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Neglected tropical diseases – the present and the future

Andrea Sylvia Winkler, Katharina Klohe, Veronika Schmidt, Ingeborg Haavardsson, Annette Abraham, Ulrich Fabien Prodjinotho, Bernard Ngowi, Chummy Sikasunge, Emilia Noormahomed, John Amuasi, Joyce Kaducu, Helena Ngowi, Bernadette Abele-Ridder, Wendy Elizabeth Harrison, Clarissa Prazeres da Costa About the authors

Neglected tropical diseases are a diverse group of diseases that predominantly but not exclusively affect people in tropical and subtropical climatic zones. The collaboration between the WHO, non-governmental organisations, local stakeholders and pharmaceutical companies, among others, is key to achieving control and elimination of these diseases.

The term ‘neglected tropical diseases’ was coined by Peter Hotez and colleagues in 2003 to counterbalance the attention given to HIV/AIDS, tuberculosis and malaria (1). Neglected tropical diseases have been termed a ‘chronic pandemic’ (2) and are largely associated with lower socioeconomic status. The diseases are highly prevalent both in rural and poor urban settings, mainly in low- and middle-income countries (3). It is, however, not well defined which diseases fall under this category, as indicated by the different lists of diseases included in the WHO and PLOS definitions (Table 1) (4, 5).

Table 1

Major neglected tropical diseases adjusted from the expanded list of PLOS NTD (5). The 20 diseases recognised by the WHO (4) have been underlined.

Protozoan infections

• Amoebiasis
• Balantidiasis
Chagas disease
• Giardiasis
Human African trypanosomiasis
Leishmaniasis

Helminth infections

Taenia solium (neuro)cysticercosis/taeniosis
Dracunculiasis
Echinococcosis
Foodborne trematodiases
• Loiasis
Lymphatic filariasis
Onchocerciasis
Schistosomiasis
Soil-transmitted helminthiases (ascariasis, hookworm diseases, trichuriasis, strongyloidiasis)
• Toxocariasis and other larva migrans diseases

Bacterial Infections

• Bartonellosis
• Bovine tuberculosis in humans
Buruli ulcer
• Cholera
• Diarrhoeal diseases (shigella, salmonella, E. coli)
Leprosy
• Leptospirosis
• Relapsing fever
Trachoma
• Treponematoses (endemic syphilis (=bejel), pinta, syphilis, yaws)

Viral Infections

Dengue and chikungunya fevers
• Japanese encephalitis
• Jungle yellow fever
• Other arboviral Infections
Rabies
• Rift Valley fever
• Viral haemorrhagic fevers

Fungal Infections1

Mycetoma, paracoccidiomycosis, chromoblastomycosis, other deep mycosis

Ectoparasitic1 Infections

Scabies, myiasis

Venom1

Snakebite envenoming

1Have been added recently in 2017 on the occasion of the 10th meeting of the Strategic and Technical Advisory Group for Neglected Tropical Diseases

Neglected tropical diseases are characterised by a high burden of disease, measured in disability-adjusted life years (6). Estimates vary from 26 million to 48 million years lost to the diseases. Compared to tuberculosis (49 million years), malaria (83 million years) and HIV/AIDS (82 million years), the disease burden of neglected tropical diseases is also substantial (7). An estimated one billion people are currently affected by neglected tropical diseases worldwide and approximately 350 000–500 000 die from them each year (2, 810). Exact numbers are, however, unknown as most diseases progress slowly. Signs and symptoms are often insidious or unspecific and are commonly not diagnosed until late stages of disease progression. As affected individuals tend to be poor and lack the necessary information and financial resources to access health care, many cases go unreported.

Parasites cause more than 50 % of all neglected tropical diseases and include both protozoan and helminthic infections, and of late also ectoparasites (scabies), followed in order of frequency by bacterial, viral and fungal infections. In endemic areas, especially in sub-Saharan Africa, individuals often suffer from more than one neglected tropical disease. For possible symptoms and signs that patients may suffer from, refer to Box 1. Moreover, areas endemic for neglected tropical diseases tend to be endemic for HIV/AIDS, tuberculosis and malaria, and co-infection, especially with soil-transmitted helminths and schistosomes, has been shown to exacerbate the progression of the aforementioned diseases (2, 8, 11).

Importantly, neglected tropical diseases are not only confined to the tropics. Increase in prevalence has been observed in southern Europe (e.g. dengue fever, Chagas disease, leishmaniasis, opisthorchiasis and schistosomiasis). This may be due to increased poverty, migration and climate change (12).

