First therapeutic use of Artesunate in treatment of human herpesvirus 6B myocarditis in a child
BACKGROUND: Human herpesvirus 6 (HHV-6) is an important cause of fulminant or acute viral myocarditis. However, insufficiency of standard antiviral treatment against HHV-6 is an emerging problem. OBJECTIVES: To describe the case of child with HHV-6 myocarditis who was treated by unloading with a left ventricular assist device and Artesunate. STUDY DESIGN: Case report supported by histological and viral diagnoses via a combination of histology/immunohistochemistry and polymerase chain reaction techniques performed on cardiac tissues before and after treatment. RESULTS: Following therapeutic intervention, the clinical status and heart function improved. Endomyocardial biopsies revealed decreased levels of HHV-6B DNA in the myocardium and the disappearance of histological findings in support of lymphocytic myocarditis. Left ventricular assist device could be explanted. No adverse effects of Artesunate were noted. CONCLUSIONS: In addition to existing heart failure treatments, Artesunate can be considered as an effective candidate for clinical use in cases of HHV-6B associated myocarditis.
Available from: PubMed Central
- "Promisingly, ARM has been shown to exert anticancer activity in tumor cell lines, while ART has shown anticancer properties in mice with established human tumors –. Several research groups have additionally reported that artemisinin derivatives have antiviral properties in vitro
, . However, clinical research regarding the toxic effects of these derivatives following a low dose treatment protocol over an extended time period is lacking. "
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ABSTRACT: The objective of our study was to profile and compare the systematic changes between orally administered artesunate and intramuscularly injected artemether at a low dose over a 3-month period (92 consecutive days) in dogs. Intramuscular administration of 6 mg kg-1 artemether induced a decreased red blood cell (RBC) count (anemia), concurrent extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. We also observed a prolonged QT interval and neuropathic changes in the central nervous system, which demonstrated the cortex and motor neuron vulnerability, but no behavioral changes. Following treatment with artesunate, we observed a decreased heart rate, which was most likely due to cardiac conduction system damage, as well as a deceased RBC count, extramedullary hematopoiesis in the spleen and inhibition of erythropoiesis in the bone marrow. However, in contrast to treatment with artemether, neurotoxicity was not observed following treatment with artesunate. In addition, ultra-structural examination by transmission electron microscopy showed mitochondrial damage following treatment with artesunate. These findings demonstrated the spectrum of toxic changes that result upon treatment with artesunate and artemether and show that the prolonged administration of low doses of these derivatives result in diverse toxicity profiles.
PLoS ONE 04/2014; 9(4):e94034. DOI:10.1371/journal.pone.0094034 · 3.23 Impact Factor
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ABSTRACT: Polyomavirus BK (BKV) causes polyomavirus-associated nephropathy (PyVAN) and hemorrhagic cystitis (PyVHC) in renal- and bone marrow transplant patients respectively. Antiviral drugs with targeted activity against BKV are lacking. Since the antimalarial drug artesunate recently demonstrated antiviral activity, possible effects of artesunate on BKV replication were explored in human primary renal proximal tubular epithelial cells (RPTECs), the host cells in PyVAN.At 2h post-infection (hpi), RPTECs were treated with artesunate concentrations from 0.3 to 80 μM. After one viral replication cycle (∼72 hpi), extracellular BKV DNA loads reflecting viral progeny production were reduced in a concentration-dependent manner. Artesunate at 10 μM reduced extracellular BKV load by 65%, early LT-ag mRNA and protein expression by 30% and 75%, DNA replication by 73%, and late VP1 mRNA and protein expression by 47% and 64%, respectively. Importantly, the proliferation of RPTECs was also inhibited in a concentration-dependent manner. At 72 hpi, artesunate at 10 μM reduced cellular DNA replication by 68% and total metabolic activity by 47%. Cell impedance and LDH measurements indicated cytostatic but not cytotoxic mechanism. Flow cytometry and EdU incorporation revealed decreased cell numbers in S-phase and suggested cell cycle arrest in G0 or G2. The anti-proliferative and anti-viral effects of artesunate 10 μM were both reversible. Thus, artesunate inhibits BKV replication in RPTECs in a concentration-dependent manner by inhibiting BKV gene expression and genome replication. The antiviral mechanism appears to be closely connected to cytostatic effects on the host cell, underscoring the dependence of BKV on host cell proliferative functions.
Antimicrobial Agents and Chemotherapy 10/2013; 58(1). DOI:10.1128/AAC.01800-13 · 4.48 Impact Factor
Available from: Bernhard Maisch
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ABSTRACT: Fulminant myocarditis is a clinical syndrome with signs of acute heart failure, cardiogenic shock, or life-threating rhythm disturbances in the context of suspected myocarditis. It is not an etiological diagnosis, but may have different underlying causes and pathogenetic processes - viral, bacterial, toxic, and autoreactive. Clinical management of the disease entity at the acute stage involves hemodynamic monitoring in an intensive care unit or similar setting. Rapid routine work-up is mandatory with serial EKGs, echocardiography, cardiac MRI, heart catheterization with endomyocardial biopsy for histology, immunohistology, and molecular analysis for the underlying infection and pathogenesis. Heart failure therapy is warranted in all cases according to current guidelines. For fulminant autoreactive myocarditis, immunosuppressive treatment is beneficial; for viral myocarditis, IVIg can resolve the inflammation, reduce the viral load, and even eradicate the microbial agent. ECMO, IABP, ventricular assist devices, LifeVest, or ICD implantation can bridge to recovery or to heart transplantation.
Current Heart Failure Reports 04/2014; 11(2). DOI:10.1007/s11897-014-0196-6
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