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P Deloron

Publications and source records attributed to P Deloron.

At least 73 records · Page 4Linked to original sources
PubMed1993

Neopterin levels in plasma during a longitudinal study in an area endemic for malaria.

Neopterin levels in plasma were measured during a longitudinal study of 75 patients living in an area endemic for malaria. The maximum levels were observed in August/September, the period of peak transmission of the disease. During the dry season, levels remain elevated. No relationship was found between the level of neopterin and the individual's immune status against malaria. Tumor necrosis factor (TNF), activated T lymphocytes subpopulations, soluble interleukin 2 receptors, and anti-circumsporozoite protein antibodies were not correlated with neopterin levels during the period of peak transmission. In contrast, neopterin levels were correlated with anti-Plasmodium falciparum antibodies detected by immunofluorescence. It was concluded that, in a population of chronic parasite carriers subjected to repeated infestations, neopterin was a good indicator of slowly acquired immunity in stable transmission area, but it poorly reflected acute immune responses.

Adolescent↗
PubMed1993

Global occurrence of Plasmodium vivax-like human malaria parasite.

A Plasmodium vivax-like human malaria parasite was recently identified from Madang, a holoendemic malarious region in Papua New Guinea. The complete nucleotide sequence of the circumsporozoite (CS) protein gene of this parasite is presented here. The CS protein of this parasite has an 11-mer repeat sequence and is different from the other known CS protein genes of human malaria parasites. However, it is identical to the CS protein gene of a monkey malaria parasite, Plasmodium simiovale. This P. vivax-like malaria parasite was found in Sepik, another malarious region of Papua New Guinea, and in Brazil, Indonesia, and Madagascar. No pure isolate of this parasite was identified. Specific oligonucleotide probes were used to determine relative proportion of the P. vivax-like parasite in P. vivax (type 1 and type 2) mixed field isolates. Compared with P. vivax or Plasmodium falciparum, the circumsporozoite protein of P. vivax-like parasites showed markedly less polymorphism.

Amino Acid Sequence↗
PubMed1993

Quantification of antibody-secreting lymphocytes that react with Pf155/RESA from Plasmodium falciparum: an ELISPOT assay for field studies.

We have adapted the enzyme-linked immunospot assay (ELISPOT) to enumerate the cells from Plasmodium falciparum-primed donors that produce IgG in vitro in response to malaria antigens. In vitro activation of cell cultures with two synthetic peptides (EENVEHDA)4, and (LGRSGGDIIKMQTL) corresponding to immunodominant T cell epitopes of the ring-infected erythrocyte surface antigen (Pf155/RESA) gave specific antibody-secreting cells (ASC) in five and six of the 15 P. falciparum-primed donors from Cameroon. Antibodies produced after a stimulation by synthetic peptides reacted also with total parasite proteins. However, crude P. falciparum antigen did not trigger a higher number of cells than did synthetic peptides. The absence of significant relation between the presence of sera antibodies and in vitro ASC against the same peptide suggests that the kinetics of circulating primed lymphocytes and antibodies are different. We evaluated 0.04-0.29% of peripheral blood B cells to be the frequency of memory cells specific to a single Pf155/RESA epitope in these donors. This study suggests that the ELISPOT assay should permit the analysis of B cell responses to malarial antigens at the single-cell level and its applicability to epidemiological field studies. This assay should be well suited to the identification of T helper epitopes capable of inducing the production of antibodies by human B cells, and will constitute an important tool for the selection of immunogens to be included in a subunit vaccine.

Adolescent↗
PubMed1993

Ring-infected erythrocyte surface antigen (Pf/155RESA) induces tumour necrosis factor-alpha production.

Cerebral malaria is probably related to an overstimulation of the immune system and the cytokine network. We have previously demonstrated that tumour necrosis factor (TNF) secretion by human macrophages can be induced by soluble and heat-stable malarial antigens. Indirect evidence from epidemiological and in vitro studies suggests that Pf155/RESA can be considered as a candidate for triggering TNF secretion. Thus we conducted experiments to investigate the relationship between Pf155/RESA and TNF production. The SGE1 strain of Plasmodium falciparum was compared with the P. falciparum FCR3 strain, which does not express Pf155/RESA protein, for ability to induce TNF secretion by normal human macrophages in vitro. Synthetic peptides from the Pf155/RESA antigen ((EENV)4, (EENVEHDA)4, (DDEHVEEPTVA)3), were used in some experiments. TNF levels were measured by an immunoradiometric assay. We observed that the RESA-defective strain induces lower levels of TNF after schizont rupture than the SGE1 strain. Moreover, substantial TNF secretion was detected when macrophages were incubated with all three peptides, maximum levels being obtained with the (EENV)4 peptide. Although previous reports have described TNF-inducing activity of phospholipid from P. falciparum, these findings strengthen the evidence for Pf155/RESA antigens also being involved in TNF production during malaria.

