Search PubMed⌕ Search

Biomedical subjects

J Le Bras

Publications and source records attributed to J Le Bras.

At least 163 records · Page 9Linked to original sources

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↗

Malaria, arbovirus and hepatitis infections in Macaca fascicularis from Malaysia.

Naturally occurring malaria, arbovirus infection and hepatitis in monkeys can be a hazard for the investigator and might interfere with the outcome of experiments. 63 young adult Macaca fascicularis from Malaysia were screened for these infections. About 1 year after their arrival in France, parasitaemia due to Plasmodium spp., was present in 6.4% of the animals and specific antibodies in 55.5%. 19 of 35 initially positive monkeys were tested again 2 years later. Parasitaemia was found in 1 of 4 monkeys and antibodies in 11 of 19 monkeys which were initially positive. 9 of the monkeys initially tested had low titres of antibodies to the Flavivirus genus. All animals were negative for the hepatitis B surface antigen and anti-HBc. The prevalence of IgG antibodies against hepatitis A was 46.0%. The implications in terms of control are discussed.

Animals↗

[Plasmodium falciparum: interpretation of the semi-microtest of in vitro chemosensitivity by H3-hypoxanthine incorporation].

Recent advances in cultivation methods and knowledge of in vitro response of Plasmodium falciparum to antimalarials have led to improved chemosensitivity tests. The semimicrotest is a useful tool for screening presumptive antimalarials, and also for the testing sensitivity of strains recovered from patients in hospital and field studies to currently used drugs. Microscopic parasite counts on thin blood films can be replaced by measurement of 3H-hypoxanthine by the uptake parasite. Conditions which ensure optimal parasite growth and high radioisotope incorporation are described. Wells containing less than 3. 10(4) asexual parasites can be studied with this method. Results of the semi-microtest are closely correlated with those of microscopic parasite count. Advantages of both methods are discussed.

Animals↗

[4-Aminoquinoline-sensitivity of Plasmodium falciparum in Madagascar. I. Study in two regions of the west coast].

Two three weeks field studies were performed in Morondava (West Coast) and Nosy Be (North West Coast) respectively in January and April 1983. Among 110 malarial patients recruited through passive detection, 70 in vivo tests and 37 in vitro tests were performed. In vivo, within 7 days 10 mg/kg chloroquine failed in 8 of the 21 treated patients, 25 mg/kg chloroquine failed in 1/43 and none of these patients treated with 10 mg/kg amodiaquine failed. In vitro, 5 among 37 isolates had chloroquine IC50 more than 250 nM/1 which is predictive for resistance with the semi-microtest. All isolates were sensitive in vitro to low doses of amodiaquine, piperaquine and dichlorquinazine.

Adolescent↗

[4-Aminoquinoline-sensitivity of Plasmodium falciparum in Madagascar. III. Studies in three regions of the interior].

Among 273 malarial patients recruited through passive detection, 177 in vivo tests were performed in Andekaleka and Ankazobe and 23 in vitro tests in Ifanadiana, and Ankazobe (inland of Madagascar). In vivo, chloroquine failed within 7 days at 10 mg/kg in 28/86 patients, at 25 mg/kg in 7/34 and amodiaquine failed in 5/55 with 10 mg/kg and in 0/14 with 25 mg/kg. In vitro, the semi-microtest revealed resistance to chloroquine of 1/23 isolates (IC50 = 750 nM/1) but high sensitivity to amodiaquine, dichlorquinazine and piperaquine of all studied isolates (max IC50 = 92 nM/1).

Aminoquinolines↗

[Drug sensitivity of Plasmodium falciparum in Madagascar. V. Study of the in vitro activity of quinine, mefloquine and halofantrine].

