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[The concept of neglected disease].

"Neglected disease", "neglected population" and more generally "public health negligence" are emerging concepts being put forward by numerous humanitarian groups. Sleeping sickness provides a typical example to illustrate these concepts. After causing a major epidemic in the 1930s, sleeping sickness had been practically eradicated by the end of decolonization. Because of more urgent priorities, independent national governments relinquished control activities thus allowing the disease to return insidiously. By the beginning of the 1990s the situation was comparable to that prevailing in 1930 without inciting a response commensurate with the extent of the problem. Sleeping sickness is currently not a priority and, more simply, is not given proper attention because it affects only a few people living in regions presenting little economic interest. This point underlines the especially devastating combination of neglected disease and neglected population. As early as 1999 the World Health Organization with the determined support of Medecins Sans Frontieres launched a campaign not only to promote control measures for sleeping sickness at the international level but also to use initiatives in the domain to illustrate the enormous potential for progress against neglected disease. The effects of this campaign are now beginning to be felt.

Africa↗

Neglected diseases of neglected populations: thinking to reshape the determinants of health in Latin America and the Caribbean.

BACKGROUND: People living in poverty throughout the developing world are heavily burdened with neglected communicable diseases and often marginalized by the health sector. These diseases are currently referred to as Neglected Diseases of Neglected Populations. The neglected diseases create social and financial burdens to the individual, the family, the community, and the nation. DISCUSSION: Numerous studies of successful individual interventions to manage communicable disease determinants in various types of communities have been published, but few have applied multiple interventions in an integrated, coordinated manner. We have identified a series of successful interventions and developed three hypothetical scenarios where such interventions could be applied in an integrated, multi-disease, inter-programmatic, and/or inter-sectoral approach for prevention and control of neglected diseases in three different populations: a slum, an indigenous community, and a city with a mix of populations. SUMMARY: The objective of this paper is to identify new opportunities to address neglected diseases, improve community health and promote sustainable development in neglected populations by highlighting examples of key risk and protective factors for neglected diseases which can be managed and implemented through multi-disease-based, integrated, inter-programmatic, and/or inter-sectoral approaches. Based on a literature review, analysis and development of scenarios we visualize how multiple interventions could manage multiple disease problems and propose these as possible strategies to be tested. We seek to stimulate intra- and inter-sectoral dialogue which will help in the construction of new strategies for neglected diseases (particularly for the parasitic diseases) which could benefit the poor and marginalized based on the principle of sustainability and understanding of key determinants of health, and lead to the establishment of pilot projects and activities which can contribute to the achievement of the Millennium Development Goals.

Animals↗

[Drugs for 'neglected diseases': a bitter pill].

Neglected diseases are diseases restricted to poor areas; diseases for which there exist no commercial incentives to invest in the development of new treatments. Patients suffering from these diseases often have no access to essential drugs; this can be a matter of life and death. Lack of research and patent protection play a crucial role. Both are cost driven; greed in the West curtails the availability of life-saving drugs for all. Treatment options for trypanosomiasis and visceral leishmaniasis are lacking. It is recommended that drugs for the treatment of 'neglected diseases' be developed via a centralised, public approach that is not based on profit, rather than leaving it to free enterprise.

Africa↗

Peripheral arterial disease: a high risk - but neglected - disease population.

Peripheral arterial disease (PAD) is a common, progressive manifestation of atherothrombotic vascular disease, which should be managed no different to cardiac disease. Indeed, there is growing evidence that PAD patients are a high risk group, although still relatively under-detected and under treated. This is despite the fact that PAD patients are an increased mortality rate comparable to those with pre-existing or established cardiovascular disease [myocardial infarction, stroke]. With a holistic approach to atherothrombotic vascular disease, our management of PAD can only get better.

Age Factors↗

Drug development for neglected diseases: a deficient market and a public-health policy failure.

There is a lack of effective, safe, and affordable pharmaceuticals to control infectious diseases that cause high mortality and morbidity among poor people in the developing world. We analysed outcomes of pharmaceutical research and development over the past 25 years, and reviewed current public and private initiatives aimed at correcting the imbalance in research and development that leaves diseases that occur predominantly in the developing world largely unaddressed. We compiled data by searches of Medline and databases of the US Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products, and reviewed current public and private initiatives through an analysis of recently published studies. We found that, of 1393 new chemical entities marketed between 1975 and 1999, only 16 were for tropical diseases and tuberculosis. There is a 13-fold greater chance of a drug being brought to market for central-nervous-system disorders or cancer than for a neglected disease. The pharmaceutical industry argues that research and development is too costly and risky to invest in low-return neglected diseases, and public and private initiatives have tried to overcome this market limitation through incentive packages and public-private partnerships. The lack of drug research and development for "non-profitable" infectious diseases will require new strategies. No sustainable solution will result for diseases that predominantly affect poor people in the South without the establishment of an international pharmaceutical policy for all neglected diseases. Private-sector research obligations should be explored, and a public-sector not-for-profit research and development capacity promoted.

