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 The chemotherapeutic arsenal available for treating NTD is limited and outdated, which poses a challenge in controlling and eradicating these diseases.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.

Innovating Leishmaniasis Treatment: A Critical Chemist's Review of Inorganic Nanomaterials.

Leishmaniasis, a critical Neglected Tropical Disease caused by Leishmania protozoa, represents a significant global health risk, particularly in resource-limited regions. Conventional treatments are effective but suffer from serious limitations, such as toxicity, prolonged treatment courses, and rising drug resistance. Herein, we highlight the potential of inorganic nanomaterials as an innovative approach to enhance Leishmaniasis therapy, aligning with the One Health concept by considering these treatments' environmental, veterinary, and public health impacts. By leveraging the adjustable properties of these nanomaterials─including size, shape, and surface charge, tailored treatments for various diseases can be developed that are less harmful to the environment and nontarget species. We review recent advances in metal-, oxide-, and carbon-based nanomaterials for combating Leishmaniasis, examining their mechanisms of action and their dual use as standalone treatments or drug delivery systems. Our analysis highlights a promising yet underexplored frontier in employing these materials for more holistic and effective disease management.

An Overview of Tsetse Fly Repellents: Identification and Applications.

Tsetse flies are vectors of the parasite trypanosoma that cause the neglected tropical diseases human and animal African trypanosomosis. Semiochemicals play important roles in the biology and ecology of tsetse flies. Previous reviews have focused on olfactory-based attractants of tsetse flies. Here, we present an overview of the identification of repellents and their development into control tools for tsetse flies. Both natural and synthetic repellents have been successfully tested in laboratory and field assays against specific tsetse fly species. Thus, these repellents presented as innovative mobile tools offer opportunities for their use in integrated disease management strategies.

Leprosy knowledge among primary care physicians in Southern Brazil: are we underdiagnosing?

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.

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.

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.

A Neglected Fracture of Acetabulum Treated With Total Hip Replacement.

Total hip replacement (THR) for osteoarthritis or inflammatory arthritis yields better outcomes than THR for patients with neglected acetabular fractures. The inferior clinical results mostly arise from an unforeseen bone deficit, making the treatment more time-consuming and complex for instances requiring acetabular restoration and bone grafting. There is a lack of research on the clinical results of THR in cases where acetabular fractures have been overlooked. A 55-year-old male patient presented with a malunited anterior column of the acetabulum, non-union of the posterior column with protrusion, and a significant impaction fracture in the femoral head. He was then treated with open reduction and internal fixation (ORIF) of acetabular columns, along with the use of a reconstruction cage and bone grafting. At the five-year follow-up, the patient had a good outcome. The keys to success include meticulous preoperative planning using radiography and computed tomography (CT) scans, sufficient exposure to define the fracture pattern, and the availability of a full range of devices and backup implants. If there are any prior implants, they should only be removed if they are infected or in the way of cup implantation. However, if there is a significant amount of bone loss, complex fractures may require extensive repair using revision total hip arthroplasty (THA) implants.

Extensive Gouty Tophus in Neglected Femoral Neck Fracture: A Case Report.

Femoral neck fractures are extremely common injuries, especially in the elderly, who often have multiple associated comorbidities. Despite advances in surgical technique and implant technology, neglected fractures are still a reality in developing countries due to the lack of access to healthcare services or socioeconomic conditions of patients. This case report presents a 61-year-old male patient referred from a rural area to a trauma referral hospital with a neglected femoral neck fracture. The patient had multiple comorbidities, and during the surgical approach for total hip arthroplasty, the intraoperative finding of an extensive gouty tophus led to an increase in surgical time and modifications in the surgical procedure. The epidemiological profile of the patient in question fits the pattern of patients with diffuse gouty arthropathy, warranting suspicion of hip involvement when manifested in other joints. Performing complementary exams in patients preoperatively with proximal femur fractures and coxarthrosis can be an indispensable tool for the successful implementation of the therapeutic plan. This report presents these findings and the outcome of the method used.

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.

Neglected Posterior Dislocation Hip Post Acetabulum Fixation: Case Report.

Introduction: An acetabular fracture is a relatively uncommon injury. An acetabular fracture can occur in conjunction with a posterior hip dislocation. Oni defined neglected hip dislocation as dislocation lasting more than 1 week after injury. Case Report: We present a 31-year-old male involved in a road traffic accident 6 months ago. He had 5 cm of shortening on examination, and the sciatic nerve was intact. The patient had post-traumatic arthritis and was counseled for total hip arthroplasty (THA) and its complications. Conclusion: Neglected posterior dislocation of the hip after acetabular fracture fixation is rare these days. It is a time-sensitive medical emergency that must be reduced within 6 h to avoid its complications, especially avascular necrosis and post-traumatic arthritis.

