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P Deloron

Publications and source records attributed to P Deloron.

At least 91 records · Page 5Linked to original sources
PubMed1991

Persistence of cellular and humoral response to synthetic peptides from defined Plasmodium falciparum antigens.

The cellular and humoral immune responses to synthetic peptides reproducing the repeat sequences of two major vaccine candidates (circumsporozoite protein and Pfl55/RESA) were investigated in two groups of African subjects according to the length of their stay outside endemic areas. The relation between the lymphoproliferative response and the antibody levels to these antigens was studied. The results confirm the existence of T-cell epitopes within the repeat sequences of the CS protein and the Pfl55/RESA capable of inducing lymphocyte proliferation. Cellular response to all studied peptides was more frequently observed in individuals living in France for less than one year than in individuals living in France for a longer time. T-cell proliferation in the presence of the tetrapeptide and of the octapeptide from the C-terminus repeat of Pfl55/RESA was related, with an immunodominance of the tetrapeptide over the octapeptide. Cellular responses to the CS protein repeat and to the 11-amino-acid peptide from the Pfl55/RESA N-terminus were the longest lasting after termination of exposure. In a given individual, cellular and humoral responses were not related for any peptide studied.

Adolescent↗
PubMed1991

In vitro and in vivo potentiation of chloroquine against malaria parasites by an enantiomer of amlodipine.

A combination of chloroquine and amlodipine, a derivative of 1,4-dihydropyridine calcium channel blocker, was tested against Plasmodium falciparum in vitro and P. yoelii in mice. The dextrorotary enantiomer of amlodipine, practically devoid of calcium channel blocking action, increased chloroquine accumulation inside the infected mouse erythrocytes and potentiated chloroquine action against the resistant strains of P. falciparum in vitro and P. yoelii in mice. Unlike the racemate, the dextrorotary amlodipine was not toxic to the host animal, even at the highest dose of 250 mg/kg. No potentiating effect was noted in the chloroquine-susceptible strains of P. falciparum. The results of this study indicate that chloroquine potentiation of amlodipine is probably independent of calcium channels and that a combination therapy of the dextrorotary enantiomer of amlodipine and chloroquine might be a potentially useful therapeutic strategy against chloroquine-resistant falciparum malaria.

Amlodipine↗
PubMed1991

Protective value of elevated levels of gamma interferon in serum against exoerythrocytic stages of Plasmodium falciparum.

In vitro experiments suggested that gamma interferon, CD8+ T cells, and anticircumsporozoite antibodies inhibited the exoerythrocytic stages of malaria parasites. To assess the role played in vivo by these factors, we conducted a prospective study in Madagascar. Forty individuals with a negative blood smear were followed for 8 weeks to detect the appearance of parasites in blood. Nineteen subjects remained negative for malaria, whereas 21 individuals became positive during follow-up. Among these, seven presented with blood parasites within the first 2 weeks and were excluded, as they probably were infected by sporozoites at enrollment. When measured at enrollment, antibodies to the synthetic peptide (NANP)5, lymphocyte proliferation with (NANP)5, and various lymphocytes subsets were similar among individuals that later presented with a Plasmodium falciparum blood infection or were not infected. Conversely, the level of gamma interferon in serum was higher in individuals that did not present with a P. falciparum infection during follow-up. These data suggest that gamma interferon may inhibit the malaria exoerythrocytic stages of development under in vivo conditions, as it does in vitro.

Adolescent↗
PubMed1991

Levels of cytokines in plasma during Plasmodium falciparum malaria attacks.

The variation of levels of tumor necrosis factor, granulocyte-macrophage colony-stimulating factor, gamma interferon, neopterin, and interleukin-2 receptors in plasma were monitored in 16 patients presenting with an acute Plasmodium falciparum malaria attack. Relations among cytokine levels and between cytokine levels and hematological and parasitological data were assessed.

Adult↗
PubMed1991

Lymphoproliferative responses to synthetic peptides from merozoite ring-infected erythrocyte surface antigen and circumsporozoite protein: a longitudinal study during a falciparum malaria episode.

