Tracking antimalarial drug resistance using mosquito blood meals: a cross-sectional study

Ehrlich, Hanna Y.; Some, Anthony; Bazié, Thomas; Ebou, Cathérine Neya; Dembélé, Estelle Lotio; Balma, Richard; Goodwin, Justin; Wade, Martina; Bei, Amy K.; Ouédraogo, Jean‐Bosco; Foy, Brian D.; Dabiré, Roch K.; Parikh, Sunil

doi:10.1016/s2666-5247(23)00063-0

Cited by 2 publications

(3 citation statements)

References 29 publications

(44 reference statements)

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“…An obstacle in malaria eradication is the parasite's resistance to current drug ments, with both the parasite and the vector being extraordinarily adaptable [14][15][16] treatment for malaria depends on factors such as the type of the infecting parasit geographical location of the acquired infection, and the patient's condition [17][18][19]. T fore, finding specific drugs to treat malaria in the long term is challenging [14,20,21] Marine natural products have gained significance in developing drugs for tre malaria due to the diverse secondary metabolites produced by marine organisms. T compounds exhibit remarkable structural arrangements, resulting in various biolo activities.…”

Section: Introductionmentioning

confidence: 99%

“…An obstacle in malaria eradication is the parasite’s resistance to current drug treatments, with both the parasite and the vector being extraordinarily adaptable [ 14 , 15 , 16 ]. The treatment for malaria depends on factors such as the type of the infecting parasite, the geographical location of the acquired infection, and the patient’s condition [ 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…The treatment for malaria depends on factors such as the type of the infecting parasite, the geographical location of the acquired infection, and the patient’s condition [ 17 , 18 , 19 ]. Therefore, finding specific drugs to treat malaria in the long term is challenging [ 14 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Probing the Antiplasmodial Properties of Plakortinic Acids C and D: An Uncommon Pair of Marine Peroxide-Polyketides Isolated from a Two-Sponge Association of Plakortis symbiotica and Xetospongia deweerdtae Collected near Puerto Rico

Amador,

Colón-Lorenzo,

Rodríguez

et al. 2024

Life

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Plakortinic acids C (1) and D (2), an unseparable pair of endoperoxide polyketides isolated and purified from the symbiotic association of Caribbean Sea sponges Plakortis symbiotica-Xestospongia deweerdtae, underwent in vitro evaluation for antiplasmodial activity against the malaria parasite Plasmodium berghei using a drug luminescence assay. Initial screening at 10 µM revealed 50% in vitro parasite growth inhibition. The title compounds displayed antiplasmodial activity with an EC50 of 5.3 µM toward P. berghei parasites. The lytic activity against erythrocytes was assessed through an erythrocyte cell lysis assay, which showed non-lytic activity at lower concentrations ranging from 1.95 to 3.91 µM. The antiplasmodial activity and the absence of hemolytic activity support the potential of plakortinic acids C (1) and D (2) as promising lead compounds. Moreover, drug-likeness (ADMET) properties assessed through the pkCSM server predicted high intestinal absorption, hepatic metabolism, and volume of distribution, indicating favorable pharmacokinetic profiles for oral administration. These findings suggest the potential suitability of these metabolites for further investigations of antiplasmodial activity in multiple parasitic stages in the mosquito and Plasmodium falciparum. Notably, this study represents the first report of a marine natural product exhibiting the unique 7,8-dioxatricyclo[4.2.2.02,5]dec-9-ene motif being evaluated against malaria.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Probing the Antiplasmodial Properties of Plakortinic Acids C and D: An Uncommon Pair of Marine Peroxide-Polyketides Isolated from a Two-Sponge Association of Plakortis symbiotica and Xetospongia deweerdtae Collected near Puerto Rico

Amador,

Colón-Lorenzo,

Rodríguez

et al. 2024

Life

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Ex vivo drug susceptibility and resistance mediating genetic polymorphisms of Plasmodium falciparum in Bobo-Dioulasso, Burkina Faso

Somé,

Conrad,

Kabré

et al. 2024

Antimicrob Agents Chemother

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Malaria remains a leading cause of morbidity and mortality in Burkina Faso, which utilizes artemether–lumefantrine as the principal therapy to treat uncomplicated malaria and seasonal malaria chemoprevention with monthly sulfadoxine–pyrimethamine plus amodiaquine in children during the transmission season. Monitoring the activities of available antimalarial drugs is a high priority. We assessed the ex vivo susceptibility of Plasmodium falciparum to 11 drugs in isolates from patients presenting with uncomplicated malaria in Bobo-Dioulasso in 2021 and 2022. IC 50 values were derived using a standard 72 h growth inhibition assay. Parasite DNA was sequenced to characterize known drug resistance-mediating polymorphisms. Isolates were generally susceptible, with IC 50 values in the low-nM range, to chloroquine (median IC 50 10 nM, IQR 7.9–24), monodesethylamodiaquine (22, 14–46) piperaquine (6.1, 3.6–9.2), pyronaridine (3.0, 1.3–5.5), quinine (50, 30–75), mefloquine (7.1, 3.7–10), lumefantrine (7.1, 4.5–12), dihydroartemisinin (3.7, 2.2–5.5), and atovaquone (0.2, 0.1–0.3) and mostly resistant to cycloguanil (850, 543–1,290) and pyrimethamine (33,200, 18,400–54,200), although a small number of outliers were seen. Considering genetic markers of resistance to aminoquinolines, most samples had wild-type PfCRT K76T (87%) and PfMDR1 N86Y (95%) sequences. For markers of resistance to antifolates, established PfDHFR and PfDHPS mutations were highly prevalent, the PfDHPS A613S mutation was seen in 19% of samples, and key markers of high-level resistance (PfDHFR I164L; PfDHPS K540E) were absent or rare (A581G). Mutations in the PfK13 propeller domain known to mediate artemisinin partial resistance were not detected. Overall, our results suggest excellent susceptibilities to drugs now used to treat malaria and moderate, but stable, resistance to antifolates used to prevent malaria.

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Tracking antimalarial drug resistance using mosquito blood meals: a cross-sectional study

Cited by 2 publications

References 29 publications

Probing the Antiplasmodial Properties of Plakortinic Acids C and D: An Uncommon Pair of Marine Peroxide-Polyketides Isolated from a Two-Sponge Association of Plakortis symbiotica and Xetospongia deweerdtae Collected near Puerto Rico

Probing the Antiplasmodial Properties of Plakortinic Acids C and D: An Uncommon Pair of Marine Peroxide-Polyketides Isolated from a Two-Sponge Association of Plakortis symbiotica and Xetospongia deweerdtae Collected near Puerto Rico

Ex vivo drug susceptibility and resistance mediating genetic polymorphisms of Plasmodium falciparum in Bobo-Dioulasso, Burkina Faso

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