease is essential to the implementation of effective control measures. This study aims to assess the knowledge, attitudes, practices (KAP) and treatment-seeking behaviour concerning CL among rural populations in the western highlands of Yemen. A community-based cross-sectional study was conducted among 289 household heads in four rural areas of the Utmah District. Data were collected using a pre-tested questionnaire. All the participants had heard about the disease; however, only 9.3% attributed it to sandflies. Nearly half (48.1%) of the participants could not mention any preventive measures for CL, and nearly two-thirds (65.4%) could not do so for sandflies. The overall ‘good’ knowledge about CL was found to be 51.2%, and it was 33.9% for sandflies. The participants’ attitude and prevention practices towards CL were not satisfactory, as only 38.1% and 16.3% had a positive attitude and good CL-related prevention practices, respectively. Moreover, 45.7% believed CL to be a stigmatising disease, and 50% had used traditional remedies to treat suspected CL lesions. Multivariate analyses showed that age, sex, presence of CL-confirmed cases in the same household, residency, occupation and monthly household income were the significant predictors associated with KAP concerning CL among the participants. The findings support an urgent need for integrated health education and community mobilisation interventions to improve awareness of these vulnerable populations about this devastating disease.

Abstract Background Neglected tropical diseases (NTDs) such as leprosy, lymphatic filariasis (LF), schistosomiasis and onchocerciasis are endemic in several African countries. These diseases can lead to severe pain and permanent disability, which can negatively affect the economic productivity of the affected person(s), and hence resulting into low economic performance at the macrolevel. Nonetheless, empirical evidence of the effects of these NTDs on economic performance at the macrolevel is sparse. This study therefore investigates the effects of the above-mentioned NTDs on economic performance at the macrolevel in Africa. Methods The study employs a panel design with data comprising 24 to 45 African countries depending on the NTD in question, over the period, 2002 to 2019. Gross domestic product (GDP) is used as the proxy for economic performance (Dependent variable) and the prevalence of the above-mentioned NTDs are used as the main independent variables. The random effects (RE), fixed effects (FE) and the instrumental variable fixed effects (IVFE) panel data regressions are used as estimation techniques. Results We find that, an increase in the prevalence of the selected NTDs is associated with a fall in economic performance in the selected African countries, irrespective of the estimation technique used. Specifically, using the IVFE regression estimates, we find that a percentage increase in the prevalence of leprosy, LF, schistosomiasis and onchocerciasis is associated with a reduction in economic performance by 0.43%, 0.24%, 0.28% and 0.36% respectively, at either 1% or 5% level of significance. Conclusion The findings highlight the need to increase attention and bolster integrated efforts or measures towards tackling these diseases in order to curb their deleterious effects on economic performance. Such measures can include effective mass drug administration (MDA), enhancing access to basic drinking water and sanitation among others.