Amino Acid Sequence↗
PubMed1993

Isotypic analysis of Plasmodium falciparum-specific antibodies and their relation to protection in Madagascar.

We previously reported that antibodies to the central repeat (DDEHVEEPTVA) of Pf155/RESA, a major Plasmodium falciparum antigen, were negatively related to antimalarial protection. We measured levels of isotype antibodies to this epitope and to P. falciparum in 76 Madagascan subjects. Immunoglobulin G (IgG) and isotype antibodies specific for P. falciparum had similar levels in individuals who were considered protected and those who were not (as determined during a longitudinal follow-up). The levels of IgG1 antibodies to (DDEHVEEPTVA)3 were higher in nonprotected subjects. The levels of total IgG and of other isotype antibodies had a similar tendency to be higher in nonprotected than in protected individuals.

Amino Acid Sequence↗
PubMed1993

Evaluation of a nonisotopic DNA assay kit for diagnosing Plasmodium falciparum malaria in Madagascar.

This study evaluated a nonisotopic DNA assay kit for diagnosing Plasmodium falciparum malaria in an area of Madagascar where all Plasmodium species of human malaria are present and where malaria is endemic. Blood samples from 440 healthy children and 20 healthy adults were processed and assayed in a single day in a blind protocol. The parasitemia levels of the four Plasmodium species were determined by microscopic examinations and by counts of numbers of malaria parasites per 1,000 white blood cells. Relative to P. falciparum infections, the DNA assay results agreed with those of microscopy for 207 positive and 239 negative samples; two samples were scored as positive by the DNA probe that were not detected by microscopy, and 12 samples were scored as positive by microscopy but were not detected by the assay. Relative to microscopy, the sensitivity of the assay was 95%, the specificity was 99%, and the effective sensitivity threshold of the DNA probe assay was approximately 30 parasites/mm3 of blood. The assay did not detect infections with either P. vivax, P. malariae, or P. ovale alone, but detected mixed infections of P. falciparum with either P. vivax or P. ovale. With this nonisotopic DNA probe assay, we were able to process large numbers of samples efficiently and to detect P. falciparum malaria infections with high sensitivity and specificity in a population that did not display overt disease symptoms.

Adolescent↗
PubMed1993

Human immune responses to the Plasmodium falciparum ring-infected erythrocyte surface antigen (Pf155/RESA) after a decrease in malaria transmission in Madagascar.

A resurgence of falciparum malaria occurred in the central highlands of Madagascar in the 1980s and was responsible for an outbreak in 1986-1987. Since 1989, transmission has decreased dramatically. In April 1991, we investigated the humoral and cellular immune responses of 53 inhabitants of the village of Manarintsoa to six synthetic peptides that reproduced the major B and/or T cell epitopes of the Pfl 55/ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum. The presence of RESA peptide-reactive T cells was assessed by lymphocyte proliferation assay as well as by detection of in vitro production of interferon-gamma and interleukin-2. The mean values of these cellular responses were low, and the results obtained in these three tests showed no correlation. Twenty-seven subjects presented with anti-RESA antibodies as detected by modified immunofluorescent assay, but the mean levels of anti-peptide antibodies were low. When compared with data obtained in January 1988 from the same subjects with three of the six peptides, the present data demonstrated a decrease in the response to these peptides in terms of both proliferative response and mean antibody titers. The mean values of anti-RESA antibodies remained unchanged. The fact that cellular and humoral responses to the major Pfl 55/RESA epitopes decreased but did not disappear probably reflects both the remainder of the acquired immunity resulting from the 1986-1987 malaria outbreak, and its conservation by the very low level of transmission since 1989.

Adolescent↗
PubMed1993

Humoral and cellular immune responses to the circumsporozoite protein of Plasmodium vivax in Madagascar.

