Neglected Tropical Diseases Research Articles

Intestinal parasitic infections and risk factors among the population in Cambodia.

Many species of helminths and protozoa caused intestinal parasitic infections (IPIs). It belongs to neglected tropical diseases (NTDs) and remains a major public health problem in several Southeast Asian countries. The present study aimed to investigate the prevalence of IPIs and associated risk factors among the population in Kratie Province in northeastern Cambodia and Phnom Penh is the capital that locates in southern Cambodia. Fecal specimens (n=366) were collected in 10 villages in Kratie Province and Phnom Penh from 2019 to 2021. They were processed using the formalin ethyl-acetate concentration technique (FECT) to investigate parasites at egg and cyst stages and then examined under a light microscope. The results revealed that the prevalence of IPIs among the population in Kratie Province (n=317) and Phnom Penh (n=49) was 16.12% (n=59); of Kratie Province (n=50, 13.66%) and Phnom Penh (n=9, 2.46%), 12.02% (n=44) were helminths and 4.10% (n=15) were protozoa. The parasitic infection rate was higher in males (9.02%) than in females (7.10%) and more likely to be due to helminths (7.38%) than protozoa (1.64%). Prevalence of Opisthorchis viverrini was the highest (5.74%), followed by those of Entamoeba coli (4.10%), hookworm (3.83%), Ascaris lumbricoides (1.10%), Hymenolepis nana (1.09%), Taenia spp. (0.54%), Trichuris trichiura (0.55%), and Enterobius vermicularis (0.27%), respectively. Moreover, O. viverrini infection was the most common infection in the <20-year age group in Kratie Province. In addition, the bivariate and multivariate analyses showed that the association between gender. Gender was a significant risk factor positively associated with O. viverrini and hookworm infections (ORadj=0.318, 95% CI=0.122-0.8270, P=0.019 and ORadj=0.085, 95% CI=0.017-0.436, P=0.003, respectively). In conclusion, the IPIs were highly prevalent, especially O. viverrini and hookworm infections, among the population in Cambodia. These IPIs impact the public health burden but can be prevented by education regarding good sanitary practices in this community.

Exploring the repositioning of the amodiaquine as potential drug against visceral leishmaniasis: The in vitro effect against Leishmania infantum is associated with multiple mechanisms, involving mitochondria dysfunction, oxidative stress and loss of cell cycle control

Visceral leishmaniasis (VL) is a progressive, debilitating, and potentially fatal disease if left untreated. As a neglected tropical disease (NTD), the available treatment is restricted to a few drugs, which typically must be administered over a long period but are associated with serious adverse effects and have variability in efficacy. In this sense, drug repositioning has been considered an excellent strategy in the search for alternative treatments, especially in reducing the time and cost of the research. In this work, the repositioning potential of amodiaquine (AQ), a well-known antimalarial drug, was investigated for the treatment of VL. AQ showed significant and selective activity against promastigotes (IC50 = 11.6 μg/mL) and intracellular amastigotes (IC50 = 2.4 μg/mL) of L. infantum, being 10 times more destructive to the intracellular parasites than the host cell. In addition, pre-treatment of macrophages with AQ caused a significant reduction in the infection index, indicating a prophylactic effect of this drug. SEM images showed that AQ induces strong shape alterations of the promastigotes with an increase in cell volume with rounding and ribbing (vertical ridges), as well as a shortened flagellum. In addition, AQ induced depolarization of the ΔΨm, an increase in ROS and neutral lipids levels, and changes in the cell cycle in promastigotes, without alterations to the permeability of the parasite plasma membrane. L. infantum-infected macrophages treated with AQ induced the activation of oxidative mechanisms by infected host cells, with an increase in ROS and NO levels. Finally, in vitro interactions between AQ and miltefosine were found to have an additive effect in both biological stages of the parasite, with the ∑FIC50 values ranging from 0.74 to 1.16 μg/mL and 0.54–1.11 μg/mL for promastigotes and intracellular amastigotes, respectively. Overall, these data highlight the utility of drug repurposing and indicate future preclinical testing for AQ itself or in combination as a potential VL treatment.

