Current Practices and Environmental Factors
No single strategy will control, eliminate and eventually eradicate malaria; rather, a multi-pronged, sustainable approach must be taken that fuses vector and parasite control, treatment, vaccination, monitoring and surveillance. Malaria vector control aims to reduce vector capacity to below the necessary threshold to maintain the malaria infection rate by draining breeding sites, using insecticides and preventing human contact through screens and bed nets. The primary interventions have been the utilization of long-lasting insecticide-treated nets (LLINs/ITNs), indoor residual spraying of long-lasting insecticides (IRS), larvicides that target mosquitoes' larval life stage, biological agents such as larvivorous fish and fungi, and environmental management like draining bodies of still water that are mosquitoes' breeding grounds. Please see figure below for advantages of these interventions.
Vector Control, Transmission Blocking, Elimination and Eradication Strategies
Intervention Strategies [Adapted from Birkholtz et al. Malaria Journal 2012, 11:431
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Roll over the tabs to see advantages of various intervention strategies for control of transmission. | |
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Malaria is a complex problem, and environmental factors make control and eventual eradication much more challenging. High-income Western countries with minimal terrain conducive to mosquito breeding were able to drain swampy breeding grounds and utilize DDT indiscriminately, which eventually led to the eradication of malaria in their region. In contrast, poor developing nations where malaria is still endemic face many environmental challenges to eradication. The vast tropical landscape of these endemic regions make draining and spraying difficult. Moreover, the controversy surrounding DDT and the rise in resistance to insecticides forces modern health professionals in these developing regions to limit insecticide use and look towards alternative and innovative interventions.
Click here for a map and article on insecticide resistance
Previous World Health Organization (WHO) guidelines recommended that all fevers in malarial regions be treated presumptively with antimalarial drugs. However, declining malarial transmission in parts of sub-Saharan Africa and Asia, declining proportions of fevers due to malaria, the availability of rapid diagnostic tests and the emergence of drug-resistant malaria has led to a review and change in global practices.
Current Antimalarial Medicines
Antimalarials attack the parasite by various mechanisms and have a long history of use, dating back to the 17th century with quinine. Until recently, the derivative chloroquine was the most widely used antimalarial for prevention and treatment. Introductions in the latter years of the 20th century included sulfadoxine-pyrimethamine, amodiaquine, mefloquine and atovaquone. One of the most important antimalarial drugs today, artemisinin, is extracted from the leaves of Artemisia annua (sweet wormwood) and has been used in China for the treatment of fever for over a thousand years. It is potent and rapidly active against all Plasmodium species. In P. falciparum malaria, artemisinin also kills the gametocytes - including the stage 4 gametocytes, which are otherwise sensitive only to primaquine. Artemisinin and its derivatives inhibit an essential calcium adenosine triphosphatase, PfATPase 6, and have now largely given way to the more potent dihydroartemisinin and its derivatives, artemether, artemotil and artesunate. The three latter derivatives are converted back in vivo to dihydroartemisinin. These are critical antimalarials and should be given as combination therapy to protect them from resistance (WHO Malaria Treatment Guidelines, 2010).
The Importance of Combination Therapy
Widespread and indiscriminate use of antimalarials exerts a strong selective pressure on malaria parasites to develop high levels of resistance. Resistance can be prevented, or its onset slowed considerably, by combining antimalarials with different mechanisms of action and ensuring very high cure rates through full adherence to correct dose regimens (WHO Malaria Treatment Guidelines, 2010). As a result of the spread of resistance of monotherapy treatments, the WHO adopted a policy in 2001 that recommends combination therapy (treatment using two unrelated drugs) and advises one of the drugs should be an artemisinin derivative. This has led to the increased use of Artemisinin-based Combination Therapies (ACTs) as the global frontline treatment, and appears to be potent and effective in malaria endemic regions (Baird, J Kevin, Effectiveness of Antimalarial Drugs. The New England Journal of Medicine. 2013; 352:15).
Combination therapy reduces the likelihood of having resistant species emerge by simply reducing the probability that a resistant mutant will survive. For example, if the probability of a random mutation that renders drug A ineffective is one in a million, and the probability of a separate mutation that provides resistance to drug B is also one in a million, then the probability of having random mutations that provide resistance to both drugs is one in 1,000,000,000,000. As a result, an organism that had a mutation providing resistance to one of the drugs would be unable to propagate, because it would most likely be killed by the other drug.