Neglected tropical diseases: progress towards addressing the chronic pandemic.

The concept of neglected tropical diseases (NTDs) emerged more than a decade ago and has been recognised as a valid way to categorise diseases that affect the poorest individuals. Substantial progress in control and elimination has been achieved and policy momentum has been generated through continued bilateral, philanthropic, and non-governmental development organisation (NGDO) support, and donations of drugs from pharmaceutical companies. WHO has defined a Roadmap to reach 2020 targets, which was endorsed by member states in a World Health Assembly Resolution in 2013. NTDs have been included within the Sustainable Development Goal targets and are a crucial component of universal health coverage, conceptualised as "leaving no one behind". WHO reported that more than 1 billion people in 88 countries have benefited from preventive chemotherapy in 2014. The research agenda has defined the need for affordable products (diagnostics, drugs and insecticides). However challenges such as insecurity and weak health systems continue to prevail in the poorest countries, inhibiting progress in scaling up and also in achieving Roadmap goals.

The changing global landscape of health and disease: addressing challenges and opportunities for sustaining progress towards control and elimination of neglected tropical diseases (NTDs).

The drive to control neglected tropical diseases (NTDs) has had many successes but to reach defined targets new approaches are required. Over the last decade, NTD control programmes have benefitted from increased resources, and from effective partnerships and long-term pharmaceutical donations. Although the NTD agenda is broader than those diseases of parasitic aetiology there has been a massive up-scaling of the delivery of medicines to some billion people annually. Recipients are often the poorest, with the aspiration that NTD programmes are key to universal health coverage as reflected within the 2030 United Nations sustainable development goals (SDGs). To reach elimination targets, the community will need to adapt global events and changing policy environments to ensure programmes are responsive and can sustain progress towards NTD targets. Innovative thinking embedded within regional and national health systems is needed. Policy makers, managers and frontline health workers are the mediators between challenge and change at global and local levels. This paper attempts to address the challenges to end the chronic pandemic of NTDs and achieve the SDG targets. It concludes with a conceptual framework that illustrates the interactions between these key challenges and opportunities and emphasizes the health system as a critical mediator.

The feasibility of eliminating podoconiosis.

Podoconiosis is an inflammatory disease caused by prolonged contact with irritant minerals in soil. Major symptoms include swelling of the lower limb (lymphoedema) and acute pain. The disease has major social and economic consequences through stigma and loss of productivity. In the last five years there has been good progress in podoconiosis research and control. Addressing poverty at household level and infrastructure development such as roads, water and urbanization can all help to reduce podoconiosis incidence. Specific control methods include the use of footwear, regular foot hygiene and floor coverings. Secondary and tertiary prevention are based on the management of the lymphoedema-related morbidity and include foot hygiene, foot care, wound care, compression, exercises, elevation of the legs and treatment of acute infections. Certain endemic countries are taking the initiative to include podoconiosis in their national plans for the control of neglected tropical diseases and to scale up interventions against the disease. Advocacy is needed for provision of shoes as a health intervention. We suggest case definitions and elimination targets as a starting point for elimination of the disease.

La podoconiose est une maladie inflammatoire provoquée par un contact prolongé avec des minéraux irritants présents dans le sol. Les principaux symptômes incluent un gonflement des membres inférieurs (lymphœdème) et une douleur aiguë. Cette maladie a d'importantes conséquences sociales et économiques, car elle entraîne stigmatisation et perte de productivité. Ces cinq dernières années ont été marquées par des progrès satisfaisants en matière de recherche sur la podoconiose et de contrôle de cette maladie. Combattre la pauvreté au niveau des foyers et développer des infrastructures routières, d'approvisionnement en eau et urbaines peut contribuer à réduire son incidence. Les méthodes de lutte contre la podoconiose incluent le port de chaussures, une bonne hygiène des pieds et des revêtements de sol. La prévention secondaire et la prévention tertiaire reposent sur la gestion de la morbidité liée aux lymphœdèmes et passent par l'hygiène des pieds, les soins des pieds, les soins des plaies, la compression, des exercices, l'élévation des jambes et le traitement des infections aigües. Certains pays où la podoconiose est endémique ont pris l'initiative de l'inclure dans leur plan national pour la lutte contre les maladies tropicales négligées et de multiplier les interventions contre cette maladie. Des actions de sensibilisation sont nécessaires en vue de la distribution de chaussures comme mesure sanitaire. Nous recommandons de préciser les définitions de cas et les objectifs d'élimination pour servir de point de départ à l'éradication de cette maladie.

