Parasites, people and policy: infectious diseases and the Millennium Development Goals

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1 Forum TRENDS in Ecology and Evolution Vol.22 No.10 Parasites, people and policy: infectious diseases and the Millennium Development Goals Robert M. May Department of Zoology, Oxford University, Oxford, OX1 3PS, UK Here, I briefly review past history and present patterns in the interactions between parasites (defined broadly to include viruses and bacteria along with protozoan, helminth and arthropod parasites) and human populations in developed and developing countries. Against this background, I offer thoughts on current public health initiatives at national and international levels, with particular reference to the Millennium Development Goals. The news is both good and bad: mortality and morbidity from infectious diseases in the developing world are significantly lower than they were 50 years ago, but we should and could be doing better, particularly in relation to neglected tropical diseases. Introduction The eight Millennium Development Goals, or MDG, enunciated by the UN are set out in Box 1. Parasitic infections relate directly to three of these eight (namely, numbers 4, 5 and 6) and are closely involved in two others (namely, the important numbers 1 and 2). In making this claim, I define parasites broadly to include both microparasites and macroparasites, in the sense defined by Anderson and May [1,2]; that is, I include viruses and bacteria along with the protozoan, arthropod and helminth agents of conventionally defined parasitology. In what follows, I sketch some past and present patterns in the interactions between humans and parasites. The general trend here could be called good news. I then turn to the bad news : the persisting distinction between diseases of the rich and diseases of the poor. Against this background, I discuss possible actions to achieve a fairer world: this discussion covers, among other things, research priorities (basic knowledge), economic impediments to developing medical products for diseases of the poor, and ideas for new incentives. I conclude with some worries about new or re-emerging infectious diseases. Good news: the past 50 years and the present A comparison of survivorship curves for a typical developed country and a typical developing country 50 years ago (Figure 1) shows that the curve for developing countries is better, but not much better, than those inferred for our hunter-gatherer ancestors before the dawn of agriculture (Figure 2). Corresponding author: May, R.M. (robert.may@zoo.ox.ac.uk). Available online 27 September As a global average, life expectancy at birth 50 years ago was 46 years, with an average difference of 26 years between developed and developing countries. Today, as a result of better understanding of the transmission dynamics of infectious diseases and of methods for their treatment and control (better hygiene, improved water supplies, vaccination, control of vectors, simple rehydration procedures for infant diarrhoea, etc.), average life expectancy at birth is 64 years. In India, for example, average life expectancy in 1950 was 39.4 and 38.0 years for males and females, respectively. The corresponding figures in 1998 were 62.1 and This change occurred primarily because the average gap between developed and developing countries has diminished to a still-distressing 12 years. It is, however, interesting to compare Figure 1 with Figure 3, which shows the survivorship curve in mid-19th century Liverpool, which is fairly typical of early industrial centres in the West. In the 19th and early 20th century slums in Western cities, mortality rates were appalling. A child born in Liverpool in 1860 had only a 50% chance of living beyond five years [3]. By contrast, in 2006, 130 million children were born, and although some ten million will not survive the first five years (for a mortality rate of 8%), the odds are better than in the past for the developed world. Why are today s developing, low-income countries much healthier than today s high-income countries were at comparable stages of development? Interestingly, recent studies indicate that such improvements in public health come mainly from scientific and technological advances, rather than simply from income growth (as some economists have rather mystically suggested). One such study finds that income growth explains only 10% 25% of increasing life expectancy [4]. Another finds that a decline in infant mortality owes 5% to income growth, as against 21% to better education (Jamieson, D.T. et al. (2001) Commission on Macroeconomics and Health Working Paper WG1:4, [ Bad news: diseases of the rich and diseases of the poor These encouraging trends must, however, be set against the still-wide gap in life expectancy, and general health, between the developed and developing worlds. A more meaningful measure of disease burden goes beyond life /$ see front matter ß 2007 Elsevier Ltd. All rights reserved. doi: /j.tree

