Why malaria? Over-researched, over-funded, diminishing returns? Rambling on the need for student mentorship.
Last week I gave an informal lecture on survey sampling to a small group of graduate students from a number of countries. With only one exception, all of the students were working on various aspects of malaria, primarily in basic sciences. The lone non-malaria student was from Vietnam and is interested in Dengue fever.
I praised her for working on Dengue. Dengue presents a serious threat to human health in all countries where the vectors exist, but the burden of disease will be particularly felt in rapidly urbanizing areas of developing countries.
Developing countries are ill equipped to deal with Dengue, and the antiquated nature of their health care systems, leftover by the colonialists, means that diagnostics are mostly non-existent and drugs wholly unavailable. Any fever in most of Sub-Saharan Africa is diagnosed simply as malaria, drugs administered and the patient left on their own.
We have extensive experience, however, with malaria. While there are numerous challenges to reducing malaria incidence, preventing recrudescence and postponing drug resistance, the basic fact is that the best way to eliminate or control malaria is to simply make people less poor. Even countries with holoendemic transmission, wealthier people get malaria less often than poor people, and poor people who live in wealthier areas get sick less than wealthier people in poor areas. This is known (in Game of Thrones parlance).
So, as we discussed the topic during lecture, I softly tried to encourage the students to look at other areas where they might be able to better apply their skills. They were mostly unresponsive, which is fine. Someone has to tell them, it might as well be me.
One of the students, however, indicated that “malaria is where the money is.” I couldn’t disagree. The reason that we put so much money and effort into diseases like malaria and HIV is simply because they yield marketable products. Medications for diseases like tungiasis (jiggers) are so simple as to not be profitable, customers too poor to buy them, and governments and donors too distracted by big diseases like malaria, HIV and TB to be concerned with dumping money to provide them for free.
And this is where the problem lies. We have a self propagating system of companies, researchers and donors, which simply float money between one another with little regard for the needs of the poorest of the poor. Breaking the cycle is difficult, but it starts with academics who need to push students to do work with neglected, overlooked or under-researched diseases. Even small grants can support small, but meaningful projects.
We have reached a point where malaria funding for malaria research is yielding ever diminishing returns. Money needs to be put into programs to deliver the tools we have and make ITNs, ACTs and IRS available to the people who need them, who often have trouble getting them. Moreover, we need economic development to make people less poor in developing coutnries so that fewer of their babies die. Human resources in developed countries need to start focusing on emerging (or already emerged but ignored) threats lke antibiotic resistance, Dengue fever, emerging zoonotics and others. That starts with us as mentors.
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.
I was just reading a post from development economist Ed Carr’s blog, where he reflects on a book he wrote almost five years ago. Reflection is a pretty depressing excercise for any academic, but Carr seems to remain positive about his book.
He sums it up in three points:
“1. Most of the time, we have no idea what the global poor are doing or why they are doing it.
2. Because of this, most of our projects are designed for what we think is going on, which rarely aligns with reality
3. This is why so many development projects fail, and if we keep doing this, the consequences will get dire”
Well, yeah. This is a huge problem. In academics, we filter the experiences of the poor through a lens of academic frameworks, which we haphazardly impose with often no consultation with our subjects. Granted, this is likely inevtiable, but when designing public health interventions, it helps to have some idea of what the poorest of the poor do and why or our efforts are doomed to fail.
I remember a set of arguments a few years back on bed nets. Development and public health people were all upset because people were seen using nets for fishing. The reaction, particularly from in country workers was that poor people are stupid and will shoot themselves in the foot at any opportunity.
I couldn’t really understand the condescension and was rather fascinated that people were taking a new product and adapting it to their own needs. Business would see this as an opportunity and would seek to figure out why people were using nets for things other than malaria prevention and attempt to develop some new strategy to satisfy both needs (fishing and malaria prevention) at once. Academics simply weren’t interested.
To work with the poor, we have to understand them and understanding them requires that we respect their agency. If we don’t do this, we risk alienating the people we seek to help.
