Featured
-
-
Article
| Open AccessStrong positive selection biases identity-by-descent-based inferences of recent demography and population structure in Plasmodium falciparum
Identity-by-descent (IBD) is used to infer malaria parasite population demography, but positive selection imposed by drug pressure can bias IBD estimates. This study shows that strong selection distorts IBD distributions impacting downstream inferences and presents an approach to correct these biases.
- Bing Guo
- , Victor Borda
- & Shannon Takala-Harrison
-
Article
| Open AccessBeyond the microcirculation: sequestration of infected red blood cells and reduced flow in large draining veins in experimental cerebral malaria
Cerebral malaria can lead to fatal brain swelling. Oelschlegel et al. find infected red blood cells and reduced flow in large draining cerebral veins in mouse model of cerebral malaria, suggesting that impaired venous efflux could cause the swelling.
- A. M. Oelschlegel
- , R. Bhattacharjee
- & G. Nishanth
-
Article
| Open AccessGenomic malaria surveillance of antenatal care users detects reduced transmission following elimination interventions in Mozambique
Routine sampling of pregnant women at first antenatal care (ANC) visits could be used for malaria surveillance. Here, the authors compare the genetic structure of Plasmodium falciparum parasite populations between samples from first ANC users and children from the community in Mozambique, and show that it can inform about changes in transmission beyond epidemiological data.
- Nanna Brokhattingen
- , Glória Matambisso
- & Alfredo Mayor
-
Article
| Open AccessMalaria blood stage infection suppresses liver stage infection via host-induced interferons but not hepcidin
Blood and liver stages of malaria parasites can affect each other, but it’s not clear how this may affect live-attenuated whole parasite vaccination. Here the authors show that malaria parasite blood stage infection subdues new infection and vaccination by suppressing growth of its liver stage via host cytokines.
- Hardik Patel
- , Nana K. Minkah
- & Stefan H. I. Kappe
-
Article
| Open AccessGene expression analyses reveal differences in children’s response to malaria according to their age
Here the authors use dual RNA sequencing to characterize host and parasite gene expression from 136 Malian children with symptomatic Plasmodium falciparum infection. They find that parasitemia levels correlate with neutrophil and T cell levels and that the child’s age correlates with innate immune gene expression as well as gametocyte levels.
- Kieran Tebben
- , Salif Yirampo
- & David Serre
-
Article
| Open AccessFlexible and cost-effective genomic surveillance of P. falciparum malaria with targeted nanopore sequencing
Genomic surveillance of Plasmodium falciparum could improve monitoring of drug resistance, but implementation has been hampered due to the large and complex genome. Here, de Cesare et al. develop a flexible and cost-effective nanopore sequencing approach to detect drug resistance and diagnostic escape for P. falciparum malaria.
- Mariateresa de Cesare
- , Mulenga Mwenda
- & Jason A. Hendry
-
Article
| Open AccessAssessing emergence risk of double-resistant and triple-resistant genotypes of Plasmodium falciparum
Emergence of malaria parasites resistant to artemisinin has prompted the need for new drug regimens to ensure effective treatment. In this simulation study, the authors evaluate the risk of multidrug resistance under regimens with either concurrent or cyclic use of different first-line therapies.
- Eric Zhewen Li
- , Tran Dang Nguyen
- & Maciej F. Boni
-
Article
| Open AccessEnvironmental modulation of global epistasis in a drug resistance fitness landscape
Global epistasis can be used to reconstruct fitness landscapes and infer adaptive trajectories. Here, the authors investigate how environmental variation impacts patterns of global epistasis, finding that global epistasis in the malaria parasite P. falciparum can be modulated by drug concentration in the environment.
- Juan Diaz-Colunga
- , Alvaro Sanchez
- & C. Brandon Ogbunugafor
-
Article
| Open AccessCytolytic circumsporozoite-specific memory CD4+ T cell clones are expanded during Plasmodium falciparum infection
It is important to understand why some individuals in endemic regions acquire natural immunity against malaria while others remain susceptible. Here authors show that during episodes of Plasmodium falciparum malaria, circumsporozoite-specific cytolytic memory CD4+ T cells are clonally expanded in patients, and those with clinical immunity demonstrate reduction in the chemotactic and inhibitory receptor expression in ZEB2+ memory CD4+ T cells.
