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Nature Reviews. Drug Discovery Oct 2023Recent antimalarial drug discovery has been a race to produce new medicines that overcome emerging drug resistance, whilst considering safety and improving dosing... (Review)
Review
Recent antimalarial drug discovery has been a race to produce new medicines that overcome emerging drug resistance, whilst considering safety and improving dosing convenience. Discovery efforts have yielded a variety of new molecules, many with novel modes of action, and the most advanced are in late-stage clinical development. These discoveries have led to a deeper understanding of how antimalarial drugs act, the identification of a new generation of drug targets, and multiple structure-based chemistry initiatives. The limited pool of funding means it is vital to prioritize new drug candidates. They should exhibit high potency, a low propensity for resistance, a pharmacokinetic profile that favours infrequent dosing, low cost, preclinical results that demonstrate safety and tolerability in women and infants, and preferably the ability to block Plasmodium transmission to Anopheles mosquito vectors. In this Review, we describe the approaches that have been successful, progress in preclinical and clinical development, and existing challenges. We illustrate how antimalarial drug discovery can serve as a model for drug discovery in diseases of poverty.
Topics: Animals; Female; Humans; Antimalarials; Plasmodium; Drug Resistance; Drug Discovery
PubMed: 37652975
DOI: 10.1038/s41573-023-00772-9 -
Virulence Dec 2023Infections with and cause over 600,000 deaths each year, concentrated in Africa and in young children, but much of the world's population remain at risk of infection.... (Review)
Review
Infections with and cause over 600,000 deaths each year, concentrated in Africa and in young children, but much of the world's population remain at risk of infection. In this article, we review the latest developments in the immunogenicity and pathogenesis of malaria, with a particular focus on , the leading malaria killer. Pathogenic factors include parasite-derived toxins and variant surface antigens on infected erythrocytes that mediate sequestration in the deep vasculature. Host response to parasite toxins and to variant antigens is an important determinant of disease severity. Understanding how parasites sequester, and how antibody to variant antigens could prevent sequestration, may lead to new approaches to treat and prevent disease. Difficulties in malaria diagnosis, drug resistance, and specific challenges of treating pose challenges to malaria elimination, but vaccines and other preventive strategies may offer improved disease control.
Topics: Child; Humans; Child, Preschool; Virulence; Malaria; Malaria, Falciparum; Plasmodium falciparum; Plasmodium vivax; Protozoan Proteins
PubMed: 36419237
DOI: 10.1080/21505594.2022.2150456 -
Trends in Parasitology Oct 2023Meiosis is sexual cell division, a process in eukaryotes whereby haploid gametes are produced. Compared to canonical model eukaryotes, meiosis in apicomplexan parasites... (Review)
Review
Meiosis is sexual cell division, a process in eukaryotes whereby haploid gametes are produced. Compared to canonical model eukaryotes, meiosis in apicomplexan parasites appears to diverge from the process with respect to the molecular mechanisms involved; the biology of Plasmodium meiosis, and its regulation by means of post-translational modification, are largely unexplored. Here, we discuss the impact of technological advances in cell biology, evolutionary bioinformatics, and genome-wide functional studies on our understanding of meiosis in the Apicomplexa. These parasites, including Plasmodium falciparum, Toxoplasma gondii, and Eimeria spp., have significant socioeconomic impact on human and animal health. Understanding this key stage during the parasite's life cycle may well reveal attractive targets for therapeutic intervention.
Topics: Animals; Humans; Plasmodium; Eukaryota; Plasmodium falciparum; Meiosis; Toxoplasma
PubMed: 37541799
DOI: 10.1016/j.pt.2023.07.002 -
Medecine Tropicale Et Sante... Jun 2023Malaria, a parasitic disease the pathogen of which was discovered by Alphonse Laveran in 1880 in the blood of febrile patients, remains in 2022 the most frequent endemic...
Malaria, a parasitic disease the pathogen of which was discovered by Alphonse Laveran in 1880 in the blood of febrile patients, remains in 2022 the most frequent endemic disease in tropical and subtropical countries. In its latest "World Malaria Report" available in November 2021, the WHO deals in great detail with the data collected in the field in 2019-2020, their progression over the last 20 years, and the measures to be taken to try to better control this life-threatening endemic. The number of malaria cases is estimated at 232 million in 2019 in 87 endemic countries, down from 245 million in 2000. The WHO African Region alone accounts for 94% of cases and the most frequent and severe infections due to species. If children under the age of 5 are not treated promptly, they can die. Globally, the number of malaria deaths declined steadily over the period 2000-2019, from 897,000 in 2000 to 568,000 in 2019, with nearly 95% of deaths occurring in 31 countries, primarily in sub-Saharan Africa. In other WHO regions, including Southeast Asia, malaria deaths decreased by 74%, with 35,000 deaths in 2000 compared to 9,000 in 2019. Malaria can be controlled worldwide, and possibly eradicated, if public information campaigns are strengthened and sufficient funds are made available.
Topics: Child; Humans; Malaria; Plasmodium; Africa South of the Sahara; Asia, Southeastern; Endemic Diseases
PubMed: 37525676
DOI: 10.48327/mtsi.v3i2.2023.375 -
Turkiye Parazitolojii Dergisi Sep 2023Cats have an important and different place due to their close relationships with humans. Since most of the parasites they carry are zoonotic, it is important to detect... (Review)
Review
Cats have an important and different place due to their close relationships with humans. Since most of the parasites they carry are zoonotic, it is important to detect them. According to the research, spp., spp., spp., and sp. were found to be higher in cats compared to other parasites. It has been determined that scabies and flea infestations are common as ectoparasites. This review aims to present the reported parasites and their prevalence rates in cats in Türkiye.
