Clinical manifestations, prognostic factors, and outcomes of adenovirus pneumonia after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Severe pneumonia is one of the most important causes of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adenovirus (ADV) is a significant cause of severe viral pneumonia after allo-HSCT, and we aimed to identify the clinical manifestations, prognostic factors, and outcomes of ADV pneumonia after allo-HSCT. METHODS: Twenty-nine patients who underwent allo-HSCT at the Peking University Institute of Hematology and who experienced ADV pneumonia after allo-HSCT were enrolled in this study. The Kaplan-Meier method was used to estimate the probability of overall survival (OS). Potential prognostic factors for 100-day OS after ADV pneumonia were evaluated through univariate and multivariate Cox regression analyses. RESULTS: The incidence rate of ADV pneumonia after allo-HSCT was approximately 0.71%. The median time from allo-HSCT to the occurrence of ADV pneumonia was 99 days (range 17-609 days). The most common clinical manifestations were fever (86.2%), cough (34.5%) and dyspnea (31.0%). The 100-day probabilities of ADV-related mortality and OS were 40.4% (95% CI 21.1%-59.7%) and 40.5% (95% CI 25.2%-64.9%), respectively. Patients with low-level ADV DNAemia had lower ADV-related mortality and better OS than did those with high-level (≥ 106 copies/ml in plasma) ADV DNAemia. According to the multivariate analysis, high-level ADV DNAemia was the only risk factor for intensive care unit admission, invasive mechanical ventilation, ADV-related mortality, and OS after ADV pneumonia. CONCLUSIONS: We first reported the prognostic factors and confirmed the poor outcomes of patients with ADV pneumonia after allo-HSCT. Patients with high-level ADV DNAemia should receive immediate and intensive therapy.

Hospital Outcomes Among Children With Congenital Heart Disease and Adenovirus Pneumonia.

BACKGROUND: The aim of the study is to evaluate the mortality risk factors and hospitalization outcomes of adenovirus pneumonia in pediatric patients with congenital heart disease. METHODS: In this retrospective multicenter cohort study utilizing the Pediatric Health Information System database, we analyzed congenital heart disease patients with adenovirus pneumonia from January 2004 to September 2018, categorizing them into shunts, obstructive lesions, cyanotic lesions and mixing lesions. Multivariate logistic regression analysis was employed to identify mortality risk factors with 2 distinct models to mitigate collinearity issues and the Mann-Whitney U test was used to compare the hospital length of stay between survivors and nonsurvivors across these variables. RESULTS: Among 381 patients with a mean age of 3.2 years (range: 0-4 years), we observed an overall mortality rate of 12.1%, with the highest mortality of 15.1% noted in patients with shunts. Model 1 identified independent factors associated with increased mortality, including age 0-30 days (OR: 8.13, 95% CI: 2.57-25.67, P < 0.005), sepsis/shock (OR: 3.34, 95% CI: 1.42-7.83, P = 0.006), acute kidney failure (OR: 4.25, 95% CI: 2.05-13.43, P = 0.0005), shunts (OR: 2.95, 95% CI: 1.14-7.67, P = 0.03) and cardiac catheterization (OR: 6.04, 95% CI: 1.46-24.94, P = 0.01), and Model 2, extracorporeal membrane oxygenation (OR: 3.26, 95% CI: 1.35-7.87, P = 0.008). Nonsurvivors had a median hospital stay of 47 days compared to 15 days for survivors. CONCLUSION: The study revealed a 12.1% mortality rate in adenoviral pneumonia among children with congenital heart disease, attributed to risk factors such as neonates, sepsis, acute kidney failure, shunts, cardiac catheterization, extracorporeal membrane oxygenation use and a 3-fold longer hospital stay for nonsurvivors compared to survivors.

What is the risk of a deadly adenovirus pandemic?

