Global Dilemma and Needs Assessment Toward Achieving Sustainable Development Goals in Controlling Leishmaniasis.

Leishmaniasis is a disease of poverty that imposes a devastating medical, social, and economic burden on over 1 billion people nationwide. To date, no in-depth study to analyze the major global challenges and needs assessment has been carried out. This investigation aimed to explore a comprehensive narrative review of leishmaniasis's main challenges and initially highlight obstacles that might impede the implementation of control measures. Also, we propose a specific list of priorities for needs assessment. The presence of socioeconomic factors, multiple clinical and epidemiological forms, various Leishmania species, the complexity of the life cycle, the absence of effective drugs and vaccines, and the lack of efficient vector and reservoir control make this organism unique and sophisticated in playing a tangled role to react tricky with its surrounding environments, despite extensive efforts and implementation of all-inclusive former control measures. These facts indicate that the previous strategic plans, financial support, and basic infrastructures connected to leishmaniasis surveillance are still insufficient. Strengthening the leishmaniasis framework in a context of accelerated programmatic action and intensification of cross-cutting activities along with other neglected tropical diseases (NTDs) is confidently expected to result in greater effectiveness, cost-benefit, and fruitful management. Sensitive diagnostics, effective therapeutics, and efficacious vaccines are vital to accelerating advancement toward elimination, and reducing morbidity/mortality and program costs. Collective actions devoted by all sectors and policy-makers can hopefully overcome technical and operational barriers to guarantee that effective and coordinated implementation plans are sustained to meet the road map for NTDs 2021- 2030 goals.

Involving patients in drug development for Neglected Tropical Diseases (NTDs): A qualitative study exploring and incorporating preferences of patients with cutaneous leishmaniasis into Target Product Profile development.

BACKGROUND: Target Product Profiles (TPPs) are instrumental to help optimise the design and development of therapeutics, vaccines, and diagnostics - these products, in order to achieve the intended impact, should be aligned with users' preferences and needs. However, patients are rarely involved as key stakeholders in building a TPP. METHODOLOGY: Thirty-three cutaneous leishmaniasis (CL) patients from Brazil, Colombia, and Austria, infected with New-World Leishmania species, were recruited using a maximum variation approach along geographic, sociodemographic and clinical criteria. Semi-structured interviews were conducted in the respective patient's mother tongue. Transcripts, translated into English, were analysed using a framework approach. We matched disease experiences, preferences, and expectations of CL patients to a TPP developed by DNDi (Drug for Neglected Diseases initiative) for CL treatment. PRINCIPAL FINDINGS: Patients' preferences regarding treatments ranged from specific efficacy and safety endpoints to direct and significant indirect costs. Respondents expressed views about trade-offs between efficacy and experienced discomfort/adverse events caused by treatment. Reasons for non-compliance, such as adverse events or geographical and availability barriers, were discussed. Considerations related to accessibility and affordability were relevant from the patients' perspective. CONCLUSIONS/SIGNIFICANCE: NTDs affect disadvantaged populations, often with little access to health systems. Engaging patients in designing adapted therapies could significantly contribute to the suitability of an intervention to a specific context and to compliance, by tailoring the product to the end-users' needs. This exploratory study identified preferences in a broad international patient spectrum. It provides methodological guidance on how patients can be meaningfully involved as stakeholders in the construction of a TPP of therapeutics for NTDs. CL is used as an exemplar, but the approach can be adapted for other NTDs.

European priority review vouchers for neglected disease product development.

