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At least 685 records · Page 38Linked to original sources
PubMed1987

The effect of mefloquine-sulfadoxine-pyrimethamine vs quinine on patients with complicated falciparum malaria.

Sixty-six patients with complicated falciparum malaria (defined as anaemia, hyperpyrexia, jaundice, or more than 2% of RBC parasitised) were studied. Patients with cerebral signs and symptoms were not included in the study. Patients were randomised in pairs to receive either mefloquine 750 mg, sulfadoxine 1500 mg and pyrimethamine 75 mg (MSP) single oral dose or quinine (10 mg/kg tds X 7 days oral therapy). All the patients were admitted in hospital for 7 days and were followed on days 14, 21 and 28. All patients survived. The parasite clearance times in MSP treated patients were significantly shorter then those treated with quinine. There was no difference in fever clearance time in the two groups of patients. One patient was resistant to MSP at RII level and 5 patients were resistant at RI level. Among patients treated with quinine 3 patients were resistant at RI level.

Adult↗
PubMed1987

Malaria on the Thai-Burmese border: treatment of 5192 patients with mefloquine-sulfadoxine-pyrimethamine.

Multidrug-resistant falciparum malaria is a major health problem along the Thai-Burmese border. From July 1985 until December 1986 a total of 5192 patients with falciparum malaria (1734 males, 3458 females) from this area were given supervised treatment with the combination mefloquine-sulfadoxine-pyrimethamine (MSP). The radical cure rate, assessed 21 days after drug administration, was 98.4% for the first 1975 patients, and 98.8% when assessed at 28 days for the remaining 3217 patients. In 3.8% of cases, parasites were still detected in peripheral blood smears on day 7 after treatment but this had fallen to 0.27% by day 9. Adverse reactions among the first 1975 patients were: vertigo (7.5% of patients), vomiting (5.8%), epigastric pain (0.6%), and transient confusional state (one case). MSP is an effective and well-tolerated drug for the treatment of drug-resistant falciparum malaria; however, delayed parasite clearance may give a false impression of RII resistance.

Adult↗
PubMed1978

Clearance of falciparum parasitaemia with a single dose sulfadoxine-pyrimethamine in Vientiane, Laos.

A total of 49 semi-immune Laotians aged 3 to 49 years, with falciparum malaria were treated with a single dose of sulfadoxine pyrimethamine (1500 mg, 75 mg, adult dose), in Vientiane, Laos. On day 7 after treatment the 49 cases were asymptomatic with complete disappearance of patent asexual parasitaemia. The result is compared with that obtained from treating 48 similar cases with a standard dose of chloroquine over 3 days.

Adolescent↗
PubMed1979

Single-dose therapy of falciparum malaria with mefloquine or pyrimethamine-sulfadoxine.

A single oral dose (1.5 g) of mefloquine hydrochloride cured all of 37 patients with falciparum malaria, and a single dose of pyrimethamine (75 mg) plus sulfadoxine (1.5 g) cured 34 of 38 patients. The rates at which parasitaemia and fever abated were similar for the two regimens but mefloquine was associated with a higher incidence of gastrointestinal side effects.

Clinical Trials as Topic↗
PubMed1979

Studies on Plasmodium falciparum in continuous cultivation. I. The effect of chloroquine and pyrimethamine on parasite growth and viability.

Recent advances in the in vitro study of human malaria have provided the knowledge to maintain Plasmodium falciparum in continuous culture. Using relatively cheap and easily obtainable materials it is now possible to study many parameters including parasite chemotherapy. The activity of two standard antimalarials, chloroquine and pyrimethamine, has been examined in vitro. The effect on the parasite is easily observed and can be measured not only as a decrease in parasite density, but also as the viability of the remaining parasites after drug pressure. Both chloroquine and pyrimethine showed activity against P. falciparum in vitro in concentrations equivalent to those obtained in plasma levels in vivo. The technique is very reproducible and offers a most valuable tool to the research worker.

Animals↗
PubMed1985

A double-blind clinical trial of a combination of mefloquine, sulfadoxine and pyrimethamine in symptomatic falciparum malaria.