Background: This study investigates the impact of the COVID-19 pandemic on the prevalence, management, and control of the neglected tropical diseases (NTDs) highlighting the current or prospective impact of COVID-19 on research and development funding for, and execution of, NTD programmes. This review was conducted to determine if, and how, NTDs were affected by COVID-19, and whether those effects will delay the elimination goals of the Sustainable Development goals. Methods: Using open-source available data from policy and documentation from official websites of the relevant stakeholders including but not limited to World Health Organization (WHO) documents and policies, government foreign aid documents, and the Policy Cures G-Finder reports, this scoping review explored ongoing challenges to supporting research and development (R&D) for the NTDs and in maintaining NTD control programs; examined the constraints posed for NTD management by the pandemic from disruptions to healthcare services, reduction of finance and explored the potential long-term implications and consequences for those poorer, neglected populations in low and middle income-countries (LMICs). This was done by a scoping review literature search, publications were subject to an initial practical screening step to ensure the most relevant publications were selected for full screening, with the focus on scoping the designated topic of the impact of COVID-19 on NTDs. We further undertook an evaluation of the socio-economic factors exacerbating the impact of COVID-19 on NTD burden. Results: Multiple disruptions and setbacks, likely to affect NTD programmes and progress towards their elimination targets were identified in this study. R&D funding for the NTDs and AIDs and TB has declined since the funding high point of 2019, and for malaria since the high point of 2018. Significant changes in allocation of R&D funding within the NTDs are observed post pandemic, likely because of prioritization among donors. Diseases for which the least R&D investment was reported in place, prior to the pandemic (mycetoma, taeniasis/cysticercosis, trachoma and Buruli ulcer) have been particularly impacted post pandemic. We identified specific NTDs including schistosomiasis, leprosy, and rabies that have been affected by the COVID-19 pandemic and disruptions caused to on ongoing NTD control and elimination programs. Pandemic restrictions disrupted essential medical supply manufacturing and distribution impacting immunization programs and hindered efforts to control the spread of infectious diseases. NTD programmes have experienced numerous setbacks including delays in mass drug administration programs (e.g. for schistosomiasis), cancelled or delayed vaccination programs (e.g. for rabies) and closure of testing facilities has resulted in reduced diagnosis, treatment, and disease elimination for all NTDs. Lockdowns and clinic closures causing disruption to essential healthcare services restricted NTD surveillance and treatment programs. Community fears around contracting COVID-19 exacerbated the constraints to service delivery. Disparities in global vaccine distribution have widened with LMICs facing limited access to vaccines and disruption to immunization programs. Finally, the pandemic has led to increased poverty with poor and marginalized communities, impacting nutrition, healthcare access and education all of which have long term implications for NTD management and control. Conclusions: The COVID-19 pandemic profoundly impacted global health research and global health equity. Attention and funding were diverted from all sectors, significantly affecting research and development efforts set out in the World Health Organization's NTD elimination Roadmaps. Ongoing changes to funding, economic crises, logistics and supply chain disruptions as well as deepening poverty has put a strain on already weak healthcare systems and exacerbated LMIC healthcare challenges. In particular, the delays and constraints to NTD management and elimination programs will have long-reaching consequences highlighting the need for global cooperation and renewed investment to put the NTD roadmap back on track. Targets and milestones are unlikely to be met without significant investment for recovery, in place. [ABSTRACT FROM AUTHOR]

