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Genomic 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
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Theileria parasites sequester host eIF5A to escape elimination by host-mediated autophagy
Theileria parasites have evolved mechanisms to evade host cell defenses. Here, Villares et al use an anti-parasite drug to show how intracellular parasites sequester host eIF5A to escape elimination by autophagy pathways.
- Marie Villares
- , Nelly Lourenço
- & Jonathan B. Weitzman
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Q586B2 is a crucial virulence factor during the early stages of Trypanosoma brucei infection that is conserved amongst trypanosomatids
Sleeping sickness caused by African trypanosome parasites induces a chronic, and potentially lethal, infection in humans. Here, the authors uncover a conserved protein, Q586B2, playing an important regulatory role in Trypanosomatid infection establishment.
- Benoit Stijlemans
- , Patrick De Baetselier
- & Carl De Trez
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Natural selection and genetic diversity maintenance in a parasitic wasp during continuous biological control application
Parasitoid wasps are reared and released as biocontrol agents to manage aphids and protect crops. Here, the authors use genomes from 542 wasps to show that, in spite of wide scale release of low-diversity captive individuals, diversity in wild populations is maintained.
- Bingyan Li
- , Yuange Duan
- & Hu Li
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Predicting the risk and speed of drug resistance emerging in soil-transmitted helminths during preventive chemotherapy
Resistance to chemotherapy for soil-transmitted helminth infection has been detected in veterinary settings but not yet in human infections. Here, the authors investigate the risk of resistance in humans and how it may change as a result of scaling-up preventative deworming programs.
- Luc E. Coffeng
- , Wilma A. Stolk
- & Sake J. de Vlas
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PRL2 regulates neutrophil extracellular trap formation which contributes to severe malaria and acute lung injury
Excessive inflammatory responses contribute to severe malaria. Here, Du et al, show that the protein tyrosine phosphatase PRL2 contributes to neutrophil activation and extracellular trap release in an experimental model of severe malaria.
- Xinyue Du
- , Baiyang Ren
- & Zhaojun Wang
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Multiple pathways for glucose phosphate transport and utilization support growth of Cryptosporidium parvum
The parasite Cryptosporidium has a reduced genome and is dependent on glycolysis for energy production. Here, Xu et al demonstrate that multiple pathways and glucose transporters exist in this organism which are essential for growth and facilitate energy acquisition and utilization.
- Rui Xu
- , Wandy L. Beatty
- & L. David Sibley
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Antigen recognition reinforces regulatory T cell mediated Leishmania major persistence
Upon skin infection with the parasite Leishmania major, a small group of infected cells remain present in healed skin. Here, Zayats et al. show that regulatory T cells focused towards parasite-derived proteins have strong suppressive capabilities and facilitate parasite persistence in vivo.
- Romaniya Zayats
- , Zhirong Mou
- & Thomas T. Murooka
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Cytolytic 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
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IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection
Trypanosome brucei is known to colonise the subcutaneous white adipose tissue and the interaction with the cellular locale could play key roles in pathogenesis and host response. Here the author’s use single cell approaches and in vivo animal models, and show a role for IL-17 in the adipose tissue response and parasite burden in a chronic murine model of infection.
- Matthew C. Sinton
- , Praveena R. G. Chandrasegaran
- & Juan F. Quintana
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Production of leishmanin skin test antigen from Leishmania donovani for future reintroduction in the field
As leishmaniasis control programs and new vaccines are advancing, it is necessary to re-introduce the leishmanin skin test to monitor transmission and immunity. This study describes the generation and validation of a new leishmanin skin test antigen for future re-introduction into endemic countries.
- Ranadhir Dey
- , Jalal Alshaweesh
- & Greg Matlashewski
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Epidemiology 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
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Metabolic heterogeneity of tissue-resident macrophages in homeostasis and during helminth infection
Gauging the in vivo metabolism of immune cells at the single-cell level has proven challenging. Here the authors use spectral flow cytometry to investigate metabolic profiles in tissue-resident macrophages from several organs and changes in response to helminth infection.
- Graham A. Heieis
- , Thiago A. Patente
- & Bart Everts
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CD8+ tissue-resident memory T-cell development depends on infection-matching regulatory T-cell types
Type-1 regulatory T cells promoted the generation of CD8+ tissue-resident memory T (TRM) cells during intracellular infections in the gut. Here, the authors show that the establishment TRM cells more broadly depends on the presence of regulatory T cells matching the type of infection.
- Leandro Barros
- , Daryna Piontkivska
- & Cristina Ferreira
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Neutrophil metalloproteinase driven spleen damage hampers infection control of trypanosomiasis
Trypanosoma brucei infection is characterised by activation of neutrophil associated genes. Here, Pham et al. further dissect the role neutrophils play in tissue pathology, disease outcome and maintenance of adaptive immunity.
