Sunday, August 4, 2013

Malaria control in Africa must move beyond vaccines, pyrethroids and antimalarials

Malaria kills 1.2 million people each year, according to new research and published in the British medical journal the Lancet in February 2012. This is more than twice as many deaths as reported by the World Malaria Report published in 2011. Africa is hit the hardest, accounting for nearly 81% of malaria deaths globally. These deaths primarily occur among children under five years of age and pregnant women. How do we turn the tide against an ancient scourge, and ultimately to eradicate the canny malaria parasite?

The economic cost of malaria
Leading economists have estimated that malaria is responsible for an “economic growth penalty” of up to 1.3 percent per year in malaria-endemic African countries. Malaria costs African countries an estimated US$12 billion per year (circa 36% of Kenya’s annual GDP) in lost productivity. Treatment of severe episodes takes up to 25% of household income and accounts for up to 40% of public sector health expenditures in sub Saharan Africa. Professor Jeffery Sachs of the Earth Institute at Columbia University has shown that the global distribution of per-capita gross domestic product has a striking correlation with malaria and poverty. In a paper published in the journal Nature in 2002, Sachs concluded that where malaria prospers, human societies have prospered the least.  

The debilitating effect of malaria undermines household productivity. The real effect of malaria is through the productive time lost by the sick and the family members who provide care for the sick. Repeated bouts of malaria in smallholder farm households have been shown to cause a decline in both food security and income, hence exacerbating poverty. For instance, in Ivory Coast, farmers suffering from malaria for more than two days out of a growing season had 47% lower yields and 53% lower revenues than their neighbors who missed no more than two days.

It is estimated that malaria accounts for about 15% of health-related absenteeism form school and may impair as much as 60% of school children’s learning ability. Cross-country studies of percentages of school-age children in school have been inversely linked to the prevalence of malaria. Such associations have persuaded some scholars to speculate that malaria in childhood is likely to have effects on general cognitive and behavioral development where malaria is endemic. Our understanding of the precise causal mechanisms remains unclear. However, of greater significance is the link between malaria during pregnancy and low birth weight and the correlation between low birth weight and subsequent cognitive problems.

Malaria and HIV
Scientists have shown that malaria may be accelerating the spread of HIV in areas of sub-Saharan Africa where there is a substantial overlap between the two diseases. HIV infection disrupts the acquired immune response to malaria, increasing the incidence and severity of malaria. Acute malaria has been shown to elevate HIV viral load and may increase the risk of HIV transmission. Hence malaria co-infection in HIV positive individuals could play a key role in promoting the spread of HIV in sub Saharan Africa. HIV infection may be associated with reduced efficacy of antimalarial treatment. 

A study published in the Lancet Journal in 2004 revealed that HIV magnifies the effect of malaria among pregnant women and their infants. HIV-infected pregnant women have significant alterations in immunity to malaria. Hence HIV positive women are at greater risk of pregnancy associated malaria and experience greater rates of anemia and adverse birth outcomes than HIV negative women. More importantly some therapies for malaria and HIV interact, leading to unanticipated effects on drug efficacy or toxicity. These interactions remain a major public health concern in most areas affected by the two diseases. For instance, caution is advised in the co-administration of quinine with nevirapine.

Agriculture and climate change and malaria
Human activity through land use and land use change has been recognized as critical to mosquito ecology and vector efficiency. Studies in western Kenya have shown that deforestation is associated with a marked increase of malaria risk, with vector efficiency increasing by 78%. Similar studies in the Peruvian Amazon have shown that mosquito-biting rate was 278 times higher in non-forest sites compared to forested areas. Similarly a global review of the effect of irrigation and large dams on the burden of malaria revealed that irrigated villages in Rusizi Valley in Burundi had higher malaria prevalence and 150-fold higher vector efficiency compared neighboring villages without large dams.

Maize pollen is known to provide nutrition for mosquito larva. A study published in 2005 in the American Journal of Tropical Medicine and Hygiene showed that the cumulative incidence of malaria in high maize cultivation areas was 9.5 times higher than in areas with less maize in Ethiopia. Entomologists have shown that maize pollen is correlated with duration of larval development and the size of resulting mosquito adults. Thus, the intensity of maize cultivation is associated with exacerbated malaria risk.

