Review
Immunology
Annemarie Voorberg-van der Wel, Clemens H. M. Kocken, Anne-Marie Zeeman
Summary: Recent studies on liver stage malaria parasite-host interactions have shed light on the intricate cross-talk between the parasite and its mammalian host, particularly focusing on the interactions between hypnozoites and hepatocytes. Understanding these interactions may help identify factors that could awaken dormant parasite reservoirs, potentially leading to the total eradication of malaria.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biology
Abdirahman Abdi, Fiona Achcar, Lauriane Sollelis, Joao Luiz Silva-Filho, Kioko Mwikali, Michelle Muthui, Shaban Mwangi, Hannah W. Kimingi, Benedict Orindi, Cheryl Andisi Kivisi, Manon Alkema, Amrita Chandrasekar, Peter C. Bull, Philip Bejon, Katarzyna Modrzynska, Teun Bousema, Matthias Marti
Summary: The malaria parasite life cycle involves asexual replication in human blood and differentiation into gametocytes for transmission to mosquitoes. Host factors influence the commitment to differentiate into gametocytes, but the exact mechanism is still unclear. In this study, we analyzed data from 828 children in Kenya over 18 years to understand the relationship between host immunity, parasite growth, and transmission investment. We found that reduced plasma lysophosphatidylcholine levels, which are associated with inflammatory responses, are correlated with increased transmission investment and reduced asexual replication.
Editorial Material
Gastroenterology & Hepatology
Debashree Goswami, Nana K. Minkah, Stefan H. I. Kappe
Summary: Malaria caused by Plasmodium parasite species is a significant global health burden, with the majority of cases reported in sub-Saharan Africa. The infection begins with a mosquito bite, where sporozoites enter the liver cells and develop into liver stages. Recent advancements in research have provided insights into the liver stage biology and immunology, particularly for the two most important human malaria parasites, P. falciparum and P. vivax.
JOURNAL OF HEPATOLOGY
(2022)
Article
Multidisciplinary Sciences
Raquel A. Rodrigues, Gabriel M. F. Felix, Mauro Pichorim, Patricia A. Moreira, Erika M. Braga
Summary: The study investigated avian haemosporidian parasites in a protected area in northeastern Brazil, showing that migration and temperature may predict parasite prevalence. Individual-level traits and other species-specific factors were not related to infection probability.
Article
Microbiology
Lianne I. M. Lansink, Oliver P. Skinner, Jessica A. Engel, Hyun Jae Lee, Megan S. F. Soon, Cameron G. Williams, Arya SheelaNair, Clara P. S. Pernold, Pawat Laohamonthonkul, Jasmin Akter, Thomas Stoll, Michelle M. Hill, Arthur M. Talman, Andrew Russell, Mara Lawniczak, Xiaoxiao Jia, Brendon Chua, Dovile Anderson, Darren J. Creek, Miles P. Davenport, David S. Khoury, Ashraful Haque
Summary: Understanding how host inflammatory responses affect malaria parasite maturation is important. This study found that systemic host inflammation caused by innate immune stimulus or acute Plasmodium infection slows down parasite progression and inhibits maturation in vitro. The researchers also identified candidate inhibitory metabolites in the plasma that may impair parasite growth in vivo.
Article
Microbiology
Clare K. Cimperman, Mirna Pena, Sohret M. Gokcek, Brandon P. Theall, Meha V. Patel, Anisha Sharma, ChenFeng Qi, Daniel Sturdevant, Louis H. Miller, Patrick L. Collins, Susan K. Pierce, Munir Akkaya
Summary: Hundreds of thousands of lives are lost each year due to brain damage caused by malaria. The majority of these deaths occur in sub-Saharan African children. Host genetic background plays a crucial role in determining the course and outcome of the disease.
