How to (or Not to) Integrate Vertical Programmes for the Control of Major Neglected Tropical Diseases in Sub-Saharan Africa

Combining the delivery of multiple health interventions has the potential to minimize costs and expand intervention coverage. Integration of mass drug administration is therefore being encouraged for delivery of preventive chemotherapy (PCT) to control onchocerciasis, lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma in sub-Saharan Africa, as there is considerable geographical overlap of these neglected tropical diseases (NTDs). With only a handful of countries having embarked on integrated NTD control, experience on how to develop and implement an efficient integrated programme is limited. Historically, national and global programmes were focused on the control of only one disease, usually through a comprehensive approach that involved several interventions including PCT. Overcoming the resulting disease-specific structures and thinking, and ensuring that the integrated programme is embedded within the existing health structures, pose considerable challenges to policy makers and implementers wishing to embark on integrated NTD control. By sharing experiences from Uganda, Tanzania, Southern Sudan, and Mozambique, this symposium article aims to outlines key challenges and solutions to assist countries in establishing efficient integrated NTD programmes.     

Scoping review of Neglected Tropical Disease Interventions and Health Promotion: A framework for successful NTD interventions as evidenced by the literature

BackgroundNeglected Tropical Diseases (NTDs) affect more than one billion people globally. A Public Library of Science (PLOS) journal dedicated to NTDs lists almost forty NTDs, while the WHO prioritises twenty NTDs. A person can be affected by more than one disease at the same time from a range of infectious and non-infectious agents. Many of these diseases are preventable, and could be eliminated with various public health, health promotion and medical interventions. This scoping review aims to determine the extent of the body of literature on NTD interventions and health promotion activities, and to provide an overview of their focus while providing recommendations for best practice going forward. This scoping review includes both the identification of relevant articles through the snowball method and an electronic database using key search terms. A two-phased screening process was used to assess the relevance of studies identified in the search–an initial screening review followed by data characterization using the Critical Appraisal Skills Program (CASP). Studies were eligible for inclusion if they broadly described the characteristics, methods, and approaches of (1) NTD interventions and/or (2) community health promotion.Principal findings90 articles met the CASP criteria partially or fully and then underwent a qualitative synthesis to be included in the review. 75 articles specifically focus on NTD interventions and approaches to their control, treatment, and elimination, while 15 focus specifically on health promotion and provide a grounding in health promotion theories and perspectives. 29 of the articles provided a global perspective to control, treatment, or elimination of NTDs through policy briefs or literature reviews. 19 of the articles focused on providing strategies for NTDs more generally while 12 addressed multiple NTDs or their interaction with other infectious diseases. Of the 20 NTDs categorized by the WHO and the expanded NTD list identified by PLOS NTDs, several NTDs did not appear in the database search on NTD interventions and health promotion, including yaws, fascioliasis, and chromoblastomycosis.ConclusionsBased on the literature we have identified the four core components of best practices including programmatic interventions, multi sectoral and multi-level interventions, adopting a social and ecological model and clearly defining ‘community.’ NTD interventions tend to centre on mass drug administration (MDA), particularly because NTDs were branded as such based on their being amenable to MDA. However, there remains a need for intervention approaches that also include multiple strategies that inform a larger multi-disease and multi-sectoral programme. Many NTD strategies include a focus on WASH and should also incorporate the social and ecological determinants of NTDs, suggesting a preventative and systems approach to health, not just a treatment-based approach. Developing strong communities and incorporating social rehabilitation at the sublocation level (e.g. hospital) could benefit several NTDs and infectious diseases through a multi-disease, multi-sectoral, and multi-lateral approach. Finally, it is important the ‘community’ is clearly defined in each intervention, and that community members are included in intervention activities and viewed as assets to interventions.     