Fansimef is a combination of 250 mg of mefloquine, 500 mg of sulfadoxine, and 25 mg of pyrimethamine per tablet. A total of 150 adult male Zambian patients who had symptomatic Plasmodium falciparum parasitaemia were treated in a double-blind randomized fashion with either one, two or three tablets of Fansimef. All patients in the three treatment groups showed an S-type response. The rates of clearance of parasitaemia and fever were similar in all treatment groups. Tolerance was good at all dose levels. The main side-effects were abdominal discomfort, weakness and lassitude, dizziness, and pruritus, but these were mild, transient and required no specific treatment. Vomiting occurred only in 4% of patients given the highest dose of three tablets. The results of various haematological and biochemical investigations and urinalysis were not adversely altered by the administration of Fansimef.

Adolescent↗
PubMed1979

Structural changes of Toxoplasma gondii bradyzoites and cysts following therapy with sulfamethoxypyrazine-pyrimethamine: studies by light and electron microscopy. Consequences for chemotherapy.

Mastomys natalensis chronically infected with Toxoplasma gondii strain ALT over two months were treated with sulfamethoxypyrazine-pyrimethamine for 10 and 25 days. 72 hours after discontinuation of therapy the animals were sacrificed. The brains were removed and, following corresponding preparation, studied for the presence of the parasite and structural changes of cysts by light and transmission electron microscopy. More or less pronounced structural changes could be found in cyst walls, bradyzoites, and in particular in the endodyogeny stages. The degree of damage proved to be proportional to the intensity of the bradyzoite metabolism. The combination of drugs used was capable of passing the cyst membrane as long as the bradyzoites maintained their metabolism irrespective of its intensity. In cysts with a largely dormant metabolism that had been subject to therapy, no micromorphological differences of the ultrastructure could be recognized when compared with untreated controls of identical age; these cysts could not be influenced by treatment.

Animals↗
PubMed1983

[Fragility of the X chromosome and inhibition of dihydrofolate reductase. Comparison of the effects of 2 antibiotics: trimethoprim and pyrimethamine].

The increase in frequency of the Xq27 gap is investigated after addition to the culture medium of two inhibitors of dihydrofolate reductase : trimethoprim (TMP) and pyrimethamine (PMT). Neither antibiotic induced the gap in ten normal subjects. In five Xqfra, mentally retarded, untreated boys, TMP (26,7 mg/l) and PMT (1,25 mg/l) increased equally the gap frequency. In two out of four women carrying the Xqfra and in three out of four Xfra mentally retarded boys, treated for a few months, with oral folic acid (one milligram/kg/day), TMP increased the frequency of the gap, while PMT was practically inactive. PMT is a much more powerful inhibitor of dihydrofolate reductase than TMP : it was concluded therefore that TMP could also act on some other steps of the monocarbons' metabolism. The only patient who reacted strongly to both TMP and PMT had previously suffered a severe neurologic regression during an antibiotherapy with TMP. It is stressed that dihydrofolate reductase inhibitors should be avoided when treating Xqfra patients.

Adult↗
PubMedDate not supplied

[Polyresistance of asiatic P. falciparum to chloroquine and pyrimethamine-sulfadoxine combination. Apropos of a new case].

The authors report a case of a multi-drug resistant Asiatic P. falciparum strain in a first non-immune man treated out of an endemic zone after failure of chemoprophylaxis by pyrimethamine-sulfadoxine. The authors compare this care with the lately published cases in Germany and Switzerland. They call again that I and II resistances were observed at the time of the drug's trials in and out of endemic zones. They ascertain that this resistances are often associated with chloroquino-resistance and that their number increases chiefly in certain areas.

Adult↗
PubMed1981

[Contribution to the determination of four antimalarial molecules (chloroquine, quinine, pyrimethamine, sulfadoxime) mixed in biological fluids. I. Spectrophotometry UV (author's transl)].

Antimalarial therapy is directed more and more towards the use of associated substances: Pyrimethamine, sulfadoxime, quinine et chloroquine. The authors propose a method of direct determination of these four molecules mixed in biological fluids. The recommended extraction process followed by a spectrophotometric UV determination is fast, reproductible and sufficiently sensitive to study the evolution of a therapy.

Antimalarials↗
PubMed1995

Efficacy of a 3-day oral regimen of quinine in an area of northern Nigeria with low-grade resistance of Plasmodium falciparum to chloroquine and sulphadoxine-pyrimethamine.