Natural Products and Synthetic Derivatives as Promising Candidates Against Neglected Tropical Diseases

Neglected Tropical Diseases (NTD) are a group of endemic diseases that cause up to one million deaths annually. Leishmaniasis and Chagas Disease are classified as NTD whose current treatments are of limited access. There is an urgent need to develop new agents to combat or alleviate the symptoms of these pathologies. The present work highlights the activities of several natural products and their derivatives which have been tested against the causative parasites of both diseases. The activities of natural products illustrate their potential to assist in the combat against NTD. Research in this area could provide an opportunity to advance medical research and to provide treatments to low- and middle-income countries.

Artemether and Praziquantel a green light to treat the resistance schistosomiasis: A case Report

Schistosomiasis is a neglected tropical disease (NTD) that remains one of the most prevalent parasitic infections in Africa , S. mansoni and S. haematobium are the most common species that infect humans and the Praziquantel (PZQ) is the drug of choice for treatment despite the recent resistance to it .In this case report, we present an augmenting evidence to support the use of combination regimen of antimalarial drug, Artemether (ART) along with Praziquantel, as an efficient methodology in the treatment of resistant urinary schistosomiasis.

Prevention, Treatment and Eradication of NTDs by Concerted Efforts-Prognosis and Prediction

Abstract: Neglected Tropical Diseases (NTDs) are diseases of poverty most prevalent in continents Africa, some parts of Asia, and the low-income regions of G20 countries. The name was given because of the neglect of the global burden of this category of diseases leading to lesser and lesser control strategies by one and all. Although medically diverse, neglected diseases share features that allow them to persist in extreme poverty. The mortality rates with these diseases are relatedly low, but morbidity rates, the main concern, are comparatively higher. This review covers the importance of the control of the NTDs at different levels of control community, national and international levels missed by many of the publications. The visual impact of most diseases is manifested in the form of disfigurement, blindness, and disabilities believed to be dreadful stigmas that people try to hide. Keeping in mind this aspect, there is an urgent need to convince most people to contribute to controlling and preventing the further spread of these diseases. Thus, motivating community-level control. The first detailed study on the global burden of these diseases and the risk factors involved was initiated by the World Bank in 1992. A follow-up study was performed in 2005. This was the basis for the start of the fight against these diseases, initially selecting the eight most affecting diseases and then gradually increasing to 13 by 2006. World Health Organization also released its first report on NTDs in 2010, compiling all the related aspects. The report was the basis for selecting diseases as targets and reached 17 diseases by 2013. Most of the reviews have not highlighted the importance of the various pharmacoeconomics and pharmacoepidemiology strategies which can be incorporated to get better results in eradicating these diseases. The main bottleneck is the inaccurate and imprecise measurement of the disease burden from the data, which does not give a clear picture of the disease. The detail of parameters selected for most of the measurement of disease burden, Disability- Adjusted Life Year (DALY), and measuring tools, which have been incorporated from time to time to meet the requirement, are also covered. The review also highlights the role played by different strata of a system for better control of these diseases.

The impact of neglected tropical diseases on women and girl refugees: A call for increased awareness and strategic intervention

As the number of forcibly displaced women and girls increases, it becomes ever important to recognize the negative health impacts of being displaced. Women and girl refugees are disproportionately affected by sexual and gender-based violence and mental health concerns. In addition to these health concerns in women, crowding and lack of clean water in refugee camps leads to the spread of infectious diseases in general. Neglected tropical diseases (NTDs) are infectious diseases of poverty found in tropical areas, and longstanding infections lead to significant morbidity. Particularly for women, these diseases can impact fertility, chronic disease in pregnancy, and social stigma. Despite being a high-risk group, there are minimal data on the impact of NTDs on the health of Women and girl refugees. Diseases such as schistosomiasis, soil-transmitted helminth infections, strongyloidiasis, and leishmaniasis have all been shown to affect Women and girl refugees, but the majority of these data describe NTDs in this population only after resettlement. Access to medical care with providers that are knowledgeable about NTDs while in situations of displacement as well as after third-country resettlement is crucial to their timely diagnosis and treatment to prevent longstanding sequalae. More studies in this at-risk population are needed to understand the extent of this issue and begin to work towards lasting, equitable healthcare.