Plasmodium vivax malaria is prevalent during the rainy season in the central highlands of Madagascar. In April 1991, we investigated the cellular and antibody immune responses of 53 inhabitants of Manarintsoa, a village in this area, to four antigens corresponding to B and T cell epitopes of the P. vivax circumsporozoite (CS) protein. Cellular responses were assessed by lymphocyte proliferation assay as well as by detection of interferon-gamma and interleukin-2 production in vitro. Cell culture was performed with two overlapping synthetic peptides (CSVTCGVGVRVRSRVNA [amino acids 311-326]) and VRVRSRVNAANKKPED [amino acids 319-334]) from the vicinity of the highly conserved region II of the CS protein. In at least one of the three assays, cells from seven subjects showed a positive response to CSVTCGVGVRVRSRVNA, while cells form 14 subjects responded to VRVRSRVNAANKKPED. Antibodies directed against the two recombinant antigens, NS1(81)V20 and rPvCS-2, both of which contain the entire central repeat region of the P. vivax CS protein, plus regions I and II in the case of rPvCS-2, were measured by the Falcon assay screening test-enzyme-linked immunosorbent assay. Eight and nine subjects had antibodies to NS1(81)V20 and rPvCS-2, respectively. The presence of antibody responses to both recombinant antigens was related (P = 0.02, by Fisher's exact test), but was not related to the presence of a cellular response to peptides from vicinity of region II (P > 0.1, by Fisher's exact test).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Is immunity to malaria really short-lived?

Protection against Plasmodium falciparum malaria is usually considered to be the cumulative product of repeated exposure to parasites, and thus a function of age, in endemic areas. The recent outbreak of malaria in the central highlands of Madagascar gave Philippe Deloron and Claire Chougnet the opportunity to compare the incidence of malaria in children and young adults exposed to malaria for the first time, with that in older adults who spent their childhood in the study area before malaria control was introduced. Protection, as well as immune responses to two major P. falciparum antigens, was not related to age. Individuals older than 40 years were more protected than were younger adults. This increased protection was probably due to immunological memory.

Journal Article↗
PubMed1992

Kinetics of lymphocyte subsets from peripheral blood during a Plasmodium falciparum malaria attack.

Variations of lymphocyte subsets were followed longitudinally in 16 patients during an acute falciparum malaria attack. Before treatment, lymphocyte numbers were highly reduced, but the subset distribution was similar to that of healthy individuals. After parasite clearance, lymphocyte counts were normalized and the subset distribution was unchanged. This led to a normalization of all the absolute counts of lymphocyte subsets, except CD8+. The fast normalization of lymphocyte counts suggests that the initial decrease in lymphocyte numbers may reflect sequestration. Magnitude and kinetics of this variation were not related to parasite density or to severity of the attack. Activated T cells (CD3+HLA-DR+) were fewer in African than in European patients, suggesting the importance of the past exposure to malaria parasites in reallocation phenomena. These variations in lymphocyte numbers must be taken into account in the design and the analysis of cellular investigations in patients experiencing a falciparum malaria attack.

Adult↗
PubMed1991

Human immune response in Plasmodium falciparum malaria. Synthetic peptides corresponding to known epitopes of the Pf155/RESA antigen induce production of parasite-specific antibodies in vitro.

Autologous cell mixtures containing T cells, B cells, and adherent accessory cells from individuals primed to the malaria parasite Plasmodium falciparum by repeated natural infections were investigated for induction of Ig and antibody secretion in vitro. In vitro activation of cell cultures with two synthetic peptides corresponding to immunodominant T cell epitopes of the merozoite Ag ring-infected erythrocyte surface Ag (Mr 155,000) (Pf155/RESA), one from its carboxyl-terminal repeat and one from its nonrepeated amino-terminal region, gave rise to significant IgG secretion. Supernatants from lymphocyte cultures activated with either one of these peptides contained antibodies reacting with P. falciparum Ag in immunofluorescence assays and with Pf155/RESA peptides in a slot blot assay. No anti-P. falciparum antibodies were induced in the medium controls by lymphocyte stimulation with either tetanus toxoid or PWM. Induction in vitro of anti-Pf155/RESA antibodies was correlated with the presence of such antibodies in the sera of the lymphocyte donors, suggesting that the induction of antibody secretion reflected a secondary response in vitro of in vivo primed cells. Inspection of antibody profiles in individual donors revealed that the peptide corresponding to a sequence in the 3' repeat region induced anti-Pf155/RESA peptide antibodies reacting with identical or related and cross-reacting sequences in the 3' or 5' repeat region of the molecule. In contrast, the peptide corresponding to a nonrepeated T cell epitope in the amino terminus of the molecule only induced antibodies to an immunodominant amino-terminal B cell epitope partly overlapping with the T cell reactive sequence. Similar findings were made in the lymphocyte donors' plasma, frequently displaying significant correlations between antibody reactivities to the repeat peptides but not between these reactivities and those to the amino-terminal peptide. The marked specificity of this antibody formation in vitro suggests an underlying process of cognate recognition involving Ag-specific T and B cells reacting with different segments of the inducer peptide. The present experimental system should be well suited for identification of Th epitopes capable of inducing the production of antibodies of defined specificity in the human system.

