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Flowcytometric and ImageStream RNA-FISH gene expression, quantification and phenotypic characterization of blood and liver stages from human malaria species

September 1, 2021 - 16:22 -- Open Access
Luiza-Batista C, Nardella F, Thiberge S, Serra-Hassoun M, Ferreira MU, Scherf A, Garcia S
J Infect Dis. 2021 Aug 28:jiab431

We adapted the RNA FISH stellaris® method to specifically detect the expression of Plasmodium genes by flowcytometry and ImageStream (FlowFISH). This new method accurately quantified the erythrocytic forms of P. falciparum and vivax, and the sexual stages of P. vivax from patient isolates.

Simplified binomial estimation of human malaria transmission exposure distributions based on hard classification of where and when mosquitoes are caught: statistical applications with off-the-shelf tools

August 4, 2021 - 15:29 -- Open Access
Killeen GF, Monroe A, Govella NJ
Parasit Vectors. 2021 Aug 3;14(1):384

The impacts and limitations of personal protection measures against exposure to vectors of malaria and other mosquito-borne pathogens depend on behavioural interactions between humans and mosquitoes. Therefore, understanding where and when they overlap in time and space is critical. Commonly used approaches for calculating behaviour-adjusted estimates of human exposure distribution deliberately use soft classification of where and when people spend their time, to yield nuanced and representative distributions of mean exposure to mosquito bites across entire human populations or population groups.

Reducing mosquito-borne disease transmission to humans: A systematic review of cluster randomised controlled studies that assess interventions other than non-targeted insecticide

August 3, 2021 - 17:35 -- Open Access
Oliver J, Larsen S, Stinear TP, Hoffmann A, Crouch S, Gibney KB
PLoS Negl Trop Dis. 2021 Jul 29;15(7):e0009601

Mosquito control interventions are widely used to reduce mosquito-borne diseases. It is unclear what combination of interventions are most effective in reducing human disease. A novel intervention study for Buruli ulcer targeting mosquito vectors was proposed for a Buruli ulcer-endemic area of Victoria, Australia. The local community expressed a preference for avoiding widespread residual spraying of pyrethroids. To inform the design of a future cluster randomised control study (cRCT) for Buruli ulcer prevention in Victoria, we conducted a systematic literature review.

Comparison of four outdoor mosquito trapping methods as potential replacements for human landing catches in western Kenya

June 16, 2021 - 09:45 -- Open Access
Abong'o B, Gimnig JE, Oxborough RM, et al.
Parasit Vectors. 2021 Jun 12;14(1):320

Longitudinal monitoring of outdoor-biting malaria vector populations is becoming increasingly important in understanding the dynamics of residual malaria transmission. However, the human landing catch (HLC), the gold standard for measuring human biting rates indoors and outdoors, is costly and raises ethical concerns related to increased risk of infectious bites among collectors. Consequently, routine data on outdoor-feeding mosquito populations are usually limited because of the lack of a scalable tool with similar sensitivity to outdoor HLC.

NOT Open Access | Metabolome modulation of the host adaptive immunity in human malaria

June 15, 2021 - 15:13 -- NOT Open Access
Abdrabou W, Dieng MM, Diawara A, Sermé SS, Almojil D, Sombié S, Henry NB, Kargougou D, Manikandan V, Soulama I, Idaghdour Y
Nat Metab. 2021 Jun 10

Host responses to infection with the malaria parasite Plasmodium falciparum vary among individuals for reasons that are poorly understood. Here we reveal metabolic perturbations as a consequence of malaria infection in children and identify an immunosuppressive role of endogenous steroid production in the context of P. falciparum infection. We perform metabolomics on matched samples from children from two ethnic groups in West Africa, before and after infection with seasonal malaria.

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).


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