Lower respiratory infections by adenovirus in children. Clinical features and risk factors for bronchiolitis obliterans and mortality.
Murtagh Patricia,Giubergia Verónica,Viale Diana,Bauer Gabriela,Pena Hebe Gonzalez
UNLABELLED:Adenovirus (Ad) respiratory infections have a profound impact in Argentina. Severe chronic disease and a high mortality rate are observed in children after acute lower respiratory infections (ALRI) by Ad. METHODS:A retrospective observational study was performed to describe clinical characteristics and to analyze risk factors for bronchiolitis obliterans (BO) and death in 415 children hospitalized with ALRI caused by Ad from March 1988 to May 2005. RESULTS:Mean age of patients was 10.7 months (+/-9.2) Overall 80% of patients were healthy before ALRI. Forty-nine percent recovered, sequelae were observed in 36% and 15% died. Independent risk factors for BO were: >30 days of hospitalization (odds ratio (OR) 27.2, 95% confidence interval (CI) 14.6-50.9), multifocal pneumonia (OR 26.6, 95% CI 5.3-132) and hypercapnia (OR 5.6, 95% CI 3.5-9). Independent risk factors for death in acute stage of disease were: mechanical assistance (OR 121, 95% CI 18.2-814), multifocal pneumonia (OR 102, 95% CI 9.5-31.1), hypercapnia (OR 42.6, 95% CI 10.2-177.1), coagulation disorders (OR 17, 95% CI 8.25-35), neurological symptoms (OR 12.7, 95% CI 3.5-6.6) and co-infection with measles (OR 9.6, 95% CI 2.1-44.2). CONCLUSIONS:High incidence of sequelae and mortality in previously healthy children after Ad infection was observed in a population of children from Argentina.
Respiratory adenoviral infections in Taiwanese children: a hospital-based study.
Hsieh Wang-Ying,Chiu Nan-Chang,Chi Hsin,Huang Fu-Yuan,Hung Chia-Chien
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi
BACKGROUND AND PURPOSE:Adenoviruses are a common etiology of respiratory tract infections in children, with several serotypes responsible for most epidemic respiratory infections. This study examined the molecular epidemiology and clinical features of pediatric adenoviral infections in a 1-year period. METHODS:From May 1999 to April 2000, virus specimens collected from children with respiratory tract infections were identified. The presence of adenovirus was confirmed by direct fluorescent staining, and viral types were determined by polymerase chain reaction sequencing. RESULTS:Adenoviruses were identified from 272 children (mean +/- standard deviation age, 48.3 +/- 30.5 months), 227 (83.5%) of whom were aged 6 years or younger. Inpatients were younger than outpatients (44.1 +/- 30.7 months vs 53.0 +/- 29.4 months; p = 0.006). The commonest serotype identified was serotype 3 (164 patients; 60.3%), 73.1% of which were identified between September 1999 and January 2000. Serotype 3 was more common in inpatients (p = 0.015), while serotypes 1, 2, 5, and 6 were more common in outpatients (p = 0.021). Patients with pneumonia were younger than those with other infections (31.8 +/- 20.2 months vs 50.3 +/- 31.0 months; p = 0.001). Most of the children (90.1%) had fever for a mean of 3.80 +/- 2.65 days before seeing a doctor. The clinical manifestations were similar regardless of the serotype. CONCLUSIONS:Adenovirus serotype 3 caused the most adenovirus infections in autumn and winter of 1999 to 2000. The children were mostly preschool age and required hospital admission.
Underlying Diseases and Causative Microorganisms of Recurrent Pneumonia in Children: A 13-Year Study in a University Hospital.
Tural-Kara Tuğçe,Özdemir Halil,Yıldız Nihan,Aldemir Kocabaş Bilge,Erat Tuğba,Yahşi Aysun,Doğu Figen,Tutar Ercan,İnce Erdal,Çiftçi Ergin
Journal of tropical pediatrics
Pneumonia is a significant cause of death for children, particularly those in developing countries. The records of children who were hospitalized because of pneumonia between January 2003 and December 2015 were retrospectively reviewed, and patients who met the recurrent pneumonia criteria were included in this study. During this 13-year period, 1395 patients were hospitalized with pneumonia; of these, 129 (9.2%) met the criteria for recurrent pneumonia. Underlying diseases were detected in 95 (73.6%) patients, with aspiration syndrome (21.7%) being the most common. Rhinovirus (30.5%), adenovirus (17.2%) and respiratory syncytial virus (13.9%) were the most frequent infectious agents. These results demonstrate that underlying diseases can cause recurrent pneumonia in children. Viruses are also commonly seen in recurrent pneumonia. Appropriate treatments should be chosen based on an analysis of the underlying disease, the patient's clinical condition and the laboratory and radiological data.
Lung Microbiota and Pulmonary Inflammatory Cytokines Expression Vary in Children With Tracheomalacia and Adenoviral or Pneumonia.
Wang Heping,Zhou Qian,Dai Wenkui,Feng Xin,Lu Zhiwei,Yang Zhenyu,Liu Yanhong,Xie Gan,Yang Yonghong,Shen Kunling,Li Yinhu,Li Shuai Cheng,Xu Ximing,Shen Yongshun,Li Dongfang,Zheng Yuejie
Frontiers in pediatrics
Community-acquired pneumonia (CAP) is a worldwide infectious disease caused by bacteria, viruses, or a combination of these infectious agents. is an atypical pneumonia pathogen that causes high morbidity and mortality in children, and adenovirus can lead to severe pneumonia. However, the etiology of different types of pneumonia is still unclear. In this study, we selected a total of 52 inpatients with pneumonia (MPP) ( = 21), adenovirus pneumonia (AVP) ( = 16), or tracheomalacia ( = 15) to serve as a disease control. Bronchoalveolar lavage fluid (BALF) samples that had been obtained for clinical use were analyzed. We compared the differences in microbiota and the expression of 10 inflammatory cytokines in samples between MPP, AVP, and tracheomalacia. We found that the bacterial diversity in MPP was lower than that in AVP and tracheomalacia. , and were predominant in samples of MPP, AVP, and tracheomalacia, respectively. The expression levels of IL-6, IL-8, and IL-10 were significantly higher in inpatients with AVP compared to children hospitalized with tracheomalacia or MPP. The lung microbiota in MPP was remarkably correlated with IL-2, IL-4, IL-5, IL-6, TNF-α, and IL-1α expressions, while this was not found in tracheomalacia and AVP. Microbiota analysis identified a high load of multi-drug resistant in the lung microbiota of several inpatients, which might be associated with the long hospitalization length and intra-group differences at the individual level. This study will help to understand the microbial etiology of tracheomalacia, AVP, and MPP and to identify effective therapies for these diseases.
Clinical features, adenovirus types, and local production of inflammatory mediators in adenovirus infections.