Proliferative responses of peripheral blood lymphocytes to synthetic peptides representing major epitopes of two malaria antigens (the merozoite ring-infected erythrocyte surface antigen and the sporozoite circumsporozoite protein) were investigated in Madagascar during a clinical Plasmodium falciparum episode. Thirty-seven patients greater than 10 years of age were enrolled at the beginning of the malaria transmission season and followed for four weeks. At enrollment, when the subjects presented with an acute infection, lymphocytes recovered from approximately 30% of them proliferated after peptide stimulation. These proliferative responses decreased sharply one and two weeks after treatment, with less than 10% responding to each peptide. Four weeks after treatment, the responses were only partially restored. The amplitude of these variations was not related to the initial parasitemia. At the individual level, proliferative response to each peptide varied greatly during the followup period, and this variation was unrelated to the presence of parasites in the blood.

Adolescent↗
PubMed1990

Longitudinal study of the cellular response to Pf155/RESA and circumsporozoite protein in Madagascar.

In a community follow-up conducted in the Central Highlands of Madagascar, the cellular responses to synthetic peptides from the immunodominant regions of Pf155/RESA and the repeat region of the circumsporozoite protein were studied. Seasonal variations of the T cell response were measured at the individual level; the relationship between this response and the presence of parasites in blood was assessed; the question of the possible protective value of the lymphocyte proliferation in presence of a specific antigen was addressed.

Adolescent↗
PubMed1990

Activities of pefloxacin and ciprofloxacin against experimental malaria in mice.

We investigated the in vivo antimalarial activities of pefloxacin and ciprofloxacin in Swiss albino mice infected intravenously with 5 x 10(6) Plasmodium yoelii N67 parasites 1 h before treatment. Groups of 20 mice received a subcutaneous injection of 40, 80, or 160 mg of ciprofloxacin or pefloxacin per kg of body weight every 8 h for 3 days. Parasitologic activity was assessed on day 4, and survival was assessed on day 21. Control mice had a fulminant course with a parasitemia of 61.3% +/- 12.1% on day 4, and 90% of the mice were dead on day 21. The lower dosages of pefloxacin and ciprofloxacin (40 and 80 mg/kg) were not efficient. With 160 mg/kg, ciprofloxacin achieved an 85.8% reduction in parasitemia and 17 of 20 mice survived. Pefloxacin achieved a 92.8% reduction in parasitemia, and all mice survived. All treated, noninfected control mice survived. With ciprofloxacin, the antimalarial activity was similar with injections of 240 mg/kg every 12 h but was strongly diminished with injections of 160 mg/kg every 12 h. With pefloxacin, similar activities were observed with injections of 160 mg/kg every 8 h or injections of 160 or 240 mg/kg every 12 h. With both drugs, this activity was highly reduced when the treatment was delayed by 24 h. This underlines the need to provide treatment within the first hours after infection to achieve an optimal effect in this rapidly lethal experimental model of malaria. Pefloxacin and, to a lesser extent, ciprofloxacin are potent antimalarial drugs which might prove useful in the treatment of less rapidly aggressive human malaria.

Animals↗
PubMed1990

Humoral and cell-mediated immune responses to the Plasmodium falciparum antigens PF155/RESA and CS protein: seasonal variations in a population recently reexposed to endemic malaria.

Resurgence of falciparum malaria occurred in the Central Highlands of Madagascar in the 1980s and the disease is currently hyperendemic. We determined the humoral and cellular responses to synthetic peptides reproducing the repeat sequences of 2 major Plasmodium falciparum antigens: the Pf155/RESA and the circumsporozoite (CS) protein. Blood samples from 83 subjects living in a rural community near Antananarivo were obtained at the beginning and the end of the transmission season. At enrollment, 40 subjects presenting with and 43 without blood parasites had similar T cell proliferative response and antibody level to all antigens tested. However, P. falciparum-infected individuals exhibited a decrease in the absolute number of T lymphocytes, due to a diminished number of CD8+ and natural killer lymphocytes. The number of CD4+ cells was similar in both groups. In the overall population, 45% of subjects had a T cell response to at least 1 RESA peptide (29-35% responding to a given peptide) and 35% to the CS protein peptide. Thirty-two percent of the donors presented with RESA antibodies and 23% had CS protein antibodies. After 20 weeks, at the end of the transmission season, cellular proliferative responses to all antigens markedly decreased as evidenced by a decrease of both the number of responders and mean stimulation indexes. Humoral response to RESA, as detected by erythrocyte membrane immunofluorescence (number of responders and mean antibody titers) markedly increased. Humoral responses to the CS protein and RESA peptides were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Newly transmitted Plasmodium falciparum malaria in the central highland plateaux of Madagascar: assessment of clinical impact in a rural community.

