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

Seventeen adult patients with acute Plasmodium falciparum malaria, admitted to the Hospital for Tropical Diseases, were studied. Serial measurements of the serum concentration of C-reactive protein, serum amyloid A protein, and percentage parasitaemia were determined, together with initial measurement of serum electrolytes, liver function, haemoglobin, white cell and platelet counts. Initial C-reactive protein and serum amyloid A concentrations were increased (C-reactive protein mean 49.0 mg/l serum amyloid A 28 mg/l) falling towards the normal range by the seventh day of treatment. There was a significant correlation between the pretreatment parasite count and clinical and laboratory markers of inflammation. C-reactive protein and serum amyloid A concentrations correlated inversely with the serum sodium. These results indicate that measurement of acute phase reactants such as C-reactive protein and serum amyloid A may prove valuable in assessing the severity of P falciparum malaria, and in following the response to antimalarial treatment.
 ...
PMID:Measurement of acute phase proteins for assessing severity of Plasmodium falciparum malaria. 170 16

Tumor necrosis factor, lymphocyte-activating factor, and enhanced levels of type I interferon were found in serum samples taken 2 h after mice infected with Plasmodium vinckei subsp. petteri received a small intravenous injection of endotoxin. These three mediators are among those released when mice receive an endotoxin injection 2 weeks after Mycobacterium bovis BCG or Corynebacterium parvum have been administered. There is indirect evidence that this wider range of mediators is also released in P. vinckei subsp. petteri-infected mice given parenteral endotoxin. A recent report that endotoxin is detectable in the plasma of malaria-infected mice and children implies that these mediators may also be released in the acute phase of the natural infection. We propose that these macrophage-derived mediators may be important in the glucocorticoid antagonism, bone marrow depression, fever, hypergammaglobulinemia, splenomegaly, elevation of serum amyloid A, consumptive coagulopathy, and shock syndrome with associated organ damage which can accompany malaria. The intraerythrocytic parasite death seen at crisis in some malarias, as well as the subsequent development of specific protective immunity, may also depend on these mediators.
 ...
PMID:Possible importance of macrophage-derived mediators in acute malaria. 616 64

Serum retinol concentrations decrease during illness and thus may not accurately reflect the vitamin A status of populations with a high prevalence of illness. To quantify the contribution of illness to low serum retinol in a field study of children aged 6-59 mo in northern Ghana, serum retinol values were compared with two indicators of recent illness; symptoms reported by parents and acute-phase protein concentrations in serum. Serum retinol was not associated with symptoms of illness but showed a significant negative correlation with both alpha 1-acid glycoprotein (AGP) and serum amyloid A (SAA). Elevated AGP was associated with a 24% decrease in mean serum retinol. A large proportion of asymptomatic children had elevated AGP or SAA concentrations, suggesting that subclinical infections may have had important effects on serum retinol. A significant negative correlation between malaria parasite density and serum retinol indicated that malaria may have been one of the subclinical infections responsible. Measurement of AGP may improve interpretation of serum retinol data from populations with a high prevalence of morbidity.
 ...
PMID:Influence of morbidity on serum retinol of children in a community-based study in northern Ghana. 833 47

Advancements in the field of proteomics have provided great opportunities for the development of diagnostic and therapeutic tools against human diseases. In this study, we analyzed haptoglobin and amyloid A protein levels of vivax malaria patients with combinations of depletion of the abundant plasma proteins, 2-dimensional gel electrophoresis (2-DE), image analysis, and mass spectrometry in the plasma between normal healthy donors and vivax malaria patients. The results showed that the expression level of haptoglobin had become significantly lower or undetectable in the plasma of vivax malaria patients due to proteolytic cleavage when compared to healthy donors on 2-DE gels. Meanwhile, serum amyloid A protein was significantly increased in vivax malaria patient's plasma with high statistical values. These 2 proteins are common acute phase reactants and further large scale evaluation with a larger number of patient's will be necessary to establish the possible clinical meaning of the existential changes of these proteins in vivax malaria patients. However, our proteomic analysis suggests the feasible values of some plasma proteins, such as haptoglobin and serum amyloid A, as associating factor candidates for vivax malaria.
 ...
PMID:Proteomic analysis of haptoglobin and amyloid A protein levels in patients with vivax malaria. 2087 98