Review
Immunology
Erica M. Pasini, Clemens H. M. Kocken
Summary: This article reviews the modeling of relapsing parasites Plasmodium vivax and Plasmodium ovale in non-human primates, highlighting the contribution of these models to our current understanding of the factors that govern parasite-host interactions.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Microbiology
Kelly T. Rios, Taylor M. Dickson, Scott E. Lindner
Summary: In this study, we have identified a significant problem in the conduct of many studies on the sexual stages of rodent malaria parasites. The routine method of isolating gametocytes in rodent-infectious malaria models through drug treatment with sulfadiazine not only kills asexual blood-stage parasites but also has a substantial impact on host-to-vector transmission.
Article
Biochemical Research Methods
Aleena Das, Welka Sahu, Deepak Kumar Ojha, K. Sony Reddy, Mrutyunjay Suar
Summary: An untargeted metabolomics approach was used to identify the changes in metabolic pathways and metabolites in the serum of mice with different pathological stages of malaria. The study provides insights into the host biology during malaria and could be helpful for the selection of animal models for evaluating diagnostic and therapeutic interventions against malaria.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Microbiology
Danielle Stanisic, Mei-Fong Ho, Reshma Nevagi, Emily Cooper, Maddison Walton, Md Tanjir Islam, Waleed M. Hussein, Mariusz Skwarczynski, Istvan Toth, Michael F. Good
Summary: Malaria vaccine research has shifted towards whole-parasite vaccines, which present a broad repertoire of antigens to the immune system to limit antigenic polymorphism. This study developed an enhanced liposomal vaccine that induced protective immune responses in mice and strong cellular immune responses, making significant progress towards evaluating the vaccine in clinical trials.
Article
Chemistry, Medicinal
Elina Lidumniece, Chrislaine Withers-Martinez, Fiona Hackett, Michael J. Blackman, Aigars Jirgensons
Summary: The widespread resistance to current antimalarial therapies highlights the need for new classes of drugs with different mechanisms of action. The subtilisin-like serine protease SUB1 is a potential target for drugs aimed at disrupting the asexual blood stage of the malaria parasite. This mini-perspective provides an overview of SUB1's function and structure, and summarizes the published inhibitors of SUB1, which were discovered using both rational design and screening methods.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biology
Emily R. Ebel, Frans A. Kuypers, Carrie Lin, Dmitri A. Petrov, Elizabeth S. Egan
Summary: The study on 121 healthy donors of African ancestry found that various genes and phenotypes related to red blood cell variation were closely associated with the adaptability of Plasmodium falciparum within red blood cells, indicating globally widespread variations play a role in modulating parasite fitness.
Article
Microbiology
Coralie Boulet, Ghizal Siddiqui, Taylah L. Gaynor, Christian Doerig, Darren J. Creek, Teresa G. Carvalho
Summary: The development of antimalarial drug resistance poses a challenge to malaria elimination progress, with host-directed therapies (HDT) and drug repurposing offering promising strategies for the development of new antimalarials. Research suggests that host BCL-x(L) plays a critical role in malaria development, providing new insights for the development of host-directed antimalarial therapies and drug repurposing efforts.
Article
Immunology
Mohd Kamil, Gozde Deveci, Umit Y. Kina, Stefan H. Kappe, Ahmed S. Aly
Summary: The study demonstrates that axenic liver stages serve as a novel live whole parasite malaria vaccine platform, providing effective protection through subcutaneous immunization without infecting the host.
Review
Microbiology
Silvio Paone, Anna Olivieri
Summary: Apicomplexa parasites modify the host cell environment and manipulate the host cytoskeleton and organelles to adapt to their parasitic lifestyle. Small GTPases play a crucial role in these processes and could be potential targets for novel host-targeted therapies against Apicomplexa infections.
Article
Biochemistry & Molecular Biology
Diana Moita, Helena Nunes-Cabaco, Antonio M. Mendes, Miguel Prudencio
Summary: Efforts have been made to develop efficient vaccines against malaria, with Whole-sporozoite (Wsp) vaccines showing promise in inducing immune responses against Plasmodium parasites. Various approaches for Wsp PE vaccination are currently under evaluation, with clinical trials focusing on assessing protective efficacy and investigating immune responses.