Spent the week in Kwale, a sleepy town on near the Mombasa coast. The security situation prevents me from spending a whole lot of time there. I find this to be incredibly saddening but its unavoidable. Some people brave it out and stick with it, but I just can’t justify the awful risks.
The Japanese folks are mostly oblivious to it all, or maybe just indifferent. I’m convinced that they have no real concept of threat, given the relative safety of Japan itself. It’s a horribly dangerous situation but fortunately they stay locked inside. Japanese people love to sit at desks, even when they don’t really have to. Japan has yet to appropriate the concept of the mobile office. (Sorry, generalizations abound….)
I’ve caught some infection, but it’s hard to say exactly what it is. At first, it looked a lot like malaria, but then everything looks like malaria. Now, I’m just in a general state of not feeling well. It’s not responding to antibiotics, which makes me suspect that it’s not bacterial in nature. I started a round of ACTs just in case. They leave me a bit loopy, but I’m improving somewhat. A malaria test turned out faintly negative, but it’s possible the antibiotics are skewing the result or that the guy doing the test spilled to much assay onto the test. So, I’m not sure. I have a somewhat better appreciation for why the tests are treated with suspicion by the locals.
In any case, I feel like total hell, but thankfully have a normal appetite and digestion. I deeply crave red meat though, which leads me to suspect that the dizziness is anemia and thus, the cause could be malaria. This might be wishful thinking though. I could simply be exhausted.
Kenyatta is universally hated on the Coast, which explains a lot of the violence here. Though people apt to disregard domestic politics when talking of terrorism here, it’s hard to rule it out given the vast resentment toward the Jubilee party here on the coast. In fact, the lack of attention to security by the Kenyatta administration is likely fueling even more resentment, which might be fueling even more violence or at least, helping improve recruiting numbers for Al Shabab. As crazy as I think Luo politics are, Raila Odinga would have made a far better president.
People here are convinced that Kenyatta is a weed-head. “He is smoking the mari-ju-a-na.”
I spent the last two days convalescing in a hotel located within the Shimba Hills Nature Reserve. As much as I wanted to tough out the guest house in Kwale (which really isn’t so bad at all), I really needed a decent few hours of rest in a somewhat pleasant environment. It was worth it. A real hot shower and a set of clean sheets is worth the extra cash every now and again. The only wildlife to be seen were bush babies and squirrels, who seem to have worked out a deal where one begs for food in the day, and the other at night.
Malaria transmission here is low and it shows. Malaria endemic areas are characterized by low levels of education, part of which may be attributable to the inhibited cognitive development of children due to repeated malaria infections. Even if educational opportunities are available, kids in malaria endemic areas appear to have worse outcomes. It’s somewhat staggering at times, after having worked in Western. Part of it also could be the influence of Islam.
I’m now flying back to Nairobi where I’ll crawl into my bed. If I’m lucky, I’ll not come out for a few days.
I’m not exactly sure what we’re all supposed to be doing on World Malaria Day that we shouldn’t be doing every day, but at least we have a day! There’s no such thing as “World Helminth Day,” unfortunately.
What I think we should be doing on World Malaria Day:
1. Reducing ridiculous bureaucracy in developing countries which inflates the price of goods at the border.
2. Eliminate ridiculous protectionist policies in wealthy countries which selectively hobbles imports from developing countries.
3. Encourage true democracy in African States (where it doesn’t already exist) and eliminate unproductive authoritarian dead weight.
4. Guarantee rights to representation, legal fairness, political expression and property.
5. Create a global tax on capital and reinvest monies fairly in locally developed infrastructure projects in developing countries.
6. Encourage deep state investments in health care and health delivery in malarious countries while creating conditions favorable for the private sector to meet health needs.
7. Invest in the development of new pharmaceutical tools to prepare for the day when ACTs are no longer effective.
Wait, only points 6 and 7 had anything to do with malaria, you say, but I say they all do. Malaria is a complex disease, the root cause of which is poverty, the root cause of which is politics and economics. We will never be able to eliminate malaria unless we take care of all of the other problems which create the context that allows it to exist.
