Search PubMed⌕ Search

Biomedical subjects

J Le Bras

Publications and source records attributed to J Le Bras.

At least 145 records · Page 8Linked to original sources

Treatment of imported cases of falciparum malaria in France with halofantrine.

Halofantrine is a 9-phenanthrenemethanol which is effective against multi-drug resistant strains of Plasmodium falciparum. It has been shown to be highly effective and extremely well tolerated in the treatment of imported cases of falciparum malaria in France. A total of 1,500 mg administered in three 500 mg doses at six-hour intervals results in a 100% cure rate in semi-immune subjects. This dosage should be repeated after 14 days to obtain the same cure rate in non-immune patients. Minor clinical side effects included epigastric pains, nausea and, in one case, a skin rash.

Adult↗

[A fatal case of chloroquine-resistant neuromalaria in a traveller to Cameroon].

A death from chloroquinoresistant falciparum malaria contracted by a traveller under chloroquine chemoprophylaxis during a stay in the Cameroon provides the authors with an opportunity to analyze the extension of chloroquinoresistance in Africa. Having appeared there about 10 years ago, it remained for a long time localized in East Africa. In recent years, it has moved West. Today, 17 countries located from the North to the South between Sudan and Mozambique, and from East to West between Kenya and the Cameroon are affected, as are the Malagasy Republic, the Comores and Zanzibar. The strains resistant to chloroquine are still sensitive to amodiaquine. In certain regions which are widespread in the continent, resistance to pyrimethamine has become evident in the last 30 years; resistance to pyrimethamine-sulfadoxine and pyrimethamine-dapsone has appeared in the last 3 years in East Africa. In the light of the complexity of the problem of malaria chemoprophylaxis, the authors emphasize the necessity of resensitizing the public at large with respect to personal protection against biting anopheline mosquitos, especially during the hours of darkness. The medical profession should equally be made aware of these new problems. Three types of chemoprophylaxis in relation to the areas visited are proposed: the first for West Africa; the second for Central Africa, neighbouring regions and the Malagasy Republic and the Comores; the third for the 3 East Africa countries the most affected, which are Kenya, Burundi and Tanzania.

Africa↗

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↗

The interferon compartment of the immune response in human malaria: I. Interferon inducers in Plasmodium falciparum cultures.

The present study concerns the interferon (IFN) compartment of the immune response in human malaria. It was undertaken with Plasmodium falciparum parasitized human red blood cell culture supernatants (PF-RBCS). Investigations were conducted in order to verify whether supernatants of such protozoa cultures had the capacity to induce gamma interferon previously identified in sera of P. falciparum infected patients and to verify whether a T-cell mitogen recently characterized in vitro could be correlated with the eventual IFN-inducing activity. Investigations were performed with nonsynchronized P. falciparum cultures and highly synchronized PF-RBC cycles. Results obtained with the first type of experiment demonstrated the presence of an immune interferon inductor in PF-RBCS controlled for their positive mitogenic activity. In supernatants from highly synchronized PF-RBC cycles it was possible to further correlate the mitogen activity with the capacity to induce IFN-gamma. Both activities were found in the time-interval situated near the end of the parasite cycle shortly previous of the merozoite stage. At an earlier time, at the peak of the ring stage, when no mitogen activity was detected, an interferon-induction activity, solely of IFN-alpha, was also demonstrated.

Cells, Cultured↗

Chloroquine uptake by Plasmodium falciparum-infected human erythrocytes during in vitro culture and its relationship to chloroquine resistance.

Chloroquine uptake by Plasmodium falciparum-infected human erythrocytes (RBC) was studied in vitro before and during culture by measuring the chloroquine gradient between the cells and medium (C/M) by high-pressure liquid chromatography. The C/M values were 5.9 +/- 2.7 (n = 23) for uninfected RBC, 13 to 34 for six chloroquine-susceptible isolates (concentration required to inhibit 50% of parasite growth, less than 100 nmol/liter) in partially infected RBC (parasitemia from 0.3 to 5%) (n = 28), and 8.4 to 4.9 for four chloroquine-resistant isolates (concentration required to inhibit 50% of parasite growth, 320 to 1,500 nmol/liter) in partially infected RBC (parasitemia from 0.4 to 5%) (n = 26). Two isolates were studied before and after adaptation to continuous culture. C/M was found to decrease (34.2 to 2.1 and 19.3 to 4.9), whereas the concentration required to inhibit 50% of parasite growth increased (35 to 1,400 and 54 to 1,500 nmol/liter), thus indicating the acquisition of chloroquine resistance. These results demonstrate that chloroquine uptake decreased in RBC in which the infective strain, initially susceptible, became resistant in culture and imply that the drug is bound to ferriprotoporphyrin IX to a lesser extent or that a parasite protein competes with ferriprotoporphyrin IX to a greater extent. We suggest that genotypic modifications in the mechanism of chloroquine uptake might occur in the parasite.

Chloroquine↗

[8 cases of drug-resistant Plasmodium falciparum malaria contracted in Mozambique].

Between April and June 1984, eight chloroquine-resistant P. falciparum malaria cases were observed in non-immune patients after their emergency sanitary return from NE Mozambique. In vivo resistance to amodiaquine and pyrimethamine were demonstrated from two isolates. Radical cure was obtained with mefloquine in all cases. These patients came from an expatriate community of 35 adult men among which six other chloroquine-resistant malarial cases were probable. The epidemic pattern of this chloroquine-resistant focus is underlined.

Adult↗

[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↗

[Treatment with halofantrine of Plasmodium falciparum malaria imported into France].

Halofantrine is a 9-phenanthrene-methanol effective against multiresistant strains of Plasmodium falciparum. It is extremely effective and well-tolerated in treating cases of malaria imported into France. 1,500 mg in 3 doses at 8 hour intervals produced 100% cure rate in semi-immune patients. This dosage could be repeated after 14 days in order to obtain the same cure rate in non-immune patients. Side-effects are minor and include epigastric pain, nausea and one case of skin rash.

Adult↗