La podoconiosis es una enfermedad inflamatoria causada por un contacto prolongado con sustancias minerales irritantes del suelo. Los síntomas principales incluyen la hinchazón de las extremidades inferiores (linfedema) y un dolor agudo. Dicha enfermedad comporta graves consecuencias tanto en el entorno social como económico, ya que provoca estigmas y pérdida de productividad. En los últimos cinco años ha habido progresos satisfactorios en la investigación y el control de la podoconiosis. El tratamiento de la pobreza a nivel doméstico y el desarrollo de infraestructuras como carreteras, riegos y en urbanización pueden ayudar a reducir los casos de podoconiosis. Entre los métodos de control específico se encuentran el uso de calzado, una buena higiene de los pies y recubrimientos para el suelo. La prevención secundaria y terciaria se basa en la gestión de la morbilidad relacionada con el linfedema, esto incluye una buena higiene de los pies y el cuidado de los mismos, la cura de las lesiones, ejercicios de compresión, elevar las piernas y tratar las infecciones agudas. Algunos países endémicos han tomado la iniciativa de incluir la podoconiosis en sus planes nacionales de control sobre enfermedades tropicales desatendidas y aumentar el número de intervenciones para afrontar dicha enfermedad. Se necesita ayuda para suministrar calzado en clave de intervención sanitaria. Nuestra sugerencia para abolir la enfermedad es empezar por definir los casos y eliminar los obstáculos.

Elimination of lymphatic filariasis as a public health problem in Malawi.

BACKGROUND: Lymphatic filariasis (LF) is a parasitic disease transmitted by mosquitoes, causing severe pain, disfiguring, and disabling clinical conditions such as lymphoedema and hydrocoele. LF is a global public health problem affecting 72 countries, primarily in Africa and Asia. Since 2000, the World Health Organization (WHO) has led the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to support all endemic regions. This paper focuses on the achievements of the Malawi LF Elimination Programme between 2000 and 2020 to eliminate LF as a public health problem, making it the second sub-Saharan country to receive validation from the WHO. METHODOLOGY/PRINCIPAL FINDINGS: The Malawi LF Programme addressed the widespread prevalence of LF infection and disease across the country, using the recommended WHO GPELF strategies and operational research initiatives in collaboration with key national and international partners. First, to stop the spread of infection (i.e., interrupt transmission) and reduce the circulating filarial antigen prevalence from as high as 74.4% to below the critical threshold of 1-2% prevalence, mass drug administration (MDA) using a two-drug regime was implemented at high coverage rates (>65%) of the total population, with supplementary interventions from other programmes (e.g., malaria vector control). The decline in prevalence was monitored and confirmed over time using several impact assessment and post-treatment surveillance tools including the standard sentinel site, spot check, and transmission assessment surveys and alternative integrated, hotspot, and easy-access group surveys. Second, to alleviate suffering of the affected populations (i.e., control morbidity) the morbidity management and disability prevention (MMDP) package of care was implemented. Specifically, clinical case estimates were obtained via house-to-house patient searching activities; health personnel and patients were trained in self-care protocols for lymphoedema and/or referrals to hospitals for hydrocoele surgery; and the readiness and quality of treatment and services were assessed with new survey tools. CONCLUSIONS: Malawi's elimination of LF will ensure that future generations are not infected and suffer from the disfiguring and disabling disease. However, it will be critical that the Malawi LF Elimination programme remains vigilant, focussing on post-elimination surveillance and MMDP implementation and integration into routine health systems to support long-term sustainability and ongoing success. SUMMARY: Lymphatic filariasis, also known as elephantiasis, is a disabling, disfiguring, and painful disease caused by a parasite that infected mosquitoes transmit to millions of people worldwide. Since 2000, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) has supported endemic countries such as Malawi in south-eastern Africa, to eliminate the disease as a public health problem. The Malawi National LF Elimination Programme has worked tirelessly over the past two decades to implement the GPELF recommended strategies to interrupt the transmission with a two-drug regime, and to alleviate suffering in patients with lymphoedema and/or hydrocoele through morbidity management and disability prevention. Additionally, the LF Programme has collaborated with national and international stakeholders to implement a range of supplementary operational research projects to address outstanding knowledge gaps and programmatic barriers. In 2020, the World Health Organisation validated that Malawi had successfully eliminated LF as a public health problem, making it the second country in sub-Saharan Africa to achieve this, which is remarkable given that Malawi previously had very high infection rates. The LF Programme now remains vigilant, putting its efforts towards post-elimination surveillance and the continued implementation of care for patients with chronic conditions. Malawi's elimination of LF will ensure that future generations are not affected by this devastating disease.

