Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The high resistance to malaria in the nomadic Fulani population needs further understanding. The ability to cope with multiclonal Plasmodium falciparum infections was assessed in a cross-sectional survey in the Fulani and the Dogon, their sympatric ethnic group in Mali. The Fulani had lower parasite prevalence and densities and more prominent spleen enlargement. Spleen rates in children aged 2-9 years were 75% in the Fulani and 44% in the Dogon (P<0.001). There was no difference in number of P. falciparum genotypes, defined by merozoite surface protein 2 polymorphism, with mean values of 2.25 and 2.11 (P=0.503) in the Dogon and Fulani, respectively. Spleen rate increased with parasite prevalence, density and number of co-infecting clones in asymptomatic Dogon. Moreover, splenomegaly was increased in individuals with clinical malaria in the Dogon, odds ratio 3.67 (95% CI 1.65-8.15, P=0.003), but not found in the Fulani, 1.36 (95% CI 0.53-3.48, P=0.633). The more susceptible Dogon population thus appear to respond with pronounced spleen enlargement to asymptomatic multiclonal infections and acute disease whereas the Fulani have generally enlarged spleens already functional for protection. The results emphasize the importance of spleen function in protective immunity to the polymorphic malaria parasite.
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PMID:Spleen enlargement and genetic diversity of Plasmodium falciparum infection in two ethnic groups with different malaria susceptibility in Mali, West Africa. 1629 5

Plasmodium falciparum infection may result in severe malaria in susceptible individuals. The pathogenesis of severe disease is probably a combination of the sequestration of infected erythrocytes and overstimulation of the immune response. Monocytes are a key source of many of the pro-inflammatory agents implicated but also are found sequestered in blood vessels. However, little is known about the monocyte phenotype in malaria disease. Flow cytometry was performed on fresh whole blood to determine surface expression of four receptors during acute severe and non-severe malaria and again during convalescence when uninfected. Three hundred and fifty-six children with P. falciparum infection were studied and were found to show increased expression of intercellular adhesion molecule-1 (ICAM-1), urokinase plasminogen activator receptor (uPAR), CD23 and chemokine receptor 5 (CCR5) (P<0.001) during acute disease compared with convalescent levels. Using multivariate analysis, it was found that large increases in expression of ICAM-1 (odds ratio (OR) 2.44, 95% CI 1.80-3.32) and uPAR (OR 3.14, 95% CI 1.93-5.09) but small increases in expression of CD23 (OR 0.82, 95% CI 0.68-0.96) were independently associated with severe malaria. These results give an insight into the cellular processes occurring in severe malaria and suggest that pathology is based on a complex repertoire of pro- and anti-inflammatory processes.
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PMID:The effect of Plasmodium falciparum infection on expression of monocyte surface molecules. 1676 92

Protective immunity to malaria is acquired after repeated exposure to the polymorphic Plasmodium falciparum parasite. Whether the number of concurrent antigenically diverse clones in asymptomatic infections predicts the risk of subsequent clinical malaria needs further understanding. We assessed the diversity of P. falciparum infections by merozoite surface protein 2 genotyping in a longitudinal population based study in Tanzania. The number of clones was highest in children 6-10 years and in individuals with long time to previous anti-malarial treatment. Individual exposure, analysed by circumsporozoite protein antibody levels, was associated with parasite prevalence but not with the number of clones. The risk of subsequent clinical malaria in children free of acute disease or recent treatment was, compared to one clone, reduced in individuals with multiclonal infections or without detectable parasites, with the lowest hazard ratio 0.28 (95% confidence interval 0.10-0.78 Cox regression) for 2-3 clones. The number of clones was not associated with haemoglobin levels. A reduced risk of malaria in asymptomatic individuals with multiclonal persistent P. falciparum infections suggests that controlled maintenance of diverse infections is important for clinical protection in continuously exposed individuals, and needs to be considered in the design and evaluation of new malaria control strategies.
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PMID:Multiclonal asymptomatic Plasmodium falciparum infections predict a reduced risk of malaria disease in a Tanzanian population. 1719 13

Failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to pathogenesis of severe malaria. To determine whether this balance is maintained by classical regulatory T cells (CD4(+) FOXP3(+) CD127(-/low); Tregs) we compared cellular responses between Gambian children (n = 124) with severe Plasmodium falciparum malaria or uncomplicated malaria infections. Although no significant differences in Treg numbers or function were observed between the groups, Treg activity during acute disease was inversely correlated with malaria-specific memory responses detectable 28 days later. Thus, while Tregs may not regulate acute malarial inflammation, they may limit memory responses to levels that subsequently facilitate parasite clearance without causing immunopathology. Importantly, we identified a population of FOXP3(-), CD45RO(+) CD4(+) T cells which coproduce IL-10 and IFN-gamma. These cells are more prevalent in children with uncomplicated malaria than in those with severe disease, suggesting that they may be the regulators of acute malarial inflammation.
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PMID:Distinct roles for FOXP3 and FOXP3 CD4 T cells in regulating cellular immunity to uncomplicated and severe Plasmodium falciparum malaria. 1934 13

Human ficolin-2 (L-ficolin; FCN2) is a serum protein binding to sugar moieties of different human micro-pathogens forcing phagocytosis. Here, we investigate the clinical significance of FCN2 in African children with either mild or severe malaria (n = 130 and n = 108, respectively) from Gabon by analyzing three promoter SNPs (-986G>A, -602G>A, and -4A>G) and one single nucleotide polymorphisms (SNP) in exon 8 (+6424G>T) using quantitative TaqMan, real-time polymerase chain reaction (PCR). In addition, we measured the ficolin-2 plasma levels at two time points: on admission (t(0), acute disease) and 4 weeks after treatment (t(1), healthy phase). Comparison of ficolin-2 plasma levels shows that ficolin-2 concentration is highest during acute severe disease. In addition, we determined polymorphisms in the promoter and all coding regions of FCN2 in 40 Gabonese. Linkage disequilibrium data revealed polymorphic allelic combination patterns in the FCN2 promoter region; strong allelic combinations at -986 and -4, and -557 and -64 were found. No FCN2 promoter haplotypes were significantly distributed between mild and severe cases.
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PMID:Ficolin-2 levels and genetic polymorphisms of FCN2 in malaria. 2093 40

The structure of a parasite system is formed and its functioning takes place in qualitatively different environments. The aquatic environment serves as a source of new elements and modules, energy, and information for parasite systems. And the parasite systems, for their part, affect the physical and biological parameters of the environment. Many intestinal infections caused by pathogenic microorganisms generally characterized by an acute disease course are related to a water factor. Such are typhus, typhoids, dysentery, cholera, salmonellosis, virus hepatitis, and others. Many parasitic diseases caused by pathogenic intestinal protistae (lambliasis, amebiasis, balantidiasis), blood parasite protistae (malaria), helminthes (opisthorchiasis, fascioliasis, diphyllobothriasis, cercariosis, pseudoamphistomosis) are also closely related to a water factor. Ascaridiasis, hymenolepiasis, trichocephalosis, and echinococcosis have a less close but still self-evident relationship to a water factor. The clbse relationships of many parasitic diseases to a water factor are also determined by the fact that the life cycles of many parasites necessarily include various intermediate hosts and parasite vectors, such as fishes, mollusks, crustaceans, and insects, which are aquatic organisms at some stages of their life. The results of continuous exposure of people to parasitic diseases are quite similar to the suppressive effects of the environment in the ecologically troublesome regions. The most prognostically useful information is formed while mapping by medical and ecological regions, by employing a combination of current mathematical and cartographical methods. The former include cluster analysis, quartering method, informational logical analysis, which are all described in this article and others. Regional mapping using the parasitological criteria should achieve at least two goals: 1) a scientific one that aids in finding causative connections and to prognosticate a situation; 2) a practical one that assists in developing regional programs for disease control and prevention. It is necessary to use the recommendations described in detail in the article in order to have the maximum results during medical and ecological mapping by the regions with a future goal of obtaining useful prognostic information.
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PMID:[Approaches to developing a procedure for mapping water basin regions, by using the parasitological criteria]. 2193 40

