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Exposure of Anopheles mosquitoes to trypanosomes reduces reproductive fitness and enhances susceptibility to Plasmodium

February 17, 2020 - 12:10 -- Open Access
Dieme C, Zmarlak NM, Brito-Fravallo E, Travaillé C, Pain A, Cherrier F, Genève C, Calvo-Alvarez E, Riehle MM, Vernick KD, Rotureau B, Mitri C
PLoS Negl Trop Dis 14(2): e0008059

During a blood meal, female Anopheles mosquitoes are potentially exposed to diverse microbes in addition to the malaria parasite, Plasmodium. Human and animal African trypanosomiases are frequently co-endemic with malaria in Africa. It is not known whether exposure of Anopheles to trypanosomes influences their fitness or ability to transmit Plasmodium. Using cell and molecular biology approaches, we found that Trypanosoma brucei brucei parasites survive for at least 48h after infectious blood meal in the midgut of the major malaria vector, Anopheles coluzzii before being cleared.

RNA-Seq Analysis Illuminates the Early Stages of Plasmodium Liver Infection

February 14, 2020 - 16:49 -- Open Access
Toro-Moreno M, Sylvester K, Srivastava T, Posfai D, Derbyshire ER
mBio. 2020 Feb 4;11(1). pii: e03234-19

The apicomplexan parasites Plasmodium spp. are the causative agents of malaria, a disease that poses a significant global health burden. Plasmodium spp. initiate infection of the human host by transforming and replicating within hepatocytes. This liver stage (LS) is poorly understood compared to other Plasmodium life stages, which has hindered our ability to target these parasites for disease prevention. We conducted an extensive transcriptome sequencing (RNA-Seq) analysis throughout the Plasmodium berghei LS, covering as early as 2 h postinfection (hpi) and extending to 48 hpi.

Molecular characterization of RNase III protein of Asaia sp. for developing a robust RNAi-based paratransgensis tool to affect the sexual life-cycle of Plasmodium or Anopheles fitness

February 11, 2020 - 15:47 -- Open Access
Majid Asgari, Mahdokht Ilbeigikhamsehnejad, Elham Rismani, Navid Dinparast Djadid, Abbasali Raz
Parasit Vectors. 2020; 13:42

According to scientific recommendations, paratransgenesis is one of the solutions for improving the effectiveness of the Global Malaria Eradication Programme. In paratransgenesis, symbiont microorganisms are used for distorting or blocking the parasite life-cycle, affecting the fitness and longevity of vectors or reducing the vectorial competence. It has been revealed recently that bacteria could be used as potent tools for double stranded RNA production and delivery to insects. Moreover, findings showed that RNase III mutant bacteria are more competent for this aim. Asaia spp. have been introduced as potent paratransgenesis candidates for combating malaria and, based on their specific features for this goal, could be considered as effective dsRNA production and delivery tools to Anopheles spp. Therefore, we decided to characterize the rnc gene and its related protein to provide the basic required information for creating an RNase III mutant Asaia bacterium.

Optimal timing of primaquine to reduce Plasmodium falciparum gametocyte carriage when co-administered with artemether–lumefantrine

January 24, 2020 - 14:49 -- Open Access
Seif Shekalaghe, Dominic Mosha, Ali Hamad, Thabit A. Mbaga, Michael Mihayo, Teun Bousema, Chris Drakeley and Salim Abdulla
Malaria Journal 2020 19:34, 21 January 2020

Primaquine is an important gametocytocidal drug that is combined with conventional malaria treatment for prevention of Plasmodium falciparum malaria transmission. Primaquine has been administered together on the first or the last day of conventional treatment but the impact of primaquine timing has never been examined. This study aimed to assess safety, efficacy and optimal timing of single full-dose (0.75 mg/kg) primaquine when added to a standard 6-dose regimen of artemether–lumefantrine (AL).

Clustering of asymptomatic Plasmodium falciparum infection and the effectiveness of targeted malaria control measures

January 24, 2020 - 14:47 -- Open Access
Jeffrey G. Shaffer, Mahamoudou B. Touré, Nafomon Sogoba, Seydou O. Doumbia, Jules F. Gomis, Mouhamadou Ndiaye, Daouda Ndiaye, Ayouba Diarra, Ismaela Abubakar, Abdullahi Ahmad, Muna Affara, Davis Nwakanma, Mary Lukowski, James C. Welty, Frances J. Mather, Joseph Keating & Donald J. Krogstad
Malaria Journal 2020 19:33, 21 January 2020

Because clustering of Plasmodium falciparum infection had been noted previously, the clustering of infection was examined at four field sites in West Africa: Dangassa and Dioro in Mali, Gambissara in The Gambia and Madina Fall in Senegal.