The development of an artificial intelligence-based digital pathology for neglected tropical diseases: A platform specific analysis of the World Health Organization diagnostic target product profile for soil-transmitted helminthiasis

The World Health Organization (WHO) recently published target product profiles (TPPs) for neglected tropical diseases (NTDs) to inform and accelerate the development of diagnostics tools necessary to achieve targets in the decade ahead. These TPPs describe the minimal and ideal requirements for various diagnostic needs related to NTD specific use-cases. An early step towards the manufacture and implementation of new diagnostics is to critically review the TPPs and translate these into an initial design and ultimately into user requirement specifications (URS). Artificial intelligence-based digital pathology (AI-DP) may overcome critical shortcomings of current standards for most NTDs reliant on microscopy, such as poor reproducibility and error-prone manual read-out. Furthermore, a digitalised workflow can create opportunities to reduce operational costs via increased throughput and automated data capture, analysis, and reporting. Despite these promising benefits, a critical review of the NTD TPPs with consideration to an AI-DP diagnostic solution is lacking. We present a systematic analysis of one of the WHO TPPs with the aim to inform the development of a URS for an AI-DP solution for NTDs. As a case study we focused on monitoring and evaluation (M&amp;amp;E) of programs designed to control soil-transmitted helminths (STHs). To this end, we start by outlining a brief overview of diagnostic needs for STHs, after which we systematically analyse the recently published WHO TPPs, highlighting the technical considerations for an AI-DP diagnostic solution to meet the minimal requirements for this TPP. Finally, we further reflect on the feasibility of an AI-DP informing STH programs towards the WHO 2030 targets in due time.

Prevalence of skin Neglected Tropical Diseases and superficial fungal infections in two peri-urban schools and one rural community setting in Togo.

Skin neglected tropical diseases (NTDs), are endemic and under-diagnosed in many lower-income communities. The objective of this study was to determine the prevalence of skin NTDs and fungal infections in two primary schools and a community setting in rural Togo. This was a cross-sectional study that took place between June-October 2021. The two primary schools are located on the outskirts of Lomé, the capital city. The community setting was Ndjéi, in north-east Togo. Study sites were purposively selected. Dermatologists examined the skin of study participants. Diagnosis of skin NTDs were made clinically. A total of 1401 individuals were examined, 954 (68.1%) from Ndjéi community, and 447 (31.9%) were children in the schools. Cutaneous skin infections were diagnosed in 438 (31.3%) participants, of whom 355 (81%) were in community settings. There were 105 observed skin NTDs (7.5%). Within the school setting, there were 20 individuals with NTDs (4.5% of 447 participants), and 85 NTDs (8.9%) from 954 community participants. Across all settings 68/1020 (6.7%) NTDs were in children, and 37/381 (9.7%) in adults. In addition, there were 333 observed mycoses (23.8% prevalence). The main cutaneous NTDs diagnosed were scabies (n = 86; 6.1%) and suspected yaws (n = 16, 1.1%). The prevalence of scabies in schools was 4.3%, and 7.0% in the rural community. One case of leprosy was diagnosed in each school and the rural community, and one suspected Buruli Ulcer case in the community. In the school setting, five (6%) children with a skin NTD reported being stigmatised, four of whom had refused to attend school because of their dermatosis. In Ndjéi, 44 (4.6%) individuals reported having experienced stigma and 41 (93.2%) of them missed at least one day of school or work. This study shows that the burden of scabies and skin infections such as superficial mycoses is high in the school and rural community settings in Togo, with associated presence of stigma. Improved health promotion and education across institutional and community settings may reduce stigma and encourage early reporting of skin infection cases to a health facility.

Molecular Modeling, Virtual Screening, and Molecular Dynamics for Leishmania infantum Methionyl-tRNA Synthetase.