Malaria is a significant global burden but after >30 years of effort there is no vaccine on the market. While the complex life cycle of the parasite presents several challenges, many years of research have also identified several mechanisms of immune evasion by Plasmodium spp. Recent research on malaria, has investigated the programmed cell death-1 (PD-1) pathway which mediates exhaustion of T cells, characterized by poor effector functions and recall responses and in some cases loss of the cells by apoptosis. Such studies have shown exhaustion of CD4(+) T cells and an unappreciated role for CD8(+) T cells in promoting sterile immunity against blood stage malaria. This is because PD-1 mediates up to a 95% reduction in numbers and functional capacity of parasite-specific CD8(+) T cells, thus masking their role in protection. The role of T cell exhaustion during malaria provides an explanation for the absence of sterile immunity following the clearance of acute disease which will be relevant to future malaria-vaccine design and suggests the need for novel therapeutic solutions. This review will thus examine the role of PD-1-mediated T cell exhaustion in preventing lasting immunity against malaria.
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PMID:Malaria drives T cells to exhaustion. 2490 61

Vaccines are one of the most effective interventions to improve public health, however, the generation of highly effective vaccines for many diseases has remained difficult. Three chronic diseases that characterise these difficulties include malaria, tuberculosis and HIV, and they alone account for half of the global infectious disease burden. The whole organism vaccine approach pioneered by Jenner in 1796 and refined by Pasteur in 1857 with the "isolate, inactivate and inject" paradigm has proved highly successful for many viral and bacterial pathogens causing acute disease but has failed with respect to malaria, tuberculosis and HIV as well as many other diseases. A significant advance of the past decade has been the elucidation of the genomes, proteomes and transcriptomes of many pathogens. This information provides the foundation for new 21st Century approaches to identify target antigens for the development of vaccines, drugs and diagnostic tests. Innovative genome-based vaccine strategies have shown potential for a number of challenging pathogens, including malaria. We advocate that genome-based rational vaccine design will overcome the problem of poorly immunogenic, poorly protective vaccines that has plagued vaccine developers for many years.
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PMID:Genome-based vaccine design: the promise for malaria and other infectious diseases. 2519 70

Severe malaria is a density-dependent disease that comprises infected-erythrocyte sequestration, with or without monocytic infiltration, as seen in renal, placental, and lung tissues from severe malaria patients. HIV induces a chronic proinflammatory state with higher numbers of inflammasome-activated monocytes and platelets circulating. The epidemiological and pathological study of S. E. Hochman et al. that was published in a recent issue of mBio (Hochman SE, Madaline TF, Wassmer SC, Mbale E, Choi N, et al., mBio 6:e01390-15, 2015, doi:10.1128/mBio.01390-15) analyzes a large cohort of Malawian children and shows that cerebral malaria in younger HIV-negative children presents as an acute disease predominated by sequestered infected erythrocytes. In contrast, they show that case presentation in older HIV-positive children is as a more lethal acute on chronic disease marked by double the monocytic infiltrates and 5 times as many platelets. This study suggests that cerebral involvement in severe malaria is a pathology similar to that of other organ involvement of severe malaria, with a bias in HIV-positive individuals toward more monocytic infiltrates. The study also addresses the important association of severe malaria and HIV prevalence.
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PMID:A Single Human Cerebral Malaria Histopathologic Study Can Be Worth a Thousand Experiments. 2639 42

Malaria is endemic in India with the incidence of P. falciparum Malaria increasing gradually over the last decade. Severe malaria is an acute disease, caused by P. falciparum, but increasingly also by P. vivax with major signs of organ dysfunction and/or high levels of parasitaemia (>10%) in blood smear. Use of exchange transfusion with antimalarial drug therapy as an additional modality of treatment in severe Falciparum malaria is controversial and is unclear. We report a case of severe malaria complicated by multiorgan failure and ARDS. Patient responded well to manual exchange transfusion with standard artesunate-based chemotherapy.
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PMID:Exchange Transfusion in Severe Falciparum Malaria. 2704 3


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