No abstract

Herpes virus (CMV, HSV, VZV) and invasive fungal infections continue to cause significant morbidity and mortality in allogeneic hematopoietic cell transplant (HCT) recipients despite the availability of effective therapies. In this study, we developed an internet-based survey, which was distributed to all HCT centers participating in the CIBMTR program, to gather information on strategies utilized for the prevention of disease due to herpes virus and fungal infections between 1999 and 2003. The survey response rate was 72%, representing 175 programs from 32 countries. Generally, reported center strategies were in accord with the CDC guidelines published in 2000, with 81% of programs using low-dose acyclovir prophylaxis for HSV seropositive patients, 99% of programs reporting use of a CMV prevention strategy during the first 100 days post-transplant for all patients at risk of CMV disease, and 90% of programs using antifungal prophylaxis. Seventy percent of programs reported routine use of a CMV prevention strategy in high-risk patients after day 100. The greatest departure from published guidelines was the use of acyclovir prophylaxis for VZV seropositive recipients in 75% of programs. There were very few reported changes within centers in practices over the study time period. Significant regional variations were found with regard to surveillance procedures and treatment durations. There were no significant differences in treatment practices by center size and very few differences found between those centers that reported treating primarily pediatric patients versus primarily adult patients. In summary, our survey demonstrates overall agreement with published guidelines for the prevention of disease due to herpesviruses and fungal infections with significant regional differences found in duration of antiviral prophylaxis, duration of preemptive therapy, and duration and dosing of antifungal prophylaxis. Center size and age of primary patient population were not associated with many reported differences in strategies.

Cytomegalovirus (CMV) transmission via stem cells or marrow in CMV donor seropositive/recipient seronegative (D+/R−) hematopoietic cell transplantation (HCT) is surprisingly inefficient, and factors associated with transmission in these high-risk HCT recipients are unknown. In a retrospective cohort of D+/R− HCT recipients, cumulative incidence curve estimates were used to determine posttransplantation rates of CMV and multivariable Cox proportional models to assess risk factors associated with transmission. A total of 447 patients from 1995 to 2007 were eligible for enrollment. Overall, 85 of 447 (19.0%) acquired CMV at a median of 49 days (IQR 41–60) posttransplantation. CMV disease before day 100 occurred in 6 of 447 (1.3%) patients and in 7 of 447 (1.6%) after day 100. The donor graft, specifically the total nucleated cell count (adjusted hazard ratio [HR] 2.7; 95% confidence interval [CI], 1.4–4.7, P = .0002), was the only factor associated with CMV transmission in multivariable analyses. Notably, the source stem cells (marrow versus peripheral blood stem cell [PBSC]), screening method, and graft-versus-host disease (GVHD) were not associated with transmission. Thus, a highly cellular graft was the only identifiable risk factor associated with CMV transmission, suggesting that viral genomic content of the donor graft determines transmission efficiency in D+/R− HCT recipients.

Problem Female genital tract secretions inhibit HSV infection, however, the intra- and inter-subject variability, contribution of specific mediators, and impact of reproductive hormones have not been defined. Method of Study Cervicovaginal lavage (CVL) (n=89) obtained from nine cyclers and seven women on hormonal contraception, who completed between three and eight weekly visits, were examined for anti-HSV activity and concentrations of mediators. Results CVL inhibited HSV infection by a mean of ~ 57% during the follicular or luteal phase, but only by 36% in hormonal contraceptive users. Human neutrophil peptides1-3 (HNP1-3) (p=0.03), IL-8 (p=0.003), lactoferrin (p=0.005), lysozyme (p=0.003), IgA (p=0.002), and IgG (p=0.02) correlated with antiviral activity. Intra-subject and inter-subject variability was observed, suggesting that factors other than hormones contribute to innate defense. Conclusions Endogenous antimicrobial activity may provide a biomarker of healthy mucosal immunity and may be reduced in the setting of hormonal contraception. However, larger prospective studies are needed.