Leishmaniases in Ethiopia: a scoping review protocol to determine the scope of research and remaining gaps.

INTRODUCTION: The leishmaniases are among the group of neglected tropical diseases that cause significant morbidity and mortality each year. Currently, the East Africa region has the highest visceral leishmaniasis burden in the world. Ethiopia is one of the East African countries that reports both visceral and cutaneous forms of the disease. As part of the Nairobi Declaration, Ethiopia showed commitment to the elimination of visceral leishmaniasis by 2030. In this endeavour, it is important to understand the scope of research conducted on leishmaniases in the country and identify where the research gaps exist. Determining the research landscape is vital in the plan towards leishmaniases control and elimination. It will help to reference conducted research, determine if systematic reviews are warranted and help prioritise future research directions. METHODS AND ANALYSIS: This protocol was developed with reference to the JBI Scoping Review Methodology Group's guidance on conducting scoping reviews and the PRISMA-ScR reporting guidelines for scoping reviews. The following databases will be searched: PubMed, Embase via Embase.com, Web of Science Core Collection, Cochrane CENTRAL, Global Index Medicus, ClinicalTrials.gov, the Pan African Clinical Trials Registry and PROSPERO. Locally published literature that may not be indexed in the above-mentioned systems will be identified through team members familiar with the setting. Each record will be dually and blindly reviewed in an abstract-title screen and full-text screen using inclusion-exclusion criteria. Included articles must contain an in-depth discussion of leishmaniasis in Ethiopia. Data extracted will consist of study themes, study types, and categories and subcategories each defined in the developed codebook, in addition to type of leishmania, year of publication, funding source and the number of citations. Results will be reported with summary statistics. ETHICS AND DISSEMINATION: Individual consenting and ethical approvals are not applicable. We plan to disseminate our findings to the appropriate stakeholders.

Cyclodextrins as a Strategy for Enhancing Solubility of Therapeutic Agents for Neglected Tropical Diseases: A Systematic Review.

BACKGROUND: Neglected Tropical Diseases (NTD) are chronic infectious conditions that primarily affect marginalized populations. The chemotherapeutic arsenal available for treating NTD is limited and outdated, which poses a challenge in controlling and eradicating these diseases. This is exacerbated by the pharmaceutical industry's lack of interest in funding the development of new therapeutic alternatives. In addition, a considerable number of drugs used in NTD therapy have low aqueous solubility. To address this issue, solubility enhancement strategies, such as the use of inclusion complexes with cyclodextrins (CD) can be employed. OBJECTIVE: Therefore, this systematic review aims to present the application of CD in complexing with drugs and chemotherapeutic compounds used in the therapy of some of the most prevalent NTD worldwide and how these complexes can enhance the treatment of these diseases. METHODS: Two bibliographic databases, Science Direct and PubMed, were used to conduct the search. The selection of studies and the writing of this systematic review followed the criteria outlined by the PRISMA guidelines. RESULTS: From a total of 978 articles, 23 were selected after applying the exclusion criteria. All the studies selected were consistent with the use of CD as a strategy to increase the solubility of therapeutic agents used in NTD. CONCLUSION: The results indicate that CD can enhance the solubility of chemotherapeutic agents for the treatment of Neglected Tropical Diseases (NTD). This review presents data that clearly highlights the potential use of CD in the development of new treatments for neglected tropical diseases. It can assist in the formulation of future treatments that are more effective and safer.

Immunological Activity of Vaccine Systems Containing Liposomal Nanocarriers against Protozoan-Induced Diseases: A Systematic Review.

BACKGROUND: Neglected parasitic diseases constitute a broad spectrum of clinical conditions that, in the chronic phase, lack effective therapies for the target population. The utilization of vaccines based on liposomal nanocarrier systems is emerging, thereby enhancing clinical outcomes in various comorbidities. Consequently, this study aims to assess the immunological activity induced by liposomal nanocarriers against neglected parasitic diseases. METHODS: For the review, the Pubmed, Embase, and Lilacs databases were used using the descriptors vaccine, parasite, and liposome. The following inclusion criteria were adopted: in vivo and in vitro experimental articles. As exclusion criteria: book chapters, editorials, literature reviews and duplicate articles found during the database search. RESULTS: A total of 226 articles were identified, from which 34 were selected for review. The primary diseases identified included Babesia bovis, Entamoeba histolytica, Leishmania braziliensis, Leishmania donovani, Leishmania major, Leishmania infantum, Plasmodium falciparum, Plasmodium chabaudi, Plasmodium chabaudi, Plasmodium yoelii, Toxoplasma gondii and Trypanosoma cruzi. An elevation in cytokines such as GM-CSF, MCP-1, INF-γ, TNF-α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, and IL-17 was observed in the studies evaluated regarding the parasitic diseases. Furthermore, cytokines such as IL-4, IL-10, and TGF-ß were diminished with the administration of the vaccine systems in those studies. CONCLUSION: Therefore, the administration of liposomal nanovaccine systems can effectively ameliorate the clinical condition of patients by modulating their immunological profile.

