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)

In Manarintsoa, near Antananarivo, Madagascar, two groups of patients were defined in terms of malaria clinical immune status: Group MA+ consisted of 36 patients who suffered from between one to four malaria attacks (MA) during the 20-week study, and Group MA- who comprised of 48 persons who did not have any malaria attacks during this time. In group MA+, IgM and IgG antibody levels to Plasmodium falciparum exoantigens (E-Ag) were inversely related to the number of malaria attacks. The level of IgM antibodies were significantly higher in group MA+. In contrast, IgG, IgG1, IgG2, IgG3 and IgG4 antibodies to E-Ag were significantly higher in group MA-. The level of IgG1 antibodies was inversely correlated, and IgG2 antibodies were positively correlated to the number of malaria attacks.
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PMID:IgG1 and IgG2 antibody responses to Plasmodium falciparum exoantigens correlate inversely and positively, respectively, to the number of malaria attacks. 880 51

A critical role has been proposed for cytophilic IgG1 and IgG3 subclass antibodies and monocytes and macrophages in antimalarial immunity. Here we compared the isotype composition and avidity of naturally acquired antibodies, as measured by enzyme immunoassay against a detergent-soluble extract of Plasmodium falciparum schizonts, in clinically immune Senegalese adults (n = 33) and semi-immune, adult Amazonian patients (n = 25). Plasma were collected during an acute symptomatic P. falciparum attack and two months later, and in the absence of recrudescence or reinfection. Specific IgG, IgM, IgA, and IgG subclass antibodies were assessed. The results are summarized as follows: 1) high-avidity cytophilic antibodies predominated in clinically immune Senegalese subjects; 2) acutely ill Amazonian patients produced high levels of low-avidity cytophilic antibody; 3) such a response was shortlived, since two months later, the concentrations of cytophilic antibodies were significantly lower; 4) however, affinity maturation of IgG antibodies was observed in Amazonian patients two months after the acute malaria attack. A considerable proportion (35-46%) of anti-P. falciparum IgG1 antibodies produced by African and Amazonian patients was shown to recognize periodate-sensitive carbohydrate epitopes. The potential impact of these findings on the design and evaluation of antimalarial vaccines is discussed.
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PMID:The isotype composition and avidity of naturally acquired anti-Plasmodium falciparum antibodies: differential patterns in clinically immune Africans and Amazonian patients. 884 22

Isotypes of antibodies in adults and 7-15 yr old children living in a malaria endemic area of Sri Lanka were measured by radioimmunoassay against synthetic target antigens derived from two Plasmodium falciparum surface proteins. Greater than 50 per cent of the sample population possessed IgM antibodies while < or = 13 per cent developed each of the IgG antibody isotypes against a repetitive epitope present on the circumsporozoite protein (CS repeat). A more even distribution of IgM, IgG1, IgG2, IgG3 and IgG4 antibodies was seen against a non-repetitive epitope (P103) on a 45 kDa merozoite surface protein. This difference is attributed to a T-independent antibody response against the CS repeat.
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PMID:Isotypes of naturally acquired antibodies to a repetitive & non-repetitive epitope on Plasmodium falciparum surface proteins in an endemic area of Sri Lanka. 906 39

Antibodies to the sexual-stage surface antigens of Plasmodium falciparum, Pfs230 and Pfs48/45, can abolish the infectivity of gametes to mosquitoes; these antigens have been proposed as candidates for inclusion in a malaria transmission-blocking vaccine. One possible mechanism of antibody-mediated transmission blocking is complement-mediated gamete lysis. We have used a panel of human sera from geographically distinct regions where malaria is endemic to investigate whether this may be a mechanism of naturally acquired transmission-blocking immunity to P. falciparum. By immunoprecipitation, we have shown that antibody recognition of Pfs230 and Pfs48/45 is limited, despite universal exposure to P. falciparum gametocytes. In vitro complement-mediated lysis of P. falciparum gametes was positively associated with the presence of antibodies to Pfs230 but not with antibodies to the N-terminal region of the precursor molecule (Pfs260), which is shed from the gametocyte surface at the time of gametogenesis. Similarly, antibodies to two other gametocyte-specific proteins, Pfs48/45 and Pfg27/25, were not associated with gamete lysis. All sera which mediate gamete lysis contain immunoglobulin G1 (IgG1) and/or IgG3 antibodies to gamete surface proteins as determined by an enzyme-linked immunosorbent assay. These data suggest that Pfs230 is a major target of complement-fixing antibodies which may be important for antibody-mediated transmission-blocking immunity.
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PMID:Complement-mediated lysis of Plasmodium falciparum gametes by malaria-immune human sera is associated with antibodies to the gamete surface antigen Pfs230. 923 48

