atovaquone / Generic mfg. - LARVOL DELTA

Atovaquone/proguanil use and zoster vaccination are associated with reduced Alzheimer's disease risk in two cohorts: implications for a latent Toxoplasma gondii mechanism. (PubMed, Brain Behav Immun) - "In exploratory analyses, the magnitude of the association between atovaquone-proguanil and subsequent dementia appeared to differ according to prior VZV vaccination status, suggesting a possible interaction between protozoal suppression and antiviral immunity. Together, these findings provide population-level evidence consistent with a latent T. gondii-related mechanism in AD pathogenesis, and highlight testable targets for future mechanistic and interventional research."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Herpes Zoster • Varicella Zoster

Hypoxia Alleviation-Potentiated Chemotherapy Enhances Anti-PD-L1 Treatment for Triple-Negative Breast Cancer via Improving Tumor Immunogenicity and Inhibiting STAT3 Activation. (PubMed, ACS Appl Mater Interfaces) - "The combination of anti-PD-L1 and paclitaxel (PTX) is a standard-of-care regimen for triple-negative breast cancer (TNBC)...This project aims to construct an albumin-based nanomedicine coloaded with atovaquone (ATO) and PTX for targeted tumor delivery, thereby enhancing the therapeutic efficacy of ICBs...This transformative approach significantly enhances the therapeutic efficacy of combination chemotherapy, leading to potent suppression of primary tumors while concurrently preventing postoperative recurrence and pulmonary metastases. This project has the potential to introduce innovative strategies and methodologies aimed at overcoming the limited efficacy of PTX combined with ICBs in the treatment of TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • STAT3

ATACC AML: Atovaquone (Mepron®) Combined With Conventional Chemotherapy for de Novo Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: Baylor College of Medicine | Active, not recruiting ➔ Completed

Trial completion • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Exploring the prognostic molecular mechanisms of medulloblastoma through methylation-transcriptome integration. (PubMed, SAGE Open Med) - "Drug prediction suggested that atovaquone and embelin may reverse tumor progression. Inhibin beta B and ubiquitin-specific peptidase 2 are key marker genes for predicting medulloblastoma patient prognosis stratification, with their expression patterns closely linked to molecular subtypes and the immune microenvironment. This study provides novel molecular targets and strategies for precision therapy and prognostic assessment in medulloblastoma."

Journal • Brain Cancer • Embryonal Tumor • Medulloblastoma • Oncology • Solid Tumor • Targeted Protein Degradation • INHBB

SPIRIT-ALT: Positioning Second-line Therapies for Pneumocystis Jirovecii Pneumonia (PCP Alternatives) (clinicaltrials.gov) - P4 | N=416 | Not yet recruiting | Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

New P4 trial • Human Immunodeficiency Virus • Infectious Disease • Pneumonia • Respiratory Diseases

Clinical outcomes after switching from sulfamethoxazole-trimethoprim to atovaquone due to intolerance in patients with non-HIV Pneumocystis pneumonia: a single-center retrospective study. (PubMed, J Pharm Health Care Sci) - "Our data suggest that switching from SMX/TMP to Atov may not be associated with worse survival. Long-term administration of SMX/TMP is often challenging due to its side effects, and in this study, more than 30% of patients were unable to tolerate its therapeutic dose. Our findings support the role of Atov as a viable second-line treatment for PCP in immunocompromised patients, such as those with non-HIV PCP."

Clinical data • Journal • Retrospective data • Infectious Disease • Pneumonia • Respiratory Diseases

Integrating machine learning and multi-omics analysis to explore Treg-associated programmed cell death features in clear cell renal cell carcinoma. (PubMed, Cancer Cell Int) - "We explored the significance of Treg and programmed cell death characteristics in the ccRCC tumor microenvironment and established clinically translatable tools for ccRCC diagnosis, prognosis, and personalized therapy selection, thus promoted the application of explainable machine learning models in precision oncology. Furthermore, We have identified SLC11A1 as a highly promising therapeutic target for ccRCC."

IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CASP9 • SLC11A1

Pneumocystis jirovecii pneumonia in a human caused by long-term use of veterinary drug oclacitinib: A case report. (PubMed, IDCases) - "He was initially treated with trimethoprim-sulfamethoxazole and corticosteroids; however, the regimen was switched to atovaquone owing to hepatotoxicity. To our knowledge, this is the first reported case of PJP associated with oclacitinib use in humans. As JAK inhibitors are increasingly being used, clinicians should be aware of their potential to cause opportunistic infections, even with veterinary formulations without approved human indications."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

Real world treatment outcome with azacytidine (AZA)-tocilizumab (TCZ) for reducing steroid dependence in vexas syndrome with myelodysplastic syndrome (MDS): A single-center, 1.5-year longitudinal observational study (ASH 2025) - "Treatment and outcome: The patient was initiated on high-dose prednisone (PRD) at 40 mg daily and Erythropoiesis-Stimulating Agent, leading to clinical improvement...Acyclovir, atovaquone and voriconazole were used for anti-microbial prophylaxis... As VEXAS syndrome is a novel disease, there is absence of standardized treatment guidelines. This case highlights the promise of AZA-TCZ combination therapy in steroid dependent VEXAS syndrome with MDS. Further investigation into targeted steroid-sparing regimens along with patient specific guidelines is warranted for durable disease control and improved outcomes."