Urogenital schistosomiasis among adult male population in an endemic area of southern Tanzania: a descriptive cross-sectional study.

BACKGROUND: Urogenital schistosomiasis (UGS) caused by Schistosoma haematobium is endemic in Southern Tanzania. The disease has significant implications for both socioeconomic and public health. Because infections with S. haematobium usually peak in childhood, the majority of studies have concentrated on school-aged children leaving other groups such as males which might be continuous reservoir of infection transmission. However, despite its chronic consequences in the male population, the disease has received insufficient attention, especially in sub-Saharan Africa. This study was conducted to describe the previous and current schistosomiasis status among adult males living in high-endemic areas of southern Tanzania DESIGN, SETTING AND PARTICIPANTS: A descriptive cross-sectional study was employed to gather data on the prevalence of UGS among adult men residing at schistosomiasis endemic in the Mtama District Council. Quantitative methods of data collection which included questionnaire and laboratory procedures were used. RESULTS: Out of 245 participants, macrohaematuria and microhaematuria were found in 12 (4.9%, 95% CI 2.4% to 7.8%) and 66 (26.9%, 95% CI 21.6% to 32.7%) participants, respectively. S. haematobium ova were recovered from the urine samples of 54 (22.0%, 95% CI 16.7% to 27.3%) participants. The median intensity of infection was 20 eggs per 10 mL of urine ranging from 1 to 201 eggs per 10 mL of urine (IQR) 60.5). Out of 245 participants 33 (13.5% 95% CI 9.0% to 17.6%) had light intensity of infection and 21 (38.9%, 95% CI; 25.0% to 52.5%) had heavy intensity of infection. Overall, the prevalence of heavy intensity of infection was 8.6% (95% CI 4.9% to 12.6%). The prevalence and intensity of UGS varied significantly by age, marital status and village of residence. CONCLUSION: This study sheds light on the prevalence of UGS among adult males in endemic areas of southern Tanzania. The results highlight the urgent need for comprehensive intervention strategies to address the burden of the disease.

Compound management in a virtual research organization: The cornerstone of a reliable MMV discovery engine.

Despite the efforts towards malaria eradication, latest estimates show that the number of malaria cases is still rising, and malaria continues to have a devastating impact on people's health and livelihoods particularly in populations located in sub-Saharan Africa 1. As a Product Development Partnership (PDP), MMV Medicines for Malaria Venture (MMV) plays a crucial role by using public and philanthropic funds to engage the pharmaceutical industry and academic research institutions to discover, develop and deliver the new drugs needed to control and eradicate malaria. MMV Discovery, working with partners, has developed a robust pipeline of molecules and a reliable discovery engine able to support research projects from screening to candidate nomination, providing access to centers of expertise and evaluating the profile and potential of molecules. To efficiently support this malaria discovery effort, MMV and its partners have established a state-of-the-art compound management network, supporting all discovery activities. This network serves both discovery projects and open innovation initiatives, such as MMV Open, tailoring workflows to align with distinct project objectives. In addition to this, MMV has implemented reliable integrated logistic tools and interfaces. These tools enable the efficient management and tracking of individual not solubilized (dry) samples of project compounds, as well as dedicated, solubilized libraries of compounds designated for primary screens targeting malaria and other neglected diseases.

Enabling product development partnerships to bring forward the next generation of health technologies.

