Biomedical subjects

A Sabchareon

Publications and source records attributed to A Sabchareon.

31 records · Page 2Linked to original sources

PubMed1988

In vivo and in vitro responses to quinine and quinidine of Plasmodium falciparum.

A total of 66 Thai children with uncomplicated falciparum malaria were treated orally with regimens of either quinine or quinidine. Radical cures were observed in 85% (28 of 33) of the children who received quinine and in 88% (29 out of 33) of those who received quinidine. Treatment failures in both groups were RI responses.The mean trough level of quinidine (10 mumol/l) was about 2.5-times less than that of quinine (25 mumol/l). The electrocardiograms of the two treatment groups differed significantly in that there was an acute prolongation of the QT(c) interval in 56% of those who received quinidine compared with 21.0% of those given quinine. In vitro assays of the pretreatment drug susceptibilities of the isolates of Plasmodium falciparum indicated that the mean minimum inhibitory concentration (MIC) for quinidine (1.44 mumol/l) was about half that for quinine (3.02 mumol/l). Although both drugs are equally effective, quinine is recommended for treatment of multidrug-resistant malaria in paediatric patients, primarily because of the cardiac effects produced by quinidine.

Animals↗

PubMed1987

Human monoclonal anti-Plasmodium falciparum antibodies produced by stable EBV-transformed lymphocytes from patients with falciparum malaria.

Peripheral blood lymphocytes (PBL) from 10 persons living in a malaria endemic area and 18 patients recovered from falciparum malaria were studied, nine of whom were admitted to the Hospital for Tropical Diseases and the remaining nine patients were from Trad District Hospital. PBL were divided into two portions, one of which was transformed directly by EBV in the presence of cyclosporin A to eliminate T cell suppression and the other was pre-incubated before transformation with the extract of ultrasonically disrupted, schizont-enriched P. falciparum parasites from in vitro culture. The products of transformed cells were tested for antibodies against blood stages and sporozoites and cells from positive wells were cloned and propagated. With antigen pre-stimulation, cells from 212 of 317 wells (64.5%) were transformed, and this level of transformation was not significantly different from that in the absence of antigen stimulation in which 193 of 311 wells (62.5%) showed transformation (p greater than 0.05). In contrast, 85 of 212 (40.2%) clones from antigen prestimulated wells secreted antibodies whereas 18 of 193 (9.3%) wells without prior antigen stimulation did (p less than 0.0001). Only 44 of 103 antibody-positive clones were subjected to further analysis, of which 42 had activities against blood stages and two against sporozoites. Based on indirect immunofluorescent reactivities, our anti-blood stage monoclonal antibodies (MABs) were conformed to group I (21 clones), III (11 clones) and V (5 clones) and group VI (5 clones).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

A phase-III clinical trial of mefloquine in children with chloroquine-resistant falciparum malaria in Thailand.

Mefloquine is a highly effective drug for the treatment of falciparum malaria among adults, but studies of its effects on children are lacking. An open, noncomparative trial of mefloquine was therefore carried out among 84 children aged 5-12 years who were patients at the Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand. The drug was administered as a single dose of 18-29 mg base per kg body weight. Eighty-two of the 84 children completed a 42-day period of post-treatment observation. The drug was well tolerated also by 11 children with glucose-6-phosphate dehydrogenase deficiency, and all the children in the study cleared their parasitaemia initially (average clearance time, 65 hours). Furthermore, the clinical-chemical parameters measured exhibited no drug-related changes during the study. The radical cure rate of nearly 98% and high tolerance indicate that mefloquine can be used effectively and safely for the treatment of children aged 5-12 years who are suffering from uncomplicated falciparum malaria.

Child↗

PubMed1987

Evaluation of an in vitro test method for the assessment of sensitivity of Plasmodium falciparum to pyrimethamine and sulfadoxine.

