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)

Serum levels of malaria antigens, antimalaria antibodies, immune complexes and complement components have been followed up in 23 patients suffering from acute malaria infection and recovering under therapy. Malarial antigens in serum were detected by counterimmunoelectrophoresis: the peak was observed before therapy started and their levels rapidly decreased. Specific antimalarial antibodies became detectable 5--7 days after starting treatment in patients with a first infection. Immune complexes were detected in 21 of 23 sera with a peak level between days 5 and 9. A marked decrease of C4 and C3 was observed in the presence of normal levels of factor B.
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PMID:[Demonstration of soluble parasite antigens, the corresponding antibodies and immune complexes in acute malaria]. 39 Jun 95

In 17 semi-immune adult volunteers, chemoprophylaxis with 300 mg chloroquine base weekly for six months was found to be effective in suppressing malaria. However, following 3 months of chemoprophylaxis, a significant reduction of IFA titres was seen lasting up to 2 months after chloroquine withdrawal. There was resurgence of malaria in the post-intervention phase. 2 months after drug withdrawal, serum concentrations of IgG and factor B were significantly reduced. 3 months after initiation of chloroquine prophylaxis, a temporary but significant decrease of IgG and IgM serum concentrations was found with a corresponding decline in the number of B-lymphocytes and regulatory T-cells. These returned to normal at 6 months of chemoprophylaxis. Our findings suggest that short-term malaria chemoprophylaxis may significantly interfere with humoral and cell-mediated immunity in areas of intensive P. falciparum transmission.
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PMID:The effect of short-term malaria chemoprophylaxis on the immune response of semi-immune adult volunteers. 207 77

Chloroquine, a well-known anti-malarial and anti-inflammatory agent, was studied with respect to its effect on the serum complement system. The drug exhibited significant in vitro anti-complementary activity only at a very high non-therapeutic dose of 48 mg/ml. Chloroquine-induced in vitro complement consumption was observed to take place even in the absence of Ca2+ and Mg2+ ions. The drug also haemolyses rabbit erythrocytes in the presence of Mg2+-EGTA and immunoelectrophoretic studies of fresh human serum and chloroquine incubation mixture against specific anti-C3 and anti-factor B antisera have demonstrated that it cleaves both C3 and factor B. In another experiment, chloroquine failed to exert inhibitory effects on complement utilisation by immune complexes. Studies of the serum complement profile of Plasmodium falciparum-infected malaria patients receiving chloroquine therapy indicated that, in contrast to the situation in vitro, the serum C3 level is invariably decreased. Marginal reductions in the levels of C4, factor B and properdin were also found in some of these patients, while administration of chloroquine to normal human individuals failed to produce any significant change in their serum complement profile. It is, therefore, probable that malarial parasites and not chloroquine are responsible for complement activation in patients suffering from malaria.
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PMID:Effects of chloroquine on the serum complement system. 390 2

Monocytes and polymorphonuclear leukocytes from normal blood donors phagocytosed preferentially Plasmodium falciparum-infected red blood cells (IRBC) in presence of sera from individuals living in areas endemic for malaria. Total complement or factor B heat inactivation of immune or normal serum does not alter opsonic activity directed against IRBC.
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PMID:Independence of complement on in vitro immune phagocytosis of plasmodium falciparum parasitised erythrocytes by human monocytes and polymorphonuclear leukocytes. 636 95

The nucleotide and deduced amino acid sequence of a serine protease (AgSp14D1) from the human malaria vector, Anopheles gambiae, is presented. The gene product is a 360 amino acid protein that contains two domains and has the highest sequence similarity to the Drosophila melanogaster serine protease easter and to prophenol oxidase activating enzyme (pPAE) from Manduca sexta. The catalytic domain is at the carboxy terminus and has the conserved serine, histidine and aspartic acid residues found in serine proteases as well as six cysteines common to invertebrate enzymes. The amino terminus contains critical cysteines that define a clip (=disulphide knot) domain which places this gene product in a subfamily of regulatory serine proteases that includes not only easter and pPAE but also the Drosophila proteins masquerade, stubble and snake as well as proclotting enzyme and factor B from the horseshoe crab. In situ hybridization to the polytene chromosomes detects a single band at 14D and Southern analysis with a probe from the 5' end of the gene confirms the single copy status of this gene. Northern analysis reveals changes in transcript abundance during development and following blood feeding. Interestingly, this analysis also shows an increase in transcript levels following wounding or injection of bacteria.
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PMID:An easter-like serine protease from Anopheles gambiae exhibits changes in transcript abundance following immune challenge. 1046 50

After ingestion by mosquitoes, gametocytes of malaria parasites become activated and form extracellular gametes that are no longer protected by the red blood cell membrane against immune effectors of host blood. We have studied the action of complement on Plasmodium developmental stages in the mosquito blood meal using the rodent malaria parasite Plasmodium berghei and rat complement as a model. We have shown that in the mosquito midgut, rat complement components necessary to initiate the alternative pathway (factor B, factor D, and C3) as well as C5 are present for several hours following ingestion of P. berghei-infected rat blood. In culture, 30 to 50% of mosquito midgut stages of P. berghei survived complement exposure during the first 3 h of development. Subsequently, parasites became increasingly sensitive to complement lysis. To investigate the mechanisms involved in their protection, we tested for C3 deposition on parasite surfaces and whether host CD59 (a potent inhibitor of the complement membrane attack complex present on red blood cells) was taken up by gametes while emerging from the host cell. Between 0.5 and 22 h, 90% of Pbs21-positive parasites were positive for C3. While rat red and white blood cells stained positive for CD59, Pbs21-positive parasites were negative for CD59. In addition, exposure of parasites to rat complement in the presence of anti-rat CD59 antibodies did not increase lysis. These data suggest that parasite or host molecules other than CD59 are responsible for the protection of malaria parasites against complement-mediated lysis. Ongoing research aims to identify these molecules.
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PMID:Interaction between host complement and mosquito-midgut-stage Plasmodium berghei. 1144 87

Cerebral malaria (CM) is the most severe manifestation of clinical malaria syndromes and has a high fatality rate especially in the developing world. Recent studies demonstrated that C5(-/-) mice are resistant to experimental CM (ECM) and that protection was due to the inability to form the membrane attack complex. Unexpectedly, we observed that C4(-/-) and factor B(-/-) mice were fully susceptible to disease, indicating that activation of the classical or alternative pathways is not required for ECM. C3(-/-) mice were also susceptible to ECM, indicating that the canonical C5 convertases are not required for ECM development and progression. Abrogation of ECM by treatment with anti-C9 antibody and detection of C5a in serum of C3(-/-) mice confirmed that C5 activation occurs in ECM independent of C5 convertases. Our data indicate that activation of C5 in ECM likely occurs via coagulation enzymes of the extrinsic protease pathway.
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PMID:The C5 convertase is not required for activation of the terminal complement pathway in murine experimental cerebral malaria. 2268 74