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Revue Medicale Suisse May 2024A malaria vaccine represents an essential complementary tool to curb the stagnation, or even increase, in malaria cases observed over the last decade due to the...
A malaria vaccine represents an essential complementary tool to curb the stagnation, or even increase, in malaria cases observed over the last decade due to the emergence of resistance to insecticides impregnated on mosquito nets, wars and internal conflicts, as well as global warming. In October 2021, WHO recommended the use of the RTS,S/ASO1 vaccine for children aged 5-17 months in areas of moderate to high transmission. In October 2023, a second vaccine received WHO approval for deployment in the same population, following demonstration of around 70 % efficacy in protecting young children against malaria for one year. Given their partial efficacy, however, these vaccines are not generally recommended for travelers to endemic countries.
Topics: Humans; Malaria Vaccines; Malaria; World Health Organization; Infant; Disease Eradication
PubMed: 38693799
DOI: 10.53738/REVMED.2024.20.872.872 -
BMJ Global Health Apr 2024In October 2021, the WHO recommended the world's first malaria vaccine-RTS,S/AS01-to prevent malaria in children living in areas with moderate-to-high transmission in... (Review)
Review
In October 2021, the WHO recommended the world's first malaria vaccine-RTS,S/AS01-to prevent malaria in children living in areas with moderate-to-high transmission in sub-Saharan Africa (SSA). A second malaria vaccine, R21/Matrix-M, was recommended for use in October 2023 and added to the WHO list of prequalified vaccines in December 2023. This study analysis assessed the country status of implementation and delivery strategies for RTS,S/AS01 by searching websites for national malaria policies, guidelines and related documents. Direct contact with individuals working in malaria programmes was made to obtain documents not publicly available. 10 countries had documents with information relating to malaria vaccine implementation, 7 referencing RTS,S/AS01 and 3 (Burkina Faso, Kenya and Nigeria) referencing RTS,S/AS01 and R21/Matrix-M. Five other countries reported plans for malaria vaccine roll-out without specifying which vaccine. Ghana, Kenya and Malawi, which piloted RTS,S/AS01, have now integrated the vaccine into routine immunisation services. Cameroon and Burkina Faso are the first countries outside the pilot countries to incorporate the vaccine into national immunisation services. Uganda plans a phased RTS,S/AS01 introduction, while Guinea plans to first pilot RTS,S/AS01 in five districts. The RTS,S/AS01 schedule varied by country, with the first dose administered at 5 or 6 months in all countries but the fourth dose at either 18, 22 or 24 months. SSA countries have shown widespread interest in rolling out the malaria vaccine, the Global Alliance for Vaccines and Immunization having approved financial support for 20 of 30 countries which applied as of March 2024. Limited availability of RTS,S/AS01 means that some approved countries will not receive the required doses. Vaccine availability and equity must be addressed even as R21/Matrix-M becomes available.
Topics: Humans; Malaria Vaccines; Africa South of the Sahara; World Health Organization; Malaria; Immunization Programs; Health Policy
PubMed: 38688566
DOI: 10.1136/bmjgh-2023-014719 -
JCI Insight Apr 2024A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical... (Randomized Controlled Trial)
Randomized Controlled Trial
A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole-sporozoite PfSPZ vaccine in African infants. Innate immune activation and myeloid signatures at prevaccination baseline correlated with protection from P. falciparum parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ vaccine dose. Machine learning identified spliceosome, proteosome, and resting DC signatures as prevaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline circumsporozoite protein-specific (CSP-specific) IgG predicted nonprotection. Prevaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8+ T cell responses after vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naive mice while diminishing the CD8+ T cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity by whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggests that PfSPZ vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways.
Topics: Malaria Vaccines; Immunity, Innate; Humans; Animals; Malaria, Falciparum; Plasmodium falciparum; Mice; Vaccines, Attenuated; Sporozoites; CD8-Positive T-Lymphocytes; Infant; Protozoan Proteins; Antibodies, Protozoan; Female; Parasitemia; Immunoglobulin G; Vaccine Efficacy
PubMed: 38687615
DOI: 10.1172/jci.insight.167408 -
In silico-based vaccine design against Naegleria fowleri causing primary amebic meningoencephalitis.Indian Journal of Pharmacology Mar 2024
Topics: Naegleria fowleri; Humans; Central Nervous System Protozoal Infections; Protozoan Vaccines; Computer Simulation; Meningoencephalitis; Amebiasis; Animals
PubMed: 38687320
DOI: 10.4103/ijp.ijp_482_23 -
Avian Diseases Mar 2024Intestinal health is one of the key factors required for the growth and production of turkeys. Histomoniasis (blackhead disease), caused by a protozoan parasite, , is a...
