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Biomedical subjects

J Le Bras

Publications and source records attributed to J Le Bras.

At least 73 records · Page 4Linked to original sources
PubMed1993

In vitro activity of cycloguanil against African isolates of Plasmodium falciparum.

The in vitro activity of cycloguanil was assessed against 86 African isolates of Plasmodium falciparum by a semi-micro assay system. A bimodal distribution of susceptibility patterns was observed, with 44% of the isolates being cycloguanil susceptible. Cycloguanil alone retains a high activity against the intraerythrocytic forms of some isolates and, together with its activity against the hepatic stages, may be useful for chemoprophylaxis when combined with chloroquine.

Animals↗
PubMed1993

Efficacy of intramuscular amopyroquin for treatment of Plasmodium falciparum malaria in the Gabon Republic.

The efficacy of a 12-mg/kg (of body weight) intramuscular amopyroquin (ApQ) regimen (two successive 6-mg/kg injections at a 24-h interval), previously established from kinetic studies on healthy volunteers and multicenter studies on patients with malaria, was investigated in 152 patients (children and adults) in Gabon with Plasmodium falciparum malaria. All children in the present study (ages, 1 to 14 years) showed higher degrees of parasitemia and temperatures and lower hematocrit values than did adults at the time of admission. No major side effects in the patients were observed. On day 7, all patients were apyretic; clearance of parasites was obtained in 143 of 152 patients (94%); a low level of parasitemia was observed in nine patients, all of whom were children (6%). In vitro chemosusceptibility tests carried out on P. falciparum isolates from patients demonstrated 51% of resistance to chloroquine (Cq). A correlation was found between the in vitro chemosusceptibilities to Cq and ApQ, but no relationship between the in vitro activity and the in vivo efficacy of ApQ could be found. Concentrations of ApQ in blood assayed by high-performance liquid chromatography on day 2 did not differ significantly between the groups in whom therapy was a success or a failure, although the mean ApQ concentration in blood for the group that failed therapy was 31% lower. Concentrations greater than 100 nmol of self-prescribed Cq and amodiaquine per liter, which were assayed simultaneously with ApQ, were observed in 78 patients (51%). They did not correlate with degrees of parasitemia compared with ApQ alone, which did. Successful treatment by day 7 was obtained in 69 of 74 patients (93%) who had no other 4-aminoquinolines in their blood. The results of the present study show that an ApQ regimen of 12 mg/kg over 2 days may be an alternative for the treatment of Cq-resistant malaria, at least in adult patients, in the field.

Adolescent↗
PubMed1993

Efficacy of micronized halofantrine in semi-immune patients with acute uncomplicated falciparum malaria in Cameroon.

Fifty subjects with acute uncomplicated falciparum malaria were treated orally with a new micronized formulation of halofantrine. The dose given corresponded to one-half the normal dose for the standard formulation. Parasitemia cleared in all subjects within 78 h. There was recrudescence of falciparum malaria in seven subjects after day 14. The mean +/- standard deviation clearance times of parasitemia and fever were 49.0 +/- 14.2 and 24.3 +/- 13.2 h, respectively. Other clinical symptoms related to malaria cleared within the first 3 days. Pruritus occurred in two subjects, back pain occurred in one subject, and diarrhea occurred in one subject; all of these symptoms were mild. Hematological and biochemical indices were not adversely affected by treatment except in five subjects in whom minor and transitory increases in aspartate aminotransferase and alanine aminotransferase were observed. Micronized halofantrine appears to be a safe, well-tolerated, and effective treatment for acute falciparum malaria in semiimmune patients.

Adolescent↗
PubMed1993

Parasite virulence factors during falciparum malaria: rosetting, cytoadherence, and modulation of cytoadherence by cytokines.

To determine virulence factors of isolates of Plasmodium falciparum and the potential role of cytokines in cerebral malaria, 46 Malagasy patients presenting with cerebral (n = 10), severe (n = 10), and uncomplicated (n = 26) malaria were enrolled in a study. The capacity of 21 of 46 P. falciparum isolates to form rosettes in vitro and to adhere to human umbilical vein endothelial cells (HUVECs) that express intercellular adhesion molecule-1 receptors and to C32 amelanotic melanoma cells that express mainly CD36 receptors was investigated together with the effects of tumor necrosis factor alpha (TNF-alpha), granulocyte macrophage-colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-6 alone and in two-by-two combinations on the cytoadherence of infected erythrocytes to HUVECs. Plasma levels of these cytokines were also measured in the patients at admission. The percentage of rosette formation was higher for the isolates from patients with cerebral (n = 6; 19.5%) and severe (n = 6; 30.5%) malaria than for those from patients with uncomplicated malaria (n = 9; 5%) (P < 0.002). The cytoadherence properties of the isolates did not differ among the three groups whatever the target cell used, but adherence to melanoma cells was systematically higher than that to HUVECs. Adhesion to HUVECs was increased more after TNF-alpha stimulation than after GM-CSF, IL-3, or IL-6 stimulation (P < 0.01). Only the combination of TNF-alpha and IL-3 enhanced cytoadherence more than TNF-alpha used alone (P < 0.02). No difference in the modulation of cytoadherence by cytokines was found in relation to the severity of the disease. TNF-alpha and IL-6 levels in peripheral blood were higher in the patients with cerebral and severe malaria than in the patients with uncomplicated malaria (P < 0.005). Most of the patients' sera contained little or no IL-3 or GM-CSF. Our results challenge the role of intercellular adhesion molecule-1 as the principal receptor mediating the cytoadherence of P. falciparum-infected erythrocytes and contrast with data obtained in the murine model.

