Report from the Neglected Tropical Diseases and Emerging/Re-Emerging Infectious Diseases: Focus on Populations Underserved - Conference

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Presentations from the seminar:

• John Amuasi - African Research Network for Neglected Tropical Diseases (ARNTD), the Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana
• Kristine Husøy Onarheim - Department of Global Public Health and Primary Care, University of Bergen, Norway
• Karianne Johansen - CEPI 
• Detlef Böcking - DLR Project Management Agency, Federal Ministry of Education and Research, Germany
• Piers Millett - Future of Humanity Institute
• Bjarne Bjorvatn - Department of Global Public Health and Primary Care, University of Bergen, Norway

Background

In Global Health, critical challenges persist from communicable diseases affecting the poorest, most remote or ‘neglected’ populations. These diseases are hence termed Neglected Tropical Diseases and prevail in tropical and subtropical conditions in 149 countries (Figure 1) (1). These NTDs, as well as headline-grabbing EIDs such as H1N1, Ebola, Zika, and others, are immensely important in the field of Global Health, as all require extensive and multi-sectoral international cooperation and efforts.

The World Health Organization (WHO) has a priority list of 20 major NTDs and almost twice as many are put forward by PLOS Neglected Tropical Diseases, a dedicated NTD-focused journal. Despite the progress made in research, as well as successes in recent scaled-up preventive chemotherapy strategies and other health interventions, NTDs and EIDs rank among the world’s greatest global health challenges and hazards. For virtually all of the NTDs (including those prioritized in the 2012 London Declaration for NTDs (2,3) and a 2013 World Health Assembly resolution (4)), outreach, control mechanisms and tools are still needed, including new drugs, vaccines, diagnostics, and vector control agents and strategies (5).

NTDs and EIDs disproportionately impact the world's poorest, who are generally living without adequate sanitation and food and often in close contact with livestock, domestic animals and infectious vectors. This represents a significant and underappreciated global disease burden, and is a major barrier to alleviating poverty and improving health.

Emerging infectious disease epidemics pose a clear and ongoing risk to global health security. As a global strategy and preparedness plan, the WHO is spearheading a global coalition to avert epidemics by making R&D outbreak-ready. The WHO R&D Blueprint allows the rapid activation of R&D activities during epidemics. It aims to fast track the availability of effective tests, vaccines and medicines in order to avert large scale crises (6). Experiences with past epidemics highlight the need and the opportunity to improve emergency preparedness. It also underlines research as an important and integral element of the response to any epidemic.

“We are here today because there have been actions taken after the Ebola health crisis in 2014-2016, such as establishment of CEPI and the Norwegian government pledging over NOK 1.6 billion towards the cause of epidemic preparedness.” - Lene Lothe, Assistant Director of Department for Education and Global Health in NORD introducing the meeting.

In an era of a “globalized” environment of interdependent trade, travel and migration, many factors play an important role in the rise, emergence, and re-emergence of infectious diseases. Importantly, zoonotic diseases (i.e., infectious diseases that are transmitted from animals to humans) account for the majority of EIDs. Yet many of these diseases are also “neglected”, lacking adequate research, funding and innovation for prevention and treatment while impacting the world's poorest populations (7,8). Therefore, NTDs and EIDs seem to be inextricably linked and the specificity of both terms can be questioned.

The role of NTDs and EIDs in the Sustainable Development Goals (SDGs)

NTDs and EIDs both have the greatest relevance for achieving the health goal (SDG 3) in Agenda 2030. However, these diseases affect and are affected by many of the other development areas covered under the 2030 Agenda. For example, both NTDs and EIDs are affected by and impact development in SDGs 1 - to “end poverty in all its forms everywhere”, 2 - to “end hunger, achieve food security and improved nutrition and promote sustainable agriculture”, 4 - to “ensure inclusive and equitable quality education and promote lifelong learning opportunities for all”, and 6 - to “ensure availability and sustainable management of water and sanitation for all”, in terms of improving conditions for people living in slums, unsafe environments, or improving waste management; SDG 11 – to “make cities and human settlements inclusive, safe, resilient and sustainable” could contribute to detecting and addressing emerging vector-born threats (9); they also touch on 17 - to “strengthen the means of implementation and revitalize the Global Partnership for Sustainable Development” (10). Additionally, climate change, change of habitats and loss of biodiversity (addressed by SDG 12 and 15) threatens to overturn the global food system and promote EIDs and re-emerging diseases (11).

