SEARCH · PubMed Health

Results for “PYRIMETHAMINE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources

PubMed1992

Synergistic activity of azithromycin and pyrimethamine or sulfadiazine in acute experimental toxoplasmosis.

The efficacy of azithromycin administered alone or combined with pyrimethamine or sulfadiazine was examined in a murine model of acute toxoplasmosis. Outbred Swiss mice acutely infected with tachyzoites of the virulent RH strain were treated for 10 days from day +1 postinfection. The efficacy of each regimen was assessed in terms of survival rates and sequential titration of parasites in blood, brain, and lungs by using a tissue culture method. Administration of azithromycin at 300, 150, or 75 mg/kg of body weight per day resulted in prolonged survival relative to that of untreated controls; sequential examination of parasite burden showed early eradiaction of Toxoplasma gondii from the lungs, whereas dissemination to the brain was not prevented. A remarkable synergistic effect was observed when azithromycin (150 mg/kg/day) was administered in combination with pyrimethamine or sulfadiazine at noncurative dosages, i.e., 12.5 and 200 mg/kg/day, respectively. In mice treated with azithromycin plus sulfadiazine and azithromycin plus pyrimethamine, parasite burdens in blood and organs, relapses after cessation of therapy, and mortality were all markedly reduced relative to mice treated with any of the agents alone. These results show that azithromycin, which is remarkably active on pulmonary Toxoplasma infection, significantly potentiates the curative effect of sulfadiazine or pyrimethamine.

Animals↗

PubMed2001

Activity of gatifloxacin alone or in combination with pyrimethamine or gamma interferon against Toxoplasma gondii.

The activity of gatifloxacin against Toxoplasma gondii, either alone or in combination with pyrimethamine or gamma interferon (IFN-gamma), was examined in vitro and in vivo. In vitro, gatifloxacin significantly inhibited intracellular replication of tachyzoites of the RH strain with a 50% inhibitory concentration of 0.21 microg/ml at 48 h after addition of the drug to the cultures. Toxicity for host cells was not observed at this concentration. A synergistic effect (combination indices < 0.5) was demonstrated in vitro following 48 h of treatment with the combination of gatifloxacin and pyrimethamine (1:1 ratio). Doses of gatifloxacin of 100 and 200 mg/kg of body weight/day administered orally to mice for 10 days resulted in significant (P values of 0.056 and <0.0001, respectively) prolongation in time to death following infection with a lethal inoculum of tachyzoites. A dose of 400 mg/kg resulted in 20% survival (P = 0.0001). Mortality was 100% in untreated control mice and in mice treated with 25 or 50 mg/kg/day. Treatment of infected mice with a combination of gatifloxacin at 200 mg/kg/day and pyrimethamine at 12.5 mg/kg/day resulted in 85% survival, whereas 100 and 80% of mice treated with gatifloxacin alone or pyrimethamine alone, respectively, died (P < 0.0001). Moreover, a gatifloxacin dose of 200 mg/kg/day administered orally for 10 days plus 2 microg of recombinant murine IFN-gamma/day administered intraperitoneally for 10 days resulted in significant survival compared with IFN-gamma alone (P < 0.0001) or gatifloxacin alone (P < 0.007).

Animals↗

PubMed2001

In vitro generation of novel pyrimethamine resistance mutations in the Toxoplasma gondii dihydrofolate reductase.

Pyrimethamine is a potent inhibitor of dihydrofolate reductase and is widely used in the treatment of opportunistic infections caused by the protozoan parasite Toxoplasma gondii. In order to assess the potential role of dhfr sequence polymorphisms in drug treatment failures, we examined the dhfr-ts genes of representative isolates for T. gondii virulence types I, II, and III. These strains exhibit differences in their sensitivities to pyrimethamine but no differences in predicted dhfr-ts protein sequences. To assess the potential for pyrimethamine-resistant dhfr mutants to emerge, three drug-sensitive variants of the T. gondii dhfr-ts gene (the wild-type T. gondii sequence and two mutants engineered to reflect polymorphisms observed in drug-sensitive Plasmodium falciparum) were subjected to random mutagenesis and transfected into either wild-type T. gondii parasites or dhfr-deficient Saccharomyces cerevisiae under pyrimethamine selection. Three resistance mutations were identified, at amino acid residues 25 (Trp-->Arg), 98 (Leu-->Ser), and 134 (Leu-->His).