Twenty three Plasmodium falciparum isolates collected from two highly pyrimethamine/sulfadoxine-resistant areas of Thailand were evaluated for their in vitro responses to pyrimethamine, sulfadoxine and combinations of these two drugs in various conditions. The test procedure was based on inhibition of parasite multiplication and of schizont formation, using the recommended modified RPMI medium 1640 with PABA 0.5 mug per litre and folic acid 10 mug per litre (LPLF). The optimum blood/medium ratios and inoculum sizes for parasite multiplication and for schizont formation were 1:19, 100 mul/well and 1:9, 50 mul/well, respectively. The appropriate incubation period was 48 hours. It was found that inhibition of either parasite multiplication or schizont formation could be used as the endpoint for evaluating the antiplasmodial action of pyrimethamine and combined pyrimethamine/sulfadoxine in vitro for field investigations; however, inhibition of only parasite multiplication should be used for determination of sulfadoxine activity. The actions of pyrimethamine in the combination pyrimethamine/sulfadoxine in ratios of 1:80 and 1:200 were similar. In vitro testing using combined pyrimethamine/sulfadoxine should be more precise than pyrimethamine alone for monitoring parasite susceptibility to the combined drug (Fansidar).

Animals↗

PubMed1986

Analysis of resistance to pyrimethamine/sulphadoxine of isolates of Plasmodium falciparum from Eastern Thailand.

The in vitro susceptibility of five field isolates of Plasmodium falciparum from the region of the Thai-Kampuchean border to pyrimethamine, sulphadoxine, and their combination, was determined using a microtitre test system and media deficient in p-aminobenzoic acid and folic acid. Two-fold serial dilutions of pyrimethamine ranging from concentrations of 8.0 to 0.125 microM and sulphadoxine ranging from 800 to 50 microM were evaluated for antimalarial activity. Viability was based on the maturation of the ring stages to normally-appearing schizonts. Tested singly the parasites had an average ID90 of 3.82 microM for pyrimethamine and greater than 800 microM for sulphadoxine. Analysis of the drugs interaction showed maximum potentiation at approximately 0.8 microM of pyrimethamine and 80 microM of sulphadoxine. These results suggest that resistance to Fansidar is due to the resistance to both components. Although there was a potentiating effect it was probably not sufficient enough for the drugs to be effective in vivo. This may, in part, explain the reduction in clinical cures with the sulphadoxine-pyrimethamine combination in eastern Thailand.

Drug Resistance, Microbial↗

PubMed1985

In vitro susceptibility of Plasmodium falciparum collected from pyrimethamine-sulfadoxine sensitive and resistant areas in Thailand.

Seventy Plasmodium falciparum isolates, collected from two geographically separate areas of Thailand, were tested for their in vitro responses to pyrimethamine, sulfadoxine, and a combination of these two drugs. The effects of pyrimethamine and pyrimethamine-sulfadoxine combinations against P. falciparum isolates were found to be significantly greater in a northern area where the combined drug was an effective therapeutic agent than in a south-eastern area, near the Thai-Kampuchean border, where the combined drug was no longer effective. However, the actions of sulfadoxine against parasites obtained from the two areas were not significantly different. There was no significant difference between the mean values of plasma 4-aminobenzoic acid (PABA) in falciparum malaria patients and in healthy controls. The test for PABA determinations used in this study gave positive readings with both PABA and sulfadoxine.

4-Aminobenzoic Acid↗

PubMed1985

In vitro sensitivity of Plasmodium falciparum to sulfadoxine and pyrimethamine.

An in vitro microtechnique of Rieckmann et al., (1978) modified by Yisunsri and Rieckmann (1980) using 3 media; Waymouth, Waymouth plus 10% human serum, and RPMI was assessed to determine the sensitivity of P. falciparum to sulfadoxine, pyrimethamine and its combination. The study confirmed the synergism between sulfadoxine and pyrimethamine. There was no interaction between media and drug tested. MIC1 and MIC2 of sulfadoxine in different media showed significant difference (p less than 0.001). No significant difference was observed in MIC1 and MIC2 of pyrimethamine in the three media used (p greater than 0.05). For sulfadoxine-pyrimethamine combination, MIC1 and MIC2 in Waymouth alone and plus 10% human serum showed no significance (p greater than 0.05) while in RPMI showed positive correlation (p less than 0.001). MIC1 might be more applicable for clinical evaluation than MIC2. At present Waymouth medium with 5% patient serum, is considered to be the most suitable for testing sensitivity of malarial parasites.

Culture Media↗

PubMed1983

Treatment of quinine resistant falciparum malaria in Thai children.

