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plasmodium falciparum

NOT Open Access | Safety, Pharmacokinetics, and Causal Prophylactic Efficacy of KAF156 in a Plasmodium falciparum Human Infection Study

October 13, 2021 - 12:43 -- NOT Open Access
Author(s): 
Kublin JG, Murphy SC, Prince WT, et al.
Reference: 
Clin Infect Dis. 2021 Oct 5;73(7):e2407-e2414

KAF156 is a novel antimalarial drug that is active against both liver- and blood-stage Plasmodium parasites, including drug-resistant strains. Here, we investigated the causal prophylactic efficacy of KAF156 in a controlled human malaria infection (CHMI) model.

Divergent acyl carrier protein decouples mitochondrial Fe-S cluster biogenesis from fatty acid synthesis in malaria parasites

October 12, 2021 - 10:19 -- Open Access
Author(s): 
Falekun S, Sepulveda J, Jami-Alahmadi Y, Park H, Wohlschlegel JA, Sigala PA
Reference: 
Elife. 2021 Oct 6;10:e71636

Most eukaryotic cells retain a mitochondrial fatty acid synthesis (FASII) pathway whose acyl carrier protein (mACP) and 4-phosphopantetheine (Ppant) prosthetic group provide a soluble scaffold for acyl chain synthesis and biochemically couple FASII activity to mitochondrial electron transport chain (ETC) assembly and Fe-S cluster biogenesis. In contrast, the mitochondrion of Plasmodium falciparum malaria parasites lacks FASII enzymes yet curiously retains a divergent mACP lacking a Ppant group. We report that ligand-dependent knockdown of mACP is lethal to parasites, indicating an essential FASII-independent function. Decyl-ubiquinone rescues parasites temporarily from death, suggesting a dominant dysfunction of the mitochondrial ETC.

NOT Open Access | In silico identification of noncompetitive inhibitors targeting an uncharacterized allosteric site of falcipain-2

October 12, 2021 - 09:59 -- NOT Open Access
Author(s): 
Hernández González JE, Salas-Sarduy E, Hernández Alvarez L, Barreto Gomes DE, Pascutti PG, Oostenbrink C, Leite VBP
Reference: 
J Comput Aided Mol Des. 2021 Oct 7

Falcipain-2 (FP-2) is a Plasmodium falciparum hemoglobinase widely targeted in the search for antimalarials. FP-2 can be allosterically modulated by various noncompetitive inhibitors that have been serendipitously identified. Moreover, the crystal structures of two inhibitors bound to an allosteric site, termed site 6, of the homolog enzyme human cathepsin K (hCatK) suggest that the equivalent region in FP-2 might play a similar role.

Naturally Acquired Antibodies against Plasmodium falciparum: Friend or Foe

October 12, 2021 - 09:55 -- Open Access
Author(s): 
Tijani MK, Lugaajju A, Persson KEM
Reference: 
Pathogens. 2021 Jul 2;10(7):832

Antibodies are central to acquired immunity against malaria. Plasmodium falciparum elicits antibody responses against many of its protein components, but there is also formation of antibodies against different parts of the red blood cells, in which the parasites spend most of their time. In the absence of a decisive intervention such as a vaccine, people living in malaria endemic regions largely depend on naturally acquired antibodies for protection.

NOT Open Access | Plasmodium falciparum goes bananas for sex

October 11, 2021 - 19:35 -- NOT Open Access
Author(s): 
Dixon MWA, Tilley L
Reference: 
Mol Biochem Parasitol. 2021 Jul;244:111385

The sexual blood stages of the human malaria parasite Plasmodium falciparum undergo a remarkable transformation from a roughly spherical shape to an elongated crescent or "falciform" morphology from which the species gets its name. In this review, the molecular events that drive this spectacular shape change are discussed and some questions that remain regarding the mechanistic underpinnings are posed.