- Hien Thi Thu Pham
- , Stefan Magez
- & Magdalena Radwanska
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γδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection
Trypansome brucei infection can result in colonisation of the skin but how this impacts the skin architecture and immune response has not been fully resolved. Here the authors apply a spatially resolved single cell transcriptomics approach in a murine model of infection, and suggest a role for IL-17- producing γδ T cells in the immune response to T. brucei skin infection.
- Juan F. Quintana
- , Matthew C. Sinton
- & Annette MacLeod
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Effect of experimental hookworm infection on insulin resistance in people at risk of type 2 diabetes
A beneficial effect of parasitic worms on metabolic health has been postulated based on epidemiological and animal studies. Here, the authors show in a phase I clinical trial that treatment of people at risk of type 2 diabetes with hookworms is safe and may improve key measures of metabolic health.
- Doris R. Pierce
- , Malcolm McDonald
- & Paul R. Giacomin
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Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo
Only praziquantel is available for treating schistosomiasis, a disease affecting >200 million people. Here, the authors identify compounds active against schistosome infections meeting the criteria for lead progression indicated by WHO with better activity against juvenile worms than praziquantel.
- Valentina Z. Petukhova
- , Sammy Y. Aboagye
- & Pavel A. Petukhov
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Giardia hinders growth by disrupting nutrient metabolism independent of inflammatory enteropathy
Giardia lamblia intestinal infection is independently associated with faltering linear growth in children in low-middle income countries, yet the mechanistic pathway has not been clearly identified. Authors utilise the MAL-ED cohort, and a gnotobiotic murine model, to explain Giardia-induced effects on childhood growth.
- Natasa Giallourou
- , Jason Arnold
- & Luther A. Bartelt
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Pulmonary inflammation promoted by type-2 dendritic cells is a feature of human and murine schistosomiasis
Schistosomiasis, a parasitic helminth infection, causes pulmonary symptoms during acute and chronic infection. Here, Houlder et al characterise the pulmonary immune response and demonstrate the role type 2 dendritic cells play in lung inflammation.
- E. L. Houlder
- , A. H. Costain
- & A. S. MacDonald
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The Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas
This work reveals the diversity and extent of human antibody specificities in Chagas disease and provides a wealth of well-defined antigenic markers for diagnosis and development of serological applications for this neglected infectious disease.
- Alejandro D. Ricci
- , Leonel Bracco
- & Fernán Agüero
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Cryptosporidium uses CSpV1 to activate host type I interferon and attenuate antiparasitic defenses
Cryptosporidium parvum virus 1 is a virus harbored by the pathogenic protozoan Cryptosporidium parvum, and whose role in parasite biology and host interactions remains unclear. Here, Deng et al. demonstrate the impact this virus has on host response and infection outcome.
- Silu Deng
- , Wei He
- & Xian-Ming Chen
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Gasdermin-D activation promotes NLRP3 activation and host resistance to Leishmania infection
Here, de Sá et al. show that Gasdermin-D is transiently activated in Leishmania-infected macrophages and promotes NLRP3 inflammasome activation, but not cell death. Gasdermin-D is cleaved into a noncanonical fragment, indicating that Leishmania subverts Gasdermin-D-mediated host response to establish leishmaniasis.
- Keyla S. G. de Sá
- , Luana A. Amaral
- & Dario S. Zamboni
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Impact of pulmonary African trypanosomes on the immunology and function of the lung
A number of human African trypanosomiasis, or sleeping sickness, patients suffer from respiratory symptoms commonly attributed to cardiac insufficiency. Here, the authors characterise the role of pulmonary Trypanosoma brucei in respiratory infection.
- Dorien Mabille
- , Laura Dirkx
- & Guy Caljon
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IL-33 induces thymic involution-associated naive T cell aging and impairs host control of severe infection
Immunosuppression as a result of severe infection impairs pathogen clearance and can increase susceptibility to secondary infection. Here, the authors dissect how T cell aging and the thymic involution that occurs during this process contribute to immunosuppression and find a key role for IL-33.
- Lei Xu
- , Chuan Wei
- & Xiaojun Chen
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Neutralizing and interfering human antibodies define the structural and mechanistic basis for antigenic diversion
The Plasmodium falciparum Merozoite Surface Protein 1 (MSP-1) is a prime vaccine candidate for malaria. Here, the authors structurally and functionally characterise a panel of naturally acquired MSP-1 specific antibodies to identify one with potent broadly neutralising activity and better understand immune evasion mechanisms.
- Palak N. Patel
- , Thayne H. Dickey
- & Niraj H. Tolia
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Defining the early stages of intestinal colonisation by whipworms
Whipworms are large parasites causing chronic disease in humans and other mammals. Here, the authors show how larvae create tunnels inside the gut lining and reveal the early host response to infection via Isg15 in mice and murine caecaloids.