Anti-Infective Agents↗

Giardia and Cryptosporidium join the 'Neglected Diseases Initiative'.

Giardia and Cryptosporidium are ubiquitous enteric protozoan pathogens that infect humans, domestic animals and wildlife worldwide. Both pathogens are significant causes of diarrhea and nutritional disorders in institutional and community settings. They are also significant waterborne pathogens. In developing regions of the world, Giardia and Cryptosporidium constitute part of the complex group of parasitic, bacterial and viral diseases that impair the ability to achieve full potential and impair development and socio-economic improvements. All diseases included in the WHO Neglected Diseases Initiative have a common link with poverty and, as the current view is to take a comprehensive approach to all these diseases, both Giardia and Cryptosporidium were included in 2004. Our current state of knowledge of Giardia and Cryptosporidium is summarized here, and some important questions are raised that need to be addressed if control strategies are to be effective.

Animals↗

Choosing the right incentive strategy for research and development in neglected diseases.

For the first time in history, worldwide neglected disease budgets may be large enough to deliver a new drug every few years. That said, sponsors will only succeed if they extract maximum value from every dollar spent. This paper reviews possible cost-containment strategies and provides an evidence-based framework for choosing between them. Current proposals can be categorized as "end-to-end" proposals which require the sponsor to set a single reward for companies that complete the entire drug discovery process or "pay-as-you-go" schemes in which sponsors offer repeated rewards as drug candidates progress through the pipeline. A generic weakness of end-to-end proposals is that rewards are likely to be 20-30% higher than they would be in an equivalent pay-as-you-go programme. However, the benefits of pay-as-you-go programmes may be lost if commercial pharmaceutical companies are substantially better at choosing successful programmes than are their non-profit counterparts. The efficiency of pay-as-you-go methods depends on sponsors' willingness to withdraw funding from failed drug discovery programmes.

Global Health↗

Stimulating pharmaceutical research and development for neglected diseases.

New vaccines and drug treatments are needed for tackling the neglected diseases (NDs) of poor countries. These diseases are associated with high levels of mortality and/or morbidity, but lack appropriate vaccines and drug treatments because of bacterial resistance, toxicity, long-treatment protocols, problems with administration or because none are available. Current initiatives directed at research and development (R&D) of NDs are being led predominantly by the governmental, inter-governmental and private not-for-profit sectors implemented by way of public-private partnerships. Push and pull mechanisms targeted at the pharmaceutical industry have also been proposed as another way to stimulate R&D of NDs; however, these should be viewed with some caution. Stimulating R&D for NDs is important as part of a wider long-term public health strategy and must be addressed simultaneously with resolving more immediate problems of access to medicines and health system sustainability in less developed countries.

Anti-Infective Agents↗

Prevention, control, and elimination of neglected diseases in the Americas: pathways to integrated, inter-programmatic, inter-sectoral action for health and development.

BACKGROUND: In the Latin America and Caribbean region over 210 million people live below the poverty line. These impoverished and marginalized populations are heavily burdened with neglected communicable diseases. These diseases continue to enact a toll, not only on families and communities, but on the economically constrained countries themselves. DISCUSSION: As national public health priorities, neglected communicable diseases typically maintain a low profile and are often left out when public health agendas are formulated. While many of the neglected diseases do not directly cause high rates of mortality, they contribute to an enormous rate of morbidity and a drastic reduction in income for the most poverty-stricken families and communities. The persistence of this "vicious cycle" between poverty and poor health demonstrates the importance of linking the activities of the health sector with those of other sectors such as education, housing, water and sanitation, labor, public works, transportation, agriculture, industry, and economic development. SUMMARY: The purpose of this paper is three fold. First, it focuses on a need for integrated "pro-poor" approaches and policies to be developed in order to more adequately address the multi-faceted nature of neglected diseases. This represents a move away from traditional disease-centered approaches to a holistic approach that looks at the overarching causes and mechanisms that influence the health and well being of communities. The second objective of the paper outlines the need for a specific strategy for addressing these diseases and offers several programmatic entry points in the context of broad public health measures involving multiple sectors. Finally, the paper presents several current Pan American Health Organization and other institutional initiatives that already document the importance of integrated, inter-programmatic, and inter-sectoral approaches. They provide the framework for a renewed effort toward the efficient use of resources and the development of a comprehensive integrated solution to neglected communicable diseases found in the context of poverty, and tailored to the needs of local communities.

