pyrimethamine / Generic mfg. - LARVOL DELTA

Cerebral Toxoplasmosis in a Renal Transplant Recipient-A Rare Complication. (PubMed, Life (Basel)) - "She was maintained on cyclosporine, mycophenolate mofetil, and prednisone...Treatment with pyrimethamine, sulfadiazine, and leucovorin, alongside adjustment of immunosuppressive therapy, led to marked neurological improvement and radiological regression of the lesion...Although cerebral toxoplasmosis is uncommon after kidney transplantation, it should be considered in immunosuppressed patients presenting with neurological symptoms. Early detection and targeted therapy are key to reducing morbidity and mortality in this population."

Journal • Brain Cancer • Chronic Kidney Disease • Glioblastoma • Glomerulonephritis • Human Immunodeficiency Virus • Infectious Disease • Lupus Nephritis • Nephrology • Oncology • Pain • Renal Disease • Solid Tumor • Transplantation

Spinal Cord Toxoplasmosis: Mapping the Journey of a Rare Entity Through a Case Report and Review of the Literature. (PubMed, Microorganisms) - "Sulfadiazine-pyrimethamine with additional folinic acid and trimethoprim-sulfamethoxazole (TMP-SMX) remains the treatment of choice for treating cerebral toxoplasmosis in people living with HIV (PLHIV), with no particular recommendation regarding patients with spinal cord involvement. In the reviewed cases, neurological sequelae occurred in 52.2% of patients, and mortality was as high as 30.4%."

Journal • Human Immunodeficiency Virus • Infectious Disease

A heterologous marker-free selection approach for CRISPR/Cas9-based gene editing in the malaria parasite Plasmodium falciparum. (PubMed, mSphere) - "Here, we developed a heterologous marker-free CRISPR/Cas9 gene editing strategy (CRISPR/Cas9pyrR) for P. falciparum based on the simultaneous editing of a gene of interest and introduction of pyrimethamine (PYR) resistance-conferring mutations into the dihydrofolate reductase-thymidylate synthase (pfdhfr-ts) gene...In this study, we developed and successfully applied a modified CRISPR/Cas9 strategy, termed CRISPR/Cas9pyrR, that avoids the use of a heterologous drug resistance marker for the selection of genetically modified parasites. CRISPR/Cas9pyrR thus complements the CRISPR/Cas9 toolbox available for gene editing in P. falciparum and overcomes some of the limitations of currently employed protocols."

Journal • Infectious Disease • Malaria • DHFR • TYMS

Leveraging allelopathy for drug discovery: ocean phytoplankton metabolomes as anti-T. gondii drug candidates: a bioassay strategy (IMMUNOLOGY 2026) - "Current treatments, namely sulfadiazine and pyrimethamine, are ineffective and cause adverse effects. Using an allelopathic inhibition approach, select phytoplankton extracts contain compounds with promising inhibition of T. gondii invasion of MRC5 human fibroblasts. Future studies will evaluate biochemically isolated phytoplankton extracts for inhibition of T. gondii and other apicomplexan parasites."

Late-breaking abstract • Infectious Disease

TOXOPLASMOSIS SCREENING, PROPHYLAXIS AND TREATMENT PRACTICES ACROSS EBMT CENTERS: A SURVEY ON BEHALF OF THE INFECTIOUS DISEASES WORKING PARTY (EBMT 2026) - "If trimethoprim-sulfamethoxazole is contraindicated, most employed alternatives are atovaquone ± pyrimethamine (45/126, 36%) or nothing (27/126, 21%).In asymptomatic patients, anti-toxoplasma therapy is initiated after a single positive blood PCR in 19/67 (28%) centers, in 2/67 (3%) only if the patient is considered high-risk, in 7/67 (10%) only if the PCR-value is very high...Specific assessments are variably performed: cerebral MRI (49/67, 73%), lung CT (42/67, 63%), ophthalmic examination (43/67, 64%), lumbar puncture (20/67, 30%) and bone marrow assessment (10/67; 15%).Anti-toxoplasma therapy relies on trimethoprim-sulfamethoxazole, pyrimethamine-sulfadiazine and pyrimethamine-clindamycin with similar distribution for infection (73/134, 54%; 49/134, 37%; 10/134, 7%) and disease (66/132, 50%; 54/132, 41%; 9/132, 7%)... This survey highlights significant variability across EBMT centers in toxoplasmosis management, underscoring the need for ongoing harmonization,..."