- María A. Duque-Correa
- , David Goulding
- & Matthew Berriman
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Identifying regions for enhanced control of gambiense sleeping sickness in the Democratic Republic of Congo
Gambiense human African trypanosomiasis (sleeping sickness or gHAT) has been targeted for elimination of transmission by 2030. Here, the authors project impacts of gHAT interventions in the Democratic Republic of the Congo and derive a priority list of health zones requiring enhanced control to achieve this target.
- Ching-I Huang
- , Ronald E. Crump
- & Kat S. Rock
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Cost-effectiveness of sleeping sickness elimination campaigns in five settings of the Democratic Republic of Congo
Gambiense human African trypanosomiasis has been targeted for elimination of transmission by 2030. Here, the authors assess the cost-effectiveness of elimination strategies in the Democratic Republic of the Congo and find that those which lead to elimination of transmission might also be considered cost-effective by conventional thresholds.
- Marina Antillon
- , Ching-I Huang
- & Fabrizio Tediosi
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Different gut microbial communities correlate with efficacy of albendazole-ivermectin against soil-transmitted helminthiases
Little is known about the cause of treatment failure of soil-transmitted helminth infections. Here, the authors show that pre-treatment gut microbial community composition enables predicting treatment outcome for Trichuris trichiura and hookworm infections.
- Pierre H. H. Schneeberger
- , Morgan Gueuning
- & Jennifer Keiser
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Bicyclic azetidines target acute and chronic stages of Toxoplasma gondii by inhibiting parasite phenylalanyl t-RNA synthetase
Current treatments for toxoplasmosis are limited by adverse reactions and inability to cure chronic infections dominated by semi-dormant cyst forms. Here the authors demonstrate the potential of small molecule inhibitors of PheRS for controlling acute and chronic toxoplasmosis.
- Joshua B. Radke
- , Bruno Melillo
- & L. David Sibley
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Emulator-based Bayesian optimization for efficient multi-objective calibration of an individual-based model of malaria
Individual-based models have become important tools in the global battle against infectious diseases, yet model complexity can make calibration challenging. Here, the authors propose a Bayesian optimization framework to calibrate a complex malaria transmission simulator.
- Theresa Reiker
- , Monica Golumbeanu
- & Melissa A. Penny
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Rhesus macaques self-curing from a schistosome infection can display complete immunity to challenge
To date there is only one single drug with modest efficacy and no vaccine available to protect from schistosomiasis. Here, Amaral et al. characterize the self-cure process of rhesus macaques following primary infection and secondary challenge with Schistosoma mansoni to inform future vaccine development studies.
- Murilo Sena Amaral
- , Daisy Woellner Santos
- & Sergio Verjovski-Almeida
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A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes
Mircobial symbionts of mosquitoes can affect transmission of human pathogens. Here, Herren et al. identify a microsporidian symbiont in Anopheles gambiae that impairs transmission without affecting mosquito fecundity or survival.
- Jeremy K. Herren
- , Lilian Mbaisi
- & Steven P. Sinkins
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Coupling chemical mutagenesis to next generation sequencing for the identification of drug resistance mutations in Leishmania
Here, Bhattacharya et al. chemically mutagenize Leishmania and identify genes associated with resistance to miltefosine and paromomycin by next generation sequencing. The study shows that a protein kinase (CDPK1) can mediate resistance to paromomycin by affecting translation.
- Arijit Bhattacharya
- , Philippe Leprohon
- & Marc Ouellette
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Leishmania RNA virus exacerbates Leishmaniasis by subverting innate immunity via TLR3-mediated NLRP3 inflammasome inhibition
NLRP3 activation by Leishmania parasites is critical to the outcome of the disease. Here the authors show that LRV, a virus infecting Leishmania strains associated with more severe human disease, enables the parasite to suppress the inflammasome by activating type 1 interferon through TLR3, which leads to autophagy-mediated NLRP3 degradation.
- Renan V. H. de Carvalho
- , Djalma S. Lima-Junior
- & Dario S. Zamboni
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Cis-regulatory CYP6P9b P450 variants associated with loss of insecticide-treated bed net efficacy against Anopheles funestus
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
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TFF3 interacts with LINGO2 to regulate EGFR activation for protection against colitis and gastrointestinal helminths
TFF3 secretion by goblet cells regulates mucus viscosity and wound healing, but a receptor for TFF3 has not been identified. Here, the authors show that TFF3 binds LINGO2 to de-repress and enhance EGFR signaling that drives wound healing and immunity against helminths.
