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R Perraut

Publications and source records attributed to R Perraut.

At least 19 recordsLinked to original sources
PubMed2005

Efficacy comparison between anti-malarial drugs in Africans presenting with mild malaria in the Central Republic of Africa: a preliminary study.

Drug resistance to Plasmodium falciparum contributes to major health problems in central Africa and, as a consequence, poverty. We have analyzed the efficacy of three currently available antimalarial drugs to treat symptomatic, uncomplicated P. falciparum malaria in semi-immune adults living in Bangui, Central Republic of Africa. 210 consecutive individuals were enrolled in the survey, of which 45 were excluded. Those having received dihydroartemisin proved significantly less parasitemic than those having received quinine per os or sulfadoxin-pyrimethamin (chi2 = 16.93; p < 0.05), and 75% recovered in two days compared to 57 and 44%, respectively. The 25% who did not recover benefited from a second cure with dihydroartemisin, which proved 100% efficient. The most accurate protocol remains to be established by analyzing clinical and parasitological data and taking into account the economics of the country.

Adolescent↗
PubMed2004

[Post-transfusion malaria: is the risk irreconciliable with biological silence?].

Despite the relatively high frequency of imported malaria in metropolitan France, the transmission of malaria by transfusion is exceptional. The screening of donations to determine those at risk is performed by an interview, and by the testing of serology for defined groups of donors. However, the exclusion of a candidate 'at risk' as a blood donor, by a pre-donation interview, is not completely mastered and the discrimination by biological examination lacks sensitivity, as much for methodological reasons as for reasons linked to the complex parasitic pathogenic agent (Plasmodium ssp.), as for the specific host defence system. The risk of introducing an unsafe-potentially dangerous (transfusion-transmitted malaria is often lethal)-element into the transfusional circuit is not completely covered. Is serology testing the most adequate test to avoid the risk of infected donations, in particular by Plasmodium falciparum; what are the alternatives and what will be the eventual added-costs of the biological qualification of such donations? The transfusional risk linked to Plasmodium seems, however, to be reduced to a minimum, concerning the circulation of plasma, which could represent an alternative for donors at real risk (rare) and those with a supposed risk (relatively numerous).

Animals↗
PubMed2002

Distinguishing features of anti-beta2 glycoprotein I antibodies between patients with leprosy and the antiphospholipid syndrome.

Anticardiolipin (ACA), anti-beta2 glycoprotein I (beta2GPI), and antiprothrombin antibodies of IgG and IgM classes were quantitated by enzyme-linked immunosorbent assays in 176 untreated leprosy patients across the histopathological spectrum. Positivity rates ranged from 21% (IgG ACA) to 30% (IgM anti-prothrombin) versus 4% in healthy controls (p <10(-2) to 10(-3)). Levels of IgM anti-beta2GPI and IgG ACA were significantly higher in lepromatous leprosy and multibacillary patient subgroups. IgG3 was the most common subclass reactive to both beta2GPI and prothrombin in selected high-titer leprosy sera, unlike antibodies from patients with the antiphospholipid syndrome (APS) largely restricted to IgG2. In leprosy patients, but not in the APS control group, there was no statistical correlation between ACA and anti-beta2GPI antibody levels. Likewise, a large fraction of anti-beta2GPI positive sera (36/45 and 28/44 for IgG and IgM, respectively) were unreactive in the standard ACA assay. Most assayed anti-beta2GPI antibodies from leprosy patients showed (i) ability to recognize both human and bovine beta2GPI immobilized on non-irradiated polystyrene plates, (ii) concentration-dependent inhibition of binding by cardiolipin, and (iii) relatively high avidity binding to fluid-phase beta2GPI, thereby differing from those found in APS. Finally, the location of the major epitopic region on the beta2GPI molecule targeted by autoantibodies was different in leprosy and APS, as assessed by direct binding to domain I- and V-deleted mutants and competition with the mouse monoclonal antibody 8C3, directed at domain I. Thus, leprosy-related antiphospholipid antibodies comprise persistent IgG and IgM anti-beta2GPI that differ from APS-related ones with respect to IgG subclass, avidity and epitope specificity, possibly reflecting distinct pathophysiological significance.