- Raquel Furtado
- , Mahinder Paul
- & Grégoire Lauvau
-
Article
| Open AccessSingle cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets
The use of single cell sequencing has enabled more detailed analysis of the immune response to infection. Here the authors characterise the immune response to malaria infection in an endemic region using single cell transcriptomics indicating regulatory signatures associated with infection.
- Nicholas L. Dooley
- , Tinashe G. Chabikwa
- & Michelle J. Boyle
-
Article
| Open AccessMalaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal
Senegal has initiated a national sentinel surveillance program for malaria parasite genetics. Here, the authors report data from the first year of the program and use it to investigate local malaria incidence, patterns of transmission, and genetic loci under selection.
- Stephen F. Schaffner
- , Aida Badiane
- & Sarah K. Volkman
-
Article
| Open AccessEpidemiology of Plasmodium malariae and Plasmodium ovale spp. in Kinshasa Province, Democratic Republic of Congo
Non-falciparum malaria may cause a significant disease burden in highly endemic regions, but epidemiological data is limited. In this study, the authors estimate the incidence and prevalence of P. malariae, P. ovale spp., in Kinshasa, Democratic Republic of Congo and compare to P. falciparum, which known to be common in the region.
- Rachel Sendor
- , Kristin Banek
- & Jonathan B. Parr
-
Article
| Open AccessExtracellular vesicles could be a putative posttranscriptional regulatory mechanism that shapes intracellular RNA levels in Plasmodium falciparum
Here, Kioko et al. describe a putative posttranscriptional RNA regulation mechanism involving secreted extracellular vesicles to maintain the intracellular steady-state RNA levels during the asexual blood stage of malaria parasites.
- Mwikali Kioko
- , Alena Pance
- & Abdirahman I. Abdi
-
Article
| Open AccessClinically relevant atovaquone-resistant human malaria parasites fail to transmit by mosquito
Malaria parasites from patients who fail atovaquone therapies are highly drug-resistant, with mutations at Y268 in cytochrome b. Here the authors show that this mutation results in multiple defects in the parasite’s development and prevents transmission from mosquitoes to mice.
- Victoria A. Balta
- , Deborah Stiffler
- & Theresa A. Shapiro
-
Article
| Open AccessStructure guided mimicry of an essential P. falciparum receptor-ligand complex enhances cross neutralizing antibodies
The AMA1-RON2 complex is important for Plasmodium falciparum invasion and a potential vaccine target. Here the authors engineer a fusion protein of AMA1 and RON2 loop that mimics the receptor-ligand complex and show that it induces antibodies that neutralize non-vaccine type parasites.
- Sean Yanik
- , Varsha Venkatesh
- & Prakash Srinivasan
-
Comment
| Open AccessZoonotic malaria requires new policy approaches to malaria elimination
WHO guidelines for classification of malaria elimination in a country require that the risk of human infection from zoonotic, as well as nonzoonotic, malaria parasites is negligible. In this Comment, the authors discuss the implications of this policy for countries, such as Malaysia, with no recent reported nonzoonotic cases but ongoing zoonotic transmission.
- Kimberly M. Fornace
- , Chris J. Drakeley
- & Kamruddin Ahmed
-
Article
| Open AccessEstimating the burden of severe malarial anaemia and access to hospital care in East Africa
Severe malarial anaemia is a clinical manifestation of severe malaria, with the burden highly concentrated in children. In this work, authors statistically model household survey and in-hospital data to estimate the proportion of severe malarial anaemia cases that access hospital care.
- Peter Winskill
- , Aggrey Dhabangi
- & Lucy C. Okell
-
Article
| Open AccessStructure-based design of a strain transcending AMA1-RON2L malaria vaccine
Here the authors use structure-based design to engineer a single component immunogen that mimics the malaria parasite AMA1-RON2 complex required for invasion of host cells, and show that it elicits a potent strain-transcending antibody response in rats.
- Palak N. Patel
- , Thayne H. Dickey
- & Niraj H. Tolia
-
Article
| Open AccessOuter membrane vesicles from a mosquito commensal mediate targeted killing of Plasmodium parasites via the phosphatidylcholine scavenging pathway
Here, Gao and colleagues show that the mosquito symbiotic bacterium Serratia ureilytica produces vesicles that deliver an anti-Plasmodium effector to the Plasmodium parasite and render mosquitoes resistant to the infection of malaria parasites.
- Han Gao
- , Yongmao Jiang
- & Sibao Wang
-
Article
| Open AccessElucidation of the low-expressing erythroid CR1 phenotype by bioinformatic mining of the GATA1-driven blood-group regulome
This study provides a systematic approach to explore how blood group expression is regulated by transcription factors. As proof-of-principle, the genetic basis underlying the very low levels of CR1 on red cells of the Helgeson phenotype is explained.
