pyrimethamine / Generic mfg. - LARVOL DELTA

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

Validation of solvent proteome profiling for antimalarial drug target deconvolution. (PubMed, Int J Parasitol Drugs Drug Resist) - "Here, we successfully generated solvent denaturation curves for the P. falciparum proteome, and demonstrated the utility of SPP with five antimalarial compounds: pyrimethamine, atovaquone, cipargamin, MMV1557817 and OSM-S-106. This alternative method simplifies the experimental workflow and includes positive controls to affirm the performance of the experiment. Overall, this study demonstrates that SPP can be successfully applied in both lysate and live-cell treatment conditions to elucidate drug targets in P. falciparum, as well as providing additional information regarding the mechanisms of drug action, offering insights for the optimisation of existing antimalarials and the development of novel therapies."

Journal • Infectious Disease • Malaria • DHFR • TYMS

Therapeutic effect of baicalein as an antiparasitic agent against Toxoplasma gondii in vitro and in vivo. (PubMed, J Zhejiang Univ Sci B) - "The most common medications for the treatment of zoonotic toxoplasmosis are pyrimethamine and sulfadiazine, which may cause serious undesirable side effects. Furthermore, alterations in cytokine levels indicated that BAI not only effectively suppressed the growth of T. gondii but also prevented excessive inflammation in mice. Collectively, these findings underscore the significant inhibitory efficacy of BAI against T. gondii, positioning it as a promising alternative therapeutic agent for toxoplasmosis."

Journal • Preclinical • Infectious Disease • Inflammation

Repurposing itraconazole and pyrimethamine as a combinatorial treatment for glioblastoma (WFNOS 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 • Glioma • Solid Tumor

Integrated multi-omic analysis unravels the characteristics of the metabolism-related intratumoral microbes and establishes a novel signature for predicting prognosis and therapeutic response in lung adenocarcinoma. (PubMed, Transl Cancer Res) - "Additionally, a microbial prognostic-predictive signature was established comprising Succinimonas, Collimonas, and Marichromatium, which also exhibited potential for indicating immunotherapeutic benefit and predicting drug sensitivity to cisplatin, cytarabine, pyrimethamine, olaparib, bicalutamide and vorinostat in LUAD treatment. This study identified intratumoral microbes associated with metabolism, revealed distinct subtypes and their roles in LUAD, and established a predictive signature for the prognosis and therapeutic responsiveness of LUAD."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BCL3 • KLF3 • NFKB2

Focus CNS symptomatology (DGHO 2025) - "Prior to identification of a potentially causative pathogen, empiric or preemptive anti-infective treatment should be initiated (e.g., a 3rd generation cephalosporine plus high-dose ampicillin and acyclovir) to avoid treatment delay. If fungal CNS disease is suspected, for example, in a patient with aspergillosis of the lungs, antifungal treatment (e.g., voriconazole or isavuconazole) should also be given. Suspected or proven neurotoxoplasmosis might be treated with a combination of pyrimethamine and sulfadiazine...Frequently, a multidisciplinary approach including different experts (e.g., haematologists/oncologists, infectious diseases specialists, neurologists and neurosurgeons) might be useful. An increasing amount of data suggests that novel diagnostics, such as CSF next-generation sequencing (NGS), might be helpful to establish the correct diagnosis in some patients."

Bone Marrow Transplantation • CNS Disorders • Epstein-Barr Virus Infections • Infectious Disease • Respiratory Diseases

Hemophagocytic Lymphohistiocytosis Due to Disseminated Toxoplasmosis in a Kidney Transplant Patient (KIDNEY WEEK 2025) - "He received HLH-94 protocol with Intravenous Etoposide and Dexamethasone. Toxoplasmosis was managed with Sulfadiazine, Pyrimethamine and Leucovorin...Relapse is common, hence close follow up is needed at time of discharge. Hemophagocytes on bone marrow biopsy (H&E stain)"

Clinical • Autosomal Dominant Polycystic Kidney Disease • Fatigue • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Polycystic Kidney Disease • Rare Diseases • Rheumatology • Septic Shock • Transplantation

DeepTarget predicts anti-cancer mechanisms of action of small molecules by integrating drug and genetic screens. (PubMed, NPJ Precis Oncol) - "We experimentally validate DeepTarget's predictions in two case studies: (a) Demonstrating that pyrimethamine, an anti-parasitic drug, affects cellular viability through modulation of mitochondrial function, specifically the oxidative phosphorylation pathway, and (b) Confirming that T790-mutated EGFR mediates ibrutinib response in BTK-negative solid tumors. We provide DeepTarget as an open-source tool ( https://github.com/CBIIT-CGBB/DeepTarget ) along with predicted target profiles for 1,500 cancer-related drugs and 33,000 unpublished natural product extracts. DeepTarget represents a significant computational advancement among target discovery methods that complements the leading structure-based methods by considering cellular context and can potentially accelerate drug development and repurposing efforts in oncology."

