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P Deloron

Publications and source records attributed to P Deloron.

At least 109 records · Page 6Linked to original sources

DNA hybridization for assessment of response of Plasmodium falciparum to chloroquine therapy.

We studied the accuracy of PFR1-AP, a synthetic DNA hybridization probe conjugated to alkaline phosphatase, in monitoring Plasmodium falciparum parasitemia during in vivo drug susceptibility surveys. Duplicate blood samples were collected from six children enrolled in a 14-day in vivo chloroquine study in Rwanda. Results obtained by microscopic examination of Giemsa-stained thick blood smears and by DNA hybridization were compared. Both techniques successfully monitored an infection with chloroquine-susceptible parasites and infections exhibiting various levels of resistance to treatment. For each patient, temporal evolution of the microscopic parasite counts and the DNA hybridization signals were closely parallel, although a wide range of rapidly changing levels of parasitemia occurred through the course of the study. This suggests that DNA hybridization assay using PFR1-AP detects P. falciparum parasites sensitively and specifically and is a valuable tool for drug resistance surveys.

Animals↗

Parasitologic and clinical efficacy of 25 and 50 mg/kg of chloroquine for treatment of Plasmodium falciparum malaria in Rwandan children.

The standard chloroquine treatment for Plasmodium falciparum malaria is 25 mg (base)/kg (C25) given over 3 days. In Rwanda, 50 mg/kg (C50) administered over 6 days has been recommended by the Faculty of Medicine, Ministry of Health. The present study compared clinical and parasitological efficacy and side effects of C25 and C50 in children less than or equal to 5 years of age. In vitro studies with chloroquine, mefloquine, pyrimethamine, and quinine were also performed. Ninety children were given a 3-day treatment of C25 and 48 a 5-day treatment of C50. Cases were followed for a total of 15 days (D0 to D14). At day 14, 73% of the C25 and 67% of the C50 children were still parasitemic, but the mean geometric parasite density had decreased by at least 96% in both groups. Clinically, 44 C25 and 12 C50 children had fever on day 0; by day 14 only 4 (9%) C25 and 4 (33%) C50 children still had fever. Side effects were found to be minimal. The chloroquine in vitro tests corroborated the in vivo findings. P. falciparum was found to be quite sensitive to mefloquine and quinine, but showed a high (59%) resistance to pyrimethamine.

Animals↗

Amodiaquine and sulfadoxine-pyrimethamine as treatment for chloroquine-resistant Plasmodium falciparum in Rwanda.

The efficacy of amodiaquine and sulfadoxine-pyrimethamine combination as a second-line therapy for chloroquine-resistant Plasmodium falciparum infections was investigated in Rwanda in September 1986. Children less than or equal to 5 years old presenting with a P. falciparum parasitemia 14 days after treatment with chloroquine were administered either amodiaquine (25 mg/kg over 3 days, 64 patients) or sulfadoxine-pyrimethamine (as a single dose with tablets containing 500 mg of sulfadoxine and 25 mg of pyrimethamine: 1/4 tablet for children under 1 year, 1/2 for those 1-3 years old, and 1 tablet for those 4-5 years old; 34 patients) and followed for 7 days. Seven days after starting treatment with amodiaquine, 50 (76%) children were aparasitemic. All the children who had received sulfadoxine-pyrimethamine were aparasitemic 7 days after initiation of therapy.

Amodiaquine↗

Immunological characteristics of malaria antibodies in two regions of Madagascar.

Antibodies directed against antigens of the asexual blood stages of Plasmodium falciparum were studied in the plasma of 29 individuals infected with P. falciparum and living in two areas of Madagascar. These plasma samples were investigated by four immunological methods: indirect fluorescence, immunoprecipitation of radiolabeled P. falciparum polypeptides, inhibition of the in vitro growth of P. falciparum, and double diffusion in a gelose plate. A multifactorial correspondence analysis of the results obtained for each sample revealed that the nature of several of the antibodies varied according to the age and place of residence of the subjects. In comparison with plasma samples from older individuals, specimens from young children had a higher immunofluorescence titer, immunoprecipitated several additional peptides (90, 110, and 118 kilodaltons), revealed more precipitation lines in the Ouchterlony plate technique, and did not inhibit the in vitro growth of P. falciparum to the same extent. Furthermore, as opposed to plasma samples from individuals living in the high central plateau, plasma samples from individuals living on the east coast of the island inhibited the penetration of erythrocytes by merozoites of one of the two studied P. falciparum strains and preferentially immunoprecipitated low-, rather than high-, molecular-weight peptides.