Forty-one African patients suffering from clinically defined severe malaria were studied in the intensive medical care unit of the main hospital in Dakar, Senegal, West Africa. All of these individuals lived in Greater Dakar, an area of low and seasonal Plasmodium falciparum endemicity. Twenty-seven patients (mean age +/- 1 standard deviation, 19.2 +/- 12.7 years) survived this life-threatening episode, but 14 (30.8 +/- 16.2 years old) died despite initiation of adequate treatment. On the day of admission (day 0) and 3 days later, one to two blood samples (i.e., approximately 10 to 15 ml) were obtained from each subject, and different biological parameters were evaluated in the two groups. Plasma samples were tested for their content in tumor necrosis factor alpha (TNF-alpha), soluble receptors I and II for TNF-alpha (TNF-alpha sRI and TNF-alpha sRII), interleukin-6 (IL-6), IL-6 sR, IL-10, and IL-2 sR. The concentrations of all these cytokines and/or their receptors was significantly elevated in patient plasma samples on day 0, and it rapidly decreased in the group of individuals who survived. By comparison, the mean concentration of the same parameters decreased slowly in the group of patients who died (except for IL-10, which dramatically fell in all patient plasma samples soon after initiation of antimalarial treatment). The TNF-alpha sRI level remained significantly elevated among the patients who died, and the highest levels of soluble TNF-alpha sRI receptor were found among the older patients. Parasite-specific immunoglobulin M (IgM), total IgG, IgG1, IgG2, IgG3, and IgG4 were evaluated by enzyme-linked immunosorbent assay using a crude extract of a local P. falciparum isolate as antigen and human class- and subclass-specific monoclonal antibodies. Parasite-specific IgM, total IgG, and IgG1 were detectable in the plasma samples of most of these African patients, whereas IgG2 and IgG4 mean values were low. The mean level of parasite-specific IgG3 was different (P = 0.024) at day 0, i.e., before initiation of intensive medical care, between the group of the 27 surviving subjects and the group of 14 patients dying of severe malaria. As a consequence, most of the African patients who died had only trace amounts or almost no detectable level of parasite-specific IgG3 at the time of admission. In contrast, the presence of even limited IgG3 activity at day 0 was found to be associated with a significantly increased probability of recovering from severe malaria. Therefore, in our study, both an elevated level of TNF-alpha sRI and absence of IgG3 activity were of bleak prognostic significance, whereas a favorable outcome was usually observed when parasite-specific IgG3 activity was detectable. This finding was strongly suggestive of a prime role for these parasite-specific immunoglobulins in the capacity to help recovery from severe malaria.
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PMID:Prognostic value of anti-Plasmodium falciparum-specific immunoglobulin G3, cytokines, and their soluble receptors in West African patients with severe malaria. 923 86

In malaria-endemic areas, infants are relatively protected against malaria infection. Such protection is, though, to be related principally to the transplacental transfer of maternal antibodies. The authors measured total and Plasmodium falciparum-specific IgG (including subclasses), IgM, and IgE antibodies in 154 paired maternal-cord serum samples from an area of meso- to hyperendemic malaria in South Cameroon. Among maternal peripheral blood samples, total IgG and IgM were detected in all samples, IgE in all but two. P. falciparum-specific IgG antibodies were detected in all serum samples, IgM and IgE in 75% of samples. The prevalence rates of anti-P. falciparum IgG subclasses varied from 75% to 97%. With the exception of P. falciparum-specific IgG, all antibody class and subclass levels were lower in cord blood than in peripheral mother blood. P. falciparum-specific IgG1 and IgG3 isotypes were transferred to the offspring more often and more efficiently than IgG2 and IgG4. The detection of total and P. falciparum-specific IgM and IgE in some cord serum samples demonstrated that fetuses can mount humoral response against malaria parasites. The authors also determined whether transplacentally acquired antibodies protect against malaria infection by relating the antibody levels at birth to the risk of acquiring P. falciparum infection during the first 6 months of life. Among various classes and subclasses of P. falciparum-specific antibodies, only IgG2 antibodies were related to a decrease in the risk of acquiring a P. falciparum peripheral blood infection from birth to 6 months of age.
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PMID:Isotypic analysis of maternally transmitted Plasmodium falciparum-specific antibodies in Cameroon, and relationship with risk of P. falciparum infection. 936 4