- Ping Chun Wu
- , Yan Quan Lee
- & Martin L. Olsson
-
Article
| Open AccessDevelopment of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures
Suitable in vitro models allowing to assess Plasmodium liver stage development are still limited. Here, Yang et al. show that hepatocytes derived from human hepatocyte organoids (HepOrgs) can support P. falciparum development. This allowed for the identification and validation of the importance of the host factor, scavenger receptor B1 (SRB1), in parasite development.
- Annie S. P. Yang
- , Devanjali Dutta
- & Robert W. Sauerwein
-
Article
| Open AccessPreventing antimalarial drug resistance with triple artemisinin-based combination therapies
Triple artemisinin-based combination therapies have shown high efficacy for treatment of malaria in preliminary studies. Here, the authors use mathematical modelling to assess whether these therapies could also delay the emergence and spread of antimalarial drug resistance when compared against frontline therapies.
- Tran Dang Nguyen
- , Bo Gao
- & Ricardo Aguas
-
Article
| Open AccessHearing of malaria mosquitoes is modulated by a beta-adrenergic-like octopamine receptor which serves as insecticide target
Malaria mosquitoes use their ears to detect the flight tones of mating partners in the swarm as part of the courtship ritual. Here, the authors describe the auditory role of octopamine as a modulator of auditory plasticity in malaria mosquitoes and identify the main receptors involved in this process.
- Marcos Georgiades
- , Alexandros Alampounti
- & Marta Andrés
-
Article
| Open AccessDetecting temporal and spatial malaria patterns from first antenatal care visits
Pregnant people visiting antenatal clinics may represent a useful sentinel surveillance population for monitoring infections such as malaria. Here, the authors investigate the potential of this approach by comparing malaria prevalence in pregnant people and children living in the same area of southern Mozambique.
- Arnau Pujol
- , Nanna Brokhattingen
- & Alfredo Mayor
-
Article
| Open AccessMultiplexed ddPCR-amplicon sequencing reveals isolated Plasmodium falciparum populations amenable to local elimination in Zanzibar, Tanzania
Sequencing malaria parasites from low density infections in small amounts of dried blood is important for large-scale genomic surveillance. Here, the authors develop and validate a highly multiplexed droplet digital PCR-based amplicon deep sequencing assay and apply it to data from Zanzibar, Tanzania.
- Aurel Holzschuh
- , Anita Lerch
- & Cristian Koepfli
-
Article
| Open AccessNo evidence of sustained nonzoonotic Plasmodium knowlesi transmission in Malaysia from modelling malaria case data
Plasmodium knowlesi is a zoonotic malaria parasite that can infect humans, but whether human-mosquito-human transmission occurs is not known. Here, the authors use data from Malaysia and show, through mathematical modelling, that sustained non-zoonotic transmission is unlikely to be occurring in this setting.
- Kimberly M. Fornace
- , Hillary M. Topazian
- & Chris Drakeley
-
Article
| Open AccessStructural basis of epitope selectivity and potent protection from malaria by PfCSP antibody L9
The cryo-EM structure of the highly potent malaria antibody L9 reveals a key role of light-chain derived homotypic interactions in antigen binding and parasite inhibition, enabling antibody engineering and next-generation malaria vaccine design.
- Gregory M. Martin
- , Monica L. Fernández-Quintero
- & Andrew B. Ward
-
Article
| Open AccessModelling the impact of interventions on imported, introduced and indigenous malaria infections in Zanzibar, Tanzania
Malaria elimination is defined by WHO as the absence of recent indigenous cases in an area. In this study, the authors develop a metapopulation model that identifies indigenous cases and use it to investigate the likelihood of malaria elimination in Zanzibar under different intervention scenarios.
- Aatreyee M. Das
- , Manuel W. Hetzel
- & Nakul Chitnis
-
Article
| Open AccessPlasmodium falciparum has evolved multiple mechanisms to hijack human immunoglobulin M
Malaria parasites use various molecular tactics to hijack IgM antibodies and escape the human immune system.
- Chenggong Ji
- , Hao Shen
- & Junyu Xiao
-
Article
| Open AccessPlasmepsin X activates the PCRCR complex of Plasmodium falciparum by processing PfRh5 for erythrocyte invasion
Plasmodium falciparum is known to secrete an aspartic protease called plasmepsin X. Here, Triglia et al present a characterisation of plasmepsin X function in the context of erythrocyte invasion and its regulation of PCRCR, a complex that anchors the leading vaccine candidate PfRh5 to the parasite surface.