Adolescent↗
PubMed1993

In vitro activity of monodesethylamodiaquine and amopyroquine against African isolates and clones of Plasmodium falciparum.

The in vitro activity of monodesethylamodiaquine and amopyroquine was evaluated against chloroquine-susceptible and chloroquine-resistant African clones of Plasmodium falciparum. The chloroquine-resistant clone (50% inhibitory concentration [IC50] = 1,630 nM) was 26 and 3.7 times less susceptible to monodesethylamodiaquine and amopyroquine, respectively, than the chloroquine-susceptible clone (IC50 = 36.5 nM). Cross-resistance patterns of chloroquine, monodesethylamodiaquine, and amopyroquine were determined against 62 African isolates of P. falciparum obtained from imported cases of malaria in France, using an isotopic semimicro drug susceptibility test. Chloroquine-resistant isolates (n = 38) were significantly less susceptible to both monodesethylamodiaquine (IC50 = 74.8 nM) and amopyroquine (IC50 = 18.9 nM), as compared with the 24 chloroquine-susceptible isolates (IC50 = 28.2 nM and 16.1 nM, respectively). A significant positive correlation was found between chloroquine and monodesethylamodiaquine (r = 0.903) and between chloroquine and amopyroquine (r = 0.371), indicating in vitro cross-resistance among these drugs. These in vitro results suggest that the clinical response to amodiaquine and amopyroquine needs to be closely monitored in Africa.

Aminoquinolines↗
PubMed1993

In vitro activity of artemisinin derivatives against African isolates and clones of Plasmodium falciparum.

The in vitro activities of chloroquine, quinine, mefloquine, halofantrine, artemisinin, arteether, artemether, and artelinate were evaluated against African clones and isolates of Plasmodium falciparum, using an isotopic, semimicro, drug susceptibility test. The chloroquine-resistant FCM 29 clone was 1.6 and 6.2 times more susceptible to artemisinin when compared with the chloroquine-susceptible, mefloquine-, and halofantrine-resistant L-3 and L-16 clones, respectively. Cross-resistance patterns between the standard antimalarial drugs and artemisinin were determined against 36 African isolates of P. falciparum obtained from imported cases of malaria in France. Chloroquine-resistant isolates (n = 21) were significantly more susceptible to artemisinin (50% inhibitory concentration [IC50] 7.67 nM), arteether (IC50 3.88 nM), artemether (IC50 3.71 nM), and artelinate (IC50 3.46 nM), as compared with the 15 chloroquine-susceptible isolates (IC50 11.4, 5.66, 5.14, and 5.04 nM, respectively). Arteether, artemether, and artelinate were equally effective and twice as potent as artemisinin. A significant positive correlation was found between artemisinin and mefloquine (r = 0.424, P = 0.022), artemisinin and halofantrine (r = 0.569, P < 0.001), chloroquine and quinine (r = 0.651, P < 0.001), and mefloquine and halofantrine (r = 0.863, P < 0.001), suggesting in vitro cross-resistance among these drugs. The present in vitro findings require confirmation in clinical studies.

Animals↗
PubMed1993

[Frequency of bronchopulmonary isolation of Aspergillus species in patients infected with human immunodeficiency virus: pathogenic role?].

