Assessing the Integration of Skin Screening into a Mass Drug Administration Campaign against Neglected Tropical Diseases: A Cross-sectional Observational Study from two Districts in Côte d'Ivoire, 2023.

BACKGROUND: The World Health Organization advocates integrating neglected tropical diseases (NTDs) into common delivery platforms to combat them in resource-constrained settings. However, limited literature exists on the benefits of integration. This study examines the feasibility and impact of adding skin screening to a mass drug administration (MDA) campaign in Côte d'Ivoire. METHODS: In June 2023, the Ministry of Health and Public Hygiene of Côte d'Ivoire piloted screening for skin-related NTDs alongside a national MDA campaign targeting soil-transmitted helminthiases and schistosomiasis. Two districts, Fresco and Koro, were selected for the pilot. The study applied both quantitative and qualitative assessments. The quantitative aspect focused on campaign costs and outputs, using an ingredient approach for costing. The qualitative evaluation employed an empirical phenomenological approach to analyze the campaign's operational feasibility and appreciation by stakeholders. FINDINGS: MDA activities cost $ 0·66 per treated child and skin screening $ 0·62 per screened person, including medical products. The MDA campaign exceeded coverage targets in both districts, whereas skin screening coverage varied by locality and age group. Both the service delivery team and the beneficiaries expressed appreciation for the integrated campaign. However, opportunities for improvement were identified. CONCLUSION: Integrating MDA and skin NTD screening proved operationally feasible in this context but had not recorded cost-saving effects. The performance of the MDA campaign was not negatively affected by additional skin screening activities, but effective integration requires thorough joint planning, strengthened training, and proper supervision.

Bioassay-guided isolation of leishmanicidal cucurbitacins from Momordica charantia.

Introduction: Leishmaniasis, a neglected tropical parasitic disease, is regarded as a major public health problem worldwide. The first-line drugs for leishmaniasis suffer from limitations related to toxicity and the development of resistance in certain parasitic strains. Therefore, the discovery of alternative treatments for leishmaniasis is imperative, and natural products represent a valuable source of potential therapeutic agents. Methods: The present study aimed at finding new potential antileishmanial agents from the aerial parts of the medicinal plant Momordica charantia. This study was based on bioassay-guided fractionation of the M. charantia extract against promastigotes and amastigotes of Leishmania (Leishmania) amazonensis. The cytotoxicity of the extract, fractions, and isolated compounds were evaluated against peritoneal murine macrophages by employing the MTT assay for assessing cell metabolic activity. Results: Antileishmanial assay-guided fractionation of the M. charantia extract led to the bioactive cucurbitacin-enriched fraction and the isolation of four bioactive cucurbitacin-type triterpenoids, which exhibited significant antileishmanial activity, with IC50 values between 2.11 and 3.25 µg.mL-1 against promastigote and amastigote forms, low toxicity and selectivity indexes ranging from 8.5 to 17.2. Conclusion: Our findings demonstrate that the fractions and cucurbitacin-type triterpenoids obtained from the aerial parts of M. charantia are promising natural leishmanicidal candidates.

Noma in the WHO's list of neglected tropical diseases: A review of its impact on undeveloped and developing tropical regions.

Background: Noma is a neglected tropical disease and a global health concern. Objectives: To elucidate the epidemiology, management, prevention, and public health implications of Noma. Methods: PubMed, Scopus, and Web of Science, supplemented by Google Scholar and World Health Organization databases, were searched using keywords to gather both published and grey literature from 1970 to 2023 in English. Results: Approximately 30,000-40,000 cases occur annually, with varying incidences across various African countries, such as Nigeria, Niger, and Chad. Incidence in Nigerian and Ethiopian states range from 0.6 to 3300 and 1.64 to 13.4 per 100,000 population, respectively. Mortality is approximately 8.5% in Niger. Risk factors include malnutrition, immunocompromised status, poor dental hygiene, inadequate sanitation, gingival lesions, low socioeconomic status, chronic and infectious diseases, low birth weight, high parity, diarrhoea, and fever. Diagnosis is primarily made based on clinical signs/symptoms and accordingly staging of disease is done. Stage I, II and II presents with acute necrotizing gingivitis, facial edema with halitosis, and necrotizing stomatitis, respectively. If the patient survives acute stages, the progress to Stage IV and Stage V manifests as trismus, difficulty in deglutition and phonation, and facial disfigurement, with increased severity in last stage. Treatment encompasses antibiotic therapy (amoxicillin, metronidazole, chlorhexidine, ampicillin, gentamicin), surgical interventions, wound management (honey dressing, ketamine), and nutritional support. Prevention strategies include oral hygiene, vaccination, health education, and community-based interventions. Conclusion: Noma's recent inclusion in WHO list of neglected tropical diseases is a milestone in recognizing the importance of prevention and early intervention to globally enhance health outcomes.

