Thursday, February 9, 2012

The politics of malaria control?

Anopheles albimanus mosquito feeding
It has been said that malaria has killed more human beings than any other single cause during the course of our evolutionary history. It is certainly a scourge but because control is a combat against both an insect carrier and a parasite, both of which reproduce faster than we do and can evolve treatment-resistance, it's a challenge to global public health.

The news had recently been that we were making overall progress. But a new studypublished in The Lancet, and described on the BBC websitereports that the global number of deaths from malaria between 1980 and 2010 was double previous reports, though the number is falling, and has been falling since it peaked in 2004. That's good news and bad news -- the revised mortality statistic, suggesting that the disease has been even more devastating than previously thought, and the falling number of deaths due to malaria, which continues to be welcome news, presumably indicating success in eradication measures.

Malaria statistics are notoriously unreliable because malaria is most prevalent in parts of the world where the public health infrastructure is thin and unreliable itself as a source of case counts. So, the authors collected as much actual data as they could for the years between 1980 and 2010, and then developed models to account for missing data. They built into their models predictors of malaria mortality such as prevalence of the parasite, drug resistance rates, and mosquito control measures.

They estimate that the number of deaths from malaria increased from 995,000 in 1980 (with a 95% uncertainty interval of 711,000-1,412,000) to 1,817,000 in 2004 (1,430,000-2,366,000), decreasing to 1,238,000 in 2010 (929,000-1,685,000). Deaths in Africa decreased by about 30% between 2004 and 2010, and by nearly 80% elsewhere. We needn't quibble about the assumptions upon which the uncertainty intervals were estimated. But this doesn't take into account increasing population sizes, so the decrease in mortality rates (deaths per thousand or hundred thousand) based on counts alone, rather than people-at-risk, would be even steeper.
Our findings show that the malaria mortality burden is larger than previously estimated, especially in adults. There has been a rapid decrease in malaria mortality in Africa because of the scaling up of control activities supported by international donors. Donor support, however, needs to be increased if malaria elimination and eradication and broader health and development goals are to be met.
From the CDC web page on malaria
This study was funded by the Bill and Melinda Gates Foundation, so the fact that the findings support increased funding of malarial control is perhaps not a surprise.  And, declining mortality from malaria is extremely good news, and we certainly do not question the benefit of bed nets and the best treatment.  But, we do wonder if the decline is as easy to explain as this paper makes it sound.  This is not at all to say that control measures aren't working, as clearly they are!  But, the story is more complex. 

For example, a paper in Malaria Journal in 2011 (which we blogged about here at the time) reported that:
A longitudinal decline in the density of malaria mosquito vectors was seen during both study periods despite the absence of organized vector control. Part of the decline could be associated with changes in the pattern of monthly rainfall, but other factors may also contribute to the dramatic downward trend.
And, a report in The Lancet in 2010, title, suggests that the story is indeed more complex than the recent paper suggests.  Indeed, this paper states that malaria declined in Ethiopia between 1998 and 2004, and:
It is very likely that the massive scale-up of ITNs [insecticide treated bednets], indoor residual spraying, community-based management of fevers, and environmental management of mosquito breeding sites all contributed to these results. However, the incidence of malaria was already declining at the beginning of the surveillance period, before these interventions were introduced.
And in the coastal area of Kenya, where "pediatric malaria admissions declined by as much as 75% between 2003 and 2007" and parasite prevalence has declined dramatically:
Although ITN use has increased concurrently with the decline in paediatric admissions, the prevalence of malaria infection declined from 35% to 10% before ITN coverage reached 25%, and before the introduction of ACTs [artemisinin combination therapies, currently the best treatment available].
In Rwanda, data from 20 facilities representing every district in the country showed a decline of more than 50% between 2005 and 2007 in both inpatient and outpatient slide-confirmed malaria cases. Before 2005, the number of cases had been increasing annually, but began to decline shortly before or at the same time as mass distribution of long-lasting insecticidal bednets and the use of ACTs in 2006–07.
An urban hospital in Libreville, Gabon reported an 80% decline in the number of children with positive blood smears in the inpatient and outpatient services. The decline began in 2003 and persisted until the end of the surveillance period in 2008. The decline pre-dated both the introduction of ACTs in 2006 and ITN distribution in 2005, the coverage of the latter reaching 50% in 2008.
And so on.  The 2011 Lancet paper concludes:
Alternative explanations for these changes should be considered. Previous experience in Europe and North America has shown that malaria declines as social conditions and education improve. However, these changes (eg, improvements in house construction) are likely to be gradual and cannot account for the sudden changes seen during the past few years, although they might have contributed. Malaria transmission is strongly affected by climate. However, climate has been carefully monitored in several case studies, and although there have been fluctuations from year to year, no overall pattern emerges that can explain the remarkable reductions in malaria cases in some countries. A highly speculative explanation for the reductions is a change in the parasite or its mosquito vector that has reduced transmissibility of the infection. Both of these are biological possibilities, but such a change seems unlikely on the opposite sides of the continent at the same time. Finally, the transmissibility of P falciparummalaria might not be as high as has been previously thought, making it easier for any transmission blocking intervention directed at either the parasite (ACTs) or the vector (ITNs or indoor residual spraying) to reduce transmission.
A student in our department  is working on malaria in southeast Asia, and he tells us that there are still many unknowns.  For example, infection is higher in males than females in Thailand, which suggests that men are becoming infected while working in the fields, so that the usual approaches of mosquito control in living quarters, and the use of bed nets, aren't enough to control infection there.  Also, infection peaks at unexpected times of the year, which suggests that the life cycle of the parasite (primarily plasmodium vivax in Southeast Asia but not entirely) is not well-understood, or may be changing.  And, climate change, as predicted, is changing the distribution of mosquitoes in all malarial zones, so that infection is now occurring or increasing in places (higher altitudes, e.g.) where it has been rare to non-existent before.

Climatic factors (rainfall amounts, temperature changes, e.g.), and even agricultural practices, such as the use or interruption in the use of irrigation, will explain seasonality of infection and short-term trends, but so will newly developed resistance of mosquitoes to treatments or insecticides, a chronic problem for malarial control. And, determining when a trend is short or long-term, and thus what is causing it, can be difficult.  

If we can find all this with a little poking around the web, presumably it's all well-known in the international health arena, too, so it's curious that a paper attributing all of the decline to improved control could be published so prominently. Could there be an element of coloring of the situation to serve the purpose of massaging donors ('MalariaGates'?), to keep the money coming?  If there is any of that involved, it would do a disservice to the understanding of the complexity of factors underlying malarial transmission and control.

Evolutionarily one must expect a continuing race between human susceptibility, drugs, attacks on the parasites and carriers, and the latters' ability to change in response.  Hopefully, in this case, the problem can be understood well enough that technology can be fast enough that we can win.  But for this to happen, all the variables need to be understood, not just the easy ones.

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