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P Deloron

Publications and source records attributed to P Deloron.

At least 127 records · Page 7Linked to original sources

[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. II. Study in two regions of the east coast].

In Manakara and Foulpointe (East Coast of Madagascar) 184 malarial patients were selected among 742 patients attending dispensaries. The 7 days in vivo tests was performed in 144 patients. 13/36 failure to alternative (10 mg/kg) and 1/61 failure to standard (25 mg/kg) chloroquine WHO tests were observed. 10 mg/kg oral amodiaquine failed within 7 days in 5/47 patients. The in vitro semi-microtest was performed with 27 isolates. 2/24 Plasmodium falciparum isolates were chloroquino-resistant (IC50 = 270 and 280 nM/1), 27/27 were sensitive to low doses of amodiaquine (max IC50 = 76 nM/1), 25/25 were very sensitive to dichlorquinazine (max IC50 = 83 nM/1) and with pipéraquine 22/24 were very sensitive (IC50 less than 75 nM/1) and 2 less sensitive (IC50 = 240 and greater than 140 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↗

[Distribution of chloroquine and desethylchloroquine in blood, plasma and erythrocytes of healthy subjects and malaria patients. Assay using HPLC].

Chloroquine (Cq) and desethyl-chloroquine ( CqM ) levels were measured by HPLC in the blood, plasma, and erythrocytes of 9 healthy subjects under standard prophylactic treatment (100 mg/day for 10 days) and 8 malarial patients given a therapeutic regimen (10 or 25 mg/kg). Chloroquine levels in various fractions of the healthy subjects were as follows: whole blood: 1 265 +/- 598 nmol/l; plasma: 145 +/- 63 nmol/l of whole blood; erythrocytes: 827 +/- 460 nmol/l of whole blood. The CqM /Cq ratio in malarial patients varied from 0.4 to 0.8. These results show that Cq levels and Cq metabolization varied significantly from one individual to the next. Above all, they demonstrate the presence of Cq in other types of blood cells. This underlines the practical importance of the conditions of chloroquine assay in blood.

Chloroquine↗

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↗

[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↗

Efficacy of a 3-day oral regimen of a quinine-quinidine-cinchonine association (Quinimax) for treatment of falciparum malaria in Madagascar.

In the search for an effective, safe and field-adapted alternative to chloroquine for therapy of chloroquine-resistant Plasmodium falciparum infections in Africa, a 3-d oral regimen of Quinimax (an association of quinine, quinidine and cinchonine) was evaluated in 35 individuals with P. falciparum in Madagascar, an area with chloroquine resistance. 63% of the parasite strains isolated were resistant in vitro to chloroquine, and 59% of the infections were present despite previous chloroquine intake. Three daily oral doses of 10 mg/kg Quinimax for 3 d cleared parasitaemia and improved clinical status in all subjects. Mean parasite and fever clearance times were 51.7 and 37.4 h, respectively. All patients were aparasitaemic at the end of the 7-d follow-up. When formulating therapy guidelines, the 3-d Quinimax regimen should be considered as a valuable alternative to chloroquine for treating falciparum malaria in African areas with clinical resistance to chloroquine.

Animals↗

Serological reactivity to the ring-infected erythrocyte surface antigen and circumsporozoite protein in gravid and nulligravid women infected with Plasmodium falciparum.

To investigate potential mechanisms for pregnancy-associated alterations in the immune response to malaria, we tested plasma samples from Plasmodium falciparum-infected nulligravida (42), primigravida (23) and multigravida (38) Kenyan women for reactivity to the ring-infected erythrocyte surface antigen (RESA) by a modified indirect fluorescent antibody assay and to synthetic peptides derived from amino acid sequences of RESA and the circumsporozoite (CS) protein of P. falciparum by an enzyme-linked immunosorbent assay. Reactivity to RESA showed the lowest titres in primigravid women, intermediate titres in nulligravid women and the highest titres in multigravid women (loge mean antibody = 3.28, 4.64, and 5.28, respectively, P less than 0.03), but was not associated with initial parasite density or response to chloroquine treatment. No relationship in antibody reactivity to the 3 synthetic peptides of the RESA molecule was observed by gravidity (0, 1, or greater than or equal to 2), age, initial parasite density or response to treatment. Levels of antibody to the synthetic peptides of the CS protein increased with age and were higher in gravid than in nulligravid women in the 15-19 year age group. The increased malaria prevalence and parasite density and the decreased response to antimalarial treatment in pregnant women is not explained by lower levels of antibody to RESA or CS protein during pregnancy.

