Interleukin-22 Polymorphisms in Plasmodium falciparum-Infected Malaria Patients.
Ontology highlight
ABSTRACT:
SUBMITTER: Aljarba NH
PROVIDER: S-EPMC7049855 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Interleukin-22 Polymorphisms in <i>Plasmodium falciparum</i>-Infected Malaria Patients.
Aljarba Nada H NH Al-Anazi Mashael R MR Shafeai Mohammed I MI Rudiny Fuad H FH Bin Dajem Saad M SM Alothaid Hani H Darraj Majid M Alkahtani Saad S Alghamdi Jahad J Al-Ahdal Mohammed N MN Al-Qahtani Ahmed A AA
Mediators of inflammation 20200219
<i>Background and Objectives</i>. Malaria infection, caused by <i>Plasmodium falciparum</i>, is the most lethal and frequently culminates in severe clinical complications. Interleukin-22 (IL-22) has been implicated in several diseases including malaria. The objective of this study was to investigate the role of IL-22 gene polymorphisms in <i>P</i>. <i>falciparum</i> infection. <i>Material and Methods</i>. Ten single-nucleotide polymorphisms (SNPs), rs976748, rs1179246, rs2046068, rs1182844, rs22 ...[more]
Similar Datasets
Project description:Malaria is often characterized by a complicated disease course due to multifaceted intrinsic genetic factors of the host and the parasite. This study aimed to investigate the role of interleukin-27 (IL-27) gene polymorphisms in Plasmodium falciparum malaria infection in a Saudi Arabian cohort. This case-control study obtained blood samples from 250 malaria patients with P. falciparum and 200 randomly identified healthy control subjects from the Malaria Center in the Jazan area. Malaria patients were grouped into three cohorts as follow: low (<500 parasites/µl of blood), moderate (500-1000 parasites/µl of blood), and high (>1000 parasites/µl of blood) parasitemia. The results show that the IL-27 variant rs181209 was significantly associated with malaria patients (P = 0.026). Similarly, the homozygous GG genotype of rs26528 was also associated with risk of developing P. falciparum malaria (P = 0.032). The minor allele C of variant rs181206 exhibited an association with low to moderate parasitemia (P = 0.046). Furthermore, the rs181209 AA genotype was statistically significant in age group 1-5 years (P = 0.049). In conclusion, this study suggests that variant rs181209 and rs26528 could be associated with the risk of malaria infection by P. falciparum in the population studied.
| S-EPMC10357889 | biostudies-literature
Project description:Patients infected with Plasmodium falciparum sustain diverse disease outcome; we wanted to determine if parasites derived ex vivo have diverse biological states. To explore parasite in vivo biology we measured parasite steady state whole genome transcription using a previously reported custom made Affy array (Scrmalaria) based on the laboratory strain 3D7. Extensive bioinformatic analysis was carried out including cross species comparisions to yeast. For sample cluster analysis, a filtered gene list containing 3937 genes was generated by thresholding gene expression levels to a minimum of 50 EU and removing any genes that varied less than 3 fold or 100 EU across the dataset. To minimize potential effects of different dates of collection and hybridizations, the data was rank ordered by expression level and each gene was given an ordinal value. Keywords: ex vivo
2007-12-13 | GSE9152 | GEO
Project description:BackgroundAcute malarial anemia remains a major public health problem. Hepcidin, the major hormone controlling the availability of iron, is raised during acute and asymptomatic parasitemia. Understanding the role and mechanism of raised hepcidin and so reduced iron availability during infection is critical to establish evidence-based guidelines for management of malaria anemia. Our recent clinical evidence suggests a potential role of IL-10 in the regulation of hepcidin in patients with acute P. falciparum malaria.MethodsWe have measured secretion of hepcidin by primary macrophages and the hepatoma cell line HepG2 stimulated with IL-10, IL-6 and Plasmodium falciparum-infected erythrocytes.FindingsWe have observed that IL-10 and IL-6 production increased in primary macrophages when these cells were co-cultured with Plasmodium falciparum-infected erythrocytes. We found that IL-10 induced hepcidin secretion in primary macrophages in a dose-dependent manner but not in HepG2 cells. These effects were mediated through signal transducer and activator of transcription (STAT) 3-phosphorylation and completely abrogated by a specific STAT3 inhibitor.ConclusionIL-10 can directly regulate hepcidin in primary macrophages but not in HepG2 cells. This effect can be modulated by Plasmodium falciparum. The results are consistent with a role for IL-10 in modulating iron metabolism during acute phase of infection.
