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Phosphorylation of Rhoptry Protein RhopH3 Is Critical for Host Cell Invasion by the Malaria Parasite

October 7, 2020 - 15:56 -- Open Access
Author(s): 
Ekka R, Gupta A, Bhatnagar S, Malhotra P, Sharma P
Reference: 
mBio. 2020 Oct 6;11(5):e00166-20.

Merozoites formed after asexual division of the malaria parasite invade the host red blood cells (RBCs), which is critical for initiating malaria infection. The process of invasion involves specialized organelles like micronemes and rhoptries that discharge key proteins involved in interaction with host RBC receptors. RhopH complex comprises at least three proteins, which include RhopH3.

Spatial and spatio-temporal methods for mapping malaria risk: a systematic review

October 7, 2020 - 15:54 -- Open Access
Author(s): 
Odhiambo JN, Kalinda C, Macharia PM, Snow RW, Sartorius B
Reference: 
BMJ Glob Health. 2020 Oct;5(10):e002919

Approaches in malaria risk mapping continue to advance in scope with the advent of geostatistical techniques spanning both the spatial and temporal domains. A substantive review of the merits of the methods and covariates used to map malaria risk has not been undertaken. Therefore, this review aimed to systematically retrieve, summarise methods and examine covariates that have been used for mapping malaria risk in sub-Saharan Africa (SSA).

Acquisition of human plasminogen facilitates complement evasion by the malaria parasite Plasmodium falciparum

October 7, 2020 - 15:51 -- Open Access
Author(s): 
Reiss T, Theis HI, Gonzalez-Delgado A, Vega-Rodriguez J, Zipfel PF, Skerka C, Pradel G
Reference: 
Eur J Immunol. 2020 Oct 6

The human complement system represents a severe threat for the malaria parasite Plasmodium falciparum. We previously showed that blood stage parasites bind the complement inhibitor factor H to inactivate the complement cascade. Here we investigated the potential role of plasminogen in complement evasion. Plasminogen is a zymogen of the fibrinolysis system that following processing by specific activators converts into the serine protease plasmin.

NOT Open Access | Asymptomatic Malaria Co-infection of HIV-infected Adults in Nigeria. Prevalence of and Impact on Cognition, Mood and Biomarkers of Systemic Inflammation

October 7, 2020 - 15:43 -- NOT Open Access
Author(s): 
Bharti AR, McCutchan JA, Umlauf A, Okwuegbuna OK, Letendre S, Cherner M, Burdo T, Jumare J, Williams K, Blattner W, Royal W
Reference: 
J Acquir Immune Defic Syndr. 2020 Oct 1

HIV and malaria are associated with immunological perturbations and neurocognitive disorders even when asymptomatic. However, the effect of asymptomatic malaria (AM) in HIV-infected adults on neurocognitive impairment (NCI) is not well understood. This study investigated the biomarkers of systemic inflammation and neurocognition in dually-infected Nigerian adults.

Metabolic profiling during malaria reveals the role of the aryl hydrocarbon receptor in regulating kidney injury

October 7, 2020 - 15:42 -- Open Access
Author(s): 
Lissner MM, Cumnock K, Davis NM, Vilches-Moure JG, Basak P, Navarrete DJ, Allen JA, Schneider D
Reference: 
Elife. 2020 Oct 6;9:e60165.

Systemic metabolic reprogramming induced by infection exerts profound, pathogen-specific effects on infection outcome. Here, we detail the host immune and metabolic response during sickness and recovery in a mouse model of malaria.

