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The re-emergence of infectious diseases on the public health agenda
By Richard Levins
Submitted by Chee Yoke Ling, Third World Network, Malaysia
THIS DOCUMENT APPLIES TO THESE EVENTS:
The re-emergence of infectious diseases on the public health agenda
by Richard Levins
(Third World Resurgence #155/156)
A SCIENCE fiction story I read too long ago to be able to cite began, more or less, ‘It was the 25th century, and disease had long ago disappeared.’
Of course, infectious disease never did disappear. But in the 1970s the doctrine of the epidemiological transition proposed that with economic development the emphasis in public health would have to shift from infections to chronic and degenerative diseases. Medical students were discouraged from studying infectious disease - they were told it was a dying field. The Department of Epidemiology at Harvard dropped infectious disease from its concerns in order to concentrate on heart disease and cancer. Ministers of health from Third World countries boasted that their people were now dying of cancer and heart disease instead of tuberculosis and malaria, and saw this as a sign of modernisation.
Then Lyme disease, legionnaires’ disease, toxic shock syndrome, Nipah virus, HIV/AIDS, Venezuelan haemorrhagic fever, Bolivian haemorrhagic fever, Argentine haemorrhagic fever, hanta virus, hepatitis C, Ebola, Lassa fever, Marburg virus, Jacob-Creutzfeld disease (the human version of mad cow), Pfeisteria neuropathy, all rushed into the headlines. Cholera reappeared in a worldwide outbreak, tuberculosis returned with a vengeance and malaria, after ceding ground to the World Health Organisation’s (WHO) international programme, resurged even where it was thought on the verge of elimination. There are frequent outbreaks of bacterial meningitis, cryptosporidium, and dengue. More than 30 new or resurgent diseases arose within a few short years to change the outlook of the profession. In the United States the Institute of Medicine, the Harvard Working Group on New and Resurgent Diseases, and the new journal Emerging Infectious Diseases all took up the challenge.
But before we rush into looking for new vaccines, it is worth examining why public health was caught by surprise. In one sense, surprise is inevitable in science because the only way to study the new is treating it like the old, already known. There is enough coherence in the world so that new phenomena are sufficiently similar to the old to make science possible. A new virus disease such as SARS appears and very quickly laboratories go through their protocols and a virus is identified. But things in the world are also surprisingly different, making science necessary. An entirely new disease agent, the prion, was eventually implicated in the neuro-degenerative diseases such as mad cow disease, and chronic wasting disease, its analog in wild cervids. But diseases strongly linked to social relations are less easily studied. It took some 50 years for the United States to acknowledge black lung disease among miners after the British recognised it as an occupational disease. The difference was that the British workers in those days had their own political party. And the harmful effects of tobacco were militantly denied by industry for several generations of smokers.
But if surprise in science is inevitable, particular surprises can be avoided and we needn’t have been so surprised by the stubbornness of infectious disease. After all, the proponents of the ‘epidemiological transition’ were serious scientists, just as smart as we are. If they made a major error of strategy, it could not have been simple carelessness: the doctrine was plausible for a number of reasons.
The expectation that infectious disease would disappear rested on several grounds:
1. Infectious disease had been declining in the developed industrial countries for one or two centuries. Leprosy, polio, typhoid fever, yellow fever and others were much reduced, smallpox was on the verge of eradication.
2. In the ‘war’ with the microbes, the pathogens depended on the same old weapons they always had (mutation) whereas we were developing new tools through active research, especially antibiotics and vaccines. This led to a naive optimism that expected parasites of humans to be eliminated as we have practically eliminated predators. (There are only a very few cases per year of people killed as prey by lions, tigers, crocodiles or sharks.)
3. Economic development would bring the affluence of the advanced industrial countries (the ‘West’) to the whole world, making the new advances of clinical medical technology available to everyone.
4. Infectious disease affects mostly the young. An aging population would therefore be less vulnerable.
Each of these arguments was flawed.
History and ecology
The examination of only the recent history of Euro-North America hid a greater pattern. The most elementary kind of prediction proposes that things will continue as they had been. Only a little more sophisticated is the idea that existing trends will continue. But a look at the longer sweep of history and a broader geographic perspective would have shown that infectious disease waxes and wanes with changing conditions.
The pandemics of plague in 6th century Rome and 14th century Europe occurred in populations already stressed by social pressures. Agricultural development, especially irrigation and dams, allowed the spread of mosquitoes and snails carrying malaria, Rift Valley Fever, schistosomiasis and other infections.