The Intergovernmental Panel on Climate Change (IPCC) concluded that climate change would be associated both with geographical expansion and contraction of malaria distribution. According to the projections of the integrated weather–disease model, malaria will disappear in the northern Sahel but will expand in the highlands. An increase in temperature, rainfall, and humidity may cause a proliferation of the malaria-carrying mosquitoes at higher altitudes, resulting in an increase in malaria transmission in areas in which malaria has not been previously reported. Under current climate change projections the East African highlands will turn into malaria epidemic-prone areas by 2050.

Evolution to the rescue
In order to survive within the red blood cell, the malaria parasite has to remodel specific proteins and evolutionary pressure has resulted in mutations in the human red blood cells that prevent this remodeling. Nearly 70 years ago, British geneticist Anthony Allison established that carriers of one gene that caused sickle-cell anemia are protected from malaria. Sickle cell anemia is a genetic disease that slightly alters the structure of hemoglobin, the oxygen carrying protein in red blood cells. The disease is prevalent in Africa where incidence of malaria is high.  In a study conducted by Centres for Disease Control and Prevention (CDC) and the Kenya Medical Research Institute in western Kenya showed that the sickle cell trait provides 60% protection against overall mortality. Most of this protection occurs between 2-16 months of life, before the onset of clinical immunity in areas with intense transmission of malaria.

Malaria Control Initiatives
International funding for malaria control increased sharply over the last decade, reaching US$1.5 billion in 2009. Increased global funding resulted in robust expansion of antimalarial programs: rapid scale-up of distribution of long lasting insecticide-treated mosquito nets – reaching 76% of the population at risk; expansion of indoor residual spaying, reaching 13 million in 2005 to 75 million in 2009; increase in the use of rapid diagnostic test, prior to treatment, for all patients with suspected malaria from less than 5% at the start of the decade to 35% in 2009. Because of these interventions, it is estimated that more than 274 million cases and 1.1 million deaths have been avoided in the past decade. 

New commitments for malaria control programs have stalled, falling short of the estimated US$6 billion needed beyond. This is especially worrying because progress and gains against malaria remain fragile in a majority of high-risk malaria countries in Africa. The stalling of funding for antimalarial programs is especially troubling. Moreover, a vaccine against malaria, like a HIV vaccine, remains elusive goal. But there is some hope. A vaccine candidate known as RTS,S/AS01 is in the midst of a large phase three clinical trial. Results published so far show that it provides additional protection against clinical and severe malaria for infants and children in settings where bed nets are also widely used.

In his book Mosquitoes, malaria and man: a history of hostilities since 1880, historian Gordon Harrison wrote in an eerily prescient manner of the persistence of malaria “Failure so universal, so apparently ineluctable, must be trying to tell us something. The lesson could be of course that we have proved incompetent warriors. It could also be that we have misconstrued the problem”. Researchers from Australia’s Queensland Institute of Medical Research argue that three factors account for the failure to maintain control malaria, namely: parasite resistance to safe and affordable antimalarials and insecticides; the shambolic state of vector control programs in developing tropical countries, and; the failure to develop a vaccine that prevents malaria.

Beyond vaccines, pyrethroids, and antimalarials
To deal robustly with malaria, Africa must look beyond drug therapy, insecticides and vaccines. New strategies for malaria control and prevention must deploy integrated malaria management.
Integrated malaria management solutions include flexible and adaptive management of ecological, environmental, hydrological conditions and knowledge of patterns of malaria transmission, and human settlement planning, which: improve management of reservoirs and irrigation systems; eradicate vector larvae through biological control; reduce vector breeding sites; locate human settlement away from corrals and potential mosquito breeding sites; and, better housing design and construction.

Integrated solutions work. Studies have shown that the cost of environmental management for malaria in copper mining communities in Zambia is lower than the cost of control programs that utilize insecticides and chemoprophylaxis implemented in countries like South Africa and Kenya. For Africa integrated management is the sensible policy approach. 

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