Alleles↗

PubMed2003

Combination of drug level measurement and parasite genotyping data for improved assessment of amodiaquine and sulfadoxine-pyrimethamine efficacies in treating Plasmodium falciparum malaria in Gabonese children.

Many African countries currently use a sulfadoxine-pyrimethamine combination (SP) or amodiaquine (AQ) to treat uncomplicated Plasmodium falciparum malaria. Both drugs represent the last inexpensive alternatives to chloroquine. However, resistant P. falciparum populations are largely reported in Africa, and it is compulsory to know the present situation of resistance. The in vivo World Health Organization standard 28-day test was used to assess the efficacy of AQ and SP to treat uncomplicated falciparum malaria in Gabonese children under 10 years of age. To document treatment failures, molecular genotyping to distinguish therapeutic failures from reinfections and drug dosages were undertaken. A total of 118 and 114 children were given AQ or SP, respectively, and were monitored. SP was more effective than AQ, with 14.0 and 34.7% of therapeutic failures, respectively. Three days after initiation of treatment, the mean level of monodesethylamodiaquine (MdAQ) in plasma was 149 ng/ml in children treated with amodiaquine. In those treated with SP, mean levels of sulfadoxine and pyrimethamine in plasma were 100 microg/ml and 212 ng/ml, respectively. Levels of the three drugs were higher in patients successfully treated with AQ (MdAQ plasma levels) or SP (sulfadoxine and pyrimethamine plasma levels). Blood concentration higher than breakpoints of 135 ng/ml for MdAQ, 100 micro g/ml for sulfadoxine, and 175 ng/ml for pyrimethamine were associated with treatment success (odds ratio: 4.5, 9.8, and 11.8, respectively; all P values were <0.009). Genotyping of merozoite surface proteins 1 and 2 demonstrated a mean of 4.0 genotypes per person before treatment. At reappearance of parasitemia, both recrudescent parasites (represented by common bands in both samples) and newly inoculated parasites (represented by bands that were absent before treatment) were present in the blood of most (51.1%) children. Only 3 (6.4%) therapeutic failures were the result not of treatment inefficacy but of new infection. In areas where levels of drug resistance and complexity of infections are high, drug dosage and parasite genotyping may be of limited interest in improving the precision of drug efficacy measurement. Their use should be weighted according to logistical constraints.

Amodiaquine↗

PubMed2003

Sulfadoxine-pyrimethamine in treatment of malaria in Western Kenya: increasing resistance and underdosing.

Between 1993 and 1999, we monitored the efficacy of sulfadoxine-pyrimethamine in 1175 children aged <24 months receiving 2789 treatments for falciparum malaria in western Kenya using a widely deployed age-based dose regimen: infants, 125 plus 6.25 mg (sulfadoxine plus pyrimethamine); children aged 12 to 23 months; 250 plus 12.5 mg. Cumulative treatment failure by day 7, defined as early clinical failure by day 3 or presence of parasitemia on day 7, increased from 18% in 1993 to 1994 to 22% in 1997 to 1998 (P-trend test = 0.20). Based on body weight, the median dose received was 20 plus 1.00 mg/kg, and 73% of the treatments were given at lower than the recommended target dose of 25 plus 1.25 mg/kg. Underdosing accounted for 26% of cumulative treatment failures. After the dose was increased in 1998 (median, 36 plus 1.8 mg/kg), only 4.2% of patients received less than 25 plus 1.25 mg/kg and there was no association with treatment failure. However, the proportion of cumulative treatment failure continued to increase to 27% by 1999 (P-trend test = 0.03). These results raise concern about the longevity of sulfadoxine-pyrimethamine in these settings. Underdosing may have contributed to the rate at which sulfadoxine-pyrimethamine resistance developed in this area. Treatment guidelines should ensure that adequate doses are given from the initial deployment of antimalarials onward.

Anti-Infective Agents↗

PubMed2005

Novel Plasmodium vivax dhfr alleles from the Indonesian Archipelago and Papua New Guinea: association with pyrimethamine resistance determined by a Saccharomyces cerevisiae expression system.