Visceral leishmaniasis is a neglected tropical disease (NTD) caused by Leishmania infantum and L. donovani that is lethal in cases of nontreatment. The treatments are limited by serious drawbacks involving safety, resistance, stability, and high costs. In this work, we aimed to identify inhibitors of Leishmania infantum methionyl-tRNA synthetase (LiMetRS), a validated molecular target for leishmaniasis drug discovery, using a combination of strategies. A virtual database of compounds was organized by filtering compounds from the ZINC15 database. Homology modeling was used to obtain the structure of LiMetRS based on the crystal coordinates of the enzyme from Trypanosoma brucei (TbMetRS). A virtual screening using molecular docking identified 10 candidate compounds from among more than 5 million that were included in the initial database. The selected hits were further evaluated using a script created in this work to select only the ligands that interacted with specific amino acids in the catalytic site of the enzyme. Furthermore, suitable pharmacokinetic profiles were predicted for the selected compounds, especially a good balance between aqueous solubility and lipophilic character, no ability to cross the blood-brain barrier, good oral absorption, and no liability toward P-gp efflux for most compounds. Six compounds were then subjected to all-atom molecular dynamics. Two compounds showed good stability when bound to the leishmanial enzyme, which provided a deeper understanding of the structural differences between TbMetRS and LiMetRS that can guide further drug discovery efforts for visceral leishmaniasis.

Limitations of current chemotherapy and future of nanoformulation-based AmB delivery for visceral leishmaniasis-An updated review.

Visceral leishmaniasis (VL) is the most lethal of all leishmaniasis diseasesand the second most common parasiticdisease after malaria and,still, categorized as a neglected tropical disease (NTD). According to the latest WHO study, >20 Leishmania species spread 0.7-1.0 million new cases of leishmaniasis each year. VL is caused by the genus, Leishmania donovani (LD), which affects between 50,000 and 90,000 people worldwide each year. Lack of new drug development, increasing drug resistance, toxicity and high cost even with the first line of treatmentof Amphotericin B (AmB), demands new formulation for treatment of VLFurther the lack of a vaccine, allowedthe researchers to develop nanofomulation-based AmB for improved delivery. The limitation of AmB is its kidney and liver toxicity which forced the development of costly liposomal AmB (AmBisome) nanoformulation. Success of AmBisome have inspired and attracted a wide range of AmB nanoformulations ranging from polymeric, solid lipid, liposomal/micellar, metallic, macrophage receptor-targetednanoparticles (NP) and even with sophisticated carbon/quantum dot-based AmBnano delivery systems. Notably, NP-based AmB delivery has shown increased efficacy due to increased uptake, on-target delivery and synergistic impact of NP and AmB. In this review, we have discussed the different forms of leishmaniasis disease and their current treatment options with limitations. The discovery, mechanism of action of AmB, clinical status of AmB and improvement with AmBisome over fungizone (AmB-deoxycholate)for VL treatment was further discussed. At last, the development of various AmB nanoformulation was discussed along with its adavantages over traditional chemotherapy-based delivery.

Integrated survey of helminthic neglected tropical diseases and comparison of two mosquito sampling methods for lymphatic filariasis molecular xenomonitoring in the River Galana area, Kilifi County, coastal Kenya.

A lymphatic filariasis (LF) endemic focus along the River Galana/ Sabaki in Kilifi County, coastal Kenya, provided a platform to conduct an integrated survey for three helminthic neglected tropical diseases (NTDs), namely soil-transmitted helminthiasis (STH), schistosomiasis (SCH) and LF. Additionally, the study compared the performance of two mosquito trapping methods for LF molecular xenomonitoring (MX). Cross-sectional surveys measuring STH, SCH and LF prevalence were conducted in four villages. Mosquitoes were trapped using the CDC light trap (CDC-LT) and the Ifakara A tent trap (Ifakara-TT) methods and stored in pools which were tested for Wuchereria bancrofti DNA using the real-time polymerase chain reaction assay. A total of 907 people (436 adults; 471 children) participated in the parasitological testing. Among the STH infections, Trichuris trichiura and hookworms were most prevalent among the children and adult populations, respectively. The schistosome worm eggs detected belonged to the species Schistosoma haematobium and the prevalence of the infection was generally higher among the children compared with the adult population. The prevalence of LF infection among the adult population ranged from 1.8% to 7.6% across all 4 villages (P < 0.05). A total of 3,652 mosquitoes, including Anopheles, Culex, Mansonia, and Aedes species were collected. One mosquito pool consisting of Anopheles mosquitoes tested positive for filarial DNA out of 1,055 pools that were tested. The CDC-LT caught significantly more mosquitoes compared with the Ifakara-TT (P < 0.001). This study demonstrated that integrated epidemiological surveys using standard parasitological and entomological methods can provide useful information on co-endemic parasitic diseases which could help direct interventions and surveillance activities.

