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Scientific Reports May 2023Little is known about the existence of drug-resistant Toxoplasma gondii strains and their possible impact on clinic outcomes. To expand our knowledge about the existence...
Little is known about the existence of drug-resistant Toxoplasma gondii strains and their possible impact on clinic outcomes. To expand our knowledge about the existence of natural variations on drug susceptibility of T. gondii strains in Brazil, we evaluated the in vitro and in vivo susceptibility to sulfadiazine (SDZ) and pyrimethamine (PYR) of three atypical strains (Wild2, Wild3, and Wild4) isolated from free-living wild birds. In vitro susceptibility assay showed that the three strains were equally susceptible to SDZ and PYR but variations in the susceptibility were observed to SDZ plus PYR treatment. Variations in the proliferation rates in vitro and spontaneous conversion to bradyzoites were also accessed for all strains. Wild2 showed a lower cystogenesis capacity compared to Wild3 and Wild4. The in vivo analysis showed that while Wild3 was highly susceptible to all SDZ and PYR doses, and their combination, Wild2 and Wild4 showed low susceptibility to the lower doses of SDZ or PYR. Interestingly, Wild2 presented low susceptibility to the higher doses of SDZ, PYR and their combination. Our results suggest that the variability in treatment response by T. gondii isolates could possibly be related not only to drug resistance but also to the strain cystogenesis capacity.
Topics: Sulfadiazine; Pyrimethamine; Toxoplasma; Antiprotozoal Agents; Brazil
PubMed: 37147353
DOI: 10.1038/s41598-023-34502-3 -
Antimicrobial Agents and Chemotherapy Oct 2009To determine the pharmacokinetic disposition of sulfadoxine (SDOX) and pyrimethamine (PYR) when administered as intermittent presumptive treatment during pregnancy...
To determine the pharmacokinetic disposition of sulfadoxine (SDOX) and pyrimethamine (PYR) when administered as intermittent presumptive treatment during pregnancy (IPTp) for malaria, 30 Papua New Guinean women in the second or third trimester of pregnancy and 30 age-matched nonpregnant women were given a single dose of 1,500 mg of SDOX plus 75 mg of pyrimethamine PYR. Blood was taken at baseline and 1, 2, 4, 6, 12, 18, 24, 30, 48, and 72 h and at 7, 10, 14, 28, and 42 days posttreatment in all women. Plasma samples were assayed for SDOX, N-acetylsulfadoxine (NASDOX), and PYR by high-performance liquid chromatography. Population pharmacokinetic modeling was performed using NONMEM v6.2.0. Separate user-defined mamillary models were fitted to SDOX/NASDOX and PYR. When the covariate pregnancy was applied to clearance, there was a significant improvement in the base model for both treatments. Pregnancy was associated with a significantly lower area under the concentration-time curve from 0 to infinity for SDOX (22,315 versus 33,284 mg x h/liter), NASDOX (801 versus 1,590 mg x h/liter), and PYR (72,115 versus 106,065 microg x h/liter; P < 0.001 in each case). Because lower plasma concentrations of SDOX and PYR could compromise both curative efficacy and posttreatment prophylaxis in pregnant patients, IPTp regimens incorporating higher mg/kg doses than those recommended for nonpregnant patients should be considered.
Topics: Adolescent; Adult; Antimalarials; Drug Combinations; Female; Humans; Pregnancy; Pyrimethamine; Sulfadoxine; Young Adult
PubMed: 19620325
DOI: 10.1128/AAC.00335-09 -
Critical Reviews in Toxicology 1985Although pigs are suitable animals for experimental teratology, use of miniature pigs developed as a medicobiological experimental animal is essential for this purpose.... (Review)
Review
Although pigs are suitable animals for experimental teratology, use of miniature pigs developed as a medicobiological experimental animal is essential for this purpose. Miniature pigs are established genetically so that the background data on the naturally occurring birth defects are reliable, whereas the commercial breeds are always improved genetically to seek higher productivity. In this review the authors summarized pyrimethamine teratogenesis in Goettingen miniature pigs. Pyrimethamine administration to a pregnant sow during the early stage of the organogenetic period caused cleft palate and other birth defects, and also hind leg paralysis, a functional defect in newborns.
Topics: Abnormalities, Drug-Induced; Animal Feed; Animals; Animals, Newborn; Female; Housing, Animal; Pregnancy; Pyrimethamine; Species Specificity; Swine; Swine, Miniature
PubMed: 3902373
DOI: 10.3109/10408448509037463 -
Infection 1996Prophylaxis for toxoplasma encephalitis was performed with pyrimethamine alone (50 mg daily) in 56 patients with advanced HIV infection. Thirty-eight patients were at...