Journal • Oncology • Solid Tumor • EGFR

Caffeic acid reduces Toxoplasma gondii proliferation in human extravillous trophoblast cells (HTR8/SVneo) through induction of pro-inflammatory cytokines and a death process suggestive of apoptosis. (PubMed, Microbes Infect) - "CA is a potential candidate for further research aimed at the development of novel therapies for congenital toxoplasmosis."

Journal • Infectious Disease • IL1B • MIF • TGFB1

Rat-Specific Expression of Placental MATE1 Contributes to Species Difference in Fetal Transfer of Metformin and 1-Methyl-4-Phenylpyridinium. (PubMed, Mol Pharm) - "To evaluate the function of the placental MATE1, we compared the placental transfer of two dual substrates of MATE1 and OCT3, metformin and 1-methyl-4-phenylpyridinium (MPP+), in pregnant rats and mice in the presence and absence of pyrimethamine, a MATE1 inhibitor. These findings demonstrate that functional placental MATE1 expression is specific to rats, which, in part, contributes to the low fetal transfer of cationic compounds compared with other species. This is of significant concern, as it suggests that nonclinical developmental and reproductive toxicity studies of MATE1 substrate drugs in rats may underestimate fetal exposure and toxicity when extrapolated to humans."

Journal • Preclinical • SLC22A3 • SLC2A3

Evaluation of ethanolic extract and isolated α-bisabolol from Siparuna guianensis in the treatment of experimental neurotoxoplasmosis. (PubMed, Exp Parasitol) - "The most commonly used therapy for neurotoxoplasmosis involves a combination of sulfadiazine, pyrimethamine, and folinic acid, but this treatment is associated with numerous side effects, leading to high rates of discontinuation. Biochemical and histopathological analysis of the livers and kidneys indicated low liver and kidney toxicity of EE. Based on these results, it is concluded that EE at a concentration of 200 mg/kg/day was more effective in controlling T. gondii, being able to cross the blood-brain barrier, as well as being less toxic to the host, showing an action similar to conventional treatment."

Journal • Infectious Disease • Transplantation

CEREBRAL TOXOPLASMOSIS AFTER LYMPHOMA THERAPY (CHEST 2025) - "CASE PRESENTATION: A 71-year-old man with Epstein-Barr virus-positive classic Hodgkin lymphoma and low-grade B cell lymphoma, previously treated with 2 doses of rituximab (last dosed 2 months prior) and 6 cycles of BV-AVD (brentuximab vedotin, doxorubicin, vinblastine and dacarbazine; last dosed 2 months prior), presented with several weeks of encephalopathy. A computed tomography (CT) brain scan revealed multifocal expansile edema, most pronounced in the left basal ganglia, prompting initiation of dexamethasone...Treatment includes trimethoprim-sulfamethoxazole or pyrimethamine with sulfadiazine and leucovorin. While toxoplasmosis is typically associated with T cell deficiency, this case demonstrates its occurrence in patients receiving B cell-targeted therapies like rituximab. Clinicians should maintain a high index of suspicion for opportunistic infections in patients treated with immunosuppressive agents, as these therapies can impair T cell immunity despite their B..."

B Cell Lymphoma • Classical Hodgkin Lymphoma • CNS Disorders • CNS Lymphoma • Epilepsy • Epstein-Barr Virus Infections • Gastrointestinal Disorder • Hematological Malignancies • Hodgkin Lymphoma • Human Immunodeficiency Virus • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Genetic diversity and molecular markers of Plasmodium falciparum drug resistance in two different malaria-endemic areas from 2016-2022 in Mali. (ASTMH 2025) - "Mutations associated with pyrimethamine resistance were highly prevalent in both sites (dhfr-108N:90% vs 91, p = 0.8), and (dhfr-59R: 88% and 88, p = 0.5)...Regarding chloroquine and amodiaquine, pfmdr1-86Y was infrequent and similar across sites (5.1% vs 4.3%; p > 0.9), while the pfmdr1-184F allele showed moderate frequencies (59% vs 54%; p = 0.5)...Genome-wide FST values were generally low (0.15) indicated region-specific genetic divergence. Despite ecological contrasts, parasite populations shared similar resistance profiles and genetic backgrounds, with localized divergence underscoring the value of ongoing genomic surveillance."