The efficacy in vivo of a 3-day oral regimen of quinine (30 mg/kg/day) was assessed in 34 children with falciparum malaria in an area of northern Nigeria with previously documented low-grade parasite resistance to chloroquine and sulphadoxine-pyrimethamine (SDX/PYR). By day 4, all 34 children were free of parasites. Mean parasite clearance time and fever clearance time were 2.7 and 1.7 days, respectively. However, on day 14, 5 (14.7%) children were again parasitaemic and 4 of them were clinically ill. They were again treated successfully with a standard course of oral chloroquine. No adverse drug effects were recorded. Of the 34 children, 9 parasite isolates were successfully cultured in vitro. EC50 and EC99 were 14.0 and 126.0 pmol per well respectively, indicating decreased parasite sensitivity but no resistance in vitro. In conclusion, the 3-day course of quinine was found to be an effective alternative to standard chloroquine treatment in the study area.

Administration, Oral↗
PubMed1994

In vivo sensitivity of Plasmodium falciparum to chloroquine, amodiaquine and sulfadoxine-pyrimethamine in western Uganda.

In an in vivo study of antimalarial sensitivity in Kabarole District, Western Uganda, 82% of asymptomatic malarial infections and 86% of symptomatic infections were chloroquine sensitive. Of persons with symptomatic malaria, 88% were sensitive to sulfadoxine-pyrimethamine (Fansidar). Amodiaquine cleared parasites in all persons in whom it was used. Over the course of the past five years, there appears to be no substantial increase in the extent of chloroquine resistance in Western Uganda.

Adult↗
PubMedDate not supplied

The effects of chronic administration of pyrimethamine on spermatogenesis and fertility in male rats.

The present study examines whether the antifertility effects of pyrimethamine (PYR), an inhibitor of dihydrofolate reductase, are mediated by a reduction in intratesticular testosterone (T) concentrations or whether PYR exerts its effect by a cytotoxic insult to spermatogenic cells that is independent of intratesticular testosterone. Adult male rats were treated daily with 100 mg/kg (n = 16) or 400 mg/kg (n = 16) of PYR in honey for 8 weeks. Control rats (n = 16) received honey without PYR. Eight weeks after treatment, five rats from each PYR-treated group and five control rats were mated with normal cycling female rats, and fertility was assessed. These rats were euthanized after the fertility trial; testis weight, testicular sperm, and epididymal sperm counts were determined, and serum levels of T, LH, FSH, and seminiferous tubule fluid T (STF-T) concentrations were measured by RIA. Testes from three rats per group were perfusion-fixed for histological evaluation. PYR was discontinued in the remaining rats for 8 weeks and similar parameters were evaluated after 8 weeks of recovery. PYR (100 mg/kg/day) treatment for 8 weeks did not have any effects on organ weights, testicular and epididymal sperm counts, and hormone levels when compared to controls. In contrast, PYR (400 mg/kg/day) treatment significantly reduced testis and epididymis weights, testicular and epididymal sperm counts, and fertility. Despite these effects, serum T, LH, FSH, and STF-T concentrations were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Sensitivity of Plasmodium falciparum to pyrimethamine in vivo and to sulphadoxine/pyrimethamine combination in vitro in pregnant women of northern Nigeria.

The in-vivo response of Plasmodium falciparum to a single dose of 25 mg pyrimethamine was evaluated in pregnant women in a semi-rural area of Zaria, northern Nigeria. Forty-four women were enrolled in the study and followed up for 14 days. Thirty-one (70%) of the women had cleared their parasitaemia by Day 7 and they remained parasite negative throughout the 14-day period of observation. The MPCT was 2.48 +/- 0.76 days. Thirteen (30%) of the 44 women were parasite positive either on Day 7 (7.16%) or Day 14 (6.14%) and re-treatment with a curative dose of chloroquine (25 mg kg-1 over 3 days) resulted in complete parasite clearance. Of the eight P. falciparum isolates successfully cultured from these women, seven (87.5%) were highly sensitive and one was resistant in vitro to the SDX/PYR combination.

Adolescent↗
PubMed1993

Characterization of a lipophilic antifolate resistance provoked by treatment of mammalian cells with the antiparasitic agent pyrimethamine.