Bone Marrow Transplantation • Infectious Disease • Ophthalmology • CD4

Trapped by Toxoplasma: Ventricular Compromise in a Previously Undiagnosed HIV Patient (SCCM 2026) - "Treatment with sulfadiazine, pyrimethamine and leucovorin was initiated. Early imaging, aggressive critical care management, and timely multidisciplinary coordination were essential to this patient's stabilization and recovery. This case highlights the need for a high index of suspicion for toxoplasmosis in patients with unexplained neurologic decline, even before HIV is confirmed, and supports a multidisciplinary approach to optimize outcomes in severe opportunistic infections."

Clinical • Human Immunodeficiency Virus • Infectious Disease • CD4

Contrasting evolutionary trajectories of pyrimethamine resistance in human and zoonotic malaria parasites. (PubMed, Malar J) - "Antifolate drug pressure has driven human malaria dhfr-ts genes toward fixation, whereas zoonotic orthologues evolve under a mutation-selection-drift balance. These findings highlight both the potential utility of antifolates against zoonotic malaria and the evolutionary consequences of sustained drug pressure."

Journal • Infectious Disease • Malaria • DHFR • TYMS

Consequence of malaria and dengue on reproductive vigor. A scoping review. (PubMed, Clin Ter) - "Antimalarial-drugs (chloroquine, quinine, quinacrine, pyrimethamine) cause male infertility. Acute dengue infection leads to temporary alterations in sperm but not long-term infertility; during pregnancy it causes an increased risk of premature delivery, fetal death, and hemorrhagic complications. Malaria/dengue affect reproductive health in humans, indirect effect being infertility due to antimalarial-drugs."

Journal • Review • Dengue Fever • Hematological Disorders • Infectious Disease • Infertility • Malaria • Sexual Disorders

ORBIT: Optimizing Reversal of HIV Latency With Combination Therapy (clinicaltrials.gov) - P1/2 | N=49 | Active, not recruiting | Sponsor: Erasmus Medical Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease • CD4

Pyrimethamine-based targeting of HEXA gene mutations in Tay-Sachs disease: a computational analysis. (PubMed, J Biomol Struct Dyn) - "The W485R variation showed greater deviation than the native protein and W474C. The study provides insight into the most deleterious mutants, the drug's interaction with protein structures, and its stability with native and selected variants."

Journal • CNS Disorders • Genetic Disorders • Metabolic Disorders

Severe congenital toxoplasmosis with isolated central hypothyroidism: A rare case report. (PubMed, J Neonatal Perinatal Med) - "Treatment included pyrimethamine, sulfadiazine, folinic acid, and levothyroxine replacement. Early recognition and hormone replacement therapy are essential to prevent further neurological impairment. Systematic endocrine evaluation is recommended in neonates with severe central nervous system involvement due to congenital toxoplasmosis."

Journal • Cataract • CNS Disorders • Endocrine Cancer • Endocrine Disorders • Genetic Disorders • Infectious Disease • Ocular Inflammation • Ophthalmology • Retinal Disorders • Uveitis • Ventriculomegaly

Identification of Compound 15 (MMV1581361) as a PfATP4 Inhibitor with Transmission-Blocking Activity and In Vivo Efficacy in a SCID Mouse Model of Malaria. (PubMed, J Med Chem) - "It was found to display a moderate rate-of-kill profile similar to pyrimethamine in vitro and efficacy in the humanized P. falciparum Pf3D70087/N9 NODscidIL2Rγnull mouse model at a single dose of 25 mg/kg, with similar kinetics to chloroquine. Mechanism-of-action studies revealed that compound 15 disrupts Na+ ion homeostasis in P. falciparum, indicating that it functions as a PfATP4 inhibitor. However, due to the resistance risk associated with the PfATP4 target and the presence of more advanced clinical candidates, further development of 15 into a viable antimalarial drug is currently deprioritised."

