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Natural Products: A Potential Source of Malaria Transmission Blocking Drugs

September 23, 2020 - 09:00 -- Open Access
Author(s): 
Moyo P, Mugumbate G, Eloff JN, Louw AI, Maharaj VJ, Birkholtz LM
Reference: 
Pharmaceuticals (Basel). 2020 Sep 17;13(9):E251

The ability to block human-to-mosquito and mosquito-to-human transmission of Plasmodium parasites is fundamental to accomplish the ambitious goal of malaria elimination. The WHO currently recommends only primaquine as a transmission-blocking drug but its use is severely restricted by toxicity in some populations. New, safe and clinically effective transmission-blocking drugs therefore need to be discovered.

An open label study of the safety and efficacy of a single dose of weekly chloroquine and azithromycin administered for malaria prophylaxis in healthy adults challenged with 7G8 chloroquine-resistant Plasmodium falciparum in...

September 16, 2020 - 12:48 -- Open Access
Author(s): 
Jeffrey Livezey, Patrick Twomey, Paige Waterman, et al.
Reference: 
Malaria Journal 2020 19:336, 16 September 2020

Malaria remains the top infectious disease threat facing the U.S. military in many forward operating environments. Compliance with malaria chemoprophylaxis remains a critical component in preventing malaria in the deployed Service Member. Studies of previous military operations show that compliance is consistently higher with weekly versus daily dosing regimens. Current FDA approved weekly chemoprophylaxis options have contraindications that can limit prescribing. The combination of chloroquine (CQ) with azithromycin (AZ) has previously been shown to be an efficacious treatment option for malaria, has pharmacokinetics compatible with weekly dosing, and has shown synergy when combined in vitro.

NOT Open Access | Ape Origins of Human Malaria

September 10, 2020 - 14:23 -- NOT Open Access
Author(s): 
Sharp PM, Plenderleith LJ, Hahn BH
Reference: 
Annu Rev Microbiol. 2020 Sep 8;74:39-63

African apes harbor at least twelve Plasmodium species, some of which have been a source of human infection. It is now well established that Plasmodium falciparum emerged following the transmission of a gorilla parasite, perhaps within the last 10,000 years, while Plasmodium vivax emerged earlier from a parasite lineage that infected humans and apes in Africa before the Duffy-negative mutation eliminated the parasite from humans there.

Not Open Access | Probing the B- & C-rings of the antimalarial tetrahydro-β-carboline MMV008138 for steric and conformational constraints

September 10, 2020 - 08:33 -- NOT Open Access
Author(s): 
Ding S, Ghavami M, Butler JH, Merino EF, Slebodnick C, Cassera MB, Carlier PR
Reference: 
Bioorg Med Chem Lett. 2020 Sep 5:127520

The antimalarial candidate MMV008138 (1a) is of particular interest because its target enzyme (IspD) is absent in human. To achieve higher potency, and to probe for steric demand, a series of analogs of 1a were prepared that featured methyl-substitution of the B- and C-rings, as well as ring-chain transformations.

Human exposure to zoonotic malaria vectors in village, farm and forest habitats in Sabah, Malaysian Borneo

September 8, 2020 - 11:58 -- Open Access
Author(s): 
Brown R, Chua TH, Fornace K, Drakeley C, Vythilingam I, Ferguson HM
Reference: 
PLoS Negl Trop Dis. 2020 Sep 4;14(9):e0008617

The zoonotic malaria parasite, Plasmodium knowlesi, is now a substantial public health problem in Malaysian Borneo. Current understanding of P. knowlesi vector bionomics and ecology in Sabah comes from a few studies near the epicentre of human cases in one district, Kudat. These have incriminated Anopheles balabacensis as the primary vector, and suggest that human exposure to vector biting is peri-domestic as well as in forest environments.

NOT Open Access | Decoding the complexities of human malaria through systems immunology

January 20, 2020 - 14:38 -- NOT Open Access
Author(s): 
Tran TM, Crompton PD
Reference: 
Immunological Reviews Volume293, Issue1 January 2020 Pages 144-162

The complexity of the Plasmodium parasite and its life cycle poses a challenge to our understanding of the host immune response against malaria. Studying human immune responses during natural and experimental Plasmodium infections can enhance our understanding of malaria‐protective immunity and inform the design of disease‐modifying adjunctive therapies and next‐generation malaria vaccines.

NOT Open Access | In Vivo Efficacy and Pharmacokinetics of the 2-Aminomethylphenol Antimalarial, JPC-3210, in the Aotus Monkey-Human Malaria Model

December 23, 2019 - 15:10 -- NOT Open Access
Author(s): 
McCallum F, Birrell GW, Chavchich M, Harris I, Obaldia N 3rd, Van Breda K, Heffernan GD, Jacobus DP, Shanks D, Edstein MD
Reference: 
Antimicrob Agents Chemother. 2019 Dec 16. pii: AAC.01538-19

Nonimmune Aotus monkeys infected with Plasmodium falciparum and Plasmodium vivax were cured of their infections when treated with a single oral dose of 5 mg/kg and 10 mg/kg of the 2-aminomethylphenol, JPC-3210, respectively.

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