Human scabies and sarcoptic mange in northeast Brazil: Results from a rapid assessment method covering an entire state.

Scabies is a neglected tropical disease and has been highlighted as a target for control. Sarcoptic mange affects animals, but mange is also considered a zoonosis. We present rapid assessment data on scabies and sarcoptic mange collected from key informants via a web-based questionnaire in Ceará State (1265 data entries). A total of 181/184 (98.3%) municipalities reported the occurrence of human scabies; 149 (80.9%) current occurrence; 168 (91.3%) severe cases; and 113 (61.4%) severe cases currently. Sarcoptic mange was reported from 149/184 (80.9%) municipalities, and severe mange from 128 (69.9%), most commonly in dogs (117 municipalities), cats (79), pigs (17), cattle (15), horses (15), and goats (2). Respondents from 171 (92.9%) municipalities observed seasonality of occurrence. Scabies and sarcoptic mange are important public health issues in a northeast Brazilian state. The wide distribution of severe cases requires an integrated One Health approach effectively and sustainably to reduce the disease burden.

Technical-scientific production and knowledge networks about medicinal plants and herbal medicines in the Amazon.

Introduction: This paper explores the role of Brazilian research institutions in the global and national context of study of medicinal plants. Most of these plants have ethnopharmacological use and herbal medicines related to the Amazon. It highlights Brazil's position in scientific production and the importance of Amazonian resources in developing phytomedicines. The study aims to provide an overview of the technical-scientific production of medicinal plants and herbal medicines related to the Amazon, focusing on scientific impact, collaboration, Technology Readiness Level (TRL) of scientific production, and innovation system maturity. Methods: The study employs a comprehensive methodological approach, including data collection from Scopus covering the period from 2002 to 2022. The data was cleaned and analyzed using bibliometric and network analysis techniques. Advanced natural language processing techniques, such as Latent Dirichlet Allocation and Jaccard distance measure, were used for TRL classification. Results: The findings reveal a predominant contribution from Brazilian institutions and authors, with 1,850 publications analyzed. Key areas identified include Pharmacology, Toxicology, Pharmaceuticals, Medicine, and Biochemistry. The study also uncovers various collaborative networks and technological maturity levels, with a significant focus on early-stage development phases. Discussion: The research concludes that Brazilian institutions, particularly those in the Amazon region, play a significant role in the scientific exploration and development of medicinal plants and herbal medicines. Despite this, countries like the USA were proportionally more productive in clinical trial research. The study underscores the potential of Brazil's rich biodiversity and traditional knowledge in the pharmaceutical industry, particularly for neglected diseases. It suggests the need for stronger research systems and international collaboration to leverage these resources for global health benefits.

Revolutionizing Leishmaniasis Treatment with Cutting Edge Drug Delivery Systems and Nanovaccines: An Updated Review.

Leishmaniasis, one of the most overlooked tropical diseases, is a life-threatening illness caused by the parasite Leishmania donovani that is prevalent in underdeveloped nations. Over 350 million individuals in more than 90 different nations worldwide are at risk of contracting the disease, which has a current fatality rate of 50 000 mortalities each year. The administration of liposomal Amp B, pentavalent antimonials, and miltefosine are still considered integral components of the chemotherapy regimen. Antileishmanial medications fail to treat leishmaniasis because of their numerous drawbacks. These include inadequate effectiveness, toxicity, undesired side effects, drug resistance, treatment duration, and cost. Consequently, there is a need to overcome the limitations of conventional therapeutics. Nanotechnology has demonstrated promising outcomes in addressing these issues because of its small size and distinctive characteristics, such as enhanced bioavailability, lower toxicity, biodegradability, and targeted drug delivery. This review is an effort to highlight the recent progress in various nanodrug delivery systems (nDDSs) over the past five years for treating leishmaniasis. Although the preclinical outcomes of nDDSs have shown promising treatment for leishmaniasis, further research is needed for their clinical translation. Advancement in three primary priority domains─molecular diagnostics, clinical investigation, and knowledge dissemination and standardization─is imperative to propel the leishmaniasis field toward translational outcomes.