Additionally, although not explicitly on the Agenda 2030, strategies used in veterinary public health and the One Health approach are connected with all health and environmental SDGs and, thus, recognize that the health of people is connected to the health of animals and the environment. This is particularly relevant to a subset of NTDs and EIDs - the neglected zoonotic diseases.

Diseases of the neglected millions

During the meeting, key challenges for combatting NTDs and EIDs, and possible solutions and ways forward were highlighted by the presenters and the audience.

John Amuasi, Executive Director of the African Research Network for NTDs (ARNTD) and Executive Committee Member of the West African Task for Emerging and Re-emerging infectious diseases (WATER) brought to the forefront the meaning of “neglect”. It is neglected populations, neglected R&D, as well as neglected channels of access to already available diagnostics, treatments and prevention strategies. The neglect is caused by an overall failure by the governments to fulfil their ultimate responsibility to protect the interest of the public, and by the private sector with little incentive to invest in R&D for the most neglected people and the most neglected diseases.

Amuasi, together with Kristine Husøy Onarheim, Doctoral Research Fellow at the University of Bergen, spoke of the paradoxical NTD burden, which describes that outside of Sub-Saharan Africa, the largest number of NTDs occur among poor people in the middle- rather than low-income countries, and include nations belonging to the G20, such as Brazil, China, India, Indonesia and Nigeria (12,13). Furthermore, approximately 300 000 cases appear every year in the US (majority in Mesoamerica and Texas), as described by Peter Hotez in his book Blue Marble Health (14,15).

The meeting continued with the US-based neurologist and founder of Hope for Humans, Suzanna Gazda. Hope for Humans is an organization that provides comprehensive care to children suffering from Nodding Syndrome in Northern Uganda. Gazda offered hope to a seemingly hopeless NTD that emerged in Northern Uganda in 2007, but so far has not been labelled as such. Currently, there are no known causes for the disease and thus no causal treatment, but based on Gazda's experience, the microbiota is likely at the root of the neurological changes observed in children with Nodding Syndrome. Other attractive hypotheses represent subacute sclerosing panencephalitis, a post-measles disorder, due to interruption of vaccination programs during civil war in northern Uganda and a potentially O. volvulus associated autoimmune disorder based on cross-reactivity of specific antibodies between neurons of affected children and parasite antigen (16,17). Gazda’s report on Nodding Syndrome also raises the question whether the NTD concept as propagated by the WHO (18) should not be expanded to include non-communicable diseases.

"If we come to a medical problem with research with an open-minded strategy, we will certainly help the people solve these issues.” - Suzanne Gazda

The case of Uganda

Joyce Moriku Kaducu, the Minister of State for Primary Health Care in Uganda, spoke about the progress and challenges in Uganda from the primary healthcare level. Key aspects that contributed to the Ugandan success, such as the elimination of the Guinea worm and reduction of the burden of disease for many NTDs include:

• Inclusion of NTDs into district budgets;
• Decentralizing and implementing NTD strategy at the district level;
• Creating interventions that are guided by evidence and continuing research efforts;
• Ensuring that the data on gender is collected to ensure gender-sensitivity;
• Creating interventions that are pro-poor and pronounced in slums and poor rural and urban areas; and
• Working in partnership with other departments such as agriculture and education, and neighboring countries where cross-border transmission may occur.

Kaducu’s key strategies tie in nicely with the following statement: "Solutions to address NTDs are a public health best-buy and have a strong economic case." - John Amuasi (19).

Panel 1 – Important challenges to focus on

A panel tying together the first session of the meeting discussed the key challenges and barriers for addressing NTDs and EIDs. It is the neglect of the poor in particular where NTDs and EIDs share great similarities. These viral, bacterial and vector-transmitted diseases know no boundaries and borders and are likely to present further challenges unless a global approach is adopted. The global approach needs to take into account the changes to the global climate and include both local and high-level political commitment.