Article
Chemistry, Medicinal
Ana Teresa Silva, Isabel S. Oliveira, Joana Gomes, Luisa Aguiar, Diana Fontinha, Denise Duarte, Fatima Nogueira, Miguel Prudencio, Eduardo F. Marques, Catia Teixeira, Ricardo Ferraz, Paula Gomes
Summary: By combining room-temperature ionic liquids derived from primaquine and cinnamic acids with natural fatty acids, novel surface-active ionic liquids with enhanced antimalarial activity have been developed, offering new perspectives for the cost-effective recycling of classical drugs.
Article
Immunology
Luisa Canto e Castro, Andreia Gomes, Marta Serrano, Ana Helena Guia Pereira, Rita Ribeiro, Patricia Napoleao, Ines Domingues, Claudia Silva, Julia Fanczal, Angela Afonso, Andreia Lopes, Ionela Toader, Maria Jose Rego de Sousa, Jose Germano Rego de Sousa, Germano de Sousa, Maria M. Mota, Bruno Silva-Santos, Marc Veldhoen, Ruy M. Ribeiro
Summary: During the COVID-19 pandemic in Portugal, there were three waves of SARS-CoV-2 infection. The study found a significant increase in seroprevalence of SARS-CoV-2 antibodies in the Portuguese population from September 2020 to March 2021, indicating long-lasting infection immunity. Additionally, vaccinated individuals had higher levels of antibodies compared to those previously infected after 3 weeks post-vaccination.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Lovepreet Singh, Diana Fontinha, Denise Francisco, Miguel Prudencio, Kamaljit Singh
Summary: With its strong impact on vector-borne diseases and malaria, ivermectin has been proven to be a promising antimalarial therapeutic. By modifying the structure of ivermectin and combining it with existing antimalarial agents, novel molecular hybrids with enhanced activity against Plasmodium parasites have been developed. These compounds displayed structure-dependent antiplasmodial activity, outperforming ivermectin itself, suggesting the superiority of this hybridization strategy in designing new antimalarial agents.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Elizabeth A. Lopes, Raquel Mestre, Diana Fontinha, Jenny Legac, Jinxin Pei, Margarida Sanches-Vaz, Mattia Mori, Adele M. Lehane, Philip J. Rosenthal, Miguel Prudencio, Maria M. M. Santos
Summary: Malaria remains a prevalent infectious disease in developing countries. The emergence of resistance to current treatments necessitates the discovery of new effective drugs. A study reports the identification of a new scaffold with dual-stage antiplasmodial activity, highlighting the potential of new compounds as antimalarial agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Delphine Jublot, Pierre Cavailles, Salima Kamche, Denise Francisco, Diana Fontinha, Miguel Prudencio, Jean-Francois Guichou, Gilles Labesse, Denis Sereno, Corinne Loeuillet
Summary: This study reports on the potential of a histone deacetylase inhibitor called JF363, which has antiviral effects against a range of Toxoplasma strains and Plasmodium parasites. The drug administered in vivo delayed the spread of T. gondii infection and controlled the formation of brain cysts in infected mice. Furthermore, the compound showed promising binding efficiency to the active site of T. gondii HDACs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Viriato M'Bana, Aparajita Lahree, Sofia Marques, Ksenija Slavic, Maria M. Mota
Summary: The UIS4 protein interacts with host cell actin, suppressing filamentous actin formation to avoid parasite elimination. Host cell actin dynamics increase around UIS4-deficient parasites, leading to parasite elimination.
Correction
Chemistry, Medicinal
Ana Teresa Silva, Isabel S. Oliveira, Joana Gomes, Luisa Aguiar, Diana Fontinha, Denise Duarte, Fatima Nogueira, Miguel Prudencio, Eduardo F. Marques, Catia Teixeira, Ricardo Ferraz, Paula Gomes
Review
Parasitology
Aparajita Lahree, Joao Mello-Vieira, Maria M. Mota
Summary: Malaria is a febrile illness caused by Plasmodium parasites, which infect erythrocytes and lead to clinical symptoms and pathology. Understanding the metabolism of liver-stage parasites is crucial for identifying cellular pathways essential for infection and developing treatments. This review provides a summary of current knowledge on nutrient acquisition and biosynthesis by liver-stage parasites, highlighting gaps in knowledge and challenges in this field.