Adolescent↗
PubMed1991

Assessment of the protective value of antibodies to the Plasmodium falciparum ring-infected erythrocyte surface antigen (RESA): an epidemiologic study in Madagascar.

The ring-infected erythrocyte surface antigen (RESA), a Plasmodium falciparum merozoite antigen, is a major vaccine candidate against falciparum malaria. To investigate the protective role of antibodies to RESA and its 4-mer, 8-mer, and 11-mer repeated amino acid sequences under conditions of natural exposure, a case-control and a cohort study were carried out in 1988 in a rural community in Madagascar where malaria reappeared recently. Fifty cases with greater than 1,000 P. falciparum per microliter of blood, and 45 controls with a negative blood smear were enrolled and sera were collected. Forty-one controls were followed for 20 weeks to identify malarial attacks. Protection against clinical malaria was assessed by the absence of malarial attacks requiring therapy. At enrollment, positivity rates and reactivity levels to RESA or repeats were similar in cases and controls. The 11-mer repeat antibody level was higher in the 26 controls who experienced at least one malarial attack during follow-up than in the 15 other controls (p less than 0.01). Thus, antibodies to the 11-mer repeat were predictors of the subsequent appearance of the disease. After adjustment for antibodies to the 11-mer repeat, antibodies to whole RESA had a negative predictive value on the occurrence of malarial attacks (p = 0.04). Different epitopes within the RESA molecule may elicit production of antibodies with different activities.

Adult↗
PubMed1991

Relationships between clinical protection and antibodies to Plasmodium falciparum RESA (ring-infected erythrocyte surface antigen) peptides.

A longitudinal study involving 76 individuals living in Dafinso and Vallée du Kou (near Bobo-Dioulasso, Burkina Faso, West Africa) was performed in June 1987 (beginning of the transmission period), August-September 1987 (during) and January 1988 (after). The serological antibody (Ab) responses against synthetic peptides representing repeat amino acid sequences of the P. falciparum Ring-Infected Erythrocyte Surface Antigen (RESA): (EENV)5, (EENVEHDA)4, (DDEHVEEPTVA)2 were evaluated by ELISA. The clinical longitudinal study during the transmission period allowed us to define three different groups in terms of age and occurrence of clinical malarial attack (greater than 5000 parasites mm-3 of blood and axillary fever greater than 37.7 degrees C). Levels (A620) of Ab to (EENVEHDA)4 and (DDEHVEEPTVA)2 were correlated with age. The adult group (III) had the highest prevalences of Ab to RESA peptides. No significant difference was found between groups of children with or without malaria attack. Nevertheless, at the beginning of the transmission period, children who had at least one malaria attack during the study presented the lowest level of antibodies to RESA peptides.

Animals↗
PubMed1991

Transmission and epidemiology of newly transmitted falciparum malaria in the central highland plateaux of Madagascar.

The recent reappearance of Plasmodium falciparum in the central highland plateaux of Madagascar has led to an important increase in both morbidity and mortality in the population. To understand the phenomena that originated this outbreak, and to evaluate the clinical and biological reactions of the population, we conducted entomological surveys during the whole malaria transmission season of 1988. In parallel, 41 individuals presenting with a malaria attack in January were given a curative antimalarial treatment and were followed weekly for 20 weeks, until the end of the transmission season, in June. During the follow-up, individuals presenting with a clinical malaria attack or with a parasite density above 5000 per mm3 of blood were again given antimalarial treatment. Overall, individuals presented with an average of 5.6 thick blood smears positive for P. falciparum, and 1.4 malaria attacks requiring treatment. Plasmodium falciparum prevalence rates gradually increased to 53.8% in April, one to two months after the observed peak of transmission, then decreased to 15.4% at the end of follow-up. The proportion of P. falciparum infections with clinical symptoms did not follow a similar temporal evolution and was significantly lower than at enrollment. Splenic rates gradually decreased from 29.3-2.6%, while anti-P. falciparum and anti-Pfl55/RESA antibodies increased. For the whole transmission season individuals experienced a mean 1.5 infective bites; the malaria vectors were Anopheles gambiae s. 1 and An. funestus. This study demonstrates that, in this population newly exposed to P. falciparum infections, almost all sporozoite inoculations lead to blood parasite infection requiring treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