Adolescent↗

Antibodies to the ring-infected erythrocyte surface antigen and the circumsporozoite protein of Plasmodium falciparum in a rural community from Burkina Faso.

A population-based study in Burkina Faso was conducted to determine, under conditions of natural exposure to malaria parasites, the prevalence rate and seasonal variation of antibodies to the repeated amino acid sequences of the Plasmodium falciparum ring-infected erythrocyte antigen (RESA) and the circumsporozoite (CS) protein, and the relationship of the presence of malaria parasites in the blood with the level of these antibodies. A random sample of households was selected and visited twice during 1988, in April just before the rainy season and in September at the end of the rainy season. Serological testing included an immunofluorescent assay for total anti-blood stage antibodies; a modified immunofluorescent assay on glutaraldehyde-fixed parasitized erythrocytes to detect antibodies to RESA; and an enzyme-linked immunosorbent assay (ELISA) using synthetic peptides representing repeat amino acid sequences of RESA [(EENV)5, (EENVEHDA)4, and (DDEHVEEPTVA)2] and CS protein [(PNAN5)]. In April, at the end of the dry season, 98% of the individuals had total P. falciparum antibodies, and 39% had anti-RESA antibodies. 32%, 82%, 80%, and 41% of the individuals had antibodies to the respective peptides. All prevalence rates increased with age. After the rains, in September, prevalence rates and levels of reactivity increased in each serological assay, except in the ELISA with (DDEHVEEPTVA)2. Presence of P. falciparum parasitaemia was inversely related to antibody response to the CS protein (PNAN)5 peptide but not to any other assay.

Adolescent↗

Immune response to Plasmodium falciparum liver stage antigen-1: geographical variations within Central Africa and their relationship with protection from clinical malaria.

Two populations of schoolchildren from Gabon and Cameroon were tested in 1995 for their immunological reactivity to synthetic peptides (LSA-Rep, LSA-J and LSA-CTL) from Plasmodium falciparum liver stage antigen-1 (LSA-1). The prevalence and levels of both cellular (lymphocyte proliferation, tumour necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma), and interleukin-10 (IL-10)) and humoral (immunoglobulin G) responses were determined. Protection from clinical malaria, determined after a prospective 1 year study in both sites, was associated with elevated proliferative responses to LSA-Rep and LSA-CTL in the Gabonese children, as well as with higher antibody levels to both schizont extract and LSA-Rep. The prevalence of peptide-stimulated TNF-alpha secretion was higher in the Cameroonian group, but higher levels of antibodies to LSA-Rep and LSA-J were found in the Gabonese children. The immunological differences observed between children in the 2 study sites are discussed in the context of both epidemiological and individual host factors.

Animals↗

Sulfadoxine-pyrimethamine for the treatment of Plasmodium falciparum malaria in Gabonese children.

Chloroquine can no longer be recommended as the first-line treatment for falciparum malaria in several parts of Africa, given the increasing resistance of Plasmodium falciparum to this drug. The sulfadoxine-pyrimethamine combination (SP) is obviously an alternative candidate, that has already been selected as first-line antimalarial treatment by a few African countries. However, the extent of resistance to SP appears to be highly variable within Africa. Therefore, we investigated the efficacy of SP to treat uncomplicated malaria attacks in children from south-east Gabon. Sixty-six children presenting with a P. falciparum malaria attack were given a standard regimen of SP, and were followed at Days 3, 7, 14, and 21. No RIII response was observed, but relatively high prevalences of RII (18.2%) and RI (12.1%) were present. Moreover, analysis of the clinical outcome according to CDC criteria showed that initial clinical response was lacking in 8.5% of children, and that clinical failure occurred in 9.1%.

Antimalarials↗