Prophylaxis for toxoplasma encephalitis was performed with pyrimethamine alone (50 mg daily) in 56 patients with advanced HIV infection. Thirty-eight patients were at high risk for toxoplasma encephalitis (CD4+ counts < or = 200/microliter, and presence of serum IgG antibodies to Toxoplasma gondii). The overall treatment period was 697 months (mean 12.5 +/- 12.1). During prophylaxis, only one patient developed toxoplasma encephalitis, four patients discontinued treatment due to adverse reactions. Steady state pyrimethamine plasma concentrations were measured by gas chromatography. Mean plasma level was 1,887 +/- 1,161 ng/ml, during liver enzyme-inducing comedication plasma levels were significantly (p = 0.0001) reduced (1,488 +/- 884 ng/ml versus 1,978 +/- 1,196 ng/ml without comedication). All patients received a folinic acid supplement of 7.5 mg daily. Serum folate levels ranged from 5.7-105 (43.7 +/- 29.2) nmol/l; severe hematological side effects did not occur.
Topics: AIDS-Related Opportunistic Infections; Adult; Animals; Encephalitis; Female; Follow-Up Studies; Humans; Male; Pyrimethamine; Toxoplasma; Toxoplasmosis
PubMed: 8875286
DOI: 10.1007/BF01743370 -
Veterinary Parasitology Jan 2018Neospora caninum is a member of Apicomplexa phylum, the causative agent of neosporosis. The neosporosis combat is not well established and several strategies related to...
Neospora caninum is a member of Apicomplexa phylum, the causative agent of neosporosis. The neosporosis combat is not well established and several strategies related to vaccine, chemotherapy and immune modulation are under development. In this work, we evaluated the effects of artemisinin (Art), methylene blue (MB) and pyrimethamine (Pyr) alone or associated, on N. caninum proliferation and elimination using LacZ tagged tachyzoites. The reactive oxygen species (ROS) production after incubation with Art were also performed. Our results indicate that combinations of classical antimalarial drugs improve the parasite control, allowing the use of three drugs in a single dose. Additionally, artemisinin demonstrated distinct ROS production patterns in intra and extracellular N. caninum forms. The drug repurposing appears as a suitable approach, allowing a fast and safe method to evaluate old drugs but novel candidates against neosporosis.
Topics: Animals; Antimalarials; Artemisinins; Chlorocebus aethiops; Coccidiosis; Drug Synergism; Drug Therapy, Combination; In Vitro Techniques; Methylene Blue; Neospora; Pyrimethamine; Vero Cells
PubMed: 29279093
DOI: 10.1016/j.vetpar.2017.11.014 -
The Medical Journal of Australia Mar 1985The dapsone-pyrimethamine combination (100 mg of dapsone, 12.5 mg of pyrimethamine [Folaprim; Maloprim, one tablet a week) is considered to provide adequate prophylaxis...
The dapsone-pyrimethamine combination (100 mg of dapsone, 12.5 mg of pyrimethamine [Folaprim; Maloprim, one tablet a week) is considered to provide adequate prophylaxis for Plasmodium falciparum malaria, but to be inadequate for the prevention of P. vivax malaria. Field trials and case reports, however, have shown the comparable efficacy of this combination in the suppression of parasitaemias caused by both parasites. In Lae, Papua New Guinea, 12 patients with clinical signs of malaria had serum concentrations of dapsone-pyrimethamine which were consistent with appropriate weekly use of this combination. The fact that 10 of these patients had P. vivax malaria supports the hitherto unsubstantiated view that dapsone-pyrimethamine can be ineffective in suppressing parasitaemias caused by this parasite. In the two patients with P. falciparum malaria, host factors rather than parasite resistance to dapsone-pyrimethamine were implicated in the development of the parasitaemias.