2 498 Forum TRENDS in Ecology and Evolution Vol.22 No.10 Box 1. UN Millennium Development Goals These are the goals that the UN aspires to achieve as the new millennium begins. Conspicuous by its absence is any reference to halting population growth (although it could be seen as implicit in 3 and 7). 1. Eradicate extreme poverty and hunger. 2. Achieve universal primary education. 3. Promote gender equality and empowerment for women. 4. Reduce child mortality. 5. Improve maternal health. 6. Combat HIV/AIDS, malaria and other diseases. 7. Ensure environmental sustainability. 8. Develop a global partnership for development. expectancy to assess Disability Adjusted Life Years (DALY; [5]). This quantitative measure combines premature mortality with years of productive life lost owing to morbidity or disability. One DALY equals one year of healthy life lost. Figures 4a and 4b contrast the causes of DALY in high-income (developed) countries with those in lowincome (developing) countries, respectively [6]. In the rich world, communicable infections account for only 7% of DALY. The corresponding fraction for poor countries is an order of magnitude higher at 57%. Table 1 reinforces the contrast shown in Figure 4a and 4b, by giving a catalogue of infectious diseases for which 99% of the global burden falls on the developing world. Some facts associated with these differences in DALY between rich and poor countries include the following: (i) Health care infrastructure. In Europe, there are, on average, 3.9 physicians per 1000 people; 2.7 in the USA, and only 0.1 in sub-saharan Africa, where the problem is compounded by patterns of absenteeism (assessed at 40% in one study [6]). (ii) Basic research on diseases of the poor. Table 2 shows the results of a study of research papers published in Figure 2. Age-specific survivorship curve for a community of pre-agricultural people, constructed from skeletons unearthed on the Moroccan Mediterranean coast (modified with permission from Ref. [1], from data in Ref. [22]). four leading medical journals in 2002 and 2003 [7]. The study assessed the overall proportion of papers relating to diseases of importance to developing countries. Given that such papers include those on HIV/AIDS and on tuberculosis (TB) (both of which are also significant problems in OECD countries), the small fraction is surprising, as well as lamentable. (iii) Drug development. In a study by Pecoul et al. [8], of 1233 pharmaceutical drugs licensed (worldwide) in , only 13 (1%) were for tropical diseases. Moreover, of these 13, five came from veterinary Figure 1. Typical age-specific survivorship curves for human populations in developed (open circles) and developing (black dots) countries 50 years ago. Modified with permission from Ref. [23]. Figure 3. Age-specific survivorship curves for Liverpool in 1860 (black dots) and for England in the 1990s (dashed line) [3].

3 Forum TRENDS in Ecology and Evolution Vol.22 No Figure 4. Disease burden (in DALYs) for (a) high-income countries and (b) low-income countries [5]. research and two from modifications of existing medicines. Another two were developed by the USA Military, and only four were developed by pharmaceutical companies specifically for tropical diseases of humans. (iv) Pharmaceutical sales. Figure 5 shows world sales of pharmaceutical drugs, broken down by regions. North America, Europe and Japan account for 82% of sales, wereas Africa accounts for only 1%. (v) Disease burdens and research efforts. Table 3 shows the global burden of disease, measured in DALY, for several major afflictions, along with expenditure on research and development (R&D). This R&D expenditure in relation to DALY shows great variation, with malaria (by this comparative measure) receiving less than one-tenth the attention given to cardiovascular problems. Actions for a fairer world What is currently being done to reduce the inequities documented above? And what more might we do? Private benefactors No account of actions for a fairer world can be complete without acknowledging the example and inspiration provided by the actions of individual private benefactors, of which those of the Rockefeller Foundation over the years, and the Bill and Melinda Gates Foundation more recently (selflessly enlarged very recently by a massive gift from

4 500 Forum TRENDS in Ecology and Evolution Vol.22 No.10 Table 1. Diseases for which at least 99% of the global burden fell on low- and middle- income countries in 1990 Disease a Deaths per year DALYs (thousands) Diarrhoeal diseases b Malaria Measles Pertussis Tetanus Syphilis Lymphatic filariasis Anclyostomiasis and necatoriasis (hookworm) Leishmaniassis Schistosomiasis Trichoriasis Trypanosomiasis Trachoma Onchoceriasis (river blindness) Chagas disease Dengue Japanese encephalitis Poliomyelitis Leprosy Diptheria a Global Burden, from Ref. [19]. b Diarrhoeal diseases differ from the diseases in this list because they are a variety of diseases, caused by different pathogens. the world s second-richest person, Warren Buffet), are particularly notable. Public incentives for private sector drug development One major fact that underlies many of the above-mentioned problems is the understandable failure of free-market Table 2. Proportion of papers published in four leading medical journals relating to infectious diseases of