Public Awareness and Knowledge of Neglected Tropical Diseases (NTDs) Control Activities in Abuja,Nigeria

The need to engage the public in Neglected Tropical Diseases (NTDs) control activities has become imperative in the context of morbidity reduction through preventive chemotherapy and community participation. Therefore, a survey was conducted among the general public to assess their knowledge and awareness of NTDs control activities in Nigeria. A simple questionnaire was administered to the general public attending a job fair in Abuja, Nigeria. Of the 461 respondents, a significant proportion 337 (73.1%) have heard of NTD before, but only 291 (63.1%) have good knowledge about NTDs. However, among the specific NTDs, only the control of onchocerciasis (50.8%) was of average public awareness in Nigeria, while all the other NTDs control activities were significantly less known to the general public. 397 (87.1%) stated that government support for NTD control activities is poor and were willing to assist to advocate for NTDs control. This survey demonstrates that despite government''s numerous activities towards the control of NTDs in Nigeria, there is little sensitization of the general public. There is a need for policy changes that would raise the participation and involvement of the general public in NTDs control activities for sustainability.     

Historical Perspective and Risk of Multiple Neglected Tropical Diseases in Coastal Tanzania: Compositional and Contextual Determinants of Disease Risk

BackgroundIn the past decade, research on neglected tropical diseases (NTDs) has intensified in response to the need to enhance community participation in health delivery, establish monitoring and surveillance systems, and integrate existing disease-specific treatment programs to control overlapping NTD burdens and detrimental effects. In this paper, we evaluated the geographical distribution of NTDs in coastal Tanzania.ConclusionsNTD risks were inequitably distributed over geographic space, which has several important policy implications. First, it suggests that localities of high burden of NTDs are likely to diminish within statistical averages at higher (regional or national) levels. Second, it indicates that curative or preventive interventions will become more efficient provided they can be focused on the localities, particularly as populations in these localities are likely to be burdened by several NTDs simultaneously, further increasing the imperative of multi-disease interventions.     

Temporal and Spatial Analysis of Neural Tube Defects and Detection of Geographical Factors in Shanxi Province,China

BackgroundNeural tube defects (NTDs) are congenital birth defects that occur in the central nervous system, and they have the highest incidence among all birth defects. Shanxi Province in China has the world’s highest rate of NTDs. Since the 1990s, China’s government has worked on many birth defect prevention programs to reduce the occurrence of NTDs, such as pregnancy planning, health education, genetic counseling, antenatal ultrasonography and serological screening. However, the rate of NTDs in Shanxi Province is still higher than the world’s average morbidity rate after intervention. In addition, Shanxi Province has abundant coal reserves, and is the largest coal production province in China. The objectives of this study are to determine the temporal and spatial variation of the NTD rate in rural areas of Shanxi Province, China, and identify geographical environmental factors that were associated with NTDs in the risk area.MethodsIn this study, Heshun County and Yuanping County in Shanxi Province, which have high incidence of NTDs, were selected as the study areas. Two paired sample T test was used to analyze the changes in the risk of NTDs from the time dimension. Ripley’s k function and spatial filtering were combined with geographic information system (GIS) software to study the changes in the risk of NTDs from the spatial dimension. In addition, geographical detectors were used to identify the risk geographical environmental factors of NTDs in the study areas, especially the areas close to the coal sites and main roads.ResultsIn both Heshun County and Yuanping County, the incidence of NTDs was significantly (P<0.05) reduced after intervention. The results from spatial analysis showed that significant spatial heterogeneity existed in both counties. NTD clusters were still identified in areas close to coal sites and main roads after interventions. This study also revealed that the elevation, fault and soil types always had a larger influence on the incidence of NTDs in our study areas. In addition, distance to the river was a risk factor of NTDs in areas close to the coal sites and main roads.ConclusionThe existing interventions may have played an important role to reduce the incidence of NTDs. However, there is still spatial heterogeneity in both counties after using the traditional intervention methods. The government needs to take more measures to strengthen the environmental restoration to prevent the occurrence of NTDs, especially those areas close to coal sites and main roads. The outcome of this research provides an important theoretical basis and technical support for the government to prevent the occurrence of NTDs.     

Eliminating the Neglected Tropical Diseases: Translational Science and New Technologies

Today, the World Health Organization recognizes 17 major parasitic and related infections as the neglected tropical diseases (NTDs). Despite recent gains in the understanding of the nature and prevalence of NTDs, as well as successes in recent scaled-up preventive chemotherapy strategies and other health interventions, the NTDs continue to rank among the world’s greatest global health problems. For virtually all of the NTDs (including those slated for elimination under the auspices of a 2012 London Declaration for NTDs and a 2013 World Health Assembly resolution [WHA 66.12]), additional control mechanisms and tools are needed, including new NTD drugs, vaccines, diagnostics, and vector control agents and strategies. Elimination will not be possible without these new tools. Here we summarize some of the key challenges in translational science to develop and introduce these new technologies in order to ensure success in global NTD elimination efforts.     

Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence,Distribution, and Disease Burden

The neglected tropical diseases (NTDs) are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA), and together produce a burden of disease that may be equivalent to up to one-half of SSA''s malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA''s poorest people, including 40–50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases), accounting for 93% of the world''s number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46–51 million cases) and onchocerciasis (37 million cases) are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region''s agricultural productivity. There is a dearth of information on Africa''s non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases). However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa''s NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur.     

Diagnostic testing holds the key to NTD elimination

“Fit-for-purpose” diagnostic tests have emerged as a prerequisite to achieving global targets for the prevention, control, elimination, and eradication of neglected tropical diseases (NTDs), as highlighted by the World Health Organization’s (WHO) new roadmap. There is an urgent need for the development of new tools for those diseases for which no diagnostics currently exist and for improvement of existing diagnostics for the remaining diseases. Yet, efforts to achieve this, and other crosscutting ambitions, are fragmented, and the burden of these 20 debilitating diseases immense. Compounded by the Coronavirus Disease 2019 (COVID-19) pandemic, programmatic interruptions, systemic weaknesses, limited investment, and poor commercial viability undermine global efforts—with a lack of coordination between partners, leading to the duplication and potential waste of scant resources. Recognizing the pivotal role of diagnostic testing and the ambition of WHO, to move forward, we must create an ecosystem that prioritizes country-level action, collaboration, creativity, and commitment to new levels of visibility. Only then can we start to accelerate progress and make new gains that move the world closer to the end of NTDs.

Ahead of the second-ever World Neglected Tropical Disease (NTD) Day in January 2021, and amid the global Coronavirus Disease 2019 (COVID-19) crisis, the World Health Organization (WHO) launched a new roadmap for the prevention, control, elimination, and eradication of NTDs—a group of 20 diseases affecting more than one billion people worldwide [1]. Diagnostic testing is central to safeguarding decades of progress in NTDs and must be strategically leveraged to reach the goals laid out in the new NTD roadmap.Stepping back, we recognize the massive progress that has been made to combat NTDs. Today, 500 million fewer people need treatment for these debilitating diseases than in 2010, and 40 countries or areas have eliminated at least one of the 20 [1]. Yet, despite these gains, NTDs continue to impose a devastating human, social, and economic toll on the world’s poorest and most vulnerable communities [2–6]. COVID-19 is compounding the situation by wreaking havoc on health systems, which impacts progress on NTDs: this includes interruptions to mass treatment campaigns for diseases controlled through preventive chemotherapy (PCT) or individual case management interventions, as well as rerouting the already sparse available funding and resources [7].Diagnostic testing has been central to the COVID-19 response even with the introduction of vaccines. The rapid ramp up of research and development (R&D), the scaling up of low-cost and decentralized testing, and country-led approaches to tailored testing strategies for COVID-19, as well as lessons learned, can also provide new thinking around testing for NTDs. The new NTD roadmap offers a series of multisectoral actions and intensified, cross-cutting approaches to get us back on track—with diagnostics central to unlocking and accelerating this progress [1].However, the NTD roadmap shows that, of all 20 diseases or disease groups, just 2 (yaws and snakebite envenoming) are supported by adequate and accessible diagnostic tools. Six have no diagnostic tests available at all, with tools for each of the remaining conditions in urgent need of adaptation, modification, and/or improved accessibility (likely a more cost-effective option than the development of new diagnostics for these NTDs) [1]. This has to change. NTDs cannot continue to be neglected in favor of other competing priorities, or we risk losing the progress made to date.Until the COVID-19 pandemic thrust testing into the spotlight, diagnostics have been a “silent partner” in healthcare, receiving little by way of international attention and funding, specific country strategies, and dedicated budget lines. NTDs are no exception. Just 5% of the (limited) funding made available to NTDs has been invested in new diagnostics, compared with 44% and 39% on basic research and medicines and vaccines, respectively [1]. For most NTDs, diagnostics are a market failure situation, and as such, are not commercially viable enough to attract private investment. Consequently, very few diagnostic developers engage in this area—contrary, for example, to COVID-19, where developers are in the hundreds. Furthermore, as some diseases approach the last mile of elimination, falling infection rates precipitate the need for increasingly sensitive tests [1]. But progress in R&D is slow and fragmented, with a lack of engagement and coordination between governments, industry, donors, and development actors, leading to the duplication—and potential waste—of scant resources. While serial testing using multiple diagnostic tools or techniques can compensate for low sensitivity [8], such approaches are associated with increased costs of testing, sample collection, and transportation.Closing the diagnostic gap then, is a prerequisite to achieving the global ambition for NTDs, with the new NTD roadmap giving a blueprint for action. It is for this reason that we call on governments, industry, donors, and development actors to

