Monday, September 1, 2014

Lunch with the Captain

These days I’m having trouble finding time to write, especially to blog.

My colleagues and I are busy building a team and a large network of collaborators for a series of related malaria elimination projects.  Our initial goal in this project is to wipe malaria out in very specific populations.  If this works, and from our initial work at a smaller scale it appears as though it can, it will be vastly scaled up – reaching throughout Southeast Asia.

The impetus for this work is the so-called evolutionary arms race.  This part of the world has a very long history of popping out drug and multi-drug resistant strains of falciparum malaria (C Wongsrichanalai et al., 2001; Chansuda Wongsrichanalai, Pickard, Wernsdorfer, & Meshnick, 2002).  We (malaria workers) roll out a new line of defense (antimalarials) against our chosen adversary, and our adversary quickly develops a defense strategy against us.  These strains can subsequently move from this part of the world to others, parts of sub-Saharan Africa for example, where the malaria burden is much heavier and the results would be much more devastating (Payne, 1987).

Occasionally there are deaths from malaria infections here along the Thailand-Myanmar border (though usually the major toll the illness takes here is in time spent ill and therefore unable to work.)  Not that long ago, a 15 year old boy died from malaria.  He was not far from health care clinics that would have treated him.  The story I hear is that he was without close family members, he lived alone and worked in the agricultural fields, and that he essentially lay in those fields dying from the disease through an apparent gap in his and his community’s social network.  Everyone was devastated.  If complete drug resistance were to reach Africa, this story would be magnified in both space and time.  Even where the social networks were strong, the health clinics wouldn’t be able to adequately treat people with malaria.  The geographic reach would be huge and the numbers of death would likely dramatically increase.  This can’t happen.

Today our last, best tool against malaria is artemisinin and its derivatives.  But already throughout Southeast Asia researchers and health care workers are seeing parasites survive much longer in the human hosts after being treated with artemisinin (Ashley et al., 2014).  How much longer will it work at all?  And should we really wait to find out?  It often feels as though everyone around here has been doing the same “malaria control” game for a very long period of time, regardless of the fact that the outcome is always the same.  Our drugs stop working and we have to start over again.  Sometimes this problem is exacerbated by a lack of information and/or the dissemination of scientific knowledge.  Many of my Thai colleagues who actually work in direct malaria care in this area just learned last year (2013) that resistance to artemisinins might be occurring or even growing and spreading in their region.  A major scientific paper on this (that I’m aware of) came out 5 years ago (Dondorp, Nosten, & Yi, 2009), with rumors of it almost 10 years ago (Noedl et al., 2008)!  Shouldn’t the people who live in the war zone know that a war is happening!?  What a failure of science – and of our strategy over the long term.  It is time for a change.

So what we’re working on is a tool that we’re calling “targeted chemo-elimination.”  Essentially this is a form of mass drug administration.  That is, everyone in a targeted community would take drugs (antimalarials) regardless of whether or not they felt sick (some recent thoughts on this here, here, and here).  It is much more complicated than this though, in that it isn’t a single strong dose of the antimalarials, we’ll be using a cocktail of drugs so that we can hope to avoid further driving resistance, and since the administration will occur over time, over several stages, we’ll be able to vary this cocktail if necessary.

Logistically this is extremely difficult to pull off.  It is hard enough to get people in easy to reach populations in places like the U.S. to take medicine when they feel sick, let alone to take a vaccine that would prevent them from being sick.  How do we go about convincing people in extremely remote populations, frequently in the middle of old or continuing conflict zones, to take medicine, over a long period of time, regardless of whether or not they are currently feeling sick?  It isn’t easy.

But it can be done and the way to do it is through community engagement – drawing on notions and principles well-known in anthropology and other social sciences.  It can happen when there is understanding, trust, and social cohesion.  Sometimes these things are lacking in our target communities between members of the community, and/or between us and members of the community, and it is therefore important to build them up.  Sometimes we need to plant a seed, water it, foster it, and help it to grow.

This is exhausting work, physically, psychologically, and emotionally.

A little while back I made a trip to one of the communities in our target area, to visit local people and share some of what our project is about.  I wound up eating lunch at a table full of “freedom fighters”, some dressed in fatigues and drinking whisky out of small coffee cups.  A captain who was sitting at the table gave me a history lesson, translated to English through one of my colleagues who speaks both my tongue and the local language.  I heard stories about being betrayed by colonialists who promised these people their own land but never followed through and of people who were willing to die for that land, many of whom did in fact pay that price.

Among the things he said to me was that he admired two major things about Americans.  One is that their time is their money (time is extremely valuable).  And the other is that they realize they have a burden, to help others, that is bigger than a mountain (we were sitting at the base of a relatively large one).

I don’t know if this generalization is true of all Americans and I don’t care to go into that.  But I do know that time is of the essence and that I feel a burden.  There is a lot of work to do, and not so much time in which to do it.

*** As always, my opinions are my own.  This post and my opinions do not necessarily reflect those of Shoklo Malaria Research Unit, Mahidol Oxford Tropical Medicine Research Unit, or the Wellcome Trust. 

Ashley, E. a., Dhorda, M., Fairhurst, R. M., Amaratunga, C., Lim, P., Suon, S., … White, N. J. (2014). Spread of Artemisinin Resistance in Plasmodium falciparum Malaria. New England Journal of Medicine, 371(5), 411–423. doi:10.1056/NEJMoa1314981

Dondorp, A., Nosten, F., & Yi, P. (2009). Artemisinin resistance in Plasmodium falciparum malaria. The New England Journal of MedicineEngland Journal of …, 455–467. Retrieved from

Noedl, H., Se, Y., Schaecher, K., Smith, B., Socheat, D., & Fukuda, M. (2008). Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med, 359(24), 2619–2620.

Payne, D. (1987). Spread of chloroquine resistance in Plasmodium falciparum. Parasitology Today (Personal Ed.), 3(8), 241–6. Retrieved from

Wongsrichanalai, C., Pickard, A. L., Wernsdorfer, W. H., & Meshnick, S. R. (2002). Epidemiology of drug-resistant malaria. Lancet Infectious Diseases, 2, 209–218.

Wongsrichanalai, C., Sirichaisinthop, J., Karwacki, J. J., Congpuong, K., Miller, R. S., Pang, L., & Thimasarn, K. (2001). Drug resistant malaria on the Thai-Myanmar and Thai-Cambodian borders. Southeast Asian J Trop Med Public Health, 32(1), 41–49.


Ken Weiss said...

A typically profound and thoughtful (and interesting) post. I just have looked at it because we were in Europe when you posted it.

Multiple simultaneous agents make sense statistically, but it's a numbers game of parasite mutation rate, numbers, and exposure to the agents. Cancer chemotherapy seems to address similar issues and avoidance of antibiotic resistance must do so as well. I imagine you know this literature in at least some detail, which I don't

Ken Weiss said...
This comment has been removed by the author.