Over the past quarter century, product development partnerships (PDPs) have importantly brought health technologies, particularly for neglected diseases, to market for low- and middle-income countries (LMICs). With public sector financing, PDPs de-risk the gulf between where the global burden of disease falls and where paying markets exist. From fighting COVID-19 to developing novel antibiotics, the work of PDPs now extends beyond these traditional bounds. As PDPs have shepherded more health technologies to market, they are also confronting new access challenges. This article lays out 5 areas to strategically leverage the PDP model for better access to new health technologies. Making the case for enhanced support of the PDP approach will require greater transparency, as well as recognition of the contributions made by both public and private sector partners. The governance and funding of PDPs must be accountable to meeting the needs and building capacity of target beneficiaries in LMICs. To take an end-to-end approach, PDPs must work in tandem with other public sector institutions as well as local manufacturers as part of a larger innovation ecosystem. PDPs will need to keep pace with both the dynamics of diseases and markets in delivering the next generation of much needed health technologies.

Product development partnerships (PDPs) play an important role in bringing new and needed health technologies to market, particularly in low- and middle-income countries. As these products emerge from the R&D pipeline, new access challenges in paying for and delivering them in the health care system have emerged. The COVID-19 pandemic has also both stretched and tapped into this work. These developments provide a window of opportunity, both to take stock of lessons learned and of strategic opportunities to leverage the PDP model beyond its traditional bounds of neglected diseases. Greater transparency and recognition of the contributions of PDPs, accountability of governance and surety of financing, and coordination with pooled procurement and local manufacturing initiatives can build a foundation for even more impactful contributions in the future.

Py-CoMFA, docking, and molecular dynamics simulations of Leishmania (L.) amazonensis arginase inhibitors.

Leishmaniasis is a disease caused by a protozoan of the genus Leishmania, affecting millions of people, mainly in tropical countries, due to poor social conditions and low economic development. First-line chemotherapeutic agents involve highly toxic pentavalent antimonials, while treatment failure is mainly due to the emergence of drug-resistant strains. Leishmania arginase (ARG) enzyme is vital in pathogenicity and contributes to a higher infection rate, thus representing a potential drug target. This study helps in designing ARG inhibitors for the treatment of leishmaniasis. Py-CoMFA (3D-QSAR) models were constructed using 34 inhibitors from different chemical classes against ARG from L. (L.) amazonensis (LaARG). The 3D-QSAR predictions showed an excellent correlation between experimental and calculated pIC50 values. The molecular docking study identified the favorable hydrophobicity contribution of phenyl and cyclohexyl groups as substituents in the enzyme allosteric site. Molecular dynamics simulations of selected protein-ligand complexes were conducted to understand derivatives' interaction modes and affinity in both active and allosteric sites. Two cinnamide compounds, 7g and 7k, were identified, with similar structures to the reference 4h allosteric site inhibitor. These compounds can guide the development of more effective arginase inhibitors as potential antileishmanial drugs.

N-Pyrazolyl- and N-Triazolylamines and -Ureas as Antileishmanial and Antitrypanosomal Drugs.

Three types of modifications of antileishmanial pyrazole lead compounds 7 and 8 were conducted to expand understanding of the relationships between structural features and antileishmanial/antitrypanosomal activity: (1) the pyrazole core was retained or replaced by a 1,2,4-triazole ring; (2) various aryl moieties including 2-fluorophenyl, pyridin-3-yl and pyrazin-2-yl rings were attached at 3-position of the core azole; (3) either arylmethylamino or ureido substituents were introduced at 5-position of the azole core. The synthesis followed established routes starting with esters 9 or 15 and anhydride 21. The synthesized 3-arylpyrazoles and 3-aryl-1,2,4-triazoles had only very low antileishmanial activity. The 2-fluorophenyl-substituted pyrazole 18c revealed the highest antileishmanial activity of this series of compounds, but its IC50 value (20 µM) still indicates low activity. However, low micromolar antitrypanosomal activity was detected for the pyridin-3-yl-substituted pyrazoles 12b (IC50=4.7 µM) and 14a (IC50=2.1 µM). Their IC50 values are comparable with the IC50 values of the reference compounds benznidazole and nifurtimox. Whereas only low unspecific cytotoxicity at the primary peritoneal mouse macrophages (PMM) was detected, considerable cytotoxicity at MRC-5 human fibroblast cells was found for both pyrazoles 12b an 14a. The activity of pyrazole 12b against T. cruzi is 4-fold higher than its unspecific MRC-5 cytotoxicity.

Effect of an exercise-based cardiac rehabilitation program on quality of life of patients with chronic Chagas cardiomyopathy: results from the PEACH randomized clinical trial.