Every once in a while, you run across something that just gives you the chills.
“A report presented to the World Health Organization (WHO) in 1948 states: “It is not enough to quote that about 3,000,000 deaths are caused yearly by malaria in the world, or that every year about 300,000,000 cases of malaria occur …… that malaria is prevalent in tropical and subtropical areas where food production and agricultural resources are potentially very high, and that, by affecting the mass of rural workers, it decreases their vitality and reduces their working capacity and thus hampers the exploitation of the natural resources of the country. At a time when the world is poor, it seems that control of malaria should be the first aim to achieve in order to increase agricultural output” (WHO, 1948).
Snow RW, Amratia P, Kabaria CW, Noor AM, Marsh K: The changing limits and incidence of malaria in Africa: 1939-2009. Adv Parasitol 2012, 78:169-262.
A new study which just appeared in Malaria Journal, however, calls this optimism into question.
This review presents two central arguments: (i) that empirical studies measuring change are biased towards low transmission settings and not necessarily representative of high-endemic Africa where declines will be hardest-won; and (ii) that current modelled estimates of broad scale intervention impact are inadequate and now need to be augmented by detailed measurements of change across the diversity of African transmission settings.
So, our ability to accurately determine whether transmission intensity has declined is hampered by the fact that most studies of the disease occur in areas of low transmission. This would make sense. It is much easier for us to evaluate the malaria situation in Kenyan context than in the Democratic Republic of Congo due to availability of surveillance infrastructure, official mechanisms which allow research projects to move forward, and security issues.
The obvious problem with this, is the relationship of governance, economy an instability to malaria itself. People in the poorest countries are at the highest risk for malaria and people in the poorest parts of the poorest countries are at the highest risk of all. The trouble is, despite being the populations we are most concerned about, they are the hardest to reach, and the hardest to help.
Worse yet, the estimates of malaria prevalence found in a number of studies were considerably lower than estimates for the entire African continent.
The combined study area represented by measurements of change was 3.6 million km2 (Figure 1), approximately 16% of the area of Africa at any risk of malaria . The level of endemicity within these studied areas (mean PfPR2-10 = 16%) was systematically lower than across the continent as a whole (mean PfPR2-10 = 31%) (Figure 2). While 40% of endemic Africa experienced ‘high-endemic’ transmission in 2010 (PfPR2-10 in excess of 40%) , only 9% of the studied areas were from these high transmission settings.
This is a huge issue and one that shouldn’t be limited to malaria. While it is helpful to hear good news of malaria declines in formerly afflicted areas, we need to be careful about overstating the impact of interventions. Funding for malaria projects such as the distribution of insecticide treated bed nets was incredibly high throughout the 00’s but it is unlikely that trend will continue. Offering an positive picture can show that our efforts are valuable, but might also lead policy makers and donors to suggest that money be put toward other goals. If Sri Lanka is any indication, where malaria was nearly eliminated at one time but experienced a rapid and devastating resurgence, even a brief relaxation of malaria control efforts could erase current gains completely.
Not that the Economist has ever made a habit of ignoring tropical diseases. Far from it, the Economist as a British magazine is quite good at reporting on the Isles former colonies.
Here they’ve written on the issues of mass drug administrations as a tool in malaria eradication. Specifically, they focus on a Chinese group seeking to ramp up efforts to create a successful regimen of artemisinin and piperaquine to eliminate the disease by prophylacticly preventing infection, and interrupting the cycle of transmission long enough to eliminate the parasite entirely.
Dr Li’s approach is to attack not the mosquito, but the disease-causing parasite itself. This parasite’s life cycle alternates between its insect host (the mosquito) and its vertebrate one (human beings). Crucially, as far as is known, humans are its only vertebrate host. Deny it them and it will, perforce, wither away—an approach that worked for the smallpox virus, which had a similarly picky appetite. In the case of smallpox, a vaccine was used to make humans hostile territory for the pathogen. Since there is no vaccine against malaria, Dr Li is instead using drugs.