| S-EPMC3919761 | biostudies-literature
Project description:Splenic filtration of Plasmodium falciparum-infected red blood cells has been hypothesized to influence malaria pathogenesis. We have developed a minimum cylindrical diameter (MCD) filtration model which estimates physical splenic filtration during malaria infection. The key parameter in the model is the MCD, the smallest tube or cylinder that a red blood cell (RBC) can traverse without lysing. The MCD is defined by a relationship between the RBC surface area and volume. In the MCD filtration model, the MCD filtration function represents the probability of a cell becoming physically removed from circulation. This modelling approach was implemented at a field site in Blantyre, Malawi. We analysed peripheral blood samples from 120 study participants in four clinically defined groups (30 subjects each): cerebral malaria, uncomplicated malaria, aparasitaemic coma and healthy controls. We found statistically significant differences in the surface area and volumes of uninfected RBCs when healthy controls were compared with malaria patients. The estimated filtration rates generated by the MCD model corresponded to previous observations in ex vivo spleen experiments and models of red blood cell loss during acute malaria anaemia.There were no differences in the estimated splenic filtration rates between cerebral malaria and uncomplicated malaria patients. The MCD filtration model estimates that at time of admission, one ring-stage infected RBC is physically filtered by the spleen for each parasite that remains in peripheral circulation. This field study is the first to use microfluidic devices to identify rheological diversity in RBC populations associated with malaria infection and illness in well-characterized groups of children living in a malaria endemic area.
| S-EPMC3501548 | biostudies-literature
Project description:Plasmodium falciparum is the major cause of malaria globally and is transmitted by mosquitoes. During parasitic development, P. falciparum-infected erythrocytes (P. falciparum-IEs) express multiple polymorphic proteins known as variant surface antigens (VSAs), including the P. falciparum erythrocyte membrane protein 1 (PfEMP1). VSA-specific antibodies are associated with protection from symptomatic and severe malaria. However, the importance of the different VSA targets of immunity to malaria remains unclear, which has impeded an understanding of malaria immunity and vaccine development. In this study, we developed assays using transgenic P. falciparum with modified PfEMP1 expression to quantify serum antibodies to VSAs among individuals exposed to malaria. We found that the majority of the human antibody response to the IE targets PfEMP1. Furthermore, our longitudinal studies showed that individuals with PfEMP1-specific antibodies had a significantly reduced risk of developing symptomatic malaria, whereas antibodies to other surface antigens were not associated with protective immunity. Using assays that measure antibody-mediated phagocytosis of IEs, an important mechanism in parasite clearance, we identified PfEMP1 as the major target of these functional antibodies. Taken together, these data demonstrate that PfEMP1 is a key target of humoral immunity. These findings advance our understanding of the targets and mediators of human immunity to malaria and have major implications for malaria vaccine development.
