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High malaria resistance, drug cost threaten elimination efforts

By Chukwuma Muanya
07 April 2015   |   7:30 am
DESPITE huge funds spent yearly on prevention, control and treatment of malaria, over 40 per cent of deaths in sub-Saharan Africa occur in Nigeria and the Democratic Republic of Congo.
malaria

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DESPITE huge funds spent yearly on prevention, control and treatment of malaria, over 40 per cent of deaths in sub-Saharan Africa occur in Nigeria and the Democratic Republic of Congo.

The drug of choice remains unaffordable to most of the vulnerable population.

The World Health Organisation (WHO) in a study scheduled to be published in Management Science said that the private sector ‘supply chain’ manages 74 per cent of the drug volume in Congo and 98 per cent in Nigeria where malaria-stricken patients rely on ‘drug shops’ and other for-profit retail outlets to get life-saving medicine.

The new research in Management Science determined that the ‘shelf life’ of malaria-fighting drugs plays significant role in how donors should subsidise the medicine to ensure better affordability for patients.

According to the report, new concerns over the emergence of drug-resistant parasites are yet one more reason that private donors who fund malaria drug programmes remain intent on making medicine available and affordable to patients. Artemisinin-based combination therapies, known as ACTs, are considered the best anti-malaria drugs, but the lack of affordable ACT supplies for the poor motivates private donors to intervene and improve access.

The study is entitled: “Subsidising the Distribution Channel: Donor Funding to Improve the Availability of Malaria Drugs.”

Meanwhile, according to results of an intermittent preventive treatment in pregnancy, clinical trial pregnant women with high levels of iron were at significantly increased risk for contracting malaria.

The study is published in Open Forum Infectious Disease.

Dr. Violeta Moya-Alvarez of the Institut de Recherche pour le Dévelopment in Paris, France, and colleagues wrote in Open Forum Infectious Disease: “Benefits of iron supplementation during pregnancy for reducing iron-related diseases are undeniable. However, epidemiological studies have questioned the benefits of iron supplementation in the context of malaria-endemic countries.”

Also, a test for malaria could be as easy as a breathalyzer. Until now, although more than half a million people die of malaria every year, most of them children under the age of five in Africa, and in the areas where it is most endemic, it remains relatively expensive to diagnose.

But a group of scientists in Missouri, United States, are working on a groundbreaking method to test for the disease that, if successful, could save time, money, and most importantly, lives.

Their research was recently published in the journal mBio.

Assistant professor of pediatrics and molecular microbiology at Washington University in St. Louis, United States, Audrey Odom, said: “If you could diagnose (children with malaria) earlier, and get them treatment earlier, the studies are pretty clear that early treatment reduces mortality dramatically.”

There is still work to be done, but the results Odom and her team at Washington University have come up with so far are promising. Their research, recently published in the journal mBio, indicates that the malaria parasite produces a class of compounds, which might attract mosquitos. Meaning that: if mosquitoes can smell the malaria-born compounds then they should also be detectable through a noninvasive test similar to a breathalyzer, without the need for a microscope or blood sample.

Meanwhile, associate professor, University of California (UC) Berkeley’s Haas School of Business, Terry Taylor, and co-author from New York University’s Stern School of Business, Wenqiang Xiao, analyzed purchase subsidies versus sales subsidies.

The researchers of the Management Science study said donors structure their purchase and sales subsidies per each product unit. A purchase subsidy is a discount or rebate offered to the retailer at the point of sale or when he places his order. In contrast, the retailer only benefits from a sales subsidy when he sells the product to the consumer.

By analyzing the product characteristics (short versus long life), customer population (degree of heterogeneity or diverse makeup), and the size of the donor’s budget, Taylor and Xiao found that for long shelf life products, such as ACTs (with a 24 to 36-month life from the factory to expiration), donors should only offer a purchase subsidy. In contrast, if a product has a short shelf life, a sufficiently large donor budget and a diverse customer population, it is optimal to offer a sales subsidy in addition to a purchase subsidy. Why?

Taylor said: “The sales subsidy becomes more attractive for perishable products because you don’t have to subsidise a purchased product that doesn’t sell.”