Adolescent↗

Antibodies to the PF155 antigen of Plasmodium falciparum: measurement by cell-ELISA and correlation with expected immune protection.

Plasmodium falciparum polypeptide Pf155 is one of the main candidates for a vaccine against asexual blood stages of P. falciparum. Antibodies against Pf155 can be detected by a cell-ELISA technique with glutaraldehyde-fixed and air dried P. falciparum-infected erythrocytes as antigen. Using this assay, we measured the level of antibodies in sera from 230 subjects with various degrees of past exposure to P. falciparum. Significant levels of antibodies (OD492 greater than 0.5) were detected in 41/50 sera from Central African adults and in 34/50 sera from West African adults. All sera from 50 European adults suffering primary malarial attack and 28/30 sera from West African children (10 to 12 years old) were negative. Intermediate results were obtained with 50 sera from West African adults living in France for greater than or equal to 2 years (12 positive). Mean OD values of the sera of these five groups of subjects varied in the same direction as the positivity rates. These preliminary results suggest that the level of anti-Pf155 antibodies as detected by cell-ELISA might provide an assessment of protective immunity against P. falciparum which could complement clinical or epidemiological criteria.

Adult↗

Antibodies to Pf155, a major antigen of Plasmodium falciparum: seroepidemiological studies in Haiti.

The presence of malaria parasites and the serological antibody responses against whole Plasmodium falciparum and the Pf155 antigen were studied in the population of a small rural locality in Haiti in December 1985. Only 7 (1.5%) of the individuals were found to be infected with P. falciparum, the only species observed. Antibodies to P. falciparum were detected in an ELISA in 38.2% of the sera, the positivity rates being age-related. Anti-Pf155 antibodies were detected in 12.5% and 13.6% of individuals by two different techniques used. The anti-Pf155 positivity rates increased only after 25 years of age. No trends were detected for a clear-cut protective value of Pf155 antibodies against clinical malaria and further longitudinally conducted field surveys are needed to satisfactorily assess the potential protective effect of Pf155 antibodies.

Adolescent↗

[Sensitivity of Plasmodium falciparum to quinolines and therapeutic strategies: comparison of the situation in Africa and Madagascar between 1983 and 1986].

One thousand and twenty six P. falciparum strains isolated from cases imported in France and field surveys in four regions of Africa and Madagascar were studied in vitro against chloroquine, monodesethylamodiaquine, quinine and mefloquine, 917 in vivo tests were performed during field studies with chloroquine (10 and 25 mg/kg) and amodiaquine (10, 25, 35 mg/kg). In Madagascar, the chemoresistance remained low and stable during the study period, concerning mostly chloroquine (11% in vitro and in vivo) without obvious geographical variation. 25 mg/kg chloroquine or amodiaquine were satisfactory as respectively first and second line therapeutic regimen. In Central Africa, chemoresistance emerged with an epidemic profile and increased dramatically in disseminated urban focus. High level and prevalence of chloroquine resistance and multiresistance were observed few months after the index cases in these foci. In South West Cameroon, amodiaquine remained efficient as curative treatment but only at a dose of 35 mg/kg/5 days. Decrease of in vitro sensitivity and in vivo efficacy of quinine is a matter of concern. Given the heterogeneous and evolutive situation of drug resistance, the need for epidemiological surveillance and monitoring of P. falciparum drug sensitivity in Africa is obvious to adjust therapeutic regimen.

Amodiaquine↗

Geographic diversity of Plasmodium falciparum antibodies in Madagascar.

Plasma samples from 50 subjects living in three distinct regions in Madagascar (Ankazobe, Manakara, and Foulpointe) were studied by sodium dodecyl sulphate polyacrylamide gel electrophoresis of immunoprecipitated proteins from a Plasmodium falciparum strain (FCM22/Madagascar) which had been biosynthetically labelled with 35S-methionine and maintained in long-term in-vitro culture. Four major proteins with molecular weights of 96, 100, 110, and 118 kD were precipitated by plasma from Ankazobe, whereas low molecular weight proteins (27, 40, and 47 kD) were recognised more often by plasma from Foulpointe. Plasma from Manakara immunoprecipitated proteins of intermediate molecular weight. Variations in the immunological response according to the area, or antigenic diversity among the parasitic isolates might account for these results.