Adolescent↗
PubMed2002

[Re-assessment of culture inhibition assays and reinvasion of P. falciparum for the appraisal of immunity of individuals living in an endemic area].

We conducted an analysis to reevaluate the in vitroculture inhibition assays as a reliable criteria of functional activity of anti-P. falcipanrm antibodies in premunized individuals. Several strains of P. falcipanrm adapted to in vitro culture were compared, and various technical conditions of parasite growth factors such as culture medium or incubation conditions were explored. A subsequent degree of variation was evidenced related to the parasite strain used and the culture conditions. The culture inhibition and the merozoite reinvasion inhibition assays were performed using a collection of plasma from premunized individuals living in two different endemic area of transmission in Senegal. High levels of inhibition were evidenced with a limited degree of variation according to the two different locations of individual's samples. A Significant relationship between anti-merozoite Ab levels and the culture inhibition assays was found contrary to the merozoite re-invasion inhibition assays. Taken together, our results show that such inhibition assays can be managed in facilities of southern laboratories near endemic areas. However, strictly defined culture conditions, homogeneous withdrawals of patients and standardized protocols are necessary for the assessment of such functional assaysas a potential markerof protection-associated mechanisms in longitudinal studies.

Adolescent↗
PubMed2001

In vitro production of immunoglobulins of various classes and subclasses by cord blood B cells in African neonates: modeling and assessment of determination.

Cord blood B cells obtained from neonates of healthy Senegalese mothers were assayed in vitro for their capacity to fully differentiate and secrete immunoglobulins (Ig) of various classes and subclasses. Stimulation of mononuclear cells with SAC particles or anti-micro antibodies in the presence of IL-4, or with IL-2 and IL-10 induced a strong production of IgG, provided that an additional CD40/CD40L signal was present, in contrast to adult cell cultures. Cord blood mononuclear cells differentially stimulated with various cytokines in order to lead to Ig heavy chain switching and production of the various classes/subclasses consistently produced IgG1, IgG3, IgG4, IgE and IgA. This system has been applied to immune cells from African neonates that have not been extensively studied previously. Estimation of Ig production as OD ratios could be applied to cultures where cord blood B cells are stimulated with defined antigens of human pathogens to which the fetus immune system was primed in utero.

B-Lymphocytes↗
PubMed2001

Experimental IgG antibody production in vitro by peripheral blood and tonsil surface gamma+ B lymphocytes from Plasmodium falciparum-immune West Africans.

Antigen reactive B cells in tonsil specimens from teenagers from a region moderately exposed to P. falciparum were capable of being differentiated in vitro and producing specific immunoglobulin (Ig)G in up to 33% of individual experiments. Mononuclear cells or purified (s)gamma+ CD19+ B cells from peripheral blood or tonsil specimens from P falciparum-immune Senegalese subjects produced antigen-specific IgG upon appropriate stimulation in vitro. One fraction of this IgG was produced de novo by differentiated B cells and another fraction was likely bound on the surface of circulating or resident CD19+ sgamma+ B cells which were found in significantly greater numbers in individuals from rural Senegal as compared to nonimmune European controls. This study further documents the baseline levels of in vitro driven anti-P. falciparum IgG antibody production by mononuclear cells from blood and tonsils in immune populations exposed to P. falciparum differentially. Furthermore, this study demonstrates the relevance and potential utility of tonsils as a source of B lymphocytes to characterize further specific antibody responses to P. falciparum antigens in immune populations.

Adult↗
PubMed2001

[Differential changes in IgG1 and IgG3 against a major antigen of blood stage Plasmodium falciparum (MSP1(19)) as a function of the parasite transmission period: study among immune Senegalese adults].

This study examined the evolution of P. falciparum specific IgG1 and IgG3 antibodies "before" and "after" the highest transmission period in clinically immune Senegalese adults settle in Dielmo, a holoendemic area for P. falciparum transmission. Plasma was tested for antibodies to an antigen (Q-KNG- MSP1(19)) known to react with IgG1 and/or IgG3 in the majority of these individuals. There was a decrease in titers in individuals with low, but not high titer IgG1 whereas specific IgG3 remained unchanged following the highest transmission period. These results raise the question of the differential role of anti-MSP1(19)g-IgG1 antibody fractions in the maintenance of immunity to P. falciparum.