Modern water management created the habitat for Legionella, previously a widespread but never very abundant bacterium because it was a poor competitor. In the pipes of cooling and heating systems its higher temperature tolerance and ability to avoid chlorine by encysting inside proctists finally gave it the competitive advantage it lacked in the wild. Hospitals promoted the transmission of nosocomial infections such as Staphylococcus aureus by hospital staff among weakened patients. More common use of injections in poor communities leads to improperly sterilised reused needles that can transmit HIV. Dengue spread in the rapidly growing tropical cities. Mad cow disease introduced us to prions, a new class of disease agents, and was spread by the industrial recycling of animal waste in feed in the United Kingdom along with Margaret Thatcher’s deregulation of the process that allowed the lowering of the sterilisation temperatures for processing that material in order to reduce expenses.
A new doctrine was needed: Every change in demography, vegetation, land use, technology, economics and social relations is also a potential change in the ecology of pathogens and their reservoirs and vectors and therefore a change in the pattern of infectious disease epidemiology.
Physicians are well-educated people, and in Europe at least they knew their classical history. If the past was not examined even when diseases were known since Biblical times, it may have been because there was a sense of modernity erasing the past. History is irrelevant because our world is so new, with science and technology rooted in the present. Or as Henry Ford said, ‘History is bunk!’
Disease in other species
Public health epidemiology did not pay attention to animal and plant disease. But similar phenomena were occurring in domestic and wild animals (avian influenza, African swine fever, feline leukaemia, mad cow analogs in ungulates, die-offs of marine mammals and amphibians) and crops (tristeza of citrus, tungra virus in rice, Gemini viruses such as golden mosaic in beans that are spread by whiteflies).
Had we stepped back and looked at the whole pattern, it would have been obvious that something is going on making many species more vulnerable to infections. Each case is unique, and it is possible to offer specific explanations without seeing the whole. For instance the chytrid fungi have been implicated in the dying of amphibians, but why has this world-wide pathogen suddenly become capable of decimating many species?
Evolution of pathogens
Since the time of Koch and Pasteur, epidemic research emphasised the pathogens, identified as the ‘causes’ of diseases. And these were treated independently of each other, with the critical events being exposure and infection. Even when cases of antibiotic resistance were recognised, they were for a long time treated as unfortunate problems that we would solve with new drugs.
But something new is happening. Human activity has created new opportunities for pathogens to exchange genes directly or through plasmids. When the use of antibiotics disrupts the community of hundreds of species in our bodies, many decline and the survivors become highly abundant so that there are more opportunities to meet and interact both ecologically in competitive and mutualistic ecological relations and also genetically. Travel and voluntary or involuntary migration brings local strains together allowing for gene exchange. The careless use of antibiotics has created the environments that favour strong natural selection for antibiotic resistance. The result has been the appearance of multi-resistant strains of tuberculosis, streptococcus, and other bacteria, and the first appearance of HIV resistant to drug therapy has been reported. Mae-Wan Ho, in the pages of this journal (see TWR No. 151-52 and the article on pp.18-19 of this issue), has argued that laboratory research in genetic engineering has increased the rate of recombination among viruses by many orders of magnitude, allowing for the release of new plagues.
This requires further comment. Modern laboratories have an advanced technology employed to contain the viruses and prevent accidental release. The probability of an accidental release is quite small. But the more complex any engineered system, the more places for things to go wrong. As we have seen in the case of the Columbia shuttle disaster, the cutting of corners to save expense increases the risks. In the case of the Milwaukee outbreak of Cryptosporidium, a modern water purification system was relatively safe, but only relatively. And when it did break down the effects were far-reaching, with some 400,000 cases of infection. The Exxon Valdez was also a modern tanker, safer than the older, smaller ships. But when human error led to the spill, it was a big one.
Thus, modern precautions are no guarantee against major disasters. A large number of pharmaceutical and biotech firms racing for patents, eager to exaggerate the benefits of their products and belittle the harm that they might cause, is a recipe for disaster.
Therefore the pathogens also have new and enhanced means to create genetic novelty and spread it in the environment.
Chemical therapies as the primary defence against infection may be losing their effectiveness. The era of antibiotics may be a brief episode, a successional stage in our relations with the pathogens, and whole new approaches may be required. But research is still dominated by the quest for chemical weapons, in part because of the enormous profitability of drugs and in part because of the philosophical bias in favour of working with molecules and genes as somehow more fundamental than studying ecosystems or poverty. Instead of seeing public health as a war against an irreconcilable foe, we have to see it as renegotiating our relations with the microbial world in the direction of benign co-existence.
One possible evolutionary strategy is to treat severe cases of a disease curatively and with isolation and mild cases palliatively. Then those genetic variants of the pathogen which are less virulent will be selected over the more virulent kind and may eventually join our body’s flora as good citizens along with the several hundred kinds of bacteria that normally live in our guts without causing harm and indeed contributing to our well-being.
Whose affluence?
