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J Le Bras

Publications and source records attributed to J Le Bras.

At least 127 records · Page 7Linked to original sources
PubMed1987

Cloning and sequencing of Plasmodium falciparum DNA fragments containing repetitive regions potentially coding for histidine-rich proteins: identification of two overlapping reading frames.

DNA sequences, potentially coding for histidine-rich proteins, were isolated from a P. falciparum genomic library using an oligonucleotide probe consisting of histidine codon repeats. Sequencing revealed that the different DNA fragments contain long repetitive regions very homologous to the probe. One clone was fully sequenced and contains two open reading frames that overlap in the repetitive region but are located on opposite strands. Analysis suggests that both are coding. One frame could code for a small histidine-rich protein, the other for a protein containing many aspartic acid residues. Southern blotting revealed that these sequences are conserved in all three P. falciparum strains studied.

Amino Acid Sequence↗
PubMed1987

Disposition of monodesethylamodiaquine after a single oral dose of amodiaquine and three regimens for prophylaxis against Plasmodium falciparum malaria.

The disposition of monodesethylamodiaquine was studied in four healthy subjects after a single oral dose of 10 mg/kg amodiaquine base. Amodiaquine was not found in any sample, but the major metabolite monodesethylamodiaquine was detected and was assumed to be the sole derivative that contributed significantly to antimalarial activity in the blood. The best fit for the decay of the metabolite was obtained with a three-compartment model. The half-lives of the first two phases were 3.2 to 11.4 h for t1/2 alpha 1 and 22.7 to 50.3 h for t1/2 alpha 2 in plasma. The half-life of the terminal phase (t1/2 beta) was between 9 and 18.2 days. The concentration in whole blood was 4- to 6-times higher than in plasma. Three schedules (alternate days, weekly, daily) of the conventional prophylactic dose of 10 mg/kg per week were compared in six other healthy subjects. There were significant differences in the plasma monodesethylamodiaquine levels between the three schedules.

Adult↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

[Drug sensitivity of malaria in a population of children in Pointe-Noire, Congo, in the first half of 1986].

The study by an isotopic semi-microtest of the sensitivity of 44 P. falciparum strains isolated from Congolese children living in Pointe-Noire demonstrated a high prevalence of chloroquine resistance and partial cross resistance to monodesethylamodiaquine. The sensitivity to quinine was high except for 3 isolates. The assay of amino-4-quinolines by H. P. L. C. on 37 subjects revealed the extent of self-treatment and drug-pressure in this population. A 3-day treatment with 25 mg/kg of chloroquine or amodiaquine in 24 subjects resulted in the disappearance of clinical symptoms in all patients and a parasitological cure on day 7 in 75%. The partial maintenance of efficacy of amino-4-quinolines in this chloroquine-resistant region implies that chloroquine and amodiaquine can be used as first choice drugs for uncomplicated acute malaria, but on condition that the levels of resistance and transmission are monitored.

Adolescent↗
PubMed1987

[2 cases of multiresistant Plasmodium falciparum malaria contracted in Douala with atypical clinical presentation].

We present two cases of Plasmodium falciparum malaria contracted in Douala despite adequate prophylaxis by Fansidar for one and by chloroquine for the other. Failure of curative treatment by Fansidar for the first case (in vitro chloroquine-resistant strain) and by amodiaquine plus erythromycin for the second. After these therapeutic failures, both patients presented without fever, but with splenomegaly and anaemia. The successful therapeutic was mefloquine.

Adolescent↗
PubMed1987

[The OCCGE (Organisation de Coordination et de Coopération pour la Lutte contre les Grandes Endémies) and the surveillance of the drug sensitivity of Plasmodium falciparum to antimalarials].

Spreading of chemoresistance from East Africa to Central Africa is a very worrying problem for Western Africa. In fact, chemotherapy of febrile attacks is at present admitted as malaria control strategy in the framework of Primary Health Care. This new strategy is based on the fact that commonly used antimalarial drugs as chloroquine are surely efficacious. Thus, the surveillance of chemosensitivity of Plasmodium falciparum local strains becomes a priority. From studies carried out in Burkina Faso during many years, Centre Muraz of O.C.C.G.E. has organized a surveillance system with several levels: a Reference Center, a National Center for each country and sentinel centers located in the different epidemiological features of the countries. This surveillance concerning many states can allow to detect more quickly some possible problems in relation with chemoresistance and to take measures to limit its impact.

Africa, Western↗
PubMed1987

[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↗
PubMed1987

[Current aspects of imported drug-resistant Plasmodium falciparum].

24 cases of Plasmodium falciparum malaria in a group of 73 non-immune subjects coming mostly from central Africa have been tested in vitro for chloroquine sensitivity: 5 are sensitive, 19 are resistant among whom one is also quinine-resistant. The comparison of the major clinical and biological features in the two groups by methods of statistical calculation shows that the parasitological diagnosis is retarded and that hemolysis is more frequent in the strains of Plasmodium falciparum resistant to chloroquine. Thrombopenia is more frequent with chemosensitives strains. In any case, the delay between the first symptoms and the parasitological diagnosis is increased with an average of 17 days in comparison to what was observed in the 1970's. Under the influence of several complex factors including human ones, the clinical aspects are changed in comparison to forms usually observed. In this context of an extension of the emergence of the chemoresistance and in the aim of efficiency, only the quinine I.V., with an average dose of 16.5 mg/kg per day of quinine-base, has been chosen as a curative treatment during 5 days allowing a rapid recovery without after-effects for all the cases.

Adult↗