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Adipose tissue parasite sequestration drives leptin production in mice and correlates with human cerebral malaria

March 26, 2021 - 16:05 -- Open Access
Mejia P, Treviño-Villarreal JH, Mitchell JR, et al.
Sci Adv. 2021 Mar 24;7(13):eabe2484

Circulating levels of the adipokine leptin are linked to neuropathology in experimental cerebral malaria (ECM), but its source and regulation mechanism remain unknown. Here, we show that sequestration of infected red blood cells (iRBCs) in white adipose tissue (WAT) microvasculature increased local vascular permeability and leptin production. Mice infected with parasite strains that fail to sequester in WAT displayed reduced leptin production and protection from ECM.

Comparative intravital imaging of human and rodent malaria sporozoites reveals the skin is not a species-specific barrier

March 24, 2021 - 14:05 -- Open Access
Hopp CS, Kanatani S, Archer NK, Miller RJ, Liu H, Chiou KK, Miller LS, Sinnis P
EMBO Mol Med. 2021 Mar 22:e11796

Malaria infection starts with the injection of Plasmodium sporozoites into the host's skin. Sporozoites are motile and move in the skin to find and enter blood vessels to be carried to the liver. Here, we present the first characterization of P. falciparum sporozoites in vivo, analyzing their motility in mouse skin and human skin xenografts and comparing their motility to two rodent malaria species.

Preliminary review on the prevalence, proportion, geographical distribution, and characteristics of naturally acquired Plasmodium cynomolgi infection in mosquitoes, macaques, and humans: a systematic review and meta-analysis

March 17, 2021 - 17:21 -- Open Access
Kotepui M, Masangkay FR, Kotepui KU, Milanez GJ
BMC Infect Dis. 2021 Mar 12;21(1):259

Plasmodium cynomolgi is a simian malaria parasite that has been reported as a naturally acquired human infection. The present study aims to systematically review reports on naturally acquired P. cynomolgi in humans, mosquitoes, and macaques to provide relevant data for pre-emptive surveillance and preparation in the event of an outbreak of zoonotic malaria in Southeast Asia.

Metabolic Retroversion of Piperaquine (PQ) via Hepatic CYP-mediated N-oxidation and Reduction: not an Important Contributor to the Prolonged Elimination of PQ

March 9, 2021 - 15:48 -- Open Access
Xie Y, Zhang Y, Liu H, Xing J
Drug Metab Dispos. 2021 Mar 5:DMD-AR-2020-000306

As a partner antimalarial with an extremely long elimination half-life (~30 days), piperaquine (PQ) is mainly metabolized into a pharmacologically active N-oxide metabolite (PN1) in humans. In the present work, the metabolic retroversion of PQ and PN1, potentially associated with decreased clearance of PQ, was studied. The results showed that interconversion existed for PQ and its metabolite PN1. The N-oxidation of PQ to PN1 was mainly mediated by CYP3A4, and PN1 can rapidly reduce back to PQ via CYP/FMO enzymes. In accordance with these findings, the CYP non-selective inhibitor (1-ABT) or CYP3A4 inhibitor (ketoconazole) inhibited the N-oxidation pathway in liver microsomes (>90%), and the reduction metabolism was inhibited by 1-ABT (>90%) or methimazole (~50%).

Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum

March 4, 2021 - 11:18 -- Open Access
Milne K, Ivens A, Spence PJ, et al.
Elife. 2021 Mar 2;10:e62800

Falciparum malaria is clinically heterogeneous and the relative contribution of parasite and host in shaping disease severity remains unclear. We explored the interaction between inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variation observed in controlled human malaria infection (CHMI).

A New Test of a Theory about Old Mosquitoes

March 3, 2021 - 16:42 -- Open Access
Smith DL, Musiime AK, Maxwell K, Lindsay SW, Kiware S
Trends Parasitol. 2021 Mar;37(3):185-194

In vector control, it is widely accepted that killing adult mosquitoes would sharply reduce the proportion of old mosquitoes and cause the greatest changes to malaria transmission. The principle is based on a mathematical model of the sporozoite rate (the proportion of infective mosquitoes) that emphasized changes in mosquito age.

Role of human Pegivirus infections in whole Plasmodium falciparum sporozoite vaccination and controlled human malaria infection in African volunteers

January 27, 2021 - 15:30 -- Open Access
Tumbo AM, Schindler T, Daubenberger C, et al.
Virol J. 2021 Jan 26;18(1):28

Diverse vaccination outcomes and protection levels among different populations pose a serious challenge to the development of an effective malaria vaccine. Co-infections are among many factors associated with immune dysfunction and sub-optimal vaccination outcomes. Chronic, asymptomatic viral infections can contribute to the modulation of vaccine efficacy through various mechanisms. Human Pegivirus-1 (HPgV-1) persists in immune cells thereby potentially modulating immune responses. We investigated whether Pegivirus infection influences vaccine-induced responses and protection in African volunteers undergoing whole P. falciparum sporozoites-based malaria vaccination and controlled human malaria infections (CHMI).

NOT Open Access | Malaria-induced Alterations of Drug Kinetics and Metabolism in Rodents and Humans

January 6, 2021 - 12:46 -- NOT Open Access
De-Oliveira ACAX, Paumgartten FJR
Curr Drug Metab. 2021 Jan 1

Infections and inflammation lead to a downregulation of drug metabolism and kinetics in experimental animals. These changes in the expression and activities of drug-metabolizing enzymes may affect the effectiveness and safety of pharmacotherapy of infections and inflammatory conditions.

Rapid adaptation to malaria facilitated by admixture in the human population of Cabo Verde

January 5, 2021 - 14:55 -- Open Access
Hamid I, Korunes KL, Beleza S, Goldberg A
Elife. 2021 Jan 4;10:e63177

Humans have undergone large migrations over the past hundreds to thousands of years, exposing ourselves to new environments and selective pressures. Yet, evidence of ongoing or recent selection in humans is difficult to detect. Many of these migrations also resulted in gene flow between previously separated populations. These recently admixed populations provide unique opportunities to study rapid evolution in humans.

Extensive new Anopheles cryptic species involved in human malaria transmission in western Kenya

October 1, 2020 - 15:59 -- Open Access
Zhong D, Hemming-Schroeder E, Wang X, Kibret S, Zhou G, Atieli H, Lee MC, Afrane YA, Githeko AK, Yan G
Sci Rep. 2020 Sep 30;10(1):16139

A thorough understanding of malaria vector species composition and their bionomic characteristics is crucial to devise effective and efficient vector control interventions to reduce malaria transmission. It has been well documented in Africa that malaria interventions in the past decade have resulted in major changes in species composition from endophilic Anopheles gambiae to exophilic An. arabiensis.


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