| S-EPMC3428085 | biostudies-literature
Project description:Studies to identify phenotypically-associated polymorphisms in the Plasmodium falciparum 23 Mb genome will require a dense array of marker loci. It was considered promising to undertake initial allelic association studies to prospect for virulence polymorphisms in Thailand, as the low endemicity would allow higher levels of linkage disequilibrium (LD) than would exist in more highly endemic areas.Assessment of LD was first made with 11 microsatellite loci widely dispersed in the parasite genome, and 16 microsatellite loci covering a approximately 140 kb region of chromosome 2 (an arbitrarily representative non-telomeric part of the genome), in a sample of 100 P. falciparum isolates. The dispersed loci showed minimal LD (Index of Association, I(S) (A) = 0.013, P = 0.10), while those on chromosome 2 showed significant LD values mostly between loci <5 kb apart. A disease association study was then performed comparing parasites in 113 severe malaria cases and 245 mild malaria controls. Genotyping was performed on almost all polymorphisms in the binding domains of three erythrocyte binding antigens (eba175, eba140 and eba181), and repeat sequence polymorphisms approximately 2 kb apart in each of three reticulocyte binding homologues (Rh1, Rh2a/b, and Rh4). Differences between cases and controls were seen for (i) codons 388-90 in eba175, and (ii) a repeat sequence centred on Rh1 codon 667.Allelic association studies on P. falciparum require dense genotypic markers, even in a population of only moderate endemicity that has more extensive LD than highly endemic populations. Disease-associated polymorphisms in the eba175 and Rh1 genes encode differences in the middle of previously characterised erythrocyte binding domains, marking these for further investigation.
| S-EPMC2674215 | biostudies-literature
Project description:BackgroundArtemisinins (ART) are the key component of the frontline antimalarial treatment, but their impact on Plasmodium falciparum sexual conversion rates in natural malaria infections remains unknown. This is an important knowledge gap because sexual conversion rates determine the relative parasite investment between maintaining infection in the same human host and transmission to mosquitoes.MethodsThe primary outcome of this study was to assess the impact of ART-based treatment on sexual conversion rates by comparing the relative transcript levels of pfap2-g and other sexual ring biomarkers (SRBs) before and after treatment. We analysed samples from previously existing cohorts in Vietnam, Burkina Faso and Mozambique (in total, n=109) collected before treatment and at 12 h intervals after treatment. As a secondary objective, we investigated factors that may influence the effect of treatment on sexual conversion rates.FindingsIn the majority of infections from the African cohorts, but not from Vietnam, we observed increased expression of pfap2-g and other SRBs after treatment. Estimated parasite age at the time of treatment was negatively correlated with the increase in pfap2-g transcript levels, suggesting that younger parasites are less susceptible to stimulation of sexual conversion.InterpretationWe observed enhanced expression of SRBs after ART-based treatment in many patients, which suggests that in natural malaria infections sexual conversion rates can be altered by treatment. ART-based treatment reduces the potential of a treated individual to transmit the disease, but we hypothesise that under some circumstances this reduction may be attenuated by ART-enhanced sexual conversion.FundingSpanish Agencia Estatal de Investigación (AEI), European Regional Development Fund (ERDF, European Union), Belgium Development Cooperation (DGD), Canadian University Health Network (UHN), TransGlobalHealth-Erasmus Mundus (European Union).
| S-EPMC9385555 | biostudies-literature
Project description:Malaria elimination is still pending on the development of novel tools that rely on a deep understanding of parasite biology. Proteins of all living cells undergo myriad posttranslational modifications (PTMs) that are critical to multifarious life processes. An extensive proteome-wide dissection revealed a fine PTM map of most proteins in both Plasmodium falciparum, the causative agent of severe malaria, and the infected red blood cells. More than two-thirds of proteins of the parasite and its host cell underwent extensive and dynamic modification throughout the erythrocytic developmental stage. PTMs critically modulate the virulence factors involved in the host-parasite interaction and pathogenesis. Furthermore, P. falciparum stabilized the supporting proteins of erythrocyte origin by selective demodification. Collectively, our multiple omic analyses, apart from having furthered a deep understanding of the systems biology of P. falciparum and malaria pathogenesis, provide a valuable resource for mining new antimalarial targets.