INTRODUCTION: Neglected diseases are a significant global health challenge. Encouraging the development of therapeutics and vaccines for these diseases would address an important unmet medical need. We propose a priority review voucher programme for the European Union (EU). The developer of a drug or vaccine for a neglected disease would receive a voucher for accelerated assessment of a different product at the European Medicines Agency (EMA). METHODS: This study uses retrospective observational data to estimate the potential commercial value of the proposed voucher programme using a five-step approach: (1) estimating the time saved in the EMA accelerated regulatory review; (2) gauging time reductions in accelerated pricing and reimbursement decisions by EU member states; (3) selecting 10 high-revenue products launched between 2015 and 2020 representing typical voucher users; (4) analysing IQVIA MIDAS sales data for the selected products and (5) calculating the net present value (NPV) of the voucher based on the 10 products. RESULTS: The accelerated EMA review would reduce regulatory time by an average of 182 days. Additionally, products could save more than a year in many member states through an expedited 120-day pricing and reimbursement review. The estimated NPV of regulatory acceleration by two quarters would be €100 million. In addition, if France, Italy and Spain reviewed pricing and reimbursement in only 120 days, then the value would double. CONCLUSION: An EU voucher estimated at more than €100 million, coupled with a US$100 million counterpart, offers a meaningful incentive for novel product development. However, the voucher programme should be part of a comprehensive strategy for tackling neglected diseases, rather than a standalone solution.

Healthcare Policies to Eliminate Neglected Tropical Diseases (NTDs) in India: A Roadmap.

The need for systemic healthcare policies to systematically eliminate NTDs globally and in India has been stressed for more than two decades. Yet, the present policies and the research on them do not meet the need. We present an ontological framework, a research roadmap, and a policy brief to address the gap. The ontology clearly, concisely, and comprehensively represents the combinations of diseases, the objectives regarding the diseases, the entities to address them, the outcomes sought, and the potential policy instruments to invoke. The paper explicates the state of the-policies and state of the research on policies to eliminate NTDs in India. It highlights the significant gaps in the diseases covered, balance in the objectives, comprehensiveness of policies, portfolio of outcomes, and involvement of entities. Last, it presents a set of systemic policies congruent with the ontology to systematically address the gaps. The recommendations are aligned with the present research, policies, practices, and recommendations in India and of the WHO, UN agencies, and other similar bodies. The approach can be generalized to provide roadmaps for other countries facing a similar challenge and for other diseases of similar complexity. The roadmaps, with continuous feedback and learning, can help navigate the challenge efficiently and effectively.

Addressing neglected tropical diseases in Africa: a health equity perspective.

Africa accounts for over one-third of the global burden of neglected tropical diseases (NTDs). Although continental efforts have been made to combat these diseases, there still exists a significant gap in the fight, ranging from a lack of data to multisectoral participation and, most critically, health inequity. Here, we assess the effort made to combat challenges caused by health disparities to prevent and control neglected tropical diseases. This article engages a health equity view to addressing the need for inclusion in achieving universal health coverage towards eradicating NTDs and outlines strategies to achieve such. Health disparities exist, and there is substantial and irrefutable evidence for them. Inequitable distribution and limited access to basic and essential life resources such as water, housing, toilets, soap, and literacy continue to facilitate the existence of NTDs such as Schistosomiasis, soil-transmitted helminths, and trachoma, the occurrence of which can be avoided if affected populations have better access to those resources. To eradicate NTDs, health disparities must be addressed to provide excellent health care to all populations and adequate universal health coverage for long-term sustainability. NTD programmes need to be data-driven to ensure better decision-making and ensure the inclusion of diverse population groups including women, children, and youths. This will ensure that no one is left behind, drawing upon the sustainable development goals. Community participation and engagement should also be considered as an essential approach to ensure people are at the centre of health programmes and their implementation.

A global call for action to tackle skin-related neglected tropical diseases (skin NTDs) through integration: An ambitious step change.

On 8 June 2022, the World Health Organization (WHO) released pivotal guidance, "Ending the neglect to attain the Sustainable Development Goals: A strategic framework for integrated control and management of skin-related neglected tropical diseases." Skin-related neglected tropical diseases, or skin NTDs, comprise a group of NTDs that produce signs and symptoms on the skin and include at least 9 diseases or disease groups. Moving away from disease-specific approaches, it is anticipated that synergies will be identified and integrated building on this shared feature, where possible, to achieve a greater health impact. This paper intends to draw attention to the prospects created by this scheme. The framework is a key basis for a proposal produced by WHO dedicated to skin NTD integration and describes the practical opportunities for this evolving strategy. It underlines the wider health benefits that will follow, thus working towards Universal Health Coverage and skin health for all.

Investing in a global pooled-funding mechanism for late-stage clinical trials of poverty-related and neglected diseases: an economic evaluation.