Prevalence of aspergillosis in patients infected with the human immunodeficiency virus (HIV) is unknown. Mycologic findings in bronchopulmonary specimens from 614 HIV-positive patients sent to a parasitology laboratory between June 1, 1989 and May 31, 1991 were analyzed retrospectively; medical records of Aspergillus sp--positive patients were studied to evaluate the potential pathogenic role of this organism. Prevalence of Aspergillus sp. was 2.7% in bronchoalveolar lavage (BAL) specimens, (21/757), 15.1% in sputum specimens (3/53), 12.6% in bronchial aspirates (11/87), 7% in protected brush specimens (2/28), and 16.6% in lung biopsy specimens (4/24). A total of 20 patients (rate = 3.14%) had lung specimens positive for Aspergillus sp. (A. fumigatus 95% and A. niger 5%). Among them, 66% had a single positive specimen (14.3% with a positive smear) and 33% had several positive specimens (mean 4.9 +/- 3.3). Four patients (20%) with a more than 20-month history of AIDS and less than 36 CD4+ cells per microliter had documented pulmonary aspergillosis; three of these patients also had a current or past history of pulmonary mycobacterial infection. Rate of recovery of Aspergillus sp. in LAB specimens was low. The other specimens were harvested because of clinically suggestive manifestations. However, in 20% of patients with positive specimens. A. fumigatus was the cause of patent infection; these patients had severe AIDS-related immunodeficiency.

AIDS-Related Opportunistic Infections↗
PubMed1993

Evolution of chloroquine resistance in central and west Africa.

The evolution of in vitro chloroquine susceptibility of clinical isolates of Plasmodium falciparum obtained from travellers returning to France was studied between 1986 and 1991 using the isotopic semi-microtest. Based on the analysis of 1,147 interpretable tests on isolates originating from Central and West Africa, the study showed that the proportion of chloroquine-resistant falciparum malaria remained stable between 1986 and 1988 and has diminished between 1989 and 1991. The diminution of chloroquine-resistant imported malaria may be associated, at least in part, with a better compliance of French travellers with the recommendation to use either mefloquine or a combination of chloroquine and proguanil since 1989 and an increasing proportion of African immigrants who tend to neglect regular chemoprophylaxis during the visit to their countries. The reason for the stabilisation of chloroquine resistance is unknown, and this phenomenon may be temporary, necessitating a continuous surveillance of drug susceptibility.

Africa, Central↗
PubMed1992

In vitro antimalarial activity and chloroquine potentiating action of two bisbenzylisoquinoline enantiomer alkaloids isolated from Strychnopsis thouarsii and Spirospermum penduliflorum.

The bisbenzylisoquinolines 7-O-demethyltetrandrine and limacine, respectively, isolated from Strychnopsis thouarsii Baill. and Spirospermum penduliflorum Thou. were evaluated for their intrinsic antimalarial activity in vitro and chloroquine potentiating action against the chloroquine-resistant Plasmodium falciparum FCM 29 originating from Cameroon. They both showed significant antiplasmodial potency in vitro with very similar IC50 values of respectively, 740 nM and 789 nM (IC50 = 214 nM for chloroquine used as standard drug), which demonstrated that the stereochemistry of the C-1 and C-1' configuration likely plays a role in the chloroquine potentiating effect of these drugs. If confirmed in vivo, these results may account for the traditional use of the two plants as antimalarials and adjuvant to chloroquine in Madagascan folklore remedies.

Alkaloids↗
PubMed1992

In vitro activity of pyronaridine against African strains of Plasmodium falciparum.

The in vitro activity of pyronaridine was determined and compared with the activity of monodesethylamodiaquine and amopyroquine against 31 clinical isolates and two clones of Plasmodium falciparum originating from Central and West Africa using a semi-micro drug susceptibility test. Pyronaridine and amopyroquine were 2.5 and four times less active, respectively, against the highly chloroquine-resistant clone, than against the chloroquine-susceptible clone but were equally active against chloroquine-susceptible and chloroquine-resistant clinical isolates. Compared with chloroquine-susceptible isolates, monodesethylamodiaquine was three times less active against chloroquine-resistant parasites. Pyronaridine is highly active against chloroquine-resistant strains of P. falciparum and may be a promising candidate for the treatment of resistant malaria.

Africa↗
PubMed1992

In vitro activity of the enantiomers of mefloquine, halofantrine and enpiroline against Plasmodium falciparum.

The in vitro activity of the enantiomers of mefloquine, halofantrine and enpiroline was compared against chloroquine-resistant and -susceptible strains of Plasmodium falciparum using a semi-micro drug susceptibility test. For each strain, the corresponding enantiomers exhibited similar activities. The enantiomers of halofantrine were the most active against both susceptible and resistant strains, followed by the enantiomers of mefloquine and enpiroline.

Animals↗
PubMed1992

In vitro activities of chloroquine in combination with chlorpromazine or prochlorperazine against isolates of Plasmodium falciparum.

The combinations of chloroquine plus chlorpromazine and chloroquine plus prochlorperazine were evaluated in vitro for potentiation against isolates of Plasmodium falciparum. Potentiation was observed against all chloroquine-resistant isolates. There was no potentiation against 8 of 10 chloroquine-susceptible isolates. The results indicated that the phenothiazines can potentiate chloroquine action against resistant parasites found in natural conditions.