In a nine month fields study in 1983 in Madagascar, in vitro sensitivity to others drugs than 4 aminoquinolines were tested for 39 Plasmodium falciparum isolates, including 2 chloroquine resistant ones. Sensitivity to quinine, mefloquine and halofantrine were recorded from 28, 39 and 11 of these isolates respectively. IC50 with semi-microtest were under 20 nM/1 for mefloquine, under 12 nM/1 for halofantrine and under 560 nM/1 for quinine. All these values are under maximal values observed elsewhere with isolates coming from patients successfully treated with the three drugs.

Antimalarials↗

Plasmodium falciparum: drug sensitivity in vitro of isolates before and after adaptation to continuous culture.

Fifteen strains of Plasmodium falciparum have been cultivated since 1979 using the Trager and Jensen method of continuous culture on isolates from malaria patients. One hundred and two drug sensitivity studies have been carried out on these strains using a semimicro test. Three isolates, initially resistant to chloroquine, adapted rapidly to in vitro cultivation and maintained their high level of resistance (ED50 above 660 nM). Eleven isolates, initially chloroquine sensitive (ED50 under 90 nM) became resistant to this drug (ED50 = 190 to 1950 nM) after the 2-15 weeks required for their adaptation to continuous culture. The resistance of these strains never decreased during the following 15 months of continuous culture. The sensitivity to quinine varied initially from one strain to another (ED50 = 160 to 660 nM) and fluctuated during cultivation in the ratio of 1:3.5 for a given strain. The sensitivity of mefloquine remained high for all strains (ED50 under 150 nM) but one (ED50 = 560 nM). These results suggest that there might be a relationship between in vitro adaptation to culture of P. falciparum by the Trager-Jensen method and a chloroquine-resistant characteristic of the strain. There is the possibility of the emergence of a drug-resistant subpopulation or of changes in the metabolic pathways.

Adaptation, Physiological↗

In vitro study of drug sensitivity of Plasmodium falciparum: evaluation of a new semi-micro test.

A modification of Rieckmann's microtechnique was used to determine the drug sensitivity of Plasmodium falciparum. The technique was found to be reliable and adequately sensitive with either blood from a malarial patient or strains of P. falciparum from in vitro continuous culture, with a success rate of 50%. Minor variations in the method had little influence on the results. Inhibition of maturation of parasites was compared with the inhibition of increase in parasitemia.

Antimalarials↗

[Attempt to isolate from Ascaris suum an antigenic fraction for use in the immunologic diagnosis of onchocerciasis].

For the purpose of immunological diagnosis of onchocerciasis, the authors attempted to isolate an antigenic fraction from Ascaris suum which would only detect anti-Onchocerca volvulus antibodies. Chromatofocusing was done on a crude antigenic preparation from the ascaris. Immunoelectrophoresis showed that the fraction eluted between pH 5.6 and pH 4.9 contained antigens which reveal anti-Onchocerca antibodies; anti-Loa loa antibodies are revealed by the fraction eluted at pH less than 4. From the fraction which reveal anti-Onchocerca antibodies, affinity chromatography isolated a system in which three components were detected by electrofocusing at a Pi of about pH 5.5. The specificity and sensitivity of this system are being studied.

Animals↗

[Standardisation of the in vitro chemosensitivity test for Plasmodium falciparum ].

Reliable in vitro tests are needed to study the epidemiology, pharmacology, genetics and the treatment of Falciparum malaria. We have studied the reproducible nature of an in vitro method using either patients blood or a continuous strain with which we did 254 chemosensitivity tests with chloroquine, mefloquine and quinine. The method is based on ED50 determination which is done by assessing the plasmodial maturation on thin blood film after 24-48 hours incubation. This method is simple to carryout but long to interpret. It has proved reliable and sensitive enough to be used for the proposed studies. The blood group, the limited variations of erythrocyte concentrations, of the composition and volume of the culture medium, of the atmosphere and of the incubation time had little influence on the ED50. It was considered that 47 p. cent of the tests could be interpreted and that this percentage could be improved with a better understanding of the in vitro behaviour of P. falciparum.

Antimalarials↗