SARS-CoV-2 has spread throughout the world and become the cause of the infectious coronavirus disease 2019 (COVID-19). As low- and middle-income countries shift increasingly to focus on identifying and treating COVID-19, questions are emerging about the impact this shift in focus will have on ongoing efforts to control other infectious diseases, such as malaria.
Nigeria bears 25% of global malaria burden despite concerted efforts towards its control and elimination. The emergence of drug resistance to first line drugs, artemisinin combination therapies (ACTs), indicates an urgent need for continuous molecular surveillance of drug resistance especially in high burden countries where drug interventions are heavily relied on. This study describes mutations in Plasmodium falciparum genes associated with drug resistance in malaria; Pfk13, Pfmdr1, PfATPase6 and Pfcrt in isolates obtained from 83 symptomatic malaria patients collected in August 2014, aged 1–61 years old from South-west Nigeria.
Studies of the susceptibility of Plasmodium falciparum to the artemisinin family of antimalarial drugs provide a complex picture of partial resistance (tolerance) associated with increased parasite survival in vitro and in vivo. We present an overview of the genetic loci that, in mutant form, can independently elicit parasite tolerance. These encode kelch propeller domain protein PfK13, ubiquitin hydrolase UBP-1, actin filament-organising protein Coronin, also carrying a propeller domain, and the trafficking adaptor subunit AP-2μ.
Malaria is a particular problem in pregnancy because of enhanced sensitivity, the possibility of placental malaria, and adverse effects on pregnancy outcome. Artemisinin-containing combination therapies (ACTs) are the most effective antimalarials known. WHO recommends 7-day quinine therapy for uncomplicated Plasmodium falciparum malaria in the first trimester despite the superior tolerability and efficacy of 3-day ACT regimens because artemisinins caused embryolethality and/or cardiovascular malformations at relatively low doses in rats, rabbits, and monkeys.
Malaria is a prominent vector-borne illness caused by Plasmodium parasites.
About half the world's population is at risk of malaria, with Plasmodium falciparum malaria being responsible for the most malaria related deaths globally. Antimalarial drugs such as chloroquine and artemisinin are directed towards the proliferating intra-erythrocytic stages of the parasite, which is responsible for all the clinical symptoms of the disease.
Plasmodium species, the causative agent of malaria, rely on glucose for energy supply during blood stage. Inhibition of glucose uptake thus represents a potential strategy for the development of antimalarial drugs. Here, we present the crystal structures of PfHT1, the sole hexose transporter in the genome of Plasmodium species, at resolutions of 2.6 Å in complex with D-glucose and 3.7 Å with a moderately selective inhibitor, C3361.
Chloroquine remains the first-line treatment for uncomplicated malaria in Haiti, and until recently, sulfadoxine-pyrimethamine was the second-line treatment. A few studies have reported the presence of molecular markers for resistance in Plasmodium falciparum parasites, and in vivo therapeutic efficacy studies (TESs) have been limited. Recognizing the history of antimalarial resistance around the globe and the challenges of implementing TESs in low-endemic areas, the Ministry of Health established a surveillance program to detect molecular markers of antimalarial resistance in Haiti.
All malaria infections are harmful to both the pregnant mother and the developing fetus. One in ten maternal deaths in malaria endemic countries are estimated to result from Plasmodium falciparum infection. Malaria is associated with a 3-4 times increased risk of miscarriage and a substantially increased risk of stillbirth. Current treatment and prevention strategies reduce, but do not eliminate, malaria's damaging effects on pregnancy outcomes.
Resistance towards known antimalarial drugs poses a significant problem, urging for novel drugs that target vital proteins in the malaria parasite Plasmodium falciparum. However, recombinant production of malaria proteins is notoriously difficult. To address this, we have investigated two putative K+ channels, PfKch1 and PfKch2, identified in the P. falciparum genome.