To date, the group has been running trials in the Comoros islands off the coast of Mozambique and had some success, but haven’t come close to full elimination. Elimination on islands surrounded by salt water (mosquitoes which transmit malaria breed in fresh water) should be a fairly easy proposition, but the issue of human mobility from the African continent guarantees reintroduction.
I’m personally involved in an island malaria elimination project in Kenya, but am under no illusions that results from an island are in the least bit generalization to the continent. Falciparum malaria is far too efficient and the lack of a winter renders transmission far too consistent to allow easy elimination. Add the issue of the intense mobility of Africans and one can’t help but be discouraged.
Dr. Li from the Guangzhou group seems to be optimistically under the mistaken impression that all it will take to eradicate malaria is the right combination of magic pills, but he’s gravely mistaken. The only thing that will consistently control malaria on the continent will be a full on, sustained assault using every tool known, along with intense economic development. The continent has only seen gains in malaria control during the 00’s, when incredible amounts of money and effort was thrown at the disease and, not coincidentally, when African economies finally started to take off. Eradicating malaria won’t be about a few pills.
More troubling to me are the ethical issues. Mass drug administrations require the participation. If even a small group of people refuse the medication, the entire effort might be for naught. Obtaining full, informed consent, however, is near impossible in these areas. While most people are willing to participate once the benefits are explained to them, the risks are often glossed over. Moreover, as communities will often follow the behavior of their neighbors or community leaders, it is difficult to judge whether people participate of their own volition or whether they are merely bowing to community pressure. Educational barriers might also compromise the ability to obtain truly informed consent.
Further, I don’t doubt the intent of the Guangzhou group, but I do wonder if Chinese institutions truly have the same level of ethical review and monitoring that United States’ institutions have (which isn’t even perfect and sometimes ill suited to developing countries). I’m sure that China would love to claim a success like malaria elimination, but I worry that a zeal for victory might lead to a violation of basic ethics and even a masking of failures, complicating the issue in the long term. I hope that I’m wrong.
Does malaria facilitate the development of exploitative agricultural estates? Interview with Dr. Luis Chavez
My friend Luis just published a paper in PlosOne on land consolidation or the formation of “latifundia” in Spain. Latifundia were large agricultural estates owned by the Romans, often dependent on slave labor, the growth of which has been implicated in Rome’s fall.
Luis creates a mathematical model to describe the formation of these large estates. He then tests the hypothesis that malaria transmission exacerbated the situation, by forcing land owners to sell cheaply to opportunistic land owners in less malarious areas.
Luis, an ecologist who works on issues of disease transmission (and all around great guy), is somewhat unique in the world of quantitative sciences. He took a few minutes to talk to me so that you can see why.
Who are you and what’s your background?
If you ask the japanese they might say: O gata no hen na gaijinsan. As to my academic background, I studied biology/parasitology as an undergraduate, then mathematical ecology for a M.Sc. and then was granted a Ph.D. in ecology and evolutionary biology (note: at the University of Michigan).
Nevertheless, I have always been interested in the humanities, especially history since it gives the best vantage point to understand the present. I grew up in a household where mixing things/topics was usual. Both my father and grandfather went to grad school, something unusual in Latin America, and since i was child lunch time talk was heavy on the side of human rights and solidarity, science and the need for change. When Nelson Mandela died i remembered that a lovely family activity during my childhood was going to a cultural/educational event in solidarity with Nelson Mandela and the South African people to end the apartheid.
For lay people, what’s the paper about and what motivated you to explore it?
The paper presents a mathematical model that can explain the formation of latifundia (large estates) when the profitability of land varies across landowners in a landscape. The model is also used to show that when such differences are not present latifundia still can emerge if there are differences in the risk of acquiring an infectious diseases. I built the model based on historical records to show that both patterns have been observed in societies as different as “latin” Europe (Italy and Spain) and China.