Clinical • HEOR • Observational data • Real-world • Real-world evidence • Eosinophilia • Hematological Disorders • Hematological Malignancies • Inflammation • Leukopenia • Musculoskeletal Diseases • Myelodysplastic Syndrome • Neutropenia • Ocular Inflammation • Ophthalmology • Orthopedics • Renal Disease • Retinal Vein Occlusion • Uveitis

Babesiosis masquerading as ITP in a patient with CLL (ASH 2025) - "Patient's home medications included only ramipril and metoprolol succinate...Patient was started on atovaquone and azithromycin...And patient was diagnosed with Babesiosis. This case highlights how Babesiosis can masquerade as ITP and present as severe thrombocytopenia without any symptoms suggestive of infection."

Clinical • Cardiovascular • Chronic Lymphocytic Leukemia • Coronary Artery Disease • Dyslipidemia • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Thrombocytopenia • HP

Babesia induced cytokine storm: A rare cause of secondary hemophagocytic lymphohistiocytosis (ASH 2025) - "Initially, this was thought to be a tick-borne illness such as anaplasmosis and doxycycline was empirically started...Treatment with Dexamethasone and Etoposide was initiated per HLH-94 guidelines (Henter et al., 2007)...The tick panel was positive for Babesia, and antibiotics were switched to Azithromycin and Atovaquone...Early identification can prevent further spread including CNS spread and prevent the need for hematopoietic stem cell transplants. Screening tools like HScore distinguish hemophagocytic syndromes such as HLH from sepsis or acute hematologic malignancies, allowing for earlier HLH diagnosis and improved outcomes (Fardet et al., 2014)."

Cytokine storm • Bone Marrow Transplantation • Cardiovascular • Coronary Artery Disease • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hepatology • Immunology • Infectious Disease • Rare Diseases • Septic Shock • Thrombocytopenia • IL2 • IL2RA

Pneumocystis jirovecii pneumonia in patients with hematologic malignancy: Risky business, but for whom? (ASH 2025) - "Many of these patients had undergone advanced,immunomodulatory treatments, including 11 (20%) with hematopoietic cell transplantation, 3 (5.5%) withchimeric antigen receptor T-cell therapy, 2 (3.6%) with bispecific T-cell engager therapy, and 16 (29%) withrituximab. Six of the 55 patients (10.9%) were on PJP prophylaxis at the time of infection, including 4(7.3%) on atovaquone and 2 (3.6%) on trimethoprim-sulfamethoxazole... Recent advances in chemo-immunotherapy have drastically altered the treatment landscape for HM,often inducing profound immunosuppression. Our study highlights the importance of optimizing PJPprophylaxis among these patients, particularly those undergoing treatment with novel therapies. Most ofthe patients were not on PJP prophylaxis at the time of diagnosis, underscoring the need to further refinethe institutional guidelines on criteria for prophylaxis."

Clinical • Acute Myelogenous Leukemia • Adult T-Cell Leukemia-Lymphoma • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases

Survival outcomes in tickborne infection-associated hemophagocytic lymphohistiocytosis treated with antibiotics alone versus antibiotics and HLH-directed therapy: A multicenter real-world study (ASH 2025) - "Patients werestratified into two treatment groups: (1) antimicrobial therapy alone (e.g., doxycycline, atovaquone), and(2) antimicrobial therapy plus HLH-directed therapy (defined as corticosteroids, etoposide, IVIG, oranakinra). In our study, HLH-directed therapy in the context of tickborne infection–associated HLH wasassociated with worse survival compared to antimicrobial therapy alone. The difference in survivalbecame increasingly apparent after 10 days from diagnosis, with persistent separation in time-to-deathanalysis at 14, 30 and 90 days. Higher rates of organ dysfunction in the HLH therapy group may reflectunderlying disease severity, treatment-related toxicity, or inappropriate immunosuppression."

