Oxamniquine derivatives overcome Praziquantel treatment limitations for Schistosomiasis.

Human schistosomiasis is a neglected tropical disease caused by Schistosoma mansoni, S. haematobium, and S. japonicum. Praziquantel (PZQ) is the method of choice for treatment. Due to constant selection pressure, there is an urgent need for new therapies for schistosomiasis. Previous treatment of S. mansoni included the use of oxamniquine (OXA), a drug that is activated by a schistosome sulfotransferase (SULT). Guided by data from X-ray crystallography and Schistosoma killing assays more than 350 OXA derivatives were designed, synthesized, and tested. We were able to identify CIDD-0150610 and CIDD-0150303 as potent derivatives in vitro that kill (100%) of all three Schistosoma species at a final concentration of 71.5 µM. We evaluated the efficacy of the best OXA derivates in an in vivo model after treatment with a single dose of 100 mg/kg by oral gavage. The highest rate of worm burden reduction was achieved by CIDD -150303 (81.8%) against S. mansoni, CIDD-0149830 (80.2%) against S. haematobium and CIDD-066790 (86.7%) against S. japonicum. We have also evaluated the ability of the derivatives to kill immature stages since PZQ does not kill immature schistosomes. CIDD-0150303 demonstrated (100%) killing for all life stages at a final concentration of 143 µM in vitro and effective reduction in worm burden in vivo against S. mansoni. To understand how OXA derivatives fit in the SULT binding pocket, X-ray crystal structures of CIDD-0150303 and CIDD-0150610 demonstrate that the SULT active site will accommodate further modifications to our most active compounds as we fine tune them to increase favorable pharmacokinetic properties. Treatment with a single dose of 100 mg/kg by oral gavage with co-dose of PZQ + CIDD-0150303 reduced the worm burden of PZQ resistant parasites in an animal model by 90.8%. Therefore, we conclude that CIDD-0150303, CIDD-0149830 and CIDD-066790 are novel drugs that overcome some of PZQ limitations, and CIDD-0150303 can be used with PZQ in combination therapy.

Using Passive Surveillance to Maintain Elimination as a Public Health Problem for Neglected Tropical Diseases: A Model-Based Exploration.

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

New Tools and Nuanced Interventions to Accelerate Achievement of the 2030 Roadmap for Neglected Tropical Diseases.

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

Exploring the Resurgence of a Neglected Disease: Lessons From the 2023-2024 Mpox Outbreak in Rio de Janeiro, Brazil.

Following the 2022 global mpox outbreak, diagnoses decreased worldwide, even in settings with limited vaccine access. In 2023-2024, a new outbreak emerged in Rio de Janeiro, Brazil, highlighting the importance of continuous surveillance, preventive measures such as vaccination in vulnerable populations, and treatment options, emphasizing equitable global health technology distribution.

An Ensemble Framework for Projecting the Impact of Lymphatic Filariasis Interventions Across Sub-Saharan Africa at a Fine Spatial Scale.

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2030. Although mass treatments have led to huge reductions in LF prevalence, some countries or regions may find it difficult to achieve elimination by 2030 owing to various factors, including local differences in transmission. Subnational projections of intervention impact are a useful tool in understanding these dynamics, but correctly characterizing their uncertainty is challenging. METHODS: We developed a computationally feasible framework for providing subnational projections for LF across 44 sub-Saharan African countries using ensemble models, guided by historical control data, to allow assessment of the role of subnational heterogeneities in global goal achievement. Projected scenarios include ongoing annual treatment from 2018 to 2030, enhanced coverage, and biannual treatment. RESULTS: Our projections suggest that progress is likely to continue well. However, highly endemic locations currently deploying strategies with the lower World Health Organization recommended coverage (65%) and frequency (annual) are expected to have slow decreases in prevalence. Increasing intervention frequency or coverage can accelerate progress by up to 5 or 6 years, respectively. CONCLUSIONS: While projections based on baseline data have limitations, our methodological advancements provide assessments of potential bottlenecks for the global goals for LF arising from subnational heterogeneities. In particular, areas with high baseline prevalence may face challenges in achieving the 2030 goals, extending the "tail" of interventions. Enhancing intervention frequency and/or coverage will accelerate progress. Our approach facilitates preimplementation assessments of the impact of local interventions and is applicable to other regions and neglected tropical diseases.