Caribbean Region↗

An ounce of prevention on a budget: a nonprofit approach to developing vaccines against neglected diseases.

This article provides a perspective on vaccine development for neglected tropical diseases in the nonprofit setting, with particular emphasis on recombinant protein vaccines. The Human Hookworm Vaccine Initiative is discussed as a model product development public-private partnership, and the major challenges are covered that accompany antigen selection, gene cloning, fermentation and purification process development, assay development, vaccine formulation and testing and clinical evaluation for those developing vaccines, especially against neglected tropical diseases, in the nonprofit sector. Throughout this perspective, special emphasis is placed on the growing promise that product development public-private partnerships hold for developing vaccines for the world's poorest people.

Budgets↗

Hepatosplenic schistosomiasis: a great neglected disease of the liver.

Schistosomiasis mansoni and japonica, helminth infections involving the livers of 100 million people, are among the 'great neglected diseases of mankind' on the basis both of their prevalence and the relative lack of interest shown in them by clinicians and biomedical investigators. Schistosomiasis is not only an interesting disease in itself but has the added advantage of providing unique human and animal models of hepatic pathophysiology, immunopathogenesis, and collagen metabolism.

Collagen↗

Vaccines for the prevention of neglected diseases--dengue fever.

Dengue and dengue hemorrhagic fever have spread to all tropical areas of the developing world, but still remain largely neglected diseases. Several promising vaccine candidates in the form of live attenuated and chimeric vaccines have been developed and are currently in human clinical trials. However, significant practical, logistic, and scientific challenges remain before these vaccines can widely and safely be applied to vulnerable populations. Vector control, community education and public health measures must be pursued in parallel with vaccine development.

Dengue↗

Building local research and development capacity for the prevention and cure of neglected diseases: the case of India.

This paper examines the proposal to build research and development (R&D) capabilities for dealing with neglected infectious and tropical diseases in countries where they are endemic, as a potentially cost- and time-effective way to fill the gap between the supply of and need for new medicines. With reference to the situation in India, we consider the competencies and incentives needed by companies so that their strategy can be shifted from reverse engineering of existing products to investment in R&D for new products. This requires complex reforms, of which the intellectual property rights agreement is only one. We also consider whether Indian companies capable of conducting research and development are likely to target neglected diseases. Patterns of patenting and of R&D, together with evidence from interviews we have conducted, suggest that Indian companies, like multinational corporations, are likely to target global diseases because of the prospect of much greater returns. Further studies are required on how Indian companies would respond to push and pull incentives originally designed to persuade multinational corporations to do more R&D on neglected diseases.

Communicable Diseases↗

Drugs for neglected diseases: a failure of the market and a public health failure?

Infectious diseases cause the suffering of hundreds of millions of people, especially in tropical and subtropical areas. Effective, affordable and easy-to-use medicines to fight these diseases are nearly absent. Although science and technology are sufficiently advanced to provide the necessary medicines, very few new drugs are being developed. However, drug discovery is not the major bottleneck. Today's R&D-based pharmaceutical industry is reluctant to invest in the development of drugs to treat the major diseases of the poor, because return on investment cannot be guaranteed. With national and international politics supporting a free market-based world order, financial opportunities rather than global health needs guide the direction of new drug development. Can we accept that the dearth of effective drugs for diseases that mainly affect the poor is simply the sad but inevitable consequence of a global market economy? Or is it a massive public health failure, and a failure to direct economic development for the benefit of society? An urgent reorientation of priorities in drug development and health policy is needed. The pharmaceutical industry must contribute to this effort, but national and international policies need to direct the global economy to address the true health needs of society. This requires political will, a strong commitment to prioritize health considerations over economic interests, and the enforcement of regulations and other mechanisms to stimulate essential drug development. New and creative strategies involving both the public and the private sector are needed to ensure that affordable medicines for today's neglected diseases are developed. Priority action areas include advocating an essential medicines R&D agenda, capacity-building in and technology transfer to developing countries, elaborating an adapted legal and regulatory framework, prioritizing funding for essential drug development and securing availability, accessibility, distribution and rational use of these drugs.

Communicable Diseases, Emerging↗