This article explores the field of immunology and its connection to inborn errors of immunity (IEI) and protozoa. IEI refers to a range of diseases caused by genetic defects that affect the immune system, making individuals more susceptible to infections. The article emphasizes the need to understand the characteristics of the disease and the infective agent to identify compromised immune mechanisms. It also discusses the global health challenges posed by neglected tropical diseases (NTDs) and their impact on marginalized populations. The article presents a case study of a child with an inborn error of immunity and unusual infections, highlighting the need for innovative diagnostic assays and treatment protocols. The case underscores the importance of collaboration among immunologists in Brazil to enhance diagnostic capabilities and improve patient care for uncommon infections. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Human mycoses cover a diverse field of fungal diseases from skin disorders to systemic invasive infections and pose an increasing global health problem based on ineffective treatment options, the hampered development of new efficient drugs, and the emergence of resistant fungal strains. Niclosamide is currently applied for the treatment of worm infections. Its mechanisms of action, which include the suppression of mitochondrial oxidative phosphorylation (also known as mitochondrial uncoupling), among others, has led to a repurposing of this promising anthelmintic drug for the therapy of further human diseases such as cancer, diabetes, and microbial infections. Given the urgent need to develop new drugs against fungal infections, the considerable antifungal properties of niclosamide are highlighted in this review. Its chemical and pharmacological properties relevant for drug development are also briefly mentioned, and the described mitochondria-targeting mechanisms of action add to the current arsenal of approved antifungal drugs. In addition, the activities of further salicylanilide-based niclosamide analogs against fungal pathogens, including agents applied in veterinary medicine for many years, are described and discussed for their feasibility as new antifungals for humans. Preliminary structure–activity relationships are determined and discussed. Various salicylanilide derivatives with antifungal activities showed increased oral bioavailabilities when compared with niclosamide. The simple synthesis of salicylanilide-based drugs also vouchsafes a broad and cost-effective availability for poorer patient groups. Pertinent literature is covered until 2024. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a neglected tropical disease and an important parasite negatively impacting socio-economic factors. Ethiopia's Federal Ministry of Health targeted the elimination of schistosomiasis infection in school-aged children by 2020. However, Schistosoma mansoni still affects approximately 12.3 million school-aged children in Ethiopia. Although the study was conducted in some regions of the country, previous studies were conducted on urban school children and were limited to the burden of infection. Overall, there is a lack of information about schistosomiasis in eastern Ethiopia, particularly among school children. Therefore, this study aimed to assess the prevalence and factors associated with Schistosoma mansoni infection among primary school children in Kersa district, Eastern Ethiopia. Methods: A cross-sectional study was conducted among 419 school children using systematic random sampling from April 10 to May 09, 2019. The stool samples were collected and examined using the Keto-Katz method. A structured and pretested questionnaire was used to collect data from participants. Data were entered using Epi-Data version 3.1 and analysed using SPSS version 24. A bivariable and multivariable logistic regression analyses were used to identify factors associated with Schistosoma mansoni infection. P-value < 0.05 and adjusted odds ratio (AOR) (95% confidence interval (CI)) were used to identify statistically significant associations. Results: This study's overall prevalence of S. mansoni was 19.4% (95% CI [16–23]). Absence of the latrines in household (AOR = 2.35, 95% CI [1.25–4.38]), swimming in the river (AOR = 2.82, 95% CI [1.33–5.88]), unprotected water sources (AOR = 3.5, 95% CI [1.72–7.10]), irregular shoe wearing habits (AOR = 2.81, 95% CI [1.51–5.23]), and water contact during cross of river (AOR = 2.192; 95% CI [1.113–4.318]) were factors independently associated with S. mansoni infection. Conclusion: Schistosoma mansoni infection remains a public health problem in the study area. Using a latrine in each household, using protected water, wearing shoes regularly, and reducing water contact were necessary to control Schistosoma mansoni infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Great progress is being made toward the goal of elimination as a public health problem for neglected tropical diseases such as leprosy, human African trypanosomiasis, Buruli ulcer, and visceral leishmaniasis, which relies on intensified disease management and case finding. However, strategies for maintaining this goal are still under discussion. Passive surveillance is a core pillar of a long-term, sustainable surveillance program. Methods We use a generic model of disease transmission with slow epidemic growth rates and cases detected through severe symptoms and passive detection to evaluate under what circumstances passive detection alone can keep transmission under control. Results Reducing the period of infectiousness due to decreasing time to treatment has a small effect on reducing transmission. Therefore, to prevent resurgence, passive surveillance needs to be very efficient. For some diseases, the treatment time and level of passive detection needed to prevent resurgence is unlikely to be obtainable. Conclusions The success of a passive surveillance program crucially depends on what proportion of cases are detected, how much of their infectious period is reduced, and the underlying reproduction number of the disease. Modeling suggests that relying on passive detection alone is unlikely to be enough to maintain elimination goals. [ABSTRACT FROM AUTHOR]

The World Health Organization roadmap for neglected tropical diseases (NTDs) sets out ambitious targets for disease control and elimination by 2030, including 90% fewer people requiring interventions against NTDs and the elimination of at least 1 NTD in 100 countries. Mathematical models are an important tool for understanding NTD dynamics, optimizing interventions, assessing the efficacy of new tools, and estimating the economic costs associated with control programs. As NTD control shifts to increased country ownership and programs progress toward disease elimination, tailored models that better incorporate local context and can help to address questions that are important for decision-making at the national level are gaining importance. In this introduction to the supplement, New Tools and Nuanced Interventions to Accelerate Achievement of the 2030 Roadmap for Neglected Tropical Diseases, we discuss current challenges in generating more locally relevant models and summarize how the articles in this supplement present novel ways in which NTD modeling can help to accelerate achievement and sustainability of the 2030 targets. [ABSTRACT FROM AUTHOR]

Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The venom of African spitting cobras often causes permanent injury via tissue-destructive dermonecrosis at the bite site, which is ineffectively treated by current antivenoms. To address this therapeutic gap, we identified the etiological venom toxins in Naja nigricollis venom responsible for causing local dermonecrosis. While cytotoxic three-finger toxins were primarily responsible for causing spitting cobra cytotoxicity in cultured keratinocytes, their potentiation by phospholipases A2 toxins was essential to cause dermonecrosis in vivo. This evidence of probable toxin synergism suggests that a single toxin-family inhibiting drug could prevent local envenoming. We show that local injection with the repurposed phospholipase A2-inhibiting drug varespladib significantly prevents local tissue damage caused by several spitting cobra venoms in murine models of envenoming. Our findings therefore provide a therapeutic strategy that may effectively prevent life-changing morbidity caused by snakebite in rural Africa. [ABSTRACT FROM AUTHOR]