Panelists wondered whether the balance was tipped towards the influence and importance of pharmaceutical companies and drug donations. They emphasized both the need for innovation and effectively using the treatment and prevention strategies that already exist. What the panelists all agreed upon was the fact that most of the NTDs and EIDs concern primary healthcare facilities and district healthcare facilities and therefore, resource mobilization and coordinated funding in this sector is most needed. It was also raised that while neglect is a political issue, discussions tend to talk little about the role of politicians, governments and decision makers.

Global research for NTDs and EIDs

Karianne Johansen, Interim Secretariat, CEPI, during the second part of the procession, provided the background for the inception of CEPI following the Ebola virus outbreak. CEPI is a step towards a collaboration to combat EIDs with pandemic potential (20). Its role is to fill the gaps that are created by the lack of market incentives to develop vaccines against priority infectious diseases with pandemic potential. CEPI will finance and coordinate the development of new vaccines to prevent and contain infectious disease epidemics. As epidemics disproportionately affect low-income countries, CEPI will ensure that the vaccines we help develop are affordable, so that price is never a barrier to access, and they are available to populations with the most need (21). Within one year, the public and private funders were able to come together and set off the organization by the end of January 2017.

Detlef Böcking, DLR Project Management Agency, Federal Ministry of Education and Research, Germany, described Germany’s role in funding global health research (examples in Figure 2). When assessing the contributing factors that apply to EIDs, such as microbial adaptation, climate and weather change, change in human demographics, poverty and social inequality as well as diagnostic, treatment and prevention instruments, intersection with the NTDs is evident. Although each set of diseases has to be addressed separately, there is a lot of overlap in systems and approaches for combatting both EIDs and NTDs such as universal health coverage (UHC), health systems strengthening, capacity building, surveillance, diagnostic platforms and vector control. From a research funder’s perspective, Germany is focused on coordinating efforts that reflect the objectives of the WHO and strengthening the national research community, but also international coordination as well as R&D. Ownership of the most affected countries is a prerequisite of research programs (22).

Unfortunately there is still duplication of efforts on the same disease from different funders. “Joining forces in global health research is a common framework building on a common set of principles,” said Böcking. There is a strong need for information on what is happening in the field, identification of gaps and priorities as well as coordination platforms for funding activities. From there, decisions on what is best tackled by horizontal and vertical approaches can be made, and initiatives, like CEPI, can be successfully built.

Figure 2. Courtesy by Detlef Böcking, DLR Project Management Agency, Federal Ministry of Education and Research, Germany

Piers Millet from the WHO described one example of the formation of such common principles, frameworks and methods of global health initiatives. Millet outlined the process of forming the WHO R&D Blueprint, which bloomed from experiences and lessons of the Ebola crisis in West Africa. The scope of the Blueprint closely aligns with EIDs and re-emerging infectious diseases, however it only considers diseases with the potential to cause public health emergencies. The methodology for prioritization of diseases was developed by the WHO and based on best practice with a focus on balancing repeatable methodology and expert input. Prioritization consisted of 8 criteria and 39 sub-criteria, which included: human transmissibility, medical countermeasures, severity, human-animal interface, public health context of the affected region, potential social impacts and evolutionary potential, amongst others. There is also a strong push for One Health to become one of the factors contributing to disease selection.

Bjarne Bjorvatn, University of Bergen, who contributed to the development of WHO position papers on the use of vaccines gave his own overview of which vaccines he believes are most relevant today in the context of NTDs (Figure 3). Based on his experience, the criteria he had used to construct the list below included the prevalence, burden and current infection control of the disease as well as the feasibility of creating the vaccine, but also, whether the disease is better solved by improving health systems and intervening with conscious public health work, rather than by technological solutions.

Figure 3. Shortlist of priority vaccines by Bjarne Bjorvatn, University of Bergen

Panel 2 – Timely surveillance and the One Health approach

The panelists engaged in a rich discussion that ensued from the preceding presentations. The topics that were discussed where the importance of the efficiency and efficacy of measures that are employed, as well as the issue of timely surveillance to detect EIDs. While the importance of a One Health approach and discussion was considered to be at the center of the joint approach for NTDs and EIDs, it was raised that this aspect had not come out enough in the discussions and presentations and required more attention.

Tying it together

The last panel including all the speakers converged on the fact that poverty is a key and common factor of neglected and emerging diseases, which follows a cycle from changed food availability due to changing patterns of rain that result from climate change, limited or access to safe water supplies, inadequate hygiene practices and close proximity to farmed and wild animals that serve as disease reservoirs. Such global dynamics need to play a more important role in the discussion and tackling of both disease groups.

