Post-hematopoietic stem cell transplantation (HSCT) adenovirus infections were identified in 31 of 204 consecutive pediatric HSCT patients, 18 of whom had severe manifestations of infection. Cidofovir treatment led to clinical improvement in 8 of 10 patients with severe infection and to virologic clearance in 9 patients. In vitro susceptibility to cidofovir was demonstrated in 12 clinical adenovirus isolates. Cidofovir is a promising treatment option for this population.Adenoviruses are serious pathogens among immunocompromised patients [1,2], with an incidence of infection of up to 20% among hematopoietic stem cell transplant (HSCT) recipients [3] and case-fatality rates that approach 60% [4]. Respiratory, gastrointestinal, and genitourinary infections with adenovirus are common in children undergoing HSCT [5,6], and disseminated illness is often fulminant and fatal. Cidofovir has in vitro activity against adenoviruses [7][8][9], and several case studies [3,[10][11][12][13][14] report successful use of cidofovir for treatment of adenovirus infection in HSCT and solid organ transplant recipients. We reviewed the findings regarding adenovirus infection in a pediatric HSCT population and describe our experience with cidofovir therapy.Methods. We reviewed data from a database on 204 con- secutive patients who underwent HSCT at our institution during the period of 1 January 1994 and 31 March 2003, and we analyzed records for patients with adenovirus infection for a minimum of 200 days after transplantation, because data for each patient were available for at least this duration at the start of the study. Testing for adenovirus infection was performed only for symptomatic patients; there was no routine surveillance. Diagnosis was confirmed by detection of adenovirus antigen in respiratory specimens by immunofluorescence, by observation of typical adenovirus particles in stool specimens concentrated by ultracentrifugation, and by conventional and shell-vial centrifugation culture of nasal secretions, bronchoalveolar lavage specimens, urine samples, or stool samples, with use of monoclonal antibodies and immunofluorescence for confirmation. Serotyping of adenovirus isolates was not done. Patients with adenovirus detected from 11 site during the same illness were classified as having disseminated infection.Patients with adenovirus infection were categorized as having severe infection either if they had disseminated infection or if infection at 1 site was accompanied by severe clinical manifestations attributable to the infection [12]; all other infections were categorized as mild. Resolution of infection was defined as clinical improvement and as virologic evidence of clearance; patients with intermittent positive test results after having symptomatic illness were considered to have continued infection until specimens yielded consistently negative test results with continued absence of symptoms over a 30-day period. Recurrence of infection was defined as evidence of adenovirus at any site 130 days after resolution of pr...
The proportion of acyclovir (ACV)-resistant herpes simplex virus (HSV) isolates in clinical specimens and laboratory isolates was determined. HSV isolates in clinical specimens and laboratory isolates were cultured in the absence or presence of 5 g of ACV per ml. The frequency of ACV-resistant HSV was calculated as (average virus titer in the wells with ACV)/(average virus titer in the wells without ACV). The mutation frequency of HSV type 1 isolates in clinical samples (directly from patient lesions) was 7.5 ؋ 10 ؊4 ؎ 2.5 ؋ 10 ؊4(mean ؎ standard error), and that of HSV type 2 isolates was 15.0 ؋ 10 ؊4 ؎ 4.6 ؋ 10 ؊4 . The mutation frequencies of isolates derived in the laboratory from these clinical samples were very similar. Similarly, the 50% inhibitory concentrations for isolates in clinical samples and laboratory isolates were identical. The frequencies of ACV-resistant HSV types 1 and 2 were in a narrow range of 7.5 ؋ 10 ؊4 to 15.0 ؋ 10 ؊4 among isolates in clinical specimens and did not change for laboratory-derived pools of viral isolates.Acyclovir (ACV) is widely used for the treatment of primary and recurrent herpes simplex virus (HSV) and varicella-zoster virus infections because of its very favorable therapeutic ratio. Since 1982, 2.0 ϫ 10 6 kg of ACV and other nucleoside analogues has been distributed, with more than 50% of that amount distributed in the United States. ACV is a nucleoside analogue of guanine that is preferentially phosphorylated to ACV monophosphate by viral thymidine kinase and that is then further phosphorylated to ACV triphosphate by cellular enzymes. ACV triphosphate inhibits viral DNA polymerase and is incorporated into viral DNA, ultimately preventing elongation of viral DNA (7). HSV develops resistance predominantly (95%) as a result of mutations in genes that code for thymidine kinase, but resistance can also result from mutations in DNA polymerase (1,3,4,9,16).ACV-resistant variants have been isolated from clinical specimens obtained before ACV was introduced (13). These variants are also readily detected in pools of laboratory strains of ACV-sensitive HSV. Mutation frequencies of 2.7 ϫ 10 Ϫ6 to 1.0 ϫ 10 Ϫ3 for HSV type 1 and 5.0 ϫ 10 Ϫ5 to 8.0 ϫ 10 Ϫ3 for HSV type 2 were detected, and these studies indicate that some proportion of HSV growing in cell culture is always resistant to ACV, even when the inoculum is considered to be susceptible to ACV by conventional plaque reduction assays (PRAs) (2,10,11,15). Although this conclusion was initially obtained from studies with a small number of multiply passaged laboratory virus pools, there is now comparable information from studies with clones of a small number of clinical specimens (15).Given the continuing strong selection pressure provided by extensive use of ACV and related compounds and concern that the level of antiviral resistance of HSV will increase, we have sought to develop additional baseline information on the prevalence of resistant mutants in clinical samples and isolates prepared from those samples. Moreover, co...
Viral RNAs extracted from fifteen mumps virus isolated from throat swab, saliva, blood, urine or CSF during mumps epidemics between 1997-1998 in Korea were amplified by reverse transcriptasepolymerase chain reaction (RT-PCR) and compared by nucleotide sequencing of the small hydrophobic (SH) gene. The deduced amino acid sequences of the SH gene were aligned with the published sequences of mumps virus isolated in different geographic areas. A comparison of the SH gene of mumps viruses in Korea indicated 96.2-100% and 91.2-100% similarity at the nucleotide and amino acid levels, respectively. Phylogenetic analysis, using the neighbor-joining method, showed that Korean mumps virus strains formed a genetically distinct monophyletic group from previously reported genotypes based on the 315-bp length nucleotide and 57 deduced amino acid sequences of the SH gene, and possibly be designated as a new genotype (I).
Subjects received topical penciclovir for 4 days during successive episodes of recurrent herpes labialis. Isolation of herpes simplex virus (HSV) was attempted from lesions obtained before initiation of treatment and on each day of therapy. Isolates remained sensitive to penciclovir when tested by a plaque reduction assay, and there was no significant change in sensitivity during any treatment course or between successive treatments. The proportion of nucleoside-resistant variants present within a subset of these isolates was further investigated using a more-sensitive plating efficiency assay. Although the proportion of antiviral-resistant HSV variants increased on successive days, it invariably remained a minor subpopulation. Moreover, isolates from successive episodes obtained before treatment showed no change in the proportion of resistant HSV variants. We conclude that antiviral-resistant variants, which are readily detected in HSV isolates from peripheral lesions, do not accumulate in the sensory ganglia of immunocompetent patients receiving multiple courses of nucleoside analogues.
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