The Hidden Hand of Asymptomatic Infection Hinders Control of Neglected Tropical Diseases: A Modeling Analysis.

BACKGROUND: Neglected tropical diseases are responsible for considerable morbidity and mortality in low-income populations. International efforts have reduced their global burden, but transmission is persistent and case-finding-based interventions rarely target asymptomatic individuals. METHODS: We develop a generic mathematical modeling framework for analyzing the dynamics of visceral leishmaniasis in the Indian sub-continent (VL), gambiense sleeping sickness (gHAT), and Chagas disease and use it to assess the possible contribution of asymptomatics who later develop disease (pre-symptomatics) and those who do not (non-symptomatics) to the maintenance of infection. Plausible interventions, including active screening, vector control, and reduced time to detection, are simulated for the three diseases. RESULTS: We found that the high asymptomatic contribution to transmission for Chagas and gHAT and the apparently high basic reproductive number of VL may undermine long-term control. However, the ability to treat some asymptomatics for Chagas and gHAT should make them more controllable, albeit over relatively long time periods due to the slow dynamics of these diseases. For VL, the toxicity of available therapeutics means the asymptomatic population cannot currently be treated, but combining treatment of symptomatics and vector control could yield a quick reduction in transmission. CONCLUSIONS: Despite the uncertainty in natural history, it appears there is already a relatively good toolbox of interventions to eliminate gHAT, and it is likely that Chagas will need improvements to diagnostics and their use to better target pre-symptomatics. The situation for VL is less clear, and model predictions could be improved by additional empirical data. However, interventions may have to improve to successfully eliminate this disease.

Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?

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

Harnessing artificial intelligence microscopy to improve diagnostics for soil-transmitted helminthiasis and schistosomiasis: a review of recent advances and future pathways.

PURPOSE OF REVIEW: This opinion piece aims to explore the transformative potential of integrating artificial intelligence with digital microscopy to enhance diagnostics for soil-transmitted helminthiasis (STH) and schistosomiasis (SCH), two pervasive neglected tropical diseases (NTDs). By aligning innovative artificial intelligence-driven solutions with WHO's strategic objectives and calls for better, more accessible, and more integrated diagnostics, we highlight the latest advancements that may support improved health outcomes in affected communities. RECENT FINDINGS: The review covers recent advancements in artificial intelligence-based diagnostic technologies, emphasizing automated egg detection and quantification. These technologies promise to mitigate challenges such as human error and the need for skilled technicians. SUMMARY: The findings have significant implications for public health, ethical considerations and regulatory pathways, particularly in resource-limited settings. The authors advocate for interdisciplinary collaboration and a strategic focus on meeting WHO target product profiles to ensure uptake, ultimately to support reaching WHO NTD targets.

Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis.

Tsetse transmit African trypanosomiasis, which is a disease fatal to both humans and animals. A vaccine to protect against this disease does not exist so transmission control relies on eliminating tsetse populations. Although neurotoxic insecticides are the gold standard for insect control, they negatively impact the environment and reduce populations of insect pollinator species. Here we present a promising, environment-friendly alternative to current insecticides that targets the insect tyrosine metabolism pathway. A bloodmeal contains high levels of tyrosine, which is toxic to haematophagous insects if it is not degraded and eliminated. RNA interference (RNAi) of either the first two enzymes in the tyrosine degradation pathway (tyrosine aminotransferase (TAT) and 4-hydroxyphenylpyruvate dioxygenase (HPPD)) was lethal to tsetse. Furthermore, nitisinone (NTBC), an FDA-approved tyrosine catabolism inhibitor, killed tsetse regardless if the drug was orally or topically applied. However, oral administration of NTBC to bumblebees did not affect their survival. Using a novel mathematical model, we show that NTBC could reduce the transmission of African trypanosomiasis in sub-Saharan Africa, thus accelerating current disease elimination programmes.