A study was carried out to assess the efficacy of a modified 7 day course of quinine in children with falciparum malaria, in comparison with those of a 7 day course of quinine at standard dosage and a combination of a 7 day course of quinine and sulfadoxine-pyrimethamine, and in relation to the MIC, and to the serum levels of quinine during the course of treatment. Seventy seven children aged 2 years to 12 years with falciparum malaria were randomly treated with one of the 3 regimens. Group I, quinine 10 mg base per kg body wt. 8 hourly for 7 days, 21 of 28 cases (75%) were cured, while 6 cases (21%) showed RI and 1 case (4%) RII failure. Group II, quinine 10 mg base per kg body wt. 8 hourly for the first 4 days then 15 mg base per kg body wt. 8 hourly for the next 3 days, 20 of 23 cases (87%) were cured, while 3 cases (13%) showed RI failure. Group III, quinine 10 mg base per kg body wt. 8 hourly for 7 days and then sulfadoxine 30 mg per kg body wt. and pyrimethamine 1.5 mg per kg body wt., 16 of 26 cases (62%) were cured and 10 cases (38%) showed RI failure. The cure rates in the 3 groups were not statistically different. The three groups had similar serum quinine concentration profiles. Treatment with quinine was successful in cases in which serum quinine levels could be maintained above MIC for 7 days. There was no additional effect of sulfadoxine-pyrimethamine on quinine.

Child↗

PubMed1982

Serum quinine concentrations following the initial dose in children with falciparum malaria.

Serum quinine concentrations were determined in 51 children with uncomplicated falciparum malaria and 22 controls. Quinine 10 mg salt/kg was given one-hour, two-hour, four-hour intravenously in group A (14 patients, 5 controls), group B (12 patients, 6 controls), Group C (10 patients, 6 controls) and given orally in group D (15 patients, 5 controls). In malaria patients, the highest serum quinine levels were observed at the end of intravenous infusion and by the 4th hour after oral medication. Mean of the peaks of the drug concentrations of the 4 schedules were not significantly different, ranging from 22 to 28 n mol/ml. Serum concentrations in the patients were significantly higher than those of the controls. The total clearance of quinine in the patients were approx. 1 ml/min/kg, which was significantly less than those of the controls. The total apparent volume of distribution of the drug was similarly reduced. In patients it was about 0.8 litre/kg. The elimination half times of quinine ranged from 9 to 11 hours, whereas the value in the controls ranged from 3 to 7 hours. Side effects of quinine were not observed.

Child↗

PubMed1981

Sulfadoxine-pyrimethamine resistant falciparum malaria in Thai children.

Sixty-eight children with uncomplicated falciparum malaria admitted to the Hospital for Tropical Diseases in Bangkok during April-December 1980 were randomly divided into 3 groups and given 3 regimens. Group 1 of 27 cases were treated with a single dose of sulfadoxine 20 mg per kg body wt and pyrimethamine 1.0 mg per kg body wt. Two cases (7.4%) were cured (S) while 4 cases (14.8%) showed RI failure, 17 cases (63.0%) RII failure and 4 cases (14.8) RIII failure. In Group 2, 18 cases were treated with a single dose of sulfadoxine 30 mg per kg body wt and pyrimethamine 1.5 mg per kg body wt. Two cases (11.1%) were cured (S), while 7 cases (38.9%) showed RI failure, 7 cases (38.9%) RII failure and 2 cases (11.1%) RIII failure. In Group 3, 23 cases were treated with quinine 10 mg base per kg body wt 8 hourly for 5 days plus sulfadoxine 20 mg per kg body wt and pyrimethamine 1.0 mg per kg body wt, single dose given with the last dose of quinine. Thirteen cases (56.5%) were cured (S), while 10 cases (43.5%) showed RI failure.

Child↗

PubMed1980

Treatment of giardiasis in children with quinacrine, metronidazole, tinidazole and ornidazole.

One hundred and twenty four children with symptomatic and parasitologically confirmed giardiasis were treated in a comparative trial. The dosage of antigiardia drug was adjusted to the body surface area of the patients from the adult basic dosage as 100 mg of quinacrine t.i.d. for 5 days, 200 mg of metronidazole t.i.d. for 7 days, 2 gm of metronidazole once, 2 gm of tinidazole once or 2 gm of ornidazole once. They were hospitalized for follow-up for 30 days. The parasitological follow-up consisted of daily examination of stool specimens. Reinfections were unlikely. The rates of success were: a 5-day course of quinacrine, cured all of them, 20 patients; a 7-day course of metronidazole, 12 of 20; metronidazole, single dose, 11 of 21; tinidazole, single dose, 18 of 21; ornidazole, single dose, 21 of 22; placebo, none of 20. After a single dose, 5 patients had transient elevation of transaminases, one patient in each of metronidazole and tinidazole group 3 patients in ornidazole group. A 5-day course of quinacrine gave excellent result but the drug is not widely marketed. Ornidazole or tinidazole were more effective, both of them were recommended as a drug of choice as single dose therapy, however transient increase of transaminases may occur in some cases.