The short-term impact of Schistosoma mansoni infection on health-related quality of life: implications for current elimination policies.

The WHO aims to eliminate schistosomiasis as a public health problem by 2030. However, standard morbidity measures poorly correlate to infection intensities, hindering disease monitoring and evaluation. This is exacerbated by insufficient evidence on Schistosoma's impact on health-related quality of life (HRQoL). We conducted community-based cross-sectional surveys and parasitological examinations in moderate-to-high Schistosoma mansoni endemic communities in Uganda. We calculated parasitic infections and used EQ-5D instruments to estimate and compare HRQoL utilities in these populations. We further employed Tobit/linear regression models to predict HRQoL determinants. Two-thirds of the 560 participants were diagnosed with parasitic infection(s), 49% having S. mansoni. No significant negative association was observed between HRQoL and S. mansoni infection status/intensity. However, severity of pain urinating (ß = -0.106; s.e. = 0.043) and body swelling (ß = -0.326; s.e. = 0.005), increasing age (ß = -0.016; s.e. = 0.033), reduced socio-economic status (ß = 0.128; s.e. = 0.032), and being unemployed predicted lower HRQoL. Symptom severity and socio-economic status were better predictors of short-term HRQoL than current S. mansoni infection status/intensity. This is key to disentangling the link between infection(s) and short-term health outcomes, and highlights the complexity of correlating current infection(s) with long-term morbidity. Further evidence is needed on long-term schistosomiasis-associated HRQoL, health and economic outcomes to inform the case for upfront investments in schistosomiasis interventions.

Consequences of geographical accessibility to post-exposure treatment for rabies and snakebite in Africa: a mini review.

Introduction: Rabies and snakebite envenoming are two zoonotic neglected tropical diseases (NTDs) transmitted to humans by animal bites, causing each year around 179,000 deaths and are most prevalent in Asia and Africa. Improving geographical accessibility to treatment is crucial in reducing the time from bite to treatment. This mini review aims to identify and synthesize recent studies on the consequences of distance and travel time on the victims of these diseases in African countries, in order to discuss potential joint approaches for health system strengthening targeting both diseases. Methods: A literature review was conducted separately for each disease using Pubmed, Google Scholar, and snowball searching. Eligible studies, published between 2017 and 2022, had to discuss any aspect linked to geographical accessibility to treatments for either disease in Africa. Results: Twenty-two articles (8 on snakebite and 14 on rabies) were eligible for data extraction. No study targeted both diseases. Identified consequences of low accessibility to treatment were classified into 6 categories: (1) Delay to treatment; (2) Outcome; (3) Financial impacts; (4) Under-reporting; (5) Compliance to treatment, and (6) Visits to traditional healers. Discussion and conclusion: Geographical access to treatment significantly influences the burden of rabies and snakebite in Africa. In line with WHO's call for integrating approaches among NTDs, there are opportunities to model disease hotspots, assess population coverage, and optimize geographic access to care for both diseases, possibly jointly. This could enhance the management of these NTDs and contribute to achieving the global snakebite and rabies roadmaps by 2030.

Predictor Variables in the Spread of Chagas Disease in Rural Areas.

