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NOT Open Access | Atovaquone/Proguanil Resistance in an Imported Malaria Case in Chile

March 31, 2021 - 14:35 -- NOT Open Access
Chenet SM, Oyarce A, Fernandez J, Tapia-Limonchi R, Weitzel T, Tejedo JR, Udhayakumar V, Jercic MI, Lucchi NW
Am J Trop Med Hyg. 2021 Mar 29:tpmd201095

In November 2018, we diagnosed a cluster of falciparum malaria cases in three Chilean travelers returning from Nigeria. Two patients were treated with sequential intravenous artesunate plus oral atovaquone/proguanil (AP) and one with oral AP. The third patient, a 23-year-old man, presented with fever on day 29 after oral AP treatment and was diagnosed with recrudescent falciparum malaria.

Status of insecticide susceptibility in Anopheles arabiensis and detection of the knockdown resistance mutation (kdr) concerning agricultural practices from Northern Sudan state, Sudan

March 30, 2021 - 14:26 -- Open Access
Korti MY, Ageep TB, Adam AI, Shitta KB, Hassan AA, Algadam AA, Baleela RM, Saad HA, Abuelmaali SA
J Genet Eng Biotechnol. 2021 Mar 29;19(1):49

Chemical control has been the most efficient method in mosquito control, the development of insecticide resistance in target populations has a significant impact on vector control. The use of agricultural pesticides may have a profound impact on the development of resistance in the field populations of malaria vectors. Our study focused on insecticide resistance and knockdown resistance (kdr) of Anopheles arabiensis populations from Northern Sudan, related to agricultural pesticide usage.

Novel anti-malarial drug strategies to prevent artemisinin partner drug resistance: A model-based analysis

March 30, 2021 - 14:22 -- Open Access
Kunkel A, White M, Piola P
PLoS Comput Biol. 2021 Mar 25;17(3):e1008850

Emergence of resistance to artemisinin and partner drugs in the Greater Mekong Subregion has made elimination of malaria from this region a global priority; it also complicates its achievement. Novel drug strategies such as triple artemisinin combination therapies (ACTs) and chemoprophylaxis have been proposed to help limit resistance and accelerate elimination. The objective of this study was to better understand the potential impacts of triple ACTs and chemoprophylaxis, using a mathematical model parameterized using data from Cambodia.

NOT Open Access | Structure-switching aptamer sensors for the specific detection of piperaquine and mefloquine

March 24, 2021 - 15:06 -- NOT Open Access
Coonahan ES, Yang KA, Pecic S, De Vos M, Wellems TE, Fay MP, Andersen JF, Tarning J, Long CA
Sci Transl Med. 2021 Mar 17;13(585):eabe1535

Tracking antimalarial drug use and efficacy is essential for monitoring the current spread of antimalarial drug resistance. However, available methods for determining tablet quality and patient drug use are often inaccessible, requiring well-equipped laboratories capable of performing liquid chromatography-mass spectrometry (LC-MS). Here, we report the development of aptamer-based fluorescent sensors for the rapid, specific detection of the antimalarial compounds piperaquine and mefloquine-two slow-clearing partner drugs in current first-line artemisinin-based combination therapies (ACTs).

Inducible mechanisms of disease tolerance provide an alternative strategy of acquired immunity to malaria

March 23, 2021 - 14:56 -- Open Access
Nahrendorf W, Ivens A, Spence PJ
Elife. 2021 Mar 23;10:e63838

Immunity to malaria is often considered slow to develop but this only applies to defense mechanisms that function to eliminate parasites (resistance). In contrast, immunity to severe disease can be acquired quickly and without the need for improved pathogen control (tolerance). Using Plasmodium chabaudi, we show that a single malaria episode is sufficient to induce host adaptations that can minimise inflammation, prevent tissue damage and avert endothelium activation, a hallmark of severe disease.

Sub-lethal aquatic doses of pyriproxyfen may increase pyrethroid resistance in malaria mosquitoes

March 23, 2021 - 14:40 -- Open Access
Opiyo MA, Ngowo HS, Mapua SA, Mpingwa M, Nchimbi N, Matowo NS, Majambere S, Okumu FO
PLoS One. 2021 Mar 18;16(3):e0248538

Pyriproxyfen (PPF), an insect growth hormone mimic is widely used as a larvicide and in some second-generation bed nets, where it is combined with pyrethroids to improve impact. It has also been evaluated as a candidate for auto-dissemination by adult mosquitoes to control Aedes and Anopheles species. We examined whether PPF added to larval habitats of pyrethroid-resistant malaria vectors can modulate levels of resistance among emergent adult mosquitoes.

Potential metabolic resistance mechanisms to ivermectin in Anopheles gambiae: a synergist bioassay study

March 23, 2021 - 14:39 -- Open Access
Nicolas P, Kiuru C, Wagah MG, Muturi M, Duthaler U, Hammann F, Maia M, Chaccour C
Parasit Vectors. 2021 Mar 20;14(1):172

Despite remarkable success obtained with current malaria vector control strategies in the last 15 years, additional innovative measures will be needed to achieve the ambitious goals for malaria control set for 2030 by the World Health Organization (WHO). New tools will need to address insecticide resistance and residual transmission as key challenges. Endectocides such as ivermectin are drugs that kill mosquitoes which feed on treated subjects. Mass administration of ivermectin can effectively target outdoor and early biting vectors, complementing the still effective conventional tools. Although this approach has garnered attention, development of ivermectin resistance is a potential pitfall. Herein, we evaluate the potential role of xenobiotic pumps and cytochrome P450 enzymes in protecting mosquitoes against ivermectin by active efflux and metabolic detoxification, respectively.

Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance

March 23, 2021 - 14:31 -- Open Access
Cao H, Antonopoulos A, Vickers MA, et al.
Nat Commun. 2021 Mar 19;12(1):1792

In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. Here, we report that patches of high mannose N-glycans (Man5-9GlcNAc2), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs.

Surveillance of Plasmodium falciparum pfcrt haplotypes in southwestern uganda by high‐resolution melt analysis

March 3, 2021 - 15:30 -- Open Access
Kennedy Kassaza, Anna C. Long, Yap Boum II, et al.
Malaria Journal 2021 20:114, 25 February 2021

Chloroquine (CQ) resistance is conferred by mutations in the Plasmodium falciparum CQ resistance transporter (pfcrt). Following CQ withdrawal for anti-malarial treatment, studies across malaria-endemic countries have shown a range of responses. In some areas, CQ sensitive parasites re-emerge, and in others, mutant haplotypes persist. Active surveillance of resistance mutations in clinical parasites is essential to inform treatment regimens; this effort requires fast, reliable, and cost-effective methods that work on a variety of sample types with reagents accessible in malaria-endemic countries.

NOT Open Access | Novel Antimalarial Tetrazoles and Amides Active against the Hemoglobin Degradation Pathway in Plasmodium falciparum

February 25, 2021 - 09:46 -- NOT Open Access
Lawong A, Gahalawat S, Phillips MA, et al.
J Med Chem. 2021 Feb 23

Malaria control programs continue to be threatened by drug resistance. To identify new antimalarials, we conducted a phenotypic screen and identified a novel tetrazole-based series that shows fast-kill kinetics and a relatively low propensity to develop high-level resistance. Preliminary structure-activity relationships were established including identification of a subseries of related amides with antiplasmodial activity.


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