Management of the diseases

Integrated intervention-centred approaches to management of neglected tropical diseases focus on outreach to poor and marginalised communities through preventive chemotherapy, intensified case management, vector control, veterinary public health as well as safe water, sanitation and hygiene (2, 13). Preventive chemotherapy through mass drug administration refers to distribution of disease-specific medication to individuals in endemic areas, without the need for individual diagnosis, at low cost (between USD 0.30 and USD 0.50 per person treated) (14). It is therefore at the core of programmes that fight neglected tropical diseases.

Box 1 Clinical signs and symptoms associated with neglected tropical diseases (1, 3, 11, 14)

  • Skin diseases with severe itching, blindness, acute and chronic diarrhoea, anaemia (with potentially severe adverse effects in children and pregnant women), acute and chronic pain, hepatic disease and other end organ damage as well as cancer

  • Psychiatric and neurological conditions, including epilepsy

  • Malnutrition

  • Stunting and cognitive impairment leading to compromised education and loss of productivity in adults

  • Stigma and social exclusion due to disability and disfigurement

Repeated mass drug administration aims at morbidity control as it tends to lead to reduction in the force of infection as well as having the potential to break disease transmission, as seen in programmes on river blindness (onchocerciasis). Mass drug administration programmes are carried out by non-governmental organisations in collaboration with national governments. Guidelines for national control and elimination programmes have been developed by the World Health Organization based on expert opinion. In addition, the Neglected Tropical Diseases Non-Governmental Organisations Network, a group of more than 60 non-governmental organisations, has developed a comprehensive ‘Behaviour, Environment, Social Inclusion and Equity, as well as Treatment and Care’ framework the BEST framework) to facilitate the uptake of this type of holistic and multidisciplinary approach (15).

Overall, progress has been made with regard to the 2020 targets outlined by the World Health Organization in its Roadmap on neglected tropical diseases, including eradication, national/regional elimination and control, see Box 2 (2, 16). This progress has been possible due to strong global partnerships, donations by the pharmaceutical industry, new diagnostic tools, new drug development, commitment by governments to global collaboration and the support of public and private partners (13, 17).

Box 2 WHO Roadmap strategy on control, elimination and eradication of neglected tropical diseases (2, 16).

Control 
Dengue fever, Buruli ulcer, cutaneous leishmaniasis, foodborne trematode infections, Taenia solium (neuro)cysticercosis/taeniosis, echinococcosis, soil-transmitted helminthiasis

Regional elimination 
Lymphatic filariasis, onchocerciasis, leprosy, human African trypanosomiasis, trachoma, schistosomiasis, rabies, Chagas disease, visceral leishmaniasis

Eradication 
Guinea worm, endemic treponematoses (yaws)

Nonetheless, efforts are still largely focused on the diseases for which medication and large-scale treatment options are available, including lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis and trachoma. Zoonotic diseases, such as T. solium (neuro)cysticercosis/taeniosis, do not necessarily benefit from preventive chemotherapy and need a different, even more cross-sectoral approach, including e.g. environmental studies. Despite vaccines and medication for animals being readily available, zoonotic neglected tropical diseases have received less attention and are sometimes referred to as the most neglected among the neglected tropical diseases (18). Advocacy for and investment in both domestic and wild animal health and community livelihood are key to successful control and elimination of zoonotic neglected tropical diseases.

One promising approach to push this agenda forward would be the integration of management of neglected tropical diseases and that of emerging infectious diseases. These groups of diseases share important characteristics, such as their tendency to affect largely underserved populations, their zoonotic nature and the need for vector control, as well as scarcity of point-of-care diagnostics, drugs and vaccines. Thus, strong and resilient health systems with adequate access to health care and universal health coverage as well as a cross-sectoral ‘one-health approach’ combining human, animal and environmental health should be given highest priority (2, 10).

Politics and future directions

Important steps have been taken towards reaching the 2020 World Health Organization Roadmap targets on neglected tropical diseases, published in 2012, as shown in Box 2 (16). The number of people treated for neglected tropical diseases is increasing, with one billion people having been provided with preventive chemotherapy in 2015 (19), and some countries having been able to announce the elimination of certain diseases.

Furthermore, this disease group was included in the Sustainable Development Goal agenda, the German G7 summit and G20 communications, which is the result of the hard work of the neglected tropical disease lobby in raising political awareness that this group of diseases clearly deserves (20, 21). It is now imperative to go beyond the focus on the preventive chemotherapy of neglected tropical diseases and to address the zoonotic neglected tropical diseases that do not yet benefit from the pharmaceutical and governmental support that the others enjoy. The one-health approach needed to tackle zoonotic neglected tropical diseases provides an important opportunity to link these diseases with emerging infectious diseases and can thereby create leverage for resources and political attention. In addition, and most urgently, strengthening global health systems is required in order to prevent, diagnose, treat and eventually eliminate neglected tropical diseases.

