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Biomedical subjects

J Le Bras

Publications and source records attributed to J Le Bras.

At least 109 records · Page 6Linked to original sources

[Uncomplicated attack of malaria in an area with high resistance to chloroquine. I. Evaluation of a short treatment with quinine].

The good results achieved in the treatment of malaria with a 7 and 5 days one of quinine (orally dose 8 mg/kg/8 h), incited the authors to try a 3 days long treatment at the same dose. They experimented this protocol on hospitalised children. All patients were free of parasites at day 7 with an average residual concentration quinine of 2.7 +/- 0.8 mg/l. Among the 7 patients with malaria at day 14, 4 didn't require another treatment and 2 presented new infestation. 50% of plasmodial isolated strains were chloroquine resistant and 40% amodiaquine resistant. The efficiency of this protocol could be in favour of its larger use.

Adolescent↗

[Plasmodium falciparum drug resistance in the Congo. Evaluation of surveys carried out from 1985 to 1989].

Surveys on drug sensitivity of Plasmodium falciparum carried out between 1985 and 1989 included 7-day in vitro tests and in vivo tests. 485 in vivo tests were carried out in eight surveys conducted in Brazzaville and in several inland regions. The subjects were congolese children aged between 3 months and 15 years old. They were recruited in hospital, mother-child clinics or at school. The drugs studied were chloroquine, amodiaquine and the sulfadoxine-pyrimethamine combination. 182 strains were tested in vitro in two surveys (December 1985 and January 1987); amino-4-quinolines, quinine and mefloquine were studied. Although resistance to amino-4-quinolines is a recent occurrence, by 1985 it had spread widely in the indigenous population in the Centre and South of the country. Resistance has since increased gradually, especially for chloroquine which undergoes specific surveillance. The situation is less serious in the North, a less densely populated region which is still enclosed. In an in vivo comparative study with chloroquine conducted in Brazzaville in November 1986, amodiaquine was found to be only slightly more effective at a similar dosage. At that time, certain isolated observations already seem to imply that the sulfadoxine-pyrimethamine combination was also affected by resistance. This was not corroborated in an in vivo study carried out in 1989 on 40 children presenting with a malarial attack. Although the sensitivity to quinine may probably be decreased. This drug cannot yet be considered as being truly affected by resistance. The activity of mefloquine, the use of which is still limited, was satisfactory in 1987 in two different regions of the country.

Adolescent↗

Pharmacokinetics of intramuscular amopyroquin in healthy subjects and determination of a therapeutic regimen for Plasmodium falciparum malaria.

The disposition of amopyroquin was investigated in 10 healthy volunteers after a single 2-mg/kg (body weight) intramuscular dose of amopyroquin base. The major form of the drug in plasma and in whole blood was nonmetabolized amopyroquin, and only very low levels of its primary amine derivative were detected. After a rapid absorption phase (15 min), levels in plasma declined, following a tri-exponential model with a terminal elimination half-life of 129.6 +/- 92.5 h. The apparent volume of distribution (V/F) and the systemic clearance (CL/F) were 238 +/- 75 liters/kg and 2,063 +/- 1,159 ml/min, respectively. The renal clearance, calculated by using urine excreted during the first 48 h, was 119 +/- 99 ml/min and represented about 6% of the systemic clearance. About 1.2 and 0.2% of the amopyroquin dose was excreted in the urine during the first 48 h as nonmetabolized amopyroquin and its primary amine metabolite, respectively. Twenty-two Plasmodium falciparum malaria patients were studied after treatment with one of the following regimens of intramuscularly injected amopyroquin base: 3 mg/kg (body weight), 6 mg/kg, or 6 mg/kg followed by 3 mg/kg 24 h later. Parasitemia was cleared at day 7 in one of six, four of seven, and seven of nine patients, respectively. On the basis of this study, a regimen of 12 mg/kg (body weight) administered in two or three injections is suggested.

Adolescent↗

[Utilization of modern and traditional health systems in the rural Ivory Coast area].

The authors carried out a questionnaire survey among the potential users of three rural health centers in Côte d'Ivoire. Between 58 and 90% of heads of family visit their zonal health center, between 18 and 50% also visit more distant centers. The utilization of other modern health structures is rare, but appeal to the herbalist healers is common and varies according to the characteristics of the families. Utilization of the two systems is not exclusive, 51% starting with the biomedical service. Of interrogated heads of family, 24% procure health care for others than members of their own family.

Cote d'Ivoire↗

[Surveillance of Plasmodium falciparum drug sensitivity in Yaounde and its surroundings (Cameroon). In vivo and in vitro study].

Among 172 strains collected in Yaoundé 60% are chloroquine-resistant, 37% are amodiaquine-resistant, instead of quinine and mefloquine which are completely efficient. Among 30 strains collected at a rural health center (where self treatment decreases), 27% are chloroquine-resistant. New therapeutic schemes for first and second line treatment in endemic areas must be evaluated.

Adolescent↗

[Plasmodium falciparum drug resistance and sulfadoxine-pyrimethamine in Africa].