• Prioritize country-level diagnostic action: As we enter a new era in NTD management and control, we need to shift from traditional, donor-led models to country-driven initiatives. Government ministries must engage with, and advocate on behalf of, their poorest and most vulnerable populations so that no one is left behind. Political frameworks should prioritize diagnostics for NTDs in line with local disease burdens, and as part of fully funded, national health action plans that include a commitment to seeing the process through. Capacity building for diagnostics is also essential at country, sub-regional, and regional levels, including the establishment of laboratory networks, so that testing can be implemented in field settings.
• Collaborate and create: There is never going to be a one-size-fits-all for NTD diagnostics. If targets are to be achieved, we need global frameworks that enable industry, manufacturers, and pharmaceutical companies to engage in the whole process, from R&D to supply chain logistics. Companies need to share knowledge, learnings, and innovation across multiple diseases. This will mean breaking silos and finding new ways to harness the power of existing products, technologies, and infrastructures. Further, it will mean creating economies of scale through regional manufacturing hubs and finding new, cross-cutting approaches to drive systemic change. To obtain the maximum access to technology and relevant intellectual property rights for NTD diagnostics, it is important to ensure that such rights are broadly available (non-exclusively) in NTD-endemic countries and are affordable (e.g., zero royalty rights).
• Commit to new levels of visibility: The resources needed to realize that this ambition is limited, with a lack of visibility around the diagnostic landscape undermining progress in NTD management and control. Creating an ecosystem with visibility, transparency, and integration at its core will help streamline programmatic action, reduce the risk of duplication, and leverage the full potential from this limited pool. To do this, industry, donors, and other development actors must provide the information needed to map both funding and product landscapes. Using this information to create a virtual product pipeline will bring an unprecedented level of transparency to diagnostic developments—harmonizing multisectoral efforts and creating a robust information platform from which new collaborations, synergies, and innovation can grow. Developing an online open-access diagnostic pipeline for WHO NTD roadmap priority pathogens would serve multiple purposes: (i) drive advocacy to address critical product and funding gaps; and (ii) reduce the likelihood of duplication of efforts. Together, this would strengthen partnerships across all stakeholders, from donors to industry partners, to accelerate development, evaluation, and adoption of diagnostic solutions for NTDs. The newly established NTD Diagnostic Technical Advisory Group (DTAG) to WHO NTD department has already identified the priority diagnostic needs for NTD programs not only in terms of developing new tools, but also the accessibility of existing tools [9]. Several sub-groups that focus more narrowly on single diseases or specific topics (i.e., skin NTDs or cross-cutting) have been established and have been tasked to develop tool and biomarker agnostic target product profiles (TPPs), which are now available (for the most part) on WHO website for use by any diagnostic manufacturer to support development of their specific technology. Alignment with these diagnostic priorities by all stakeholders is strongly recommended to facilitate attainment of WHO 2030 NTD roadmap goals.

• Establish NTD biobanks: Biobanks are required for the clinical evaluation and validation of new diagnostic tests. Establishing local biobanks would support a country-driven approach as well as allowing for head-to-head comparisons between tests and assessments of cross-reactivity across different NTDs.
• Invest in existing diagnostics: The development of new diagnostics is a complex process, and the time from development to implementation can be lengthy. Training laboratory staff in the use of existing diagnostics and the establishment of robust quality control systems are effective approaches to achieving shorter-term improvements.