Biomarker • Late-breaking abstract • Infectious Disease • Malaria • ABCB1 • DHFR

High-density temporal and spatial surveillance in Rwanda reveals increasing validated Plasmodium falciparum kelch13 mutations and complex patterns of recent emergence and spread 2022-2024 (ASTMH 2025) - "For high-level pyrimethamine resistance, dhfr I164L, increased (17.0% 2022; 19.3% 2024) despite no official usage in Rwanda. crt K76T (8.4%) and mdr1 N86Y (0.28%) were almost fixed to wildtype—associated with lumefantrine resistance the partner drug in Rwanda, K76T was higher near Burundi and DRC borders where amodiaquine may be selecting for these mutations. Overall our high-resolution deep sampling reveals high heterogeneity for specific mutations and their prevalence, revealing a complex process of spread likely impacted by multiple factors. Further study is needed to understand the dynamics that influence selection and spread of K13 and other mutations."

Infectious Disease • Malaria • ABCB1 • DHFR

Impact of COVID-19 pandemic in parasite populations from the Western Brazilian Amazon (ASTMH 2025) - "Samples were collected between 2019 and 2023 were analyzed and subjected to ex vivo assays to determine their response to artemisinin, chloroquine, pyronaridine, pyrimethamine, mefloquine, lumefantrine, ferroquine, piperaquine, and amodiaquine...A high variation in chloroquine susceptibility was observed in both P. falciparum and P. vivax isolates over the analyzed period, which included part of the COVID-19 pandemic, when hydroxychloroquine was broadly used as COVID treatment...Nucleotide insertion in the pvcrt promoter sequences were also detected in parasites with lower chloroquine susceptibility. Our findings reinforce the need for continuous monitoring of antimalarial resistance in the Amazon, highlighting the importance of ex vivo testing and the identification of genetic markers as complementary tools in malaria molecular and epidemiological surveillance."

Clinical • Infectious Disease • Malaria • Novel Coronavirus Disease • ABCB1

Changes in susceptibility of Plasmodium falciparum to antimalarial drugs in Uganda over time: 2019-2024 (ASTMH 2025) - "Between 2019 and 2024, susceptibilities increased for chloroquine (IC50 24.0 nM → 15.4 nM) and decreased for lumefantrine (5.9 nM → 20.0 nM), mefloquine (12.5 nM → 20.1 nM), and dihydroartemisinin (1.8 nM → 3.8 nM)...For aminoquinolines and pyrimethamine, genotypes associated with susceptibility were those previously identified...For DHA, susceptibility was decreased with the PfK13 C469Y (WT 2.0 nM vs. mutant 3.6 nM) or A675V (WT 2.0 nM vs. mutant 3.8 nM) and PfMDR1 Y500N (WT 1.9 nM vs. mutant 5.4 nM) mutations. Decreasing activities of lumefantrine and DHA may lead to decreased antimalarial efficacy of artemether-lumefantrine, the first-line regimen in Uganda."

Infectious Disease • Malaria • ABCB1 • WT1

Surveillance of Plasmodium falciparum molecular markers of antimalarial drug resistance in parasites from Ghana using Targeted Amplicon Deep Sequencing (ASTMH 2025) - "The prevalence of resistance markers were: pyrimethamine, pfdhfr mutations: N51I (56%, 504/901), C59R (59%, 532/901), and S108N (60%, 540/901); sulphadoxine, pfdhps mutations: A437G (41%, 366/901), K540E (1%, 10/901) and S436A (25%, 227/901). The prevalence of chloroquine resistance mutation, pfcrt K76T was quite low, 1% (9/901)...The finding of low prevalence of pfk13 validated markers supports the current drug efficacy data for the artemisinin-based combination therapy regimens with efficacies ranging between 97%-99% in the country. This study highlights the effectiveness of MaRS-TADS method for monitoring drug resistance and underscores the need for continued surveillance to inform malaria elimination strategies in Ghana."

Biomarker • Infectious Disease • Malaria • ABCB1

Drug susceptibility and PfK13 mutations in Plasmodium falciparum isolates from severe and uncomplicated malaria patients in northern Uganda (ASTMH 2025) - "Susceptibility to all 9 drugs was similar for isolates collected from severe and uncomplicated malaria patients by IC50 (median: DHA 3.9 nM vs 3.6 nM, lumefantrine 13.8 vs 16.8, piperaquine 3.8 vs 4.7, pyronaridine 0.6 vs 0.8, mefloquine 13.5 vs 15.9, monodesethylamodiaquine 6.1 vs 7.3, chloroquine 14.3 vs 11.3, quinine 78.9 vs 92.2, and pyrimethamine 26,369 vs 26,548) and DHA RSA (median survival 2.4% vs 2.4%). In summary, P. falciparum susceptibility to standard antimalarials did not differ between patients with uncomplicated or severe malaria, but ART-R-mediating PfK13 mutations were more prevalent in severe malaria isolates. These results might be explained by enhanced virulence of mutant parasites or an increased likelihood of recent treatment, selecting for PfK13 mutations, in those presenting with severe compared to uncomplicated malaria."