Adult↗
PubMed2000

Evaluation of immunogenicity and protective efficacy of carrier-free Plasmodium falciparum R23 antigen in pre-exposed saimiri sciureus monkeys.

We have reported previously that the recombinant Glutathione S-transferase GTR23, induced protection after immunisation of naive or previously exposed Saimiri monkeys. We investigated the immunogenicity of carrier-free R23 repeats in pre-exposed animals in two adjuvant formulations. Three of five monkeys immunised with alum-formulated repeats and one of two animals immunised with the Polyalphaolefine formulation produced high titres of cytophilic antibodies with a primary type kinetics, indicating that the anti-P. falciparum antibodies present on the day of challenge were R23-specific. The four responders in R23-specific antibodies were protected against a challenge infection with the virulent FUP/SP strain. The other three animals failed to respond to immunisation and experienced an infection that required drug treatment. Unlike the other three animals that experienced an infection requiring drug treatment. These experiments support further development of the R23 repeats as a vaccine candidate.

Adjuvants, Immunologic↗
PubMed2000

Stability-related studies on 17D yellow fever vaccine.

Yellow fever (YF) vaccine using the 17D strain of YF attenuated virus has been produced at the Institut Pasteur in Dakar since 1962. Until now, the stabilised YF had an expiry date of utilization of two years from the end of the lot control process under storage at +4 degrees C. We conducted a stability study to assess the three full year validity of this preparation, when correctly stored at +4 degrees C to optimise the conditions of production, storage and availability of such a vaccine. The activity of 19 consecutive batches of vaccines kept for three years at +4 degrees C was compared to that of the same batches that were kept three years at -20 degrees C. Using the in vitro microculture method, we found that three-year storage at +4 degrees C induced a higher loss of activity than storage at -20 degrees C or than the accelerated degradation test of vaccines kept for 14 days at 37 degrees C. Whatever the conditions of storage, in all cases decreases in activity were below the WHO's requirements, i.e., < 1 log PFU/dose, and residual activity of the selected batches was over 1000 mouse LD50 per dose. We demonstrated that the 17D YF vaccine produced in Dakar has a shelf-life of three years and that its required potency was maintained at +4 degrees C, after reconstitution with saline diluent, following three-year storage at +4 degrees C.

Animals↗
PubMed2000

Seasonal fluctuation of antibody levels to Plasmodium falciparum parasitized red blood cell-associated antigens in two Senegalese villages with different transmission conditions.

The recombinant R23, PfEB200, and GST-5 antigens derive from conserved antigens associated with the Plasmodium falciparum-infected erythrocyte membrane. They were identified as targets of protective antibodies in the Saimiri sciureus model. We have assessed here the humoral response to these antigens in humans. Cross-sectional surveys were conducted in two Senegalese villages with different levels of endemicity. The prevalence of specific IgG and IgM was similar and influenced by age in both localities. The anti-R23 antibodies decreased after the rainy season, particularly in the children less than ten years old. The anti-PfEB200 response did not show significant seasonal variation. The anti-GST-5 response increased in both the less-than 10-year-old and the greater-than 10-year-old groups after the rainy season in Dielmo, but only in the Ndiop villagers who were more than 10-years-old. Thus, antigen-specific seasonal variations of antibody levels were influenced differently by age in both villages. The isotype distribution was antigen-specific and differed for both seasons.

Adolescent↗
PubMed1999

Flow cytometric analysis of IgG reactive to parasitized red blood cell membrane antigens in Plasmodium falciparum-immune individuals.

Antigens exposed at the surface of Plasmodium falciparum parasitized red blood cells (pRBCs) represent potential targets for protective antibodies involved in opsonization and immune phagocytosis of pRBCs. We measured the recognition of parasitized red blood cell membrane associated antigens by IgG in the plasma of clinically immune individuals by flow cytometry and ELISA. The plasmas were selected on the basis of preexisting IgG antibodies to pRBC membrane associated recombinant proteins. In every plasma sample IgG could bind the surface of live pRBCs in flow cytometry. In addition, there was a significant correlation between the level of IgG recognition of live pRBCs and of pRBC membrane ghost proteins or major identified antigens by ELISA. Flow cytometry thus represents a technique suitable to test for the accessibility and potential functionality of IgG antibodies directed to antigens expressed by the surface of pRBCs.