INTRODUCTION: Poverty-related and neglected diseases (PRNDs) cause over three million deaths annually. Despite this burden, there is a large gap between actual funding for PRND research and development (R&D) and the funding needed to launch PRND products from the R&D pipeline. This study provides an economic evaluation of a theoretical global pooled-funding mechanism to finance late-stage clinical trials of PRND products. METHODS: We modelled three pooled-funding design options, each based on a different level of coverage of candidate products for WHO's list of PRNDs: (1) vaccines covering 4 PRNDs, (2) vaccines and therapeutics covering 9 PRNDs and (3) vaccines, therapeutics and diagnostics covering 30 PRNDs. For each option, we constructed a discrete event simulation of the 2019 PRND R&D pipeline to estimate required funding for phase III trials and expected product launches through 2035. For each launch, we estimated global PRND treatment costs averted, deaths averted and disability-adjusted life-years (DALYs) averted. For each design option, we calculated the cost per death averted, cost per DALY averted, the benefit-cost ratio (BCR) and the incremental cost-effectiveness ratio (ICER). RESULTS: Option 1 averts 18.4 million deaths and 516 million DALYs, has a cost per DALY averted of US$84 and yields a BCR of 5.53. Option 2 averts 22.9 million deaths and 674 million DALYs, has a cost per DALY averted of US$75, an ICER over option 1 of US$49 and yields a BCR of 3.88. Option 3 averts 26.9 million deaths and 1 billion DALYs, has a cost per DALY averted of US$114, an ICER over option 2 of US$186 and yields a BCR of 2.52. CONCLUSIONS: All 3 options for a pooled-funding mechanism-vaccines for 4 PRNDs, vaccines and therapeutics for 9 PRNDs, and vaccines, therapeutics and diagnostics for 30 PRNDs-would generate a large return on investment, avert a substantial proportion of the global burden of morbidity and mortality for diseases of poverty and be cost-effective.

Japan moves to bolster its vaccine R&D sector.

Major funding effort aims to address weaknesses exposed by COVID-19 pandemic.

A pan-serotype antiviral to prevent and treat dengue: A journey from discovery to clinical development driven by public-private partnerships.

While progress has been made in fighting diseases disproportionally affecting underserved populations, unmet medical needs persist for many neglected tropical diseases. The World Health Organization has encouraged strong public-private partnerships to address this issue and several public and private organizations have set an example in the past showing a strong commitment to combat these diseases. Pharmaceutical companies are contributing in different ways to address the imbalance in research efforts. With this review, we exemplify the role of a public-private partnership in research and development by the journey of our dengue antiviral molecule that is now in early clinical development. We detail the different steps of drug development and outline the contribution of each partner to this process. Years of intensive collaboration resulted in the identification of two antiviral compounds, JNJ-A07 and JNJ-1802, the latter of which has advanced to clinical development.

A strategic model for developing vaccines against neglected diseases: An example of industry collaboration for sustainable development.

Infectious diseases continue to disproportionately affect low- and middle-income countries (LMICs) and children aged <5 y. Developing vaccines against diseases endemic in LMICs relies mainly on strong public-private collaborations, but several challenges remain. We review the operating model of the GSK Vaccines Institute for Global Health (GVGH), which aims to address these challenges. The model involves i) selection of vaccine targets based on priority ranking for impact on global health; ii) development from design to clinical proof-of-concept; iii) transfer to an industrial partner, for further technical/clinical development, licensing, manufacturing, and distribution. Cost and risks associated with pre-clinical and early clinical development are assumed by GVGH, increasing the probability to make the vaccine more affordable in LMICs. A conjugate vaccine against typhoid fever, Vi-CRM197, has recently obtained WHO prequalification, within a year from licensure in India, demonstrating the success of the GVGH model for development and delivery of global health vaccines.

A systematic review and quality appraisal of the economic evaluations of schistosomiasis interventions.

