topnaman | Malaria blog

Chloroquine was discovered in Germany in 1934 (as Resochin) but was originally considered too toxic for human use. After American trials of the drug in World War 2 chloroquine became a mainstay of malaria treatment. In recent decades with the advent of worldwide drug resistance its use has declined. With perhaps the exception of Mesoamerica, the use of chloroquine for falciparum malaria is (or should be) minimal. The drug remains vital for vivax malaria, and other than Papua New Guinea, only a few stray case reports of treatment failure exist.

What’s fascinating about the drug is its potential application in other fields. Reported to have anti-viral, anti-inflammatory, and immunosuppressive properties chloroquine has been considered for many uses. Before the days of metronidazole it was a mainstay in the treatment of amoebiasis,  and I believe was used by the famous Dr. Ben Kean in his book M.D. during a fascinating attempt to dislodge the scolex (head) of a tapeworm from the patient’s intestinal wall. In India chloroquine is still used in primary health centers for the treatment of gout and in patients with suspected chikungunya during the recent outbreaks. Let’s see where it goes next.

The mosquito vector, and by extension local ecology, drives malaria transmission. So understanding vector biology is important to malaria control. Classical studies of mosquito flight range, feeding preferences, and resting habits were crucial in the development and application of control strategies. Modern vector biology research, dominated by molecular studies, has produced new tools for monitoring insecticide resistance in mosquitoes as well as identifying Anopheles sibling species among whom the potential for transmitting malaria can broadly vary.

Recently, I browsed through a malaria journal article (open access!) whose potential I have difficulty understanding. Can someone explain to me how research on variation in chromosomal inversions and their relationship with stress responses will improve malaria control? Looking carefully through the manuscript, the sole rationale that I could find was:

Polymorphism for the 2La inversion creates heterogeneity in the stress response within A.gambiae, which could directly or indirectly reduce the efficacy of vector control measures, and influence the reaction of vector populations to environmental variation including climate change.

I find this single sentence advanced by the authors both incomplete and unsatisfying. It tells you very little. So let’s think through the rationale ourselves. Understanding the ability of a vector to exploit different habitats is certainly useful – we could predict how mosquito ranges and other characteristics may change with the climate. Understanding the molecular basis of that ability might further help – if the molecular changes had a clear association with a phenotype of interest (i.e. real world characteristics of the mosquito) and were such that they could easily be monitored. Understanding polymorphisms in those molecular mechanisms and their relationship to stress response variation however is not intuitively valuable (perhaps for modelling purposes?). To be clear, my aim is not cast the research as meaningless (though it may be). Sometimes the impact of basic science take years or decades to be realized. Rather, I’m surprised the authors, and especially the reviewers, did not seek to clearly convey the value of the work. If the purpose of public health research is to improve health, then the communication of such research should describe its relevance in explicit and detailed language.

The Multilateral Initiative on Malaria conference is the largest scientific gathering for malaria with more than 2,000 attendees. The conference has a blog for the press but Tropika is the site to watch with initiatives like researcher interviews and day by day coverage. Actually, this is the first time I have seen scientific event reporting that is  accessible to the general public and innovative in its content. The usual fare consists of “advertisement” press releases  echoed around the web and in print by an uncritical press corps. More to come as news emerges.  (Thanks to Kanya)

I get a lot of emails about malaria and other global health events. Here’s a recent one that may be of some interest to those living near Washington, DC:

Malaria in the America Forum 2009:
“Counting Malaria Out” towards the 2010 targets and the UN Millennium Development Goals.

Friday, November 6, 2009
1:00pm – 4:30pm
Room B, Pan American Health Organization
525 Twenty-Third Street, NW
Washington D.C.

The Pan American Health Organization, the Pan American Health and Education Foundation and the Center for Global Health at the George Washington University in the 2009 commemoration forum for Malaria Day in the Americas on November 6, 2009 (Friday). We welcome you to take part in an engaging discussion which will highlight the progress of efforts towards achieving global goals and national targets on malaria prevention and control, the challenges of malaria elimination, and resolving various issues on malaria work with mobile populations.

Another reason this caught my eye  is I have an old malaria day of the America’s shirt from Guyana. The motto is quite a mouthful! Speaking of mobile populations and Guyana, Bill Brieger at Malaria Free Future has excellently covered both recently.

I’ve covered the Gates grand challenge exploration grants before, but some of the winners from the most recent round may take the “this just sounds crazy” cake – chewing gum for a saliva based diagnostic, and chocolate compounds as potential treatments!