What’s a “latifundium” in Spain? I dug around a bit and could find some things about Rome and Latin America, but not so much about Spain. Why choose Spain?
A latifundium is a large estate, which requires the labor of people that do not own the land. I chose Spain because a essay by Chantal Beauchamp presented a couple of striking maps showing that places where malaria was common were those where Latifundia were common during the 1930s (Fig. 2): http://www.persee.fr/web/revues/home/prescript/article/ahess_0395-2649_1988_num_43_1_283483
The pattern of association between malaria and latifundia was not new, but only Beauchamp had data amenable for a quantitative analysis.
Are you trying to say that malaria helped enable capitalist land appropriation?
It might be the case. The hypothesis that malaria helped to enable land appropriation was put forward by the great italian malariologist, Angelo Celli. He has a book on the topic [reference 8 in the paper, available at the UMICH SPH library]. Celli was probably the most advanced malaria epidemiologist at the turn of the 20th century.
Unfortunately, he and other italians [most notably Grassi] were blackbolded in the Anglo-Saxon world because they threatened the ego of Ronald Ross by saying malaria was not just due to a parasite transmitted by the bite of a mosquito [a biological fact that, nevertheless, they independently showed and published in Italian]. If you are interested just check the oldest records for malaria in the Nature archives.
Though issues of land tenure are very different in the US (given that we killed all the natives and stole it all), we did have some big and awful land plantations in the South along with a serious malaria problem. Might we also try to apply this to the United States, and, if so, how?
I think it might have helped to the consolidation of large estates in the south. Interestingly in the Midwest you never had the latifundia observed in the south, but you had malaria in Michigan (the midwest) at some point (See Humphreys M. 2001. Malaria: Poverty, Race, and Public Health in the United States. Baltimore (MD): Johns Hopkins University Press.).
Nevertheless, in the south due, for example, to Jim Crow laws there might have been a differential risk of malaria infection not observed in the Midwest. However, i found no data to go beyond speculation, well other that in the Canal Zone the Jim Crow housing organization showed the differential malaria risk: http://www.jstor.org/stable/10.1086/529265
I find these quantitative approaches to historical problems fascinating (I also started work on a paper on malaria in post-conflict Angola, maybe I should publish it). Do you think applying these methods to history as informative to present day problems? If so, how?
I think so, history probably gives the best vantage point to understand the present (Rendering history a tinker damn’s is a good strategy to sell things no matter if they are useful or even safe, Henry Ford was clear about this). In theory failures can be highly educational, something the model suggests is that equity in land tenure is an unstable equilibrium that could only be maintained by an external policy as the Chinese did before the An Lushan rebellion, and that any kind of unfair land redistribution could only be expected to not work (latifundia will be eventually formed), as observed over and over in most Latin American nations.
The mix of methods is rather novel. However, in the discipline focused and partitioned environment of academia, do you find that its hard to get an audience for this kind of work? Is there a future in it?
I can tell you this stuff is only suitable for publication on the Arxiv.org or PLoS One/ Springer Plus, if you want it to be peer reviewed and you don’t sign your paper with an address in Princeton or Oxford. I think the audience does not belong in any department, though scholars working on the diverse fields of ecology, health, sociology, maths, economics and even history might find it interesting. I think there is some future, there is the emerging field of cliodynamics that looks at historical dynamics and there is even a journal for cliodynamics where they, every once on a while, publish good food for thought like this paper: http://escholarship.org/uc/item/1ks0g7dr#page-1
I thought my data was not dynamical enough, so I didn’t try there.
This work is heavily political. Do you think there is a place for politics in science?
I think everything gets embedded in politics. Otherwise there would have been no shutdown in the CDC and other US government agencies few months ago, etc. I don’t think my work is more or less political than a risk factor analysis for lung cancer and smoking. I think i might be blackbolded by some of the references I cited, but to understand Capitalism even the Catholic Church is studying Marx [Funny the leading scholar is the Munich Bishop, whose last name is Marx]: