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Biomedical subjects

P Deloron

Publications and source records attributed to P Deloron.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cytoadherence of Plasmodium falciparum to intercellular adhesion molecule 1 and chondroitin-4-sulfate expressed by the syncytiotrophoblast in the human placenta.

Late stages of Plasmodium falciparum-infected erythrocytes (IRBCs) frequently sequester in the placentas of pregnant women, a phenomenon associated with low birth weight of the offspring. To investigate the physiological mechanism of this sequestration, we developed an in vitro assay for studying the cytoadherence of IRBCs to cultured term human trophoblasts. The capacity for binding to the syncytiotrophoblast varied greatly among P. falciparum isolates and was mediated by intercellular adhesion molecule 1 (ICAM-1), as binding was totally inhibited by 84H10, a monoclonal antibody specific for ICAM-1. Binding of the P. falciparum line RP5 to the syncytiotrophoblast involves chondroitin-4-sulfate (CSA), as this binding was dramatically impaired by addition of free CSA to the binding medium or by preincubation of the syncytiotrophoblast with chondroitinase ABC. ICAM-1 and CSA were visualized on the syncytiotrophoblast by immunofluorescence, while CD36, E-selectin, and vascular cell adhesion molecule 1 were not expressed even on tumor necrosis factor alpha (TNF-alpha)-stimulated syncytiotrophoblast tissue, and monoclonal antibodies against these cell adhesion molecules did not inhibit cytoadherence. ICAM-1 expression and cytoadherence of wild isolates was upregulated by TNF-alpha, a cytokine that can be secreted by the numerous mononuclear phagocytes present in malaria-infected placentas. These results suggest that cytoadherence may be involved in the placental sequestration and broaden the understanding of the physiopathology of the malaria-infected placenta.

Animals↗
PubMed1996

Selected P. falciparum specific immune responses are maintained in AIDS adults in Burkina Faso.

In tropical areas where Plasmodium falciparum malaria is endemic, co-infection with HIV-1 does not lead to a worsening of malaria, raising questions about the immunological interactions between both infections. Alterations of immune response to malaria during HIV-1 infection was investigated in the town of Bobo Dioulasso, Burkina Faso. Sixty-six adults were enrolled, including 37 HIV-1 positive subjects with < 250 CD4+ cells/microliter and clinical AIDS, and 29 HIV-1, negative healthy subjects. In vitro lymphocyte proliferation and cytokine (IFN-gamma, IL-2 and IL-4) production were assessed in isolated mononuclear cells (PBMC) in presence of PHA, PPD or three malarial antigens: the baculovirus-expressed protein from P. falciparum Merozoite Surface Protein-I, a P. falciparum in vitro culture and a crude schizont extract. Compared with healthy subjects. AIDS patients presented with decreased levels of cell proliferation and of IFN-gamma and IL-2 production, in response to all antigens except the schizont extract. Similar levels of IL-4 production were obtained in both groups. Mitogenic stimulation of whole blood cultures was also performed, and revealed similar trends in cytokine production as in PBMC cultures. These results show that some components of the specific human immune responses to falciparum parasites may not be modified during AIDS, in spite of the strong cellular alterations induced by HIV, namely the decrease of the CD4+ lymphocyte subset.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Malaria cellular immune responses in neonates from Cameroon.

T cell responses to leucoagglutinin, PPD, and seven Plasmodium falciparum blood stages antigens were investigated in 164 cord blood samples from Cameroonian neonates. In vitro T cell responses were measured by lymphocyte proliferation, and IL-2, IFN-gamma, and IL-4 release in the presence of crude schizont extract, purified Pf155/RESA protein, and synthetic peptides from Pf155/ RESA. Following culture in presence of leucoagglutinin or PPD, proliferation and cytokine production were very low, as compared to adults from the same area. Interestingly, following stimulation of cord blood lymphocytes by malaria antigens, the percentage of responders and the mean level of positive responses were of the same order than those observed in adults for IL-2 production, while proliferative and IL-4 responses were only marginally decreased. Conversely, IFN-gamma production was highly reduced, as compared to adults. Our results demonstrate that prenatal immune priming to malarial antigens is common in this area and that the fetal immune system is able to respond to antigenic stimuli, as cells proliferate and generate cytokines. As cord blood lymphocytes may be induced to differentiate into effector cells producing predominantly Th1 or Th2 cytokines, malaria during pregnancy might direct the functional capacity of fetal T cells to respond to further infection.

Adult↗
PubMed1996

IgG1 and IgG2 antibody responses to Plasmodium falciparum exoantigens correlate inversely and positively, respectively, to the number of malaria attacks.

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.

Adolescent↗
PubMed1995

Humoral and cellular immune responses to synthetic peptides from the Plasmodium falciparum blood-stage antigen, Pf155/RESA, in Cameroonian women.

T- and B-cell responses to the Plasmodium falciparum blood-stage antigen Pf155/RESA were investigated in 104 Cameroonian women, half of whom were pregnant. We used purified protein and six synthetic peptides representing T- and B-cell epitopes. In vitro T-cell responses were measured by proliferation and IL2, IFN-gamma, and IL4 release. B-cell responses were assessed by plasma antibodies. All peptides induced a cellular response in some individuals. A proliferative response was induced in 25% of the donors by Pf155/RESA, and in 7 to 11% by any peptide. Cytokine release occurred in 23 to 30% of the Pf155/RESA-stimulated cultures, and in 8 to 25% of the peptide-stimulated cultures. Overall, each peptide induced a cellular response (proliferation and/or cytokine release) in 44% of the donors. T-cells from 23% of the donors failed to respond to any peptide. Responding cells did not usually respond in all readouts, and proliferation and release of any of the three cytokines were not correlated. Similarly, antibody and T-cell responses were not related. Selected epitopes of Pf155/RESA, an important vaccine candidate, are well recognized in naturally exposed individuals and are able to activate T-cells to proliferate and to produce various lymphokines in numerous individuals from a malaria endemic area.

Adult↗
PubMed1995

Anti-malaria antibody-producing B cell frequencies in adults after a Plasmodium falciparum outbreak in Madagascar.

The central highlands of Madagascar offer a unique opportunity to explore the malaria immune memory, as the last murderous epidemic in the study area occurred 8 years ago. Quantification of the circulating memory B lymphocytes reacting to Plasmodium falciparum was assessed among 14 Madagascans by using a limiting dilution assay, applied to the EL4 culture system, which leads to activation, proliferation and differentiation into antibody-secreting cells (ASC) of most peripheral B cells. This system allowed us to observe, without any malaria-specific restimulation, a geometric mean frequency of one anti-P. falciparum ASC among 2992 circulating B cells, except for one Madagascan who did not have any detectable ASC. A geometric mean frequency of one anti-P. falciparum ASC among 1403 was obtained for six malaria hyperimmune Cameroonians, but conversely, no anti-malaria ASC was detected in the blood of six malaria non-immune French control subjects. Anti-P. falciparum ASC frequencies and serum specific antibodies were strongly related. Our results indicate that anti-malaria ASC are still present in peripheral blood of Madagascan subjects, who have not been exposed to P. falciparum for several years. These responder B cells reflect the malaria B cell memory acquired during the last epidemic.

Adult↗
PubMed1995

Lack of correlation between HLA class II alleles and immune responses to Pf155/ring-infected erythrocyte surface antigen (RESA) from Plasmodium falciparum in Madagascar.

To investigate the relationships between predominant HLA class II alleles and immune responses to the Plasmodium falciparum ring-infected erythrocyte surface antigen (Pf155/RESA), 50 individuals from the highlands of Madagascar were followed-up from 1988 to 1991. The T cell reactivity and antibody responses to synthetic peptides (EENV)4, (EENVEHDA)4, and (DDEHVEEPTVA)3, representing major T and B epitopes of Pf155/RESA antigen, were assessed with an average of five determinations per individual over the four-year follow-up period. The T cell reactivity was investigated by lymphocyte proliferation and assays for interferon-gamma and interleukin-2 release. Antipeptide antibodies were measured using the Falcon assay screening test-enzyme-linked immunosorbent assay. The cumulative prevalence rates of cellular (range for the three peptides = 64-68%) and antibody responders (range = 70-74%) were similar for each peptide. The HLA class II typing was performed using polymerase chain reaction-restriction fragment length polymorphisms. The prevalent alleles or groups of alleles (frequency > 20%) were similar in responders and nonresponders, both for cellular and antibody responses to each peptide. These were HLA-DR 5 group and HLA-DQA1 *0601, *0101-0102-0104, HLA-DQB1 *0301, and HLA-DPB1 *0101-2601 alleles. Allelic distribution was similar in individuals presenting with (74%) or without (26%) a malaria attack during a 20-week follow-up conducted when malaria was hyperendemic (P > 0.05, by Fisher's exact test). Despite repeated immunologic measures that better identify the responders, no relationship was found between HLA class II alleles and the cellular or antibody responses to Pf155/RESA epitopes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Short report: pefloxacin does not potentiate quinine efficacy against Plasmodium falciparum malaria.

Twenty-four patients presenting with severe Plasmodium falciparum infection at the Kamenge Hospital in Burundi were enrolled in a double-blind study comparing the efficacy of a seven-day regimen of intravenous quinine alone or in combination with pefloxacin. The aim of this study was to assess whether pefloxacin modified chloroquine efficacy or its uptake by infected erythrocytes as shown with other antimalarials. Pefloxacin did not modify the antimalarial activity of quinine, in terms of speed of parasite or fever clearance. Moreover, pefloxacin does not appear to interact with quinine uptake by erythrocytes in humans.

Adult↗
PubMed1995

Antibodies to a Plasmodium falciparum blood-stage antigen as a tool for predicting the protection levels of two malaria-exposed populations.

To evaluate the ability of antibodies to Plasmodium falciparum ring-infected erythrocyte surface antigen (Pf155/RESA) epitopes to discriminate between individuals well protected or poorly protected against malaria, a receiver operating characteristic analysis was performed in two populations living in Madagascar and Malawi. The definition of protection was based on longitudinal measurements of clinical malarial attacks during the season of high malaria transmission in the Madagascar study, and on a cross-sectional measurement of parasitemia in the Malawi study. Antibodies to peptides reproducing the 4-mer, 8-mer, and 11-mer of the Pf155/RESA were tested for their reactivities using the Falcon assay screening test-enzyme-linked immunosorbent assay. Maximal detection of poorly protected individuals (specificity = 100%) corresponded to high cutoff antibody titers (range = 1.65-3.0 optical density [OD] units in the Madagascar study and 0.67-1.42 OD units in the Malawi study) and a sensitivity less than 50%. For a given sensitivity of 50%, specificity ranged from 55% to 62% in the Madagascar study, and from 67% to 94% in the Malawi study. The antibody cutoff titers corresponding to minimal misclassification rates ranged from 0.24 to 1.73 OD units in the Madagascar study and from 0.15 to 0.55 OD units in the Malawi study. For each antibody, the highest detectability value as measured by the area under the curve was obtained for anti-R11 in the Malawi study (0.838). In demonstrating such qualities, antibodies to Pf155/RESA epitopes could be used for screening poorly protected populations in which malaria control programs have to be implemented.

Amino Acid Sequence↗
PubMed1994

Prognostic indicators in adult cerebral malaria: a study in Burundi, an area of high prevalence of HIV infection.

We examined the possible risk factors for poor prognostic in cerebral malaria in 31 adults from Burundi, an area of high prevalence rate of HIV-1 infection. Depth of coma, temperature, vomiting, seizures, parasite load, or anaemia did not modify the outcome. High levels of creatinine, bilirubin, and/or lactates were indicators of poor prognostic. HIV-1 infection did not affect the clinical or biological presentation of cerebral malaria, and did not appear to influence the outcome.

Adult↗
PubMed1994

Quantification of T cells reactive to Pf155/RESA peptides in Plasmodium falciparum-exposed individuals.

This study was designed to estimate, among T lymphocytes circulating in the peripheral blood of donors exposed to malaria parasites, the frequencies of those responding to Plasmodium falciparum antigens, and more specifically to Pf155/RESA peptides. The values of peptide-reactive T-cell frequencies were dispersed and rather low, ranging from 1:24,000 to undetectable (superior to 1:300,000). Subjects presented with different past exposure to parasites: either they had been repetitively exposed to malaria parasite infestation or they were recovering from a recent treated malaria attack. However, they had similar frequencies of T cells reactive to Pf155/RESA peptides. With cells from a minority of patients, "saw-tooth curves" were obtained, suggesting the existence of suppressor mechanisms operating in vitro in our limiting dilution assay.

Adult↗
PubMed1994

Immunologic and biochemical alterations in severe falciparum malaria: relation to neurological symptoms and outcome.

The relation between the immune response and the clinical features of severe falciparum malaria was studied in Burundian adults with (n = 31) and without (n = 17) cerebral involvement. At the time of admission, mean values for age, temperature, and blood levels of hemoglobin, creatinine, bilirubin, and glucose were similar in the two groups. Plasma levels of tumor necrosis factor alpha, interferon gamma, interleukin 10 (IL-10), and soluble intercellular adhesion molecule 1 were similarly elevated in the two groups. Mean parasite counts and mean plasma levels of soluble E-selectin were higher in severe noncerebral malaria than in cerebral malaria and were correlated with each other. After adjustment for parasitemia, levels of soluble E-selectin remained higher in noncerebral malaria. All seven patients who died had cerebral disease. These patients had higher levels of creatinine, bilirubin, IL-10, and soluble E-selectin than did patients with nonfatal cerebral malaria. After adjustment for creatinine and bilirubin levels, IL-10 and soluble E-selectin concentrations were similar in fatal and nonfatal cases of cerebral infection. In these African adults, none of the immunologic variables investigated was specific to cerebral malaria or to a fatal outcome.

Adolescent↗
PubMed1994

Antibodies to the 4-mer repeat of the ring-infected erythrocyte surface antigen (Pf155/RESA) protect against Plasmodium falciparum malaria.

To investigate the protective role of antibodies to the ring-infected erythrocyte surface antigen (Pf155/RESA) epitopes against Plasmodium falciparum clinical malaria, a cohort study was conducted in a Malagasy village over 7 months. In the 304 individuals included, 127 experienced P. falciparum attacks of under 1500 parasites/microliters with no clinical symptoms (protected individuals) and 177 experienced at least one clinical or preclinical P. falciparum attack requiring therapy (unprotected individuals). Antibodies to whole Pf155/RESA, to single epitopes of the 3' terminus, (EENV)4 and EENVEHDA(EENV)2 had higher responses in protected than in unprotected individuals (P = 0.006, P = 0.005, P = 0.05 respectively). Within the whole pattern of antibodies to the Pf155/RESA epitopes, only anti-R4 was related to protection independently of age and anti-wR. The Pf155/RESA 4-mer repeated epitope might be of interest for inclusion in a vaccine against the asexual blood stages of P. falciparum.

Adolescent↗
PubMed1994

The multifactorial and multistage character of protective immunity to Plasmodium falciparum, naturally acquired by an indigenous population in Burkina Faso.

In malaria-endemic areas, protective immunity is acquired gradually. Some authors have proposed that different stages can be distinguished during development. To test this hypothesis, several in vitro assays of the host immune response to P. falciparum were performed in three groups of individuals: 'unprotected' children with clinical attacks, 'semi-immune' children, without clinical attacks but with transient high parasitaemias during the transmission period, and 'protected' adults with low residual parasitaemias. By comparison of immune responses in these groups and multifactorial analyses, discriminant factors and potential protective mechanisms were identified. Anti-RESA antibody levels were lower in 'unprotected' than in 'semi-immune' children, while specific cellular responses, TNF levels and percentage of activated T lymphocytes were higher. Low humoral immunity and high cellular activation in children were followed by high humoral immunity and low cellular activation in adults. Therefore, protective immunity seems to pass through different stages and to result from the association of different immune mechanisms according to the level and duration of the individual experience of malaria.

Adolescent↗
PubMed1994

Soluble intercellular adhesion molecule-1 and E-selectin levels in plasma of falciparum malaria patients and their lack of correlation with levels of tumor necrosis factor alpha, interleukin 1 alpha (IL-1 alpha), and IL-10.

Intercellular adhesion molecule-1 and E-selectin levels were increased in the plasma of 60 falciparum malaria patients and were not related to levels of tumor necrosis factor alpha, interleukin 10, or interleukin 1 alpha. Soluble E-selectin was correlated to disease; its level in plasma was related to levels of both tumor necrosis factor soluble receptors and biological markers of disease severity and returned to baseline after parasite clearance faster than that of soluble intercellular adhesion molecule-1.

Animals↗