Malaria is one of the most prevalent infectious diseases worldwide with more than 250 million cases and one million deaths each year. One of the well-characterized malarial-related molecules is hemozoin (HZ), which is a dark-brown crystal formed by the parasite and released into the host during the burst of infected red blood cells. HZ has a stimulatory effect on the host immune system such as its ability to induce pro-inflammatory mediators responsible for some of the malaria related clinical symptoms such as fever. However, the host serum proteins interacting with malarial HZ as well as how this interaction modifies its recognition by phagocytes remained elusive. In the actual study, using proteomic liquid chromatographic mass spectrometry (LC-MS/MS) and immunochemical approaches, we compared the serum protein profiles of malaria patients and healthy individuals. Particularly, we utilized the malarial HZ itself to capture serum proteins capable to bind to HZ, enabling us to identify several proteins such as apolipoprotein E (ApoE), serum amyloid A (SAA), gelsolin, complement factor H and fibrinogen that were found to differ among healthy and malaria individual. Of particular interest is LPS binding protein (LBP), which is reported herein for the first time in the context of malaria. LBP is usually produced during innate inflammatory response to gram-negative bacterial infections. The exact role of these biomarkers and acute phase responses in malaria in general and HZ in particular remains to be investigated. The identification of these inflammation-related biomarkers in malaria paves the way to potentially utilize them as diagnostic and therapeutic targets.
 ...
PMID:New inflammation-related biomarkers during malaria infection. 2202 88

Vivax malaria is the most widely distributed human malaria resulting in 80-300 million clinical cases every year. It causes severe infection and mortality but is generally regarded as a benign disease and has not been investigated in detail. The present study aimed to perform human serum proteome analysis in a malaria endemic area in India to identify potential serum biomarkers for vivax malaria and understand host response. The proteomic analysis was performed on 16 age and gender matched subjects (vivax patients and control) in duplicate. Protein extraction protocols were optimized for large coverage of the serum proteome and to obtain high-resolution data. Identification of 67 differentially expressed and statistically significant (Student's t-test; p<0.05) protein spots was established by MALDI-TOF/TOF mass spectrometry. Many of the identified proteins such as apolipoprotein A and E, serum amyloid A and P, haptoglobin, ceruloplasmin, and hemopexin are interesting from a diagnostic point of view and could further be studied as potential serum biomarkers. The differentially expressed serum proteins in vivax malaria identified in this study were subjected to functional pathway analysis using multiple software, including Ingenuity Pathway Analysis (IPA), Protein ANalysis THrough Evolutionary Relationships (PANTHER) and Database for Annotation, Visualization and Integrated Discovery (DAVID) functional annotation tool for better understanding of the biological context of the identified proteins, their involvement in various physiological pathways and association with disease pathogenesis. Functional pathway analysis of the differentially expressed proteins suggested the modulation of multiple vital physiological pathways, including acute phase response signaling, complement and coagulation cascades, hemostasis and vitamin D metabolism pathway due to this parasitic infection. This article is part of a Special Issue entitled: Proteomics: The clinical link.
 ...
PMID:Serum proteome analysis of vivax malaria: An insight into the disease pathogenesis and host immune response. 2208 83

This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (p<0.05) serum proteins were identified in FM and VM respectively, and almost half (46.2%) of these proteins were commonly modulated due to both of the plasmodial infections. 13 proteins were found to be differentially expressed in FM compared to VM. Functional pathway analysis involving the identified proteins revealed the modulation of different vital physiological pathways, including acute phase response signaling, chemokine and cytokine signaling, complement cascades and blood coagulation in malaria. A panel of identified proteins consists of six candidates; serum amyloid A, hemopexin, apolipoprotein E, haptoglobin, retinol-binding protein and apolipoprotein A-I was used to build statistical sample class prediction models. By employing PLS-DA and other classification methods the clinical phenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases.
 ...
PMID:Proteomic investigation of falciparum and vivax malaria for identification of surrogate protein markers. 2291 77

India significantly contributes to the global malaria burden and has the largest population in the world at risk of malaria. This study aims to analyze alterations in the human serum proteome as a consequence of non-severe and severe infections by the malaria parasite Plasmodium falciparum to identify markers related to disease severity and to obtain mechanistic insights about disease pathogenesis and host immune responses. In discovery phase of the study, a comprehensive quantitative proteomic analysis was performed using gel-based (2D-DIGE) and gel-free (iTRAQ) techniques on two independent mass spectrometry platforms (ESI-Q-TOF and Q-Exactive mass spectrometry), and selected targets were validated by ELISA. Proteins showing altered serum abundance in falciparum malaria patients revealed the modulation of different physiological pathways including chemokine and cytokine signaling, IL-12 signaling and production in macrophages, complement cascades, blood coagulation, and protein ubiquitination pathways. Some muscle related and cytoskeletal proteins such as titin and galectin-3-binding protein were found to be up-regulated in severe malaria patients. Hemoglobin levels and platelet counts were also found to be drastically lower in severe malaria patients. Identified proteins including serum amyloid A, C-reactive protein, apolipoprotein E and haptoglobin, which exhibited sequential alterations in their serum abundance in different severity levels of malaria, could serve as potential predictive markers for disease severity. To the best of our information, we report here the first comprehensive analysis describing the serum proteomic alterations observed in severe P. falciparum infected patients from different malaria endemic regions of India. This article is part of a Special Issue entitled: Proteomics in India.
 ...
PMID:Proteomic analysis of Plasmodium falciparum induced alterations in humans from different endemic regions of India to decipher malaria pathogenesis and identify surrogate markers of severity. 2598 87