BACKGROUND: Schistosomiasis is a neglected tropical disease (NTD) that affects over 230 million people in low and middle-income countries (LMICs) and can lead to long-term debilitating health effects. It is associated with impoverishment and has been prioritised by the World Health Organization for prevention, control and elimination. This systematic review aimed to identify and evaluate existing economic evaluations of interventions to tackle schistosomiasis. METHODOLOGY: A comprehensive search strategy of four databases and additional hand-searching was employed on the 17th July 2020. The articles were screened and sorted using a two-stage classification system. Full economic evaluations published in English between 1st January 1998 and 17th July 2020 were included, and methodological quality was appraised using the international decision support initiative (iDSI), Phillips and Evers checklists. RESULTS: Eighteen economic evaluations were identified, nine trial-based and nine model-based, with the majority focused on preventative chemotherapy. Schistosomiasis interventions were collectively found to be cost-effective, but the quantity and quality of studies were limited. The outcome measures and time-horizons utilised varied substantially making comparison difficult. The majority of papers failed to address equity and affordability. CONCLUSION: Several methodological issues were highlighted which might have implications for optimal decision-making. Future research is needed to ensure the standardisation of methods, in order to ensure that scarce healthcare resources are focused on the most cost-effective programmes to tackle schistosomiasis and other NTDs.

Resuming NTD activities in the context of COVID-19: an investigation into the advantages of risk assessment processes to mitigate the transmission of COVID-19 during NTD delivery.

BACKGROUND: The neglected tropical disease (NTD) sector is adapting to the uncertain circumstances of coronavirus disease 2019 (COVID-19). The development of the Risk Assessment and Mitigation Action (RAMA) tool was driven by partners of the programme Accelerating the Sustainable Control and Elimination of NTDs (hereafter called Ascend) to enable countries to recommence NTD activities following the World Health Organization advisories of April and July 2020. This article explores the advantages of the RAMA process for NTD delivery. METHODS: The analysis used interview transcripts with NTD practitioners in Cote d'Ivoire, Guinea, Liberia and Nigeria and results from the monitoring of compliance with COVID-19 mitigation measures in Nigeria. RESULTS: Three themes emerged from the results: adaptability and innovation, collaboration and government ownership and preparedness. CONCLUSIONS: The advantages of the RAMA tool suggest its importance in mitigating the transmission of COVID-19 during NTD delivery. There is the potential for the tool to be adapted for use throughout future pandemics.

Leveraging resources and the impact of neglected tropical disease elimination programmes: getting (much) more than what you pay for.

Partnerships have been key to significant progress in combating neglected tropical diseases (NTDs). Collaboration between a range of partners, each bringing different skills and resources, helps reach more people in need with greater efficiency. Some partners have contributed in-kind donations, including drugs and volunteer time. When making resource allocation decisions donors need to consider the significant leverage their investment in NTD programmes can have. This commentary estimates the value of the leverage that the Ascend programme achieved. It is clear that funding from UK aid to Ascend delivered (much) more than what they paid for.

How can the neglected tropical disease community be inclusive and equitable in programme delivery? Reaching refugees and internally displaced persons through integrating a 'leave no one behind' approach.

As directed by the Sustainable Development Goals, the principle of 'leave no one behind' is a pivotal approach to improving coverage and equity within neglected tropical disease (NTD) programme activities. Displaced populations are an at-risk group who are often excluded from treatment and services due to their mobility and marginalisation. This article reflects on the experiences of two countries within the Ascend programme, which responded to the need to strategise and implement approaches that lead to more inclusive and accessible programme activities for displaced populations. With the increasing rate of insecurity and the threat of natural disasters, which is resulting in the displacement of communities and persons eligible for NTD treatment, the 'leave no one behind' approach is needed to move closer towards the NTD elimination agenda and to ensure effective coverage thresholds are met.

The economic evaluation of Cystic echinococcosis control strategies focused on zoonotic hosts: A scoping review.