Background: Neglected tropical diseases (NTDs) such as leprosy, lymphatic filariasis (LF), schistosomiasis and onchocerciasis are endemic in several African countries. These diseases can lead to severe pain and permanent disability, which can negatively affect the economic productivity of the affected person(s), and hence resulting into low economic performance at the macrolevel. Nonetheless, empirical evidence of the effects of these NTDs on economic performance at the macrolevel is sparse. This study therefore investigates the effects of the above-mentioned NTDs on economic performance at the macrolevel in Africa. Methods: The study employs a panel design with data comprising 24 to 45 African countries depending on the NTD in question, over the period, 2002 to 2019. Gross domestic product (GDP) is used as the proxy for economic performance (Dependent variable) and the prevalence of the above-mentioned NTDs are used as the main independent variables. The random effects (RE), fixed effects (FE) and the instrumental variable fixed effects (IVFE) panel data regressions are used as estimation techniques. Results: We find that, an increase in the prevalence of the selected NTDs is associated with a fall in economic performance in the selected African countries, irrespective of the estimation technique used. Specifically, using the IVFE regression estimates, we find that a percentage increase in the prevalence of leprosy, LF, schistosomiasis and onchocerciasis is associated with a reduction in economic performance by 0.43%, 0.24%, 0.28% and 0.36% respectively, at either 1% or 5% level of significance. Conclusion: The findings highlight the need to increase attention and bolster integrated efforts or measures towards tackling these diseases in order to curb their deleterious effects on economic performance. Such measures can include effective mass drug administration (MDA), enhancing access to basic drinking water and sanitation among others. [ABSTRACT FROM AUTHOR]

Background Access to affordable, quality healthcare is the key element of universal health coverage (UHC). This study examines the effectiveness of the neglected tropical disease (NTD) mass drug administration (MDA) campaign approach as a means to deliver UHC, using the example of the Liberia national programme. Methods We first mapped the location of 3195 communities from the 2019 national MDA treatment data reporting record of Liberia. The association between coverage for onchocerciasis and lymphatic filariasis treatment achieved in these communities was then explored using a binomial geo-additive model. This model employed three key determinants for community 'remoteness': population density and the modelled travel time of communities to their supporting health facility and to their nearest major settlement. Results Maps produced highlight a small number of clusters of low treatment coverage in Liberia. Statistical analysis suggests there is a complex relationship between treatment coverage and geographic location. Conclusions We accept the MDA campaign approach is a valid mechanism to reach geographically marginal communities and, as such, has the potential to deliver UHC. We recognise there are specific limitations requiring further study. [ABSTRACT FROM AUTHOR]

Background The mainstay of soil-transmitted helminth (STH) control is repeated mass drug administration (MDA) of anthelmintics to endemic populations. Individual longitudinal compliance treatment patterns are important for identifying pockets of infected individuals who remain untreated and serve as infection reservoirs. Methods The Geshiyaro Project censused the study population in Wolaita, Ethiopia at baseline in 2018. Individual longitudinal compliance was recorded for six rounds of community-wide MDA (cMDA). The probability distribution of treatment frequency was analysed by age and gender stratifications. Probabilities of transmission interruption for different compliance patterns were calculated using an individual-based stochastic model of Ascaris lumbricoides transmission. Results The never-treated (0.42%) population was smaller than expected from a random positive binomial distribution. The observed compliance frequency was well described by the beta-binomial distribution. Preschool-age children (odds ratio [OR] 10.1 [95% confidence interval {CI} 6.63 to 15.4]) had the highest never-treated proportion of the age groups. Conversely, school-age children (SAC) and adults (OR 1.03 [95% CI 0.98 to 1.09]) had the highest always-treated proportion of the age groups. Conclusions The study reports the largest dataset of individual longitudinal compliance to cMDA for STH control. Clear pattens are shown in the age-dependent distribution of individual compliance behaviour. The impact of compliance on the probability of elimination is significant, highlighting the importance of recording the full frequency distribution, not just the never-treated proportion. [ABSTRACT FROM AUTHOR]

