RESUMO
Cytomegalovirus (CMV)-specific T-cells, NK cells, and neutralizing antibodies (nAb) were assessed in a randomized trial of CMV prevention with preemptive antiviral therapy (PET) vs. prophylactic antiviral therapy (PRO) in donor seropositive/recipient seronegative (D+R-) liver transplant recipients (LTxR), at 100 days (end of intervention), and at 6 and 12 months post-transplant. The PET group had significantly increased numbers of circulating polyfunctional T-cells, NK cells, and nAb compared to the PRO group at day 100 and several CMV immune parameters remained significantly higher by 12 months post-transplant. Among PET recipients, preceding CMV viremia (vs. no preceding viremia) was associated with significantly higher levels of most CMV immune parameters at day 100. Higher numbers of CMV-specific polyfunctional T-cells and NKG2C+ NK cells at day 100 were associated with a decreased incidence of CMV disease in multivariable Cox regression. The strongest associations with protection against CMV disease were with increased numbers of CMV-specific polyfunctional CD4 T-cells, CD3negCD56dimCD57negNKG2Cpos, and CD3negCD56dimCD57posNKG2Cpos NK cells. PET is superior to PRO for CMV disease prevention by allowing low-level CMV replication and associated antigen exposure that is promptly controlled by antiviral therapy and facilitates enhanced CMV protective immunity in D+R- LTxR.
RESUMO
High-level isolation units (HLIUs) have been established by countries to provide safe and optimal medical care for patients with high-consequence infectious diseases. We aimed to identify global high-level isolation capabilities and determine gaps and priorities of global HLIUs, using a multiple method approach that included a systematic review of published and gray literature and a review of Joint External Evaluations and Global Health Security Index reports from 112 countries. A follow-up electronic survey was distributed to identified HLIUs. The landscape analysis found 44 previously designated/self-described HLIUs in 19 countries. An additional 33 countries had potential HLIUs; however, there were not enough details on capabilities to determine if they fit the HLIU definition. An electronic survey was distributed to 36 HLIUs to validate landscape analysis findings and to understand challenges, best practices, and priorities for increased networking with a global HLIU cohort; 31 (86%) HLIUs responded. Responses revealed an additional 30 confirmed HLIUs that were not identified in the landscape analysis. To our knowledge, this was the first mapping and the largest ever survey of global HLIUs. Survey findings identified major gaps in visibility of HLIUs: while our landscape analysis initially identified 44 units, the survey unveiled an additional 30 HLIUs that had not been previously identified or confirmed. The lack of formalized regional or global coordinating organizations exacerbates these visibility gaps. The unique characteristics and capabilities of these facilities, coupled with the likelihood these units serve as core components of national health security plans, provides an opportunity for increased connection and networking to advance the field of high-level isolation and address identified gaps in coordination, build an evidence base for HLIU approaches, and inform HLIU definitions and key components.