In plasmodia, the dihydrofolate reductase (DHFR) enzyme is the target of the pyrimethamine component of sulfadoxine-pyrimethamine (S/P). Plasmodium vivax infections are not treated intentionally with antifolates. However, outside Africa, coinfections with Plasmodium falciparum and P. vivax are common, and P. vivax infections are often exposed to S/P. Cloning of the P. vivax dhfr gene has allowed molecular comparisons of dhfr alleles from different regions. Examination of the dhfr locus from a few locations has identified a very diverse set of alleles and showed that mutant alleles of the vivax dhfr gene are prevalent in Southeast Asia where S/P has been used extensively. We have surveyed patient isolates from six locations in Indonesia and two locations in Papua New Guinea. We sequenced P. vivax dhfr alleles from 114 patient samples and identified 24 different alleles that differed from the wild type by synonymous and nonsynonymous point mutations, insertions, or deletions. Most importantly, five alleles that carried four or more nonsynonymous mutations were identified. Only one of these highly mutant alleles had been previously observed, and all carried the 57L and 117T mutations. P. vivax cannot be cultured continuously, so we used a yeast assay system to determine in vitro sensitivity to pyrimethamine for a subset of the alleles. Alleles with four nonsynonymous mutations conferred very high levels of resistance to pyrimethamine. This study expands significantly the total number of novel dhfr alleles now identified from P. vivax and provides a foundation for understanding how antifolate resistance arises and spreads in natural P. vivax populations.

Alleles↗

PubMed2005

Association between the pharmacokinetics and in vivo therapeutic efficacy of sulfadoxine-pyrimethamine in Malawian children.

Sulfadoxine-pyrimethamine (SP) has been widely used in recent years to treat acute uncomplicated Plasmodium falciparum malaria. Risk factors for SP therapeutic failure include young age, subtherapeutic SP concentrations, and resistance-conferring genetic mutations in parasite target enzymes. A substantial proportion of patients are able to clear genetically highly resistant P. falciparum genotypes. To determine whether blood SP concentrations independently affect the patient's ability to clear resistant genotypes, we compared SP pharmacokinetics of cases of adequate clinical and parasitological response (ACPR) with cases of treatment failure (TF). When patients with ACPR and TF were compared, mean values were similar for the day 3 blood pyrimethamine (205 ng/ml versus 172 ng/ml; P = 0.25) and estimated maximum sulfadoxine (79 +/- 6.52 versus 69 +/- 6.27 mug/ml; P = 0.60) concentrations, for sulfadoxine terminal-phase elimination half-lives (7.15 versus 6.41 days; P = 0.42), and for the extents of sulfadoxine absorption (areas under the concentration-time curve of 932 +/- 100 versus 888 +/- 78.9 mug day ml(-1); P = 0.72). Among patients infected with the quintuple resistant parasites, day 3 blood pyrimethamine concentrations were higher in those who cleared the infection than in those who did not (305 +/- 35.4 versus 228 +/- 21.7 ng/ml; P = 0.037). Within this subgroup, this finding remained significant after adjusting for endogenous folate levels, age, site, and resistance-conferring mutations (odds ratio: 1.011 [1.003 to 1.024]; P = 0.018). However, as a subgroup analysis, our biologically plausible observation that higher blood pyrimethamine concentrations enhance the ability of patients to clear resistant P. falciparum should be interpreted with caution and needs further validation.

Animals↗

PubMed1990

Comparison of chloroquine, pyrimethamine and sulfadoxine, and chlorproguanil and dapsone as treatment for falciparum malaria in pregnant and non-pregnant women, Kakamega District, Kenya.

OBJECTIVE: To compare treatment and protection against falciparum malaria in pregnant and non-pregnant women with three drug regimens. DESIGN: Prospective intervention study with six weeks' follow up. Patients received one of three drug regimens in order of entry. SETTING: Primary care hospital and secondary girls' school in rural western Kenya. PATIENTS: 158 of 988 pregnant women (89 primigravid and 69 multigravid) in the third trimester and 105 of 1488 non-pregnant schoolgirls of reproductive age were parasitaemic (more than 500 asexual forms/microliter. These women were divided into three treatment groups by gravid state. INTERVENTIONS: Women were treated with chloroquine base 25 mg/kg over three days or pyrimethamine 75 mg and sulfadoxine 1500 mg as a single dose or chlorproguanil 1.2 mg/kg and dapsone 2.4 mg/kg as a single dose. MAIN OUTCOME MEASURES: Parasitaemia and haemoglobin concentrations measured at seven day intervals for six weeks. RESULTS: Primigravid women were more likely to be parasitaemic on follow up than multigravidas or nulligravidas, whose response was about the same. Parasites did not clear by day 7 in primigravidas in six (20%) of 30 who received chloroquine, three (8%) of 35 treated with pyrimethamine and sulfadoxine, and none of 23 treated with chlorproguanil and dapsone. At day 28, 83%, 19%, and 67% of primigravidas in these treatment groups were parasitaemic. Haemoglobin concentrations rose in all women, but improvement was sustained only in women who remained free of parasites. CONCLUSIONS: Clearance of parasites was better with either pyrimethamine and sulfadoxine or chlorproguanil and dapsone than with chloroquine. Longest protection was obtained with pyrimethamine and sulfadoxine.