Assessing the Quality of the World Health Organization's Skin NTDs App as a Training Tool in Ghana and Kenya: Protocol for a Cross-sectional Study.

Neglected tropical diseases (NTDs) affect over 1.5 billion people worldwide, the majority of them belonging to impoverished populations in low- and middle-income countries (LMICs). Skin NTDs are a subgroup of NTDs that manifest primarily as skin lesions. The diagnosis and treatment of skin NTDs entail considerable resources, including trained personnel and financial backing. Many interventions are being launched and evaluated, particularly mobile health (mHealth) interventions, such as Skin NTDs App, a training and decision support tool offered by the World Health Organization (WHO) for frontline health workers (FHWs). As most digital health guidelines prioritize the thorough evaluation of mHealth interventions, it is essential to conduct a rigorous and validated assessment of Skin NTDs App. We aim to assess the quality of version 3 of Skin NTDs App, developed for the WHO by Universal Doctor and Netherlands Leprosy Relief as a training and decision support tool for FHWs. A cross-sectional study will be conducted in 2 LMICs: Ghana and Kenya. We will use snowball sampling recruitment to select 48 participants from the target population of all FHWs dealing with skin NTDs. The sample group of FHWs will be asked to download and use Skin NTDs App for at least 5 days before answering a web-based survey containing demographic variables and the user Mobile App Rating Scale (uMARS) questionnaire. A semistructured interview will then be conducted. Quantitative and qualitative data will be analyzed using SPSS (version 25; SPSS Inc), with statistical significance for all tests set at a 95% CI and P≤.05 considered significant. Data derived from the semistructured interviews will be clustered in themes and coded to enable analysis of various dimensions using ATLAS.ti. The estimated completion date of the study is in the third quarter of 2022. The results are expected to show that Skin NTDs App version 3 has a good reported user experience, as assessed using the uMARS scale. No differences are expected to be found, except for those related to experience in dermatology and the use of mobile technology that could influence the final score. Semistructured interviews are expected to complete the results obtained on the uMARS scale. Moreover, they will be the previous step before assessing other aspects of the app, such as its efficiency and how it should be disseminated or implemented. This study is the first step in a qualitative and quantitative assessment of Skin NTDs App as a training and support tool for FHWs diagnosing and managing skin NTDs. Our results will serve to improve future versions of the App. PRR1-10.2196/39393.

Chagas Heart Disease: Beyond a Single Complication, from Asymptomatic Disease to Heart Failure.

Chagas cardiomyopathy (CC), caused by the protozoan Trypanosoma cruzi, is an important cause of cardiovascular morbidity and mortality in developing countries. It is estimated that 6 to 7 million people worldwide are infected, and it is predicted that it will be responsible for 200,000 deaths by 2025. The World Health Organization (WHO) considers Chagas disease (CD) as a Neglected Tropical Disease (NTD), which must be acknowledged and detected in time, as it remains a clinical and diagnostic challenge in both endemic and non-endemic regions and at different levels of care. The literature on CC was analyzed by searching different databases (Medline, Cochrane Central, EMBASE, PubMed, Google Scholar, EBSCO) from 1968 until October 2022. Multicenter and bioinformatics trials, systematic and bibliographic reviews, international guidelines, and clinical cases were included. The reference lists of the included papers were checked. No linguistic restrictions or study designs were applied. This review is intended to address the current incidence and prevalence of CD and to identify the main pathogenic mechanisms, clinical presentation, and diagnosis of CC.