Journal • Preclinical • Infectious Disease • Malaria

Antiproliferative Plaque Assay for Screening in vitro Bioactive Molecules against Toxoplasma gondii Tachyzoites. (PubMed, J Vis Exp) - "Since the early 1950s, the first-line treatment of this disease has relied on the combination of sulfadiazine, pyrimethamine, and folinic acid. This work describes an optimized plaque assay protocol designed for screening active molecules against intracellular tachyzoites of T. gondii in vitro. This protocol utilizes inexpensive materials and a straightforward laboratory setup, yielding rapid and reproducible results that facilitate the identification of new active molecules against this parasite by various research groups."

Journal • Preclinical • Infectious Disease

Prediction of Prognosis, Tumor Microenvironment, and Drug Treatment of Colorectal Cancer Based on Retinoic Acid-Related Genes. (PubMed, J Environ Pathol Toxicol Oncol) - "Drug sensitivity prediction results revealed that AZ628, CGP-082996, CKM, Dasatinib, GNF-2, Saracatinib, Sorafenib, WH-4-023, and WZ-1-84 were more sensitive for patients in the HR group. AKT inhibitor VIII, Gemcitabine, JW-7-52-1, Mitomycin, NSC-87877, PAC-1, Pyrimethamine, QS11, and Roscovitine were more sensitive for those in the LR group. Our project identified correlations between RA-related genes and CRC. The model genes identified are essential indicators for evaluating CRC prognosis and further treating CRC."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor

PLUTO: Combining Latency Reversing Agents to Address the HIV Reservoir (clinicaltrials.gov) - P1/2 | N=30 | Not yet recruiting | Sponsor: Erasmus Medical Center

New P1/2 trial • Human Immunodeficiency Virus • Infectious Disease • CD4

Acetazolamide as a Novel Therapeutic Agent against Acute Experimental Toxoplasmosis: Insights into Carbonic Anhydrase Inhibition. (PubMed, Acta Trop) - "Although the current therapeutic regimens for acute toxoplasmosis, most commonly a combination of pyrimethamine and sulfadiazine, are still considered the standard of care, they are associated with numerous drawbacks, such as bone marrow suppression, and hepatotoxicity. Histopathological examination of hepatic and renal tissue sections showed amelioration of parenchymal inflammation and scanty parasite. In conclusion, Acetazolamide demonstrated a significant promise as a therapeutic agent for combating acute murine toxoplasmosis with anti-inflammatory and antioxidant effects."

Journal • Infectious Disease • Oncology • IL1B • TNFA

Pyrimethamine overcomes resistance to hypomethylating agents by reducing de-novo pyrimidine synthesis. (PubMed, Exp Hematol) - "The DNA hypomethylating agents (HMAs) 5-azacitidine and decitabine are the backbone of disease modifying therapy in myelodysplastic syndromes (MDS). We show that pyrimethamine, an FDA-approved antifolate, induces apoptosis across leukemic models, synergizes with venetoclax, and restores sensitivity in HMA- and venetoclax-resistant leukemia. Pyrimethamine promotes differentiation of stem and progenitor cells in primary MDS samples and in combination with venetoclax directly inhibits pyrimidine synthesis, revealing a clinically actionable strategy to overcome a key mechanism of therapeutic resistance."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • DNMT1

In vitro antiparasitic and synergic effects of camphene combined with pyrimethamine against Toxoplasma gondii. (PubMed, Trop Biomed) - "Additionally, the findings emphasized the potential of CP to eradicate tachyzoites through triggering apoptosis, NO production, and DNA damage, provoking cellular immunity cytokine, and increasing the plasma membrane permeability. Even so, advance evaluation is needed to clarify other mechanisms underlying its action and to evaluate its effectiveness in animal models and clinical trials."

