-
Science (New York, N.Y.) Aug 2023Malaria control demands the development of a wide range of complementary strategies. We describe the properties of a naturally occurring, non-genetically modified...
Malaria control demands the development of a wide range of complementary strategies. We describe the properties of a naturally occurring, non-genetically modified symbiotic bacterium, TC1, which was isolated from mosquitoes incapable of sustaining the development of parasites. TC1 inhibits early stages of development and subsequent transmission by the mosquito through secretion of a small-molecule inhibitor. We have identified this inhibitor to be the hydrophobic molecule harmane. We also found that, on mosquito contact, harmane penetrates the cuticle, inhibiting development. TC1 stably populates the mosquito gut, does not impose a fitness cost on the mosquito, and inhibits development for the mosquito's life. Contained field studies in Burkina Faso and modeling showed that TC1 has the potential to complement mosquito-targeted malaria transmission control.
Topics: Animals; Anopheles; Malaria, Falciparum; Plasmodium falciparum; Delftia; Symbiosis; Humans; Host-Parasite Interactions
PubMed: 37535741
DOI: 10.1126/science.adf8141 -
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 -
The Lancet. Infectious Diseases Aug 2023In October, 2021, WHO recommended that the RTS,S malaria vaccine, with its strong safety profile and high impact, be provided to children from age 5 months in regions... (Review)
Review
In October, 2021, WHO recommended that the RTS,S malaria vaccine, with its strong safety profile and high impact, be provided to children from age 5 months in regions with moderate to high Plasmodium falciparum malaria transmission. The evidence base included phase 3 trials in seven African countries and an ongoing malaria vaccine implementation programme (MVIP) in three African countries. We highlight problems with the MVIP mortality data, including potential confounding, inappropriate use of severe malaria as a surrogate marker, a statistically non-significant effect, and assessment after 2 years instead of the stipulated 4 years, which could have inflated the benefits and deflated the risks associated with the vaccine. We conclude that the claimed impact of the MVIP on mortality is not based on enough scientific evidence and that the MVIP findings do not rule out the possibility of increased mortality among vaccinated girls compared with vaccinated boys, as observed in the phase 3 studies. The MVIP should adhere fully to the planned analyses and the data should be made available for independent assessment. Roll-out of the vaccine elsewhere should include rigorous evaluation, especially of its safety.
Topics: Female; Humans; Infant; Male; Africa; Malaria; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Child, Preschool
PubMed: 37086747
DOI: 10.1016/S1473-3099(23)00126-3 -
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 -
Nature Microbiology Oct 2023Diagnosis and treatment of Plasmodium falciparum infections are required for effective malaria control and are pre-requisites for malaria elimination efforts; hence we...
Diagnosis and treatment of Plasmodium falciparum infections are required for effective malaria control and are pre-requisites for malaria elimination efforts; hence we need to monitor emergence, evolution and spread of drug- and diagnostics-resistant parasites. We deep sequenced key drug-resistance mutations and 1,832 SNPs in the parasite genomes of 609 malaria cases collected during a diagnostic-resistance surveillance study in Ethiopia. We found that 8.0% (95% CI 7.0-9.0) of malaria cases were caused by P. falciparum carrying the candidate artemisinin partial-resistance kelch13 (K13) 622I mutation, which was less common in diagnostic-resistant parasites mediated by histidine-rich proteins 2 and 3 (pfhrp2/3) deletions than in wild-type parasites (P = 0.03). Identity-by-descent analyses showed that K13 622I parasites were significantly more related to each other than to wild type (P < 0.001), consistent with recent expansion and spread of this mutation. Pfhrp2/3-deleted parasites were also highly related, with evidence of clonal transmissions at the district level. Of concern, 8.2% of K13 622I parasites also carried the pfhrp2/3 deletions. Close monitoring of the spread of combined drug- and diagnostic-resistant parasites is needed.
Topics: Humans; Plasmodium falciparum; Antimalarials; Ethiopia; Protozoan Proteins; Artemisinins; Malaria, Falciparum
PubMed: 37640962
DOI: 10.1038/s41564-023-01461-4 -
Trends in Parasitology Feb 2024Malaria is a life-threatening tropical disease caused by parasites of the genus Plasmodium, of which Plasmodium falciparum is the most lethal. Malaria parasites have a... (Review)
Review
Malaria is a life-threatening tropical disease caused by parasites of the genus Plasmodium, of which Plasmodium falciparum is the most lethal. Malaria parasites have a complex life cycle, with stages occurring in both the Anopheles mosquito vector and human host. Ring stages are the youngest form of the parasite in the intraerythrocytic developmental cycle and are associated with evasion of spleen clearance, temporary growth arrest (TGA), and drug resistance. This formidable ability to survive and develop into mature, sexual, or growth-arrested forms demonstrates the inherent population heterogeneity. Here we highlight the role of the ring stage as a crossroads in parasite development and as a reservoir of surviving cells in the human host via TGA survival mechanisms.