There is a long road ahead, but the past 10 years have shown us what can be achieved when governments, industry, donors, and development actors are bound by a shared, global goal. As we look forward to the next decade, we must prioritize country-level action, collaboration, creativity, and commitment to new levels of visibility, if we are to finally end the neglect of NTDs.     

Maternal flu or fever, medication use, and neural tube defects: a population-based case-control study in Northern China

BACKGROUND: Maternal exposure to flu or fever has been associated with increased risk for neural tube defects (NTDs); however, few studies have considered the effects of medications on the effects of flu or fever. We evaluated the effect of maternal flu or fever, medication use (antibiotics, antipyretics), and their joint effect on NTDs. METHODS: Data came from an ongoing population-based case-control study of infants with external malformations in northern China. The case group included 363 infants with NTDs identified between January 2003 and June 2005. Controls were 523 newborn infants without identified congenital anomalies matched by county, sex, maternal ethnic group, and the closest date of conception for infants with any major external malformation. Data were collected by a trained health worker through face-to-face interviews after delivery. RESULTS: NTD risks were significantly associated with maternal flu or fever (adjusted odds ratio [AOR] = 3.93, 95% CI: 2.48-6.23) and antipyretic use (AOR = 4.86, 95% CI: 1.33-17.78), but not with antibiotic use (AOR = 1.75, 95% CI: 0.91-3.38) after adjusting for potential confounders. NTD risk associated with maternal antipyretic use was markedly higher for anencephaly (AOR = 7.03, 95% CI: 1.70-29.04) than for spina bifida (AOR = 3.98, 95% CI: 0.95-16.74). Mothers with flu or fever who were also using antipyretics showed a markedly higher AOR for anencephaly (14.75 vs. 4.52), spina bifida (16.30 vs. 3.85), and all NTDs combined (13.91 vs. 4.04) than mothers with flu or fever who were not using antipyretics. Maternal antibiotics did not markedly change the effects of flu or fever on anencephaly (4.17 vs. 4.83), spina bifida (5.08 vs. 4.21), and all NTDs combined (5.05 vs. 4.29). CONCLUSIONS: Maternal flu or fever and antipyretic use during the periconceptional period increases the risk for NTDs. Maternal exposure to antipyretics together with flu or fever results in a markedly higher risk of NTDs than exposure to flu or fever alone.     

Community perceptions and acceptability of mass drug administration for the control of neglected tropical diseases in Asia-Pacific countries: A systematic scoping review of qualitative research

BackgroundPreventative chemotherapy and mass drug administration have been identified as effective strategies for the prevention, treatment, control and elimination of several NTDs in the Asia-Pacific region. Qualitative research can provide in-depth insight into the social dynamics and processes underlying effective implementation of and adherence to mass drug administration programs. This scoping review examines published qualitative literature to examine factors influencing community perceptions and acceptability of mass drug administration approaches to control NTDs in the Asia-Pacific region.MethodologyTwenty-four peer reviewed published papers reporting qualitative data from community members and stakeholders engaged in the implementation of mass drug administration programs were identified as eligible for inclusion.FindingsThis systematic scoping review presents available data from studies focussing on lymphatic filariasis, soil-transmitted helminths and scabies in eight national settings (India, Indonesia, Philippines, Bangladesh, Laos, American Samoa, Papua New Guinea, Fiji). The review highlights the profoundly social nature of individual, interpersonal and institutional influences on community perceptions of willingness to participate in mass drug administration programs for control of neglected tropical diseases (NTD). Future NTD research and control efforts would benefit from a stronger qualitative social science lens to mass drug administration implementation, a commitment to understanding and addressing the social and structural determinants of NTDs and NTD control in complex settings, and efforts to engage local communities as equal partners and experts in the co-design of mass drug administration and other efforts to prevent, treat, control and eliminate NTDs.ConclusionFor many countries in the Asia-Pacific region, the “low hanging fruit has been picked” in terms of where mass drug administration has worked and transmission has been stopped. The settings that remain–such as remote areas of Fiji and Papua New Guinea, or large, highly populated, multi-cultural urban settings in India and Indonesia–present huge challenges going forward.     