We describe the characterization of an antitumor drug resistance following multiple step selection of hamster cells to the 2,4-diaminopyrimidines (DAP) metoprine, pyrimethamine (Pyr), and trimethoprim (Tmp). Pyr and Tmp are DAP lipophilic antifolates currently used as antiparasitic and antibacterial antibiotics, respectively. Dihydrofolate reductase (DHFR) from hamster cells bore a low or poor affinity to these DAP as compared to the hydrophilic folate antagonist methotrexate (MTX). Metoprine-resistant cells over-expressed DHFR enzyme and consequently displayed a high level of resistance to both hydrophilic and lipophilic antifolates including DAP but maintained wild type sensitivity to pleiotropic drugs involved in multi-drug resistance (MDR). In contrast, although Pyr- and Tmp-resistant cells expressed parental levels of wild type DHFR, they displayed a high degree of resistance to DAP and, surprisingly, to the lipophilic MTX analogs piritrexim (PTX) and trimetrexate (TMTX), while maintaining sensitivity to MTX. These drug-resistant cells maintained wild type mRNA levels of the MDR gene product P-glycoprotein and showed collateral hypersensitivity to pleiotropic drugs. To study the underlying mechanism of this apparently new resistance phenotype, we have employed fluorescein-methotrexate (F-MTX) labeling of cells and its displacement by different antifolates. Parental AA8 and Pyr-resistant cells showed a similar level of F-MTX labeling, however, while DAP, TMTX, and PTX showed an efficient competitive displacement of F-MTX from AA8 cells, Pyr-resistant cells displayed a persistent retention of F-MTX labeling in the presence of high concentrations of these lipophilic antifolates. Pyr-resistant cells showed a wild type displacement of F-MTX with MTX. This DAP resistance phenotype was unstable as it was rapidly lost upon growth under nonselective conditions. Furthermore, when the antifolate resistance levels of Pyr-resistant cells were plotted versus the ratios of the 50% F-MTX displacement values obtained with resistant and parental AA8 cells, a good correlation (r2 > 0.98) was obtained. We conclude that Pyr-resistant cells possess a novel phenotype that derives its resistance to lipophilic antifolates solely from a predominant decrease in the accumulation of DAP and lipid-soluble analogs of MTX.

Animals↗
PubMed1996

[Granulomatous hepatitis attributed to the combination pyrimethamine-chloroquine].

After her holiday in South Africa, a 50-year-old woman was admitted because of fever and pain in the upper abdomen. The laboratory tests showed moderately increased serum liver enzyme activities. The liver biopsy showed a granulomatous hepatitis. Further investigations revealed no evidence for sarcoidosis, tuberculosis or infectious hepatitis, nor for other granulomatous diseases or infectious diseases relevant to South Africa. Upon discontinuation of the malaria prophylaxis with Daraclor (pyrimethamine and chloroquine (sulphate)) the symptoms disappeared and the liver function tests returned to normal. It was concluded that Daraclor was the probable cause of granulomatous hepatitis in this patient. This adverse effect was not published before.

Antimalarials↗
PubMed1996

In vivo efficacy of chloroquine, halofantrine, pyrimethamine-sulfadoxine and qinghaosu (artesunate) in the treatment of malaria in Calabar, Nigeria.

We used the WHO in vivo seven day test, extended to 14 day follow up to evaluate the efficacy of the alternative antimalarial drugs in Nigeria (1992), where chloroquine resistant P. falciparum (CRPD) has been confirmed. One thousand and four patients were screened. Those fulfilling recruitment criteria were randomly treated with chloroquine (CQ), n = 50, halofantrine (H), n = 53, pyrimethamine-sulfadoxine (P-S), n = 52 and qinghaosu (Q), n = 53. Parasitological treatment failures were found with all drugs i.e. CQ-53.6pc, H-9.5pc, P-S-28.5pc and Q-2.0pc. H and Q were significantly more efficacious than CQ and P-S, p < 0.003 and p < 0.006, respectively. similarly symptom clearance after 48 hours by H and Q, was 76.3pc and 94pc respectively, better than CQ. P-S was not significantly better than CQ, 64.4pc and 63.3pc, respectively, p > 0.05. The symptom clearance rate of CQ has markedly reduced from 97.7pc to 67.7pc, and in increased proportion of RIII, from 5.9pc to 14.3pc, are signs of increase in chloroquine resistant Plasmodium falciparum. Drug resistant P. falciparum in Nigeria constitutes a serious problem to malaria chemotherapy.

Adolescent↗