Over a hundred years ago after the discovery of Chagas disease (CD) in Brazil, the World Health Organization estimates a number of 6 to 7 million people infected by Trypanosoma cruzi worldwide. Therefore, the goal of this work was to identify variables related to the spread of infection by T. cruzi in humans living in rural areas, seeking predictor variables. A systematic review of the literature has been conducted, with a search in the Scopus platform, using the search string "Chagas disease" and "rural", resulting in 85 valid and analyzed scientific studies (1977 and 2022). Twenty-seven predictor variables have been acquired, and 19 of them have been grouped, such as: socioeconomic and educational, housing, environmental, sanitary, and cultural; and 8 variables related to T. cruzi seropositive individuals. The predictor variables yielded significant results (p-value < 0.05) in 59.5% of the cases (195/328), with a median of 66.7%. In other words, studies relating to 50% of the 27 variables showed significance equal to or greater than 66.7% of the time. The independent variables with the highest proportion of significant data (p-value < 0.05) were Education (87.6%), Intradomicile building (70%), Domestic animals (69.6%), and Triatomines (69.2%) in the households. Some variables reached 100%; however, few articles were found, indicating the need for further research, especially for Sanitation and Culture. It has been concluded that, in the several contexts found, the social vulnerability and lack of information led the individual to living in environments where inhabitability is inadequate, to perform limited work activity and develop habits and behaviors which impair them in an environmental insalubrity situation, favorable to the access of vectors and pathogens of anthropozoonoses such as CD.

The COVID-19 pandemic impacted the activities of the Schistosomiasis Control Program in Brazil: is the goal of controlling the disease by 2030 at risk?

BACKGROUND: Schistosomiasis continues to represent a serious public health problem in Brazil. With the coronavirus disease 2019 (COVID-19) pandemic, several control strategies were suspended, probably compromising the goals of eradicating the disease in the country. We aimed to assess the impact of the COVID-19 pandemic on Schistosomiasis Control Program (PCE) actions in all endemic states of Brazil. METHODS: We performed an ecological study using spatial analysis techniques. The PCE variables assessed were the population surveyed, the number of Kato-Katz tests, positive cases of schistosomiasis and the percentage of cases treated between 2015 and 2021. The percent change was calculated to verify if there was an increase or decrease in 2020 and 2021, along with time trend analyses provided by the Joinpoint model. Spatial distribution maps were elaborated considering the percent change. RESULTS: The surveyed population decreased in 2020 (-65.38%) and 2021 (-37.94%) across Brazil. There was a proportional reduction in the number of Kato-Katz tests (2020, -67.48%; 2021, -40.52%), a decrease in the percentage of positive cases (2020, -71.16%; 2021, -40.5%) and a reduction in the percentage of treated cases (2020, -72.09%; 2021, -41.67%). Time trend analyses showed a decreasing trend in most PCE variables. CONCLUSIONS: The PCE activities were impacted by the COVID-19 pandemic in Brazil and PCE strategies must be urgently reviewed, focusing on investments in all endemic areas.

Brucella Seropositivity at a Tertiary Care Hospital in Chandigarh.

There are reports that the neglected zoonotic tropical disease brucellosis is reemerging today. Serological tests are being widely used in the diagnosis of brucellosis. In the present study, we performed a standard agglutination test (SAT) on 1348 suspected cases of brucellosis during the period of four years from April 2018 to March 2022. We noticed an increase in seropositivity from 2.6% in the year 2018-19 to 7.4% in the year 2021-22. We also noticed a spike in seropositivity in the years 2019-20 (12.5%). Our study shows the recent trend in seropositivity of the disease in Chandigarh and, hence, can be a meaningful addition to the existing serological diagnostic data related to brucellosis.

Synergistic Manifestations in Cardiac Cysticercosis Complicated by Snake Bite: A Case Report and Literature Review.

Cysticercosis presents a prevalent issue on a global scale. Nevertheless, disseminated cysticercosis (DCC) is infrequent; even rarer is asymptomatic DCC. Here, we present a unique case of asymptomatic DCC involving the heart in a young male who came to medical attention following a fatal snake bite, ultimately leading to his demise. Despite the widespread dissemination of cysticercosis affecting multiple organs, the individual remained asymptomatic for the condition. We present a case of a 23-year-old male who was brought to the emergency department with a history of alleged snake bites. The patient was declared dead upon arrival at the All India Institute of Medical Sciences (AIIMS), Rishikesh, India. Autopsy findings revealed multiple significant cardiac abnormalities, including atheromatous changes with calcification in the root of the aorta and aortic valve, along with numerous collateral vessels originating from the left main coronary artery. Additionally, cystic nodules containing cysticercus larvae were identified within the myocardium, suggesting cardiac cysticercosis. The cause of death was determined to be complications related to the snakebite. This case emphasizes the importance of considering multiple potential etiologies in complex clinical presentations, especially in the tropics.