Moro Maria R,Bonville Cynthia A,Suryadevara Manika,Cummings Erin,Faddoul Diala,Kobayaa Hazar,Branigan Patrick J,Domachowske Joseph B
The Pediatric infectious disease journal
BACKGROUND:Adenovirus infection manifests in many ways, with respiratory and gastrointestinal symptoms predominating. METHODS:We performed a retrospective chart review on children evaluated at our center who had a nasal wash culture positive for adenovirus. Archived nasal washes were retrieved. Polymerase chain reaction for 15 respiratory viruses was performed on these samples. Patients who were coinfected with another virus were excluded. Adenovirus typing was performed using polymerase chain reaction primers directed at the conserved hexon gene. Bead proteomics was used to measure concentrations of inflammatory mediators. RESULTS:Seventy-eight patients were infected only with adenovirus. The clinical diagnosis was upper respiratory infection in 60%, pneumonia in 18%, febrile seizure in 8%, and bronchiolitis in 6%. Subgroup-C and B1 infections were most common. Seventy percent of patients with upper respiratory infection and all 5 patients with bronchiolitis had a subgroup-C infection; pneumonia was caused by subgroup-B1 and C viruses. Compared with asymptomatic control patients, adenovirus infected patients had higher nasal wash concentrations of interleukin (IL)-1alpha, IL-6, inducible protein-10, macrophage inflammatory protein-1alpha, tumor necrosis factor alpha, monokine induced by gamma interferon, and interferon-alpha (P < 0.05). In addition, we found that IL-8 and IL-1alpha (P < 0.05) were higher in the nasal washes obtained from hospitalized patients than in nonhospitalized patients. CONCLUSIONS:Adenovirus infection causes an array of clinical disease and is associated with local production of several proinflammatory cytokines. The observation that nasal wash IL-8 and IL-1alpha concentrations were higher in patients requiring hospitalization suggests that these mediators contribute to disease severity.
Epidemiology of human adenovirus infection in children hospitalized with lower respiratory tract infections in Hunan, China.
Xie Leyun,Zhang Bing,Xiao Niguang,Zhang Fei,Zhao Xin,Liu Qin,Xie Zhiping,Gao Hanchun,Duan Zhaojun,Zhong Lili
Journal of medical virology
To investigate the current genotypes of circulating human adenovirus (HAdV) strains, we molecularly genotyped HAdV in the nasopharyngeal aspirates (NPAs) of patients with acute lower respiratory tract infections (ALRTIs) and attempted to determine their associations with clinical symptoms. A total of 4751 NPA samples were collected from 4751 patients admitted to Hunan Provincial People's Hospital from September 2007 to March 2014, of which 447 (9.4%) samples were HAdV positive. Fourteen different HAdV types were identified; HAdV types 1 to 7 (HAdV 1-7) were identified in 95.7% of the 447 NPA samples with HAdV-7 and HAdV-3 being the most prevalent. In addition, 93.3% (417 of 447) of patients were younger than 5 years. The incidence of HAdV infection peaked in summer. Different HAdV types showed a predilection for different age groups and different seasonal distribution patterns. Coinfection of HAdVs and other respiratory viruses was detected in 63.3% (283 of 447) of the HAdV-positive samples. The most common clinical diagnosis was pneumonia and the most common symptoms were fever and cough. In comparison with children infected with HAdV-3 alone, those infected with HAdV-7 alone had an increased frequency of severe pneumonia involvement (11.6% vs 32.4%; P = 0.031), higher intensive care unit admission rates (7.0% vs 26.5%; P = 0.019), and a longer length of hospital stay (P = 0.03). Mixed infections in younger children were associated with a longer hospital stay (P = 0.023). Our results demonstrate the recent changes in the trends of circulating HAdV genotypes associated with ALRTIs in Hunan China.
Human lung innate immune cytokine response to adenovirus type 7.
Wu Wenxin,Booth J Leland,Duggan Elizabeth S,Patel Krupa B,Coggeshall K Mark,Metcalf Jordan P
The Journal of general virology
Adenovirus (Ad) type 7 can cause severe infection, including pneumonia, in military recruits and children. The initial inflammation is a neutrophilic interstitial infiltration with neutrophilic alveolitis. Subsequently, monocytes become evident and, finally, there is a predominantly lymphocytic infiltrate. We have established that Ad7 infection of epithelial cells stimulates release of the neutrophil chemotaxin interleukin (IL)-8, and have extended these studies to a human lung tissue model. Here, we studied cytokine responses to Ad7 in human alveolar macrophages (HAM) and our human lung tissue model. Both ELISA and RNase-protection assay (RPA) data demonstrated that, upon Ad7 infection, IP-10 and MIP-1alpha/beta are released from HAM. IP-10 and MIP-1alpha/beta protein levels were induced 2- and 3-fold, respectively, in HAM 24 h after Ad7 infection. We then investigated induction of specific cytokines in human lung tissue by RPA and ELISA. The results showed that IL-8 and IL-6 were induced 8 h after infection and, by 24 h, levels of IL-8, IL-6, MIP-1alpha/beta and MCP-1 were all increased. IP-10, a monocyte and lymphocyte chemokine, was also induced 30-fold, but only 24 h after infection. Immunohistochemistry staining confirmed that IL-8 was only released from the epithelial cells of lung slices and not from macrophages. IP-10 was secreted from both macrophages and epithelial cells. Moreover, full induction of IP-10 is likely to require participation and cooperation of both epithelial cells and macrophages in intact lung. Understanding the cytokine and chemokine induction during Ad7 infection may lead to novel ways to modulate the response to this pathogen.
Correlation of viral load of respiratory pathogens and co-infections with disease severity in children hospitalized for lower respiratory tract infection.
Franz Anna,Adams Ortwin,Willems Rhea,Bonzel Linda,Neuhausen Nicole,Schweizer-Krantz Susanne,Ruggeberg Jens U,Willers Reinhart,Henrich Birgit,Schroten Horst,Tenenbaum Tobias
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
BACKGROUND:The clinical significance of viral load and co-infections in children with respiratory infections is not clear. OBJECTIVE:To evaluate the correlation of viral load as well as viral and bacterial co-infections with disease severity in hospitalized children with lower respiratory tract infections (LRTIs). STUDY DESIGN:This is a prospective study conducted in children admitted for LRTIs for two seasons. To determine viral and bacterial load of respiratory pathogens we performed multiplex real-time polymerase chain reaction and semiquantitative bacterial cultures on nasopharyngeal aspirates (NPA). RESULTS:During the study period 244 (60%) children were hospitalized for LRTI with acute virus-induced wheezing and 160 (40%) for radiologic confirmed pneumonia. In the first NPA, viruses were identified in 315 (78%) of the 404 samples and bacteria in 198 (63.3%) of 311 samples. The viral load significantly decreased between the first and second NPA sample in most single and viral co-infections, except rhinovirus and human bocavirus infections. Viral load was inversely related to CRP in RSV infections, whereas a positive correlation was observed in adenovirus infections. Duration of hospitalization was significantly longer in RSV single infections compared to rhinovirus single infections whereas in the latter, leucocytosis and use of systemic steroids was more common. In RSV viral co-infections the presence of fever, leucocytosis, and the use of antibiotics was significantly more frequent. Positive cultures of Haemophilus influenzae dominated in RSV and rhinovirus single infections and Moraxella catarrhalis in RSV viral co-infections. CONCLUSIONS:Specific viral single and co-infections as well as viral load contribute to disease severity in children with LRTIs.
Risk Factors for Severe Adenovirus Infection in Children during an Outbreak in Singapore.