Tolerance of Gambian Plasmodium falciparum to Dihydroartemisinin and Lumefantrine detected by Ex vivo Parasite Survival Rate Assay (PSRA)

October 7, 2020 - 15:39 -- Open Access
Author(s): 
Mbye H, Bojang F, Jawara AS, Njie B, Mohammed NI, Okebe J, D'Alessandro U, Amambua-Ngwa A
Reference: 
Antimicrob Agents Chemother. 2020 Oct 5:AAC.00720-20

Monitoring of Plasmodium falciparum sensitivity to antimalarial drugs in Africa is vital for malaria elimination. However, the commonly used ex-vivo/in-vitro IC50 test is inconsistent for several antimalarials, while the alternative ring-stage survival assay (RSA) for artemisinin derivatives has not been widely adopted. Here we applied an alternative two-colour flow-cytometry based parasite survival rate assay (PSRA) to detect ex-vivo antimalarial tolerance in P. falciparum isolates from The Gambia.

NOT Open Access | Piperaquine exposure is altered by pregnancy, HIV and nutritional status in Ugandan women

October 7, 2020 - 15:38 -- NOT Open Access
Author(s): 
Hughes E, Imperial M, Savic RM, et al.
Reference: 
Antimicrob Agents Chemother. 2020 Oct 5:AAC.01013-20

Dihydroartemisinin-piperaquine (DHA-PQ) provides highly effective therapy and chemoprevention for malaria in pregnant African women. PQ concentrations >10.3 ng/mL have been associated with reduced maternal parasitemia, placental malaria and improved birth outcomes. We characterized the population pharmacokinetics (PK) of PQ in a post-hoc analysis of human immunodeficiency virus (HIV)-infected and -uninfected pregnant women receiving DHA-PQ as chemoprevention every 4 or 8 weeks.

NOT Open Access | Associations between malaria preventive regimens and Plasmodium falciparum drug resistance mediating polymorphisms in Ugandan pregnant women

October 7, 2020 - 15:35 -- NOT Open Access
Author(s): 
Nayebare P, Asua V, Conrad MD, Kajubi R, Kakuru A, Nankabirwa JI, Muhanguzi D, Dorsey G, Kamya MR, Nsobya S, Rosenthal PJ
Reference: 
Antimicrob Agents Chemother. 2020 Oct 5:AAC.01047-20

Intermittent preventive treatment in pregnancy (IPTp) with monthly sulfadoxine-pyrimethamine (SP) is recommended for malaria-endemic parts of Africa, but efficacy is compromised by resistance and, in recent trials, dihydroartemisinin-piperaquine (DP) has shown better antimalarial protective efficacy. We utilized blood samples from a recent trial to evaluate selection by IPTp with DP or SP of Plasmodium falciparum genetic polymorphisms that alter susceptibility to these drugs.

Repurposing Pyramax®, quinacrine and tilorone as treatments for Ebola virus disease

October 7, 2020 - 14:45 -- Open Access
Author(s): 
Lane TR, Dyall J, Mercer L, Goodin C, Foil DH, Zhou H, Postnikova E, Liang JY, Holbrook MR, Madrid PB, Ekins S
Reference: 
Antiviral Res. 2020 Oct;182:104908

We have recently identified three molecules (tilorone, quinacrine and pyronaridine tetraphosphate) which all demonstrated efficacy in the mouse model of infection with mouse-adapted Ebola virus (EBOV) model of disease and had similar in vitro inhibition of an Ebola pseudovirus (VSV-EBOV-GP), suggesting they interfere with viral entry.

NOT Open Access | Structural Basis for Blocking Sugar Uptake into the Malaria Parasite Plasmodium falciparum

October 7, 2020 - 14:42 -- NOT Open Access
Author(s): 
Jiang X, Yuan Y, Yan N, et al.
Reference: 
Cell. 2020 Oct 1;183(1):258-268.e12

Plasmodium species, the causative agent of malaria, rely on glucose for energy supply during blood stage. Inhibition of glucose uptake thus represents a potential strategy for the development of antimalarial drugs. Here, we present the crystal structures of PfHT1, the sole hexose transporter in the genome of Plasmodium species, at resolutions of 2.6 Å in complex with D-glucose and 3.7 Å with a moderately selective inhibitor, C3361.

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