An updated list of eumycetoma causative agents and their differences in grain formation and treatment response.

SUMMARYIn 2023, the World Health Organization designated eumycetoma causative agents as high-priority pathogens on its list of fungal priority pathogens. Despite this recognition, a comprehensive understanding of these causative agents is lacking, and potential variations in clinical manifestations or therapeutic responses remain unclear. In this review, 12,379 eumycetoma cases were reviewed. In total, 69 different fungal species were identified as causative agents. However, some were only identified once, and there was no supporting evidence that they were indeed present in the grain. Madurella mycetomatis was by far the most commonly reported fungal causative agent. In most studies, identification of the fungus at the species level was based on culture or histology, which was prone to misidentifications. The newly used molecular identification tools identified new causative agents. Clinically, no differences were reported in the appearance of the lesion, but variations in mycetoma grain formation and antifungal susceptibility were observed. Although attempts were made to explore the differences in clinical outcomes based on antifungal susceptibility, the lack of large clinical trials and the inclusion of surgery as standard treatment posed challenges in drawing definitive conclusions. Limited case series suggested that eumycetoma cases caused by Fusarium species were less responsive to treatment than those caused by Madurella mycetomatis. However, further research is imperative for a comprehensive understanding.

TurboID mapping reveals the exportome of secreted intrinsically disordered proteins in the transforming parasite Theileria annulata.

Theileria annulata is a tick-transmitted apicomplexan parasite that gained the unique ability among parasitic eukaryotes to transform its host cell, inducing a fatal cancer-like disease in cattle. Understanding the mechanistic interplay between the host cell and malignant Theileria species that drives this transformation requires the identification of responsible parasite effector proteins. In this study, we used TurboID-based proximity labeling, which unbiasedly identified secreted parasite proteins within host cell compartments. By fusing TurboID to nuclear export or localization signals, we biotinylated proteins in the vicinity of the ligase enzyme in the nucleus or cytoplasm of infected macrophages, followed by mass spectrometry analysis. Our approach revealed with high confidence nine nuclear and four cytosolic candidate parasite proteins within the host cell compartments, eight of which had no orthologs in non-transforming T. orientalis. Strikingly, all eight of these proteins are predicted to be highly intrinsically disordered proteins. We discovered a novel tandem arrayed protein family, nuclear intrinsically disordered proteins (NIDP) 1-4, featuring diverse functions predicted by conserved protein domains. Particularly, NIDP2 exhibited a biphasic host cell-cycle-dependent localization, interacting with the EB1/CD2AP/CLASP1 parasite membrane complex at the schizont surface and the tumor suppressor stromal antigen 2 (STAG2), a cohesion complex subunit, in the host nucleus. In addition to STAG2, numerous NIDP2-associated host nuclear proteins implicated in various cancers were identified, shedding light on the potential role of the T. annulata exported protein family NIDP in host cell transformation and cancer-related pathways.IMPORTANCETurboID proximity labeling was used to identify secreted proteins of Theileria annulata, an apicomplexan parasite responsible for a fatal, proliferative disorder in cattle that represents a significant socio-economic burden in North Africa, central Asia, and India. Our investigation has provided important insights into the unique host-parasite interaction, revealing secreted parasite proteins characterized by intrinsically disordered protein structures. Remarkably, these proteins are conspicuously absent in non-transforming Theileria species, strongly suggesting their central role in the transformative processes within host cells. Our study identified a novel tandem arrayed protein family, with nuclear intrinsically disordered protein 2 emerging as a central player interacting with established tumor genes. Significantly, this work represents the first unbiased screening for exported proteins in Theileria and contributes essential insights into the molecular intricacies behind the malignant transformation of immune cells.

Multiple receptor tyrosine kinases regulate dengue infection of hepatocytes.