Adolescent↗

Plasmodium falciparum in Madagascar: in vivo and in vitro sensitivity to seven drugs.

The sensitivity level of Plasmodium falciparum isolates to chloroquine and the activity of six other antimalarials were studied in the different climatic zones of Madagascar in 1983. In vivo tests were done with 10 and 25 mg kg-1 of chloroquine and amodiaquine. Early recrudescence or RII resistance was observed after treatment with 10 mg kg-1 of these drugs in 34% of the cases for chloroquine and 6.5% for amodiaquine, and after the 25 mg kg-1 dose in 7% and 0% of the cases respectively. In vitro sensitivity of 84 P. falciparum isolates to seven drugs were studied with a semi-microtest. For chloroquine, 9% of the isolates had an IC50 above 250 nM, indicating resistance. In vitro activity of piperaquine was high for all isolates except two. In vitro activity of amodiaquine, dichlorquinazine, quinine, mefloquine and halofantrine was good against all isolates (maximum IC50 was 76, 92, 560, less than or equal to 20 and less than or equal to 12 nM, respectively). Correlation between the WHO standard field test and the in vitro semi-microtest was good. Resistance of P. falciparum to chloroquine was observed in the six survey areas, but the other tested drugs showed good activity. Since no cross-resistance to 4-aminoquinolines seems to exist in Madagascar, amodiaquine (the only one available at present) should be studied as an alternative to chloroquine in the prevention and treatment of falciparum malaria in this area.

Adolescent↗

[In vivo and in vitro sensitivity to 4-aminoquinolines of Plasmodium falciparum in Madagascar: results of 2 years' study].

563 cases of Falciparum malaria were detected in 1984 and 1985 in 7 malarial zones covering 3 climatic regions in Madagascar. All subjects underwent a therapeutic test; 175 strains of Plasmodium falciparum were isolated for in vitro drug sensitivity studies. 28 strains which were moderately chloroquine resistant in vitro were identified in 1983 in these various zones. However, 16% strains studied in 1984 in Alatsinainy (plateaux area), were chloroquine-resistant in vitro. The in vitro sensitivity to the other amino-4-quinolines seemed to be retained. In vivo, 7% of resistance type RI or RII were noted with 25 mg/kg of chloroquine but none with 25 mg/kg of amodiaquine. The usual therapeutic schedule for partially immune subjects (10 mg/kg in one dose) was ineffective on day 7 in 34% of the cases with chloroquine and 5% of the cases with amodiaquine. In conclusion to this study, we recommend that chemoprophylaxis should be stopped in schools in Madagascar and that presumed malarial attacks should be treated with a minimum dose of 25 mg/kg of chloroquine in 3 days. We suggest that amodiaquine should be used in cases of therapeutic failure with chloroquine.

Aminoquinolines↗

Application of an in vitro semi-microtest to the study of drug sensitivity of 66 Plasmodium falciparum isolates from 15 countries.

The activity of four antimalarial drugs against 66 Plasmodium falciparum isolates from 15 countries was assessed by an in vitro semi-microtest. Median inhibitory concentrations (IC50) for chloroquine were less than 120 nM in 22 isolates from patients successfully treated with chloroquine, and more than 250 nM in six isolates from patients with chloroquine-resistant malaria. 10 of 15 isolates from Brazil (Amazonia), 7 of 12 isolates from Madagascar, two from Kenya and two from Thailand had IC50 for chloroquine of more than 250 nM. None of the 35 isolates from West and Central Africa had IC50 of more than 120 nM. Very different levels of sensitivity were observed in Brazil and Madagascar. 27 of 28 isolates (including two that were chloroquine-resistant in vivo) had IC50 of less than 50 nM for dichlorquinazine, a 4-aminoquinoline. The IC50 for mefloquine was less than 160 nM in 55 isolates including ten from patients who were successfully treated with mefloquine. IC50 for quinine were between 140 and 660 nM for 30 isolates. This test has proved useful in epidemiological studies, therapeutic monitoring of clinical cases and in the evaluation of new drugs.

Animals↗