Mental health and neglected tropical diseases - the neglected dimension of burden: identifying the challenges and understanding the burden.

Mental health co-morbidity and the Neglected Tropical Diseases (NTDs) has been highlighted as a major component of the ill health. The impact of mental illness is considered to be significantly underestimated in the calculations of the overall Disability-Adjusted Life Years (DALYs). This commentary discusses the DALY burden of anxiety, depression and associated stigma of NTDs. The economic losses incurred as a result of mental health conditions is assessed, and the impact on caregivers and families. It recommends that mental health care is incorporated into NTDs programme planning and implementation. Priority research is the estimation of the NTD burden of depressive and anxiety disorders and neuropsychiatric conditions of NTDs and an evaluation of the economic costs of mental illness derived from NTDs causation.

Socioeconomic aspects of neglected tropical diseases.

Although many examples of highly cost-effective interventions to control neglected tropical diseases exist, our understanding of the full economic effect that these diseases have on individuals, households, and nations needs to be improved to target interventions more effectively and equitably. We review data for the effect of neglected tropical diseases on a population's health and economy. We also present evidence on the costs, cost-effectiveness, and financing of strategies to monitor, control, or reduce morbidity and mortality associated with these diseases. We explore the potential for economies of scale and scope in terms of the costs and benefits of successfully delivering large-scale and integrated interventions. The low cost of neglected tropical disease control is driven by four factors: the commitment of pharmaceutical companies to provide free drugs; the scale of programmes; the opportunities for synergising delivery modes; and the often non-remunerated volunteer contribution of communities and teachers in drug distribution. Finally, we make suggestions for future economic research.

Quantifying conflict zones as a challenge to certification of Guinea worm eradication in Africa: a new analytical approach.