developing countries a,b Journal Proportion of articles Jan 2002 Jan 2003 USA: New England Journal of 7% (7/97) 3% (3/118) Medicine Journal of the American Medical 7% (12/180) 4% (5/138) Association UK: Lancet 21% (50/234) 23% (52/227) British Medical Journal 24% (66/273) 18% (44/242) Overall: 15% 12% a These infectious diseases are defined in accordance with the UN Global Forum on Health Research. b Based on Ref. [7]. mechanisms to deliver pharmaceutical products for diseases of the poor. Pharmaceutical companies, quite properly, have a responsibility to deliver both useful drugs and profits to shareholders. For many things, this works well better than public command and control mechanisms. However, the R&D that leads to safe and effective pharmaceutical drugs is an expensive and unpredictable process. No matter now good the intentions, it does not make sense for a wellmanaged company to make a large investment in developing a drug whose potential beneficiaries are, in aggregate, too poor to pay the true costs (direct and indirect) that are involved. One possible way out of this dilemma is for governments or other agencies to help pay for the delivery of the drug, once it is developed. However, the costs of producing and delivering a drug are typically small compared with the basic costs of research, development and clinical trials. Figure 5. The world pharmaceutical market: sales by region in Adapted from PhRMA, Annual Survey 2000, available at

5 Forum TRENDS in Ecology and Evolution Vol.22 No Table 3. Disease burden and funding comparison a Condition Global Disease Burden (million) RandD Funding (US$ Millions) RandD Funding per DALY (US$) DALYs Cardiovascular HIV/AIDS Malaria TB Diabetes Dengue a Based on Ref. [20], p Public bodies have generally been unsympathetic to the needs of the pharmaceutical company once the drug exists: once their money has been spent, and an effective product achieved, the negotiating position of the pharmaceutical companies in respect to ex post facto subsidy for delivery understandably tends to be weak. An important study by Kremer and Glennerster [6] suggests a possible way forward, of benefit to both pharmaceutical companies and the disease-afflicted poor. The basis of the idea is that the threshold for privately financed investment in R&D toward a new drug is higher than the corresponding social threshold, which takes account of the public (economic) benefit of reducing DALY. The proposal thus is that governments, individually or collectively (e.g. via the UN), in advance guarantee purchase of the drug at a price that makes both producers and consumers better off: the producers, knowing the pay-off for a successful product in advance, can take more risks than they would if worried about the pay-off; society benefits from a healthier population and work-force. The basic idea is not new, but this particular application is both new and potentially hugely important. Opposing bureaucracy or ideology masquerading as accountability Figure 6 gives an impression of the mind-boggling proliferation of different agencies and stakeholders that jostle to do good things in the developing world. The growth of well-intentioned public private partnerships for health adds to the complexity here [9,10]. There is arguably a need for egos and administrative structures to be subjugated to disciplined, coordinated and effective actions. This need is even more important when some of the organisations involved seek to impose inappropriate moral values for example, opposing condom distribution (or even disseminating lies about their being ineffective) in relation to HIV transmission. Avoiding priorities set by fashion Most current activity on diseases of the poor focuses on the Big Three : HIV/AIDS, malaria and TB. Molyneux [11], however, has emphasized that the burden of other, relatively neglected, tropical diseases is roughly a quarter of the global disease burden of HIV/AIDS, a third that of TB and half that of malaria (all as measured in DALY). More recently, Hotez et al. [12] estimated that the aggregate DALY tally for neglected tropical diseases is 56 million, which exceeds the tally for both malaria (46 million) and TB (35 million). Table 4 sets out 13 such neglected tropical diseases which, in total, cause roughly half a million deaths annually. Despite the availability of cost-effective, stable and successful agents for the control or elimination of each of these 13 diseases, large numbers of the world s poor remain afflicted or at risk from this group of parasitic infections. Molyneux et al. [13] urge that The low costs [for alreadyavailable integrated control of neglected tropical diseases] represent compelling figures to advocate for a pro-poor, proactive public health strategy of preventive chemotherapy to be delivered to all affected populations of Africa. Laxminarayan et al. [14], Canning [15] and Chan [16] further develop this message in various ways and show that DALY, thus averted, represent very good buys in economic terms. Easterly [17] further urges a focus on Figure 6. A confusing cluster of agencies aims to help Tanzania with its HIV/AIDS epidemic. Modified with permission from Ref. [20].