Topics: Adolescent; Adult; Antimalarials; Biological Availability; Child; Dapsone; Drug Combinations; Drug Resistance; Female; Humans; Malaria; Male; Papua New Guinea; Plasmodium falciparum; Plasmodium vivax; Pyrimethamine
PubMed: 3883112
DOI: 10.5694/j.1326-5377.1985.tb113407.x -
Annals of Internal Medicine Feb 1976In 81 cases of toxoplasmosis in patients with neoplasia, collagen-vascular disorders, and organ allografts, the clinical manifestations were highly variable but... (Review)
Review
In 81 cases of toxoplasmosis in patients with neoplasia, collagen-vascular disorders, and organ allografts, the clinical manifestations were highly variable but neurologic syndromes consistent with diffuse encephalopathy, meningoencephalitis, or cerebral mass lesions predominated. Many concomitant infections with DNA viruses were seen. The diagnosis of toxoplasmosis was not made until postmortem examination in most cases. Biopsy of lymph nodes or brain and serologic tests needed for definitive diagnosis were done infrequently. Twenty patients received antitoxoplasma chemotherapy (pyrimethamine and sulfonamide), 16 (80%) showing marked clinical improvement or complete remission. In immunosuppressed hosts disseminated toxoplasmosis appears to result from defects in cellular immunity that permit recrudescence of latent infection. Because cell-mediated immunity to Toxoplasma gondii can be enhanced in animals by administration of adjuvants, immunotherapy may become a useful adjunct to chemotherapy in immunoincompetent humans suffering potentially lethal infection.
Topics: Animals; Collagen Diseases; Hemagglutination; Humans; Immunoglobulin M; Immunosuppression Therapy; Immunotherapy; Neoplasms; Pyrimethamine; Sulfonamides; Toxoplasmosis; Transplantation, Homologous; Vascular Diseases
PubMed: 766683
DOI: 10.7326/0003-4819-84-2-193 -
Lancet (London, England) Apr 1982
Topics: Antimalarials; Drug Combinations; Female; Humans; Malaria; Male; Plasmodium vivax; Pyrimethamine; Sulfadoxine; Sulfanilamides; Suriname
PubMed: 6122136
DOI: 10.1016/s0140-6736(82)92190-0 -
Antimicrobial Agents and Chemotherapy May 1992Pyrimethamine levels in sera, cerebrospinal fluid (CSF), and ventricular fluid were measured by using reversed-phase high-pressure liquid chromatography. The specimens...
Pyrimethamine levels in sera, cerebrospinal fluid (CSF), and ventricular fluid were measured by using reversed-phase high-pressure liquid chromatography. The specimens were from 37 infants receiving pyrimethamine for treatment of suspect or proven congenital toxoplasmosis. Pyrimethamine half-life in serum was 64 +/- 12 h when determined by study of terminal-phase kinetics of samples obtained from nine babies. This half-life was significantly different (P = 0.008) from the pyrimethamine half-life (33 +/- 12 h) determined by terminal-phase kinetics for two babies of the same age taking phenobarbital. Serum pyrimethamine levels at various intervals after dosages of pyrimethamine were also lower for infants receiving phenobarbital. Levels measured in sera from babies taking the same dose of pyrimethamine throughout their first year of life did not appear to vary significantly over time or at different ages (P greater than 0.05). Mean +/- standard deviation serum levels 4 h after a pyrimethamine dose were 1.297 +/- 0.54 micrograms/ml for babies taking 1 mg of pyrimethamine per kg of body weight daily and 0.7 +/- 0.26 microgram/ml for babies taking 1 mg/kg each Monday, Wednesday, and Friday. Levels in CSF were approximately 10 to 25% of concomitant levels in serum. Serum folate levels for infants who took 0.64 to 1.7 mg leukovorin per kg ranged from 33 to 663 ng/ml. To determine whether the levels of pyrimethamine in serum and CSF of treated infants were in a range that affected the most virulent, rapidly replicating, and standard laboratory strain of Toxoplasma gondii, effects of various concentrations of pyrimethamine and sulfadiazine on replication of T. gondii in vitro were assessed. The levels of the antimicrobial agents effective in vitro were in the range of levels of pyrimethamine achieved in sera and CSF. Although folinic acid could inhibit the therapeutic effect of pyrimethamine and sulfadiazine in vitro, inhibition was noted only at levels (> or = 4,800 ng/ml) that were considerably higher than the folate levels found in the treated infants' sera.
Topics: Chromatography, High Pressure Liquid; Humans; Infant; Infant, Newborn; Leucovorin; Phenobarbital; Pyrimethamine; Toxoplasmosis, Congenital
PubMed: 1510391
DOI: 10.1128/AAC.36.5.1040 -
Lancet (London, England) May 1982
Topics: Dapsone; Drug Combinations; Drug Resistance; Female; Humans; Kenya; Middle Aged; Plasmodium falciparum; Pyrimethamine
PubMed: 6122906
DOI: 10.1016/s0140-6736(82)92295-4