To investigate the effect of an exercise-based cardiac rehabilitation program on the quality of life (QoL) of patients with chronic Chagas cardiomyopathy (CCC). PEACH study was a single-center, superiority randomized clinical trial of exercise training versus no exercise (control). The sample comprised Chagas disease patients with CCC, left ventricular ejection fraction < 45%, without or with HF symptoms (CCC stages B2 or C, respectively). QoL was assessed at baseline, after three months, and at the end of six months of follow-up using the SF-36 questionnaire. Patients randomized for the exercise group (n = 15) performed exercise training (aerobic, strength and stretching exercises) for 60 min, three times a week, during six months. Patients in the control group (n = 15) were not provided with a formal exercise prescription. Both groups received identical nutritional and pharmaceutical counseling during the study. Longitudinal analysis of the effects of exercise training on QoL, considering the interaction term (group × time) to estimate the rate of changes between groups in the outcomes (represented as beta coefficient), was performed using linear mixed models. Models were fitted adjusting for each respective baseline QoL value. There were significant improvements in physical functioning (ß = + 10.7; p = 0.02), role limitations due to physical problems (ß = + 25.0; p = 0.01), and social functioning (ß = + 19.2; p < 0.01) scales during the first three months in the exercise compared to the control group. No significant differences were observed between groups after six months. Exercise-based cardiac rehabilitation provided short-term improvements in the physical and mental aspects of QoL of patients with CCC.Trial registration: ClinicalTrials.gov Identifier: NCT02517632; August 7, 2015.

Spatial-temporal distribution of visceral leishmaniasis in Rio de Janeiro, Brazil, 2001-2020: expansion and challenges.

BACKGROUND: Visceral leishmaniasis results from complex interactions among humans, dogs and environment. Brazil accounts for 97% of cases in the Americas. METHODS: Twenty years (2001-2020) of the endemic disease in the state of Rio de Janeiro were studied. Incidence, lethality, sociodemographic and clinical characteristics were investigated, complemented with spatial methodologies (kernel and clusters). RESULTS: Ninety-seven human cases and 625 dogs were reported. Of the 92 cities, 22 were human endemic areas. The state had a low incidence level (0.6 per 100 000). Lethality was higher compared with the Brazilian average. More than 90% of infections occurred in urban areas. Most cases (66%) occurred in men. The predominant age groups were 0-4 y (28.7%) and 20-39 y (32.9%). Fever (89.5%), splenomegaly (83.2%) and hepatomegaly (76.8%) were the main clinical manifestations. Spatial analysis showed a displacement of the human endemic: in the first decade (2001-2010), cases were concentrated in the Metropolitan region, and in the second decade (2011-2020) in the Médio Paraíba region of the state. Most of the endemic area (56.4%) had canine infections without reported human cases. CONCLUSIONS: Disorderly urbanisation and precarious living conditions favour the transmission of the disease. Changes in the environment and migratory processes contribute to its expansion.

Impairment of health-related quality of life and its determinants among patients with podoconiosis in East Wollega Zone, Oromia Regional State, Ethiopia: institutional-based cross-sectional study.

OBJECTIVE: This study aimed to assess the impairment of health-related quality of life (HRQoL) and its determinants among patients diagnosed with podoconiosis in East Wollega Zone, Oromia Regional State, Ethiopia. METHODS: An institutional-based cross-sectional study design was used in the setting of primary healthcare facilities to assess impaired HRQoL among patients with podoconiosis in the East Wollega Zone from 1 March 2023 to 30 April 2023, using the Dermatologic Life Quality Index (DLQI). Data was collected from 494 patients with podoconiosis, and a multistage sampling technique was employed. The data was entered into EpiData V.4.6 and exported to SPSS V.27 for analysis. A linear regression model with a 95% cofidence interval (CI) was used to estimate level of HRQoL and to identify its determinants estimating beta (ß) coefficient declaring the significance level at p<0.05. RESULTS: The quality of life among patients was impaired on average by 9.6±6.1 with the lowest DLQI Score in the domain of treatment (0.8±0.97) and the highest in the domain of daily activity (2.3±1.72). The identified significant determinants of impairment of HRQoL associated with DLQI scores were duration of disease (95% CI, ß=0.11 (0.08 to 0.15)), acute dermato-lymphangio-adenitis (ADLA) (95% CI, ß=0.08 (0.01 to 0.16)), comorbidity (95% CI, ß=1.26 (0.37 to 2.16)), consistently wearing shoes (95% CI, ß=-0.06 (-0.09 to -0.03)), feeling of stigmatised (95% CI, ß=0.21 (0.16 to 0.25)) and psychological distress (95% CI, ß=0.17 (0.14 to 0.21)) and being female (95% CI, ß=1.16 (0.19 to 2.12)). CONCLUSION: Overall, HRQoL among patients with podoconiosis was moderately impaired. The duration of disease, ADLA, comorbidity, stigma, psychological distress and being female in sex significantly impaired HRQoL, whereas consistently wearing shoes significantly improved HRQoL among the patients with podoconiosis. Therefore, healthcare providers and public health experts should work on educating communities and counselling patients to avoid stigma and psychological distress, wearing shoes consistently and treating podoconiosis and other comorbidities among these patients.