Introduction: Dengue is an arboviral disease causing severe illness in over 500,000 people each year. Currently, there is no way to constrain dengue in the clinic. Host kinase regulators of dengue virus (DENV) infection have the potential to be disrupted by existing therapeutics to prevent infection and/or disease progression. Methods: To evaluate kinase regulation of DENV infection, we performed kinase regression (KiR), a machine learning approach that predicts kinase regulators of infection using existing drug-target information and a small drug screen. We infected hepatocytes with DENV in vitro in the presence of a panel of 38 kinase inhibitors then quantified the effect of each inhibitor on infection rate. We employed elastic net regularization on these data to obtain predictions of which of 291 kinases are regulating DENV infection. Results: Thirty-six kinases were predicted to have a functional role. Intriguingly, seven of the predicted kinases - EPH receptor A4 (EPHA4), EPH receptor B3 (EPHB3), EPH receptor B4 (EPHB4), erb-b2 receptor tyrosine kinase 2 (ERBB2), fibroblast growth factor receptor 2 (FGFR2), Insulin like growth factor 1 receptor (IGF1R), and ret proto-oncogene (RET) - belong to the receptor tyrosine kinase (RTK) family, which are already therapeutic targets in the clinic. We demonstrate that predicted RTKs are expressed at higher levels in DENV infected cells. Knockdown of EPHB4, ERBB2, FGFR2, or IGF1R reduces DENV infection in hepatocytes. Finally, we observe differential temporal induction of ERBB2 and IGF1R following DENV infection, highlighting their unique roles in regulating DENV. Discussion: Collectively, our findings underscore the significance of multiple RTKs in DENV infection and advocate further exploration of RTK-oriented interventions against dengue.

Unmasking the Hidden Burden: A Delayed Diagnosis of Leprosy Patients With Grade 2 Disability and Its Effects on the Healthcare System in Bangladesh.

Introduction Leprosy remains a significant cause of preventable disability worldwide. Early diagnosis and treatment of leprosy are critical not only to stop its spread but also to prevent physical and social complications and reduce the disease burden. Objectives The study aims to evaluate the factors that lead to a delayed leprosy diagnosis. Methods This study was conducted in the outpatient departments of Leprosy Control Institute and Hospital, Dhaka, Bangladesh, and at Medical College for Women and Hospital, Dhaka, Bangladesh, from March 2023 to June 2023. A total number of 252 male (148) and female (104) patients were selected with any sign of leprosy, including disability, age ranging from 15 to 74 years. Data was collected in a pre-designed structured questionnaire by the researchers. To assess the risk of independent exposures of Grade 2 leprosy disabilities, we used a logistic regression model. A chi-square test showed the association between significant effects and leprosy disabilities. A p-value of 0.05 was considered as significant. For statistical analysis, STATA version 15 (StataCorp LLC, College Station, Texas, USA) was used. Results The study participants exhibited a higher percentage of disability, with a rate of 25.8% for Grade 2 disabilities. In addition to this, males represented a more considerable proportion, 58.7%, than females among leprosy and disability patients across all levels of disability. In our study, lack of money and painless symptoms showed a significant association (p<0.001) with Grade 2 disability. Conclusion The study reveals that Grade 2 disabilities are more common in males and are particularly prevalent in lower socioeconomic groups.

Identification and Characterization of Onchocerca volvulus Heat Shock Protein 70 (OvHSP70) as Novel Diagnostic Marker of Onchocerciasis in Human Urine.

Despite several decades of mass drug administration and elimination-related activities, human onchocerciasis still represents a major parasitic threat in endemic regions. Among the challenges encountered by the elimination program is the lack of a suitable diagnostic tool that is accurate and non-invasive. Currently used methods are either invasive or not suitable for monitoring large numbers of patients. Herein, we describe the identification and characterization of Onchocerca volvulus heat shock protein 70 (OvHSP70) as a novel diagnostic biomarker for human onchocerciasis, which can directly be detected in urine samples of infected patients. This nematode-specific antigen was identified through LC-MS after differential SDS-PAGE using urine-derived protein extracts from O. volvulus-infected patients in Cameroon. Polyclonal antibodies generated in rabbits after cloning and expression of OvHSP70 in Escherichia coli reliably differentiated between urine samples from infected- and uninfected patients in a hypoendemic area of human onchocerciasis. These results provide an excellent basis for further development of a non-invasive and scalable diagnostic assay for human onchocerciasis using urine samples. Such a urine-based diagnostic assay will be of major importance for the elimination program of human onchcerciasis in endemic countries.