Infectious disease transmission dynamics and the ethics of intervention based public health research
I think a lot about ethics and ethical issues. Research in Sub-Saharan Africa presents unique risks for ethical breaches. Given income and power disparities between individuals and foreign researchers and even between individuals and local political leaders the possibility of coercive research is ever present. Pressure to produce can lead to unrealistic assumptions of risks and benefits to very poor individuals. Inadequate knowledge or willful ignorance of local political issues can compromise future research activities, both by international and domestic groups.
Recently, though, an interesting situation came across my desk that included an intersection of ethics and the dynamics of infectious disease transmission.
As everyone knows, not all infectious diseases are the same. Some, like measles, impart full immunity upon exposure, whereas diseases such as malaria impart only partial immunity, requiring repeated exposures to acquire full or adequate immunity to prevent death or serious injury. Moreover, as immunity and immune reactions change over the life course, the time (age) of exposure are sometimes crucial to prevent serious disease. Polio is a great example. Exposure in infancy leads merely to diarrhea, where exposure at older ages can lead to debilitating paralysis.
I was thinking of an population based intervention study which provides some sort of malaria medication to a small population in a holo-endemic area. Given the year round nature of malaria transmission in this area, we would expect that even with a depression in symptomatic and asymptomatic cases, active transmission in the surrounding areas would lead to recrudescence within a very short time. Given the short time frame, we would assume very little interruption in the development of immunity in small children and might even see a short term reduction of childhood mortality. Assuming that this medication presented little or no risk of serious side effects, I believe that there is little reason to assume an ethical breach. A short term reduction in malaria would suggest that the benefits far outweigh the risks.
However, conducting the same study on a very large population in the same area might have very different outcomes. Delivering a malaria medication to, say, an entire county surrounded by other areas of extremely high transmission would indicate that recrudescence is also inevitable but that the time required to return to pre-intervention levels is extended. Infectious disease transmission requires a chain of hosts. The longer that chain, the longer it will take for new hosts to become newly infected.
Theoretically, this could delay infections in small children and it is theoretically possible that we might see a spike in childhood mortality, since the timing of initial malaria infection and frequency of infections are crucial to preventing the worst outcomes.
Of course, I’m not suggesting that people should just get infected to induce immunity, but I am suggesting that a study which seeks to reduce transmission through pharmaceuticals given only intermittently (as opposed to prophylactically) consider all possible implications. Insecticide treated nets (ITNs) provide protection over time and are a form of vector control. A medication given at a single time point merely clears the parasite, but does nothing to prevent bites or kill mosquitoes.
Though I could be overthinking the issue, my worry is that ethical approvals approach the issue of mass distributions of pharmaceuticals as a one size fits all issue without taking other factors such as population size and acquired immunity into account. Malaria, as a complex vector borne disease introduces complexities that, say, measles does not. Researchers, IRBs and ethics board would do well to consider this complexity.
What are we talking about when we discuss socio-economic position and health in developing countries?
A wide body of literature has found that socio-economic position (SEP) has profound impacts on the health status of individuals. Poor people are sicker than rich people. We find this relationship all over the world and in countries like the United States, it couldn’t be more apparent.
Poor people, particularly poor minorities, are more likely to see their children die, are more likely to be obese, have worse cardiac outcomes, develop cancer more often, are disproportionately afflicted by infectious diseases and die earlier than people who are not poor. There is ample evidence to support this.
However, the exact factors which lead to this disparity are up to debate. Some focus on issues of lifestyle, diet, neighborhood effects and access to health care. Poor people, particularly minorities, live hard, eat worse, live in dangerous or toxic environments and have low access to quality care all contributing to a perfect storm of dangerous health risks.
However, even when controlling for all or any of these factors, we still find that poor people, and particularly African-Americans, still get sick more often, get sicker and die earlier. This leads us to speculate that health disparities are not simply a matter of access to material goods which promote good health, but are tightly related to something less tangible, such as social marginalization and racism, which are both incredibly difficult to measure. Though difficult to quantify, however, we do have plenty of well documented qualitative and historical data which indicate that these relationships are entirely plausible.
The awful history of slavery and apartheid, however, is somewhat (but not completely) unique to the United States. Further, our ideas of class come from another Western idea, the Marxist concept of one privileged group exploiting the weak for their own financial gain, particularly in the context of manufacturing.
Yet, though these ways of conceiving of race and class are so specific to the West, they are applied liberally to analyses of developing country health, with little consideration of their validity.
It is not uncommon to see studies of socio-economic status and health. The typical method of measuring socio-economic status in developing countries is to examine the collection of household assets such as TVs, radios, bicycles, etc. and, using statistically derived weights, sum up all of the things a household owns and call that sum a total measure of wealth. The collection of total measures for each household are then divided into categories, with the implication that they roughly approximate our conception of class.
Not surprisingly, it is usually found that people who don’t own much are, compared with people who do, at higher risk for malaria, TB, diarrheal disease, infant and maternal mortality and a host of other things that one wouldn’t wish on anyone.
But this measure is problematic. First, there is often little care taken to parse out which items are related to the disease of interest. For example, we would expect that better housing conditions are associated with a decreased risk for malaria, since mosquitoes aren’t able to enter a house at night. We would also expect that people with access to clean water would be more likely to not get cholera. If we find relationships of SEP with malaria or diarrheal disease which include these items, these associations should be treated with suspicion.