This article is part of the series ‘Global Health in the Era of Agenda 2030’, a collaboration between Norad, the Centre for Global Health at the University of Oslo and The Journal of the Norwegian Medical Association. Articles are published in English only. The views and opinions expressed in the articles are those of the authors only.

1

Smith J, Taylor EM. What is next for NTDs in the era of the Sustainable Development Goals? PLoS Negl Trop Dis 2016; 10: e0004719. [PubMed][CrossRef]

2

Molyneux DH, Savioli L, Engels D. Neglected tropical diseases: progress towards addressing the chronic pandemic. Lancet 2017; 389: 312 - 25. [PubMed][CrossRef]

3

Hotez PJ. NTDs V.2.0: “blue marble health”–neglected tropical disease control and elimination in a shifting health policy landscape. PLoS Negl Trop Dis 2013; 7: e2570. [PubMed][CrossRef]

4

World Health Organization. Neglected Tropical Diseases. 2017. http://www.who.int/neglected_diseases/diseases/en/ (20.7.2017).

5

 PLoS Neglected Tropical Diseases. Journal Information. http://journals.plos.org/plosntds/s/journal-information#loc-contents (20.7.2017).

6

World Health Organization. Health Statistics and Information Systems. 2017. http://www.who.int/healthinfo/global_burden_disease/metrics_daly/en/ (20.07.2017).

7

Hotez PJ, Alvarado M, Basáñez M-G et al. The global burden of disease study 2010: interpretation and implications for the neglected tropical diseases. PLoS Negl Trop Dis 2014; 8: e2865. [PubMed][CrossRef]

8

Hotez PJ, Molyneux DH, Fenwick A et al. Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria. PLoS Med 2006; 3: e102. [PubMed][CrossRef]

9

Hotez PJ, Molyneux DH, Fenwick A et al. Control of neglected tropical diseases. N Engl J Med 2007; 357: 1018 - 27. [PubMed][CrossRef]

10

World Health Organization. Fourth Report on NTDs - Integrating neglected tropical diseases in global health and development. Geneva: WHO, 2017. http://apps.who.int/iris/bitstream/10665/255011/1/9789241565448-eng.pdf?ua=1 (20.7.2017).

11

Kroidl I, Saathoff E, Maganga L et al. Effect of Wuchereria bancrofti infection on HIV incidence in southwest Tanzania: a prospective cohort study. Lancet 2016; 388: 1912 - 20. [PubMed][CrossRef]

12

Hotez PJ. Southern Europe’s coming plagues: vector-borne neglected tropical diseases. PLoS Negl Trop Dis 2016; 10: e0004243. [PubMed][CrossRef]

13

The WHO Strategic and Technical Advisory Group for Neglected Tropical Disease (WHO STAG). Recommendations for the adoption of additional diseases as neglected tropical diseases. http://www.who.int/neglected_diseases/diseases/Adoption_additional_NTDs.pdf?ua=1 (20.7.2017).

14

Webster JP, Molyneux DH, Hotez PJ et al. The contribution of mass drug administration to global health: past, present and future. Philos Trans R Soc Lond B Biol Sci 2014; 369: 20130434. [PubMed][CrossRef]

15

Neglected Tropical Disease NGO Network. The BEST Framework: A comprehensive approach towards Neglected Tropical Diseases. 2017. http://www.ntd-ngonetwork.org/resources/best-framework-comprehensive-approach-towards-neglected-tropical-diseases (20.7.2017).

16

World Health Organization. Accelerating Work to Overcome the Global Impact of Neglected Tropical Diseases – A Roadmap for Implementation. 2012. http://www.who.int/neglected_diseases/NTD_RoadMap_2012_Fullversion.pdf (20.7.2017).

17

World Health Organization. Uniting to Combat Neglected Tropical Diseases. London Declaration on Neglected Tropical Diseases 2012. http://www.who.int/neglected_diseases/London_Declaration_NTDs.pdf (20.7.2017).

18

Webster JP, Gower CM, Knowles SCL et al. One health - an ecological and evolutionary framework for tackling Neglected Zoonotic Diseases. Evol Appl 2016; 9: 313 - 33. [PubMed][CrossRef]

19

World Health Organization. Unprecedented Progress against Neglected Tropical Diseases, WHO reports. News Release. 2017. http://www.who.int/mediacentre/news/releases/2017/ntd-report/en/ (20.7.2017).

21

Amuasi J. Combating Neglected Tropical Diseases – Now. G20 Germany 2017; 104-105. https://issuu.com/intrinsiccommunications/docs/g20_hamburg_2017 (20.7.2017).

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