Malaria

  • Article
    | Open Access

    The chemokine CXCL10 is associated with pathogenesis of cerebral malaria in Plasmodium falciparum infection. Here the authors show that P. falciparum produces extracellular vesicles laden with RNAs that are taken up by monocytes resulting in a RIG-I and HUR-1 mediated mechanism of inhibition of CXCL10 protein translation.

    • Yifat Ofir-Birin
    • , Hila Ben Ami Pilo
    •  & Neta Regev-Rudzki
  • Article
    | Open Access

    To understand malaria symptoms, several studies investigate association between parasite’s transcriptome and disease severity. Here, Thomson-Luque et al. reanalyze available transcriptomic data of P. falciparum and find that longer circulation of infected erythrocytes without sequestering to endothelial cells associates with decreasing parasitaemia and less severe disease.

    • Richard Thomson-Luque
    • , Lasse Votborg-Novél
    •  & Silvia Portugal
  • Article
    | Open Access

    Repeating fever is a hallmark of malaria. Here, a large-scale forward genetic screen in malaria-causing Plasmodium falciparum identifies genes associated with parasite tolerance to host fever, including apicoplast targeted isoprenoid biosynthesis—sharing features with artemisinin resistance.

    • Min Zhang
    • , Chengqi Wang
    •  & John H. Adams
  • Article
    | Open Access

    RIFINs are Plasmodium surface antigens that suppress the immune response by binding inhibitory receptors such as LAIR1. Here, Xu et al. characterize the interaction between RIFIN-variable 2 domain and a LAIR1 domain and identify LAIR1-binding RIFINs in several Plasmodium species.

    • Kai Xu
    • , Yiran Wang
    •  & Peter D. Kwong
  • Article
    | Open Access

    Plasmodium vivax generally accounts for a low proportion of malaria cases in Africa, but population-level data on the distribution of infections is limited. Here, the authors use data from the Democratic Republic of the Congo and show that the prevalence is low (~3%) and diffusely spread.

    • Nicholas F. Brazeau
    • , Cedar L. Mitchell
    •  & Jonathan J. Juliano
  • Article
    | Open Access

    Release of freshwater into the oceans as a result of ice sheet melting could impact the distribution of climate-sensitive diseases. Here, the authors show that a rapid ice sheet melting in Greenland could cause an emergence of malaria in Southern Africa whilst transmission risks in West Africa may decline.

    • Alizée Chemison
    • , Gilles Ramstein
    •  & Cyril Caminade
  • Article
    | Open Access

    Applying complexome profiling, Evers et al. unravel the composition of mitochondrial oxidative phosphorylation complexes in P. falciparum asexual and sexual blood stages. Abundance of these complexes differs between both stages, supporting the hypothesis that a mitochondrial metabolic switch is central to gametocyte development and functioning.

    • Felix Evers
    • , Alfredo Cabrera-Orefice
    •  & Taco W. A. Kooij
  • Article
    | Open Access

    Here the authors use single-cell RNA-seq to profile the transmission stages of the human malaria parasite Plasmodium falciparum as it progresses through the Anopheles mosquito. They highlight unique patterns of gene usage throughout this development and identify potential pleiotropic genes that function at multiple life cycle stages.

    • Eliana Real
    • , Virginia M. Howick
    •  & Mara K. N. Lawniczak
  • Article
    | Open Access

    In placental malaria, interactions between parasite protein VAR2CSA and human glycosaminoglycan chondroitin sulfate A (CS) sequesters infected red blood cells in the placenta. Here, the authors provide cryo-EM structures of VAR2CSA and placental CS, identifying molecular interactions that could guide design of placental malaria vaccines.

    • Kaituo Wang
    • , Robert Dagil
    •  & Ali Salanti
  • Article
    | Open Access

    Indoor residual spraying (IRS) of insecticide is one of the primary malaria vector control initiatives, but implementation is limited. Here, the authors show that discontinuation of IRS in Uganda was associated with increased malaria incidence, and introduction of IRS was associated with decreased incidence.

    • Jane F. Namuganga
    • , Adrienne Epstein
    •  & Isabel Rodriguez-Barraquer
  • Article
    | Open Access

    The effect of climate change on highland malaria transmission remains unclear because of increasing and decreasing trends. Here, Rodó et al. analyze malaria case data and climate data for the Ethiopian highlands from 1968 to 2008 and find that changes in temperature and associated climate variability facilitated the effect of interventions at the beginning of the 21st century.

    • Xavier Rodó
    • , Pamela P. Martinez
    •  & Mercedes Pascual
  • Article
    | Open Access

    Plasmodium vivax reticulocyte binding protein 2b (PvRBP2b) is important for invasion of reticulocytes and PvRBP2b antibodies correlate with protection. Here, Chan et al. isolate and characterize anti-PvRBP2b human monoclonal antibodies and describe mechanisms by which these antibodies inhibit invasion.