Rajkumar Veena,Chiang Cheryl S M,Low Jia Meng,Cui Lin,Lin Raymond T P,Tee Nancy W S,Maiwald Matthias,Chong Chia Yin,Thoon Koh Cheng,Tan Natalie W H
Annals of the Academy of Medicine, Singapore
BACKGROUND:Human adenoviruses (HAdVs) can cause a variety of human illnesses, with associated temporal and geographic changes in disease incidence. We report the emergence of an outbreak of HAdV infections in Singapore, presumably caused by a change of the predominating type to HAdV-7. We examined the clinical features of children admitted with HAdV infection to 1 institution and the risk factors for severe infection. MATERIALS AND METHODS:This is a retrospective case-control study of all HAdV-infected children admitted during weeks 1 to 19 in 2013, as identified from laboratory records. A descriptive retrospective analysis of epidemiology, clinical data and the outcome of these children was also performed. Patients with severe infections were defined as cases, those with non-severe infections as controls, and the 2 groups were compared to find possible independent risk factors. RESULTS:Eighty-five patients with HAdV infection were studied, including 11 (12.9%) cases and 74 (87.1%) controls. Binary logistic regression showed that cases were more likely to be <2 years old (adjusted OR 10.6, 95% CI, 1.8 to 63.2) and to have significant comorbidities (adjusted OR 19.9, 95% CI, 3.4 to 116.1) compared to controls. The predominant type in 2013 was HAdV-7, which differed from 2011 and 2012, when HAdV-3 was more common. There was a trend towards pneumonia being more common in patients infected with HAdV-7 than in patients infected with other types, although this did not reach statistical significance (OR 2.8, 95% CI, 0.9 to 8.7). CONCLUSION:The emergence of HAdV-7 in a population where other HAdV types had circulated previously may have caused the outbreak in Singapore, and this was associated with more serious infections in children. Young age (<2 years) and significant comorbidities were associated with more severe HAdV infection.
Etiology of acute viral respiratory infections common in Pakistan: A review.
Naz Riffat,Gul Asma,Javed Urooj,Urooj Alina,Amin Sidra,Fatima Zareen
Reviews in medical virology
Respiratory infections, especially those of the lower respiratory tract, remain a foremost cause of mortality and morbidity of children greater than 5 years in developing countries including Pakistan. Ignoring these acute-level infections may lead to complications. Particularly in Pakistan, respiratory infections account for 20% to 30% of all deaths of children. Even though these infections are common, insufficiency of accessible data hinders development of a comprehensive summary of the problem. The purpose of this study was to determine the prevalence rate in various regions of Pakistan and also to recognize the existing viral strains responsible for viral respiratory infections through published data. Respiratory viruses are detected more frequently among rural dwellers in Pakistan. Lower tract infections are found to be more lethal. The associated pathogens comprise respiratory syncytial virus (RSV), human metapneumovirus (HMPV), coronavirus, enterovirus/rhinovirus, influenza virus, parainfluenza virus, adenovirus, and human bocavirus. RSV is more dominant and can be subtyped as RSV-A and RSV-B (BA-9, BA-10, and BA-13). Influenza A (H1N1, H5N1, H3N2, and H1N1pdm09) and Influenza B are common among the Pakistani population. Generally, these strains are detected in a seasonal pattern with a high incidence during spring and winter time. The data presented include pneumonia, bronchiolitis, and influenza. This paper aims to emphasise the need for standard methods to record the incidence and etiology of associated pathogens in order to provide effective treatment against viral infections of the respiratory tract and to reduce death rates.
Burden of Respiratory Syncytial Virus Disease and Mortality Risk Factors in Argentina: 18 Years of Active Surveillance in a Children's Hospital.
Gentile Angela,Lucion María Florencia,Juarez María Del Valle,Areso María Soledad,Bakir Julia,Viegas Mariana,Mistchenko Alicia
The Pediatric infectious disease journal
BACKGROUND:Respiratory syncytial virus is the leading cause of acute lower respiratory infection in children. We aimed to describe the clinical-epidemiologic pattern and risk factors for mortality associated with RSV infection. METHODS:This is a prospective, cross-sectional study of acute lower respiratory infection in children admitted to the Children's Hospital during 2000 to 2017. Viral diagnosis was made by fluorescent antibody techniques or real-time-polymerase chain reaction. We compared clinical-epidemiologic characteristics of RSV infection in nonfatal versus fatal cases. Multiple logistic regression was used to identify independent predictors of mortality. RESULTS:Of 15,451 patients with acute lower respiratory infection, 13,033 were tested for respiratory viruses and 5831 (45%) were positive: RSV 81.3% (4738), influenza 7.6% (440), parainfluenza 6.9% (402) and adenovirus 4.3% (251). RSV had a seasonal epidemic pattern coinciding with months of lowest average temperature. RSV cases show a case fatality rate of 1.7% (82/4687). Fatal cases had a higher proportion of prematurity (P < 0.01), perinatal respiratory history (P < 0.01), malnourishment (P < 0.01), congenital heart disease (P < 0.01), chronic neurologic disease (P < 0.01) and pneumonia at clinical presentation (P = 0.014). No significant difference between genders was observed. Most deaths occurred among children who had complications: respiratory distress (80.5%), nosocomial infections (45.7%), sepsis (31.7%) and atelectasis (13.4%). Independent predictors of RSV mortality were moderate-to-severe malnourishment, odds ratio (OR): 3.69 [95% confidence interval (CI): 1.98-6.87; P < 0.0001]; chronic neurologic disease, OR: 4.14 (95% CI: 2.12-8.08; P < 0.0001); congenital heart disease, OR: 4.18 (95% CI: 2.39-7.32; P< 0.0001); and the age less than 6 months, OR: 1.99 (95% CI: 1.24-3.18; P = 0.004). CONCLUSIONS:RSV showed an epidemic pattern affecting mostly young children. Malnourishment, chronic neurologic disease, congenital heart disease and the age less than 6 months were the independent risk factors for RSV mortality.
Severe Adenovirus Pneumonia Requiring Extracorporeal Membrane Oxygenation Support in Immunocompetent Children.
Chen Xuefei,Lv Jianhai,Qin Lu,Zou Chaochun,Tang Lanfang
Frontiers in pediatrics
To highlight severe adenovirus pneumonia in immunocompetent patients by analysis of severe adenovirus pneumonia associated with acute respiratory distress syndrome in whom extracorporeal membrane oxygenation (ECMO) support is required. Pediatric patients with adenovirus pneumonia and ECMO supports in our hospital from February 2018 to May 2019 were retrospectively analyzed, and having 100 common adenovirus pneumonia children as a control. A total of 8 patients, including 4 boys (50.0%), were enrolled. They were previously immunocompetent with a median age of 31 months. They were admitted as persistent fever and cough for more than one week. Median time prior to development of respiratory failure requiring intubation and invasive mechanical ventilation was 5 days. Venoarterial ECMO support as rescue ventilation was instituted after a median time of 24.5 h of conventional mechanical ventilator support. The median duration on ECMO support was 9 days and mechanical ventilation was 14 days, respectively. Six patients (75%) were recovered and 2 (25%) died. Median length of stay in ICU and hospital were 27.5 days and 47.5 days, respectively. The promising outcomes of our cases suggested that ECMO support for rescue ventilation may be considered when symptoms deteriorated in adenovirus pneumonia patients, and may improve outcome. However, sequelae of adenovirus pneumonia and ECMO-related complications should also be taken into account.
Human adenovirus Coinfection aggravates the severity of Mycoplasma pneumoniae pneumonia in children.
Gao Jiaojiao,Xu Lili,Xu Baoping,Xie Zhengde,Shen Kunling
BMC infectious diseases
BACKGROUND:Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen of community-acquired pneumonia (CAP) in children. The coinfection rate of M. pneumoniae pneumonia (MPP) can reach 52% in some areas, but the effects of coinfection with different pathogens have not been clearly recognized. METHODS:The cases of MPP hospitalized in Beijing Children's Hospital from 1/1/2014 to 12/31/2016 were screened. MPP patients coinfected with Human adenovirus (HAdV) were categorized into the research group. Patients with single M. pneumoniae infection were categorized into the control group, matching the research group by age and admission time with a ratio of 1:3. Clinical manifestations, laboratory examinations, and disease severity were compared between these two groups. RESULTS:A total of 2540 hospitalized MPP cases were screened in Beijing Children's Hospital, among which thirty cases were enrolled in the research group and ninety cases were enrolled in the control group. The results indicated that patients in the research group had longer hospital stays, longer fever durations and a higher rate of dyspnea, as well as a larger proportion applications of oxygen therapy and noninvasive continuous positive airway pressure (NCPAP). No obvious differences were found in lab examinations within the two groups. Regarding disease severity, the proportions of extremely severe pneumonia and severe disease defined by the clinical score system were higher in the research group than in the control group. CONCLUSION:Compared with single M. pneumoniae infection, MPP coinfected with HAdV in children was relatively more serious.