Clinical • Infectious Disease • Malaria

PULMONARY CRYPTOCOCCOSIS AND DISSEMINATED TUBERCULOSIS COINFECTION IN AN IMMUNOCOMPETENT INDIVIDUAL: A RARE CASE REPORT (CHEST 2025) - "The patient started on treatment for cerebral and pulmonary tuberculosis with Rifabutin, Isoniazid, Pyrimethamine, Ethambutol (RIPE) as well as prednisone for TB meningitis. Patient also received liposomal Amphotericin B and flucytosine as induction therapy for cryptococcal pneumonia and later transitioned to maintenance therapy with fluconazole... This case aims to describe a rare co-infection in an immunocompetent host and the challenges posed by two distinct disease processes with overlapping clinical presentation. Comprehensive microbiology testing is required to differentiate between these two infections and provide appropriate treatment."

Case report • Clinical • Back Pain • CNS Disorders • Cough • Human Immunodeficiency Virus • Infectious Disease • Musculoskeletal Pain • Pneumonia • Respiratory Diseases • Tuberculosis

Malaria drug resistance monitoring in Senegal reveals dramatic regional heterogeneity with general increases in markers associated with decreased susceptibility to partner drugs lumefantrine and amodiaquine. (ASTMH 2025) - "The Pfdhfr IRN haplotype (N51I, C59R, and S108N) associated with pyrimethamine (P) resistance was near fixation in Senegal, but a decrease (78.9% [75.6%, 82.3%] was seen overall, characterized by reduced C59R frequency (80.9% [77.8%, 83.4%]), while N51I (96.6% [95.1%, 98.0%]) and S108N (98.1% [97.1%, 99.2%] remained near fixation. We hypothesize these changes are due to differential population-level drug pressure including Seasonal Malaria Chemoprevention (SMC). Progressive selection of mutations associated with ART partner drugs (LUM and AQ) as well as SP (used in SMC) warrant ongoing surveillance for antimalarial resistance that threatens to undermine malaria elimination efforts in Senegal."

Heterogeneity • Infectious Disease • Malaria • ABCB1

High-density temporal and spatial surveillance in Rwanda reveals increasing validated Plasmodium falciparum kelch13 mutations and complex patterns of recent emergence and spread 2022-2024 (ASTMH 2025) - "For high-level pyrimethamine resistance, dhfr I164L, increased (17.0% 2022; 19.3% 2024) despite no official usage in Rwanda. crt K76T (8.4%) and mdr1 N86Y (0.28%) were almost fixed to wildtype—associated with lumefantrine resistance the partner drug in Rwanda, K76T was higher near Burundi and DRC borders where amodiaquine may be selecting for these mutations. Overall our high-resolution deep sampling reveals high heterogeneity for specific mutations and their prevalence, revealing a complex process of spread likely impacted by multiple factors. Further study is needed to understand the dynamics that influence selection and spread of K13 and other mutations."

Infectious Disease • Malaria • ABCB1 • DHFR

Diagnostic and therapeutic challenges in a case of cerebral mass lesions in a person living with HIV (EACS 2025) - "After ten days of cotrimoxazole, cytolytic hepatitis and acute renal failure led to a switch to pyrimethamine, clindamycine and atovaquone. This case depicts the difficulties for the initial diagnosis and management of concomitant opportunistic infections in PWAHD. Given the severe neurological presentation and potential differential diagnosis of CNS lymphoma or tuberculosis, a cerebral biopsy was performed, before the efficacy of the usual two weeks of treatment with cotrimoxazole could be evaluated. Although clinicians might fear to use high-dose corticosteroids in the context of potential risk of unmasking other opportunistic infections, it might have been an option before performing such an invasive procedure as cerebral biopsy."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Tuberculosis • CD4

Unmasking IRIS due to Toxoplasma gondii in a new HIV-positive individual with CD4 ≥200 cells/mm3 and disseminated tuberculosis (EACS 2025) - "IgG for Toxoplasma gondii was positive and atovaquone was started for primary prophylaxis (to minimize medullar toxicity related to cotrimoxazole) without pyrimethamine...Empirical treatment with pyrimethamine and sulfadiazine was initiated... This case highlights how IRIS-related Toxoplasma encephalitis can occur despite CD4 ≥200 cells/mm 3 and its prophylaxis. CD4 cell count by itself may not predict IRIS risk, especially early after initiating ART. Rapid neuroimaging, empirical treatment and high suspicion are essential for timely diagnosis and recovery, even in the presence of more than one confirmed opportunistic infection."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Tuberculosis • CD4