Second, if we do find a relationship of “class” with health, can we view it in the same way in which we might view this relationship in the United States? A Marxist approach, with a few exploiting the many for profit, in sub-Saharan Africa doesn’t make a whole lot of sense. The manufacturing capacity of African countries is tiny, and most people are sole entrepreneurs operating in an economy that hasn’t changed appreciably from pre-colonial times. Stripping away any requirements of legal protection of property rights, Africa looks incredibly libertarian.
Further, the elite in Africa hardly profit financially from the poor, receiving their cash flows mainly from abroad in the form of foreign aid or bribery and foreign activity is mostly limited to resource exploitation, which doesn’t make a dent into Africa’s vast levels of unemployment. While the West is certainly complicit is Africa’s economic woes, post slavery, the West rarely engages Africans themselves.
So, is it valid to attempt to apply the same ideas of class to African health problems? Is there a way to attribute health disparities to class in societies with limited economic capacity and where the “citizenry” is only marginally engaged and groups suffer mainly from a reluctance to cooperate and engage people of other tribes or neighboring countries?
Certainly, the causes of poverty and marginalization in Africa need to be examined, but I don’t think that we can approach them in the same way we do in the States.
According to the “pathogen stress theory of values,” the evolutionary case that Thornhill and his colleagues have put forward, our behavioral immune systems—our group responses to local disease threats—play a decisive role in shaping our various political systems, religions, and shared moral views.
If they are right, Thornhill and his colleagues may be on their way to unlocking some of the most stubborn mysteries of human behavior. Their theory may help explain why authoritarian governments tend to persist in certain latitudes while democracies rise in others; why some cultures are xenophobic and others are relatively open to strangers; why certain peoples value equality and individuality while others prize hierarchical structures and strict adherence to tradition. What’s more, their work may offer a clear insight into how societies change.
This is a reasonable view, and something I’ve long observed from working on infectious diseases in developing countries. The developmental trajectory of a country is influenced by the deliberate avoidance of illness. An example can be seen in the locations of African cities. Many African administrative capitals are located on isolated, cool hilltops, far away from rivers and lakes. Colonialists would intentionally set up shop in areas where they were unlikely to encounter malaria.
Developmentally, this has had major implications for trade within Africa. European cities are often placed along water ways amenable to domestic European trade. The lack of trade between African countries is one of the reasons the continent has developed so poorly. This is the direct result of not only colonial priorities of resource extraction to Europe, but also the unfortunate placement of economic centers in response to malaria.
Certainly, the nature of cities themselves have much to do with the control of infectious diseases. Public works often involve the management of sewage waste and the delivery of clean water. Thornhill might suggest that the development of democracy, citizen involvement and taxation to pay for urban improvements are in direct response to enteric diseases.
However, while it is interesting to try to apply this view, it can be taken to the extreme:
Fincher (a graduate student of Thornhill) suspected that many behaviors in collectivist cultures might be masks for behavioral immune responses. To take one key example, collectivist cultures tend to be both more xenophobic and more ethnocentric than individualist cultures. Keeping strangers away might be a valuable defense against foreign pathogens, Fincher thought. And a strong preference for in-group mating might help maintain a community’s hereditary immunities to local disease strains. To test his hypothesis, Fincher set out to see whether places with heavier disease loads also tended toward these sorts of collectivist values.
I’m not sure it’s that easy to boil down political differences between Asia and Europe to a need to manage infectious disease. Certainly, Sweden is more collectivist than England, but I wouldn’t say that their infectious disease profiles are all that different.
Worse yet, if taken to the extreme, this “hunt for significance” will provide one with evidence to support any crazy theory at all. Pathogens exist wherever humans do. Moreover, we risk attributing the contribution of pathogens to human development based on current conditions, assuming that the present is deterministically preordained centuries ago. Until very recently, nearly the entire world was at risk for malaria, but despite this, various societies have embarked on different social and political trajectories.
The biggest problem I have with the theory is in its basic in rational theory. It assumes that humans are making rational choices based on pathogen threats, when we know, and particularly those of us who work in the tropics, that humans often have poor conceptions of disease transmission and causes of illness. At times, despite very obvious threate, humans will act in manners which exacerbate that threat. The history of enteric disease is filled with tales of ignorance and folly.
If we are going to subscribe to a rational model of political and social development which includes pathogens, then we have to also address first, the ability of pathogens to hijack human behavior to create new opportunities for replication and survival and second, that social changes can exacerbate the worst effects of infection. For the first point, I would look to the development of international trade systems which allow pathogens such as influenza to move around the world quickly, increasing opportunities for mutation to avoid immune responses. For the second I would point to polio, a disease which becomes a problem on after the introduction of water sanitation practices.
Thornhill’s ideas are interesting, and certainly provide good material for the popular press and BBQ conversation, but they require that the reader suspend too much consideration of the details of the complex history of human social and political development. Taken with restraint, as in the example of the locations of African cities, they can provide interesting insights into how current conditions are impacted by past pathogenic threats.
This map (from “Mapping of poverty and likely zoonoses hotspots”) is pretty eye-opening. Looking at this, I’m thinking that the next big disease event will most certainly come out of India.
Note that the most virulent of infectious diseases in humans are often associated with animals. India’s high density, close contact with animals and poor regulatory environment make for a frightening mix.