- Tony Triglia
- , Stephen W. Scally
- & Alan F. Cowman
-
Article
| Open AccessPotent acyl-CoA synthetase 10 inhibitors kill Plasmodium falciparum by disrupting triglyceride formation
Drug resistance to current antimalarials is rising and new drugs and targets are urgently needed. Here the authors identify Plasmodium falciparum acyl-CoA synthetase 10 as a new target whose inhibition leads to a decrease in triacylglycerols.
- Selina Bopp
- , Charisse Flerida A. Pasaje
- & Dyann F. Wirth
-
Article
| Open AccessNon-falciparum malaria infection and IgG seroprevalence among children under 15 years in Nigeria, 2018
Nigeria has a high burden of malaria which mostly results from Plasmodium falciparum infection, but other species are also endemic. Here, the authors estimate the prevalence of active infection and previous exposure to P malariae, P ovale, and P vivax in children in Nigeria in 2018 and determine risk factors.
- Camelia Herman
- , Colleen M. Leonard
- & Eric Rogier
-
Article
| Open AccessQuantifying the direct and indirect protection provided by insecticide treated bed nets against malaria
Long lasting insecticide treated mosquito nets (LLINs) provide protection from malaria through both direct effects to the user and indirect community-level effects. Here, the authors use mathematical modelling to assess the relative contributions of these effects under different insecticide resistance and LLIN usage scenarios.
- H. Juliette T. Unwin
- , Ellie Sherrard-Smith
- & Azra C. Ghani
-
Article
| Open AccessProjected health impact of post-discharge malaria chemoprevention among children with severe malarial anaemia in Africa
Trial data have shown that post-discharge malaria chemoprevention (PDMC) reduces the risk of readmission and death in children previously hospitalised with severe malarial anaemia. Here, the authors use mathematical modelling to estimate the potential epidemiological impacts of PDMC in malaria-endemic countries in Africa.
- Lucy C. Okell
- , Titus K. Kwambai
- & Amani Thomas Mori
-
Article
| Open AccessThe overlapping burden of the three leading causes of disability and death in sub-Saharan African children
In this disease mapping study, the authors estimate disability-adjusted life year rates for three of the major causes of mortality for children under five 43 countries in sub-Saharan Africa. They identify significant heterogeneity at the subnational level, highlighting the need for a targeted intervention approach.
- Robert C. Reiner Jr.
- , Catherine A. Welgan
- & Simon I. Hay
-
Article
| Open AccessThe prognostic and diagnostic value of intraleukocytic malaria pigment in patients with severe falciparum malaria
Malaria diagnosis by microscopy provides valuable rapid diagnostic and prognostic information, which is critical to clinical management. In this work, authors carry out a meta-analysis on the prognostic and diagnostic value of polymorphonuclear leukocytes and monocytes containing malaria pigment in peripheral blood film counts taken from patients with severe malaria.
- Ketsanee Srinamon
- , James A. Watson
- & Nicholas J. White
-
Article
| Open AccessA G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin
In a recent clinical trial for oral administration of cipargamin in individuals with malaria, there was an emergence of recrudescent parasites with a G358S mutation in PfATP4. In this work, the authors investigate the effect of this mutation on the function of the ATPase, on parasite growth and susceptibility to antimalarial drugs.
- Deyun Qiu
- , Jinxin V. Pei
- & Adele M. Lehane
-
Article
| Open AccessStructure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies
Pfs48/45, a surface protein of Plasmodium falciparum, is a promising anti-malarial vaccine candidate whose structure is not entirely resolved. Here, the authors present the structure of the full-length molecule, and characterise the binding and activity of transmission blocking antibodies.
- Kuang-Ting Ko
- , Frank Lennartz
- & Matthew K. Higgins
-
Matters Arising
| Open AccessReply to: Relationship of circulating Plasmodium falciparum lifecycle stage to circulating parasitemia and total parasite biomass
- Richard Thomson-Luque
- , Lasse Votborg-Novél
- & Silvia Portugal
-
Article
| Open AccessAge-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children
Despite being key drivers of protective antibodies against malaria, little is known regarding the host and parasite factors that influence CD4 T-follicular helper cell and antibody development. Authors utilise samples from a study of children living in an area of high malaria transmission in Uganda, to characterize Tfh cells and functional antibodies to multiple parasites stages.