Small molecules containing chalcogen elements (S, Se, Te) as new warhead to fight neglected tropical diseases

Neglected tropical diseases (NTDs) encompass a group of infectious diseases with a protozoan etiology, high incidence, and prevalence in developing countries. As a result, economic factors constitute one of the main obstacles to their management. Endemic countries have high levels of poverty, deprivation and marginalization which affect patients and limit their access to proper medical care. As a matter of fact, statistics remain uncollected in some affected areas due to non-reporting cases. World Health Organization and other organizations proposed a plan for the eradication and control of the vector, although many of these plans were halted by the COVID-19 pandemic. Despite of the available drugs to treat these pathologies, it exists a lack of effectiveness against several parasite strains. Treatment protocols for diseases such as American trypanosomiasis (Chagas disease), leishmaniasis, and human African trypanosomiasis (HAT) have not achieved the desired results. Unfortunately, these drugs present limitations such as side effects, toxicity, teratogenicity, renal, and hepatic impairment, as well as high costs that have hindered the control and eradication of these diseases. This review focuses on the analysis of a collection of scientific shreds of evidence with the aim of identifying novel chalcogen-derived molecules with biological activity against Chagas disease, leishmaniasis and HAT. Compounds illustrated in each figure share the distinction of containing at least one chalcogen element. Sulfur (S), selenium (Se), and tellurium (Te) have been grouped and analyzed in accordance with their design strategy, chemical synthesis process and biological activity. After an exhaustive revision of the related literature on S, Se, and Te compounds, 183 compounds presenting excellent biological performance were gathered against the different causative agents of CD, leishmaniasis and HAT.

Neglected Tropical Diseases (NTDs) and COVID-19 Pandemic in Africa: Special Focus on Control Strategies.

Neglected Tropical Diseases (NTDs) are a group of twenty (20) chronic, communicable, infectious diseases endemic to the tropics and sub-tropics climate countries, which are intimately associated with poverty, poor sanitation, limited clean water, and healthcare delivery; and dwellers live in proximity to pathogens and diseases vectors. The pathogens are protozoans, bacteria, helminths, fungi, and viruses. NTDs currently affect about one billion people globally, out of which 500 million are Africans living in rural settlements with low political voice and support. In recent years, NTDs have received little research recognition, development, and funding because more research efforts by global health stakeholders are focused on recognized diseases like cancers, hepatitis, tuberculosis, Acquired Immune-Deficiency Syndrome (AIDS), and malaria that affects most developed countries. The emergence of the viral novel COVID-19 will exacerbate the burden of NTDs on disadvantaged communities as global health efforts are again focused on COVID-19 clearance in terms of research and development to find a drug/vaccine amidst other investigations on recognized infections. This development can result in high death tolls due to NTDs if control measures are not prioritized now. This perspective addresses the need for NTDs control amidst COVID-19 clearance efforts to mitigate another viral health crisis in Africa.

NTD Health: an electronic medical record system for neglected tropical diseases.

The use of technological resources to support processes in health systems has generated robust, interoperable and dynamic platforms. In the case of institutions working with neglected tropical diseases (NTD), there is a need for NTD-specific customizations. To establish a medical records platform, specialized for NTD, which would facilitate the analysis of treatment evolution in patients, as well as generate more accurate data about various clinical aspects. Here we developed a customized electronic medical record system based on OpenMRS for multiple NTDs. A set of forms and functionalities was developed under the OpenMRS guidelines, using shared community modules. All the customized information was packaged in a distribution called NTD Health. The platform is web-based and can be upgraded and improved by users without technological barriers. The EMR system can become a useful tool for other institutions to improve their health practices as well as the quality of life for NTD patients, simplifying the customization of healthcare systems able to interoperate with other platforms.

Molecular detection of drug resistance in clinical specimens of leprosy patients from a tertiary care leprosy centre in South India

Background Leprosy is one of the neglected tropical diseases (NTD) experiencing relative stagnancy in the global number of new cases. Objective This study aims to find the proportion of antimicrobial resistance in the clinical specimens of leprosy patients attending a tertiary care leprosy Institute in South India. Materials and methods Skin biopsy specimens (31 Nos) were tested by Polymerase chain reaction (PCR) for identification of M. leprae, and PCR followed by DNA sequencing for antimicrobial resistance (AMR) detection. Results All 31 specimens tested for M. leprae identification were positive. Resistance to dapsone was 6.5%, while rifampicin and ofloxacin showed 100% sensitivity. Conclusion This study warrants the need for a vigilant surveillance mechanism to monitor the trend of antimicrobial resistance in leprosy.