Intestinal health is one of the key factors required for the growth and production of turkeys. Histomoniasis (blackhead disease), caused by a protozoan parasite, , is a reemerging threat to the turkey industry. Increased incidences of histomoniasis have been reported in recent years due to withdrawal of antihistomonas treatments. affects ceca and causes cecal inflammation and necrosis. migrates from ceca to the liver and causes liver necrosis, resulting in high mortalities. Ironically, field outbreaks of histomoniasis are not always associated with high mortalities, while low mortalities have also been documented. There are several exacerbating factors associated with high mortality rates in histomoniasis outbreaks, with concurrent infection being one of them. Recurrent histomoniasis outbreaks in a newly constructed barn were documented, and concurrent infection of and hemorrhagic enteritis virus was confirmed. Currently, neither commercial vaccines nor prophylactic or therapeutic solutions are available to combat histomoniasis. However, there are treatments, vaccines, and solutions to minimize or prevent concurrent infections in turkeys. In addition to implementing biosecurity measures, measures to prevent concurrent infections are critical steps that the turkey industry can follow to reduce mortality rates and minimize the production and economic losses associated with histomoniasis outbreaks.
Topics: Animals; Turkeys; Poultry Diseases; Trichomonadida; Protozoan Infections, Animal; Coinfection; Disease Outbreaks; Adenoviridae Infections
PubMed: 38687109
DOI: 10.1637/aviandiseases-D-23-00059 -
Frontiers in Cellular and Infection... 2024
Topics: Antigens, Protozoan; Malaria; Humans; Plasmodium; Animals; Malaria Vaccines
PubMed: 38686096
DOI: 10.3389/fcimb.2024.1408366 -
Acta Tropica Jul 2024Malaria remains a public health challenge. Since many control strategies have proven ineffective in eradicating this disease, new strategies are required, among which...
Malaria remains a public health challenge. Since many control strategies have proven ineffective in eradicating this disease, new strategies are required, among which the design of a multivalent vaccine stands out. However, the effectiveness of this strategy has been hindered, among other reasons, by the genetic diversity observed in parasite antigens. In Plasmodium vivax, the Erythrocyte Binding Protein (PvEBP, also known as DBP2) is an alternate ligand to Duffy Binding Protein (DBP); given its structural resemblance to DBP, EBP/DBP2 is proposed as a promising antigen for inclusion in vaccine design. However, the extent of genetic diversity within the locus encoding this protein has not been comprehensively assessed. Thus, this study aimed to characterize the genetic diversity of the locus encoding the P. vivax EBP/DBP2 protein and to determine the evolutionary mechanisms modulating this diversity. Several intrapopulation genetic variation parameters were estimated using 36 gene sequences of PvEBP/DBP2 from Colombian P. vivax clinical isolates and 186 sequences available in databases. The study then evaluated the worldwide genetic structure and the evolutionary forces that may influence the observed patterns of genetic variation. It was found that the PvEBP/DBP2 gene exhibits one of the lowest levels of genetic diversity compared to other vaccine-candidate antigens. Four major haplotypes were shared worldwide. Analysis of the protein's 3D structure and epitope prediction identified five regions with potential antigenic properties. The results suggest that the PvEBP/DBP2 protein possesses ideal characteristics to be considered when designing a multivalent effective antimalarial vaccine against P. vivax.
Topics: Plasmodium vivax; Genetic Variation; Protozoan Proteins; Humans; Malaria Vaccines; Malaria, Vivax; Antigens, Protozoan; Colombia; Phylogeny; Receptors, Cell Surface
PubMed: 38685340
DOI: 10.1016/j.actatropica.2024.107231 -
NPJ Systems Biology and Applications Apr 2024Malaria vaccine development is hampered by extensive antigenic variation and complex life stages of Plasmodium species. Vaccine development has focused on a small number...
