Since its identification in April 2009 an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The 2009 A(H1N1) virus is distantly related to its nearest relatives, indicating that its gene segments have been circulating undetected for an extended period. Low genetic diversity among the viruses suggests the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predicted for adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1).

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Objectives To assess the prevalence, characteristics, and risk of sensorineural hearing loss (SNHL) through 18 years of age in children with congenital CMV infection identified through hospital-based newborn screening who were asymptomatic at birth compared to uninfected children. Methods We included 92 case-patients and 51 controls assessed using auditory brainstem response and behavioral audiometry. We used Kaplan-Meier survival analysis to estimate prevalence of SNHL, defined as ≥25 dB hearing level (HL) at any frequency, and Cox proportional hazards regression analyses to compare SNHL risk between groups. Results At the end of follow-up, SNHL prevalence was 25% (95% CI: 17–36%) among case-patients and 8% (95% CI: 3–22%) in controls (hazard ratio (HR): 4.0; 95% CI: 1.2–14.5; p-value=0.02). Among children without SNHL by age 5 years, the risk of delayed-onset SNHL was not significantly greater for case-patients than for controls (HR: 1.6; 95% CI: 0.4–6.1; P=0.5). Among case-patients, the risk of delayed-onset SNHL was significantly greater among those with unilateral congenital/early-onset loss than those without (hazard ratio: 6.9; 95% CI: 2.5–19.1; P<0.01). At the end of follow-up, the prevalence of severe to profound bilateral SNHL among case-patients was 2% (95% CI: 1–9%). Conclusions Delayed-onset and progression of SNHL among children with asymptomatic congenital CMV infection continued to occur throughout adolescence. However, the risk of developing SNHL after age 5 years among case-patients was not different than in uninfected children. An estimated 2% of case-patients developed SNHL severe enough to be candidates for cochlear implantation.

IntroductionInfections, malignant relapse, and graft-versus-host disease (GVHD), continue to cause significant morbidity and mortality after hematopoietic stem cell (HSC) or cord blood (CB) transplantation. Virus infections such as cytomegalovirus (CMV), EpsteinBarr virus (EBV), and adenovirus (AdV) are particularly problematic and remain difficult to treat, especially after umbilical CB transplantation. [1][2][3][4][5] Although ganciclovir/foscarnet may help prevent or treat CMV 6 and CD20-specific antibody may control EBV-associated lymphoproliferation, 7 these drugs are expensive and are often toxic or ineffective due to primary or secondary resistance. 6 Moreover, AdV infections are increasingly common and effective treatments are not currently available. 8 The other major cause of morbidity and mortality is relapse, occurring in more than 30% of transplant recipients with B-cell acute lymphoblastic leukemia (B-ALL), [9][10][11][12] with few appealing therapeutic options and less than 10% long-term survival. 13,14 Although donor lymphocyte infusions can be used after HSC transplantation to treat both viral infections and leukemia relapse, these are associated with potentially life-threatening GVHD, 15 have a low success rate in relapsed B-ALL, 15,16 and are unavailable for CB transplant recipients. An alternative for viral infections is the adoptive transfer of cytotoxic T lymphocytes (CTLs) directed to CMV, 17,18 EBV,19,20 and, more recently, AdV, 21,22 which can rapidly reconstitute antiviral immunity after HSC transplantation without causing GVHD. Infusion of peripheral blood-derived T-lymphocyte lines enriched in cells simultaneously recognizing CMV, EBV, and AdV (multivirus-specific CTLs [MV-CTLs]) reproducibly controls infections due to all 3 viruses after allogeneic HSC transplantation. 21 Importantly, functional CMV-, EBV-, and AdV-specific CTLs can now also be generated from naive T cells isolated from CB units. 23 It is also possible to infuse leukemia-specific CTLs into patients after HSC transplantation 24,25 ; these can be generated by stimulating peripheral blood mononuclear cells with apoptotic leukemic blasts. 25,26 Unfortunately, however, the paucity of antigen-specific CTL precursors and the need to separate graft-versus-tumor from the graft-versus-host effect may require extensive culture to generate sufficient numbers of cells for adoptive T-cell therapy. 25,26 To overcome this difficulty, investigators have used T lymphocytes engineered to express chimeric antigen receptors (CARs) directed to self-antigens expressed by tumor cells. 27,28 For example, T cells expressing a CAR specific for the CD19 molecule 29,30 may be able to prevent or treat leukemia relapse in B-ALL patients as these cells almost invariably express CD19.It would be appealing to combine these approaches to prepare a single product containing CTLs that were virus specific (through The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge paym...