Evaluation of Risk Factors for Exacerbations in Children with Adenoviral Pneumonia.
BioMed research international
PURPOSE:The aim of this work was to analyze clinical features and laboratory findings of children with adenovirus pneumonia and guide clinical diagnosis, treatment, and assessment of disease severity. . Retrospective analysis of clinical data of 285 children with adenoviral pneumonia who were hospitalized in Wuhan Children's Hospital from December 2018 to October 2019. According to the assessment criteria for severe pneumonia, it was divided into the severe group (92 cases) and the nonsevere group (193 cases). Collected clinical manifestations, complications, and laboratory test indicators in two groups of children and conducted all statistical analyses. RESULTS:The risk of fever and wheezing was significantly higher in the severe group than in the nonsevere group. The difference was statistically significant ( < 0.05). The risk of complications in the severe group was significantly higher than that in the nonsevere group. The difference was statistically significant ( < 0.05). The levels of AST, LDH-L, PCT, ferritin, and D-dimer in the severe group were significantly higher than those in the nonsevere group. The difference was statistically significant ( < 0.05). CONCLUSION:Children with severe adenovirus pneumonia have severe clinical manifestations and many complications. AST, LDH-L, PCT, ferritin, and D-dimer levels have important clinical implications for assessing disease severity.
A case series of children with adenovirus pneumonia: three-year experiences in a tertiary PICU.
Shi Jingyi,Zhou Yiping,Wang Fei,Wang Chunxia,Miao Huijie,Sun Ting,Shan Yijun,Cui Yun,Zhang Yucai
BACKGROUND:Describe the outcome of adenovirus pneumonia in a pediatric intensive care unit (PICU) over a 3-year period, to identify the risk factors that may be associated with worse outcome. METHODS:A retrospective observational study was performed in the PICU of children's hospital in Shanghai from July 2016 to June 2019. Sixty-seven children over 29 days to 14 years old with adenovirus pneumonia who were admitted to PICU with acute hypoxemic respiratory failure were included in this study. The primary outcome was hospital mortality, and secondary outcomes were hospital and PICU length of stay (LOS), and risk factors of worse outcome. RESULTS:Of 67 children with severe adenovirus pneumonia, the hospital mortality was 16.42% (11/67) and 28-day mortality was 14.93% (10/67). Median Pediatric Risk of Mortality III (PRISM III) score at admission was 13 (interquartile range [IQR], 10-15). Median PICU LOS stay was 11 days (8-18d) and hospital LOS was 22 days (16-31d). Among children with extracorporeal membrane oxygenation (n = 9), 6 cases survived and 3 cases died. The patients who need renal replacement therapy, neuromuscular blockade, parenteral nutrition, and packed red blood cell perfusion had higher hospital mortality (p < 0.001, p = 0.041, p = < 0.001, p = 0.012, respectively). Multivariate logistic analysis indicated that liver dysfunction and nosocomial infection were associated with high risk of mortality. CONCLUSIONS:The hospital mortality of adenovirus pneumonia in our PICU was 16.42%. Patients complicated liver dysfunction and co-infection & nosocomial infection were associated with poor outcome.
Plasma TNFSF13B and TNFSF14 Function as Inflammatory Indicators of Severe Adenovirus Pneumonia in Pediatric Patients.
Fan Huifeng,Lu Bingtai,Cao Can,Li Hui,Yang Diyuan,Huang Li,Ding Tao,Wu Minhao,Lu Gen
Frontiers in immunology
Background:Human adenoviruses (HAdV) infection caused pneumonia remains a major threat to global children health. Currently, diagnosis of severe HAdV pneumonia in children is hampered by the lack of specific biomarkers. Also, the severity of adenovirus pneumonia in pediatric patients is generally based on clinical features and existing biomarkers do not reliably correlate to clinical severity. Here, we asked whether local and systemic inflammatory mediators could act as biomarkers predicting severe HAdV pneumonia in children. Methods:Totally 37 common inflammatory protein levels were determined by Luminex assay in plasma and bronchoalveolar lavage (BAL) from pediatric patients who were diagnosed with HAdV pneumonia, and their correlation with the disease severity and lung lesion were assessed using statistical and bioinformatic analysis. Results:Among 37 inflammatory cytokines, the protein levels of 4 TNF superfamily (TNFSF) members and their receptors (TNF receptor superfamily, TNFRSF) [TNFSF13B, TNFSF14, sTNF-R1 and sTNF-R2] in the plasma and 7 TNFSF/TNFRSF members [TNFSF12, TNFSF13, TNFSF13B, TNFSF14, TNFRSF8, sTNF-R1, and sTNF-R2] in the BAL were enhanced in patients with HAdV pneumonia compared with control subjects with airway foreign body. Moreover, the protein levels of all the tested TNFSF/TNFRSF members (except TNFSF12) were elevated in the BAL of severe group compared with non-severe HAdV pneumonia patients, while only TNFSF13B and TNFSF14 were dramatically increased in the plasma of severe cases, and positively related to the plasma CRP levels. In addition, ROC analysis indicated that TNFSF13B and TNFSF14 displayed a great potential to predict severe HAdV pneumonia. Conclusion:In pediatric HAdV pneumonia, TNFSF/TNFRSF members function as key molecules in local and systemic inflammatory network, and the plasma TNFSF13B and TNFSF14 may be the potential local and systemic inflammatory indicators of severe HAdV pneumonia in pediatric patients.
[Analysis of the clinical features and the risk factors of severe adenovirus pneumonia in children].
Huang H,Chen Y,Ma L Y,Yan M M,Deng Y,Zhang W D,Yuan Y,Xiong P,Fang F,Liu T L
Zhonghua er ke za zhi = Chinese journal of pediatrics
To analyze the clinical characteristics, risk factors for critical illness and death of severe adenovirus pneumonia in children, so as to provide clinical evidences for early diagnosis and reliable treatment. A total of 75 pediatric cases with severe adenovirus pneumonia admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January to October 2019 were studied. The clinical features, laboratory and imaging data, therapeutic approaches, efficacy of the treatments and prognosis were investigated retrospectively. Patients were divided into severe group and critical group. Chi square test and Mann-Whitney rank sum test were used to analyze the data of the two groups. The risk factors for critical illness and death were analyzed by univariate and multivariate Logistic regression. Among the 75 children, there were 52 males and 23 females, aged from 3 months to 8 years, including 30 of severe cases and 45 of critical case. The positive rate of adenovirus antigen in nasopharyngeal swab was 21% (15/72), and the positive rate of serum adenovirus IgM antibody was only 13% (10/75). However, the positive rate of adenovirus nucleic acid in nasopharyngeal swab was 75% (21/28). What is more, the positive rates of metagenomics next generation sequencing (mNGS) in plasma and bronchoalveolar lavage fluid were 92% (33/36) and 96% (54/56), respectively, of which 95% (63/66) were confirmed as adenovirus type 7. Relatively high dose of ribavirin and integrated therapeutic approaches (respiratory support, glucocorticoids, immunoglobulin and organ supportive therapies) were used. The recovery rate was 77% (58/75), the improvement rate was 8% (6/75) and the mortality rate was 15% (11/75). The proportion of children with the duration of fever longer than 3 days after ribavirin treatment in the critical group was significantly higher than that in the severe group(51% (18/35) 8% (2/26), χ=12.949, <0.05). The risk factors for critical illness were younger than 4 years, longer duration of fever before and after admission to PICU, oxygenation index<300 mmHg (1 mm Hg=0.133 kPa), ferritin>1 000 μg/L, lactate dehydrogenase (LDH)>1 500 U/L, 5 lung lobes involvement, pleural effusion and (or) air leakage (all 0.05). Among them, 5 lung lobes involvement was the independent risk factor for critical illness (adjusted =49.641, 95% 4.186-588.618, =0.002). Risk factors for death included longer duration of fever after being admitted to PICU, oxygenation index<100 mmHg, ferritin>2 000 μg/L, interleukin (IL)-6>100 ng/L, LDH>1 500 U/L, pleural effusion and (or) air leakage (all <0.05). Among them, IL-6>100 ng/L was the independent risk factor for the mortalities of critically ill children (adjusted =16.094, 95% 2.059-25.787, =0.008). The mortality rate of severe pediatric adenovirus pneumonia caused by adenovirus type 7 is high. High positive rates of adenovirus nucleic acid in nasopharyngeal swabs and mNGS in plasma or bronchoalveolar lavage fluid contribute to early diagnosis, and mNGS can also be used for serotyping. Younger children under 4 years of age, persistent fever, extensive pulmonary lesions and significantly increased inflammatory cytokines such as IL-6 are warning indicators for critical illness and poor prognosis. Relatively high dose of ribavirin combined with integrated therapeutic approaches are beneficial for prognosis.