The economic development that promised access to all health-promoting processes never happened. Health depends not only on access to curative medical care but also on nutrition, pollution, and stressors in the physical and social environment. The GDPs of many countries certainly have increased, but that did not necessarily create the equity needed to improve health. In Figure 1 we see a representation of the relation of GDP to infant mortality (IMR). We note three things: First, there is a general trend toward lower IMR with GDP. Second, there is enormous variation around this trend line, especially at the low end, and some poor countries have outcomes as good as the rich. (The scale makes it harder to see the variation among high-income countries. However Vicente Navarro (The Political Economy of Social Inequality) has shown for the ‘West’ that in general countries with social democratic regimes have better health for their income than Christian Democratic countries, and these in turn are better off than the liberal democracies.) Finally, Cuba lies off the curve. Cuba is not moving along the development curve but following a different pathway of development. This would show up in similar graphs plotting educational expenditures, student achievement, literacy and other measures.
Within countries there is also wide variation even in the face of poverty. The states of Kerala and West Bengal in India, both under long-term left leadership, have health indicators above what would be expected for their incomes. Within the United States, there are big discrepancies by race and class so that Washington DC has indicators comparable to poor Third World countries and a third of the counties of Kansas have yet to catch up to Cuban levels.
These results are partly due to equitable access to health care. But health is determined in a larger terrain than health care or even classical prevention. What happens to people also depends on strong labour movements defending occupational health and safety, commitment to sustainable environmental relations, narrow spread of income, a broad social safety net, and investment in those localities that most need it. We have seen time and again that economic development has exposed people to chemical pollution from pesticides and from industrial activity, loss of natural enemies of disease vectors, and debasement of nutrition as production becomes the export of commodities while the dumping of agricultural surpluses from outside impoverishes farmers. A development strategy that gives priority to human needs before the accumulation of wealth, even when carried out unevenly and with many errors, contributes to health even in poor countries.
The Cuban experience is due to universal free medical care, a high degree of equity in income and social consumption, long-term commitment to science, the phasing out of pesticides and a commitment to sustainable, ecologically rational development.
The young get sick
Infectious disease afflicts the very young in part because their immune systems are not yet formed. But the main reason is that they had no previous exposure to those pathogens. If the incidence of infection is reduced it also strikes at a more advanced age and sometimes more harmfully.
Chronic disease can be infectious
The distinction between infectious disease and chronic or degenerative disease is not that absolute. It is now increasingly common to find pathogens associated with chronic conditions such as cancer (megacytomegaly virus, Human Papilloma Virus, and Helicobacter pylori, ulcers (also H. pylori), heart disease (Chlamydia) and others. Our health depends on strongly interacting processes that are separated into distinct disciplines but meet in our bodies.
We can look deeper into the sources of error. The course of development of science is not dictated by nature, but by complex interactions among the objects and tools of investigation, political economy, institutional organisation of research and education, and the prevailing philosophies. On the one hand, science reflects the general advance of human knowledge that accompanies (sometimes leading, sometimes following) our increasingly diverse and sophisticated relations with the rest of nature. But it is also the product of particular societies that support science selectively in various ways. The sciences created in Mesopotamia, Egypt, Greece, India, China, and meso-America have all been rooted in the social arrangements that determined who did science, what attracted their interest as problems, and what was considered a satisfactory solution.
In some ways, all knowledge is created in the same way: learning from experience and reflection on that experience in the light of previous knowledge. But each historical tradition is also distinct. What characterises our modern science, for the moment dominated by Euro-North America, is the sophisticated organisation of experience in order to find out. Separate institutions, procedures of recruitment and socialisation of scientists, growing commodification of the enterprise in private industry and in universities financed by them indirectly, military and commercial secrecy and proprietal rights all guide the directions of research and publishing. This creates the pattern of knowledge and ignorance with which we cope with new problems.
The emergence and re-emergence of infectious disease confronts us with the inevitability of surprise. New diseases do not fall into any special category. Some of the proximate causes are land use change, migration, new technologies, changes in the use of bush meat, sexual behaviour, and the agents may be viruses, bacteria, proctists, fungi or prions. They may be new genotypes arising by mutation or recombination, or rare organisms that have become common. They may be spread by air, food, water, or arthropod vectors. Therefore uncertainty itself has become an object of study.
One way of approaching uncertainty is by examining how other species cope with environmental change. There are four basic modes for coping, and these are not mutually exclusive:
1. Detection and response. In order to be effective, the detection has to be rapid and accurate and the response has to be rapid compared to the course of the epidemic. At present we have rapid laboratory methods for many of the known diseases, but there is a longer delay when we don’t know what to look for. A priority has to be low-cost diagnostic tools that can be used in isolated clinics where refrigeration may be unreliable. However the limiting factor is not so much the speed of lab work as the delay in recognising that there is a problem and the even longer delay in taking measures such as isolation which may impose economic costs.
