The recent identification of an outbreak of 2019‐ novel Coronavirus is currently evolving, and the impact on transplantation is unknown. However, it is imperative that we anticipate the potential ...impact on the transplant community in order to avert severe consequences of this infection on both the transplant community and contacts of transplant patients.
Given the current spread of a novel coronavirus, transplant infectious disease experts discuss the impact of emerging infections on the transplant community and suggest current management strategies.
To evaluate the impact of race and ethnicity upon the prevalence and clinical spectrum of congenital cytomegalovirus infection (cCMV).
From 2007 to 2012, 100 332 infants from 7 medical centers were ...screened for cCMV while in the hospital. Ethnicity and race were collected and cCMV prevalence rates were calculated.
The overall prevalence of cCMV in the cohort was 4.5 per 1000 live births (95% CI, 4.1-4.9). Black infants had the highest cCMV prevalence (9.5 per 1000 live births; 95% CI, 8.3-11.0), followed by multiracial infants (7.8 per 1000 live births; 95% CI, 4.7-12.0). Significantly lower prevalence rates were observed in non-Hispanic white infants (2.7 per 1000 live births; 95% CI, 2.2-3.3), Hispanic white infants (3.0 per 1000 live births; 95% CI, 2.4-3.6), and Asian infants (1.0 per 1000 live births; 95% CI, 0.3-2.5). After adjusting for socioeconomic status and maternal age, black infants were significantly more likely to have cCMV compared with non-Hispanic white infants (adjusted prevalence OR, 1.9; 95% CI, 1.4-2.5). Hispanic white infants had a slightly lower risk of having cCMV compared with non-Hispanic white infants (adjusted prevalence OR, 0.7; 95% CI, 0.5-1.0). However, no significant differences in symptomatic cCMV (9.6%) and sensorineural hearing loss (7.8%) were observed between the race/ethnic groups.
Significant racial and ethnic differences exist in the prevalence of cCMV, even after adjusting for socioeconomic status and maternal age. Although once infected, the newborn disease and rates of hearing loss in infants are similar with respect to race and ethnicity.
Severe sepsis in immunocompromised children is associated with increased mortality. This paper describes the epidemiology landscape, clinical acuity, and outcomes for severe sepsis in pediatric ...intestinal (ITx) and multi‐visceral (MVTx) transplant recipients requiring admission to the pediatric intensive care unit (PICU). Severe sepsis episodes were retrospectively reviewed in 51 ITx and MVTx patients receiving organs between 2009 and 2015. Twenty‐nine (56.8%) patients had at least one sepsis episode (total of 63 episodes) through December 2016. Bacterial etiologies accounted for 66.7% of all episodes (n = 42), occurring a median of 122.5 days following transplant (IQR 59–211.8 days). Multidrug‐resistant organisms (MDROs) accounted for 73.8% of bacterial infections; extended spectrum beta‐lactamase producers, vancomycin‐resistant enterococcus, and highly‐resistant Pseudomonas aeruginosa were the most commonly identified. Increased mechanical ventilation and vasoactive requirements were noted in MDRO episodes (OR 3.03, 95% CI 1.09–8.46 and OR 3.07, 95% CI 1.09–8.61, respectively; p < .05) compared to non‐MDRO episodes. PICU length of stay was significantly increased for MDRO episodes (7 vs. 3 days, p = .02). Graft loss was 24.1% (n = 7) and mortality was 24.1% (n = 7) in patients who experienced severe sepsis. Further attention is needed for MDRO risk mitigation and modification of sepsis treatment guidelines to ensure MDRO coverage for this population.
In pediatric intestinal and multi‐visceral transplant recipients, MDROs account for a large majority of severe sepsis episodes related to bacterial infections and are associated with an increased need for mechanical ventilation, use of vasoactive medications, and length of intensive care unit stay.
