Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study was carried out in 12 children aged 6 months to 2 years, with uncomplicated falciparum malaria admitted to the Hospital for Tropical Diseases, Bangkok. They were treated with mefloquine in the form of MSP (mefloquine 250 mg+sulfadoxine 500 mg+pyrimethamine 25 mg) at a single dose of 25 mg mefloquine base/kg body weight. All of them were cured (28 days follow-up) with minimal side effects. Pharmacokinetic parameter determination was carried out in 9 cases. The results revealed that MRT, t1/2 and tmax in this study (children 6-24 months old) are comparable to the values in children aged 5-12 years, but shorter than in adult patients. Cmax and AUC in children 6-24 months old are comparable to those in children of 5-12 years, but much higher than in adult patients. Vz/f values in this study are comparable to those in children 5-12 years old, but lower than in adult patients.
 ...
PMID:Pharmacokinetics of mefloquine in children aged 6 to 24 months. 130 57

Merozoite surface protein-1 (MSP-1, also referred to as P195, PMMSA or MSA 1) is one of the most studied of all malaria proteins. The protein is found in all malaria species investigated and structural studies on the gene indicate that parts of the molecule are well-conserved. Studies on Plasmodium falciparum have shown that the protein is in a processed form on the merozoite surface, a result of proteolytic cleavage of the large precursor molecule. Recent studies have identified some of these cleavage sites. During invasion of the new red cell most of the MSP1 molecule is shed from the parasite surface except for a small C-terminal fragment which can be detected in ring stages. Analysis of the structure of this fragment suggests that it contains two growth factor-like domains that may have a functional role.
 ...
PMID:A malaria merozoite surface protein (MSP1)-structure, processing and function. 134 16

A comparative trial of the combination of mefloquine or MSP with tetracycline was carried out in fifty-one adult Thai male patients with acute falciparum malaria. The patients were randomized to receive either the combination of tetracycline (250 mg qid for 7 days) with mefloquine 4 tablets (1,000 mg) or with MSP 4 tablets (one tablet contains 250 mg mefloquine, 500 mg sulfadoxine and 25 mg pyrimethamine). Fifty patients had a complete 28-day follow-up period. Both regimens produced similar efficacy with no difference in adverse effects. In the mefloquine plus tetracycline group, the cure rate was 72% (18/25). One patient had an RIII response, the others showed initial response to the treatment with FCT and PCT of 40.7 +/- 27.4 and 76.2 +/- 34.2 hours (mean +/- SD) respectively. However, 6 patients developed recrudescence between days 17 and 29 (RI), 3 of these had vomiting. In the MSP plus tetracycline group, the cure rate was 76% (19/25). The means (+/- SD) of FCT and PCT were 44.7 +/- 38.0 and 80.6 +/- 25.0 hours, respectively. Six patients had recrudescence between days 17 and 31 (RI), 2 of these had vomiting. Although the addition of tetracycline improved the cure rate of mefloquine when compared with standard dose of mefloquine alone (3 tablets), these combinations seem to be useful in areas where alternative drugs are not available.
 ...
PMID:Clinical trials of mefloquine with tetracycline. 148 88

Mefloquine is the treatment of choice for uncomplicated multiresistant falciparum malaria, and in combination with sulphadoxine and pyrimethamine (MSP) at a single dose of 15/30/1.5 mg/kg, respectively, has been used in Thailand for the past 6 years. In 1985-86, MSP cured over 98% of 5192 patients with falciparum malaria on the Thai-Burmese border. 4 years later we studied the efficacy of MSP in 395 patients at the same location. The cure rate at 28 days was 70.8% (95% Cl 67-77.2%). The proportion of early treatment failures (in whom parasitaemia did not clear) had risen from 0.27 to 3.7% (p less than 0.0001). Failure rates were 50% in children under 6 years old, 29% in the 6-15 age group, and 19% in adults (p less than 0.001). Patients with early treatment failure were retreated with 25 mg/kg mefloquine, but 27% had a further recrudescence of infection within 28 days. The mean (95% Cl) serum mefloquine concentration at the time of first recrudescence was 638 (546-730) ng/ml, a value previously associated with successful treatment. Mefloquine concentrations were no lower in those with recrudescent infections than in age-matched successfully treated patients, suggesting that pharmacokinetic factors were not responsible for the high treatment-failure rate. Plasmodium falciparum has developed resistance to mefloquine rapidly, despite the addition of sulphadoxine and pyrimethamine and strict control of drug administration. The MSP combination should now be abandoned.
 ...
PMID:Mefloquine-resistant falciparum malaria on the Thai-Burmese border. 167 99

The pharmacokinetics of mefloquine (M) were studied in 59 male Thai patients with falciparum malaria. Mefloquine was administered alone (750 mg orally; group 1), or with primaquine (PQ, 45 mg; group 2), or in combination with sulfadoxine (1.5 g) + pyrimethamine (75 mg) (MSP; group 3), or as MSP + PQ (group 4). All patients in groups 1, 2 and 4 initially responded to treatment, but two patients from group 1 had RI recrudescent infections. One patient in group 3 failed to respond to treatment and was considered to have RII resistance, while a further patient from this group had RI recrudescence. The pharmacokinetic parameters for group 1 and group 3 were not significantly different. Co-administration of primaquine alone had no significant effect on the pharmacokinetics of mefloquine, but there was a statistically significant decrease in the terminal elimination half-life of mefloquine for group 4 relative to that for group 3.
 ...
PMID:Pharmacokinetics of mefloquine in combination with sulfadoxine-pyrimethamine and primaquine in male Thai patients with falciparum malaria. 228 99

