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NOT Open Access | An in vitro study on the differentiated metabolic mechanism of chloroquine-resistant Plasmodium falciparum using high-resolution metabolomics

August 4, 2021 - 12:20 -- NOT Open Access
Na J, Zhang J, Choe YL, Lim CS, Park YH
J Toxicol Environ Health A. 2021 Aug 1:1-16

Chloroquine (CQ) is an important drug used therapeutically for treatment of malaria. However, due to limited number of studies on metabolic targets of chloroquine (CQ), it is difficult to attribute mechanisms underlying resistance associated with usage of this drug. The present study aimed to investigate the metabolic signatures of CQ-resistant Plasmodium falciparum (PfDd2) compared to CQ-sensitive Plasmodium falciparum (Pf3D7).

NOT Open Access | Fitness of sulfadoxine-resistant Plasmodium berghei harboring a single mutation in dihydropteroate synthase (dhps)

July 20, 2021 - 12:56 -- NOT Open Access
Yamauchi M, Hirai M, Tachibana SI, Mori T, Mita T
Acta Trop. 2021 Jul 14:106049

Genetic changes conferring drug resistance are generally believed to impose fitness costs to pathogens in the absence of the drug. However, the fitness of resistant parasites against sulfadoxine/pyrimethamine has been inconclusive in Plasmodium falciparum. This is because resistance is conferred by the complex combination of mutations in dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr), which makes it difficult to separately assess the extent and magnitude of the costs imposed by mutations in dhps and dhfr.

NOT Open Access | Functional human IgA targets a conserved site on malaria sporozoites

June 29, 2021 - 14:02 -- NOT Open Access
Tan J, Cho H, Crompton PD, et al.
Sci Transl Med. 2021 Jun 23;13(599):eabg2344

Immunoglobulin (Ig)A antibodies play a critical role in protection against mucosal pathogens. However, the role of serum IgA in immunity to nonmucosal pathogens, such as Plasmodium falciparum, is poorly characterized, despite being the second most abundant isotype in blood after IgG. Here, we investigated the circulating IgA response in humans to P. falciparum sporozoites that are injected into the skin by mosquitoes and migrate to the liver via the bloodstream to initiate malaria infection. We found that circulating IgA was induced in three independent sporozoite-exposed cohorts: individuals living in an endemic region in Mali, malaria-naïve individuals immunized intravenously with three large doses of irradiated sporozoites, and malaria-naïve individuals exposed to a single controlled mosquito bite infection.

Compensatory mechanisms in resistant Anopheles gambiae AcerKis and KdrKis neurons modulate insecticide-based mosquito control

June 9, 2021 - 13:07 -- Open Access
Perrier S, Moreau E, Deshayes C, El-Adouzi M, Goven D, Chandre F, Lapied B
Commun Biol. 2021 Jun 2;4(1):665

In the malaria vector Anopheles gambiae, two point mutations in the acetylcholinesterase (ace-1R) and the sodium channel (kdrR) genes confer resistance to organophosphate/carbamate and pyrethroid insecticides, respectively. The mechanisms of compensation that recover the functional alterations associated with these mutations and their role in the modulation of insecticide efficacy are unknown.

Malaria-Resistant Mosquitoes (Diptera: Culicidae); The Principle is Proven, But Will the Effectors Be Effective

May 25, 2021 - 13:53 -- Open Access
Adelman ZN, Kojin BB
J Med Entomol. 2021 May 21:tjab090

Over the last few decades, a substantial number of anti-malarial effector genes have been evaluated for their ability to block parasite infection in the mosquito vector. While many of these approaches have yielded significant effects on either parasite intensity or prevalence of infection, just a few have been able to completely block transmission.

Ecology of asynchronous asexual replication: the intraerythrocytic development cycle of Plasmodium berghei is resistant to host rhythms

February 23, 2021 - 14:14 -- Open Access
Aidan J. O’Donnell and Sarah E. Reece
Malaria Journal 2021 20:105, 19 February 2021

Daily periodicity in the diverse activities of parasites occurs across a broad taxonomic range. The rhythms exhibited by parasites are thought to be adaptations that allow parasites to cope with, or exploit, the consequences of host activities that follow daily rhythms. Malaria parasites (Plasmodium) are well-known for their synchronized cycles of replication within host red blood cells. Whilst most species of Plasmodium appear sensitive to the timing of the daily rhythms of hosts, and even vectors, some species present no detectable rhythms in blood-stage replication. Why the intraerythrocytic development cycle (IDC) of, for example Plasmodium chabaudi, is governed by host rhythms, yet seems completely independent of host rhythms in Plasmodium berghei, another rodent malaria species, is mysterious.

Chemoprotective Antimalarial Activity of P218 against Plasmodium falciparum: A Randomized, Placebo-Controlled Volunteer Infection Study

February 10, 2021 - 09:44 -- Open Access
Chughlay MF, El Gaaloul M, Chalon S, et al.
Am J Trop Med Hyg. 2021 Feb 8:tpmd201165

P218 is a highly selective dihydrofolate reductase inhibitor with potent in vitro activity against pyrimethamine-resistant Plasmodium falciparum. This single-center, randomized, double-blind, placebo-controlled phase Ib study evaluated P218 safety and chemoprotective efficacy in a P. falciparum sporozoite (PfSPZ) volunteer infection study (VIS). Consecutive dose safety and tolerability were evaluated (cohort 1), with participants receiving two oral doses of P218 1,000 mg 48 hours apart (n = 6), or placebo (n = 2). P218 chemoprotective efficacy was assessed (cohorts 2 and 3) with direct venous inoculation of 3,200 aseptic, cryopreserved PfSPZ (NF54 strain) followed 2 hours later with two P218 doses of 1,000 mg (cohort 2, n = 9) or 100 mg (cohort 3, n = 9) administered 48 hours apart, or placebo (n = 6).

Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

November 4, 2020 - 15:20 -- Open Access
Adolfi A, Gantz VM, James AA, et al.
Nat Commun. 2020 Nov 3;11(1):5553

Cas9/gRNA-mediated gene-drive systems have advanced development of genetic technologies for controlling vector-borne pathogen transmission. These technologies include population suppression approaches, genetic analogs of insecticidal techniques that reduce the number of insect vectors, and population modification (replacement/alteration) approaches, which interfere with competence to transmit pathogens.

NOT Open Access | Mice chronically fed a high-fat diet are resistant to malaria induced by Plasmodium berghei ANKA

October 1, 2019 - 14:33 -- NOT Open Access
Onésia Cristina Oliveira-Lima, Natália Lourenço Almeida, Camila Megale Almeida-Leite & Juliana Carvalho-Tavares
Parasitology Research, October 2019, Volume 118, Issue 10, pp 2969–2977

C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) develop neurological symptoms and die 6-–7-day post-inoculation in the absence of high parasitemia.

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