Topics: Humans; Cats; Animals; Parasites; Flea Infestations; Scabies; Toxoplasma; Toxocara
PubMed: 37724370
DOI: 10.4274/tpd.galenos.2023.85698 -
Frontiers in Immunology 2023
Topics: Animals; Poultry; Eimeria; Coccidiosis
PubMed: 37377969
DOI: 10.3389/fimmu.2023.1215513 -
Scientific Reports Sep 2023The phylum Apicomplexa comprises a large group of intracellular protozoan parasites. These microorganisms are known to infect a variety of vertebrate and invertebrate...
The phylum Apicomplexa comprises a large group of intracellular protozoan parasites. These microorganisms are known to infect a variety of vertebrate and invertebrate hosts, leading to significant medical and veterinary conditions such as toxoplasmosis, cryptosporidiosis, theileriosis, and eimeriosis. Despite their importance, comprehensive data on their diversity and distribution, especially in riverine environments, remain scant. To bridge this knowledge gap, we utilized next-generation high-throughput 18S rRNA amplicon sequencing powered by PacBio technology to explore the diversity and composition of the Apicomplexa taxa. Principal component analysis (PCA) and principal coordinate analysis (PCoA) indicated the habitat heterogeneity for the physicochemical parameters and the Apicomplexa community. These results were supported by PERMANOVA (P < 0.001), ANOSIM (P < 0.001), Cluster analysis, and Venn diagram. Dominant genera of Apicomplexa in inlet samples included Gregarina (38.54%), Cryptosporidium (32.29%), and Leidyana (11.90%). In contrast, outlet samples were dominated by Babesia, Cryptosporidium, and Theileria. While surface water samples revealed 16% and 8.33% relative abundance of Toxoplasma and Cryptosporidium, respectively. To our knowledge, the next-generation high throughput sequencing covered a wide range of parasites in Egypt for the first time, which could be useful for legislation of the standards for drinking water and wastewater reuse.
Topics: Humans; Cryptosporidium; Cryptosporidiosis; Babesia; High-Throughput Nucleotide Sequencing; Toxoplasma
PubMed: 37699953
DOI: 10.1038/s41598-023-40895-y -
Virulence Dec 2023spp. infection causes significant disease in immunosuppressed individuals and children under the age of 5 years. The severity of the pathological presentation of... (Review)
Review
spp. infection causes significant disease in immunosuppressed individuals and children under the age of 5 years. The severity of the pathological presentation of cryptosporidiosis is a function of the host and parasite genotypes, host immune status, and the enteric environment or microbiome of the host. Cryptosporidiosis often presents with abdominal pain and severe diarrhoea and is associated with intestinal dysbiosis and inflammation. Our systematic analysis of the available literature revealed that bacterial diversity is reduced during infection in larger animal models, lending support to recent studies which indicate that the use of probiotics or the presence of a naturally diverse gut microbiome can prevent or minimise pathology caused by gastrointestinal pathogens. In summary, we present evidence that the presence of a diverse gut microbiome, natural or induced, reduces both symptomatic pathology and oocyst output.
Topics: Animals; Child; Humans; Child, Preschool; Cryptosporidiosis; Cryptosporidium; Cryptosporidium parvum; Bacteria; Gastrointestinal Microbiome; Feces
PubMed: 37872759
DOI: 10.1080/21505594.2023.2273004 -
Advanced Science (Weinheim,... Apr 2024Macrophage therapy for liver fibrosis is on the cusp of meaningful clinical utility. Due to the heterogeneities of macrophages, it is urgent to develop safer macrophages...
Macrophage therapy for liver fibrosis is on the cusp of meaningful clinical utility. Due to the heterogeneities of macrophages, it is urgent to develop safer macrophages with a more stable and defined phenotype for the treatment of liver fibrosis. Herein, a new macrophage-based immunotherapy using macrophages stably expressing a pivotal cytokine from Toxoplasma gondii, a parasite that infects ≈ 2 billion people is developed. It is found that Toxoplasma gondii macrophage migration inhibitory factor-transgenic macrophage (Mφ) shows stable fibrinolysis and strong chemotactic capacity. Mφ effectively ameliorates liver fibrosis and deactivates aHSCs by recruiting Ly6C macrophages via paracrine CCL2 and polarizing them into the restorative Ly6C macrophage through the secretion of CX3CL1. Remarkably, Mφ exhibits even higher chemotactic potential, lower grade of inflammation, and better therapeutic effects than LPS/IFN-γ-treated macrophages, making macrophage-based immune therapy more efficient and safer. Mechanistically, TgMIF promotes CCL2 expression by activating the ERK/HMGB1/NF-κB pathway, and this event is associated with recruiting endogenous macrophages into the fibrosis liver. The findings do not merely identify viable immunotherapy for liver fibrosis but also suggest a therapeutic strategy based on the evolutionarily designed immunomodulator to treat human diseases by modifying the immune microenvironment.
Topics: Humans; Macrophages; Liver Cirrhosis; Toxoplasma; Inflammation; Phenotype
PubMed: 38247166
DOI: 10.1002/advs.202308750 -
Parasitology Dec 2023Avian malaria parasites or haemosporidia are found in bird species worldwide. This special issue focuses on 3 most commonly studied genera: , and . Seven research...
Avian malaria parasites or haemosporidia are found in bird species worldwide. This special issue focuses on 3 most commonly studied genera: , and . Seven research articles and reviews are provided to illustrate the breadth of knowledge of the diversity of avian malaria parasites in different regional habitats and across bird species, and the use of avian haemosporidian systems to examine host–parasite eco-evolutionary questions.
Topics: Animals; Malaria, Avian; Prevalence; Plasmodium; Haemosporida; Parasites; Birds; Bird Diseases; Phylogeny
PubMed: 38200697
DOI: 10.1017/S0031182024000040