Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains . We have formed a network of 15 virology laboratories which have isolated and identified, between May 1999 and April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The sensitivity of each isolate to ACV was evaluated by a colorimetric test (C. Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217, 2002). During this study, 3,900 isolated strains among 3,357 patients were collected; 55% of the patients were immunocompetent. Only six immunocompetent patients excreted ACV-resistant HSV strains (0.32%), including one female patient not treated with ACV who was infected primary by an ACV-resistant strain. Among the 54 immunocompromised patients from whom ACV-resistant HSV strains were isolated (3.5%), the bone marrow transplantation patients showed the highest prevalence of resistance (10.9%), whereas among patients infected by human immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the patients who excreted the ACV-resistant strains were treated with foscarnet (PFA), and 61% of them developed resistance to PFA. The collection of a large number of isolates enabled an evaluation of the prevalence of resistance of HSV strains to antiviral drugs to be made. This prevalence has remained stable over the last 10 years, as much among immunocompetent patients as among immunocompromised patients.Herpes simplex virus (HSV) infections are very common; they are localized on the face and torso in the case of HSV type 1 (HSV-1) and in the genital region in the case of HSV-2. HSV-1 infections in the genital region are on the increase (40). Ocular herpes is less frequent, and neonatal herpes and herpetic meningoencephalitis are very rare but have a severe functional and vital prognosis (37).Since acyclovir (ACV) {9-[(2-hydroxyethoxy)methyl)guanine]} was introduced to the market in 1983, it has been used primarily in the prevention and treatment of HSV infections. ACV-resistant HSV strains have been observed in vivo since the first large therapeutic trials (5, 10, 36). These resistant strains are detected in vitro by phenotypic tests which determine the antiviral concentration inhibiting viral replication by 50%. Several methods have been used to evaluate the sensitivity of the HSV strains to ACV, including techniques to detect the intensity of the cytopathic effect, such as the plaque reduction (17, 31) and colorimetric (11,22,26) techniques, but also the detection of DNA replication by hybridization (39) or antigen production by flow cytometry (30).Previous surveys among immunocompetent patients have shown a prevalence of resistance to ACV varying between 0 and 0.6%, whereas among immunocompromised patients, the prevalence varied between 3 and 6% (9,16,29). The use of ACV is co...
BK virus (BKV) infection during the first year after renal transplantation was studied prospectively in 104 unselected consecutive patients. Viral DNA in urine (DNAuria) and plasma (DNAemia) samples was detected and quantified by real-time PCR. The noncoding control region (NCCR) of BKV isolates was sequenced.DNAuria and DNAemia occurred in 57% and 29% of patients, respectively. Three groups were defined, uninfected patients (group 1, n = 45), patients with DNAuria (group 2, n = 29) and patients with positive DNAemia (group 3, n = 30). Active infection started within the first 3 months in 80% of patients. Cold ischemia duration over 24 h and the administration of tacrolimus were identified as significant risks factors for DNAuria, whereas it remains more frequently negative in patients receiving cyclosporine A. The risk for positive DNAemia was higher in patients with DNAuria (notably for viral load (VL) >4 log/mL) or treated with tacrolimus. No relationship was found with genetic variability in the NCCR sequence.Our data highlight the high frequency of active BKV infection after renal transplantation. Although high VL was detected in some patients, none developed a BKV nephropathy. A prospective follow-up of the whole population during the first year post renal transplantation is thus not useful to predict BKV disease.
Open Access. This is an open access article distributed under the terms of the CC-BY License.
Occurrence of CMV, EBV and human herpes virus 6 (HHV6) infections and immune reconstitution were compared in 15 adult patients receiving a cord blood transplantation (CBT) and 40 patients who received an allogeneic transplantation from a matched unrelated donor (MUD). Herpes virus DNA quantifications in the blood (459 samples) were performed before and then monthly up to 9 months after transplant and the main lymphocytes populations were counted at 3, 6 and 9 months. Incidence of HHV6 infection was significantly higher in the CBT group (80 vs 42.5%; Po0.0001), with higher viral load (Po0.0001). In multivariate analysis, the use of a CBT and a myeloablative conditioning regimen were found to increase the risk of HHV6 infection (odds ratio (OR) ¼ 5.4, P ¼ 0.02 and OR ¼ 3.5, P ¼ 0.04, respectively). Incidences of CMV were similar between the two groups whereas MUD increased the risk of EBV infection, in univariate analysis only. HHV6 reactivation translated toward delayed neutrophils and plts engraftment in the two groups. MUD and CBT do not share the same immune reconstitution patterns, notably for B and CD8 lymphocytes and NK cells. There is a strong and specific relationship between HHV6 infection and the use of cord blood cells.
This single centre study assessed the incidence, kinetics and predictive factors of Epstein-Barr Virus (EBV) reactivation and EBV-related lymphoproliferative diseases (LPDs) in 175 consecutive patients who received a reduced-intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT). The cumulative incidence of EBV reactivation at 6 months after allo-HSCT defined as an EBV PCR load above 1000 copies of EBV DNA/10 5 cells was 15%, and none of these patients experienced any sign or symptom of LPD. A total of 17 patients, who had EBV DNA levels exceeding 1000 copies/10 5 cells on two or more occasions, were pre-emptively treated with rituximab. With a median follow-up of 655 (range, 92-1542) days post allo-HSCT, there was no statistically significant difference in term of outcome between those patients who experienced an EBV reactivation and those who did not. In multivariate analysis, the use of antithymocyte globulin as part of the RIC regimen was the only independent risk factor associated with EBV reactivation (relative risk ¼ 4.9; 95% confidence interval, 1.1-21.0; P ¼ 0.03). We conclude that patients undergoing RIC allo-HSCT using anti-thymocyte globulin as part of the preparative regimen are at higher risk for EBV reactivation. However, this did not impact on outcome, as quantitative monitoring of EBV viral load by PCR and preemptive rituximab therapy allowed for significantly reducing the risk of EBV-related LPD.
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