Topics: Animals; Humans; Antimalarials; Drug Resistance; Life Cycle Stages; Malaria; Malaria, Falciparum; Plasmodium falciparum
PubMed: 38104024
DOI: 10.1016/j.pt.2023.11.007 -
Trends in Parasitology Nov 2023Strategic use of Plasmodium falciparum genetic variation has great potential to inform public health actions for malaria control and elimination. Malaria molecular... (Review)
Review
Strategic use of Plasmodium falciparum genetic variation has great potential to inform public health actions for malaria control and elimination. Malaria molecular surveillance (MMS) begins with a strategy to identify and collect parasite samples, guided by public-health priorities. In this review we discuss sampling design practices for MMS and point out epidemiological, biological, and statistical factors that need to be considered. We present examples for different use cases, including detecting emergence and spread of rare variants, establishing transmission sources and inferring changes in malaria transmission intensity. This review will potentially guide the collection of samples and data, serve as a starting point for further methodological innovation, and enhance utilization of MMS to support malaria elimination.
Topics: Humans; Antimalarials; Drug Resistance; Malaria; Plasmodium falciparum; Malaria, Falciparum
PubMed: 37730525
DOI: 10.1016/j.pt.2023.08.007 -
Trends in Parasitology Apr 2024Malaria parasites have coevolved with humans over thousands of years, mirroring their migration out of Africa. They persist to this day, despite continuous elimination... (Review)
Review
Malaria parasites have coevolved with humans over thousands of years, mirroring their migration out of Africa. They persist to this day, despite continuous elimination efforts worldwide. These parasites can adapt to changing environments during infection of human and mosquito, and when expanding the geographical range by switching vector species. Recent studies in the human malaria parasite, Plasmodium falciparum, identified determinants governing the plasticity of sexual conversion rates, sex ratio, and vector competence. Here we summarize the latest literature revealing environmental, epigenetic, and genetic determinants of malaria transmission.
Topics: Animals; Humans; Malaria, Falciparum; Mosquito Vectors; Malaria; Plasmodium falciparum; Culicidae
PubMed: 38443304
DOI: 10.1016/j.pt.2024.02.001 -
Trends in Parasitology May 2024The micropore, a mysterious structure found in apicomplexan species, was recently shown to be essential for nutrient acquisition in Plasmodium falciparum and Toxoplasma... (Review)
Review
The micropore, a mysterious structure found in apicomplexan species, was recently shown to be essential for nutrient acquisition in Plasmodium falciparum and Toxoplasma gondii. However, the differences between the micropores of these two parasites questions the nature of a general apicomplexan micropore structure and whether the formation process model from Plasmodium can be applied to other apicomplexans. We analyzed the literature on different apicomplexan micropores and found that T. gondii probably harbors a more representative micropore type than the more widely studied ones in Plasmodium. Using recent knowledge of the Kelch 13 (K13) protein interactome and gene depletion phenotypes in the T. gondii micropore, we propose a model of micropore formation, thus enriching our wider understanding of micropore protein function.
Topics: Apicomplexa; Toxoplasma; Plasmodium falciparum; Protozoan Proteins
PubMed: 38637184
DOI: 10.1016/j.pt.2024.03.008 -
PLoS Pathogens Oct 2023The pathophysiology of severe falciparum malaria involves a complex interaction between the host, parasite, and gut microbes. In this review, we focus on understanding... (Review)
Review
The pathophysiology of severe falciparum malaria involves a complex interaction between the host, parasite, and gut microbes. In this review, we focus on understanding parasite-induced intestinal injury and changes in the human intestinal microbiota composition in patients with Plasmodium falciparum malaria. During the blood stage of P. falciparum infection, infected red blood cells adhere to the vascular endothelium, leading to widespread microcirculatory obstruction in critical tissues, including the splanchnic vasculature. This process may cause intestinal injury and gut leakage. Epidemiological studies indicate higher rates of concurrent bacteraemia in severe malaria cases. Furthermore, severe malaria patients exhibit alterations in the composition and diversity of the intestinal microbiota, although the exact contribution to pathophysiology remains unclear. Mouse studies have demonstrated that the gut microbiota composition can impact susceptibility to Plasmodium infections. In patients with severe malaria, the microbiota shows an enrichment of pathobionts, including pathogens that are known to cause concomitant bloodstream infections. Microbial metabolites have also been detected in the plasma of severe malaria patients, potentially contributing to metabolic acidosis and other clinical complications. However, establishing causal relationships requires intervention studies targeting the gut microbiota.
Topics: Humans; Animals; Mice; Gastrointestinal Microbiome; Microcirculation; Malaria, Falciparum; Malaria; Intestinal Diseases; Plasmodium falciparum
PubMed: 37856470
DOI: 10.1371/journal.ppat.1011661