Clinical Characteristics of 204 Children With Human Adenovirus Type 7 Pneumonia Identified by Whole Genome Sequencing in Liuzhou, China.
Huang Xiaoli,Yi Yongsong,Chen Xiaogang,Wang Bo,Long Yiqin,Chen Jichang,Rongkavilit Chokechai
The Pediatric infectious disease journal
BACKGROUND:Clinical knowledge of human adenovirus type 7 (HAdV-7) pneumonia in children remains limited. Moreover, predictors for disease severity are largely unknown. METHODS:This is a retrospective study of children hospitalized at Liuzhou Maternal and Child Health Hospital, China, with HAdV-7 pneumonia in 2018-2019. Demographics, clinical characteristics, laboratory results, and imaging data were collected. HAdV-7 was identified in plasma using whole genome sequencing, which yielded quantitative HAdV-7 sequence numbers. RESULTS:There were 204 children; 145 (71%) were <2 years of age. There were 68 children with severe pneumonia (SP) and 136 with nonsevere pneumonia (NSP). Up to 43% in SP group with respiratory failure (SP-RF) were <12 months of age. Median duration of fever before hospitalization was shorter in NSP group than SP groups (P < 0.01). Fourteen (6.9%) underwent mechanical ventilation. There was a significant difference in mean plasma HAdV-7 sequence numbers among SP-RF, SP without respiratory failure (SP-NRF), and NSP groups (2485 ± 165, 2034 ± 124, and 286 ± 35, respectively) (P < 0.01). In a logistic regression analysis, we found that elevated plasma HAdV-7 sequence numbers significantly increased the risk of severe HAdV-7 pneumonia (OR 1.80, 95% confidence interval: 1.59-2.60, P < 0.01) after adjusting for age, fever duration, platelet counts, and serum lactate dehydrogenase levels. CONCLUSIONS:Over two-thirds of children hospitalized with HAdV-7 pneumonia were <2 years of age. Approximately 40% of those with SP associated with respiratory failure were <12 months of age. Those with SP exhibited higher plasma HAdV-7 sequence numbers. Thus, plasma HAdV-7 sequence numbers have a potential in predicting severity of HAdV-7 pneumonia in children.
Adenovirus viremia may predict adenovirus pneumonia severity in immunocompetent children.
Zhang Ruimu,Wang Hongmei,Tian Shufeng,Deng Jikui
BMC infectious diseases
BACKGROUND:Previous studies have demonstrated an association between adenovirus viremia and disease severity in immunocompromised children. However, few studies have focused on this association in immunocompetent children. This study explored the association between adenovirus viremia and adenovirus pneumonia severity in immunocompetent children. METHODS:We performed a retrospective, observational study of immunocompetent children with adenovirus pneumonia admitted to Shenzhen Children's Hospital in Shenzhen, China. Pneumonia was classified as severe or mild based on the Chinese guideline for the classification of pneumonia severity. Serum samples from all the children included in the study were tested for adenovirus DNA with a quantitative polymerase chain reaction. Clinical manifestations, laboratory examinations, and disease severity were compared between children with severe and mild pneumonia. RESULTS:A total of 111 immunocompetent children with adenovirus pneumonia (60 severe, 51 mild) were included. The median age was 40 months, and 64 patients were male. Five patients were admitted to the intensive care unit, and two underwent endotracheal intubation. All patients were discharged after recovery or improvement. Univariate analysis and binary logistic regression analysis showed that leukocytosis (OR = 1.1; 95% CI: 1.0 to 1.2; P = 0.033), co-infection with Mycoplasma pneumoniae (OR = 5.0; 95% CI: 2.1 to 12.3; P < 0.001), and high blood viral load (OR = 1.5; 95% CI: 1.2 to 2.0; P = 0.001) may be risk factors for severe adenovirus pneumonia. CONCLUSIONS:Leukocytosis, co-infection with Mycoplasma pneumoniae, and high blood viral load may be risk factors for severe adenovirus pneumonia in immunocompetent children. Blood viral load may predict pneumonia severity.
The Epidemiology, Molecular, and Clinical of Human Adenoviruses in Children Hospitalized With Acute Respiratory Infections.
Wen Shunhang,Lin Zupan,Zhang Yue,Lv Fangfang,Li Haiyan,Zhang Xueya,Lin Li,Zhu Hui-Hui,Xu Zhi,Li Changchong,Zhang Hailin
Frontiers in microbiology
Introduction:Human adenovirus (HAdV) is a common pathogen in children with acute respiratory infections (ARIs). The aim was to describe the epidemiology, molecular, and clinical characteristics of HAdV among children hospitalized with ARIs in Wenzhou in southeastern China. Methodology:From January 2018 to December 2019, nasopharyngeal swab or sputum specimens were prospectively collected from hospitalized children with ARIs. HAdV was detected using direct immunofluorescence. We used a multiplex PCR assay combined with capillary electrophoresis targeting the hexon gene's hypervariable region to identify HAdV types 1, 2, 3, 4, 5, 7, 14, 21, 37, 40, 41, and 55. We analyzed the epidemiological, molecular, and clinical data according to the HAdV type. Results:HAdVs were detected in 1,059 (3.5%) of the total of 30,543 children tested. A total of 947 cases with monotype HAdV identified by the PCR assay were included in the analysis. HAdV-3 (415/947, 43.8%), HAdV-7 (318/947, 33.6%), HAdV-2 (108/947, 11.4%), and HAdV-1 (70/947, 7.4%) were the predominant types. Of the 550 (58.1%) cases detected from December 2018 to August 2019, HAdV-3, and HAdV-7 were the main types. The main diagnoses included 358 cases of pneumonia, 232 cases of tonsillitis, 198 cases of bronchitis, and 159 cases of upper respiratory tract infection (URTI). Among children with pneumonia the main types were HAdV-7 (51.1%), HAdV-3 (36.9%), and HAdV-1 (2.2%). Among children with bronchitis, the main types were HAdV-3 (48.0%), HAdV-7 (28.3%), and HAdV-2 (10.6%). Among children with URTIs, the main types were HAdV-3 (49.7%), HAdV-7 (22.6%), and HAdV-2 (13.2%). Among children with tonsillitis, the main types were HAdV-3 (47.4%), HAdV-2 (22.4%), and HAdV-7 (18.5%). In total, 101 (55.2%) patients required supplemental oxygen, 15 (8.2%) required critical care, and 1 child (0.5%) with HAdV-7 pneumonia died. Conclusion:HAdV-3 -7, -2, and -1 were the predominant types identified in hospitalized children with ARIs in Wenzhou. From December 2018 to August 2019, there were outbreaks of HAdV-3 and -7. There were significant differences in HAdV types among children with pneumonia, tonsillitis, bronchitis, and URTI. HAdV-7 can cause more severe pneumonia in children than HAdV-3.