Nonpharmaceutical interventions against coronavirus disease 2019 likely have a role in decreasing viral acute respiratory illnesses (ARIs). We aimed to assess the frequency of respiratory syncytial ...virus (RSV) and influenza ARIs before and during the coronavirus disease 2019 pandemic.
This study was a prospective, multicenter, population-based ARI surveillance, including children seen in the emergency departments and inpatient settings in 7 US cities for ARI. Respiratory samples were collected and evaluated by molecular testing. Generalized linear mixed-effects models were used to evaluate the association between community mitigation and number of eligible and proportion of RSV and influenza cases.
Overall, 45 759 children were eligible; 25 415 were enrolled and tested; 25% and 14% were RSV-positive and influenza-positive, respectively. In 2020, we noted a decrease in eligible and enrolled ARI subjects after community mitigation measures were introduced, with no RSV or influenza detection from April 5, 2020, to April 30, 2020. Compared with 2016-2019, there was an average of 10.6 fewer eligible ARI cases per week per site and 63.9% and 45.8% lower odds of patients testing positive for RSV and influenza, respectively, during the 2020 community mitigation period. In all sites except Seattle, the proportions of positive tests for RSV and influenza in the 2020 community mitigation period were lower than predicted.
Between March and April 2020, rapid declines in ARI cases and the proportions of RSV and influenza in children were consistently noted across 7 US cities, which could be attributable to community mitigation measures against severe acute respiratory syndrome coronavirus 2.
Congenital cytomegalovirus (CMV) infection is an important cause of hearing loss, and most infants at risk for CMV-associated hearing loss are not identified early in life because of failure to test ...for the infection. The standard assay for newborn CMV screening is rapid culture performed on saliva specimens obtained at birth, but this assay cannot be automated. Two alternatives--real-time polymerase-chain-reaction (PCR)-based testing of a liquid-saliva or dried-saliva specimen obtained at birth--have been developed.
In our prospective, multicenter screening study of newborns, we compared real-time PCR assays of liquid-saliva and dried-saliva specimens with rapid culture of saliva specimens obtained at birth.
A total of 177 of 34,989 infants (0.5%; 95% confidence interval CI, 0.4 to 0.6) were positive for CMV, according to at least one of the three methods. Of 17,662 newborns screened with the use of the liquid-saliva PCR assay, 17,569 were negative for CMV, and the remaining 85 infants (0.5%; 95% CI, 0.4 to 0.6) had positive results on both culture and PCR assay. The sensitivity and specificity of the liquid-saliva PCR assay were 100% (95% CI, 95.8 to 100) and 99.9% (95% CI, 99.9 to 100), respectively, and the positive and negative predictive values were 91.4% (95% CI, 83.8 to 96.2) and 100% (95% CI, 99.9 to 100), respectively. Of 17,327 newborns screened by means of the dried-saliva PCR assay, 74 were positive for CMV, whereas 76 (0.4%; 95% CI, 0.3 to 0.5) were found to be CMV-positive on rapid culture. Sensitivity and specificity of the dried-saliva PCR assay were 97.4% (95% CI, 90.8 to 99.7) and 99.9% (95% CI, 99.9 to 100), respectively. The positive and negative predictive values were 90.2% (95% CI, 81.7 to 95.7) and 99.9% (95% CI, 99.9 to 100), respectively.
Real-time PCR assays of both liquid- and dried-saliva specimens showed high sensitivity and specificity for detecting CMV infection and should be considered potential screening tools for CMV in newborns. (Funded by the National Institute on Deafness and Other Communication Disorders.).
The present AST‐IDCOP guidelines update information on strategies for safe living after organ transplantation. While transplantation carries an increased risk for infection from the recipient's ...environment due to lifelong immunosuppression, the goal is for the recipient to be able to return to their home and live as normal a life as possible with a functioning graft. The current guideline provides updates to prior recommendations including additions on infections from water and food sources, exposures to animals, cannabis use as well as sexual exposures or those encountered with travel. Similar to the prior editions, many of the recommendations are based on good infection prevention standards, extrapolation from other immunocompromised hosts, and risks found from cases series in transplant patients. Enhanced education and attention to incorporating safe living strategies into daily life should help to accomplish successful transplant with recipients achieving a fulfilling life away from the hospital.
