There are broadly two competing approaches for estimating malaria burden. One extrapolates from maps and surveys of population cross-sections, the other extrapolates from routinely collected surveillance data. Both have certain assumptions and biases: the former tends to overestimate, the latter generally underestimates. How should countries proceed? A new article from WHO in PloS Medicine (open access!) describes and contrasts each in a careful and informative way including actual results from 2009. While neither method is perfect, the authors present a compelling case for investing in surveillance-based approaches in the long run particularly outside of hyperendemic settings and in the context of intervention scale-up and declining transmission. Only that approach can improve the health system, and provide disaggregated and timely data amenable to frequent updates.

An accompanying editorial by Mueller, Slutsker, and Tanner broadly agrees with the author’s outlook though it includes a careful placative statement:

The two methods thus have their unique strengths and weaknesses, and rather than seeing them as competing approaches, they should be synergistically combined.

At first pass this seems a sensible assertion but on closer examination, and without other supporting text, it’s not clear what to make of it. Which distinct synergies do they envision? Should the two methods be used globally, i.e. one in countries without quality surveillance and the other elsewhere? Or should the two methods always be used in each nation? Why? Should they be used indefinitely – what about when surveillance systems mature? Are there not trade-offs both in time and space? Such discussion, drawing on the considerable program experience of the writers, would have been more helpful than conciliatory statements of questionable sincerity.

Evidence to date suggests that the AMFm was pushed forward too far, too fast and with too much money.

 Zanzibar’s early success shows what can be achieved in Africa

It’s great, but unsurprising, that Zanzibar has reduced malaria using drugs and vector control tools of known effectiveness. Of course, the efforts of the control program should at least be maintained or even transitioned into elimination if sustained funding is possible. But Zanzibar’s experience is not relevant to the provinces of most other nations, let alone an entire continent. Political and administrative complexity matter and generally increase with size. Yet, somehow I’ve seen this example, of a tiny and geographically isolated sub-national area, repeatedly paraded as a broader lesson for vast, interconnected regions. Such extrapolation is unreasonable.

PS on an entirely unrelated note, Zanzibar holds a special place in the hearts of many medical students (including myself) who learned the mnemonic “To Zanzibar By Motor Car” for remembering the divisions of the facial nerve

Professor Nick White, one of the world’s foremost experts in treating malaria, just published a fantastic review (Malaria Journal – open access!) on the topic. The article presents a great discussion of  measurement issues and common limitations, analyzing by density reduction or time until clearance, the kinetics and trend of results, connections with stage-specific action, and much more. As we’re in the midst of analyzing two years of artesunate+sulphadoxine-pyrimethamine trial data from India’s National Antimalarial Therapeutic Efficacy Monitoring Network, we’re fortunate for the release of the article since examining the parasite clearance in our patients is one of the key concerns.

There is one important caveat here – IPTc is only “effective” where the transmission is quite high. In the communities in Burkina Faso and Mali where the study was conducted transmission was  very intense (3-13 infective mosquito bites per person per month). At medium and low levels of transmission (last two rows of the table) the strategy becomes rather untenable, expending a lot of drug (which wastes money and risks side effects and resistance), for preventing a single case. Caveat to my caveat – the interpretation of rates differences in number needed to treat calculations is not always straightforward though I believe valid in this case.

Table: Number need to treat (NNT) and post-intervention incidence rate across varying baseline transmission and IPTc efficacy

Interestingly, similar to the famous Garki project the reductions in incidence appear to be much greater than reductions in prevalence – likely due to the seasonal nature of the intervention against a high vectorial capacity and thus risk of exposure.  Since the focus here is burden reduction, and not transmission reduction as in Garki, it doesn’t matter though.

]]> http://topnaman.com/treatment/new-results-for-intermittant-preventative-therapy-in-children/feed/ 0 http://topnaman.com/vaccine/patent-thickets-in-malaria-vaccine-development/ http://topnaman.com/vaccine/patent-thickets-in-malaria-vaccine-development/#comments Thu, 22 Sep 2011 12:01:23 +0000 naman http://topnaman.com/?p=597 If next-stage malaria vaccines work (the primary challenge), they are likely to be based on multiple antigens, adjuvants, and other vaccine technology platforms.  Will intellectual property limitations, in the form of competing claims across a number of public and private players (the aptly named patent thicket), impede their development, commercialization, or access? Here’s a neat Rockefeller funded report for the Malaria Vaccine Initiative - 61% of malaria vaccine related patents are held by companies, 18% are available to the organization, and another 20% are available for public licensing. Another example of the intersection between public health and law.

On gametocytes:

Now it is to these gametocytes that an extreme interest attaches, because it is to them, and to Manson’s study of them, that we owe the solution of the malaria problem.

- Ronald Ross, 1900 Malaria and mosquitoes Nature. Vol 61(1587) p:524

On the measurement of malaria

Note to begin with that we can never obtain any such estimates exactly; and also that the degree of approximation towards the truth must always depend on the amount of time and energy we have to spare for the task…

- Ronald Ross. 1910. The Prevention of Malaria

Readers may wonder how this new business-driven aid substantially improves on the old—which to date has eradicated smallpox, exterminated malaria from 18 countries and nearly eradicated polio. To achieve its goals, old-style aid may have sometimes exaggerated the depth of the problems it sought to address. But the new aid, as depicted in “Lifeblood,” seems to exaggerate the value of its interventions.

Having closely followed all efforts malaria, I’m inclined to think her observations are right on the mark.

 (image credit: Lasker Foundation)

Congratulations to Dr Tu Youyou for her well-deserved Lasker award (considered a precursor to the Nobel prize) in clinical sciences (hat tip: Mariam).

Dr Youyou recieved the honor for her painstaking work screening traditional Chinese herbs for antimalarial properties as part of military project 523 (more on the military and malaria here). The operation isolated Artemisia (also known as sweet wormwood) extracts, refined production, removed toxic elements, and conducted initial human trials which led to the development of the most potent antimalarial drug discovered to date. Artemisinin combination therapies are now the first-line treatment for Plasmodium falciparum in nearly all countries and cure millions of patients each year. The Lasker site includes a fantastic recount (much better than sparse biographies the Nobel committee posts) detailing this great story of scientific rigor applied to a rich knowledge heritage.