| S-EPMC7857547 | biostudies-literature
Project description:BackgroundRapid diagnostic tests (RDTs) are central to fulfilling the WHO's recommendation for parasitologic confirmation of all suspected cases of malaria. RDT performance may be compromised when exposed to the high temperature conditions typical of most malaria endemic regions. However, a systematic method to monitor RDT quality and performance in endemic countries is lacking at the present time. Current methods to monitor RDT performance in the field include comparing results from RDTs to diagnoses made by light microscopy and observing health workers perform tests. These methods are not substitutes for direct quality control. In this study, the suitability of dried Plasmodium falciparum-infected blood as quality control samples for malaria RDTs was evaluated.MethodsThree cultured strains of P. falciparum at 200 and 2,000 parasites/μl were tested on 10 brands of RDT. After baseline testing to determine initial reactivity, aliquots of parasite-infected blood were air dried, stored at 35°C, room temperature (~25°C) or 4°C for one, four and 12 weeks and were then tested on the 10 RDTs after rehydration. Extended stability testing of dried blood stored at 4°C was done using P. falciparum strain 3D7 at 1,000 and 2,000 parasites/μl.ResultsAll dried blood samples at 2,000 parasites/μl retained reactivity (100% sensitivity) at all three temperatures and time points for all nine RDT brands that detect histidine-rich protein-2 (HRP2). The dried blood samples with 200 parasites/μl were detected by six of the nine HRP2-based RDTs at all storage temperatures and time points. The sensitivity for two of the three remaining HRP2-based RDTs was 100% up to four weeks of storage at all temperatures but dropped to 87.5% at week 12. Of the four RDTs that detect plasmodium lactate dehydrogenase (pLDH) in a pan-specific manner, alone or in combination with HRP2, the detection of pLDH in samples with 2,000 parasites/μL was 100% for two RDTs and 80% for the other two RDTs. The mean level for detection of pLDH at 200 parasites/μl was low (29%), with a range of 0% to100%, which was partly attributable to weak initial baseline reactivity. Reactivity of dried 3D7 at 1,000 and 2,000 parasites/μl stored at 4°C was retained at 100% for up to 52 weeks for both HRP2 and pLDH.ConclusionsIn the absence of native or recombinant positive control antigens, well-standardized P. falciparum-infected dried blood samples can be used as positive control samples for monitoring RDT performance, particularly with HRP2-detecting tests.
| S-EPMC3483274 | biostudies-literature
Project description:For more than five decades, Southeast Asia (SEA) has been fertile ground for the emergence of drug-resistant Plasmodium falciparum malaria. After generating parasites resistant to chloroquine, sulfadoxine, pyrimethamine, quinine, and mefloquine, this region has now spawned parasites resistant to artemisinins, the world's most potent antimalarial drugs. In areas where artemisinin resistance is prevalent, artemisinin combination therapies (ACTs)-the first-line treatments for malaria-are failing fast. This worrisome development threatens to make malaria practically untreatable in SEA, and threatens to compromise global endeavors to eliminate this disease. A recent series of clinical, in vitro, genomics, and transcriptomics studies in SEA have defined in vivo and in vitro phenotypes of artemisinin resistance, identified its causal genetic determinant, explored its molecular mechanism, and assessed its clinical impact. Specifically, these studies have established that artemisinin resistance manifests as slow parasite clearance in patients and increased survival of early-ring-stage parasites in vitro; is caused by single nucleotide polymorphisms in the parasite's K13 gene, is associated with an upregulated "unfolded protein response" pathway that may antagonize the pro-oxidant activity of artemisinins, and selects for partner drug resistance that rapidly leads to ACT failures. In SEA, clinical studies are urgently needed to monitor ACT efficacy where K13 mutations are prevalent, test whether new combinations of currently available drugs cure ACT failures, and advance new antimalarial compounds through preclinical pipelines and into clinical trials. Intensifying these efforts should help to forestall the spread of artemisinin and partner drug resistance from SEA to sub-Saharan Africa, where the world's malaria transmission, morbidity, and mortality rates are highest.
| S-EPMC4992992 | biostudies-literature