Many of us had refresher courses in virology, immunology, and epidemiology in 2020, and we were reminded of the fact that Homo sapiens, the wiliest predator on the planet, has been hunting everything that moves for millennia. These repeated interspecies contacts inherently lead to recurrent zoonosis (nonhuman to human) and anthroponosis (human to nonhuman). Given the accelerating changes in our ecosystems since the neolithic revolution, it was not surprising to see a virus that spreads via aerosolization and liquid droplets cause a pandemic in a few months. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic begs the question-which viruses could cause a global threat? In this Opinion, the characteristics that make adenoviruses a risk, which include efficient intra- and interspecies transmission, thermostable particles, persistent/latent infections in diverse hosts, and the ability to readily recombine and escape herd immunity, are discussed.

Fatal Neonatal Sepsis Associated with Human Adenovirus Type 56 Infection: Genomic Analysis of Three Recent Cases Detected in the United States.

BACKGROUND: Human adenovirus (HAdV)-D56 was first described in 2011 by genomics analysis of a strain isolated in France in 2008 from a fatal case of neonatal infection. Since then, it has been reported in cases of keratoconjunctivitis and male urethritis. Three epidemiologically unrelated fatal cases of neonatal sepsis associated with infection by HAdV-D strains with a similar genetic makeup were documented in the United States between 2014 and 2020. METHODS: Whole genome sequences were obtained for the isolated strains, and genomics analyses were conducted to compare them to phylogenetically related HAdV-D genomic sequences available in GenBank. RESULTS: The three new US strains were indistinguishable by in silico restriction enzyme analysis. Their genome sequences were 99.9% identical to one another and to the prototype strain isolated in 2008 from a similar context of disease. The phylogenetic reconstruction revealed a highly supported clustering of all HAdV-D56 strains isolated in various countries since 1982. Our comparison to serologically intermediate strains 15/H9 described in the literature indicated that HAdV-D56-like viruses have circulated worldwide since the late 1950s. CONCLUSION: As with other HAdV-D genotypes with the ability to infect ocular and genital mucosae, the risk of severe prenatal or perinatal HAdV-D56 infection must be considered.

Epidemiology of Adenovirus Infections and Outcomes of Cidofovir Treatment in Severely Ill Children.

BACKGROUND: An increase in human adenovirus (HAdV) infections among hospitalized children in Singapore was observed since 2013. Young age (<2 years) and significant comorbidities have been associated with severe HAdV infections which can result in significant morbidity and mortality. Cidofovir (CDV) has been used to treat severe HAdV infections despite limited data and efficacy. METHODS: This is a retrospective, observational review of infants and children 1 month to 17 years of age with laboratory-confirmed severe HAdV infection, admitted to a pediatric tertiary care hospital in Singapore between January 2013 and September 2017. Severe infection was defined as requiring intensive care unit or high dependency care at any point during hospital admission. Clinical characteristics, potential risk factors for mortality, as well as the outcome of cases treated with CDV were examined. RESULTS: A total of 1167 children were admitted for HAdV infection, of which 85 (7.3%) were severe. For severe infections, the median age was 1.5 years (interquartile range: 0.72-3.2 years). The majority had comorbidities (69.4%) and presented with pneumonia (32.9%). Genotypes HAdV-7 (29.4%) and HAdV-3 (27.0%) were the most common HAdV genotypes identified. Thirteen (15.3%) patients died. Patients who died had a higher proportion of existing neurologic comorbidity (46.2% vs. 13.9%; P = 0.014) and presentation with pneumonia (69.2% vs. 26.4%; P = 0.008) compared with survivors. Patients who presented with pneumonia had a higher risk of 30-day mortality (odds ratio 4.3, 95% confidence interval: 1.0-28.6; P < 0.05). CDV was administered to 17 (20%) children for mainly viremia (47.1%) and/or pneumonia (41.2%). Mortality rate was 41.2% for severe HAdV cases treated with CDV. A significant proportion of patients who died when compared with recovered patients presented with pneumonia (6 of 7, 85.7% vs 1 of 10, 10%; P = 0.004). All 8 patients who had viremia received CDV and survived. CONCLUSIONS: Mortality can be high in pediatric patients with severe HAdV infections. HAdV-7 and HAdV-3 were the most common genotypes identified in our cohort with severe HAdV infection. Pneumonia is a potential risk factor for mortality in severe HAdV infections in our cohort. Early CDV administration may be considered in patients with severe HAdV infection and existing comorbidities but more studies are required.