Clinical analysis of adenovirus postinfectious bronchiolitis obliterans and nonadenovirus postinfectious bronchiolitis obliterans in children.
Huang Fei,Ma Yu-Cong,Wang Fang,Li Ya-Nan
Lung India : official organ of Indian Chest Society
Background and Objective:Postinfectious bronchiolitis obliterans (PIBO) is an uncommon and severe form of chronic obstructive lung disease in children. Adenovirus (ADV) is the main pathogen of PIBO in children. However, the risk factors of ADV-PIBO are not fully understood. This study aims to analyze the clinical characteristics of PIBO caused by ADV and compared with non-ADV-PIBO. Materials and Methods:A retrospective study of children under the age of 14 years diagnosed PIBO was performed in 56 ADV-PIBO cases, 29 non-ADV-PIBO, and 39 healthy controls to determine clinical characteristics of PIBO. Results:There was no difference between ADV-PIBO and non-ADV-PIBO cases in gender, age, individual and family atopy or history of asthma, and previous history of wheezing and no difference in the clinical manifestations and signs between the two groups. However, the hospital stay, duration of ventilator use, and multifocal pneumonia incidence of ADV-PIBO group have a significant differences compared with non-ADV-PIBO. Notably, inflammatory markers lactic dehydrogenase (LDH), interleukin 8 (IL-8), and interferon-gamma (IFN-γ) were significantly increased in PIBO patients, and those expressed in ADV-PIBO patients were higher than those in non-ADV-PIBO patients. In addition, ADV-PIBO children required a longer duration of oral prednisone and azithromycin than non-ADV-PIBO cases. Conclusions:Compared with non-ADV-PIBO, ADV-PIBO has a longer hospital stay, longer duration of ventilator use, increased LDH, IL-8, and IFN-γ expressions, and longer duration of oral prednisone and azithromycin treatment. Further research is needed to determine why PIBO caused by ADVs are more severe than those caused by other pathogens.
A preliminary nomogram constructed for early diagnosis of bronchitis obliterans in children with severe pneumonia.
Sun Chao,Yan Silei,Jiang Kun,Wang Chao,Dong Xiaoyan
Background:To establish and internally validate a nomogram for early diagnosis of bronchitis obliterans in children with severe pneumonia. Methods:The diagnostic model was established using a dataset of 147 pediatric patients with severe pneumonia. The clinical characteristics of bronchitis obliterans were determined using the least absolute shrinkage and selection operator method. According to the results of the multivariate logistic regression analysis, an individual nomogram was established, the C-index, calibration plot, and decision curve analysis were used to evaluate the performance of the nomogram. Results:Adenovirus infection, length of symptoms, percentage of macrophages in bronchial alveolar lavage fluid, and mucosal abnormalities were all important clinical characteristics included in the nomogram. According to internal validation, the C-index of nomogram was 0.91 (C-index, 0.878 to 0.942), suggesting that the nomogram has excellent discrimination. The nomogram showed good calibration with the Hosmer-Lemeshow test demonstrating no statistical significance. The net reclassification index was 0.2022 (95% CI, 0.008 to 0.3968; P=0.042), and the integrated discrimination improvement was 0.0975 (95% CI, 0.026 to 0.169; P=0.008). Decision curve analysis showed that the nomogram is clinically useful. Conclusions:This nomogram can help clinicians make early diagnoses of bronchitis obliterans in children for whom membranous tissue has not yet formed.
Persistent viral shedding of human adenovirus type 7 in children with severe pneumonia.
Zeng Sai-Zhen,Xie Le-Yun,Yu Tian,Zhong Li-Li,Li Jin-Song,Duan Zhao-Jun,Zhang Bing,Zeng Qi-Yi
Journal of medical virology
To understand host-pathogen interactions and develop effective prevention and control strategies for human adenovirus (HAdV), it is essential to explore the characteristics of HAdV shedding. Hospitalized children <14 years who had severe HAdV pneumonia were tested for HAdV DNA by quantitative real-time PCR in nasopharyngeal aspirate (NPA). A total of 132 children were enrolled, including 102 patients with HAdV type 7 (HAdV-7) infection and 12 patients with HAdV type 3 (HAdV-3) infection. A total of 1372 qualified NPA samples were collected. There was a significant negative correlation between the viral load of HAdV and the course of the disease (Spearman r = -0.547, p = .000). HAdV-7 load decreased at a rate of 0.089 log10 copies/mL per day (95% CI: -0.096 to -0.081; R = 0.332), and the duration of viral shedding was predicted to be 96.9 days (y = 8.624-0.089x). However, HAdV-3 load decreased more quickly (95% CI: - 0.229 to - 0.143; R = 0.403), and the duration of viral shedding was 51.4 days (y = 9.558-0.186x). The median viral load of the HAdV-7 group at weeks 2 and 3, and more than 3 weeks postinfection was higher than that of the HAdV-3 group. No significant differences in the duration of viral shedding were found in different gender, age (>2 vs. ≤2 years), and with or without underlying diseases groups. Viral shedding in children with severe HAdV pneumonia persisted, among which HAdV-7 lasted longer than 3 months and the viral load decreased slowly than HAdV-3.
[A multicenter retrospective study on the etiology of necrotizing pneumonia in children].
Zhonghua er ke za zhi = Chinese journal of pediatrics
To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China. A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ test was used for categorical variables. A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), (SP) (61 cases), (SA) (51 cases), (13 cases), (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) 36.8% (32/87), χ6.654, 0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) 31.0% (9/29), χ²=0.314, =0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) 42.7% (146/342), χ=13.409, 0.010; 7.9% (12/152) 14.3% (49/342), χ4.023, 0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) 6.1% (6/98), =6.697, 0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ=60.688, 0.01; 4.5% (9/200) 21.4% (21/98), χ=20.819, 0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×10/L 10.5 (2.5-32.2)×10/L, 122.5 (0.5-277.3) mg/L 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) μg/L 0.24 (0.01-18.85) μg/L, =-3.719, -5.901 and -7.765, all 0.01). The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.
Epidemiology of Respiratory Pathogens Among Children Hospitalized for Pneumonia in Xiamen: A Retrospective Study.