OBJECTIVES: To quantify conflict events and access across countries that remain to be certified free of transmission of Dracunculus medinensis (Guinea worm disease) or require postcertification surveillance as part of the Guinea Worm Eradication Programme (GWEP). SETTING AND PARTICIPANTS: Populations living in Guinea worm affected areas across seven precertification countries and 13 postcertification sub-Saharan African countries. OUTCOME MEASURES: The number of conflict events and rates per 100 000 population, the main types of conflict and actors reported to be responsible for events were summarised and mapped across all countries. Chad and Mali were presented as case studies. Guinea worm information was based on GWEP reports. Conflict data were obtained from the Armed Conflict Location and Event Data Project. Maps were created using ArcGIS V.10.7 and access was measured as regional distance and time to cities. RESULTS: More than 980 000 conflict events were reported between 2000 and 2020, with a significant increase since 2018. The highest number and rates were reported in precertification Mali (n=2556; 13.0 per 100 000), South Sudan (n=2143; 19.4), Democratic Republic of Congo (n=7016; 8.1) and postcertification Nigeria (n=6903; 3.4), Central Africa Republic (n=1251; 26.4), Burkina Faso (n=2004; 9.7). Violence against civilians, protests and battles were most frequently reported with several different actors involved including Unidentified Armed Groups and Boko Haram. Chad and Mali had contracting epidemiological and conflict situations with affected regions up to 700 km from the capital or 10 hours to the nearest city. CONCLUSIONS: Understanding the spatial-temporal patterns of conflict events, identifying hotspots, the actors responsible and their sphere of influence is critical for the GWEP and other public health programmes to develop practical risk assessments, deliver essential health interventions, implement innovative surveillance, determine certification and meet the goals of eradication.

The history of the neglected tropical disease movement.

The history of the neglected tropical disease movement is seen through the lens of authors who worked during the last 4 decades in different roles and in different settings, from Western-based laboratories to clinical roles in endemic countries and in critical policy roles in the World Health Organization (WHO). The authors seek to identify key players from the introduction of the word 'neglected' by the late Kenneth Warren in his Rockefeller Foundation-supported Great Neglected Diseases of Mankind movement through to the more recent developments after the London Declaration of 2012. The role of the various actors-endemic countries, major pharmaceutical companies, the WHO, non-government development organizations, bilateral donors and academia-are discussed. The critical events and decisions are highlighted that were essential enabling factors in creating a viable and successful movement and with a resultant massive global public health and antipoverty impact. The importance of advocacy is emphasized in creating the momentum to establish a globally recognized public health 'brand' as a target in the United Nations Sustainable Development Goals.

Are current preventive chemotherapy strategies for controlling and eliminating neglected tropical diseases cost-effective?

Neglected tropical diseases (NTDs) remain a significant cause of morbidity and mortality in many low-income and middle-income countries. Several NTDs, namely lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH) and trachoma, are predominantly controlled by preventive chemotherapy (or mass drug administration), following recommendations set by the WHO. Over one billion people are now treated for NTDs with this strategy per year. However, further investment and increased domestic healthcare spending are urgently needed to continue these programmes. Consequently, it is vital that the cost-effectiveness of preventive chemotherapy is understood. We analyse the current estimates on the cost per disability-adjusted life year (DALY) of the preventive chemotherapy strategies predominantly used for these diseases and identify key evidence gaps that require further research. Overall, the reported estimates show that preventive chemotherapy is generally cost-effective, supporting WHO recommendations. More specifically, the cost per DALY averted estimates relating to community-wide preventive chemotherapy for lymphatic filariasis and onchocerciasis were particularly favourable when compared with other public health interventions. Cost per DALY averted estimates of school-based preventive chemotherapy for schistosomiasis and STH were also generally favourable but more variable. Notably, the broader socioeconomic benefits are likely not being fully captured by the DALYs averted metric. No estimates of cost per DALY averted relating to community-wide mass antibiotic treatment for trachoma were found, highlighting the need for further research. These findings are important for informing global health policy and support the need for continuing NTD control and elimination efforts.

African regional progress and status of the programme to eliminate lymphatic filariasis: 2000-2020.