An evaluation of mental health integration in the neglected tropical diseases program in Zamfara, North-west Nigeria.

BACKGROUND: Mental health and neglected tropical diseases (NTDs) are critical in healthcare systems, especially in low- and middle-income countries. Several policies are planned or designed by health stakeholders to address the mental health needs of people affected by NTDs. Still, the impact of such policies seems to be of no consequence. METHODS: The GAD-7 and PHQ-9 tools were used to determine the rate of depression and anxiety, respectively, among people affected by skin NTDs (leprosy and lymphatic filariasis [LF]) in Zamfara State, North-west Nigeria. The study also evaluated the barriers to the uptake of mental health services for people affected by skin NTDs in the state. We assessed 48 people affected by NTDs (leprosy, 32; lymphatic filariasis, 16) along with a corresponding 48 people who served as controls in the study. Qualitative interviews were carried out with the participants to elicit the barriers to mental health services for people affected by NTDs. Additionally, 48 selected healthcare workers from the state were assessed for their skills and capacity to offer mental health services. RESULTS: We found anxiety disorder present in 100% of the people living with LF and in 62% of the people living with leprosy. Depression was also found in 56% and 75% of the people living with leprosy and LF, respectively. An assessment of the barriers to the uptake of mental health services reveals that most people with NTDs are constrained by a lack of money to visit hospitals, the fear of stigmatisation and discrimination and long distances to health centres. Regarding the healthcare workers, the skills and capacity to offer mental health services were very low. CONCLUSIONS: We conclude that for mental health services to be integrated into the community health system for people with NTDs, there should be a concerted effort by all stakeholders and the intervention should be context specific instead of generalised. CONTEXTE: La santé mentale et les maladies tropicales négligées (MTN) sont des problématiques centrales dans la santé, en particulier dans les pays à revenu faible ou intermédiaire. Plusieurs politiques sont conçues par les acteurs de la santé publique pour répondre aux besoins de soins en santé mentale pour les personnes touchées par les MTN. Pourtant, le bilan reste mitigé quant à l'efficacité de ces soins. MÉTHODES: Les outils GAD-7 et PHQ-9 ont été utilisés pour déterminer le taux de dépression et d'anxiété chez les personnes atteintes de MTN cutanées (lèpre et filariose lymphatique) dans l'État de Zamfara, au nord-ouest du Nigeria. L'étude a également évalué les obstacles à l'utilisation des services de santé mentale pour les personnes atteintes de MTN cutanées dans l'État. Nous avons évalué 48 personnes atteintes de MTN (lèpre : 32, filariose lymphatique : 16) ainsi que 48 personnes correspondantes qui ont servi de témoins dans l'étude. Des entretiens qualitatifs ont été menés avec les participants afin d'identifier les obstacles aux services de santé mentale pour les personnes atteintes de MTN. En outre, 48 professionnels de la santé sélectionnés dans l'État ont été évalués pour déterminer leurs compétences et leur capacité à offrir des services de santé mentale. RÉSULTATS: Nous avons trouvé des troubles anxieux chez 100% des personnes atteintes de filariose lymphatique et chez 62% des personnes atteintes de lèpre. La dépression touche 56% et 75% des personnes vivant avec la lèpre et la filariose lymphatique respectivement. Une évaluation des obstacles à l'utilisation des services de santé mentale révèle que la plupart des personnes atteintes de MTN sont limitées par le manque d'argent pour se rendre à l'hôpital, la peur de la stigmatisation et de la discrimination, et les longues distances à parcourir pour se rendre dans les centres de santé. Les compétences et les capacités des professionnels de la santé à offrir des services de santé mentale sont très faibles. CONCLUSION: L'efficacité d'un protocole de soins pour les patients atteints de MTN (traitant la pathologie physique et d'éventuelles pathologies psychiatriques associées) nécessite une intégration des services de santé mentale dans le système de santé communautaire. ANTECEDENTES: La salud mental y las enfermedades tropicales desatendidas (ETDs), son fundamentales en los sistemas sanitarios, especialmente en los países de renta baja y media. Las partes interesadas en la sanidad planean o diseñan varias políticas para abordar las necesidades de salud mental de las personas afectadas por ETDs. Sin embargo, el impacto de dichas políticas parece ser nulo. MÉTODOS: Se utilizaron las herramientas GAD-7 y PHQ-9 para determinar la tasa de depresión y ansiedad, respectivamente, entre las personas afectadas por ETDs cutáneas (lepra y filariasis linfática) en el Estado de Zamfara, al noroeste de Nigeria. El estudio también evaluó las barreras para la aceptación de los servicios de salud mental por parte de las personas afectadas por ETDs cutáneas en el Estado. Se evaluó a 48 personas afectadas por ETDs (lepra: 32; filariasis linfática: 16) y a otras 48 que sirvieron de control en el estudio. Se llevaron a cabo entrevistas cualitativas con los participantes para determinar las barreras a los servicios de salud mental para las personas afectadas por ETDs. Además, se evaluaron las habilidades y la capacidad para ofrecer servicios de salud mental de 48 profesionales sanitarios del Estado. RESULTADOS: Encontramos trastorno de ansiedad presente en el 100% de las personas que vivían con filariasis linfática y en el 62% de las personas que vivían con lepra. También se encontró depresión en el 56% y el 75% de las personas que vivían con lepra y filariasis linfática respectivamente. Una evaluación de los obstáculos para la utilización de los servicios de salud mental revela que la mayoría de las personas con ETDs se ven limitadas por la falta de dinero para acudir a los hospitales, el miedo a la estigmatización, la discriminación y las largas distancias hasta los centros sanitarios. Por parte del personal sanitario, los conocimientos y la capacidad para ofrecer servicios de salud mental eran muy escasos. CONCLUSIONES: Para que los servicios de salud mental para personas con ETD se integren en el sistema sanitario comunitario, debe haber una concertación entre todas las partes interesadas y la intervención debe ser específica para cada contexto en lugar de generalizada.