NOT Open Access | Whole parasite vaccines for the asexual blood stages of Plasmodium

January 20, 2020 - 15:16 -- NOT Open Access
Good MF, Stanisic DI
Immunological Reviews, Volume293, Issue1 January 2020, Pages 270-282

After many decades of research, an effective vaccine for malaria is still not available. Most research efforts have focused on identifying a key target antigen and then using powerful adjuvants to generate specific antibodies that can block parasites from entering host cells (hepatocytes, red blood cells). However, the inability to generate sufficiently potent antibody responses has led to significant disappointment with current vaccine programs.

Fast and fierce versus slow and smooth: Heterogeneity in immune responses to Plasmodium in the controlled human malaria infection model

January 20, 2020 - 14:39 -- Open Access
Yap XZ, McCall MBB, Sauerwein RW
Immunological Reviews, Volume293, Issue1, January 2020

Controlled human malaria infection (CHMI) is an established model in clinical malaria research. Upon exposure to Plasmodium falciparum parasites, malaria‐naive volunteers differ in dynamics and composition of their immune profiles and subsequent capacity to generate protective immunity. CHMI volunteers are either inflammatory responders who have prominent cellular IFN‐γ production primarily driven by adaptive T cells, or tempered responders who skew toward antibody‐mediated humoral immunity. When exposed to consecutive CHMIs under antimalarial chemoprophylaxis, individuals who can control parasitemia after a single immunization (fast responders) are more likely to be protected against a subsequent challenge infection.

NOT Open Access | Identification of Selective Inhibitors of Plasmodium N-Myristoyltransferase by High-Throughput Screening

January 15, 2020 - 09:28 -- NOT Open Access
Harupa A, De Las Heras L, Colmenarejo G, Lyons-Abbott S, Reers A, Caballero Hernandez I, Chung CW, Charter D, Myler PJ, Fernández-Menéndez RM, Calderón F, Palomo S, Rodríguez B, Berlanga M, Herreros-Avilés E, Staker BL, Fernández Álvaro E, Kaushansky A
J Med Chem. 2020 Jan 8.

New drugs that target Plasmodium species, the causative agents of malaria, are needed. The enzyme N-myristoyltransferase (NMT) is an essential protein, which catalyzes the myristoylation of protein substrates, often to mediate membrane targeting. We screened ∼1.8 million small molecules for activity against Plasmodium vivax (P. vivax) NMT. Hits were triaged based on potency and physicochemical properties and further tested against P. vivax and Plasmodium falciparum (P. falciparum) NMTs. We assessed the activity of hits against human NMT1 and NMT2 and discarded compounds with low selectivity indices.

Identification of Plasmodium dipeptidyl aminopeptidase allosteric inhibitors by high throughput screening

January 15, 2020 - 09:27 -- Open Access
Sanchez MI, de Vries LE, Lehmann C, Lee JT, Ang KK, Wilson C, Chen S, Arkin MR, Bogyo M, Deu E
PLoS ONE 14(12): e0226270

Dipeptidyl aminopeptidases (DPAPs) are cysteine proteases that cleave dipeptides from the N-terminus of protein substrates and have been shown to play important roles in many pathologies including parasitic diseases such as malaria, toxoplasmosis and Chagas’s disease. Inhibitors of the mammalian homologue cathepsin C have been used in clinical trials as potential drugs to treat chronic inflammatory disorders, thus proving that these enzymes are druggable.

Can Plasmodium's tricks for enhancing its transmission be turned against the parasite? New hopes for vector control

January 14, 2020 - 12:10 -- Open Access
Emami SN, Hajkazemian M, Mozūraitis R
Pathogens and Global Health, 2020 Jan 7:1-11

Approximately 120 years ago the link between mosquito and the malaria transmission was discovered. However, even today it remains an open question whether the parasite is able to direct the blood-seeking and feeding behavior of its mosquito vector to maximize the probability of transmission. If the parasite has this ability, could it occur only through the alteration of the vertebrate host’s volatile organic compounds (VOCs) and/or the parasite alteration of the behavior of the infected vector in a manner that favors its transmission?


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