In Brazil, Plasmodium vivax infection accounts for around 80% of malaria cases. This infection has a substantial impact on the productivity of the local population as the course of the disease is usually prolonged and the development of acquired immunity in endemic areas takes several years. The recent emergence of drug-resistant strains has intensified research on alternative control methods such as vaccines.
Hydroxychloroquine and chloroquine are used extensively in malaria and rheumatological conditions, and now in COVID-19 prevention and treatment. Although generally safe they are potentially lethal in overdose. In-vitro data suggest that high concentrations and thus high doses are needed for COVID-19 infections, but as yet there is no convincing evidence of clinical efficacy.
The global challenge to the treatment of malaria is mainly the occurrence of resistance of malaria parasites to conventionally used antimalarials. Artesunate, a semisynthetic artemisinin compound, and other artemisinin derivatives are currently used in combination with selected active antimalarial drugs in order to prevent or delay the emergence of resistance to artemisinin derivatives.
The DNA polymerase module of the Pfprex enzyme (PfpPol) is responsible for duplication of the genome of the apicoplast organelle in the malaria parasite. We show that PfpPol can misincorporate oxidized nucleotides such as 8oxodGTP opposite dA. This event gives rise to transversion mutations that are known to lead to adverse physiological outcomes.
Children are highly susceptible to clinical malaria, and in regions where malaria is endemic, their immune systems must face successive encounters with Plasmodium falciparum parasites before they develop immunity, first against severe disease and later against uncomplicated malaria. Understanding cellular and molecular interactions between host and parasites during an infection could provide insights into the processes underlying this gradual acquisition of immunity, as well as to how parasites adapt to infect hosts that are successively more malaria experienced.
Falcipain-2 (FP-2) is hemoglobinase considered an attractive drug target of Plasmodium falciparum. Recently, it has been shown that peptidomimetic nitriles containing a 3-pyridine (3Pyr) moiety at P2 display high affinity and selectivity for FP-2 with respect to human cysteine cathepsins (hCats). Further characterization demonstrated that certain P3 variants of these compounds possess micromolar inhibition of parasite growth in vitro and no cytotoxicity against human cell lines.
To evaluate the extent of chloroquine underdosing and to measure the concentrations of chloroquine and desethylchloroquine in adult patients with P. vivax malaria in the Brazilian Amazon basin.
To determine the abundance and geographic distribution of the main malaria vectors, which are influenced by habitat characteristics and ecological factors that directly impact adult density and the dynamics of malaria transmission in Mexico.
WHO has included intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine as an important malaria intervention since 2012.1 Although other candidate therapies remain under investigation and despite waning sulfadoxine-pyrimethamine antimalarial efficacy due to increasing parasite resistance, IPTp with sulfadoxine-pyrimethamine remains a key component of the management of pregnant women in malaria-endemic areas. In areas of high-grade parasite resistance, the use of IPTp with sulfadoxine-pyrimethamine is associated with improved birth weight, suggesting that there are benefits of beyond antimalarial efficacy.
Trials of intermittent preventive treatment (IPTp) of malaria in pregnant women that compared dihydroartemisinin-piperaquine with the standard of care, sulfadoxine-pyrimethamine, showed dihydroartemisinin-piperaquine was superior at preventing malaria infection, but not at improving birthweight. We aimed to assess whether sulfadoxine-pyrimethamine shows greater non-malarial benefits for birth outcomes than does dihydroartemisinin-piperaquine, and whether dihydroartemisinin-piperaquine shows greater antimalarial benefits for birth outcomes than does sulfadoxine-pyrimethamine.