Clinical manifestations and risk factors of adenovirus respiratory infection in hospitalized children in Guangzhou, China during the 2011-2014 period.

To evaluate epidemiology and risk factors of severe adenovirus respiratory infection in hospitalized children in Guangzhou, China.A retrospective review study was conducted, and 542 children hospitalized for adenovirus respiratory infection, were included from January 2011 to December 2014. Patients were younger than 14 years. Disease severity was classified into severe and mild. Laboratory tests and clinical characteristics were analyzed for risk factors of adenovirus respiratory infection by multivariable logistic regression.Among these 542 children, 92.1% were aged < 6 years. Clinical diagnoses were upper respiratory infections in 11.6%, bronchiolitis in 16%, and mild pneumonia in 62.0% of children. Severe pneumonia rate was 10.3% (56/542) with a mortality rate of 0.9% (5/542). The cohort comprised 542 patients; 486 patients with mild adenovirus respiratory infection and 56 patients with severe adenovirus respiratory infection. Multivariable logistic regression was used to confirm associations between variables and adenovirus respiratory infection, after age and gender adjustment. Hospital stay, still significantly associated with adenovirus respiratory infection. Patients with longer hospital stay (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.13-1.28, P < .001), lower LYMPH (OR = 0.73 95% CI: 0.55-0.99, P = .039), and increased LDH (OR = 1.002, 95% CI: 1.001-1.003, P =  .001) had a higher risk of severe adenovirus respiratory infection.Adenovirus is a major pathogen in hospitalized children with respiratory infection. High serum LDH level and low lymphocyte count could be used as predictors of adenovirus respiratory infection severity in children.

Adenovirus Hepatitis: Clinicopathologic Analysis of 12 Consecutive Cases From a Single Institution.

Adenoviruses are common pathogens that usually cause self-limited infections. However, in the immunocompromised host they can cause severe infections involving multiple organs including the liver. A search of the pathology database at Stanford University Medical Center (1995 to 2016) identified 12 cases of adenovirus hepatitis including biopsy and autopsy specimens. There were 8 pediatric patients, 7 of which had received orthotropic liver transplants and 1 of which was receiving chemotherapy for lymphoblastic leukemia. There were 4 adult patients, of which 1 was actively receiving chemotherapy for chronic lymphocytic leukemia and 2 had undergone hematopoietic stem cell transplantation for hematologic malignancies. One patient had lymphoplasmacytic lymphoma and had received chemotherapy over a year prior but was not receiving therapy at the time he contracted adenovirus hepatitis. In all cases, histologic sections showed nonzonal coagulative hepatocyte necrosis and characteristic intranuclear inclusions. Hepatocyte necrosis ranged from spotty to massive. The majority of cases (7/12; 58%) had no associated inflammation. If present, inflammation was focal and lymphohistiocytic. In 1 case, findings were focal within the liver, requiring an image-guided biopsy. This patient underwent a simultaneous nontargeted liver biopsy that lacked histologic evidence of adenovirus. Among the pediatric patients, 63% (5/8) died secondary to organ failure, while there was 100% (4/4) mortality in the adult population.

Fatal Community-acquired Pneumonia in Children Caused by Re-emergent Human Adenovirus 7d Associated with Higher Severity of Illness and Fatality Rate.

Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), such as community-acquired pneumonia. HAdV-7d, a re-emergent genomic variant, has been recently reported in Asia and the United States after a several-decade absence. However, whether HAdV-7d is associated with higher severity than other types is currently unclear. In this study, the clinical and epidemiological investigation showed that fever, cough, and sore throat were the three most common respiratory symptoms of HAdV infections. HAdV-7 caused longer duration of fever, higher morbidity of tachypnea/dyspnea, pleural effusion, diarrhea, hepatosplenomegaly, consciousness alteration, as well as higher rates of pneumonia, mechanical ventilation and higher fatality rate (28.6%) than other types, particularly HAdV-3 and HAdV-2. The genomes of seven HAdV-7d isolates from mild, severe, and fatal cases were sequenced and highly similar with each other. Surprisingly, two isolates (2011, 2012) had 100% identical genomes with an earlier strain from a fatal ARD outbreak in China (2009), which elucidates the virus origin and confirms the unexpected HAdV genomic conservation and stability. Phylogenetic analysis indicated that L1 52/55-kDa DNA packaging protein may be associated with the higher severity of illness and fatality rate of HAdV-7. Clinicians need to be aware of HAdVs in children with ARD.

Type-specific clinical characteristics of adenovirus-associated influenza-like illness at five US military medical centers, 2009-2014.

BACKGROUND: Adenovirus is a recognized cause of influenza-like illness (ILI). The proportion of ILI attributable to adenovirus is not known. Moreover, knowledge gaps remain with respect to the epidemiologic, virologic, and clinical characteristics of adenovirus-associated ILI among otherwise healthy individuals. METHODS: An observational, longitudinal study of <65-year-old patients with febrile ILI at five medical centers was conducted from 2009 to 2014. Nasopharyngeal specimens obtained at enrollment were first tested by single-reaction PCR for adenovirus, then further evaluated by a multiplex PCR assay for other respiratory viral pathogens. Symptoms over a 28-day period were collected. RESULTS: We enrolled 1536 individuals, among whom 43 (2·8%) were positive for adenovirus. The median age of cases was 3·4 years (range: 4 months to 41 years). Three were hospitalized. Species and serotype information was available for 33 (76·7%) cases. Species C (n = 21) was the most common, followed by B3 (n = 9) and one each of E4a, D46, and A. Species C infections were more frequent in children (P < 0·01). Half of the cases were positive for at least one other respiratory viral pathogen. Symptoms were generally mild and most commonly included cough (90%), fatigue (79%), rhinorrhea (74%), loss of appetite (71%), and sore throat (64%). Children with non-C adenovirus infection were more likely to report sore throat (P = 0·05) and hoarseness (P = 0·06) than those with species C infection. CONCLUSIONS: Adenovirus is frequently detected with other respiratory viruses. Persons with non-C adenovirus infections reported more severe symptoms, suggesting there may be species-specific differences in virulence and/or host response to infection.

Detection of Multiple Respiratory Viruses Associated With Mortality and Severity of Illness in Children.

OBJECTIVE: Respiratory viral infection is a common source of morbidity and mortality in children. Coinfection with multiple viruses occurs frequently; however, the clinical significance of concomitant viral pathogens is unclear. We hypothesized that presence of more than one respiratory virus is associated with increased morbidity and mortality when compared with children with a single respiratory virus. DESIGN: Retrospective cohort study. SETTING: A tertiary care hospital. PATIENTS: All children at Duke Children's Hospital over a 2-year period with isolation of a virus on an extended viral respiratory panel result. Demographic data, comorbidities, and details of hospital encounter were recorded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred thirty-five hospital encounters demonstrated positive extended viral respiratory panels. Immunocompromised status (37%) and respiratory comorbidities (23%) were common. Twenty-eight patients (12%) tested positive for multiple viruses, with adenovirus (23/28) and respiratory syncytial virus (15/28) most prevalent in patients with multiple viruses. Viral codetection was associated with increased use of noninvasive ventilation (p = 0.02), extracorporeal membrane oxygenation (p = 0.02), increased likelihood of moderate or severe illness (p = 0.005), and increased mortality (p = 0.01). Subgroup analysis demonstrated that this mortality association persisted for children with normal immune function (p = 0.003) and children with no comorbidities (p = 0.007). CONCLUSIONS: Children with multiple respiratory viruses may be at increased risk of moderate or severe illness and mortality, with previously healthy children potentially being at greatest risk. Further studies are indicated to determine the significance and generalizability of this finding and to better understand the pathophysiology of viral coinfection.

