Antimalarial drug resistance: a review of the biology and strategies to delay emergence and spread

Abstract

The emergence of resistance to former first-line antimalarial drugs has been an unmitigated disaster. In recent years, artemisinin class drugs have become standard and they are considered an essential tool for helping to eradicate the disease. However, their ability to reduce morbidity and mortality and to slow transmission requires the maintenance of effectiveness. Recently, an artemisinin delayed-clearance phenotype was described. This is believed to be the precursor to resistance and threatens local elimination and global eradication plans. Understanding how resistance emerges and spreads is important for developing strategies to contain its spread. Resistance is the result of two processes: (i) drug selection of resistant parasites; and (ii) the spread of resistance. In this review, we examine the factors that lead to both drug selection and the spread of resistance. We then examine strategies for controlling the spread of resistance, pointing out the complexities and deficiencies in predicting how resistance will spread.

Polyamidoamine Nanoparticles as Nanocarriers for the Drug Delivery to Malaria Parasite Stages in the Mosquito Vector

“…With each replication, some of the merozoites develop into gametocytes, which can then infect susceptible mosquitoes, bringing the transmission cycle full circle. From [18], with permission.…”

Novel strategies for Plasmodium-targeted drug delivery

“…The second approach of simply administering higher antimalarial drug amounts usually results either in side effects severe enough to discourage people from taking the medicine or in the need to take several doses, which is often not fulfilled; such patient noncompliance is one of the main triggers of drug resistance evolution. [3] Finally, drug combinations can delay the selection of multiple resistance, [4] which, however, will eventually occur, ending up in loss of efficacy of even the most promising frontline drugs. [5] This scenario calls for urgent new approaches capable of breaking a century-long monotony of antimalarial therapeutics.…”

Dynamics of an age-structured two-strain model for malaria transmission

“…In the absence of an effective and safe vaccine for use against malaria in humans (although concerted global efforts are underway to develop such a vaccine [5,15,16,24,31,[39][40][41]44,48,49,53,57,59]), malaria control is based on the use of preventive measures (such as mosquito-reduction strategies and personal protection against mosquito bite) and the use of anti-malaria drugs (see, for instance, [20,21,32,46,47,61,63]). The use of anti-malarial drugs (such as Aralen, Chloroquine, Malaraquine and Nivaquine [6,43]) is, however, known to pose the problem of the emergence and transmission of drug-resistant malaria strain [3,6,20,32,33,43]. Such resistance is attributed to factors such as [3,6,20,32,33,43]:…”