TRENDS IN PARASITOLOGY
(2023)
Article
Pharmacology & Pharmacy
Joana F. Santos, Raquel Azevedo, Miguel Prudencio, Fernanda Marques, Yann Le Gal, Dominique Lorcy, Celia Fernandes
Summary: Block copolymer micelles (BCMs) were evaluated as drug delivery systems for gold(III) bis(dithiolene) complexes (AuS and AuSe) to treat malaria. The complexes showed strong antiplasmodial activity and low toxicity when encapsulated in BCMs. Encapsulated complexes exhibited controlled release and improved biocompatibility compared to the non-encapsulated counterparts. This study suggests that BCMs can be a promising alternative for conventional antimalarial treatments.
Article
Pharmacology & Pharmacy
Katerina Hradiska Breiterova, Aneta Ritomska, Diana Fontinha, Jana Kroustkova, Daniela Suchankova, Anna Host'alkova, Marcela Safratova, Eliska Kohelova, Rozalie Perinova, Rudolf Vrabec, Denise Francisco, Miguel Prudencio, Lucie Cahlikova
Summary: This study evaluated the activity of a variety of Amaryllidaceae alkaloids and their derivatives against the hepatic stage of Plasmodium infection. Some newly synthesized compounds showed nanomolar level activity, but similar derivatives of haemanthamine did not display significant activity. The liver-selective compounds are considered crucial for the development of malaria prophylactics.
Article
Biology
Ines M. Marreiros, Sofia Marques, Ana Parreira, Vincent Mastrodomenico, Bryan C. Mounce, Chantal T. Harris, Bjoern F. Kafsack, Oliver Billker, Vanessa Zuzarte-Luis, Maria M. Mota
Summary: Plasmodium parasites rely on an efficient sensing pathway to respond to amino acid fluctuations. The nek4, eIK1, and eIK2 sensor kinases play a key role in Plasmodium amino acid sensing, enabling these parasites to fine-tune replication and development in response to amino acid availability. This complex mechanism is critical for modulating parasite growth and survival.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Analytical
Maria Joao Oliveira, Soraia Caetano, Ana Dalot, Filipe Sabino, Tomas R. Calmeiro, Elvira Fortunato, Rodrigo Martins, Eulalia Pereira, Miguel Prudencio, Hugh J. Byrne, Ricardo Franco, Hugo Aguas
Summary: Early and accurate detection of pathogenic microorganisms is crucial for diagnosis and patient outcomes. The combination of a polystyrene-based microfluidic device and Surface-Enhanced Raman Spectroscopy shows excellent sensitivity and specificity in detecting malaria. The system can be easily adapted for other pathogens and has the potential for early diagnosis of infectious diseases.
Article
Immunology
Diana Moita, Catarina Rola, Helena Nunes-Cabaco, Goncalo Nogueira, Teresa G. Maia, Ahmad Syibli Othman, Blandine Franke-Fayard, Chris J. Janse, Antonio M. Mendes, Miguel Prudencio
Summary: Immunization with Plasmodium sporozoites, especially whole-sporozoite (WSpz) formulations, can provide strong protection against malaria. However, a comparative analysis of different WSpz formulations showed that early liver arresting genetically attenuated parasites (EA-GAP) formulation failed to confer complete protection at any immunization dosage, suggesting a minimum threshold of liver development is required for effective immune responses. On the other hand, radiation-attenuated sporozoites (RAS), late arresting GAP (LA-GAP), and sporozoites administered under chemoprophylaxis (CPS) formulations yielded comparable and dosage-dependent protection. Immunological analyses suggested that EA-GAP immunization may negatively impact memory cell functionality and protective immunity.