Adolescent↗

PubMed2004

Efficacy of pyrimethamine-sulfadoxine in young children with uncomplicated falciparum malaria in rural Burkina Faso.

The efficacy of pyrimethamine-sulfadoxine in the treatment of uncomplicated falciparum malaria in young children of a malaria holoendemic area in rural Burkina Faso is reported. Of 28 children treated with a standard single dose of pyrimethamine-sulfadoxine and followed-up over 14 days, only one Late Treatment Failure and four Late Parasitological Failures were observed, all with low-grade parasitaemia. In this area of very restricted use of pyrimethamine-sulfadoxine, the drug appears to be still sufficiently effective in the treatment of malaria. These findings provide further evidence for the justification of continued use of pyrimethamine-sulfadoxine as a second-line treatment for malaria in Burkina Faso.

Antimalarials↗

PubMed1988

Amodiaquine and sulfadoxine-pyrimethamine as treatment for chloroquine-resistant Plasmodium falciparum in Rwanda.

The efficacy of amodiaquine and sulfadoxine-pyrimethamine combination as a second-line therapy for chloroquine-resistant Plasmodium falciparum infections was investigated in Rwanda in September 1986. Children less than or equal to 5 years old presenting with a P. falciparum parasitemia 14 days after treatment with chloroquine were administered either amodiaquine (25 mg/kg over 3 days, 64 patients) or sulfadoxine-pyrimethamine (as a single dose with tablets containing 500 mg of sulfadoxine and 25 mg of pyrimethamine: 1/4 tablet for children under 1 year, 1/2 for those 1-3 years old, and 1 tablet for those 4-5 years old; 34 patients) and followed for 7 days. Seven days after starting treatment with amodiaquine, 50 (76%) children were aparasitemic. All the children who had received sulfadoxine-pyrimethamine were aparasitemic 7 days after initiation of therapy.

Amodiaquine↗

PubMed1996

Community pyrimethamine-sulfadoxine use and prevalence of resistant Plasmodium falciparum genotypes in Mali: a model for deterring resistance.

Pyrimethamine-sulfadoxine (PS, Fansidar; Hoffman-LaRoche, Basel, Switzerland) is now the first-line antimalarial therapy in parts of Africa with high rates of chloroquine-resistant Plasmodium falciparum. With PS resistance increasing and no suitably inexpensive and effective third antimalarial drug available, strategies for delaying the spread of PS resistance in Africa are needed. Community PS usage was measured in two Malian villages, one rural and one periurban, and prevalence of pyrimethamine-resistant P. falciparum genotypes was determined at these sites and two urban sites. The prevalence of resistant genotypes was 22.6% (n = 84) in the periurban village where PS was available from multiple sources and large stocks of PS were observed, and 13.5% (n = 89) and 23.4% (n = 77) in a large town and a city, respectively, where PS is widely available. No pyrimethamine-resistant genotypes (n = 58) were detected in Kolle, a rural village with a community-supported dispensary and clinic where PS is used sparingly and no PS was available in pharmacies or markets. The high rates of pyrimethamine resistant genotypes concurrent with higher PS usage argue for a policy of judicious PS use in Mali and in similar settings. A possible model for slowing the spread of drug-resistant malaria is illustrated by the example of the Kolle clinic.

Adolescent↗

PubMed1999

Short report: high prevalence and imbalanced age distribution of the Plasmodium falciparum dihydrofolate reductase gene Asn108 mutation in an area of low pyrimethamine usage in Nigeria.

Resistance of Plasmodium falciparum to pyrimethamine is associated with a non-silent point mutation of the parasite dihydrofolate reductase (DHFR) gene (Ser108 --> Asn108). Wide-scale use of antimalarials is thought to contribute to the emergence of drug resistance. In 131 P. falciparum-infected children in rural Nigeria, the frequency of the resistant Asn108 genotype was assessed by enzymatic restriction digestion of polymerase chain reaction-amplified DHFR sequences and compared with residual pyrimethamine blood levels. The prevalence of the Asn108 variant was 41.2%. In 18.3% of the isolates, both the Asn108 and the wild-type alleles were present. In contrast to the high prevalence of resistant genotypes, residual pyrimethamine blood levels were detected in only 4%. Furthermore, age was found to be a determinant of the parasite genotype since the proportion of Asn108 variants decreased with age (P < 0.05). These findings indicate that additional, unidentified factors, rather than selection by residual drug levels alone, might be responsible for the emergence of pyrimethamine-resistant parasite genotypes.