The impact of podoconiosis,lymphatic filariasis,and leprosy on disability and mental well-being: A systematic review

Leprosy, podoconiosis, and lymphatic filariasis (LF) are among the priority neglected tropical diseases (NTDs) in Ethiopia. The disability, psychosocial, and mental health status of people affected by these NTDs are still overlooked in global NTD discourse. The objective of this systematic review was to synthesize the existing evidence describing the disability, psychosocial, and mental health status of people affected by leprosy, podoconiosis, and LF prior to developing a holistic physical and psychosocial care package for these individuals. We searched papers reporting on disability, psychosocial, and mental health status linked to these 3 NTDs. The protocol was registered in PROSPERO with registration number CRD42019128400. Peer-reviewed articles were searched and extracted from Medline, PsycINFO, Global Health, and Embase. Articles published in English, irrespective of the year of publication, using a quantitative study methodology, were included. Abstracts and full texts were reviewed by 2 reviewers. Data were extracted and narratively summarized, as the studies were heterogeneous and used different outcome measures. Out of 1,318 titles/abstracts screened and 59 full text studies reviewed, 24 fulfilled the inclusion criteria. Fourteen studies provided evidence of the disability associated with leprosy, podoconiosis, or LF. Ten studies provided evidence on the association between the 3 NTDs and mental health or psychosocial outcomes. The prevalence of grade 2 disability varied from 3.9% to 86%. The most commonly reported mental health impacts were depression and mental distress. A high burden of mental illness was reported, varying from 12.6% to 71.7%; the suicidal ideation was also high (18.5%). In conclusion, disability and poor psychosocial and mental health status are associated with leprosy, podoconiosis, and LF. For optimum management of these NTDs, holistic care including both physical and psychosocial interventions is vital.     

Describing the Prevalence of Neural Tube Defects Worldwide: A Systematic Literature Review

BackgroundFolate-sensitive neural tube defects (NTDs) are an important, preventable cause of morbidity and mortality worldwide. There is a need to describe the current global burden of NTDs and identify gaps in available NTD data.ConclusionsMany WHO member states (120/194) did not have any data on NTD prevalence. Where data are collected, prevalence estimates vary widely. These findings highlight the need for greater NTD surveillance efforts, especially in lower-income countries. NTDs are an important public health problem that can be prevented with folic acid supplementation and fortification of staple foods.     

Human rights as a framework for eliminating female genital schistosomiasis

Female genital schistosomiasis (FGS) affects tens of millions of women and girls in sub-Saharan Africa, yet this inequitable threat is often overlooked by advocates in both the neglected tropical disease (NTD) and sexual and reproductive health and rights (SRHR) communities. FGS causes both acute infection and long-term sexual and reproductive health harm to marginalized women and girls, with gender, poverty, and rurality combining to invisibilize the disease. Human rights and gender imperatives can help to galvanize efforts to control and eliminate FGS, as they have for other NTDs. Specifically, international human rights obligations can frame state efforts to address FGS across healthcare settings, upstream social determinants of health, scientific research, and policy implementation. This article analyzes human rights–based approaches to FGS control and elimination efforts, outlining several areas for forward-looking reforms to health policy, programing, and practice. Building from the lessons learned in applying human rights–based approaches to advance progress on other NTDs, this analysis seeks to provide the NTD community with shared understanding around international legal obligations to engage SRHR advocates and draw heightened attention to FGS. Such human rights–based approaches to FGS control and elimination can help to reduce stigma and improve care for the millions of women and girls currently affected by this preventable disease.     

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.     

Reviewing Dengue: Still a Neglected Tropical Disease?

Dengue is currently listed as a “neglected tropical disease” (NTD). But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D) (2003–2013). NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a) poverty related, b) endemic to the tropics and subtropics, c) lacking public health attention, d) having poor research funding and shortcomings in R&D, e) usually associated with high morbidity but low mortality, and f) often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R&D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.     