Management of paediatric soil-transmitted helminthiasis in a non-endemic area: experience in a reference international health unit.

Soil-transmitted helminth (STH) infections inflict disability worldwide, especially in the poorest communities. Current therapeutic options against STHs show limited efficacy, particularly against Trichuris trichiura. The empirical management of patients coming from high-prevalence areas has been suggested for non-endemic areas. This study aimed to describe the management of STH infections in a non-endemic setting using an individualised approach. We performed a retrospective, descriptive study of all patients up to 16 years of age with STH infections attended at an international health unit in a non-endemic area (2014-2018), including all T. trichiura, Necator americanus, Ancylostoma duodenale, and Ascaris lumbricoides infections diagnosed using a formol-ether concentration technique and direct visualisation. Patients were treated according to current international guidelines. Sixty-one stool samples from 48 patients testing positive for STHs were collected, with 96% (46/48) reporting a previous long-term stay in endemic areas. Cure rates with 3-day benzimidazole regimens were 72% for T. trichiura, 40% for hookworms, and 83% for A. lumbricoides. The results were not influenced by any reinfection risk due to the study being performed in a non-endemic area. Patients coming from STH-endemic areas should be evaluated with appropriate diagnostic tools and followed up until cure control results. Cure rates in our cohort were moderate to low, similar to those published in studies in endemic areas. The efficacy of current treatment options is insufficient to recommend a specific empirical approach in high-income countries' healthcare systems.

Neglected Tropical Diseases: A Comprehensive Review.

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

Prevalence of trachoma in indigenous and non-indigenous areas, Northeastern Brazil, 2019-2021.