Adolescent↗
PubMed1999

Immune responses to P. falciparum-MSP1 antigen: lack of correlation between antibody responses and the capacity of peripheral cellular immune effectors to respond to this antigen in vitro.

Protective immunity to P. falciparum blood stage infection is thought to be dependent on IgG antibodies, although the mechanisms that underlie such immunity are not clearly understood. One of the antigens thought to be involved in this protective response is MSP1. The present study has examined the levels and distribution of IgG (and IgM) antibodies to the C-terminal 19 kDa fragment of MSP1 in plasma from P. falciparum immune adult Senegalese and the capacity of the peripheral blood mononuclear cells from these patients to either proliferate or secrete IFN-gamma, IL-10 or IL-4 in vitro in response to this antigen. Specific antibodies were found in 74% of individuals' plasma; 44% of mononuclear cells proved capable of proliferating in vitro and IFN-gamma, IL-10 and IL-4 were detected in 37, 23 and 0% of culture supernatants, respectively. No significant association was found between the presence of antibodies and immune cell reactivity under the culture conditions used. This study emphasizes the complexity of the mechanisms responsible for the sustained production of potentially protective antibodies in response to proposed T-cell dependent P. falciparum blood stage antigens.

Adult↗
PubMed1999

Characterization of M. tuberculosis strains from west African patients by spoligotyping.

Analysis of Mycobacterium tuberculosis strains was carried out using isolates collected from 69 Senegalese and 20 Ivory Coast tuberculosis patients. These 89 isolates were typed by means of the spoligotyping technique, showing clusterized populations of bacterial strains. In the Senegalese patients, 35 genetic profiles were observed with 10 clusters of spoligotypes from 44 isolates. Among Ivory Coast patients, 11 spoligotypes were found for 20 isolates. A particular cluster of isolates was evident both in Senegalese (10) and Ivory Coast (11) patients. These results show the existence of polymorphism of the direct repeat region for African M. tuberculosis strains. However they suggest that additionnal markers are needed for accurate epidemiological studies in areas that are highly endemic for tuberculosis.

Bacterial Typing Techniques↗
PubMed1999

Secretion of parasite-specific immunoglobulin G by purified blood B lymphocytes from immune individuals after in vitro stimulation with recombinant Plasmodium falciparum merozoite surface protein-119 antigen.

The C-terminal 19 000 MW fragment of merozoite surface protein-1 (MSP119) is one of the most promising candidate antigens for a malaria vaccine. Baculovirus recombinant Plasmodium falciparum MSP119 has been used to define conditions for the in vitro production of specific antibodies by purified human blood B cells in a culture system where T-cell signals were provided by the engagement of CD40 molecules and exogenous cytokines. MSP119 preferentially induced surface immunoglobulin G (IgG) -positive (sgamma+) B lymphocytes from P. falciparum-immune donors to differentiate and produce antigen-specific IgG. In contrast, naïve B cells or cells from non-immune donors could not be induced to secrete parasite-specific IgG in vitro. Although IgG secretion was obtained in the absence of exogenous cytokines, it was dependent on B-cell-derived interleukin-10 (IL-10) and/or B-cell factor(s) under the control of IL-10, since IgG levels were significantly decreased in the presence of neutralizing anti-IL-10 antibodies. These results demonstrate at the cellular level that a single malaria vaccine candidate polypeptide can direct parasite-specific antibody production mediated by the secretion of potentiating factors.

Adult↗
PubMed1999

Immune responses to Plasmodium falciparum-merozoite surface protein 1 (MSP1) antigen, II. Induction of parasite-specific immunoglobulin G in unsensitized human B cells after in vitro T-cell priming with MSP119.