Recent progress in integrated neglected tropical disease control

Three years have passed since the publication of the first of a series of policy papers, which first highlighted the under-appreciated global burden of the neglected tropical diseases (NTDs) and then outlined a rationale for linking vertical control strategies for the seven most prevalent NTDs in a cost-effective pro-poor package of preventive chemotherapy. Since then, global advocacy for these conditions has increased and, with it, new funds for scale-up of integrated NTD control in sub-Saharan Africa. Recent speeches by the Director General of the World Health Organization at regional meetings have referred to NTDs as important global health priorities (www.who.int/dg/speeches/2007). Outlined here is a summary of the recent progress in global efforts to integrate NTD control, with an emphasis on the challenges that lie ahead.     

Neural tube defects and associated anomalies in South Carolina

BACKGROUND: Neural tube defects (NTDs) occur as isolated malformations and in the company of other birth defects. This study was conducted to determine the frequency of coexisting anomalies and the relationship between them. METHODS: Since 1992, NTDs have been identified through prenatal and postnatal surveillance activities in South Carolina. The type of NTD and presence of associated anomalies were determined by prenatal ultrasound, postnatal and/or postmortem examination. RESULTS: During the ten-year period from 1992 to 2002, 564 NTDs were identified by the surveillance system. Seventeen percent of NTDs (98/564) had associated malformations. In approximately half (n = 51) of these cases, the NTDs and associated anomalies were components of a recognizable syndrome. In the remaining cases (n = 47), no syndrome was identified or suspected, but the associated anomalies were believed in most instances to be secondary to space limitation or neural crest abnormalities imposed by the NTD. CONCLUSION: Seventeen percent of NTDs in South Carolina have associated malformations. In most cases, the associated anomalies are considered either components of a multiple malformation syndrome or secondary to the NTD.     

Decline in the prevalence of neural tube defects following folic acid fortification and its cost-benefit in South Africa

BACKGROUND: In October 2003 South Africa embarked on a program of folic acid fortification of staple foods. We measured the change in prevalence of NTDs before and after fortification and assessed the cost benefit of this primary health care intervention. METHODS: Since the beginning of 2002 an ecological study was conducted among 12 public hospitals in four provinces of South Africa. NTDs as well as other birth defect rates were reported before and after fortification. Mortality data were also collected from two independent sources. RESULTS: This study shows a significant decline in the prevalence of NTDs following folic acid fortification in South Africa. A decline of 30.5% was observed, from 1.41 to 0.98 per 1,000 births (RR = 0.69; 95% CI: 0.49–0.98; p = .0379). The cost benefit ratio in averting NTDs was 46 to 1. Spina bifida showed a significant decline of 41.6% compared to 10.9% for anencephaly. Additionally, oro‐facial clefts showed no significant decline (5.7%). An independent perinatal mortality surveillance system also shows a significant decline (65.9%) in NTD perinatal deaths, and in NTD infant mortality (38.8%). CONCLUSIONS: The decrease in NTD rates postfortification is consistent with decreases observed in other countries that have fortified their food supplies. This is the first time this has been observed in a predominantly African population. The economic benefit flowing from the prevention of NTDs greatly exceeds the costs of implementing folic acid fortification. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

Folate-mediated one-carbon metabolism and neural tube defects: balancing genome synthesis and gene expression

Neural tube defects (NTDs) refer to a cluster of neurodevelopmental conditions associated with failure of neural tube closure during embryonic development. Worldwide prevalence of NTDs ranges from approximately 0.5 to 60 per 10,000 births, with regional and population-specific variation in prevalence. Numerous environmental and genetic influences contribute to NTD etiology; accumulating evidence from population-based studies has demonstrated that folate status is a significant determinant of NTD risk. Folate-mediated one-carbon metabolism (OCM) is essential for de novo nucleotide biosynthesis, methionine biosynthesis, and cellular methylation reactions. Periconceptional maternal supplementation with folic acid can prevent occurrence of NTDs in the general population by up to 70%; currently several countries fortify their food supply with folic acid for the prevention of NTDs. Despite the unambiguous impact of folate status on NTD risk, the mechanism by which folic acid protects against NTDs remains unknown. Identification of the mechanism by which folate status affects neural tube closure will assist in developing more efficacious and better targeted preventative measures. In this review, we summarize current research on the relationship between folate status and NTDs, with an emphasis on linking genetic variation, folate nutriture, and specific metabolic and/or genomic pathways that intersect to determine NTD outcomes.