Malaria vaccine development is hampered by extensive antigenic variation and complex life stages of Plasmodium species. Vaccine development has focused on a small number of antigens, many of which were identified without utilizing systematic genome-level approaches. In this study, we implement a machine learning-based reverse vaccinology approach to predict potential new malaria vaccine candidate antigens. We assemble and analyze P. falciparum proteomic, structural, functional, immunological, genomic, and transcriptomic data, and use positive-unlabeled learning to predict potential antigens based on the properties of known antigens and remaining proteins. We prioritize candidate antigens based on model performance on reference antigens with different genetic diversity and quantify the protein properties that contribute most to identifying top candidates. Candidate antigens are characterized by gene essentiality, gene ontology, and gene expression in different life stages to inform future vaccine development. This approach provides a framework for identifying and prioritizing candidate vaccine antigens for a broad range of pathogens.
Topics: Plasmodium falciparum; Malaria Vaccines; Antigens, Protozoan; Malaria, Falciparum; Machine Learning; Humans; Proteomics; Vaccine Development; Protozoan Proteins; Computational Biology
PubMed: 38678051
DOI: 10.1038/s41540-024-00365-1 -
Molecules (Basel, Switzerland) Apr 2024Leishmaniasis, an infectious disease caused by pathogenic parasites, affects millions of people in developing countries, and its re-emergence in developed countries,...
Leishmaniasis, an infectious disease caused by pathogenic parasites, affects millions of people in developing countries, and its re-emergence in developed countries, particularly in Europe, poses a growing public health concern. The limitations of current treatments and the absence of effective vaccines necessitate the development of novel therapeutics. In this study, we focused on identifying small molecule inhibitors which prevents the interaction between peroxin 5 (PEX5) and peroxisomal targeting signal 1 (PTS1), pivotal for kinetoplastid parasite survival. The PEX5, containing a C-terminal tetratricopeptide repeat (TPR) domain, was expressed and purified, followed by the quantification of kinetic parameters of PEX5-PTS1 interactions. A fluorescence polarization-based high-throughput screening assay was developed and small molecules inhibiting the PEX5-PTS1 interaction were discovered through the screening of a library of 51,406 compounds. Based on the confirmatory assay, nine compounds showed half maximal inhibitory concentration (IC) values ranging from 3.89 to 24.50 µM. In silico docking using a homology model of PEX5 elucidated that the molecular interactions between PEX5 and the inhibitors share amino acids critical for PTS1 binding. Notably, compound P20 showed potent activity against the growth of promastigotes, promastigotes, and blood stream form, with IC values of 12.16, 19.21, and 3.06 μM, respectively. The findings underscore the potential of targeting PEX5-PTS1 interactions with small molecule inhibitors as a promising strategy for the discovery of new anti-parasitic compounds.
Topics: Leishmania donovani; High-Throughput Screening Assays; Peroxisome-Targeting Signal 1 Receptor; Molecular Docking Simulation; Protozoan Proteins; Fluorescence Polarization; Protein Binding; Small Molecule Libraries; Antiprotozoal Agents; Humans
PubMed: 38675653
DOI: 10.3390/molecules29081835 -
Life (Basel, Switzerland) Apr 2024The neglected Chagas disease (CD) is caused by the protozoan parasite . Despite CD dispersion throughout the world, it prevails in tropical areas affecting mainly poor... (Review)
Review
The neglected Chagas disease (CD) is caused by the protozoan parasite . Despite CD dispersion throughout the world, it prevails in tropical areas affecting mainly poor communities, causing devastating health, social and economic consequences. Clinically, CD is marked by a mildly symptomatic acute phase, and a chronic phase characterized by cardiac and/or digestive complications. Current treatment for CD relies on medications with strong side effects and reduced effectiveness. The complex interaction between the parasite and the host outlines the etiology and progression of CD. The unique characteristics and high adaptability of , its mechanisms of persistence, and evasion of the immune system seem to influence the course of the disease. Despite the efforts to uncover the pathology of CD, there are many gaps in understanding how it is established and reaches chronicity. Also, the lack of effective treatments and protective vaccines constitute challenges for public health. Here, we explain the background in which CD is established, from the peculiarities of molecular biology to the development of the host's immune response leading to the pathophysiology of CD. We also discuss the state of the art of treatments for CD and current challenges in basic and applied science.
PubMed: 38672758
DOI: 10.3390/life14040488