    • Li-Jin Chan
    • , Anugraha Gandhirajan
    •  & Wai-Hong Tham
  • Article
    | Open Access

    Malaria transmission-blocking vaccines are in development, but roll-out strategies have not been assessed. Here, the authors show that transmission-blocking activity is likely to be higher in the field than in laboratory conditions, and that school-aged children are an important group to target.

    • Joseph D. Challenger
    • , Daniela Olivera Mesa
    •  & Thomas S. Churcher
  • Article
    | Open Access

    Here Arndt et al. establish rotating-crystal magneto-optical detection (RMOD) as a near-point-of-care diagnostic tool for malaria detection and report a sensitivity and specificity of 82% and 84%, respectively, as validated by analyzing a clinical population in a high transmission setting in Papua New Guinea.

    • L. Arndt
    • , T. Koleala
    •  & S. Karl
  • Article
    | Open Access

    Asymptomatic malaria infections contribute to transmission. Here, Sumner et al. infer participant-to-mosquito transmission by sampling naturally-fed mosquitoes from households in Western Kenya and find that asymptomatic infections more than double the odds of transmission to a mosquito compared to symptomatic infections.

    • Kelsey M. Sumner
    • , Elizabeth Freedman
    •  & Steve M. Taylor
  • Article
    | Open Access

    Control of mosquito populations using pesticides is important for malaria elimination, but effects of pesticides on humans aren’t well understood. Here, Prahl et al. show in a cohort of pregnant Ugandan women and their infants that household spraying with bendiocarb affects the fetal immune system and response to vaccination in infancy.

    • Mary Prahl
    • , Pamela Odorizzi
    •  & Margaret E. Feeney
  • Article
    | Open Access

    Here, the authors identify signatures of miRNA expression differentiation associated with Plasmodium falciparum infection and parasitemia in a longitudinal pediatric cohort in Burkina Faso. In particular, expression of several miRNAs known to promote lymphocyte cell death is affected during infection.

    • Mame Massar Dieng
    • , Aïssatou Diawara
    •  & Youssef Idaghdour
  • Article
    | Open Access

    Inflammasome activation plays a role in malaria pathogenesis, but details aren’t well understood. Here, the authors show that caspase-8 is a central mediator of systemic inflammation in rodent malaria and that monocytes from malaria patients express active caspases-1, -4 and -8.

    • Larissa M. N. Pereira
    • , Patrícia A. Assis
    •  & Ricardo T. Gazzinelli
  • Article
    | Open Access

    Plasmodium infection activates signaling pathways in a-nucleated erythrocytes. Here, Adderley et al. use a comprehensive antibody microarray to show that infection extensively modulates host cell signalling and that the host receptor tyrosine kinase c-MET supports Plasmodium falciparum proliferation.

    • Jack D. Adderley
    • , Simona John von Freyend
    •  & Christian Doerig
  • Article
    | Open Access

    Plasmodium falciparum IMP-specific 5′-nucleotidase 1 (PfISN1) is of interest as a potential malaria drug target. Here, the authors report that IMP is a substrate, and ATP an allosteric activator, of PfISN1 and present PfISN1 crystal structures in the ligand-free state and bound to either IMP or ATP.

    • Loïc Carrique
    • , Lionel Ballut
    •  & Nushin Aghajari
  • Article
    | Open Access

    Mosquito-derived xanthurenic acid (XA) is a trigger for gametogenesis of Plasmodium parasites. Here the authors show that the putative amino acid transporter GEP1 is required for XA-stimulated gametogenesis in Plasmodium yoelii and that it interacts with guanylyl cyclase α (GCα), a cGMP synthesizing enzyme in gametocytes.

    • Yuanyuan Jiang
    • , Jun Wei
    •  & Jing Yuan
  • Article
    | Open Access

    The transcription factor PfAP2-G is a key determinant of sexual commitment in Plasmodium falciparum. Here, Josling et al. define the transcriptional regulatory network of PfAP2-G by identifying its DNA binding sites genome-wide, which vary depending on the route of sexual conversion and rely on interactions with the PfAP2-I transcription factor.

    • Gabrielle A. Josling
    • , Timothy J. Russell
    •  & Manuel Llinás
  • Article
    | Open Access

    Duffy binding protein (DBP) of Plasmodium vivax is important for invasion and is a potential vaccine candidate. Here, the authors show that PvDBP gene amplification protects P vivax in vitro against invasion inhibitory human monoclonal antibodies and is associated to infection of patients with PvDBP binding inhibitory antibodies.

    • Jean Popovici
    • , Camille Roesch
    •  & Benoit Witkowski
  • Article
    | Open Access

    Four genome-wide associated loci are currently known for malaria susceptibility. Here, the authors expand on earlier work by combining data from 11 malaria-endemic countries and additional population sequencing informing an African-enriched imputation reference panel, with findings including a previously unreported association on chromosome 6.

    • Gavin Band
    • , Quang Si Le
    •  & Dominic P. Kwiatkowski
  • Article
    | Open Access

    Plasmodium growth is adapted to the reproductive cycle of mosquitoes, but underlying mechanisms are unclear. Here, Lampe et al. show that the blood-meal induced miR-276 balances the termination of the mosquito amino acid catabolism and egg development, providing nutrients for Plasmodium sporozoite development.