Animals↗
PubMed1992

In vitro activity of halofantrine and its relationship to other standard antimalarial drugs against African isolates and clones of Plasmodium falciparum.

The in vitro activity of halofantrine was studied in chloroquine-susceptible and chloroquine-resistant African clones of Plasmodium falciparum over a period of six months. The susceptibility level remained stable in both clones. The chloroquine-susceptible clone (50% inhibitory concentration [IC50] 6.88 nM) was less susceptible to halofantrine than the chloroquine-resistant clone (IC50 2.98 nM). Using an isotopic semimicro drug susceptibility test, the in vitro activity of halofantrine was compared with the activities of chloroquine, quinine, and mefloquine to study the cross-resistance patterns against 76 African isolates of P. falciparum isolated from cases of malaria imported into France. Chloroquine-resistant isolates (n = 47) were significantly less susceptible to quinine (IC50 234 nM), but were more susceptible to both mefloquine (IC50 3.20 nM) and halofantrine (IC50 1.14 nM) compared with the chloroquine-susceptible isolates (n = 29; IC50 147 nM for quinine, 7.16 nM for mefloquine, and 2.62 nM for halofantrine). A significant positive correlation was found between the activities of chloroquine and quinine and between those of mefloquine and halofantrine, indicating cross-resistance between these drugs, while a negative correlation was observed between chloroquine and mefloquine or halofantrine. The responses to quinine and mefloquine or halofantrine showed no correlation with each other. These results reinforce the importance of a cautious use of antimalarial drugs in Africa.

Africa↗
PubMed1992

[Contribution of molecular genetics to the understanding of chemoresistance of Plasmodium falciparum].

Resistance to pyrimethamine and proguanil is due to a single point mutation in the gene that codes for dihydrofolate reductase. A single mutation gives rise to resistance to only one of the drugs. Resistance to both drugs results from several mutations. Chloroquine resistance phenotype is due to a rapid efflux of the drug from the parasite's digestive vacuole. This efflux is associated with a transmembrane permeability glycoprotein, or P-gp, which is similar to the protein implicated in the multidrug resistant phenotype of some cancer cells. However, one or several other poorly understood major gene(s) may be involved. Drugs which can inhibit the supposed affinity of P-gp for chloroquine are under study.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Evaluating the efficacy of chloroquine in febrile Guinean children infected with Plasmodium falciparum by a simplified in vivo test.

A modified version of a simplified in vivo test was applied to assess the susceptibility of Plasmodium falciparum to chloroquine among semi-immune febrile children in Kouroussa, Guinea. In 27% of cases, a partial response (RI/RII) to chloroquine was observed; the remainder showed a good response (S/RI). This test is both practical and useful to assess the efficacy of chloroquine at the intermediate level of health care services.

Animals↗
PubMed1992

[Stability and chemosensitivity of Plasmodium falciparum to chloroquine in 1990 and 1991 in Ankazobe, a village in high plateau Madagascar].

The in vivo and in vitro response of Plasmodium falciparum to chloroquine was conducted in Ankazobe, a village located in the high plateau area. These studies confirmed the low level of chloroquine-resistance. The in vivo data indicate the absence of increase resistance during the 2 years study. Chloroquine is still the drug of choice for the treatment of malaria attack in this area.

Animals↗
PubMed1992

[Stability of P. Falciparum resistance to chloroquine between 1987 and 1989 in Mounana, Gabon].

Between 1987 and 1989 the trend in the chloroquine resistance of Plasmodium falciparum in the mining town of Mounana in south-eastern Gabon was studied in vivo and in vitro in 58 and 158 subjects, respectively, aged from 1 to 15 years. The tests used were a simplified variant of the standard WHO 7-day test for the in vivo study and the isotopic semi-microtest of chemosensitivity for the in vitro study. The health situation in 1989 showed no change from the 1987 situation, but an increase in febrile symptoms suggestive of malaria was observed in 1989. This observation may be linked to a decrease in the distribution of chloroquine since 1987, accompanied by the use of other antimalarials following the appearance of chloroquine-resistant strains. While the parasitological efficacy in vivo remained the same in 1989, there was a decrease in the proportion of strains resistant to chloroquine in vitro compared to 1987; likewise, the therapeutic efficacy as estimated from temperature readings was better in 1989 than in 1987: the modification of the prophylactic strategy since 1986 and the drop in chloroquine consumption since 1987 could be responsible for a stabilization of chloroquine resistance at Mounana. The authors consider it appropriate in this region to continue treating malaria in children with chloroquine (in a dosage of 25 mg/kg) and to use a second-line treatment in the event of the recurrence of malaria symptoms within the next two weeks.

Adolescent↗