Clinical • Real-world • Real-world evidence • Hemophagocytic lymphohistiocytosis • Immunology • Infectious Disease • Lyme Disease • Rare Diseases

Autoimmune hemolytic anemia: An underrecognized contributor to anemia and hemolysis in babesiosis infection (ASH 2025) - "Most received the standardantibiotic regimen of atovaquone, azithromycin and doxycycline. Data was analyzed for 406 patients. Median age was 73 (range 2 to 103) with a malepredominance (67.5%; 264/406). Asplenia was seen in 10.7% (42/406), and 32.5% (127/406) had Lyme-coinfection."

Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology • Infectious Disease

Pyrosequencing analysis of cytochrome b (CYTb) gene mutations in Babesia gibsoni: Correlation with drug resistance and treatment efficacy in South Korea. (PubMed, Vet Parasitol Reg Stud Reports) - "Various treatment regimens were administered based on clinical judgment, including atovaquone-azithromycin (AA), diminazene aceturate, metronidazole-clindamycin-doxycycline (MCD), and doxycycline-enrofloxacin-metronidazole (DEM). Overall, dogs with non-mutated strains tended to respond more favorably to initial treatments, whereas those with mutated strains often required more complex therapeutic approaches. This study supports the value of genetic monitoring in guiding treatment decisions and improving clinical outcomes of canine babesiosis."

Journal • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus

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

Atovaquone-induced oxidative stress activates the pentose phosphate pathway and Immunogenic cell death in ovarian cancer. (PubMed, Sci Rep) - "Moreover, increased expression of ligands for activating receptors of NK cells was observed, and coculture experiments revealed enhanced NK cell activity toward atovaquone-treated cells. These results highlight atovaquone's potential to activate immune responses, offering a new avenue for combination therapies in EOC treatment."

Journal • Epithelial Ovarian Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • CALR • HMGB1 • TFAM

Dual Function of Mitochondrial Complex III in Plasmodium falciparum. (PubMed, bioRxiv) - "MPPα knockdown also resulted in hypersensitivity of the parasites to proguanil, a drug that synergizes with mtETC inhibitors such as atovaquone. Pulldown with MPP α followed by proteomics revealed the association of multiple mitochondrially targeted proteins, in addition to all components of Complex III. These results are consistent with the suggestion that Complex III in P. falciparum serves both mtETC and protein processing functions in mitochondrial physiology."

Journal • Immunology • Infectious Disease • Malaria

Proposal of Chemical Inhibitors That Compete with the Binding of RNA Polymerase II Subunits to Essential GTPases GPN Npa3 and Gpn1. (PubMed, ACS Omega) - "Our analysis identified potential inhibitors, including atovaquone for both Npa3 and Gpn1 (docking scores: -14.4 and -13.5 kcal/mol, respectively) and tibolone for Npa3 (-13.6 kcal/mol), following flexible docking optimization. Additionally, our docking models suggest key residues in Npa3 such as F143 and W179, which may be critical for recognizing RNA polymerase II subunits and drug-like molecules. These findings can be further explored through biochemical and mutagenesis studies to assess their roles in RNA polymerase II recognition."

Journal

A Fatal Case of Hemophagocytic Lymphohistiocytosis Triggered By Babesiosis (ASH 2023) - "Case Presentation: A 77-year-old male with history of deep vein thrombosis (DVT), Parkinson's disease, and lumbar radiculopathy on chronic prednisone, presented for progressive generalized weakness, leg pain, and confusion. HLH should be strongly suspected in patients from endemic regions, especially with additional risk factors such as age, genetics, and immunosuppression. Tools such as the HScore and the HLH-2004 criteria can aid in further patient risk stratification. Urgent treatment with steroids and addressing underlying babesiosis with atovaquone, azithromycin, and potentially red blood cell exchange transfusion, remains crucial for preventing decompensation and improving outcomes."

Clinical • Anemia • Cardiovascular • CNS Disorders • Dyslipidemia • Hematological Disorders • Hemophagocytic lymphohistiocytosis • Hypertriglyceridemia • Immunology • Infectious Disease • Movement Disorders • Musculoskeletal Pain • Pain • Parkinson's Disease • Rare Diseases • Thrombocytopenia • Thrombosis • HP • IL2RA • ISG20

Cumulative Incidence and Characteristics of Infections Requiring Treatment, Delay in Treatment Administration or Hospitalisation in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti BCMA or Anti GPRC5D Bispecific Antibodies (ASH 2023) - "Among the 229 patients included, 200 (87%) received an anti-BCMA BsAb with teclistamab (n=153, ­67%) or elranatamab (n=47, 20%) and 29 patients (13%) received an anti-GPRC5D BsAb with talquetamab. 40% (n=90) of patients were treated in monotherapy, 42% (n=94) had dexamethasone in addition to the BsAb after step up doses and 18% (n=41) received a combination with an anti CD38, immunomodulatory treatment, proteasome inhibitor or other...Regarding infectious prophylaxis, n=104 (47%) infectious events occurred despite a bacterial prophylaxis (n=104), 91% (n=125) occurred under viral prophylaxis, 73% (n=166) with trimethoprim-sulfamethoxazole or atovaquone and 11% (n=25) with pentamidine use...We describe higher frequency of infections in patients receiving anti-BCMA agents compare to anti-GPRC5D group. Impact on treatment administration is huge and dosing intervals strategy and prophylaxis appear necessary and effective to improve the morbidity and mortality rate of..."