6 502 Forum TRENDS in Ecology and Evolution Vol.22 No.10 Table 4. Thirteen neglected tropical diseases and their etiologic agents a Protozoan Infections Agents African trypanosomiasis Trypanosoma gambiense, T. rhodesiense Kala-azar (visceral leishmaniasis) Leishmania donovani Helminth Infections STH Infections Ascariasis Trichuriasis Hookworm infection Schistosomiasis Urinary schistosomiasis Hepatobiliary schistosomiasis Lymphatic filariasis Onchocerciasis Dracunculiasis Bacterial Infections Trachoma Leprosy Buruli ulcer a Based on Ref. [13]. Table 5. Human population density and bushmeat harvests a Region Density (people/km 2 ) Bushmeat harvest (tonnes per year) Asia 522 Unquantified (S and SE Asia) Africa million (Congo Basin) South America (Brazilian Amazon) a Based on Ref. [21]. Ascaris lumbricoides Trichuris trichiura Necator americanus Schistosoma haematobium Schistosoma mansoni Wuchereria bancrofti Onchocerca volvulus Dracunculus medinenis Chlamydia trachomitis Mycobacterium leprae Mycobacterium ulcerans simple things done well, rather than highly complex and elaborately planned interventions. In brief, we need to look at our priorities in a more objective, analytic way, free from the understandable inertia of yesterday s activities and fashions. The future Reader, in his book Cities [18], reminds us that Bacterial and viral diseases are the price humanity has paid to live in large and densely populated cities. Virtually all the familiar infectious diseases have evolved only since the advent of agriculture, permanent settlement and the growth of cities. Most were transferred to humans from animals especially domestic animals. Measles, for instance, is akin to rinderpest in cattle; influenza came from pigs; smallpox is related to cowpox. Humans share 296 diseases with domestic animals. And the world s cities become more crowded every day. Three hundred years ago they contained 10% of the Earth s population; a century ago, 25%; today, 50%; by 2050, they will contain almost 70%. The resulting high aggregations, coupled with increasing patterns of movements of peoples, present ideal conditions for new infectious agents to emerge, or for old ones to re-appear. These opportunities are further enhanced by the increasing volume (amounting almost to globalisation) of the bushmeat trade, which previously was confined to small-scale, local operations. We would do well to remember that HIV/AIDS, in effect, came from bushmeat: HIV-1 from chimpanzees, HIV-2 from monkeys. We were luckier with SARS, which came from the internationalisation of the bushmeat trade in exotic animals (specifically civets) to serve suburban restaurants in South East Asia. Table 5 hints at the growing volume of this trade. Quite apart from the implications for conservation biology, we should be worried about the probable epidemiological consequences of this rapidly growing trade. So? In short, the world today is a healthier place than it has ever been, both in developed and developing countries. But although the inequalities are less marked than they were 50 years ago and there are encouraging signs that these problems are being addressed, work remains to be done. We should be giving more forward-looking thought to reducing the probability that new infectious diseases will appear, and to being alert and prepared if they do. Understanding both the ecology and the evolution of infectious diseases and their hosts is central to this. In particular, there should be more concern about the rapid growth of the bushmeat trade [21] and its likely implications for newly emerging diseases, and there should be more strenuous attention to planning the coordination of international responses to such events when they occur. More prosaically, our actions should be more objectively proportionate to needs, and less governed by past trends or fashions, than is currently the case. A pessimist could argue that, above all else, we need a better understanding of the evolution of altruistic or cooperative behaviour, which unfortunately remains the biggest unsolved problem in evolutionary biology. References 1 Anderson, R.M. and May, R.M. (1979) Population biology of infectious diseases: part I. Nature 280, Anderson, R.M. and May, R.M. (1991) Infectious Diseases of Humans: Dynamics and Control, Oxford University Press 3 Cairns, J. (1997) Matters of Life and Death, Princeton University Press 4 Preston, S.H. (1975) Mortality Patterns in National Populations. with special reference to recorded causes of death. Popul. Stud. 29, Murray, C.J.L. and Lopez, A.D. (1996) Global Burden of Disease and Injury Series, Vol. 1, Harvard School of Public Health, (Cambridge, MA) 6 Kremer, M. and Glennerster, R. (2004) Strong Medicine: Creating Incentives for Pharmaceutical Research on Neglected Diseases, Princeton University Press 7 Raja, A.J. and Singer, P.A. (2004) Transatlantic divide in publication of content relevant to developing countries. BMJ 329, Pecoul, B. et al. (1999) Access to essential drugs in poor countries: a lost battle? J. Am. Med. Assoc. 