What sets NTDs and EIDs apart is the concept of global security. The threat to the world that EIDs embody and pose explains why some attention is directed to them over NTDs. The global community needs to engage more with neglected diseases and neglected populations. The panel concluded on the lack of market incentive for development of vaccines and treatments for diseases of the poor, making it less attractive for commercial exploration.

The 2030 Agenda for Sustainable Development unites the two concepts of NTDs and EIDs and the necessary action to deal with them: education, poverty, hunger, planetary health, healthy cities, etc. The SDGs may thus be our last leverage to push for these diseases at different levels.

The last panel including all the speakers converged on the fact that poverty is a key and common factor of NTDs and EIDs, which follows a cycle from insecure food availability due to unpredictable patterns of rain that result from climate change, limited access to or access to safe water supplies, inadequate hygiene practices and close proximity to farmed and wild animals that serve as disease reservoirs. Such global dynamics need to play a more important role in the discussion and tackling of both disease groups.

What sets NTDs and EIDs apart is the concept of global security. The threat to the world that EIDs embody and pose explains why attention is directed to them over NTDs. The global community needs to engage more with neglected diseases and neglected populations. The panel concluded on the lack of market incentive for development of vaccines and treatments for diseases of the poor, making it less attractive for commercial exploration.

The 2030 Agenda for Sustainable Development unites the two concepts of NTDs and EIDs and the necessary action to deal with them: education, poverty, hunger, planetary health, healthy cities, etc. The SDGs may thus be our last leverage to push for these diseases at different levels (9,11).

Conclusion

NTDs and EIDs concern the most neglected and the poorest populations in nearly all countries. They are diseases of poverty, neglected people, neglected R&D, neglected knowledge, neglected data and neglected access to diagnostic, treatment and prevention mechanisms. The neglect happens at local, national and global levels. Although much has been achieved, NTD programs continue to struggle with limited financial resources, inadequate capacity including capacity to implement effective surveillance, disruptive conflicts and barriers to accessing needed health services that range from poverty to stigmatization. Strengthening health systems, community ownership of disease surveillance and programs as well as putting neglected and emerging diseases on the global agenda is required to combat the current and future challenges of NTDs and EIDs. Reciprocally, integrating programs that effectively combat NTDs and prevent the spread of EIDs into health systems has the potential to accelerate progress towards UHC while advancing the broader Sustainable Development Goals for 2030. Finally, it is imperative to address the zoonotic roots of NTDs and EIDs, the majority of which are also neglected by pharmaceutical companies and governments. Addressing zoonotic diseases is a great opportunity to tackle NTDs and EIDs in a holistic/multidisciplinary way (18, 23).

Key challenges and solutions for combatting NTDs and EIDs highlighted at the meeting and during discussions were:

• Lack of incentives for R&D of vaccines and treatments for both  NTDs and EIDs;
• Reaching neglected populations;
• Building resilient health systems;
• Timely access to already-existing treatments in rural and urban clinics in the Global South;
• Including engaged communities, civil society, political stakeholders;
• Amplifying human and financial resources from both local and international sources;
• Strengthening disease surveillance and reporting;
• Implementing infection control measures;
• Prioritizing a disease for NTD lists;
• Joining forces in global health research and building common frameworks based on a common set of principles;
• Calling for One Health research activities and strategies;
• Research to anticipate future climate patterns and natural disasters, which affect agriculture and livelihoods of people in NTD and EID affected regions and thus pre-empting the spread of NTDS and EIDs; and finally,
• Addressing the SDGs, which run through the heart of the problem of poverty, sanitation, education, hunger, health of the planet, health of cities and health of the people.

References

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20.    CEPI. We want to stop future epidemics by developing new vaccines for a safer world. Coalition for Epidemic Preparedness Innovations 2017 [cited 2018 Jan 26]. Available from: cepi.net

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22.       Federal Ministry of Education and Research, Germany. Global health in the focus of research. Funding concept: Neglected and poverty-related diseases. Berlin: BMBF; 2015 [cited 2018 Oct 22]. Available from: https://www.bmbf.de/pub/Global_health.pdf

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Agenda