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L K Basco

Publications and source records attributed to L K Basco.

103 records · Page 6Linked to original sources
PubMedDate not supplied

Point mutations in the Plasmodium falciparum cg2 gene, polymorphism of the kappa repeat region, and their relationship with chloroquine resistance.

Based on the available DNA sequence data of the Plasmodium falciparum cg2 gene, we have hypothesized that 3 amino-acid substitutions, His275Gln, Gly281Ala, and His299Gln, may represent the key mutations that confer resistance to chloroquine. The presence of 14 tandemly repeated hexamer units in the kappa region has also been suggested to be indicative of chloroquine resistance. These 2 hypotheses were tested by determining the sequence of DNA fragments containing all 3 codons and kappa repetitive region (approximately 450-basepairs) for 53 randomly selected clinical isolates (obtained in Cameroon in 1994-97) with known response in vivo and/or in vitro to chloroquine. The cg2 genotypes based on the 3 codons and the response in vitro to chloroquine, as well as the number of kappa repeat units and responses in vivo and in vitro to chloroquine, were associated (P < 0.05). cg2 gene mutations were more common in parasites from patients with failure in vivo. However, this difference did not achieve statistical significance (P = 0.055). The sensitivity and specificity of the 3 codons and kappa repeat region to predict the response in vitro to chloroquine ranged between 75% and 85%. The sensitivity and specificity of these genetic markers to predict the response in vivo to chloroquine were of lower values. The kappa repeat region of the clinical isolates is polymorphic but characterized by several conserved features.

Antimalarials↗
PubMedDate not supplied

[Mefloquine and halofantrine, new therapeutic drugs of malaria].

Mefloquine and halofantrine are quinine-related aminoalcohols recently introduced for the oral treatment (both drugs) and oral chemoprophylaxis (mefloquine) of malaria. Soon after these new drugs were launched the volume of sales testified to the need for alternative treatments in view of the resistance of Plasmodium falciparum to a variety of drugs, including chloroquine, amodiaquine and sulfadoxine-pyrimethamine. Quinine remains effective but it is difficult to handle. Both mefloquine and halofantrine are remarkably effective against the intraerythrocytic pathogenic forms of malaria; they also have a rapid and prolonged action and a low toxicity. Halofantrine is sometimes incompletely absorbed. Neurological side-effects, usually moderate, have been reported with mefloquinone. Partial cross-resistance has been demonstrated within each class of antimalarials: aminoalcohols, amino-4-quinoleins (chloroquine, amodiaquine) and antifolics-antifolinics (sulfamides, pyrimethamine, proguanil), but not between the classes. Further studies are necessary concerning the absorption and tolerability of mefloquine and halofantrine, as well as the regional level of P. falciparum sensitivity to these new drugs.

Animals↗
PubMedDate not supplied

In vitro activity of mitochondrial ATP synthetase inhibitors against Plasmodium falciparum.

The mitochondrion appears to be essential for the growth of asexual, intraerythrocytic stages of Plasmodium falciparum and may thus be a suitable chemotherapeutic target. The in vitro activity of almitrine, a mitochondrial ATP synthetase inhibitor used for the treatment of hypoxemia, was compared with other mitochondrial inhibitors against chloroquine-susceptible and chloroquine-resistant P. falciparum using an isotopic semimicro drug susceptibility assay. The 50% inhibitory concentration (IC50) values of almitrine (range: 2.6-19.8 microM) were within similar range of values of other mitochondrial ATP synthetase inhibitors and doxycycline, a mitochondrial protein synthesis inhibitor. Almitrine was equally active against chloroquine-susceptible and chloroquine-resistant parasites. Drug combination studies showed no interaction between chloroquine and almitrine. Our results suggest that almitrine, a clinically safe drug, may represent a lead compound with a specific target against the mitochondrial ATP synthetase which may be useful for antimalarial chemotherapy.

Almitrine↗
PubMedDate not supplied

Molecular epidemiology of malaria in Yaounde, Cameroon. VII. Analysis of recrudescence and reinfection in patients with uncomplicated falciparum malaria.

In an endemic area where malaria transmission is intense and continuous, reappearance of asexual parasites may be ascribed to either recrudescence or reinfection. To distinguish between recrudescence and reinfection after oral treatment with chloroquine, amodiaquine, pyronaridine, sulfadoxine-pyrimethamine, halofantrine, or artesunate, three polymorphic markers (circumsporozoite protein, merozoite surface antigens 1 and 2) from pre-treatment and post-treatment samples were amplified by the polymerase chain reaction, and the in vitro response to chloroquine was determined for comparison. Of 52 paired samples, 22 (42%) were reinfections. Recrudescence occurred more frequently on or before Day 14 (22 of 30 cases, 73%). Except for one case, all reinfections were observed beyond Day 14. The phenotype determination was not sufficiently precise to distinguish between recrudescence and reinfection. Our results suggest that beyond Day 14 (and until Day 42), recrudescence and reinfection cannot be distinguished at our study site unless molecular techniques are used and that some results derived from the polymerase chain reaction need to be compared with the microscopic examination of thick blood smear to exclude gametocyte carriers without asexual parasites after treatment.

Administration, Oral↗