2. Prediction. We have good short-range prediction: an outbreak of a disease in one location is a prediction that it may also occur in a nearby location (‘nearby’ is relative to transportation). An outbreak of mosquitoes may predict malaria or dengue. Rain may predict mosquitoes. But there is much less knowledge of longer-range prediction. Here we have to resort to comparative epidemiology to consider: what is the host range of different groups of pathogens so that we know where to look for potential reservoirs; what viruses and bacteria are found in the wildlife of the region; which groups of pathogens have shown evolutionary plasticity, allowing them to change hosts, means of transmission, tissues affected, clinical pictures; what conditions make people especially vulnerable to infection and disease (these may include malnutrition, pollution, other infections, social stressors). A monitoring of wildlife and domestic animals would also serve as early warnings. Since this knowledge can only come from long-term fundamental research, it is likely to be treated as a luxury by the ministries of health of poor countries and by medical communities that pride themselves on being practical people facing urgent tasks with inadequate resources. Therefore it is important to create an environment friendly to this kind of research.
3. Broad tolerance, the generalised capacity to cope with unexpected diseases even without prior knowledge of their identity. Schmalhausen’s Law is a general principle that organisms in unusual or extreme conditions, at the boundary of their tolerance for any one aspect of their life conditions, are extremely sensitive to stressors in all aspects of their life conditions. Thus malnutrition inhibits the immune system and makes people more vulnerable to infection. Pesticide poisoning can prevent absorption of vitamin A, and this in turn reduces the T-cells and macrophages that are part of the body’s defences. Diabetes makes bacterial infections more dangerous. Diarrhoea can make it easier for pollutants to pass through the lining of the gut, while any sexually transmitted diseases that irritate the reproductive tract facilitate the entry of HIV. Social and emotional stress and anxiety reduce immune capacity. Poor people are often afflicted by multiple insult, allowing even more ailments to accumulate. Therefore any struggle against poverty and racism and abuse based on gender is also a public health issue, and the health of a community has to be looked at not only disease by disease but also as a whole. Vulnerability itself becomes an object of study.
4. Prevention. This is a reaching out into the environment to create conditions under which the problem would not arise. Consider, for example, how the protection of health would influence the design of agriculture. Agriculture affects health in many ways. The first and most obvious is food. Malnutrition is still a major contributor to death, especially in children, deaths that are usually attributed to specific respiratory and gastrointestinal diseases. Production for the market often conflicts with other uses of water, so that a preventive strategy must protect the domestic potable water supply. Irrigation not only uses vast quantities of water but also lowers the water table sometimes beyond reach of hand pumps and can lead to sudden subsidence of the land. As in Bangladesh, the water table reached down into arsenic-laden strata. Agricultural run-off along with urban waste causes algal blooms, and along the coasts a flourishing of the vibrio of cholera that lives in the plankton. Pesticides poison people and the natural enemies of pests, allowing explosions of insects that reduce yield and facilitate outbreaks of mosquitoes that breed in the irrigation ditches. Changing crop patterns change rodent populations that carry their own viruses. Therefore prevention requires an epidemiological impact statement to accompany any major changes in land use.
A mixed strategy takes advantage of all modes of preparation. It is essential because we are so often mistaken, and a single strategy may be counterproductive. It also offsets the weight of fashion and profitability. The single-minded reliance on chemical therapies leaves us vulnerable when the pathogens adapt to the antibiotics and vaccines, the modes of defence preferred by the pharmaceutical industry. Similarly, the hype about genes ‘for’ particular diseases is usually misleading and fades away after the initial press conference. Since genes alter the quantities and locations of enzymes, they certainly affect the way people respond to stressors. But that is no excuse to ignore the stressors.
Therefore, while we decide on the most promising approaches for the major research effort, we always have to leave resources for less likely, indirect and seemingly far-out approaches. Some of these would be more holistic, ecological, evolutionary and social.
A whole-system strategy for confronting infectious disease has to be much broader than traditional medical and public health efforts. Health is determined in a much larger arena that includes land use, demography, pollution and waste disposal, wildlife and agriculture, poverty and inequality.
Clearly this is beyond the reach of existing ministries of health. A National Health Council which includes representation from other ministries such as agriculture, economy, fisheries, national parks, urban planning, and social services is needed that could look at the whole. Further, it has to support the kind of research that could integrate the diverse kinds of knowledge we need. And it is here that the scientific community has to discuss the kind of science our countries need - integrated with world science but also with its own intellectual agenda in keeping with Third World needs.
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Richard Levins, an ex-tropical farmer turned ecologist, is the John Rock Professor of Population Sciences at the Harvard School of Public Health. One of the world’s foremost biomathematicians, he is also a visiting scientist at the Institute of Ecology and Systematics in Cuba.