    • Lena Lampe
    • , Marius Jentzsch
    •  & Elena A. Levashina
  • Article
    | Open Access

    Relapse, reinfection and recrudescence can all cause recurrent infection after treatment of Plasmodium vivax malaria in endemic areas, but are difficult to distinguish. Here the authors show that they can be differentiated probabilistically and thereby demonstrate the high efficacy of primaquine treatment in preventing relapse.

    • Aimee R. Taylor
    • , James A. Watson
    •  & Nicholas J. White
  • Article
    | Open Access

    Bed nets treated with insecticides have been instrumental in reducing malaria mortality, but insecticide resistance is on the rise. Here, Mugenzi et al. identify genetic variants in the P450 gene CYP6P9b of Anopheles funestus that associate with insecticide resistance and develop a PCR-based diagnostic assay to help identify pyrethroid-resistant strains.

    • Leon M. J. Mugenzi
    • , Benjamin D. Menze
    •  & Charles S. Wondji
  • Article
    | Open Access

    Here, Proto et al. show that human infective Plasmodium falciparum isolates contain an inactivating mutation in the erythrocyte invasion associated gene PfEBA165, while homologues of ape-infective Laverania species are intact, and that expression of intact PfEBA165 is incompatible with parasite growth in human erythrocytes.

    • William R. Proto
    • , Sasha V. Siegel
    •  & Julian C. Rayner
  • Article
    | Open Access

    Pfs25 is a transmission-blocking vaccine candidate for Plasmodium. Here, McLeod et al. analyze the antibody response to Pfs25 in sera from a clinical trial evaluating a Pfs25 vaccine candidate, identify a potent transmission-blocking antibody and determine recognized epitopes on Pfs25.

    • Brandon McLeod
    • , Kazutoyo Miura
    •  & Jean-Philippe Julien
  • Article
    | Open Access

    Severe malaria can be associated with respiratory complications. Here, the authors show that malaria-associated pulmonary vascular damage is a consequence of IFNγ-activated lung endothelial cells capturing, processing, and cross-presenting malaria parasite antigen to specific CD8+ T cells induced during infection.

    • Carla Claser
    • , Samantha Yee Teng Nguee
    •  & Laurent Renia
  • Article
    | Open Access

    Here, Minkah et al. show that, while immunization with replication-competent Plasmodium parasites can confer sterile protection against infection, it also induces a type I interferon response that adversely affects anti-malaria immunity by affecting numbers of protective hepatic CD8 T cells and CD8 T cell function.

    • Nana K. Minkah
    • , Brandon K. Wilder
    •  & Stefan H. I. Kappe
  • Article
    | Open Access

    Investigating malaria transmission at three sites in Uganda, the authors identify super-spreaders and show that super-spreading is more prominent at low-intensity transmission, and that seasonality and environmental stochasticity have a greater influence on super-spreading.

    • Laura Cooper
    • , Su Yun Kang
    •  & David L. Smith
  • Article
    | Open Access

    Here, the authors show that reticulocytes derived from immortalized erythroblasts support invasion and development of Plasmodium falciparum and use CRISPR-mediated gene knockout and complementation of an invasion receptor to demonstrate utility of this model system for research in malaria invasion.

    • Timothy J. Satchwell
    • , Katherine E. Wright
    •  & Jake Baum
  • Article
    | Open Access

    Present understanding of Plasmodium vivax biology is hampered by its inability to grow in vitro. Here, the authors developed an in vitro culture of its simian counterpart, P. cynomolgi, which shares morphological and phenotypic similarities with P. vivax, initiating a new phase in vivax research.

    • Adeline C. Y. Chua
    • , Jessica Jie Ying Ong
    •  & Pablo Bifani
  • Article
    | Open Access

    Primaquine (PQ) is a widely used anti-malaria drug, but its mechanism of action is unclear. Here, Camarda et al. show that PQ’s activity against liver and sexual Plasmodium stages depends on generation of hydroxylated-PQ metabolites (OH-PQm), which, undergoing further reactions, results in production of H2O2.

    • Grazia Camarda
    • , Piyaporn Jirawatcharadech
    •  & Giancarlo A. Biagini
  • Article
    | Open Access

    Understanding genomic variation in Plasmodium falciparum parasites and inferring migration patterns can guide malaria elimination strategies. Using genome-wide data for 1722 parasites collected from 54 districts, the authors use identity-by-descent approaches to estimate regional parasite migration and spread of artemisinin drug resistance.

    • Amol C. Shetty
    • , Christopher G. Jacob
    •  & Marie A. Onyamboko
  • Article
    | Open Access

    Foreign aid is necessary to control tropical diseases in endemic countries. Here the authors outline the steps taken to control malaria in Africa since 2000 and present an economic model to propose that US$25−30 per capita will be needed to avoid a disease trap.

    • Eric Maskin
    • , Célestin Monga
    •  & Jean-Claude Berthélemy