To eliminate lymphatic filariasis (LF) by 2020, the World Health Organization (WHO) has launched a campaign against the disease. Since the launch in 2000, significant progress has been made to achieve this ambitious goal. In this article we review the progress and status of the LF programme in Africa through the WHO neglected tropical diseases preventive chemotherapy databank, the Expanded Special Project for Elimination of Neglected Tropical Diseases (ESPEN) portal and other publications. In the African Region there are 35 countries endemic for LF. The Gambia was reclassified as not requiring preventive chemotherapy in 2015, while Togo and Malawi eliminated LF as a public health problem in 2017 and 2020, respectively. Cameroon discontinued mass drug administration (MDA) and transitioned to post-MDA surveillance to validate elimination. The trajectory of coverage continues to accelerate; treatment coverage increased from 0.1% in 2000 to 62.1% in 2018. Geographical coverage has also significantly increased, from 62.7% in 2015 to 78.5% in 2018. In 2019, 23 of 31 countries requiring MDA achieved 100% geographic coverage. Although much remains to be done, morbidity management and disability prevention services have steadily increased in recent years. Vector control interventions conducted by other programmes, particularly malaria vector control, have had a profound effect in stopping transmission in some endemic countries in the region. In conclusion, significant progress has been made in the LF programme in the region while we identify the key remaining challenges in achieving an Africa free of LF.

Podoconiosis: key priorities for research and implementation.

Podoconiosis is a non-infectious tropical lymphoedema causing swelling of the lower legs. Podoconiosis is associated with stigma, depression and reduced productivity, resulting in significant socio-economic impacts for affected individuals, families and communities. It is caused by barefoot exposure to soils and affects disadvantaged populations. Evidence from the past 5 y suggests that podoconiosis is amenable to public health interventions, e.g. footwear and hygiene-based morbidity management, which reduce acute clinical episodes. Although much has been learned in recent years, advances in care for these patients and worldwide control requires further reliable and relevant research. To develop a comprehensive global control strategy, the following key research priorities are important: better understanding of the global burden of podoconiosis through extended worldwide mapping, development of new point-of-care diagnostic methods and approaches to define the presence of the environmental characteristics that contribute to the development of the condition, improving treatment through an increased understanding of the pathogenesis of dermal changes over time, improved understanding of optimal ways of providing patient care at the national level, including research to optimize behavioural change strategies, determine the optimum package of care and integrate approaches to deliver robust surveillance, monitoring and evaluation of control programmes.

Environmental factors associated with the distribution of Loa loa vectors Chrysops spp. in Central and West Africa: seeing the forest for the trees.

BACKGROUND: Loiasis is caused by the filarial parasite Loa loa, which is widespread through Central and West Africa and largely confined the tropical equatorial rainforests. The tabanid flies Chrysops silacea and Chrysops dimidiata are the main vectors driving transmission. This study aimed to better define the spatial distribution and ecological niche of the two vectors to help define spatial-temporal risk and target appropriate, timely intervention strategies for filariasis control and elimination programmes. METHODS: Chrysops spp. distributions were determined by collating information from the published literature into a database, detailing the year, country, locality, latitude/longitude and species collected. Environmental factors including climate, elevation and tree canopy characteristics were summarised for each vector from data obtained from satellite modelled data or imagery, which were also used to identify areas with overt landcover changes. The presence of each Chrysops vector was predicted using a maximum entropy species distribution modelling (MaxEnt) method. RESULTS: A total of 313 location-specific data points from 59 published articles were identified across seven loiasis endemic countries. Of these, 186 sites were included in the climate and elevation analysis, and due to overt landcover changes, 83 sites included in tree canopy analysis and MaxEnt model. Overall, C. silacea and C. dimidiata were found to have similar ranges; annual mean temperature (24.6 °C and 24.1 °C, respectively), annual precipitation (1848.6 mm and 1868.8 mm), elevation (368.8 m and 400.6 m), tree canopy cover (61.4% and 66.9%) and tree canopy height (22.4 m and 25.1 m). MaxEnt models found tree canopy coverage was a significant environmental variable for both vectors. CONCLUSIONS: The Chrysops spp. database and large-scale environmental analysis provides insights into the spatial and ecological parameters of the L. loa vectors driving transmission. These may be used to further delineate loiasis risk, which will be important for implementing filariasis control and elimination programmes in the equatorial rainforest region of Central and West Africa.