Summary: Background: Fiji has among the highest global reported prevalence of scabies. Mass drug administration (MDA) has been identified as a potentially effective strategy to control scabies, but acceptability of MDA from the perspectives of people receiving and delivering scabies MDA programs remains underexplored in Fiji and globally. Methods: A qualitative study was conducted after completion of the national MDA campaign. Participants included 44 community members and 12 key informants across the Central and Western Divisions of Fiji. Semi-structured face-to-face and virtual interviews were conducted in August and September 2023. An interpretive research approach was adopted, and data were analysed using deductive and inductive techniques. Findings: We identified several barriers and facilitators to scabies MDA acceptability. Facilitators included prior experiences of scabies and knowledge of the potential health benefit of MDA, community attitudes to MDA and neighbours’ adherence practices, endorsement of MDA by community leaders, community consultation and exposure to community sensitisation, and involvement of local key informants during planning and implementation. Barriers included a lack of trust in MDA campaigns, religious beliefs, limited reach of community sensitisation, and challenges to implementing MDA in urban locations. Interpretation: This is the first qualitative study documenting acceptability of a nationwide scabies-MDA globally. It identified diverse socio-structural factors that influenced MDA implementation and acceptability. Future MDA programs could benefit from widespread community sensitisation, tailored approaches to urban and rural MDA design and delivery, and the inclusion of communities in the co-design and implementation of MDA programs. Funding: The National Health and Medical Research Council (NHMRC) investigator grant—LR and the Macquarie Group Foundation 50th Celebration Awards–AS.

he Neglected Tropical Diseases (NTDs) are the most common infections of poor people in developing countries, where they cause severe and permanent disabilities and a high disease burden. The stigma associated with disfiguring NTDs such as Buruli ulcer, leprosy, onchocerciasis, lymphatic filariasis and cutaneous leishmaniasis, have important psycho-social effects in affected communities and has only been partly analyzed in the literature. Objective: The present article will review literature on stigma associated with cutaneous NTDs, explore the public health implications of stigma, and suggest a comprehensive approach to this cluster of diseases. Methodology/Principal findings: A literature review was done using the following datasets: PUBMED, Google Scholar, SCIELO, LILACS, and MEDLINE. Furthermore, a web search was conducted on the WHO website. Eighty three articles were found on our topic of interest. Eighty of them were related to cutaneous disfiguring NTDs; twenty had a qualitative approach. Our findings show that stigma is associated with all five cutaneous NTDs and causes remarkable psychological and public health consequences. Gender differences with regard to stigma are also considered. Conclusions: Stigma associated with disfiguring NTDs has been shown to be a major factor influencing access to health services and treatment adherence. If effective programs are to be successfully implemented, appropriate interventions are needed to prevent stigma and eliminate its negative effects. Although lymphatic filariasis and leprosy tend to show a broader research coverage of socio-cultural and psychological aspects of the disease, further research on other cutaneous stigmatizing neglected tropical is urgently needed. The literature suggests that stigma should be addressed in joint interventions rather than one disease at a time.

BackgroundFemale genital schistosomiasis (FGS) is among the most neglected of tropical diseases. FGS remains underreported, under and misdiagnosed and mostly untreated. This neglected epidemic disproportionately affects communities already burdened by HIV and cervical cancer. The study aims to assess FGS knowledge, attitude, and practices and associated factors in communities in the Shai-Osudoku District of Ghana.MethodThe study employed an analytical cross-sectional design, utilizing quantitative methods for data collection from 161 community members. Analysis was conducted using STATA 18, included both descriptive statistics and simple logistic regression.ResultsAbout half (50.31%) of the respondents demonstrated poor knowledge of FGS. Furthermore, 65.84% of the respondents exhibited a poor attitude towards FGS, Poor practice related to FGS were also observed in 60.25% of the respondents. Regression analysis showed significant associations between various factors and knowledge, attitudes, and practices regarding FGS. Specifically, married women were found to have 54% lower odds of possessing good knowledge about FGS compared single women. (AOR=0.46, 95%CI= 0.22-0.94). Respondents with poor socioeconomic status displayed 76% higher odds of engaging in good practices compared to respondents those in the poorest socioeconomic status. (AOR=0.24, 95%CI=0.06-0.96).ConclusionComprehensive, context-specific interventions are necessary to address the multifaceted challenges associated with FGS. Targeted education and awareness campaigns are crucial to improve understanding of FGS, and addressing socio-economic factors that influence attitudes and practices related to the disease is essential.