Age Distribution↗

PubMed2001

Cardiac effects of amodiaquine and sulfadoxine-pyrimethamine in malaria-infected African patients.

The cardiac effect of amodiaquine and sulfadoxine-pyrimethamine was studied in adult Cameroonian patients with acute uncomplicated Plasmodium falciparum malaria by electrocardiographic monitoring over the course of 7 days. Clinical and parasitological responses were monitored until Day 14. Bradycardia was observed in 16 of 20 amodiaquine-treated patients on Day 2, which corresponds to the time when maximal cumulative plasma concentration is reached, and in 12 of 20 patients on Day 7. A bradycardic effect lasting several days was not noted in patients treated with sulfadoxine-pyrimethamine. Significantly prolonged P, PQ, QRS, and QTc intervals were recorded on Day 2 after both 30 and 35 mg of amodiaquine base per kilogram of body weight had been administered, but these intervals were not correlated with the plasma monodesethylamodiaquine (main human active metabolite of amodiaquine) level. Electrocardiographic changes after therapy with sulfadoxine-pyrimethamine were minor and transient. All patients had fever and parasite clearance on or before Day 3 and remained free of fever and parasites until Day 14. None of the patients complained of cardiovascular adverse effects during the follow-up. These results suggest the absence of significant cardiac effects of amodiaquine and sulfadoxine-pyrimethamine at usual therapeutic doses, but they should draw the attention of clinicians treating malaria-infected patients who have taken other antimalarial drugs with cardiovascular side effects or those who are under treatment with cardiovascular drugs.

Administration, Oral↗

PubMed1987

Fatal hepatic necrosis due to pyrimethamine-sulfadoxine (Fansidar).

Pyrimethamine-sulfadoxine has been associated with severe and fatal cutaneous reactions as well as transient liver damage. We report the case of a patient who died of progressive hepatic failure caused by pyrimethamine-sulfadoxine administration. In addition, we summarize reports made to the Food and Drug Administration since 1982 that focus on hepatotoxic reactions to pyrimethamine-sulfadoxine. We suggest that fatal hepatic injury can occur after treatment with pyrimethamine-sulfadoxine and that physicians who prescribe the drug should be aware of this possibility.

Adolescent↗

PubMed1995

Twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to prevent recurrent toxoplasmic encephalitis in patients with AIDS. Spanish Toxoplasmosis Study Group.

OBJECTIVE: To evaluate the efficacy of twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to prevent toxoplasmic encephalitis relapse in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Randomized, open, multicenter trial. Patients were randomly assigned to receive sulfadiazine (500 mg) four times per day plus pyrimethamine (25 mg) plus folinic acid (15 mg) either daily (n = 60) or twice weekly (n = 45). SETTING: 8 university teaching hospitals. PATIENTS: Between February 1990 and June 1993, 105 patients with HIV infection were enrolled after each had had resolution of an acute episode of toxoplasmic encephalitis treated with sulfadiazine (1 g four times per day) plus pyrimethamine (50 mg/d) plus folinic acid (15 mg/d) for 4 to 8 weeks. MEASUREMENTS: Clinical and biological evaluations done every 30 to 60 days. End points were toxoplasmic encephalitis relapse, death, and interruption of therapy due to adverse reactions. RESULTS: After a median follow-up period of 11 months (range, 1 to 39 months), patients receiving the twice-weekly regimen had a higher rate of relapse then patients receiving the daily regimen (19.5 compared with 4.4 per 100 patient-years; incidence rate ratio, 4.36 [95% CI, 1.05 to 25.5]; P = 0.024). The estimated cumulative percentages of relapse at 12 months were 30% and 6%, respectively (P = 0.029), with an adjusted risk ratio (adjusted for age, sex, risk behavior, previous diagnosis of AIDS, Pneumocystis carinii pneumonia prophylaxis before initial episode of toxoplasmosis, CD4 cell count, baseline number of brain lesions, radiologic sequelae, and antiretroviral therapy during follow-up) of 5.6 (CI, 1.2 to 25.6; P = 0.028). Patients receiving the twice-weekly regimen had 1.6 times (CI, 0.9 to 2.9 times; P = 0.11) the adjusted risk for death of patients receiving the daily regimen. No statistical differences were found in the patients who stopped receiving the regimens due to adverse effects. No patient developed P. carinii pneumonia during the study period, even though 17 patients (10 receiving the daily regimen and 7 receiving the twice-weekly regimen) had had an episode of P. carinii pneumonia before study entry. CONCLUSIONS: At the given doses, a combination of sulfadiazine, pyrimethamine, and folinic acid was less effective when administered twice weekly than when administered daily, although the twice-weekly regimen was much more effective than historic controls.