Neglected Tropical Diseases and Mental Health: Progress, Partnerships, and Integration.

Neglected tropical diseases (NTDs) are increasingly recognised as major drivers of psychosocial morbidity in affected individuals and their caregivers. Nevertheless, there has remained a lack of prioritisation at the policy level of some of the most stigmatising and chronic NTDs, with subsequent under-representation within NTD programmes. In response, the Neglected Tropical Disease/Non-Governmental Organization/Network (NNN) has established a Mental Wellbeing and Stigma Task Group (MWS) to address these issues through a comprehensive research agenda. In our article, we highlight the progress in understanding the scope of the mental health impact of NTDs and the innovative practice emerging in this area. Finally, we examine opportunities for integration of mental and physical health for individuals with NTDs.

Cutaneous leishmaniasis and co-morbid major depressive disorder: A systematic review with burden estimates.

BACKGROUND: Major depressive disorder (MDD) associated with chronic neglected tropical diseases (NTDs) has been identified as a significant and overlooked contributor to overall disease burden. Cutaneous leishmaniasis (CL) is one of the most prevalent and stigmatising NTDs, with an incidence of around 1 million new cases of active CL infection annually. However, the characteristic residual scarring (inactive CL) following almost all cases of active CL has only recently been recognised as part of the CL disease spectrum due to its lasting psychosocial impact. METHODS AND FINDINGS: We performed a multi-language systematic review of the psychosocial impact of active and inactive CL. We estimated inactive CL (iCL) prevalence for the first time using reported WHO active CL (aCL) incidence data that were adjusted for life expectancy and underreporting. We then quantified the disability (YLD) burden of co-morbid MDD in CL using MDD disability weights at three severity levels. Overall, we identified 29 studies of CL psychological impact from 5 WHO regions, representing 11 of the 50 highest burden countries for CL. We conservatively calculated the disability burden of co-morbid MDD in CL to be 1.9 million YLDs, which equalled the overall (DALY) disease burden (assuming no excess mortality in depressed CL patients). Thus, upon inclusion of co-morbid MDD alone in both active and inactive CL, the DALY burden was seven times higher than the latest 2016 Global Burden of Disease study estimates, which notably omitted both psychological impact and inactive CL. CONCLUSIONS: Failure to include co-morbid MDD and the lasting sequelae of chronic NTDs, as exemplified by CL, leads to large underestimates of overall disease burden.

Combating the "other diseases" of MDG 6: changing the paradigm to achieve equity and poverty reduction?

This paper suggests that the 'other diseases' of Millennium Development Goal 6 (MDG 6) are ignored by policy-makers and politicians who overfocus on unachievable objectives and targets around the 'big three' diseases of HIV, tuberculosis (TB) and malaria, which if the planet was viewed by aliens would be seen as the only diseases that existed on the planet. The diseases of the majority of the poor represent 'low hanging fruit' for control and elimination and opportunities are ignored despite the availability of cheap or donated drugs and ample evidence that such interventions are effective and reduce incidence, as well as mortality and morbidity. The time frame available to achieve the MDGs of some 7-8 years requires a re-evaluation of what can be done with the tools available now and which can address the problems faced by the majority of poor people afflicted by disabling conditions which together represent a global burden greater than malaria or TB. The author considers also the volume of research relevant to the MDGs and their achievement is distorted by the focus on high tech end research which cannot be delivered by 2015 and that in terms of the 90:10 gap in research relevant to the problems of the poorest the real gap is 99:1. The concepts of distortion of donor funding for diseases of MDG 6 for implementation of largely curative interventions which do not reduce incidence as well as research which addresses problems that cannot reach poor people in the time frame to 2015 is emphasised. New paradigms are required if any impact on MDG 6 is to be achieved recognising the needs of the majority via an equitable distribution of funding.