Sun Yong-Peng,Zheng Xin-Yi,Zhang Hai-Xia,Zhou Xiao-Man,Lin Xin-Zhu,Zheng Zi-Zheng,Zhang Jun,Su Ying-Ying,Zhou Yu-Lin
Infectious diseases and therapy
OBJECTIVES:To investigate the etiology of common respiratory pathogens in children < 2 years of age hospitalized with pneumonia in Xiamen from 2014 to 2017. METHODS:The medical records of 5581 children with pneumonia were retrospectively reviewed. Direct immunofluorescent test was used for respiratory virus testing. Bacteria were detected by conventional culture method. The results of pathogen detection at admission were analyzed as well as the clinical outcomes of children. RESULTS:The burden of hospitalized children with pneumonia was highest among infants < 6 months old (58.2%). Respiratory syncytial virus (RSV) was the most common respiratory virus (26.0%) followed by parainfluenza (4.8%) and adenovirus (3.2%). Haemophilus influenzae was the most common bacteria detected (16.6%) followed by Moraxella catarrhalis (13.4%), Staphylococcus aureus (13.0%), Streptococcus pneumoniae (12.3%), Escherichia coli (5.1%) and Klebsiella pneumoniae (4.8%). Notably, RSV and K. pneumoniae were detected more frequently in severe pneumonia (35.0% and 10.9%) versus mild pneumonia (25.6% and 4.6%), with higher rates of ICU admissions, longer hospital stays and higher hospital costs compared to those infected with other respiratory pathogens. CONCLUSIONS:Among children < 2 years of age hospitalized with pneumonia in Xiamen, RSV was the most common respiratory virus, while H. influenzae and S. pneumoniae remained the predominant bacterial pathogens detected. Considering the low implementation rate of vaccines against pneumococcal and Hib pneumonia in China, there is an urgent need to increase both vaccination rates to reduce pneumococcal and Hib disease burden.
Potential Diagnostic and Prognostic Biomarkers for Adenovirus Respiratory Infection in Children and Young Adults.
Biserni Giovanni Battista,Scarpini Sara,Dondi Arianna,Biagi Carlotta,Pierantoni Luca,Masetti Riccardo,Sureshkumar Sugitha,Rocca Alessandro,Lanari Marcello
Human Adenoviruses (HAdV) are known to be potentially associated with strong inflammatory responses and morbidity in pediatric patients. Although most of the primary infections are self-limiting, the severity of clinical presentation, the elevation of the white blood cell count and inflammatory markers often mimic a bacterial infection and lead to an inappropriate use of antibiotics. In infections caused by HAdV, rapid antigen detection kits are advisable but not employed routinely; costs and feasibility of rapid syndromic molecular diagnosis may limit its use in the in-hospital setting; lymphocyte cultures and two-sampled serology are time consuming and impractical when considering the use of antibiotics. In this review, we aim to describe the principal diagnostic tools and the immune response in HAdV infections and evaluate whether markers based on the response of the host may help early recognition of HAdV and avoid inappropriate antimicrobial prescriptions in acute airway infections.
Pathogen distribution and bacterial resistance in children with severe pneumonia: A single-center retrospective study.
Su De-Quan,Huang Hong-Lin,Zhuo Zhi-Qiang
ABSTRACT:To examine the etiological distribution of pathogens in pediatric patients with severe pneumonia and analyze the drug resistance of major pathogen species.Nasopharyngeal secretion specimens were collected for bacterial culture from pediatric patients admitted to the Xiamen children's hospital who were diagnosed with severe pneumonia from January 2016 to December 2019. Pathogen species were detected by quantitative polymerase chain reaction, direct immunofluorescence, and bacterial culture and we examined the drug susceptibility of the bacterial pathogens.At least 1 species of the pathogen was detected in 576 of 734 patients and a total of 444 bacterial samples were isolated, of which 284 were gram-negative and 160 were gram-positive. The most frequently detected bacteria were Haemophilus influenzae, Streptococcus pneumonia, Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli. In addition, we isolated 186 viral samples, of which the majority were respiratory syncytial virus (n = 90) and adenovirus (n = 70) as well as 142 Mycoplasma pneumonia samples.Gram-negative bacteria are dominant among the pathogens causing severe pneumonia in pediatric patients and the major pathogen species are resistant to a variety of antibiotics. Appropriate antibiotic use has an important role in preventing the emergence of resistant strains.
Epidemiology of Adenovirus Pneumonia and Risk Factors for Bronchiolitis Obliterans in Children During an Outbreak in Jilin, China.
Yu Xiuhua,Ma Yucong,Gao Yang,You Hailong
Frontiers in pediatrics
Jilin Province, located in northeastern China, recently experienced a human adenovirus (HAdV) epidemic. Few studies involving hospitalized pediatric patients with pneumonia caused by HAdV in our region exist. HAdV pneumonia can lead to severe long-term respiratory sequelae, such as post-infectious bronchiolitis obliterans (PIBO), which has a poor prognosis and greatly influences the quality of life of pediatric patients. However, studies on the risk factors for PIBO are limited. To describe the HAdV pneumonia prevalence and determine potential risk factors for PIBO development among hospitalized children in Jilin Province, China. The data of 187 children with HAdV pneumonia (10 months-12 years old) admitted to the First Hospital of Jilin University during an outbreak between October 2018 and January 2020 were retrospectively studied. We analyzed the epidemiological characteristics of HAdV pneumonia, focusing on severe HAdV pneumonia (66 cases). The risk factors for BO development were determined by comparing the demographic and clinical data of the BO and non-BO groups. The largest number of HAdV pneumonia cases occurred in January 2019 (severe = 18, general = 21), followed by December 2018 (severe = 14, general = 11), June 2019 (general = 17), July 2019 (general, = 14), and May 2019 (general, = 13). In total, 91.98% of the children with HAdV pneumonia were <6 years old (172/187), and 50% of the pediatric patients with severe HAdV pneumonia were <2 years old (33/66). We found that 30.3% of the severe cohort developed BO (20/66), and the strongest independent risk factors for PIBO were persistent wheezing (OR 181.776, 95% CI, 3.385-9,761.543) and acute respiratory failure (OR 51.288, 95% CI, 1.858-1,415.441) during a severe pneumonia episode. The largest number of HAdV pneumonia cases, especially severe cases, occurred in winter in Northeast China, followed by summer. The majority of children admitted with HAdV pneumonia were <6 years old, and half of severe HAdV pneumonia patients were <2 years old. Children who had persistent wheezing or acute respiratory failure during the acute phase of severe HAdV pneumonia were prone to the development of BO.
Analysis of Clinical Characteristics and Risk Factors of Severe Adenovirus Pneumonia in Children.
Zhong Haiqin,Dong Xiaoyan
Frontiers in pediatrics
To analyze the clinical characteristics of adenovirus pneumonia (ADVP) in children and explore risk factors for severe ADVP. Clinical data from 7,008 hospitalized children with community-acquired pneumonia and 211 with ADVP were retrospectively analyzed between July 2014 and June 2019. Eighty-six patients were diagnosed with severe pneumonia, and related risk factors were analyzed. ADVP accounts for 3.01% (211/7008) of CAP in hospitalized children. Among 211 patients, 167 (64.9%) children aged 1-5 years old, and the onset was in winter and spring for 126 (59.7%) children. All patients had cough, and 116 (92.8%) patients with mild cases and 82 (95.4%) patients with severe cases had varying degrees of fever. The duration of fever in the severe ADVP group and mild ADVP group was 7.3 and 5.4 days, respectively. The average hospital stays were 9.8 and 5.8 days, respectively. There was no significant difference in the levels of WBC and ESR between the two groups, but the levels of %, CRP, PCT and LDH in children with severe ADVP were significantly higher than those in the mild ADVP group. The univariate analysis showed that there were significant differences between the severe ADVP group and the mild ADVP group in ≥7 days of fever and high IgE ( < 0.05). There was no significant difference in sex, age, onset season, mycoplasma infection, bacterial infection between the two groups ( > 0.05). The multivariate logistic analysis showed that ≥7 days of fever and high IgE were independent risk factors for severe ADVP ( < 0.05). Children with severe ADVP have long fever duration, a strong inflammatory response and immune function disturbance. Fever duration (≥7 days) and high IgE were independent risk factors for severe ADVP.