A baculovirus recombinant antigen corresponding to the C-terminal 19 000 MW fragment of Plasmodium falciparum merozoite surface protein 1 (MSP119), has been used to prime T cells from individuals with no previous exposure to malaria, to provide help for the induction of a parasite specific antibody response in vitro. Although MSP119 alone could induce a small but detectable T-cell response, which included interleukin-4 (IL-4) secretion, this response was significantly increased by the presence of IL-2. In addition, IL-4 was shown to synergize with IL-2 for the induction of antigen-specific T-cell responses. If interferon-gamma (IFN-gamma), IL-12, or neutralizing anti-IL-4 antibody was present at the time of priming, the T-cell responses were abolished. Parasite-specific immunoglobulin G (IgG) could be detected after secondary restimulation with MSP119, IL-10 and anti-CD40 monoclonal antibody in cultures containing MSP119 primed T cells, autologous B cells, IL-2 and IL-4. No antibody was secreted in the absence of primed T cells in this B-cell culture assay. These data show that recombinant MSP119, a leading malaria vaccine candidate, can prime non-immune human lymphocytes under defined in vitro experimental conditions, which include regulatory cytokines and/or other costimulatory molecules. This is a complementary approach for exploring immunogenic mechanisms of potential vaccine candidates such as P. falciparum antigens in humans.

Animals↗
PubMed1999

Different Plasmodium falciparum recombinant MSP1(19) antigens differ in their capacities to stimulate in vitro peripheral blood T lymphocytes in individuals from various endemic areas.

This study reports on T-cell proliferative responses to the 19-kDa C-terminal domain of the Plasmodium falciparum merozoite surface protein (MSP1(19)). Three different recombinant proteins were used: an Escherichia coli product expressing the first EGF-like domain and Saccharomyces cerevisiae and baculovirus/insect-cell-produced proteins containing both EGF-like domains, the latter protein being produced with or without N-glycosylation. Cell donors were P. falciparum-immune adults with no recent history of clinical malaria and recruited from three Senegalese settings with different epidemiological parasite transmission. Each mononuclear-blood-cell preparation was stimulated with a range of concentrations of the three proteins. Most subjects' mononuclear cells were reactive to at least one protein, but significant differences in lymphoproliferation were seen between the settings and within individual cultures depending on the protein source and concentration. Importantly, lymphoproliferation indices correlated inversely with the intensity of P. falciparum malaria transmission. When purified T lymphocytes were cultured in the presence of MSP1(19) plus autologous monocytes, B lymphocytes or a proposed CD1+ dendritic-cell population as costimulatory cells, significant differences were observed depending on the individual's previous exposure to parasites. This study shows that the stimulation of lymphocyte proliferation in vitro with MSP1(19) depends on several factors, including epidemiological conditions and protein preparations.

Adult↗
PubMed1999

[Reemergence of yellow fever in West Africa: lessons from the past, advocacy for a control program].

In French speaking West Africa, yellow fever vaccine became compulsory in 1941 for the entire African and European population. From 1941 to 1960, 146 million doses were distributed and the number of yellow fever cases declined sharply. No case was reported from 1954 to 1960. As a result of an interruption in systematic immunization after 1960, ten major epidemics broke out in West Africa between 1965 and 1995 (over 200,000 cases and 40,000 deaths). In 1967, the WHO programme for eradication of smallpox was initiated and it mobilized WHO's energy and finances. The expanded programme of immunization (EPI) was initiated in 1977 but it did not include the yellow fever vaccine. In 1978, Primary Health Care advocated an immunization strategy through fixed health facilities. In 1986, to amend this strategy, WHO recommended accelerating EPI progress and instituting National Immunization Days (NIDs). In 1990, a recommendation was made to include the yellow fever vaccine in the EPI. In 1997, the target of global poliomyelitis eradication by the year 2000 reinforced the NID programme and led to the use of mobile teams. At a time when a measles eradication programme is going to take over from the poliomyelitis programme, we must firmly advocate not omitting the yellow fever vaccine as was the case in 1977. Indeed, in yellow fever endemic areas, WHO recommends a simultaneous association of yellow fever and measles vaccines for nine month-old infants. This opportunity must be seized to initiate a yellow fever control programme.

Africa, Western↗