- Nicole Maloney Belle
- , Yingbiao Ji
- & De’Broski R. Herbert
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Inherent biomechanical traits enable infective filariae to disseminate through collecting lymphatic vessels
Stimuli affecting migration of filaria in host tissues are unclear. Using in situ imaging, Kilarski et al. here show that universal adaptations of nematodes allow Litomosoides sigmodontis infective larvae to mechanically break into pre-collecting lymphatics and follow the direction of flow towards the lymph node.
- Witold W. Kilarski
- , Coralie Martin
- & Melody A. Swartz
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Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis
Cryptosporidium infection can cause severe diarrhea with limited treatment options available. Here, Lunde et al. perform a drug repositioning screen with a library of benzoxaboroles and identify AN7973 as potent inhibitor of intracellular parasite development with good efficacy in murine and neonatal dairy calf disease models.
- Christopher S. Lunde
- , Erin E. Stebbins
- & Christopher D. Huston
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Schistosoma mansoni treatment reduces HIV entry into cervical CD4+ T cells and induces IFN-I pathways
Schistosoma mansoniinfection has been linked with an increased risk of HIV acquisition in women. Here, the authors show that standard S. mansoniinfection treatment causes a reduction of HIV entry into cervical and blood CD4+ T cells, which is sustained for up to two months and is associated with de-repression of IFN-I signaling.
- Sergey Yegorov
- , Vineet Joag
- & Rupert Kaul
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A suite of phenotypic assays to ensure pipeline diversity when prioritizing drug-like Cryptosporidium growth inhibitors
Here, the authors provide a panel of medium-throughput assays to test potential drug candidates against different life cycle stages of Cryptosporidium with the goal to support a drug development pipeline that contains compounds with diverse molecular mechanisms of action.
- Rajiv S. Jumani
- , Muhammad M. Hasan
- & Christopher D. Huston
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The parasitic worm product ES-62 normalises the gut microbiota bone marrow axis in inflammatory arthritis
Gastrointestinal infection with parasitic helminths can protect against mucosal diseases via impacting on the microbiome. Here the authors show that ES-62, a product secreted by a tissue-resident helminth modulates the host gut microbiome to protect against inflammatory arthritis in a mouse model.
- James Doonan
- , Anuradha Tarafdar
- & William Harnett
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Outcomes of controlled human malaria infection after BCG vaccination
Immune activation induces long-term alterations of setpoints, impacting responses to subsequent unrelated stimuli. Here the authors show that volunteers vaccinated with BCG respond to controlled human malaria infection with increased clinical symptoms and an inverse correlation between immune activation markers and parasitemia.
- Jona Walk
- , L. Charlotte J. de Bree
- & Robert W. Sauerwein
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Flagellar cAMP signaling controls trypanosome progression through host tissues
Trypanosoma brucei probably relies on chemotactic signals for movement through tsetse fly tissues, but the molecular basis is unknown. Here, the authors show that flagellar cAMP signaling is required for traversal of the peritrophic matrix and that, without it, parasites are trapped in the midgut lumen.
- Sebastian Shaw
- , Stephanie F. DeMarco
- & Kent L. Hill
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Industrial scale high-throughput screening delivers multiple fast acting macrofilaricides
Parasitic nematodes causing onchocerciasis and lymphatic filariasis rely on a bacterial endosymbiont, Wolbachia, which is a validated therapeutic target. Here, Clare et al. perform a high-throughput screen of 1.3 million compounds and identify 5 chemotypes with faster kill rates than existing anti-Wolbachia drugs.
- Rachel H. Clare
- , Catherine Bardelle
- & Stephen A. Ward
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Helminth-induced IL-4 expands bystander memory CD8+ T cells for early control of viral infection
Parasitic helminth infection is known to impact upon the host response to other bystander inflammatory processes. Here the authors show that IL4 production induced by helminth infection results in expansion of bystander CD8+ memory T cells and enhanced control to viral infection.
- Marion Rolot
- , Annette M. Dougall
- & Benjamin G. Dewals
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Substantiating freedom from parasitic infection by combining transmission model predictions with disease surveys
The decision when to stop an intervention is a critical component of parasite elimination programmes, but reliance on surveillance data alone can be inaccurate. Here, Michael et al. combine parasite transmission model predictions with disease survey data to more reliably determine when interventions can be stopped.
- Edwin Michael
- , Morgan E. Smith
- & Frank O. Richards
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Artemisinin kills malaria parasites by damaging proteins and inhibiting the proteasome
Artemisinin (ART) is a widely used antimalarial drug, but its mechanism of action is poorly understood. Here, Bridgford et al. show that ART kills parasites by a two-pronged mechanism, causing protein damage and compromising proteasome function, and that accumulation of proteasome substrates activates the ER stress response.
- Jessica L. Bridgford
- , Stanley C. Xie
- & Leann Tilley
A giant virus infecting the amoeboflagellate Naegleria