BACKGROUND: Cystic echinococcosis (CE) is a zoonotic neglected tropical disease (zNTD) which imposes considerable financial burden to endemic countries. The 2021-2030 World Health Organization's roadmap on NTDs has proposed that intensified control be achieved in hyperendemic areas of 17 countries by 2030. Successful interventions for disease control, and the scale-up of programmes applying such interventions, rely on understanding the associated costs and relative return for investment. We conducted a scoping review of existing peer-reviewed literature on economic evaluations of CE control strategies focused on Echinococcus granulosus zoonotic hosts. METHODOLOGY/PRINCIPAL FINDINGS: Database searches of Scopus, PubMed, Web of Science, CABI Direct and JSTOR were conducted and comprehensively reviewed in March 2022, using predefined search criteria with no date, field or language restrictions. A total of 100 papers were initially identified and assessed for eligibility against strict inclusion and exclusion criteria, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Bibliography review of included manuscripts was used to identify additional literature. Full review of the final manuscript selection (n = 9) was performed and cost data for control interventions were extracted. CONCLUSIONS/SIGNIFICANCE: There are very little published data pertaining to the cost and cost effectiveness of CE control interventions targeting its zoonotic hosts. Data given for costs are often incomplete, thus we were unable to perform an economic analysis and cost effectiveness study, highlighting a pressing need for this information. There is much scope for future work in this area. More detailed information and disaggregated costings need to be collected and made available. This would increase the accuracy of any cost-effective analyses to be performed and allow for a greater understanding of the opportunity cost of healthcare decisions and resource allocation by stakeholders and policy makers for effective and cost-effective CE control.

A refined and updated health impact assessment of the Global Programme to Eliminate Lymphatic Filariasis (2000-2020).

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease (NTD). In 2000 the World Health Organization (WHO) established the Global Programme to Eliminate Lymphatic Filariasis (GPELF). A key component of this programme is mass drug administration (MDA). Between 2000 and 2020, the GPELF has delivered over 8.6 billion treatments to at-risk populations. The last impact assessment of the programme evaluated the treatments provided between 2000-2014. The goal of this analysis is to provide an updated health impact assessment of the programme, based on the numbers treated between 2000-2020. METHODS: We updated and refined a previously established model that estimates the number of clinical manifestations and disability-adjusted life years (DALYs) averted by the treatments provided by the GPELF. The model comprises three different population cohorts that can benefit from MDA provided (those protected from acquiring infection, those with subclinical morbidity prevented from progressing and those with clinical disease alleviated). The treatment numbers were updated for all participating countries using data from the WHO. In addition, data relating to the estimated number of individuals initially at risk of LF infection were updated where possible. Finally, the DALY calculations were refined to use updated disability weights. RESULTS: Using the updated model and corresponding treatment data, we projected that the total benefit cohort of the GPELF (2000-2020) would consist of approximately 58.5 million individuals and the programme would avert 44.3 million chronic LF cases. Over the lifetime of the benefit cohorts, this corresponded to 244 million DALYs being averted. CONCLUSION: This study indicates that substantial health benefits have resulted from the first 20 years of the GPELF. It is important to note that the GPELF would have both additional benefits not quantified by the DALY burden metric as well as benefits on other co-endemic diseases (such as soil-transmitted helminths, onchocerciasis and scabies)-making the total health benefit underestimated. As with the past impact assessments, these results further justify the value and importance of continued investment in the GPELF.

An assessment of implementation and effectiveness of mass drug administration for prevention and control of schistosomiasis and soil-transmitted helminths in selected southern Malawi districts.

BACKGROUND: Mass drug administration (MDA) is one of the key interventions recommended by WHO for prevention and control of neglected tropical diseases (NTD). In Malawi, MDA is widely carried out annually since 2009 for prevention and control of schistosomiasis and soil-transmitted helminths (STH). No study has been carried out to assess effectiveness of the MDA approach and to document perceptions of health providers and beneficiaries regarding use of MDA. This study was done to understand how well MDA is being implemented and to identify opportunities for improvement in MDA delivery in Malawi. METHODS: Designed as a cross-sectional and multi-methods research, the study was carried out in three southern Malawi districts of Chiradzulu, Mangochi and Zomba. In each district, four health centres and 16 villages were randomly selected to participate. A mixed-methods approach to data collection focusing on quantitative data for coverage and knowledge, attitudes and practices assessments; and qualitative data for assessing perceptions of health providers and beneficiaries regarding MDA was used. Quantitative data were processed and analyzed using IBM SPSS software version 26 while qualitative data were analysed using NVivo 12 for Windows. RESULTS: Knowledge levels about schistosomiasis and STH in the districts varied according to disease aspects asked about. Majority are more knowledgeable about what schistosomiasis is (78%) and whether STH are treatable with drugs (97%); with least knowledgeable about the organism that transmits schistosomiasis (18%), types of schistosomiasis (11%) and what causes STH (20%). In 2018 and 2019 the districts registered high coverage rates for praziquantel and albendazole using community-based MDA (73-100%) and using school-based MDA (75-91%). Both the health authorities and community members perceived the MDA approach as good because it brings treatment closer to people. CONCLUSION: With the high MDA coverage obtained in communities and schools, the effectiveness of MDA in the target districts is satisfactory. There are, however, several challenges including disproportionate knowledge levels, which are hampering progress towards attainment of the 2030 global NTD goals. There is a need for promotion of community participation and partnerships as well as implementation of other recommended interventions for sustainable prevention and control of schistosomiasis and STH.