Pharmacokinetics and safety of intravenous cidofovir for life-threatening viral infections in pediatric hematopoietic stem cell transplant recipients.

Children undergoing hematopoietic stem cell transplantation (HSCT) are at risk for life-threatening viral infections. Cidofovir is often used as a first-line agent for adenovirus infections, despite the absence of randomized controlled trials with HSCT patients, and as a second-line agent for resistant herpesvirus infections. The frequency and severity of adverse effects, particularly nephrotoxicity, in pediatric HSCT recipients are unclear, and pharmacokinetics (PK) of cidofovir in children have not previously been reported. This study was an open-label, nonrandomized, single-dose pilot study to determine the safety and PK of cidofovir in pediatric HSCT recipients with symptomatic adenovirus, nucleoside-resistant cytomegalovirus (CMV) or herpes simplex virus (HSV), and/or human papovavirus infections. Subsequent dosing and frequency were determined by clinical response and side effects, as assessed by the treating physician. Blood and urine samples were obtained from patients for PK studies and assessment of toxicity and virologic response. Twelve patients were enrolled (median age, 9 years; 33.5 days posttransplantation). Four of seven patients with adenovirus infection were successfully treated and eventually cleared their infections. Four of twelve patients died of disseminated viral disease and multiorgan failure. Two of twelve patients had evidence of acute kidney injury after the first dose, and one of these patients developed chronic kidney disease; two other patients developed late nephrotoxicity. The mean drug half-life was 9.5 h. There was no correlation between nephrotoxicity and plasma maximum concentration, clearance, or half-life. PK were similar to those reported for adults, although the drug half-life was significantly longer than that for adults. Cidofovir was well tolerated in the majority of patients. However, effective therapeutic strategies are urgently needed to support patients until immune reconstitution is achieved.

Mesenchymal stromal cell therapy is associated with increased adenovirus-associated but not cytomegalovirus-associated mortality in children with severe acute graft-versus-host disease.

Beneficial effects of mesenchymal stromal cells (MSCs) in patients with severe steroid-refractory acute graft-versus-host disease (aGvHD) have been reported. However, controversy exists about the effect of MSCs on virus-specific T cells. We evaluated 56 patients with grade II-IV aGvHD who responded to steroids (n = 21) or were steroid refractory receiving either MSCs (n = 22) or other second-line therapy (n = 13). Although the overall incidence of cytomegalovirus (CMV), Epstein-Barr virus, and human adenovirus (HAdV) infections was not significantly increased, HAdV infection was associated with decreased survival in children treated with MSCs. Thus, we investigated in vitro the effects of MSCs on virus-specific T cells. Both CMV-specific and, to a lesser extent, HAdV-specific T-cell activation and proliferation were negatively affected by MSCs either after induction of a response in peripheral blood mononuclear cells (PBMCs) or after restimulation of virus-specific T-cell lines. In patient-derived PBMCs, CMV-specific proliferative responses were greatly decreased on first-line treatment of aGvHD with systemic steroids and slowly recovered after MSC administration and tapering of steroids. HAdV-specific T-cell proliferation could not be detected. In contrast, the proportion of CMV- and HAdV-specific effector T cells, measured as interferon-γ-secreting cells, remained stable or increased after treatment with MSCs. In conclusion, although in vitro experimental conditions indicated a negative impact of MSCs on CMV- and HAdV-specific T-cell responses, no solid evidence was obtained to support such an effect of MSCs on T-cell responses in vivo. Still, the susceptibility of steroid-refractory severe aGvHD patients to viral reactivation warrants critical viral monitoring during randomized controlled trials on second-line treatment including MSCs.

Viral epidemiology of respiratory infections among children at a tertiary hospital in Southern Brazil.