Schistosomiasis, caused by flatworm parasites, is a widespread disease resulting in chronic illness and fatalities globally. Given the risk of drug resistance and limited treatment options, finding new therapeutic options are crucial for managing and controlling this neglected tropical disease. In this research, various in-silico methods including Density-Functional-Theory (DFT) computations, Molecular-docking, molecular dynamics simulations and Pharmacokinetic evaluation were employed to identify ten potential inhibitors of Schistosoma mansoni HDAC8 (SmHDAC8). The modeled activities (pIC50) of these newly designed compounds (ranging between 7.110 and 6.959) surpassed that of the hit compound 19 (pIC50 = 6.445) and the standard reference control, Praziquantel (pIC50 = 5.989). Moreover, the MolDock scores (ranging between −188.964 and −158.351 kcal/mol) for these proposed compounds in the SmHDAC8 binding cavity outperformed the hit template 19 (MolDock score: −122.516 kcal/mol) and the Praziquantel (−110.245 kcal/mol). Furthermore, the conformational stability of the top three designed compounds (19a, 19i, and 19j) in the SmHDAC8 binding cavity was examined through a 100 ns of Molecular Dynamics simulation. Additionally, the drug-likeness and ADMET predictions of these compounds indicated favorable oral bioavailability and pharmacokinetic profiles. This study offers a reliable in-silico approach for identifying potential agents against Schistosomiasis.

IntroductionIn recent years, Europe has experienced a significant flux of migrants, often hailing from regions endemic for schistosomiasis and strongyloidiasis, diseases frequently overshadowed by tuberculosis (TB) in healthcare priorities. While TB remains a prevalent concern among this population, chronic schistosomiasis and strongyloidiasis are frequently neglected. Motivated by this observation, we aimed to investigate the prevalence of schistosomiasis and strongyloidiasis in patients attending our TB outpatient clinic.MethodsWe conducted a retrospective, observational study spanning from June 2020 to January 2024, focusing on patients attending the TB outpatient clinic of Luigi Sacco Hospital of Milan, Italy. Serology tests were performed in patients with a history suggestive of exposure to either Schistosoma spp. or Strongyloides stercoralis.ResultsAmong the 228 patients included in the study, 84 (36.8%) individuals were born in Italy, one came from Spain, 80 (35.1%) from strongyloidiasis moderate or high endemic countries and 63 (27.6%) from areas endemic for schistosomiasis and strongyloidiasis. Of these patients, 160 (70.2%) were diagnosed with tuberculosis disease, while 68 (29.8%) had tuberculosis infection. The prevalence of schistosomiasis was 26.7%, while that of strongyloidiasis was 7.8%. Notably, 3 patients tested positive for both infections.ConclusionOur study highlights the often-underestimated prevalence of schistosomiasis and strongyloidiasis among migrants accessing healthcare for TB, underscoring the importance of increased awareness and targeted screening within this population.

Leishmaniasis, a vector-borne disease, is caused by the infection of Leishmania spp., obligate intracellular protozoan parasites. Presently, human vaccines are unavailable, and the primary treatment relies heavily on systemic drugs, often presenting with suboptimal formulations and substantial toxicity, making new drugs a high priority for LMIC countries burdened by the disease, but a low priority in the agenda of most pharmaceutical companies due to unattractive profit margins. New ways to accelerate the discovery of new, or the repositioning of existing drugs, are needed. To address this challenge, our study aimed to identify potential protein targets shared among clinically-relevant Leishmania species. We employed a subtractive proteomics and comparative genomics approach, integrating high-throughput multi-omics data to classify these targets based on different druggability metrics. This effort resulted in the ranking of 6502 ortholog groups of protein targets across 14 pathogenic Leishmania species. Among the top 20 highly ranked groups, metabolic processes known to be attractive drug targets, including the ubiquitination pathway, aminoacyl-tRNA synthetases, and purine synthesis, were rediscovered. Additionally, we unveiled novel promising targets such as the nicotinate phosphoribosyltransferase enzyme and dihydrolipoamide succinyltransferases. These groups exhibited appealing druggability features, including less than 40% sequence identity to the human host proteome, predicted essentiality, structural classification as highly druggable or druggable, and expression levels above the 50th percentile in the amastigote form. The resources presented in this work also represent a comprehensive collection of integrated data regarding trypanosomatid biology.