Unlike previous research, the study’s micro-level approach focuses on distribution channel details such as demand uncertainty, supply-demand mismatch, and the impact of subsidies on stocking and pricing decisions.

Taylor said: “In principle, it would seem that you would want to use both levers to influence stocking and pricing decisions. However when we took both into account, our model shows that the purchase subsidy is more effective in increasing consumption of the medicine and ultimately, saving lives.”

Taylor hopes these findings will help guide donors in improving the private-sector distribution channel for malaria drugs. He hopes that in the future, the study’s results could also help inform subsidy decisions for other global health products such as oral rehydration salts, the first-line of treatment for childhood acute diarrhea in developing countries.

Meanwhile, the Open Forum Infectious Disease researchers monitored 1,005 Human Immuno-deficiency Virus (HIV)-negative pregnant women enrolled in the Anemia in Pregnancy: Etiology and Consequences, or APEC, observational study from January 2010 to May 2011.

Participants were assessed during two antenatal visits, and were then followed until delivery. At their first antenatal visit, all participants received an insecticide-treated net and a two-dose intermittent preventative treatment in pregnancy, administered one month apart; the first dose was given to the women after week 15 of pregnancy. Patients also were assigned 600 mg Albenza (albendazole, GlaxoSmithKline) on a systematic basis, as well as daily doses of 200 mg oral ferrous sulfate and 5 mg folic acid.

The results showed that 29 per cent of the women had at least one malarial episode during the follow-up period. The participants had an average of .52 positive smears (95% CI, 0.44-0.60).

Of the 751 placentas that the researchers analyzed, 9.2 per cent had placental malaria. Women in their first and second pregnancies were more likely to have a positive blood smear than women who had been pregnant multiple times.

There was a positive association between iron levels and risk of a positive blood smear as well as high P. falciparum density. In addition, the researchers also found that iron-deficient women were significantly less likely to have a positive blood smear and high P. falciparum density.

The researchers wrote: “Possible explanations for the increased malarial risk associated with iron levels found in our study are related to malaria pathophysiology in both the host and the parasite…

“These results warrant additional epidemiological studies to evaluate the effect of different doses of iron and folate supplementation on maternal and infant health outcomes in malaria-endemic regions.”

Odom further explained: “The compounds that we found have been described in the literature as mosquito attractants at low levels. At high levels, they’re mosquito repellants, so we think it’s a lot like perfume for people. Sometimes a little bit smells nice and a lot is repellant.”

Part of what prompted their study was previous research indicating that mosquitoes are more likely to bite people who already have malaria. This would be advantageous for the parasite because it can’t travel from human to human by itself. Rather, malaria spreads when a mosquito bites someone who already has the parasite, becomes infected, and then bites someone else.

Odom said: “There were studies in children and in mice and also in birds showing that mosquitoes would choose to bite an individual that was malaria-infected rather than one that was not, and so that really suggested that there’s something about when malaria is infecting people that can get out of the body. So, we went looking to see if we could find them.”

What they found is that the parasite contains chloroplast-like organelles, which don’t respond to light, but do manufacture a class of compound called terpenes. Two examples of terpenes are pinene, which is what gives pine trees their distinctive scent, and limonene, responsible for the characteristic smell of lemons. While the amount of compound the researchers found was not significant enough for humans to smell, they might be detectable by mosquitoes.

Odom said the much-hated insects are drawn to their targets by a variety of factors, including carbon dioxide, body warmth, and smell. Mosquitos will be drawn to stinky feet and even Limburger cheese.

The discovery of this kind of malaria generated “mosquito perfume” is, for now, based on lab work. Those results need to be duplicated in the field to be confirmed. So Odom and her team are planning field trials in Malawi to capture the breath and sweat from children with and without malaria to see if the compounds can be detected in human infections.

At this point, doctors can test for malaria using a blood test or a Malaria Rapid Diagnosis Test. The blood test requires a blood sample, a microscope, and a trained person to prepare and read the slide. The rapid diagnosis test is cheap by U.S. standards (about a dollar), but can be expensive when used at a large scale in countries in Sub-Saharan Africa, where malaria is most prevalent.