The spread of chloroquine resistant strains of P. falciparum requires new approaches to treatment especially in tropical Africa. A single dose of 3 tablets of sulfadoxine-pyrimethamine (Fansidar) is a suitable and relatively inexpensive alternative. But under drug pressure resistance to this compound has developed in some South-East Asian countries and in Brazil, giving rise to multiple resistant strains of P. falciparum. A similar pattern has arisen with quinine to which almost 50% of P. falciparum strains have become resistant in Thailand. However the combination treatment of quinine with tetracycline given for 7 days is still successful in most cases. Unfortunately compliance to this regimen is rather poor in out-patients. Mefloquine (Lariam), recently marketed, and if used as 750 mg dose in semi-immune adult patients weighing less than 60 kg, has made possible a single-dose treatment schedule for falciparum malaria. In controlled studies conducted in South-East Asia the success rate of mefloquine was 97% in 445 patients. Since there is some fear of the appearance of resistance of P. falciparum to mefloquine, a combination of this compound with sulfadoxine and pyrimethamine was developed (MSP or Fansimef). Various controlled studies in South-East Asia have shown a success rate of this compound of 97% in 278 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[The treatment of multiresistant falciparum malaria in Southeast Asia]. 266 11

A randomized double blind study was performed to evaluate the tolerance and the acceptance of mefloquine alone (Lariam) compared to a combined drug regimen consisting of mefloquine, sulfadoxine and pyrimethamine (MSP; Fansimef) in the prophylaxis of malaria. 175 Europeans travelling to different malaria endemic areas received either mefloquine alone (250 mg/week) or its combination with sulfadoxine (500 mg/week) plus pyrimethamine (25 mg/week). One person taking mefloquine and two taking MSP discontinued the drug intake because of moderate clinical side effects. Mild and moderate adverse clinical reactions predominantly concerning the gastro-intestinal tract and the autonomous nervous system were reported with a significantly higher occurrence in the MSP group. With both prophylactic regimens, reversibly elevated liver enzyme activities (glutamate oxalate transaminase and glutamate pyruvate transaminase [GPT]) were observed after prophylaxis. The increase of GPT serum activity correlated significantly with relatively high GPT levels before prophylaxis in both groups. This finding suggests a limited use of both regimens in cases of liver dysfunction. One case of mefloquine-resistant Plasmodium falciparum malaria was observed from West Africa; this patient was cured by a standard regimen of chloroquine.
 ...
PMID:Tolerance of mefloquine alone and in combination with sulfadoxine-pyrimethamine in the prophylaxis of malaria. 269 82

Malaria, particularly that due to chloroquine-resistant Plasmodium falciparum, which requires management with antimalarial drugs capable of protecting against multiresistant strains, has emerged in Malaysia. A study was carried out to assess the efficacy and tolerability of 2 dosages of mefloquine/sulfadoxine/pyrimethamine (MSP; RO 13-5112) compared to Fansidar in a malaria endemic area. 914 subjects in 3 random groups were studied. Occurrence of malaria was assessed both clinically as well as by blood films. Plasma drug levels were also measured. The results showed that the low dose of MSP was completely effective in suppressing parasitaemia. 2.7% of the study population reported adverse drug reactions, the lowest incidence being in subjects on the low dose; their blood chemical profiles were also the least affected. The plasma levels of pyrimethamine and sulfadoxine achieved in the low dose group were slightly higher than expected, but there was no significant difference in bioavailability. The study showed that, for chemoprophylaxis, a low dose of MSP provided effective protection with minimal side effects.
 ...
PMID:Chemosuppression of malaria by the triple combination mefloquine/sulfadoxine/pyrimethamine: a field trial in an endemic area in Malaysia. 269 9

In Nigeria chloroquine remains the drug of choice for the treatment of falciparum malaria since chloroquine resistance is not yet a problem. Nevertheless, in view of the rapid spread of multi-resistant Plasmodium falciparum in Africa, it is desirable to test alternative drugs for efficacy and safety. To this end we undertook a comparative controlled trial of the new triple combination, mefloquine-sulphadoxine-pyrimethamine (MSP, Fansimef, Hoffman-La Roche, Switzerland) with chloroquine in a group of Nigerian children with symptomatic falciparum malaria. Our results showed that Fansimef was a rapidly acting blood schizontocide against the Nigerian strain of P. falciparum, and was well tolerated. In particular, sinus bradycardia, which was frequently observed with Fansimef in the trials conducted in Zambia, was not seen in any of the Nigerian patients.
 ...
PMID:Comparison of the susceptibility of falciparum malaria to mefloquine-sulphadoxine-pyrimethamine and chloroquine in Nigeria. 285 65

In Nigeria chloroquine remains the drug of choice for the treatment of falciparum malaria, since chloroquine resistance is not yet a problem. Nevertheless, in view of the rapid spread of multi-resistant Plasmodium falciparum in Africa it is desirable to test alternative drugs for efficacy and safety. To this end, we undertook a comparative controlled trial of the new triple combination, mefloquine-sulphadoxine-pyrimethamine (MSP, Fansimef) with chloroquine in a group of Nigerian children with symptomatic falciparum malaria. Our results showed that Fansimef was an effective blood schizontocide against the Nigerian strain of P. falciparum and was well tolerated. In particular, sinus bradycardia, which was frequently observed with Fanismef in the trials conducted in Zambia, was not seen in any of the Nigerian patients. In vitro sensitivity tests done on 26 P. falciparum isolates showed that all isolates were susceptible to complete inhibition by mefloquine, but the minimum concentration which produced complete inhibition in some isolates was higher than expected for fully sensitive parasites.
 ...
PMID:Sensitivity of Plasmodium falciparum to mefloquine-sulphadoxine-pyrimethamine (Fansimef) in vivo and to mefloquine alone in vitro in Nigeria. 307 41


1 2 3 4 5 6 7 8 9 10 Next >>