The sulfadoxine-pyrimethamine combination has not been recommended for the prophylaxis of malaria since 1985 following serious accidents in the USA. However, this drug is worth considering for treatment since it has the advantage over mefloquine of being cheaper, having fewer side effects and it avoids using mefloquine. A study of Plasmodium falciparum resistance to Fansidar should be carried out on cases imported to France to determine an adapted utilisation of this drug. This would be an appreciable advantage for tropical Africa.

Adult↗

[Severe hypoglycemia during a pernicious attack of Plasmodium falciparum malaria treated with quinine (study of 110 cases)].

One hundred and ten patients with severe falciparum malaria have been admitted between 1985 and 1987. All had received quinine to the same protocol: 8.3 mg base/kg infused intravenously over 3 hours every eight hours. A systematic glycaemic supervision by capillary glycaemia every eight hours has been employed. Hypoglycaemia occurred in 17 patients (15.5%). Despite an early injection of glucose, recurrent hypoglycaemia was almost constant (16 over 17). The mortality of the group with hypoglycaemia is significantly higher (41% to 25%; 00.5 less than p less than 0.1). We have not found any connection between the risk of hypoglycaemia and elements of gravity of the access. If the part of the patient (age, pregnancy), high parasitemia and impaired hepatic gluconeogenesis have been finding, our results suggest than quinine-induced insulin secretion is the principal mechanism of this hypoglycaemia. Its high incidence and its severity impose preventive measures.

Adult↗

[A study of the efficacy of the chemoprevention of malaria using chlorproguanil alone or in combination with chloroquine in French expatriates in Dar-es-Salaam, Tanzania].

Seventy-nine French residents in Dar-es-Salaam, Tanzania, on 3 chemoprophylactic regimens, were included in a prospective study for a mean time of 10.8 +/- 3 months. No malaria attack was observed in the group (n = 32) taking chlorproguanil and chloroquine for chemoprophylaxis. Two attacks were reported in the group (n = 29) using chlorproguanil alone and 5 attacks in the group (n = 20) that was not taking antimalarial chemoprophylaxis. The blood concentration of chlorproguanil and chlorcycloguanil, the active metabolite, were measured, 3 hours (II3), 3 days (D3), and 7 days (D7) after the weekly dose. The urine concentration was measured at D7. The prophylaxis failure with chlorproguanil can be explained either by irregular use of the drug, or insufficiently lasting plasma concentration of chlorcyloguanil, or existence of parasite resistance to dihydrofolate reductase inhibitors.

Adolescent↗

Viruslike particles containing knob-associated histidine-rich protein are secreted into the culture medium of Plasmodium falciparum in vitro cultures.

This report describes the isolation of a viruslike particle from in vitro cultures of the human malaria parasite P. falciparum. Electronmicroscopic observations suggest that the particles are liberated into the culture medium by budding from the erythrocyte membrane. The density of the free particles is 1.16, they contain nucleic acid and two distinct molecular species of the knob-associated Histidine-rich protein. Proteins of the particles are recognized by sera from malaria patients. The previously described knobs may correspond to viral coats inserted in the membrane.

Animals↗

Susceptibility of Plasmodium falciparum to a peroxidase-mediated oxygen-dependent microbicidal system.

The viability of Plasmodium falciparum in culture was assessed by [3H]hypoxanthine incorporation during 24 h of incubation with lactoperoxidase, glucose-glucose oxidase, hydrogen peroxide, halides, or thiocyanate, alone or in combination. Synergistic inhibition was produced by the following combinations: lactoperoxidase plus hydrogen peroxide, lactoperoxidase plus glucose-glucose oxidase, and lactoperoxidase plus hydrogen peroxide plus halides or thiocyanate. These inhibitory effects were reversed by catalase and glutathione. The presence of plasmodial crisis forms inside the erythrocytes suggests that the oxygen-dependent microbicidal system of phagocytes has a killing effect.

Animals↗

[Stimulation of the chemiluminescence of human polymorphonuclear leukocytes in various stages of the intraerythrocyte development of Plasmodium falciparum].

The synchronized cultures of Plasmodium falciparum were used to stimulate in vitro the chemiluminescence of human polymorphonuclear leukocytes in the presence of immune serum. The schizonts were concentrated by Percoll gradient centrifugation method (density 1.085 and osmolarity 285 mOsmol), and placed in culture, treated 6 hours later by sorbitol. Under incubation at constant temperature and pressure, the rate of synchronization reached 85% for schizonts during 5 replicative cycles. Every asexual stages of Plasmodium falciparum were used separately to stimulate polymorphonuclear leukocytes: merozoites were the most effective, followed by schizonts, trophozoites, and lastly supernatants of cultures containing degradation products of parasites.

Animals↗

[In vitro activity of various antimalarials (chloroquine, amodiaquine, quinine and mefloquine) against 32 isolates of Plasmodium falciparum in French Guiana].

The in vitro susceptibility of various Plasmodium falciparum isolates obtained from patients infected in French Guiana was tested in a semi-microtest, using four antimalarial drugs. 90.6% of 32 isolates were resistant to chloroquine, 40% to amodiaquine and 17% to quinine. All the 17 isolates were susceptible to mefloquine.

Amodiaquine↗