AIDS-Related Opportunistic Infections↗

PubMed1999

Inhibition of dihydrofolate reductases from Toxoplasma gondii, Pneumocystis carinii, and rat liver by rotationally restricted analogues of pyrimethamine and metoprine.

Twenty-one conformationally restricted tricyclic pyrimethamine and metoprine analogues with one or two chlorine atoms, or other substituents, at different positions of the phenyl ring were tested for potency and species selectivity against dihydrofolate reductase (DHFR) from Toxoplasma gondii, Pneumocystis carinii, and rat liver. Heterocyclic systems studied included indeno[2,1-d]pyrimidines, benzo[f]quinazolines, and benzo[3,4]cyclohepta[1,2-d]pyrimidines. All but one of the analogues were more potent against T. gondii and rat liver DHFR than against P. carinii DHFR, and those with a one-carbon (CH2) bridge were generally less potent than those with a two-carbon (CH2CH2, CH=CH) or three-carbon (CH2CH2CH2) bridge. Although a number of compounds with a two- and three-carbon bridge were more potent than pyrimethamine against P. carinii DHFR, and especially T. gondii DHFR, none of them were selective for the P. carinii versus the mammalian enzyme, and only those with a one-carbon bridge showed selectivity approaching that of pyrimethamine for the T. gondii enzyme. Computer-simulated docking into the active site pocket of P. carinii and human DHFR suggested that, as a group, the rotationally restricted tricyclic structures are at a disadvantage relative to pyrimethamine and metoprine, in that torsional relief of unfavorable steric interactions between the chlorine atoms and two critical serine and threonine residues in the active site is prevented by the bridge.

Animals↗

PubMed1975

Effect of pyrimethamine and sulfadiazine on the fine structure and multiplication of Toxoplasma gondii in cell cultures.

Rhesus monkey kidney cell cultures were inoculated with Toxoplasma gondii organisms obtained from peritoneal fluid of mice infected with the RH strain. Pyrimethamine and sulfadiazine were added either singly or in combination to the cultures 4 hr after inoculation. Twenty-four hours later the effect of the drugs on the parasites were studied by light and electron microscopy. Pyrimethamine (1.0 mug/ml) inhibited multiplication of the parasites and caused striking morphological changes. Organisms were rounded and often had a fragmented nucleus. Division was inhibited as indicated by abnormal daughter membrane formation during endodyogeny. No effect was evident in sulfadiazine-treated parasites when concentrations up to 50 mug/ml were used. However, combination of ineffective levels of pyrimethamine (0.1 mug/ml) and sulfadiazine (0.5 mug/ml) produced effects similar to those seen at a higher concentration of pyrimethamine indicating a synergistic action of the 2 drugs.

Cells, Cultured↗

PubMed2001

[Danger of malaria self-treatment. Acute neurologic toxicity of mefloquine and its combination with pyrimethamine-sulfadoxine].

BACKGROUND: Mefloquine and pyrimethamine-sulfadoxine combination are recommended, as is quinine, for self-administered malaria prophylaxis. Patients should be carefully informed about appropriate use of this therapeutic scheme and advised on the importance of strict compliance to avoid overdose. CASE REPORT: We report the case of a patient who did not follow the prescribed dosage and who developed acute neurological disorders after overdosing. The patient developed seizures attributable to the sulfadoxine-pyrimethamine combination and mefloquine encephalopathy. DISCUSSION: Sulfadoxine-pyrimethamine-related seizures are exceptional and result from an overdose of pyrimethamine. The neurotoxicity of mefloquine is well-known and is particularly frequent at curative dosage. Toxic encephalopathy is a serious neurological manifestation which is slowly reversible depending on individual predisposition. Anti-malaria prophylaxis requires concerted efforts on the part of the traveler and the prescribing physician. Self-administration schemes can be both most useful and dangerous due to expected benefits and potential risks.

Adult↗