topnaman | Malaria blog

The Lancet published a series of eight articles on malaria elimination today – here are my brief summaries:

• Malaria elimination: worthy, challenging, and just possible

The comment from the editors introduces the series and summarizes a few of the pieces. Horton and Das boldly highlight Gates “immense funding power and influence (witness WHO’s instant support)” and its dangerous potential to swing funding and political priorities.

• Call to action: priorities for malaria elimination

Promotes the self-appointed Malaria Elimination Group, pushes for more Gates funding (as many editorials do), and tries to label WHO as part of the elimination agenda (where the agency internally has been hesitant, rightfully, to do so). A cautionary line “With no Global Fund support, these countries will falter with potentially disastrous consequences” wisely highlights a (likely) risk. Which makes it all the more amazing, as a friend noted, that the untested Affordable Medicines Facility for malaria is receiving $200+ million while the Global Fund is cutting support across the board.

• Eliminating malaria—all of them

I have a lot of respect for Dr Baird who raises the particular challenge of eliminating non-falciparum / non-asexual stage malaria: “If we have no suitable treatment for malarias caused by hypnozoites and gametocytes, can elimination be achieved?”

• Research priorities for malaria elimination

Gates foundation (whose primary grantees are overwhelmingly US and UK based) take note: “The development of research leadership in endemic countries is not simply a politically correct mantra, but an essential requirement for long-term success. This development takes time and much more investment than there is now. While it might be tempting to use external quick fixes [e.g. management consultants - my addition], such an approach would be fundamentally misguided.”

• Shrinking the malaria map: progress and prospects

A worthy attempt at historical review (we need more reflection on the past) between countries which eliminated malaria and those which are attempting or could do so today. Of note, while a third (32/99) of malaria endemic countries are in elimination mode or ready to begin, they represent less than 20% of the total population at-risk (counting only Yunnan and Hainan provinces in China).

• Ranking of elimination feasibility between malaria-endemic countries

I’m skeptical of summary measures to describe complex situations. The editorial praises the index as ‘scientific’ (because it has numbers?) but the assessment of feasibility of elimination for any country will be a deliberative process that takes much more into account.  Also, algorithms – even if they get the trend right – may be inferior (or no better) than simple, informed opinion when we deal with actual cases. For example, India, which arguably has the most complex malaria control situation of any nation, is ranked higher (in feasibility for eliminating malaria) than the Solomon Islands, which is a limited and restricted population.

• Operational strategies to achieve and maintain malaria elimination

The latter part of the paper (detection of cryptic infections, cross-border and re-importation measures, etc) dealing with elimination specific considerations is much stronger. The thinking about surveillance and vector control seemed murky (and not distinct from malaria control strategies) and was reinforced by imprecise language around case detection and the invention of new jargon (proactive and reactive detection).

• Costs and financial feasibility of malaria elimination

I admire the authors for publishing these negative results  (elimination is unlikely to be cost-saving over the next 50 years in the five countries studied).

Overall,  the elimination agenda is still driven by the same few US and Europe based players. The good news is they are toning down their rhetoric and adding more substance  to the vision.

Malaria isn’t just a disease of people. Over 200 species of Plasmodium have been described infecting different vertebrates including rodents, birds, reptiles, and monkeys.

Last month Liu et al described the evolutionary origins of P. falciparum, the deadliest of human malaria parasites, which arose from a zoonotic (animal to human) transmission of a gorilla parasite. Before the general belief was that P. falciparum and its related simian parasites diverged at the same time as the ancestors of humans and chimpanzees did so.

Why do we care about monkey malaria? Animal reservoirs of human parasites renders the possibility of malaria eradication near impossible as the risk of reintroduction looms.  So even if falciparum arose from a single or few chance events thousands of years ago, the key question remains: Are ape populations a source for recurring human infection?

Scientists, using molecular assays,  reported gorillas infected with P. falciparum in Gabon. However, the samples were from captive animals, though originally born in the wild, living on an island sanctuary. Whether the finding represents a reverse-zoonotic event from exposure to humans or if the infection can be maintained in the wild is of critical importance. In the latest issue of Emerging Infectious Diseases we seem to have an answer. A survey of wild chimpanzees living in an undisturbed tropical rainforest habitat found five parasites including the human Plasmodia species malariae, vivax, and ovale.

While local elimination in many settings may be feasible, it seems that malaria is here to stay.

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For teaching me about health, human rights, and life by your example -

Here’s to you Sujal

Sonia Shah continues her terrific malaria journalism with this piece on elimination. She successfully and succinctly drives home the equity argument (previously discussed here):

When public health leaders want to control a disease, they devote the majority of their resources to the areas of greatest need. When their goal is eradication, they must spend their resources on areas where eradication is most likely — the areas with the least need.

If eradication campaigns fail, resources and political capital will have been lavished on the lowest priority areas with the lightest burdens.

Well said. On the other hand, we must also support strength. Good national malaria control programs on the cusp of a sustainable end should be rewarded. How do we best balance this tension?

Check out these blasts from the past. Larry Fillion  has assembled an incredible collection of stamps on all things malaria. Nearly 150 ‘countries’ are represented – though some are colonies, others no longer exist, and many have changed names… Most seem to date from 1950s-70s when they were issued in support of the global malaria eradication effort. The artwork represents the spirit of those heady times: tumultuous change, aspirations of newly free societies, and confidence in the relentless advance of science and technology.