Towards the use of a smartphone imaging-based tool for point-of-care detection of asymptomatic low-density malaria parasitaemia

October 9, 2021 - 20:18 -- Open Access
Author(s): 
Ashlee J. Colbert, Katrina Co, Giselle Lima-Cooper, Dong Hoon Lee, Katherine N. Clayton, Steven T. Wereley, Chandy C. John, Jacqueline C. Linnes and Tamara L. Kinzer-Ursem
Reference: 
Malaria Journal 2021 20:380, 25 September 2021

Globally, there are over 200 million cases of malaria annually and over 400,000 deaths. Early and accurate detection of low-density parasitaemia and asymptomatic individuals is key to achieving the World Health Organization (WHO) 2030 sustainable development goals of reducing malaria-related deaths by 90% and eradication in 35 countries. Current rapid diagnostic tests are neither sensitive nor specific enough to detect the low parasite concentrations in the blood of asymptomatic individuals.

Performance evaluation of RDT, light microscopy, and PET-PCR for detecting Plasmodium falciparum malaria infections in the 2018 Zambia National Malaria Indicator Survey

October 9, 2021 - 10:03 -- Open Access
Author(s): 
Mulenga C. Mwenda, Abebe A. Fola, Ilinca I. Ciubotariu, Conceptor Mulube, Brenda Mambwe, Rachael Kasaro, Moonga B. Hawela, Busiku Hamainza, John M. Miller, Giovanna Carpi and Daniel J. Bridges
Reference: 
Malaria Journal 2021 20:386, 28 September 2021

Zambia continues to advance on the path to elimination with significant reductions in malaria morbidity and mortality. Crucial components that have contributed to progress thus far and are necessary for achieving the national malaria elimination goals include properly identifying and treating all malaria cases through accurate diagnosis. This study sought to compare and assess the diagnostic performance of Rapid Diagnostic Tests (RDT) and Light Microscopy (LM) with photo-induced electron transfer polymerase chain reaction (PET-PCR) as the gold standard using 2018 Malaria Indicator Survey (MIS) data across Zambia to better understand diagnostic accuracy metrics and how these vary across a transmission gradient.

Detection of high frequency of MAD20 allelic variants of Plasmodium falciparum merozoite surface protein 1 gene from Adama and its surroundings, Oromia, Ethiopia

October 9, 2021 - 09:58 -- Open Access
Author(s): 
Temesgen File, Tsegaye Chekol, Gezahegn Solomon, Hunduma Dinka and Lemu Golassa
Reference: 
Malaria Journal 2021 20:385, 27 September 2021

One of the major challenges in developing an effective vaccine against asexual stages of Plasmodium falciparum is genetic polymorphism within parasite population. Understanding the genetic polymorphism like block 2 region of merozoite surface protein-1 (msp-1) gene of P. falciparum enlighten mechanisms underlining disease pathology, identification of the parasite clone profile from the isolates, transmission intensity and potential deficiencies of the ongoing malaria control and elimination efforts in the locality. Detailed understanding of local genetic polymorphism is an input to pave the way for better management, control and elimination of malaria. The aim of this study was to detect the most frequent allelic variant of the msp-1 gene of P. falciparum clinical isolates from selected health facilities in Adama town and its surroundings, Oromia, Ethiopia.

Transcriptome-based analysis of blood samples reveals elevation of DNA damage response, neutrophil degranulation, cancer and neurodegenerative pathways in Plasmodium falciparum patients

October 9, 2021 - 09:46 -- Open Access
Author(s): 
Akua A. Karikari, Wasco Wruck and James Adjaye
Reference: 
Malaria Journal 2021 20:383, 26 September 2021

Malaria caused by Plasmodium falciparum results in severe complications including cerebral malaria (CM) especially in children. While the majority of falciparum malaria survivors make a full recovery, there are reports of some patients ending up with neurological sequelae or cognitive deficit.

Asymptomatic and sub-microscopic Plasmodium falciparum infection in children in the Mount Cameroon area: a cross-sectional study on altitudinal influence, haematological parameters and risk factors

October 9, 2021 - 09:43 -- Open Access
Author(s): 
Irene Ule Ngole Sumbele, Rene Ning Teh, Helen Kuokuo Kimbi, et al.
Reference: 
Malaria Journal 2021 20:382, 26 September 2021

The Mount Cameroon area has experienced a 57.2% decline in confirmed malaria cases between 2006 and 2013 with the implementation of different control measures but, the disease is still of public health concern. The objective of the study was to assess the burden of asymptomatic and sub-microscopic Plasmodium infection, altitudinal influence on it, their effect on haematological parameters as well as identify the risk factors of infection.

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