Buruli-RifDACC: Evaluation of the efficacy and cost-effectiveness of high-dose versus standard-dose rifampicin on outcomes in Mycobacterium ulcerans disease, a protocol for a randomised controlled trial in Ghana [version 1; peer review: 2 approved

Buruli ulcer (BU) can lead to disfiguring ulcers and permanent disability. The 2030 World Health Organization (WHO) road map for Neglected Tropical Diseases (NTDs) calls for major scaling up in diagnosis and management to eliminate disability due to the disease. Current treatment for BU is with daily oral rifampicin (10mg/kg dose) and clarithromycin (15mg/kg dose) for eight weeks, combined with standard gauze wound dressings. Dialkylcarbamoyl chloride (DACC)-coated dressings have been shown to irreversibly bind bacteria on wound surfaces resulting in their removal when dressings are changed. This trial aims to determine whether combining a high-dose oral rifampicin regimen with DACC dressings can improve the rate of wound healing relative to standard-dose oral rifampicin combined with DACC dressings. This is an individual, multi-centre Phase 3 randomised controlled trial, which will be conducted in three clinical sites in Ghana. The primary outcome measure will be the mean time to clearance of viable mycobacteria. Cost and health-related quality of life data will be collected, and a cost-effectiveness analysis will be performed. The findings from this trial could lead to a change in how BU is treated. A shorter but more efficacious regimen would lead to improved treatment outcomes and potentially substantial financial and economic savings.

Holanamine, a Steroidal Alkaloid from the Bark of Holarrhena pubescens Wall. ex G. Don Inhibits the Growth of Leishmania donovani by Targeting DNA Topoisomerase 1B.

Leishmaniasis is a group of neglected tropical diseases (NTDs) caused by about 20 species of obligate intracellular protozoan parasites of the genus Leishmania, which occurs in cutaneous, mucocutaneous, and visceral forms. Many researchers have sought to utilize natural products for novel and effective treatments to combat many infectious diseases, including leishmaniasis. Holarrhena pubescens Wall. ex G. Don (Apocynaceae) bark is a rich source of bioactive steroidal alkaloids. The total alkaloidal extract (IC50 6.12 ± 0.117 μg/mL), and the isolated alkaloid, holanamine, showed significant antileishmanial activity (IC50 2.66 ± 0.112 μM against AG83 and 3.80 ± 0.126 μM against BHU-575) against the Leishmania donovani parasite, better than miltefosine (IC50 19.61 ± 0.093 μM against AG83 and 23.20 ± 0.094 μM against BHU-575). Holanamine inhibited the L. donovani topoisomerase 1B (LdToP1B) in a non-competitive manner (IC50 2.81 ± 0.105 μM), indicating that it interacts with the free enzyme and enzyme-DNA complex without inhibiting human topoisomerase. Hydrogen bonding and hydrophobic interactions of holanamine with the N-terminal and hinge region of the large subunit of LTop1B is responsible for its potent antileishmanial activity, as shown by docking studies. Treatment with holanamine causes apoptotic-like cell death by generating cellular and mitochondrial reactive oxygen species, disrupting the mitochondrial membrane potential and inducing ultrastructural alterations in the promastigotes. Holanamine effectively clears intracellular amastigotes but minimally affects host macrophages with no significant cytotoxicity in HEK 293 and L929 cell lines. Thus, our studies show that holanamine can further be used to develop effective antileishmanial agents against evolving drug-resistant parasites.

155 Spectrum Of Skin Neglected Tropical Diseases: A Single Center Clinical Experience in Morocco

Neglected tropical diseases (NTD) as defined by the WHO are a diverse group of acute and chronic conditions (parasitic, viral, bacterial) that cause substantial illness for more than one billion people globally. The aim of our study was to evaluate and describe clinical features of patients diagnosed with NTD in our center. We performed a retrospective descriptive study from January 2017 to January 2021, we included patients with severe, multifocal forms of NTD that required systemic treatments.