Are the neglected tropical diseases under control in the tri-border region between Brazil, Argentina, and Paraguay?

INTRODUCTION: Implementation of prevention and control measures for communicable diseases in border regions can be challenging and lead to inefficient attempts to control them. We describe evidences on the strengths, weaknesses, opportunities and challenges regarding implementation of health interventions for control, prevention and treatment of selected neglected tropical diseases (NTD), a group of transmissible diseases typically prevalent in tropical countries and vulnerable populations, in the tri-border between Brazil, Argentina, and Paraguay. METHODOLOGY: A systematic literature review of observational and experimental studies was conducted, using PubMed and Bireme databases. Eligibility criteria were location (tri-border area) and subject (health interventions). RESULTS: Of a total of 595 references identified, 34 studies were included (18 pertaining to leishmaniasis, 11 to dengue, 2 to leprosy, 2 to soil-transmitted helminthiases and 1 to Chagas' disease), with an inclusion rate of 6.4%. The main strengths were the similarity of health interventions between countries and easiness of mobility and communication flows. The main weaknesses were access to rural areas and discrepancies in the number of studies between countries. As for opportunities, we identified increased tourism, economic development and recent increasing research in this field. The main challenges were the absence of studies regarding other prevalent NTD in the region and movement of goods, animals and people across borders. CONCLUSIONS: Although epidemiological studies are still needed to better understand and assess the prevalence of NTD in the area, mainly in Paraguay, these findings can inform decision-makers and health managers to plan a common strategy to address NTD.

Safely resuming neglected tropical disease control activities during COVID-19: Perspectives from Nigeria and Guinea.

Since its early spread in early 2020, the disease caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Disease 2019 (COVID-19) has caused mass disruptions to health services. These have included interruptions to programs that aimed to prevent, control, and eliminate neglected tropical diseases (NTDs). In March 2020, the World Health Organization (WHO) released interim guidelines recommending the temporary cessation of mass drug administration (MDA), community-based surveys, and case detection, while encouraging continuation of morbidity management and vector control where possible. Over the course of the following months, national programs and implementing partners contributed to COVID-19 response efforts, while also beginning to plan for resumption of NTD control activities. To understand the challenges, opportunities, and recommendations for maximizing continuity of disease control during public health emergencies, we sought perspectives from Nigeria and Guinea on the process of restarting NTD control efforts during the COVID-19 pandemic. Through semistructured interviews with individuals involved with NTD control at the local and national levels, we identified key themes and common perspectives between the 2 countries, as well as observations that were specific to each. Overall, interviewees stressed the challenges posed by COVID-19 interruptions, particularly with respect to delays to activities and related knock-on impacts, such as drug expiry and prolonged elimination timelines, as well as concerns related to funding. However, respondents in both countries also highlighted the benefits of a formal risk assessment approach, particularly in terms of encouraging information sharing and increasing coordination and advocacy. Recommendations included ensuring greater availability of historical data to allow better monitoring of how future emergencies affect NTD control progress; continuing to use risk assessment approaches in the future; and identifying mechanisms for sharing lessons learned and innovations between countries as a means of advancing postpandemic health systems and disease control capacity strengthening.