Persistence and antiviral resistance of varicella zoster virus in hematological patients.
BACKGROUND
Varicella zoster virus (VZV) infections are a relevant cause of morbidity and mortality in hematological patients and especially in hematopoietic stem cell transplant (HSCT) recipients. The present study aimed to investigate the prevalence and clinical significance of viral persistence and antiviral resistance by systematically analyzing all episodes of VZV diagnosed in our laboratory in pediatric and adult hematological patients between 2007 and 2010.


METHODS
Patient charts were reviewed to document patient and disease characteristics. VZV loads were determined in all available clinical samples from the day of diagnosis and thereafter. Persistent VZV infection was defined as a VZV infection that lasted at least 7 days. Analysis of resistance was performed in all patients with persistent VZV infection by sequence analysis of viral thymidine kinase and DNA polymerase genes.


RESULTS
In total, 89 episodes occurred in 87 patients, of whom 65 were recipients of an allogeneic HSCT. Follow-up samples were available in 54 episodes. Persistent VZV was demonstrated in 32 of these episodes (59%). Complications occurred in 16 of the persistent episodes (50%) vs 2 of 22 nonpersistent episodes (9%). Mutations possibly associated with resistance were found in 27% of patients with persistent VZV, including patients with treatment-unresponsive dermatomal zoster that progressed to severe retinal or cerebral infection.


CONCLUSIONS
In hematological patients, VZV-related complications occur frequently, especially in persistent infections. Antiviral resistance is a relevant factor in persistent infections and needs to be investigated in various affected body sites, especially when clinical suspicion of treatment failure arises.
Department of Medical Microbiology, Leiden University Medical Center, The Netherlands. m.t.van_der_beek@lumc.nl
Martha T
MT
van der Beek
Clementien L
CL
Vermont
Robbert G M
RG
Bredius
Erik W A
EW
Marijt
Caroline S
CS
van der Blij-de Brouwer
Aloys C M
AC
Kroes
Eric C J
EC
Claas
Ann C T M
AC
Vossen
D000212:Acyclovir / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D001769:Blood / Q000821:virology; D002648:Child; D003131:Combined Modality Therapy; D024882:Drug Resistance, Viral; D005260:Female; D006402:Hematologic Diseases / Q000628:therapy / Q000821:virology*; D018380:Hematopoietic Stem Cell Transplantation; D006562:Herpes Zoster / Q000188:drug therapy / Q000821:virology*; D014645:Herpesvirus 3, Human / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D011183:Postoperative Complications / Q000821:virology; D019562:Viral Load; D014775:Virus Activation; D014779:Virus Replication; D055815:Young Adult
D000914:Antibodies, Viral; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D000212:Acyclovir