INTRODUCTION: This study reports the pediatric epidemiology of respiratory syncytial virus (RSV), influenza (IF), parainfluenza (PIV), and adenovirus (ADV) at Hospital de Clínicas de Porto Alegre. METHODS: Cases of infection, hospitalizations in intensive care units (ICUs), nosocomial infections, and lethality rates were collected from 2007 to 2010. RESULTS: RSV accounted for most nosocomial infections. Intensive care units admission rates for ADV and RSV infections were highest in 2007 and 2010. During 2008-2009, H1N1 and ADV had the highest ICU admission rates. ADV had the highest fatality rate during 2007-2009. CONCLUSIONS: Each virus exhibited distinct behavior, causing hospitalization, outbreaks, or lethality.

Extracorporeal membrane oxygenation support among children with adenovirus infection: a review of the Extracorporeal Life Support Organization registry.

Overwhelming adenovirus infection requiring extracorporeal membrane oxygenation (ECMO) support carries a high mortality in pediatric patients. The objective of this study was to retrospectively review data from the Extracorporeal Life Support Organization (ELSO) registry for pediatric patients with adenovirus infection and define for this patient cohort: 1) clinical characteristics, 2) survival to hospital discharge, and 3) factors associated with mortality before hospital discharge. In this retrospective registry study, pediatric patients with adenovirus infection requiring ECMO support identified in an international ECMO registry from 1998 to 2009 were compared for clinical characteristics (demographics, pre-ECMO variables, and complications on ECMO) between survivors and nonsurvivors to hospital discharge. Descriptive statistics and univariate and multivariate logistic analysis were used to compare clinical characteristics among survivors and nonsurvivors. For children requiring ECMO support for adenovirus, the survival at hospital discharge is 38% (62/163). Among neonates (<31 days of age), the survival at hospital discharge was only 11% (6/54). Among patient factors, neonatal age (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.62-10.87), a decrease of 0.1 unit in pre-ECMO pH (OR, 1.77; 95% CI, 1.3-2.42), the presence of sepsis (OR, 4.55; 95% CI, 1.47-14.15), and increased peak inspiratory pressures (OR, 1.04; 95% CI, 1.01-1.08) were all independently associated with in-hospital mortality. ECMO complications independently associated with in-hospital mortality were presence of pneumothorax (OR, 3.57; 95% CI, 1.19-10.7), pH less than 7.2 (OR, 5.94; 95% CI, 1.04-34.1), and central nervous system hemorrhage (OR, 25.36; 95% CI, 1.47-436.7). In this retrospective cohort study of pediatric patients with adenovirus infection supported on ECMO, survival to hospital discharge was 38% but was much lower in neonates. Neonatal presentation, degree of acidosis, sepsis, and increased PIP are factors present before decisions are made regarding a trial of ECMO, whereas pneumothorax and brain hemorrhage were ECMO-related complications independently associated with mortality.

Challenges to evaluating respiratory syncytial virus mortality in Bangladesh, 2004-2008.

BACKGROUND: Acute lower respiratory illness is the most common cause of death among children, globally. Data are not available to make accurate estimates on the global mortality from respiratory syncytial virus (RSV), specifically. METHODS: Respiratory samples collected from children under 5 years of age during 2004 to 2008 as part of population-based respiratory disease surveillance in an urban community in Dhaka, Bangladesh were tested for RSV, human metapneumovirus (HMPV), human parainfluenza virus (PIV) types 1, 2, and 3, influenza and adenovirus by RT-PCR. Verbal autopsy data were used to identify children who died from respiratory illness in a nearby rural community. Significance of the correlation between detections and community respiratory deaths was determined using Spearman's coefficient. RESULTS: RSV activity occurred during defined periods lasting approximately three months but with no clear seasonal pattern. There was no significant correlation between respiratory deaths and detection of any of the respiratory viruses studied. CONCLUSION: Outbreaks of respiratory viruses may not be associated with deaths in children in the study site; however, the few respiratory deaths observed and community-to-community variation in the timing of outbreaks may have obscured an association. An accurate assessment of respiratory virus-associated deaths will require detections and death data to come from the same location and a larger study population.

The impact of RSV, adenovirus, influenza, and parainfluenza infection in pediatric patients receiving stem cell transplant, solid organ transplant, or cancer chemotherapy.