Community Feedback on Mass Medicines Administration for Neglected Tropical Diseases in Federal Capital Territory, Abuja, Nigeria.

The World Health Organization (WHO) recommends the use of annual mass drug administration (MDA) as the strategy for controlling and eliminating the five preventive chemotherapy neglected tropical diseases (PC-NTDs). The success of MDAs hinges on community acceptance, active participation, and compliance. This study aimed to explore the experiences and perceptions of community members, to obtain a more thorough understanding of their openness and willingness to participate in MDA and other NTD elimination activities. A mixed-methods approach was employed, utilizing qualitative and quantitative methods for comprehensive data collection. Eighteen key informant interviews (KIIs) and sixteen focus group discussions (FGDs) were conducted to explore community engagement, participation, medication utilization, and programme perception. Triangulation of findings from interviews and discussions with household survey results was performed to gain a deeper understanding of emerging themes. The household survey involved interviewing 1220 individuals (Abaji: 687; Bwari: 533). Audio tapes recorded KIIs and FGDs, with interview transcripts coded using Nvivo 12.0 software based on predefined themes. Descriptive analysis using SPSS version 21 was applied to quantitative data. Results indicated high awareness of mass drug administration (MDA) campaigns in both area councils (Abaji: 84.9%; Bwari: 82.9%), with a small percentage claiming ignorance (15.1%), attributed to lack of information or absence during health campaigns. Respondents primarily participated by taking medication (82.5%), with minimal involvement in other MDA campaigns. Perception of medicines was generally positive, with a significant association between participation level and performance rating (p < 0.05). The study recommends leveraging high awareness and community responsiveness to enhance engagement in various MDA activities, ensuring sustainability and ownership of the programme.

How to Overcome a Snail? Identification of Putative Neurotoxins of Snail-Feeding Firefly Larvae (Coleoptera: Lampyridae, Lampyris noctiluca).

The larvae of some lampyrid beetles are highly specialized predators of snails. They have been observed to climb on the shells of their prey and use this exposed position to bite and inject secretions potentially originating from the midgut. Besides serving the purpose of extra-oral digestion (EOD), injected compounds also seem to have a paralyzing effect. Up to now, the toxins causing this paralyzing activity have not been identified. In the current study, we provide a first compositional analysis of the midgut secretion from lampyrid larvae, with a focus on identifying putative neurotoxins causing the observed paralyzing effect. For this purpose, we utilized a combined proteo-transcriptomic approach to characterize the compounds present in the midgut secretion of larval stages of Lampyris noctiluca. In terms of the absolute numbers of identified compounds, the midgut secretion is dominated by hydrolyzing enzymes comprising peptidases, carboxylesterases, and glycosidases. However, when considering expression levels, a few rather short cysteine-rich peptides exceed all other compounds. Some of these compounds show moderate similarity to putative neurotoxins identified in the venom of other arthropods and could be responsible for paralyzing effects. In addition to these potential toxins, we provide a list of peptides typical of the midgut secretion of L. noctiluca, supplemented by the corresponding precursor sequences.

Research on Moringa (Moringa oleifera Lam.) in Africa.

While Moringa oleifera Lam. is gaining importance in Africa, especially sub-Saharan Africa, it is unclear whether research is following the quick pace of its development on the continent. Therefore, this article analyzes the landscape of research dealing with moringa in Africa. This systematic review draws upon 299 eligible articles identified through a search carried out on the Web of Science in April 2023. Research on M. oleifera is rather recent in Africa but interest is increasing among scholars. While the research field is multidisciplinary and cross-sectoral, the literature seems to focus on biological and environmental sciences. Moreover, research is performed mainly in South Africa, Nigeria, Egypt, and Ghana. The analysis suggests a significant potential contribution of moringa to food security and nutrition, climate change mitigation/adaptation, farming systems resilience, and livelihoods. Its versatility and diverse applications and uses make moringa particularly interesting for developing countries, such as African ones. However, this review also underscores some factors hindering its development. Therefore, there is a need to strengthen research on moringa to unlock its potential in Africa. Investments in research, innovation, and development can help address the many challenges that Africa faces and contribute to the transition towards sustainable and resilient food systems.

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.

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.

Novel 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidine derivatives and their antitrypanosomal activities against T.brucei.

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 <1 µM range. We have demonstrated that substituted 4-[4-(4-methylpiperazin-1-yl)phenyl]-6-arylpyrimidines present promising antitrypanosomal hit molecules with potential for further preclinical development.