Plasmodium falciparum has recently reappeared in the central highland plateaux of Madagascar. To define its role in the overall malaria pathology occurring during the rainy season, we conducted a clinical and parasitological study among the 2776 consultants of a malaria field health centre which we established in the middle of the transmission area. From January to June 1988 the overall parasite rate was 63.2% and did not vary with age; the overall splenic rate was 46.9%, decreasing in individuals over 15 years of age. After the beginning of the main transmission season, an increase in parasite rates and parasite densities was observed, while febrile illnesses associated with malaria parasitaemia decreased. During the second part of the rainy season the parasite densities started to decrease, while parasite rates and malaria-associated fevers remained at the same level. The frequency of fevers was not related to the malaria parasite density owing to individual and seasonal variations.

Adolescent↗
PubMed1990

[Ecological factors in the renewed outbreak of malaria in Madagascar].

The new epidemic of malaria which spread on the Madagascar high plateau in 1986-1987 is due to the combination of several factors (some of which are analysed by the authors, especially those related to anopheles, parasite and man). The authors compare the situations on the high Plateau and on St Mary Island, on the East Madagascar Coast, where the malaria is stable. Concerning the vector, the most interesting fact is the come-back of Anopheles funestus on the high Plateau from which it had disappeared at the beginning of the fifties. In this area, An.arabiensis seems to be the only representative of the gambiae complex whereas it is An. gambiae s.s. in St Mary Island. The parasite is getting more and more resistant to chloroquine. Nevertheless, man seems to develop protection, but it is difficult to analyse the markers which would prove the protection. However, that protection was assessed, on the humoral and cellular level, against the peptides of the RESA (Ring Infected Erythrocytes Surface Antigen), the circumsporozoite protein and the antigen E.

Adolescent↗
PubMed1989

Evolution of the levels of soluble interleukin-2 receptors during Plasmodium falciparum and P. vivax malaria.

Increased levels of soluble interleukin-2 receptors (IL-2R) in serum were observed in both Plasmodium falciparum- and P. vivax-infected individuals compared with nonparasitemic subjects. Clinical symptoms of P. falciparum malaria were associated with higher levels of soluble IL-2R. Temporal evolution in serum of IL-2R during the course of a malaria attack mimicked the kinetics of soluble IL-2R under experimental conditions.

Adolescent↗
PubMed1989

Antibodies to Plasmodium falciparum ring-infected erythrocyte surface antigen and P. falciparum and P. malariae circumsporozoite proteins: seasonal prevalence in Kenyan villages.

Two cross-sectional surveys of 954 persons in Asembo Bay and Got Nyabondo, western Kenya, were performed in August-September 1986, after long rains, and in February-March 1987, after a comparatively dry season. Serologic testing was performed using an ELISA with synthetic peptides representing repeat amino acid sequences of the Plasmodium falciparum ring-infected erythrocyte surface antigen (RESA), (EENV)5, (EENVEHDA)4, and (DDEHVEEPTVA)2 and repeat sequences (PNAN)5 and (NAAG)5 of the P. falciparum and P. malariae circumsporozoite proteins. In 1986, 45%, 73%, 72%, 85%, and 59% of the persons in Asembo Bay had antibodies to the respective peptides. In Got Nyabondo, the rates were 44%, 67%, 56%, 36%, and 41%, respectively. All positivity rates increased with age. When next determined in 1987, the positivity rates and levels of reactivity were generally unchanged in Asembo Bay, but were decreased in Got Nyabondo.

Adolescent↗
PubMed1989

[Antimalarial serology in 1987-1988 in the Highland Plateaux, the East coast and the South of Madagascar].

We studied 521 serum samples collected in 1987-88 in the Highland Plateaux and the East coast of Madagascar, two areas presenting different levels of malaria endemicity. Total anti-Plasmodium falciparum antibodies were investigated by an indirect immunofluorescence assay (IFA). Antibodies directed to the ring-infected erythrocyte surface antigen (RESA) were investigated by a modified IFA (MIFA). Results were analysed in regards to malariological parameters (parasite and splenomegaly rates) collected simultaneously. IFA appears as a good epidemiological tool as it closely parallels the classical malariological parameters. In selected studies, the presence of P. falciparum parasites in blood was less frequent in individuals presenting with anti-RESA antibody, as detected by MIFA, than in the other individuals were consistently lower in subjects with anti-RESA antibody than in others.