Images from malariastamps.com

The combined gametocidal effect of primaquine plus artemisinin-combination therapy (ACT) to reduce post-treatment transmission of P. falciparum malaria is a key operational research question for malaria treatment (previously discussed here). And the evidence of adding primaquine, particularly in areas of low to medium transmission, keeps piling up. Smithius et al. report results from a massive 5-arm study along the Thai-Myanmar border. The take home message: adding primaquine to any of the ACTs reduced gametocyte carriage by about 12 times relative to ACT alone. The absolute reduction will vary according to the number of patients initially presenting with gametocytes – which is site specific because of differences in transmission and health seeking practices or access. A key strength of the trial design was the inclusion of anemic patients and those with G6PD, who may be at risk for hemolysis from exposure to primaquine,  to reflect the population served by control programs. No serious adverse effects were reported but increases in hemoglobin within the two month follow-up period were slightly less (0.3 g/dL) among patients receiving primaquine.

My critique of strategy and equity in plans discussed so far:

Recent dialogue around malaria elimination is laden with implicit assumptions. While the elimination of malaria may be both feasible and equitable in a few areas, globally: 1) the control tools which successfully reduce malaria burden may not be sufficient to interrupt transmission over long periods of time, and 2) a malaria elimination strategy may inadvertently increase inequity.

You can find the rest of the essay Assessing Strategy and Equity in the Elimination of Malaria in the latest issue of PLoS Medicine (open access!)

19, and counting, excellent malaria posts (one previously discussed here). Dr Knols asks tough questions and we’ve both touched on hot topics from King Tut, military antimalarials, Fred Soper, DDT, counterfeit medicines, Chinese efforts in the Comoros, to science press releases.

The paradox of malaria and many tropical diseases is that those most at-risk are also some of the least likely to access, or be able to access, health facilities. Active case detection, the screening of fever cases in the community itself, helps enable case management in such remote or inaccessible areas. But it’s also time and manpower intensive. Answering the questions of where to target, and whom to target is critical to making sure that effort will be worthwhile. In practice, the usual mechanical application of the strategy ensures that it will not be efficient.

So it’s beautiful to see an example of creative thinking. Last year in the infamous Jalpaiguri district of India, I met an unique, young block medical officer. Over some hot milk tea, the clean-shaven late 20s year old commented on how most of the cases at his primary health center labored in the dense jungle along the Bhutanese border. Living in secluded villages, many sought care only after prolonged illness and often arrived with severe complications. In fact,  he had described a well known phenomenon. From central India to throughout Southeast Asia stretches a vast epidemiological belt of  ’forest malaria’. The ecotype is notorious for intense transmission due to the efficient mosquito species (A. fluviatilis, minimus, and dirus) particular to that habitat.

How did he respond? Simply, intensify active case detection in those areas. To his surprise, few of the blood smears collected turned up malaria parasites. Why?  Slides were collected during the day, exactly when most of the workers were away. Undeterred, the medical officer led his staff to the villages at dusk when workers were back from the bush. Travelling as late as 8 and 9pm by unlighted, broken roads, they again returned the following day to treat infected patients. He knew it to be unsustainable for the health workers themselves in the long run, ideally the villages could receive  a community health worker (ASHA) or later they could train community volunteers, but continued the practice for the rest of the high transmission season. It paid off. Inpatient admissions for severe malaria at the primary health center fell dramatically.

I was floored. Here he was young, new to the area, no special training in malaria, but already making a difference with the few resources at his disposal. It is the value of good management. Best of all it’s not a story about new technology or glossy strategy guides – just careful observation and dedication.

Possibly, but probably not, and certainly too early to tell. Though some would have you believe it already. The World Health Organization press release makes two claims: 1) artemisinin-resistant malaria (previously discussed here and here) has almost disappeared from areas tested in a pilot project managed by WHO and 2) the overall incidence of malaria has reduced significantly in the zone targeted by the project.

For the first claim no citation, efficacy or parasite clearance time data, or evidence of any sort are mentioned including who these researchers might be. The (presented) basis for the second claim lies in the screening of just 2,782 persons (it is unclear if this was a mass survey or several months of active case detection) in which only 2 P. falciparum cases were found. I realize this is not a scientific paper, but the ‘screening’ of a few thousand people in a border population of millions before the main malaria transmission season over the upcoming months seems little to be excited about. What was the need for this? The project just began in 2009. Why not wait another two years before making any public pronouncements? Alternatively, only provide regular updates through a somber and detailed format such as an annual project summary.

I believe in WHO. First, WHO has an unique mandate for supranational coordination. Second, WHO operates by consensus which, while time-consuming and difficult at times, allows countries large and small to have a voice at the table. And finally (related to the previous point), they maintain the trust of ministries of health in a way no other organization does – at least for now… They are losing their reputation by continuing to release shoddy statements backed by limited or poor quality data.

I’ve already complained about science and public health by press release. I understand it though from NGOs but I do not understand this trend from an organization which prides itself as a leader in developing quality health recommendations and soliciting technical excellence.

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