281, Widdus, R. (2001) Public-private partnerships for health: their main targets, their diversity, and their future directions. Bull World Health Organ. 79, Buse, K. and Harmer, A.M. (2007) Seven habits of highly effective global public-private health partnerships: practice and potential. Soc. Sci. Med. 64, Molyneux, D.H. (2004) Neglected diseases but unrecognised successes - challenges and opportunities for infectious disease control. Lancet 364, Hotez, P.J. et al. (2006) Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria: a comprehensive pro-poor health policy and strategy for the developing world. PLoS Med. 3, e Molyneux, D.H. et al. (2005) Rapid-impact interventions. How a policy of integrated control for Africa s neglected tropical diseases could benefit the poor. PLoS Med. 2, e336

7 Forum TRENDS in Ecology and Evolution Vol.22 No Laxminarayan, R. et al. (2006) Advancement of global health: key messages from the Disease Control Priorities Project. Lancet 367, Canning, D. (2006) Priority setting and the neglected tropical diseases. Trans. R. Soc. Trop. Med. Hyg. 100, Chan, M.S. (1997) The global burden of intestinal nematode infections - fifty years on. Parasitol. Today 13, Easterly, W.R. (2006) The White Man s Burden, Oxford University Press 18 Reader, J. (2004) Cities, Heineman 19 Lanjow, J.O. and Cockburn, I.M. (2001) World Dev. 29, Cohen, J. (2006) Global health. The new world of global health. Science 311, Bell, D. et al. (2004) Animal origins of SARS coronavirus: possible links with the international trade in small carnivores. Philos. Trans. R. Soc. Lond. B Biol. Sci. 359, Hassan, F.A. (1981) Demographic Archeology, Academic Press 23 Bradley, D.J. (1972) Regulation of parasite populations. A general theory of the epidemiology and control of parasitic infections. Trans. R. Soc. Trop. Med. Hyg. 66, Elsevier celebrates two anniversaries with a gift to university libraries in the developing world In 1580, the Elzevir family began their printing and bookselling business in the Netherlands, publishing works by scholars such as John Locke, Galileo Galilei and Hugo Grotius. On 4 March 1880, Jacobus George Robbers founded the modern Elsevier company intending, just like the original Elzevir family, to reproduce fine editions of literary classics for the edification of others who shared his passion, other Elzevirians. Robbers co-opted the Elzevir family printer s mark, stamping the new Elsevier products with a classic symbol of the symbiotic relationship between publisher and scholar. Elsevier has since become a leader in the dissemination of scientific, technical and medical (STM) information, building a reputation for excellence in publishing, new product innovation and commitment to its STM communities. In celebration of the House of Elzevir s 425th anniversary and the 125th anniversary of the modern Elsevier company, Elsevier donated books to ten university libraries in the developing world. Entitled A Book in Your Name, each of the 6700 Elsevier employees worldwide was invited to select one of the chosen libraries to receive a book donated by Elsevier. The core gift collection contains the company s most important and widely used STM publications, including Gray s Anatomy, Dorland s Illustrated Medical Dictionary, Essential Medical Physiology, Cecil Essentials of Medicine, Mosby s Medical, Nursing and Allied Health Dictionary, The Vaccine Book, Fundamentals of Neuroscience, and Myles Textbook for Midwives. The ten beneficiary libraries are located in Africa, South America and Asia. They include the Library of the Sciences of the University of Sierra Leone; the library of the Muhimbili University College of Health Sciences of the University of Dar es Salaam, Tanzania; the library of the College of Medicine of the University of Malawi; and the University of Zambia; Universite du Mali; Universidade Eduardo Mondlane, Mozambique; Makerere University, Uganda; Universidad San Francisco de Quito, Ecuador; Universidad Francisco Marroquin, Guatemala; and the National Centre for Scientific and Technological Information (NACESTI), Vietnam. Through A Book in Your Name, these libraries received books with a total retail value of approximately one million US dollars. For more information, visit