Animals↗
PubMed1989

[Malaria in 1988 in a village of the Malagasy Highland Plateaux. Epidemiological findings].

In 1988, the Malaria Research Unit of the Madagascar Pasteur Institute settled an out-patients clinic in Manarintsoa, a village of the Highland Plateaux where epidemic malaria appeared recently. 2776 consultants presented between January and June. In addition, the 200 schoolchildren were examined thrice. For each individual, clinical examination and thick and thin blood smears were performed. In the out-patients, parasite rates were above 50% each month and in each age group; the mean parasite rate being 74%. Splenomegaly rates were above 60% in individuals less than 15 years of age, and around 20% in adults. In schoolchildren, parasite and splenomegaly rates are consistently above 50%. Gametocyte indexes were 7.5% and 7% in May and October, respectively. Plasmodium falciparum is the most encountered species (in 85% of the cases), but P. vivax and P. ovale are also present. P. malariae is very rare. Early diagnosis and adequate therapy were very effective against mortality. During the high transmission time, monthly mortality rates varied from 12% before our arrival to 0.66% after. The number of malaria attacks was estimated at 2 per man and per year. In this area of unstable malaria, presence of fever appears to be of poor predictive value of the malaria infection. Systematic chloroquine therapy of fevers would be adapted to only 43% of the cases.

Adolescent↗
PubMed1989

[Sensitivity of Plasmodium falciparum to different antimalarials. A study in 1988 in a village in the Hauts-Plateaux of Madagascar].

Since a few years, malaria has reappeared in the Central Highland Plateaux of Madagascar. From 1983 to 1987, Plasmodium falciparum resistance to chloroquine remained stable, with a low frequency of R2 therapeutic failures. In 1988, a study was conducted in the village of Manarintsoa, 15 km from Tananarive. Ninety-one WHO in vivo standard tests were performed. In vitro efficacy of amodiaquine and quinine was also studied. In vitro, the efficacy of chloroquine, quinine, and mefloquine was measured against 104, 64, and 23 P. falciparum isolates, respectively, by an isotopic semi-microtest.

Animals↗
PubMed1988

Reduced parasitemia observed with erythrocytes containing inositol hexaphosphate.

Chemicals entrapped in erythrocytes by hypotonic hemolysis can be assessed for possible antiparasitic activity both in vivo and in vitro, regardless of whether they are able to diffuse into erythrocytes readily. Inositol hexaphosphate, a highly charged compound, produced a dramatic lowering of the percentage of cells infected by Babesia microti in vivo and both B. microti and Plasmodium falciparum in vitro. Several possible mechanisms for this observation are discussed.

Animals↗
PubMed1988

Antibodies to the ring-infected erythrocyte surface antigen of Plasmodium falciparum elicited by infection with Plasmodium malariae.

The ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum (RESA-P), found in the membrane of erythrocytes infected with young asexual stages of P. falciparum, is a promising vaccine candidate. Antibodies to RESA-P were inducible by infection with another human malaria species, P. malariae. Of 298 serum samples from inhabitants of three isolated localities in Peru where P. vivax and P. malariae were endemic and P. falciparum had never been reported, 26% had anti-RESA-P antibodies as evidenced by a modified immunofluorescent-antibody assay and confirmed by Western blot (immunoblot) analysis. These seroepidemiologic observations were corroborated by the fact that of six chimpanzees infected with P. malariae, three developed anti-RESA-P antibodies after infection. The modified immunofluorescent-antibody-reactive antibodies, purified by adsorption and elution on monolayers of glutaraldehyde-fixed and air-dried P. falciparum-infected erythrocytes, reacted in an immunofluorescent-antibody assay with both parasite structures and erythrocyte membrane in P. falciparum antigen preparations, but only with parasite structures in P. malariae antigen preparations. This serologic cross-reactivity between P. falciparum and P. malariae is of interest in view of the importance of RESA-P as a vaccine candidate and because the two species are coendemic in many areas.

Animals↗