RVIs are a significant cause of morbidity and mortality in immunocompromised children. We analyzed the characteristics and outcomes of infection by four respiratory viruses (RSV, adenovirus, influenza, and parainfluenza) treated at a pediatric tertiary care hospital in a retrospective cohort of patients who had received cancer chemotherapy, hematopoietic stem cell, or SOT. A total of 208 infections were studied among 166 unique patients over a time period of 1993-2006 for transplant recipients, and 2000-2005 for patients with cancer. RSV was the most common respiratory virus identified. There were 17 (10% of all patients) deaths overall, of which 12 were at least partly attributed to the presence of a RVI. In multivariate models, LRT symptoms in the absence of upper respiratory symptoms on presentation (OR 10.2 [2.3, 45.7], p = 0.002) and adenoviral infection (OR 3.7 [1.1, 12.6], p = 0.034) were significantly associated with poor outcome, defined as death or disability related to RVI. All of the deaths occurred in patients who had received either solid organ or HSCT. There were no infections resulting in death or disability in the cancer chemotherapy group.

Adenovirus-associated deaths in US military during postvaccination period, 1999-2010.

Adenoviruses are frequent causes of respiratory disease in the US military population. A successful immunization program against adenovirus types 4 and 7 was terminated in 1999. Review of records in the Mortality Surveillance Division, Armed Forces Medical Examiner System, identified 8 deaths attributed to adenovirus infections in service members during 1999-2010.

Deaths associated with human adenovirus-14p1 infections, Europe, 2009-2010.

Human adenovirus (HAdV) serotype 14 is rarely identified. However, an emerging variant, termed HAdV-14p1, recently has been described in the United States in association with outbreaks of acute respiratory disease with high rates of illness and death. We retrospectively analyzed specimens confirmed positive for HAdV by immunofluorescence, virus culture, or real-time PCR during July 1, 2009-July 31, 2010, and describe 9 cases of HAdV-14p1 infection with characteristic mutations in the fiber and E1A genes that are phylogenetically indistinguishable from the viruses previously detected in the United States. Three patients died; 2 were immunocompromised, and 1 was an immunocompetent adult. We propose that surveillance should be increased for HAdV-14p1 and recommend that this virus be considered in the differential diagnosis of sudden-onset acute respiratory disease, particularly fatal infections, for which an etiology is not clear.

High lethality of human adenovirus disease in adult allogeneic stem cell transplant recipients with high adenoviral blood load.

BACKGROUND: Human adenoviruses (HAdV) can cause disseminated disease as a severe complication after haematopoietic stem cell transplantation (SCT) and may originate from the reactivation of latent infections. However, data about the clinical relevance of HAdV DNAaemia and disease in adults are scarce. OBJECTIVES: To retrospectively analyse the outcome of adult allogeneic SCT recipients with high HAdV loads in peripheral blood. STUDY DESIGN: Our diagnostic database was screened for allogeneic SCT recipients with peak HAdV DNAaemia above 1.0×10(4)copies/ml (tested by quantitative real-time PCR) and medical records were reviewed retrospectively. RESULTS: From 1674 adult allogeneic SCT recipients 539 (32.2%) received HAdV DNAaemia testing. In twenty-seven of these HAdV blood loads above 1.0×10(4) (range: 1.6×10(4)-1.8×10(9))copies/ml were observed. Seven of these 27 succumbed to HAdV disease and their median peak HAdV DNAaemia was significantly higher than in patients without HAdV-associated death (1.0×10(8) vs. 3×10(5)copies/ml, p<0.001). T-cell depletion was a risk factor for fatal HAdV disease. HAdV of species C predominated (66.7%) and were of high virulence (6 of 7 fatal cases). HAdV of species B were observed more frequently (n=6) in our study than reported for paediatrics, indicating a different pattern of HAdV reactivation in adults. CONCLUSIONS: The presence of several HAdV-associated deaths in adult SCT recipients with high-level HAdV DNAaemia confirmed the clinical relevance of HAdV DNAaemia testing in adults. Quantitative HAdV DNAaemia testing is a promising tool to predict the outcome of HAdV disease.