Clinical • CNS Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Rare Diseases • Respiratory Diseases

A review on molecular markers of Plasmodium falciparum. (PubMed, J Parasit Dis) - "Atovaquone resistance can be caused by a variety of mutations in the cytochrome b gene, with the majority of mutations affecting the protein's ubiquinol binding site. Similarly, mutations in the Plasmodium falciparum chloroquine resistance transporter, Plasmodium falciparum multi-drug resistance 1, and an increase in Plasmodium falciparum Plasmepsin II and III copy numbers all lead to 4-aminoquinoline drug resistance...In order to successfully address drug resistance in malaria, it will be essential to strengthen worldwide monitoring systems and promote interdisciplinary collaboration among researchers and healthcare professionals. Furthermore, regular monitoring, identification, and limiting of drug-resistant P. falciparum strains through in vivo efficacy tests, in vitro tests, combination therapy, molecular techniques, and appropriate policies must continue to ensure the effectiveness of malaria treatment."

Biomarker • Journal • Review • Infectious Disease • Malaria • ABCC1 • DHFR

Pneumonia in a Post-Transplant Patient: The Eosinophilic Red Herring (KIDNEY WEEK 2025) - "Case Description A 47-year-old female with kidney failure due to Goodpasture syndrome, status post deceased donor kidney transplant in 2014, maintained on tacrolimus and mycophenolate mofetil (MMF) presented with two weeks of fatigue, shortness of breath, and intermittent fevers...Extensive infectious workup remained unyielding, except for a beta-D-glucan level of >500, following which voriconazole was added...Steroids were started for presumed eosinophilic pneumonia, and trimethoprim-sulfamethoxazole was added simultaneously to cover Pneumocystis Pneumonia (PJP), toxoplasma, and nocardia...She was managed with Atovaquone for 3 weeks...mcfDNA sequencing has improved sensitivity and specificity and favorably impacted the management of PJP Pneumonia. It remains an important differential for eosinophilic pneumonia."

Clinical • Post-transplantation • Acute Kidney Injury • Fatigue • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases • Transplantation

Entecavir-Associated Fanconi Syndrome in a Liver Transplant Recipient (KIDNEY WEEK 2025) - "While nucleos(t)ide analogs such as adefovir and tenofovir are well-established culprits, especially in HIV or HBV populations, Entecavir is rarely implicated...Case Description A 60-year-old male with HBV-related cirrhosis status-post liver transplantation, chronic antibody-mediated rejection (on Tacrolimus and Prednisone), type 2 diabetes mellitus, and chronic kidney disease (baseline Creatinine (Cr) 1.4–1.6 mg/dL) presented with recurrent falls and altered mental status. Notable medications included Entecavir started 5 years prior , Voriconazole (for phaeohyphomycosis), and Atovaquone/Sulfadiazine (for disseminated toxoplasmosis)...Discussion Occurrence of hallmark features—including phosphaturia, uricosuria, and hyperchloremic metabolic acidosis—suggests a potential class effect of nucleos(t)ide analogs in susceptible individuals. Thus, clinicians should maintain a high index of suspicion for Fanconi syndrome in patients receiving long-term nucleos(t)ide analog..."

Clinical • Antibody-mediated Rejection • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Fibrosis • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Metabolic Disorders • Nephrology • Renal Disease • Transplantation • Type 2 Diabetes Mellitus

Babesia Masquerade: Hemolysis After Kidney Transplant (KIDNEY WEEK 2025) - "Case Description A 32-year-old male from Seattle with ESKD secondary to anti-complement factor H antibody-associated aHUS managed with eculizumab, received a deceased donor kidney transplant in late 2023...Maintenance IS was reduced, and treatment with azithromycin and atovaquone was initiated for six weeks...Although babesiosis is rare in the PNW—with fewer than 1 case per 100,000 population according to CDC data—transfusion-transmitted infection remains a risk when blood is sourced from regions without routine screening. Given national blood redistribution, there is a need to re-evaluate current screening policies—or, at minimum, adopt greater scrutiny when transfusing immunocompromised patients, regardless of regional endemicity"

Anemia • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Musculoskeletal Pain • Nephrology • Transplantation • HP