Journal • Preclinical • Infectious Disease • Oncology • CASP3 • IFNG • IL12A • TNFA

Salts of Antifolate Pyrimethamine with Isomeric Aminobenzoic Acids: Exploring Packing Interactions and Pre-Crystallization Aggregation. (PubMed, Int J Mol Sci) - "Additionally, the pre-crystallization solutions of PYR with 2NH2-BA, 3NH2-BA, and 4NH2-BA were studied by electrospray ionization mass spectrometry technique (ESI-MS), which enabled the observation of peaks corresponding to noncovalently bonded molecules, providing insight into their specific aggregation in a solution/gas phase environment. We identified different non-covalent aggregates, including self-aggregates of aminobenzoic acids and PYR/aminobenzoic acid associates of different stoichiometries."

Journal • Infectious Disease

Fatal Congenital Toxoplasmosis with Progressive Liver Failure and Genomic Characterization of a Novel Isolate from the United States. (PubMed, Microorganisms) - "Despite initiation of standard therapy with pyrimethamine, sulfadiazine, and folinic acid on postnatal day 25, the infant died two days later. This report highlights the need for rapid recognition and targeted therapy as well as how strain genomics can inform disease mechanisms. Prevention through prenatal screening and maternal treatment during pregnancy may reduce infant mortality."

Journal • Hematological Disorders • Hepatology • Infectious Disease • Inflammation • Liver Failure • Thrombocytopenia

Design, Synthesis, and Antimalarial Evaluation of New Spiroacridine Derivatives. (PubMed, Antibiotics (Basel)) - "After computational studies, spiroacridines showed better affinity with dihydrofolate reductase (DHFR), overcoming the quadruple mutant resistance to pyrimethamine, with more stability in complex with the enzyme. Therefore, the potential of spiroacridines against malaria, with moderate resistance and selectivity profile, as well as DHFR inhibition greater than pyrimethamine, was confirmed."

Journal • Infectious Disease • Malaria • DHFR

Construction and validation of a lung adenocarcinoma prognostic model based on neutrophil extracellular traps and oxidative stress-related genes. (PubMed, Eur J Med Res) - "The constructed prognostic model by NETs and oxidative stress-relevant genes effectively predicts LUAD prognosis, correlates with immune microenvironment characteristics, and guides drug sensitivity, providing novel insights for LUAD prognostic assessment and personalized therapy."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ARHGEF3 • CD79A • CD8 • CLEC7A • EPHB2

Development and validation of a novel disulfidptosis-related gene signature for prediction of survival and immune microenvironment in osteosarcoma by WGCNA analysis. (PubMed, Discov Oncol) - "Besides, patients in the high-risk group exhibited lower IC50 values for vorinostat, elesclomol, OSI-906, pyrimethamine, thapsigargin, and doxorubicin, but a higher IC50 value for cisplatin, compared to those in the low-risk group, indicating differential drug sensitivities. In summary, we established a robust DRGs signature comprising BTN3A1, CEBPA, KCNAB2, TBX21, and MYC, which showed strong prognostic value and predictive potential for immune status and drug sensitivity in OS. Notably, functional experiments confirmed that BTN3A1 acted as a tumor suppressor in OS, highlighting it as a promising therapeutic target."

Gene Signature • IO biomarker • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • BTLA • BTN3A1 • CEBPA • LAG3 • PD-L1 • PD-L2 • TBX21

The PI3K pathway is a downstream effector of NRF2 activation in the esophagus. (PubMed, Transl Oncol) - "Furthermore, co-treatment with Pyrimethamine and Alpelisib significantly inhibited hyperproliferation and hyperkeratinization in the esophageal epithelium of Sox2CreER;LSL-Nrf2E79Q/+mice. Together, our data demonstrates the PI3K pathway as a downstream effector of NRF2 activation in the esophagus, and co-targeting of NRF2 and the PI3K pathway may offer a promising therapeutic strategy for NRF2Mut ESCC."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • EGFR • KEAP1 • PIK3CA • PTEN

Repurposing itraconazole and pyrimethamine as a combinatorial treatment for glioblastoma (SNO 2025) - "These data demonstrate potent anti-cancer effects when combining itraconazole and pyrimethamine in relevant preclinical GBM models, highlighting its potential as a combinatorial treatment for GBM. [This work was funded by a fellowship and project grant from "Fonds voor Wetenschappelijk Onderzoek" (FWO), grant number 1SH3H24N and S000825N]"

Brain Cancer • Glioblastoma • Solid Tumor