Despite clinical and laboratory screening of potential donors for transmissible disease, unexpected transmission of disease from donor to recipient remains an inherent risk of organ transplantation. ...The Disease Transmission Advisory Committee (DTAC) was created to review and classify reports of potential disease transmission and use this information to inform national policy and improve patient safety. From January 1, 2008 to December 31, 2017, the DTAC received 2185 reports; 335 (15%) were classified as a proven/probable donor transmission event. Infections were transmitted most commonly (67%), followed by malignancies (29%), and other disease processes (6%). Forty‐six percent of recipients receiving organs from a donor that transmitted disease to at least 1 recipient developed a donor‐derived disease (DDD). Sixty‐seven percent of recipients developed symptoms of DDD within 30 days of transplantation, and all bacterial infections were recognized within 45 days. Graft loss or death occurred in about one third of recipients with DDD, with higher rates associated with malignancy transmission and parasitic and fungal diseases. Unexpected DDD was rare, occurring in 0.18% of all transplant recipients. These findings will help focus future efforts to recognize and prevent DDD.
A 10‐year review finds that unexpected donor‐derived disease, while uncommon, results in significant morbidity and mortality in affected recipients.
Saliva cytomegalovirus (CMV) polymerase chain reaction for newborn screening is highly sensitive. This study uses nationally published CMV seroprevalence and breastfeeding rates to demonstrate ...false-positive rates are unlikely to be significantly influenced by breastfeeding or other perinatal exposures.
Abstract
Real-time polymerase chain reaction (PCR) of saliva is highly sensitive for newborn congenital cytomegalovirus (CMV) screening. This study uses nationally published CMV seroprevalence and breastfeeding rates to estimate the contribution of CMV DNA in breast milk to false-positive saliva PCR results. The false-positive rates adjusted for breastfeeding ranged from 0.03% in white Hispanic persons to 0.14% in white non-Hispanic persons. Saliva CMV PCR for newborn screening is highly sensitive, and the low false-positive rates in this study suggest that saliva PCR results are unlikely to be significantly influenced by breastfeeding or other perinatal exposures.
The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over ...time.
We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear ("best-ear" hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline.
A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P=0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P=0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P=0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P=0.004) and on the receptive-communication scale (P=0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P=0.64).
Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).
Objective To determine the utility of dried blood spot (DBS) polymerase chain reaction (PCR) in identifying infants with cytomegalovirus (CMV) infection–associated sensorineural hearing loss (SNHL). ...Study design Newborns at 7 US hospitals between March 2007 and March 2012 were screened for CMV by saliva rapid culture and/or PCR. Infected infants were monitored for SNHL during the first 4 years of life to determine sensitivity, specificity, and positive and negative likelihood ratios of DBS PCR for identifying CMV-associated SNHL. Results DBS at birth was positive in 11 of 26 children (42%) with SNHL at age 4 years and in 72 of 270 children (27%) with normal hearing ( P = .11). The sensitivity (42.3%; 95% CI, 23.4%-63.1%) and specificity (73.3%; 95% CI, 67.6%-78.5%) was low for DBS PCR in identifying children with SNHL at age 4 years. The positive and negative likelihood ratios of DBS PCR positivity to detect CMV-associated SNHL at age 4 years were 1.6 (95% CI, 0.97-2.6) and 0.8 (95% CI, 0.6-1.1), respectively. There was no difference in DBS viral loads between children with SNHL and those without SNHL. Conclusions DBS PCR for CMV has low sensitivity and specificity for identifying infants with CMV-associated hearing loss. These findings, together with previous reports, demonstrate that DBS PCR does not identify either the majority of CMV-infected newborns or those with CMV-associated SNHL early in life.
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