Antibody(Ab)-mediated inhibition of sporozoite invasion of hepatocytes is a mechanism that has been clearly demonstrated to act upon Plasmodium falciparum pre-erythrocytic stages in humans. Consequently we have analyzed the Ab response to a recently identified P. falciparum sporozoite surface protein, STARP, in malaria-exposed individuals and tested the inhibitory effect of these Ab upon hepatocyte invasion in vitro. STARP-specific IgG were detected in 90 and 61% of sera from regions where individuals were exposed to 100 and 1-5 infectious bites per year, respectively. These IgG were predominantly of the cytophilic IgG1 or IgG3 type. STARP and the major sporozoite surface protein, CS, elicited equivalent IgG levels in adults. When affinity purified from either African immune sera or the serum of an individual experimentally protected by irradiated sporozoite immunization, STARP-specific Ab prevented up to 90% of sporozoites from invading human hepatocytes. The dose-dependent and reproducible inhibition was more pronounced than that observed with human CS-specific Ab affinity purified under identical conditions. Substantial reduction of sporozoite invasion was also observed with Ab induced by artificial immunization with recombinant STARP protein and reactive with the native protein. Taken together with recent findings of human cytotoxic T lymphocytes specific for this antigen, these results promote the interest of studying the efficacy of STARP as a target for immune effector mechanisms operating upon pre-erythrocytic stages.
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PMID:Plasmodium falciparum sporozoite invasion is inhibited by naturally acquired or experimentally induced polyclonal antibodies to the STARP antigen. 936 3

In a cross-sectional survey carried out in west Africa (The Gambia), where Plasmodium falciparum malaria is endemic with seasonal transmission, 178 individuals 1-75 years of age were assessed for their antibody response to the malaria vaccine candidate, merozoite surface protein 2 (MSP2). Total IgG to recombinant antigens representing full-length, repetitive, and group-specific domains of both allelic families of MSP2 was determined by ELISA. The IgG-subclass profile of IgG-positive sera was assessed. Antibody prevalence was age-dependent, reaching a peak during adolescence. In MSP2-seropositive individuals, there was a predominance of cytophilic antibodies (IgG1 and IgG3); IgG1 antibodies were prevalent in children less than 10 years of age, whereas in adolescents and adults MSP2-specific antibodies were predominantly IgG3. In parallel, we conducted a longitudinal study of children (3-8 years of age) from the same community; sera collected before the malaria transmission season were tested for the presence of anti-MSP2 antibodies. The subsequent susceptibility of these children to clinical malaria was monitored and the association between anti-MSP2 antibodies of different IgG subclasses and resistance to clinical malaria was tested. The presence of IgG3 antibodies to MSP2 serogroup A was negatively associated with the risk of clinical malaria whereas IgG1 antibodies to MSP2 serogroup B were associated with an increased risk of clinical infection. Our data suggest that age/exposure-related acquisition of IgG3 antibodies to MSP2 may contribute to the development of clinically protective immunity to malaria.
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PMID:IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria. 957 83

A parasitophorous vacuole protein of Plasmodium falciparum, p126, is a potential candidate for a malaria vaccine. Its N-terminal region, composed of six repeats of eight amino acids, appears to be involved in the induction of protective immunity against P. falciparum challenge in monkeys. This study evaluated the immune response to p126 and to its N-terminal region (Nt47) in patients (n = 45) living in a malaria-endemic area of Brazil (Colina, Porto Velho, Rondonia). Cellular proliferative responses against Nt47 were low and infrequent. The study of the humoral immune response demonstrated that 95% of the patients had detectable anti-p126 antibodies and 77% had anti-Nt47 antibodies. Analysis of the antibody isotypes specific for Nt47 revealed that all four IgG subclasses were present and individuals with higher levels of anti-Nt47 cytophilic IgG antibody (IgG1 + IgG3/IgG2 + IgG4) had significantly lower parasitemia levels, suggesting that antibodies to the N-terminal region of the p126 protein may contribute to acquisition of immunity to P. falciparum malaria.
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PMID:Immune response and lack of immune response to Plasmodium falciparum P126 antigen and its amino-terminal repeat in malaria-infected humans. 966 Apr 61

The mechanisms by which Abs mediate protection during blood-stage malaria infections is controversial, with some evidence pointing to the direct effect of Abs on parasite invasion and growth, while other studies suggest that Abs act in cooperation with monocytes to achieve parasite inhibition. To determine whether the effector phase of protection in vivo to the rodent parasite Plasmodium yoelii yoelii requires Fc receptor bearing cells, we passively transferred immune sera into FcR gamma-chain knockout mice. Inflammatory macrophages from these knockout mice were unable to mediate phagocytosis or Ab-dependent cell-mediated cytotoxicity (ADCC) through Fc gamma RI, Fc gamma RII, or Fc gamma RIII. Passive transfer of either P. y. yoelii hyperimmune sera or anti-GST-PYC2 sera directed to the major merozoite surface protein (MSP-1) of this parasite enabled both BALB/cByJ mice and FcR gamma-chain-deficient mice to resist lethal P. y. yoelii 17XL (Py17XL) challenge. mAb302, a protective IgG3 Ab, also passively protected both strains of mice. Most of these samples contain Ab isotypes that would not be able to protect mice if their protective effects required Ab-dependent cell-mediated cytotoxicity. These results establish that, in this infection, protection is directly mediated by Abs and does not require the participation of Fc receptors.
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PMID:Fc receptors are not required for antibody-mediated protection against lethal malaria challenge in a mouse model. 971 60


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