The African Leaders Malaria Alliance announced during the United Nations general assembly claims it is “the first Head of State-level assembly expressly dedicated to ending deaths from the disease.” Is it just me or does this simply happen every ten years or so? If you also feel a sense of déjà vu it probably stems from the Abuja declaration signed by 44 heads of state (or their representatives) in 2000. OK, maybe the snarky comments are a bit much. Political will is important, but I have little patience for ceremony. At a glance the new alliance is seeking to exceed the goals set at Abuja (eg. No deaths vs 50% reduction) but in a longer timeline (2015 vs 2010). Also of note, according to the website only 11 countries are participating though some reliable sources are reporting 20.

The American Journal of Public Health published a terrific account (hat tip: Steven Meshnick) of a bizarre event from the 1950s where:

DDT spraying to control malaria allegedly resulted in cats being poisoned in some areas, which led to increased rodent populations and, in turn, the parachuting of cats into the highlands of the island of Borneo to kill the rodents.

Of course, why not? Everyone knows the rationale response to a rodent menace must involve flying felines – and in large numbers! Another source suggests that in “Operation Cat Drop” some 14000 live cats were parachuted into Borneo. In any case I am indebted to Patrick O’Shaughnessy for his entertaining and meticulous research.

An example of a poor use of facility-based data to claim the anti-malaria impact of interventions:

In 2007 the Millennium Village Project published early results related to agriculture, health, and economic development in their three research villages in Kenya, Ethiopia, and Malawi. I am not commenting on their work as a whole but their malaria claims were disproportionate to the evidence (especially given the bias of self-evaluation). The group does note some of their limitations but they also unequivocally state to “have reduced malaria prevalence”. It is an interesting use of the term prevalence, which usually refers to the proportion of parasitemic people in a survey, whereas they used facility based data and measured changes in the proportion of clinical malaria cases against total clinic visits. Regardless, even if prevalence or incidence decreased any credit due is unsubstantiated. Some of the obstacles in interpreting their data include the use of clinical malaria cases (which is problematic as discussed here), no demographic comparisons of facility controls, displaying a reduction in diagnostically confirmed cases without any context of testing trends, and only one year of follow up in the absence of any discussion of pre-intervention trends. To be frank the malaria portion of the paper is rather bad science. I am surprised the Proceedings of the National Academy of Sciences endorsed it.

About a year and a half ago I briefly discussed a WHO report (see comments here) claiming the success of scale-up of malaria control interventions. Now a group of CDC/ex-CDC scientists have published a superb commentary (Malaria Journal – open access) on the same evaluation and on using facility-based data more broadly (hat tip: Matt Price). The authors focus on technical pitfalls, which were aplenty, but these are often exacerbated by the incentives of the evaluators. In act of terrific political deftness, Rowe et al. avoid any discussion of possible conflicts of interest.

On an unrelated note, I found the first sentence of the abstract to be curiously phrased:

The global health community is interested in the health impact of the billions of dollars invested to fight malaria in Africa.

First,  the prima facie concern regarding the impact of malaria control is with endemic countries. They have skin in the game. It is unclear what “the global health community” really means – while it could be inclusive of endemic nations the connation of the phrase seems more aligned with a donor perspective. Thus, the rationale of this paper reads “accurate program evaluations are needed because donors want to assess their impact.” This is wrong. Quality evaluations are important first and foremost because they allow country programs to track and improve their progress in minimizing the suffering of their citizens.  Anything else is secondary and subjugate to this concern. The framing of the sentence reflects a subtle, and likely unintentional, appropriation of responsibility which may not impact practice but devalues local decision makers. Second, why “in Africa”? Neither malaria, large investments, nor the cautions highlighted in the commentary are specific to that continent.

Tales of malaria fascinate me, how could they not? It is a dangerous, exotic, haphazard, and hopelessly romantic history. No other disease is as entwined with colonialism, war, and agricultural industry. Also, the basics haven’t changed much. Little in the past few decades has altered the underlying rationale and means of practical malaria control. Thus, along with fascinating stories there is a lot we can learn. A wise man (Dr J Kevin Baird) once told me:

A malariologist troubles himself to understand all of the gathered science of malaria, without regard to what technology has been applied to gather it. This means reading the old literature, a lot. The more I read it and understand it, a clear and somewhat disturbing message sinks in. There are very few malariologists actively publishing today. And the malaria scientists of today do not read or understand malariology. We make fundamental errors of strategy and strategic thinking.

In my readings thus far, this rings true. What the old literature provides is a rare element of perspective – a vantage point of clarity in an increasingly complex landscape. And the lens of history need not restrict our ambitions but can inform and temper our methods. So, where to look? In addition to your standard archived articles at the BMJ, JAMA, and other journals, two fantastic resources are:

1) Google Books – many incredible texts such as The Prevention of Malaria by Ronald Ross (1910) and The Practical Study of Malaria and Other Blood Parasites by JWW Stephens and SR Christophers (1904)

2) The National Library of Scotland – an entire collection of rare public health reports on plague, cholera, kala-azar, and malaria from the British era of India including the classic data of devastating malaria epidemics in the Punjab