- Jo-Anne Chan
- , Jessica R. Loughland
- & Michelle J. Boyle
-
Article
| Open AccessHumanized mice for investigating sustained Plasmodium vivax blood-stage infections and transmission
Plasmodium vivax is the most widespread human malaria parasite but due to its tropism for immature red blood cells in vitro culturing and studies are difficult. Here, LuizaBatista et al. generate a humanized mouse supporting human erythropoiesis and allowing asexual and sexual development of P. vivax in bone marrow and peripheral blood, as well as transmission to mosquitoes.
- Camilla Luiza-Batista
- , Sabine Thiberge
- & Sylvie Garcia
-
Article
| Open AccessPhagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria
Here the authors show that antibody-dependent phagocytosis of ring-stage P. falciparum parasites is mediated by merozoite antigens and is a strong predictor of protection following challenge in a controlled human malaria infection study in semi-immune Kenyan adults.
- Fauzia K. Musasia
- , Irene N. Nkumama
- & Faith H. A. Osier
-
Article
| Open AccessSelective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo
During the erythrocyte (RBC) stage of P. falciparum infection variant surface antigens (VSAs) such as PfEMP1s and RIFINs expressed on RBCs are important for infection and evasion of host innate immune system. Here, Chew et al. use a NSG mouse model, which is deficient in B, T and NK cells but retains macrophages, to show that PfEMP1 surface expression is required for in vivo adaptation as well as in vitro evasion of macrophage phagocytosis.
- Marvin Chew
- , Weijian Ye
- & Peter Preiser
-
Article
| Open AccessMalaria parasite heme biosynthesis promotes and griseofulvin protects against cerebral malaria in mice
Malaria parasite heme pathway is non-essential for blood stages, but essential for mosquito and liver stages. Here, the authors show that heme pathway promotes cerebral pathogenesis by enhancing hemozoin formation and that targeting it with griseofulvin inhibits cerebral malaria in mice.
- Manjunatha Chandana
- , Aditya Anand
- & Viswanathan Arun Nagaraj
-
Article
| Open AccessInferring the epidemiological benefit of indoor vector control interventions against malaria from mosquito data
Estimating the effectiveness of malaria vector control interventions has typically relied on resource-intensive cluster randomised trials. Here, the authors estimate changes in malaria prevalence using entomological data from experimental hut trials, which may provide an alternative route to approval of interventions in some situations.
- Ellie Sherrard-Smith
- , Corine Ngufor
- & Thomas S. Churcher
-
Article
| Open AccessHost lung microbiota promotes malaria-associated acute respiratory distress syndrome
The reasons why malaria manifests with a variety of well-recognized clinical phenotypes remain poorly understood. Here, using distinct rodent models, the authors reveal that the microbiota colonizing the lung promotes respiratory distress syndrome and mortality during malaria infections.
- Debanjan Mukherjee
- , Ângelo Ferreira Chora
- & Maria M. Mota
-
Article
| Open AccessPlasmodium falciparum 7G8 challenge provides conservative prediction of efficacy of PfNF54-based PfSPZ Vaccine in Africa
Here the authors show that controlled human malaria infection with a Brazilian parasite highly divergent from vaccine and West African field strains can provide estimates of vaccine efficacy in Mali, and could replace field testing, streamlining vaccine development.
- Joana C. Silva
- , Ankit Dwivedi
- & Stephen L. Hoffman
-
Article
| Open AccessThe impact of malaria-protective red blood cell polymorphisms on parasite biomass in children with severe Plasmodium falciparum malaria
Numerous candidate malaria protective gene polymorphisms have been proposed. Here, Uyoga et al. investigate associations between malaria-protective red blood cell polymorphisms and total parasite biomass estimated from plasma concentrations of PfHRP2, in a cohort of Kenyan children suffering from severe malaria. They suggest that plasma PfHRP2 and the ratio of the plasma PfHRP2 to the peripheral parasite density (sequestration index) as powerful quantitative phenotypic traits for severe malaria.
- S. Uyoga
- , J. A. Watson
- & T. N. Williams
-
Comment
| Open AccessLearnings from Thailand in building strong surveillance for malaria elimination
On the cusp of Plasmodium falciparum (Pf) elimination, Thailand is accelerating towards zero malaria by 2024. This commentary reviews the heart of its success—effective surveillance—and what else may be needed to reach zero on time.
- Jui A. Shah