First-line treatment regimens for malaria: evaluation of plasmodium in vitro susceptibility and dormancy mechanism of artemisinin combination therapies

Combination therapy with artemisinin (ACT) is based on a derivative of artemisinin associate with another antimalarial drug in a slow and prolonged action, thus increasing the efficacy of treatment and reducing the likelihood of resistance development.

The first-line treatments in Brazil in infections by P. falciparum uncomplicated are the combinations of artemether-lumefantrine (Coartem) and artesunate-mefloquine (Farmanguinhos). The regimen of second choice is the quinine-doxycycline combination.

A parasite is considered resistant when it is able to survive and multiply in your blood stage asexual, despite the administration and proper absorption of a chemotherapeutic regimen. Today, evidence of decreased efficacy to treatment with artemisinin and its derivatives in P. falciparum isolates from Thailand and Cambodia.

Single nucleotide polymorphisms (SNPs) in some genes showed affect parasite response to different antimalarials. A phenomenon that requires further study is the dormant mechanism in P. falciparum, proposed as a mechanism of tolerance to artemisinin. Under this mechanism, the parasites are able to tolerate the action of artemisinin by blocking the maturation temporarily, similar to what occurs with some bacteria.

The adoption of ACTs as first-line treatment for P. falciparum not serious, necessitates monitoring studies that are sentinels to detect decreased sensitivity of this parasite to artemisinin derivatives and drugs used in association such as mefloquine and lumefantrine.

This study proposes the in vitro determination of phenotypic profile of P. falciparum response to artesunate and mefloquine, ACT that is used in extra-Brazilian Amazon region, in addition to proposing an unprecedented assessment of the response to lumefantrine, used in combination with artemether in area Brazilian endemic. Also unprecedented is the evaluation of dormancy mechanism isolates of P. falciparum Brazilians to ACTs adopted in the country.

Drug-based Strategies
Genetics and Genomics

Mar 2014 — Oct 2016

America, Southern
Brazil