Objective: To estimate the prevalence of trachoma in indigenous and non-indigenous populations in selected areas of the state of Maranhão, in northeastern Brazil. Methods: This was a population-based survey with probabilistic sampling. For the diagnosis of trachoma, external ocular examination was performed using head magnifying loupes, at 2.5X magnification. The prevalence of trachomatous inflammation - follicular (TF) in children aged 1-9 years and the prevalence of trachomatous trichiasis (TT) in the population aged ≥15 years were estimated. Relative frequencies of sociodemographic and environmental characteristics were obtained. Results: The study included 7 971 individuals, 3 429 from non-indigenous populations and 4 542 from indigenous populations. The prevalence of TF in non-indigenous and indigenous populations was 0.1% and 2.9%, respectively, and the prevalence of TT among indigenous populations was 0.1%. Conclusions: The prevalence of TF and TT in the two evaluation units in the state of Maranhão were within the limits recommended for the elimination of trachoma as a public health problem. However, the prevalence of TF was higher in the indigenous evaluation unit, indicating a greater vulnerability of this population to the disease. The prevalence of TF of below 5.0% implies a reduction in transmission, which may have resulted from improved socioeconomic conditions and/or the implementation of the World Health Organization SAFE strategy.

Diagnóstico de neurocisticercosis en pacientes con epilepsia residentes en el suroeste de la República Dominicana / Diagnosis of neurocysticercosis in patients with epilepsy living in the south-western Dominican Republic

Introducción La neurocisticercosis (NCC), una posible causa de epilepsia con datos epidemiológicos limitados en la República Dominicana, es endémica en cuatro provincias de la región suroeste. El objetivo de este estudio fue determinar la asociación entre la NCC y la epilepsia en personas que viven en estas regiones endémicas, así como obtener datos preliminares sobre la prevalencia de NCC en estas provincias. Sujetos y métodos Se utilizó un diseño de casos y controles compuesto por 111 pacientes con epilepsia de causa desconocida y 60 controles sin epilepsia ni NCC. El diagnóstico de NCC se basó en la tomografía computarizada y la resonancia magnética del cráneo, así como en el inmunotransferencia de Western para anticuerpos séricos contra Taenia solium, siguiendo los criterios de Del Brutto et al. Resultados Se encontró NCC en el 27% de los pacientes con epilepsia (n = 30/111) y en el 5% de los controles (n = 3/60); los casos de epilepsia tenían siete veces más probabilidades de tener NCC que los controles (odds ratio = 7,04, intervalo de confianza al 95%: 2,04-24,18; p < 0,001). Las características sociodemográficas de los participantes, como la edad, el sexo, el nivel de escolaridad, la ocupación y la provincia de residencia no mostraron significación estadística en cuanto a la asociación con NCC. Conclusiones Este estudio sugiere que la NCC está fuertemente asociada con la epilepsia en la región suroeste de la República Dominicana, y destaca la necesidad de medidas de salud pública para mejorar la prevención, el diagnóstico y el tratamiento de ambas enfermedades. (AU)

INTRODUCTION Neurocysticercosis (NCC), a possible cause of epilepsy with limited epidemiological data in the Dominican Republic, is endemic in four provinces in the country’s south-western region. This study aimed to determine the association between NCC and epilepsy among people living in these endemic regions, and to obtain preliminary data on the prevalence of NCC in these provinces. PATIENTS AND METHODS A case-control design was used, consisting of 111 patients with epilepsy with unknown causes, and 60 controls without epilepsy or NCC. The diagnosis of NCC was based on computed tomography and magnetic resonance imaging of the skull, as well as Western immunoblotting for serum antibodies using Taenia solium, following the criteria of Del Brutto et al. RESULTS NCC was found in 27% of the epileptic patients (n = 30/111) and in 5% of the controls (n = 3/60); the probability of the epileptic patients having NCC was seven times higher than the controls (odds ratio = 7.04, 95% confidence interval: 2.04-24.18; p < 0.001). The participants’ sociodemographic characteristics, including their age, sex, level of education, occupation, and province of residence presented no statistical significance in terms of their association with NCC. CONCLUSIONS This study suggests that NCC is strongly associated with epilepsy in the south-western region of the Dominican Republic, and highlights the need for public health measures to improve the prevention, diagnosis and treatment of both diseases. (AU)

Highly abundant bacteria in the gut of Triatoma dimidiata (Hemiptera: Reduviidae) can inhibit the growth of Trypanosoma cruzi (Kinetoplastea: Trypanosomatidae).