Detection of Anti-Strongyloides Antibodies in the Serum of Liver Transplant Recipients: Need of Screening for This Neglected Helminthiasis.

Immunosuppressed patients, particularly transplant recipients, can develop severe strongyloidiasis. This study aimed to detect anti-Strongyloides IgG antibodies in a panel of sera from liver transplant patients. Two techniques were used: ELISA as the initial screening test and Western blotting as a confirmatory test. ELISA reactivity of 10.9% (32/294) was observed. The 40-30 kDa fraction was recognised in 93.7% (30/32) of the patients, resulting in a positivity rate of 10.2%. These data highlight the importance of serological screening for Strongyloides stercoralis infection in liver transplant recipients.

The effects of selected neglected tropical diseases on economic performance at the macrolevel in Africa.

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

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.

Vaccines for neglected, emerging and re-emerging diseases.

Efforts to produce vaccines against SARS and MERS were prematurely halted since their scope was perceived to be geographically restricted and they were subsequently categorized as neglected diseases. However, when a similar virus spread globally triggering the COVID-19 pandemic, we were harshly reminded that several other neglected diseases might also be waiting for the perfect opportunity to become mainstream. As climate change drives urbanization, natural selection of pathogens and their intermediate vectors and reservoirs, the risk of neglected diseases emerging within a larger susceptible pool becomes an even greater threat. Availability of a vaccine for COVID-19 is widely considered the only way to end this pandemic. Similarly, vaccines are also seen as the best tools available to control the spread of neglected (sometimes referred to as emerging or re-emerging) diseases, until the water, hygiene and sanitation infrastructure is improved in areas of their prevalence. Vaccine production is usually cost and labour intensive and thus minimal funding is directed towards controlling and eliminating neglected diseases (NDs). A customised but sustainable approach is needed to develop and deploy vaccines against NDs. While safety, efficacy and public trust are the three main success pillars for most vaccines, affordability is vital when formulating vaccines for neglected diseases.

Global, regional, national epidemiology and trends of neglected tropical diseases in youths and young adults aged 15-39 years from 1990 to 2019: findings from the global burden of disease study 2019.

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

Availability and readiness of health facilities providing services for other infectious diseases to treat neglected tropical diseases in Ethiopia: implications for service integration in high burden areas.

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

Spillover, hybridization, and persistence in schistosome transmission dynamics at the human-animal interface.

Zoonotic spillover and hybridization of parasites are major emerging public and veterinary health concerns at the interface of infectious disease biology, evolution, and control. Schistosomiasis is a neglected tropical disease of global importance caused by parasites of the Schistosoma genus, and the Schistosoma spp. system within Africa represents a key example of a system where spillover of animal parasites into human populations has enabled formation of hybrids. Combining model-based approaches and analyses of parasitological, molecular, and epidemiological data from northern Senegal, a region with a high prevalence of schistosome hybrids, we aimed to unravel the transmission dynamics of this complex multihost, multiparasite system. Using Bayesian methods and by estimating the basic reproduction number (R0 ), we evaluate the frequency of zoonotic spillover of Schistosoma bovis from livestock and the potential for onward transmission of hybrid S. bovis × S. haematobium offspring within human populations. We estimate R0 of hybrid schistosomes to be greater than the critical threshold of one (1.76; 95% CI 1.59 to 1.99), demonstrating the potential for hybridization to facilitate spread and establishment of schistosomiasis beyond its original geographical boundaries. We estimate R0 for S. bovis to be greater than one in cattle (1.43; 95% CI 1.24 to 1.85) but not in other ruminants, confirming cattle as the primary zoonotic reservoir. Through longitudinal simulations, we also show that where S. bovis and S. haematobium are coendemic (in livestock and humans respectively), the relative importance of zoonotic transmission is predicted to increase as the disease in humans nears elimination.

Musculoskeletal involvement in neglected tropical diseases: a comprehensive review.

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

First report of Leishmania tropica in domestic and wild animal hosts in hyperendemic areas of human cutaneous leishmaniasis in western Yemen: a neglected tropical disease needing One Health approach.