Child, Preschool↗

PubMedDate not supplied

Pharmacokinetic study of mefloquine in Thai children aged 5-12 years suffering from uncomplicated falciparum malaria treated with MSP or MSP plus primaquine.

A triple combination of mefloquine, sulfadoxine and pyrimethamine (MSP) was used with primaquine for the radical treatment of falciparum malaria in Thailand. Primaquine was reported to inhibit hepatic microsomal enzymes and drug metabolism in animal and man. 23 children hospitalized in the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Bangkok, Thailand, were randomly allocated into two groups, group I received MSP equivalent to 20 mg base of mefloquine/kg body weight and group II received MSP plus primaquine (0.75 mg/kg). No statistical difference was noted for clinical response except the gametocyte clearance time was shorter in children given MSP plus primaquine (7 +/- 2.7 days) than the children given MSP alone (21.9 +/- 4.4 days) (P < 0.01). No serious side effects were recorded in this study. The plasma samples were obtained for kinetic calculations by HPLC in 18 children (11 in group I, 7 in group II). Mean Cmax was 7.4 +/- 5.2 h in group I and 6.6 +/- 7.0 h in group II. Mean t1/2, Cl/f and Vd/f were 9.8 +/- 1.6 days, 0.43 +/- 0.16 ml/min/kg and 8.84 +/- 4.21 l/kg in group I, 9.3 +/- 1.4 days, 0.41 +/- 0.12 ml/min/kg and 8.91 +/- 3.00 l/kg group II, respectively. The comparison of kinetic parameters in groups I and II revealed no significant difference (P > 0.05) suggesting no drug interaction. These kinetic values in children given MSP suspension were considerably different to those in adult patients with shorter tmax, t1/2 and MRT. The coadministration of MSP and primaquine in children would benefit by reducing the transmission of malaria in endemic areas.

Animals↗

PubMedDate not supplied

Efficacy and pharmacokinetics of atovaquone and proguanil in children with multidrug-resistant Plasmodium falciparum malaria.

A trial was conducted in 32 Thai children with uncomplicated multidrug-resistant falciparum malaria to assess the efficacy, safety and pharmacokinetics of atovaquone and proguanil; plasma concentrations of atovaquone, proguanil and its metabolite, cycloguanil, were measured in a subset of 9 children. The children received atovaquone (17 mg/kg/d for 3 d) plus proguanil (7 mg/kg/d for 3 d). Twenty-six children who had only Plasmodium falciparum infection and remained in hospital for 28 d were assessed for drug efficacy. The combination regimen produced a cure rate of 100%. Parasite and fever clearance times were 47 h (range 8-75) and 50 h (range 7-111), respectively. Atovaquone and proguanil were rapidly absorbed, with median time to peak concentrations of 6 h (range 6-24) and 6 h (range 6-12), respectively. Peak concentrations of cycloguanil were achieved between 6 and 12 h (median 6) after administration of proguanil. Mean peak plasma concentration of atovaquone on day 3 was 5.1 micrograms/mL (SD = 2.1). The day 3 mean peak plasma concentration of proguanil was 306 ng/mL (SD = 108) compared with 44.3 ng/mL (SD = 27.3) for cycloguanil. Mean values for the AUC (area under plasma concentration-time curve) were 161.8 micrograms/mL.h (SD = 126.9) for atovaquone, 4646 ng/mL.h (SD = 1226) for proguanil, and 787 ng/mL.h (SD = 397) for cycloguanil. Terminal elimination half-lives of atovaquone, proguanil and cycloguanil were estimated as 31.8 h (SD = 8.9), 14.9 h (SD = 3.3) and 14.6 h (SD = 2.6), respectively. No major adverse effect was attributable to the study drugs. Atovaquone/proguanil combination is safe and highly effective, and should be especially valuable for treatment of multidrug-resistant falciparum malaria.

Antimalarials↗