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a zoonosis primarily found in rural areas of Latin America. It is considered a neglected tropical disease, and Triatoma dimidiata is the main vector of the parasite in Central America. Despite efforts, Chagas disease continues to be a public health concern, and vector control remains a primary tool to reduce transmission. In this study, we tested the hypothesis that highly abundant bacteria in the gut of T. dimidiata inhibit the growth of T. cruzi. To achieve this, bacterial diversity in the gut of T. dimidiata specimens from Costa Rica was characterized by metabarcoding of the 16S rRNA, microbial isolation was performed, and the effect of freeze-dried supernatants of the isolates on T. cruzi was investigated. Metabarcoding showed that the most abundant genera in the gut were Corynebacterium, Tsukamurella, Brevibacterium, and Staphylococcus. Barcoding and sequences comparison confirmed that 8 of the 30 most abundant amplicon sequence variants (ASVs) were isolated, and 2 of them showed an inhibitory effect on the growth of T. cruzi epimastigotes. These bacteria correspond to isolates of Tsukamurella and Brevibacterium, which were respectively the second and sixth most abundant ASVs in the gut of T. dimidiata. Notably, only the isolate of Brevibacterium showed a significant difference in growth inhibition against epimastigotes of both T. cruzi strains tested. These findings suggest that the gut microbiota of T. dimidiata may play an active role in modulating parasite development.

Pull me - push you? The disparate financing mechanisms of drug research in global health.

BACKGROUND: There is an inconsistency in the way pharmaceutical research is financed. While pull mechanisms are predominantly used to incentivize later-stage pharmaceutical research for products with demand in the Global North, so-called neglected diseases are chiefly financed by push funding. This discrepancy has so far been ignored in the academic debate, and any compelling explanation for why we draw the line between push and pull at poor people is lacking. MAIN BODY: Clinical development of new pharmaceuticals is chiefly financed by free market pull mechanisms. Even in cases where markets fail to deliver adequate incentives, demand enhancement mechanisms are used to replicate pull funding artificially, for example, with subscription models for antibiotics. Push funding in clinical research is almost always used when the poverty of patients means that markets fail to create sufficient demand. The general question of whether push or pull generally is the more efficient way to conduct pharmaceutical research arises. CONCLUSIONS: If the state is efficient in directing limited budgets for pharmaceutical research, push funding should be expanded to global diseases. If private industry is the more efficient actor, there would be enormous value in experimenting more aggressively with different approaches to enhance market demand artificially for neglected diseases.

Personalised human albumin in patients with cirrhosis and ascites: design and rationale for the ALB-TRIAL - a randomised clinical biomarker validation trial.

INTRODUCTION: Human albumin is used in the treatment of complications of cirrhosis. However, the use of long-term human albumin administration is costly and resource demanding for both patients and healthcare systems. A precision medicine approach with biomarkers to predict human albumin treatment response, so-called predictive biomarkers, could make this a viable treatment option in patients with cirrhosis and ascites. METHODS AND ANALYSIS: ALB-TRIAL is a multinational, double-blind, placebo-controlled randomised controlled trial. We aim to validate a predictive biomarker, consisting of a panel of circulating metabolites, to predict the treatment response to human albumin in patients with cirrhosis and ascites. All enrolled patients are stratified into a high-expected or low-expected effect stratum of human albumin based on the biomarker outcome. After stratification, patients in each group are randomised into either active treatment (20% human albumin) or corresponding placebo (0.9% NaCl) every 10th day for 6 months. The primary outcome is the cumulative number of liver-related events (composite of decompensation episodes, transjugular intrahepatic shunt insertion, liver transplantation and death). Key secondary outcomes include time-to-event analysis of primary outcome components, an analysis of the total healthcare burden and a health economic analysis. ETHICS AND DISSEMINATION: The trial obtained ethical and regulatory approval in Denmark, Germany, the Netherlands, Belgium, Hungary and Spain through the Clinical Trials Information System (CTIS) from 13 February 2023, while UK approvals from the Health Regulatory Authority, Medicines and Healthcare products Regulatory Agency and Research Ethics Committee are pending. Findings will be published in peer-reviewed journals, presented at conferences, communicated to relevant stakeholders and in the public registry of CTIS, following trial completion. TRIAL REGISTRATION NUMBER: NCT05056220 EU CT: 2022-501006-34-01.