Cutaneous leishmaniasis (CL), a neglected tropical disease, is a major public health concern in Yemen, with Leishmania tropica identified as the main causative agent. This study aims to investigate the occurrence and distribution of Leishmania parasites in domestic and wild animals in CL endemic areas in the western highlands of Yemen. A cross-sectional study was conducted in the Utmah District of western Yemen. Blood and skin scraping specimens were collected from 122 domestic and wild animals and tested for the Leishmania DNA using internal transcribed spacer 1 (ITS1) nested polymerase chain reaction. Phylogenetic analyses were performed on 20 L. tropica sequences obtained from animals in this study and 34 sequences from human isolates (collected concurrently from the same study area) retrieved from the GenBank. Overall, L. tropica was detected in 16.4% (20/122) of the examined animals, including 11 goats, two dogs, two bulls, one cow, one donkey, one rabbit, one rat and one bat. None of the examined cats and sheep was positive. The animal sequences were segregated into four different L. tropica haplotypes, with the majority of the animal (15/20) and human (32/34) sequences composed of one dominant haplotype/genotype. These findings represent the first confirmed evidence of natural L. tropica infections in different kinds of domestic and wild animals in western Yemen, suggesting these animals potentially have a role in the transmission of CL in Yemen. Therefore, a One Health approach is required for the effective prevention and control of this devastating disease among endemic populations.

Evaluating the World Health Organization's SkinNTDs App as a Training Tool for Skin Neglected Tropical Diseases in Ghana and Kenya: Cross-Sectional Study.

BACKGROUND: Neglected tropical diseases (NTDs) affect over 1.5 billion people worldwide, primarily impoverished populations in low- and middle-income countries. Skin NTDs, a significant subgroup, manifest primarily as skin lesions and require extensive diagnosis and treatment resources, including trained personnel and financial backing. The World Health Organization has introduced the SkinNTDs app, a mobile health tool designed to train and be used as a decision support tool for frontline health care workers. As most digital health guidelines prioritize the thorough evaluation of mobile health interventions, it is essential to conduct a rigorous and validated assessment of this app. OBJECTIVE: This study aims to assess the usability and user experience of World Health Organization SkinNTDs app (version 3) as a capacity-building tool and decision-support tool for frontline health care workers. METHODS: A cross-sectional study was conducted in Ghana and Kenya. Frontline health care workers dealing with skin NTDs were recruited through snowball sampling. They used the SkinNTDs app for at least 5 days before completing a web-based survey containing demographic variables and the user version of the Mobile Application Rating Scale (uMARS), a validated scale for assessing health apps. A smaller group of participants took part in semistructured interviews and one focus group. Quantitative data were analyzed using SPSS with a 95% CI and P≤.05 for statistical significance and qualitative data using ATLAS.ti to identify attributes, cluster themes, and code various dimensions that were explored. RESULTS: Overall, 60 participants participated in the quantitative phase and 17 in the qualitative phase. The SkinNTDs app scored highly on the uMARS questionnaire, with an app quality mean score of 4.02 (SD 0.47) of 5, a subjective quality score of 3.82 (SD 0.61) of 5, and a perceived impact of 4.47 (SD 0.56) of 5. There was no significant association between the app quality mean score and any of the categorical variables examined, according to Pearson correlation analysis; app quality mean score vs age (P=.37), sex (P=.70), type of health worker (P=.35), country (P=.94), work context (P=.17), frequency of dealing with skin NTDs (P=.09), and dermatology experience (P=.63). Qualitative results echoed the quantitative outcomes, highlighting the ease of use, the offline functionality, and the potential utility for frontline health care workers in remote and resource-constrained settings. Areas for improvement were identified, such as enhancing the signs and symptoms section. CONCLUSIONS: The SkinNTDs app demonstrates notable usability and user-friendliness. The results indicate that the app could play a crucial role in improving capacity building of frontline health care workers dealing with skin NTDs. It could be improved in the future by including new features such as epidemiological context and direct contact with experts. The possibility of using the app as a diagnostic tool should be considered. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/39393.