Epidemiological characteristics, clinical characteristics, and prognostic factors of children with atopy hospitalised with adenovirus pneumonia.
Li Miao,Han Xiao-Hua,Liu Li-Yun,Yao Hui-Sheng,Yi Li-Li
BMC infectious diseases
BACKGROUND:Atopy may be associated with disease severity and a poor prognosis of human adenovirus (HAdV) pneumonia in children. Our aim was to observe the clinical characteristics and pulmonary radiological changes in children with atopy and HAdV pneumonia in China. METHODS:Children hospitalised with HAdV pneumonia from June 2018 to December 2019 were analysed. All children were divided into atopic with HAdV, non-atopic with HAdV, and atopic without HAdV infection group. Each group was further divided into the mild and severe pneumonia groups according to disease severity. Standard treatment was initiated after admission, and regular follow-up evaluations were conducted at 1 month after discharge. Baseline and clinical characteristics and pulmonary radiological changes in children with and without atopy were evaluated. Risk factors associated with small airway lesions in patients with HAdV pneumonia were analysed. RESULTS:The eosinophil count in the atopic group was significantly higher than that in the non-atopic group (P < 0.05). Severe coughing, wheezing, and small airway lesions on chest high-resolution computed tomography (HRCT) upon admission, after discharge and 1 month after discharge were significantly higher in the atopic group (with or without HAdV infection) than in the non-atopic group (P < 0.05). There were significant differences in the number of patients with wheezing and small airway lesions during hospitalisation and after discharge among the three groups (P < 0.05). The risks of small airway lesions in children with a family or personal history of asthma, severe infection, atopy, and HAdV infection were 2.1-, 2.7-, 1.9-, 2.1-, and 1.4-times higher than those in children without these characteristics, respectively. CONCLUSIONS:Children with atopy and HAdV pneumonia may experience severe coughing in mild cases and wheezing in mild and severe cases. Children with atopy are more susceptible to the development of small airway lesions, recurrent wheezing after discharge and slower recovery of small airway lesions as observed on pulmonary imaging than non-atopic children after HAdV infection. A family or personal history of asthma, atopy, severe infection, and HAdV infection are independent risk factors associated with the development of small airway lesion as observed on chest HRCT.
Epidemiology of Viruses Causing Pediatric Community Acquired Pneumonia in Shanghai During 2010-2020: What Happened Before and After the COVID-19 Outbreak?
Li Fei,Zhang Yuhan,Shi Peng,Cao Linfeng,Su Liyun,Zhang Yulan,Peng Ke,Lu Roujian,Tan Wenjie,Shen Jun
Infectious diseases and therapy
INTRODUCTION:Since the global outbreak of COVID-19, there has been a significant reduction in pediatric outpatient and emergency visits for infectious diseases. The purpose of this study was to analyze the changes in respiratory viruses in children with community-acquired pneumonia (CAP) in Shanghai in the past 10 years, especially in the first year after COVID-19. METHODS:We conducted a retrospective, observational study; the results for eight common respiratory viruses (respiratory syncytial virus (RSV), influenza virus A and B, parainfluenza virus 1-3 (PIV), adenovirus (ADV) and human metapneumovirus) tested by direct fluorescent antibody assays in hospitalized CAP cases in Children's Hospital of Fudan University during 2010-2020 were analyzed. RESULTS:Of the 5544 hospitalized CAP patients included in this study, 20.2% (1125/5544) were positive for the eight respiratory viruses. The top three pathogens were RSV, PIV3 and ADV, detected from 9.8% (543/5544), 5.3% (294/5544) and 2.0% (111/5544) of the samples, respectively. RSV had the highest positive rates among children < 2 years old. In 2020, the detection rate of all viruses showed a sharp decline from February to August compared with the previous 9 years. When the Shanghai community reopened in August 2020, the detection rate of eight viruses rebounded significantly in September. CONCLUSIONS:These eight respiratory viruses, especially RSV and PIV, were important pathogens of CAP in Shanghai children in the past 10 years. The COVID-19 pandemic had a significant impact on the detection rates for eight respiratory viruses in children with CAP in Shanghai.
Influence of the timing of bronchoscopic alveolar lavage on children with adenovirus pneumonia: a comparative study.
Xu Xue-Hua,Fan Hui-Feng,Shi Ting-Ting,Yang Di-Yuan,Huang Li,Jiang Wen-Hui,Lu Gen
BMC pulmonary medicine
BACKGROUND:Adenovirus pneumonia is prone to severe clinical and imaging manifestations in children. Bronchoscopic alveolar lavage (BAL) is an important adjunctive therapy for patients with severe imaging findings. The study aimed to evaluate the effect of the timing on the efficacy of bronchoalveolar lavage in children with adenovirus pneumonia. METHODS:This study included 134 patients with adenovirus pneumonia treated with BAL at Guangzhou Women and Children's Medical Center from January 2019 to January 2020.They were classified into the severe and mild groups. Based on the timing of BAL, each group was divided into the early BAL layer (received BAL within 1-9 days of the illness course) and the late BAL layer (received BAL within 10-14 days of the illness course). The clinical data of patients with different BAL timings were analyzed in two groups. RESULTS:Among the 134 patients, 70 were categorized into the mild group and 64 were categorized into the severe group. Of the 134 patients, 42 patients received BAL early (mild group: n = 21 and severe group: n = 21) and 92 patients received BAL later (mild group: n = 49 and severe group: n = 43). In the mild group, the fever and hospital duration were shorter in patients who received BAL early than in those who received BAL later (p < 0.05). However, in the severe group, there were no statistically significant differences in the fever and hospital duration between patients who received BAL early and those who received BAL later. However, the need for mechanical ventilation and the incidence of BAL complications, such as new need for oxygen, were higher in patients who received BAL early than in those who received BAL later in the severe group (p < 0.05). CONCLUSION:For mild adenovirus pneumonia, early BAL may shorten the fever and hospital duration. However, early BAL in severe cases might not shorten the course of the disease or improve prognosis and may even increase the risks of mechanical ventilation and BAL complications.
Clinical Characteristics and Outcomes of Severe Pneumonia in Children Under 5 Years Old With and Without Adenovirus Infection in Guangzhou.
Zheng Lingling,Liao Weiyao,Liang Feng,Li Kuanrong,Li Ling,Liang Huiying
Frontiers in pediatrics
To identify the differences of clinical characteristics and outcomes of severe pneumonia in children under 5 years old with and without adenovirus infection. A retrospective cohort study was conducted in three pediatric hospitals in Guangzhou, China. In total, 1,595 children under the age of 5 with WHO-defined severe pneumonia had adenovirus testing performed between January 1, 2009 and December 31, 2019. Demographics, complications, the first routine laboratory findings, therapeutic records, and clinical outcome were collected from electronic medical records. We compared characteristics of children with and without adenovirus infection. Adenovirus was detected in 75 (4.7%) out of 1,595 children with severe pneumonia. Cases with adenovirus infection were more likely to be boys (74.7 vs. 63.0%), older than 1 year old (78.7 vs. 25.1%), but less likely to have mixed virus infections (25.3 vs. 92.9%) and combined with cardiovascular disease (12.0 vs. 39.7%), and had more abnormal laboratory results than cases without adenovirus infection. Antiviral therapy (4.9%) was rarely used in children with severe pneumonia, but antibiotic therapy (65.3%) was commonly used, especially in cases with adenovirus infection (91.9%). Children infected with adenovirus (9.3 vs. 2.5%) were also hospitalized longer and had a higher mortality within 30 days of hospitalization. Children with severe pneumonia under 5 years old with adenovirus infection had more abnormal laboratory findings and more severe clinical outcomes than cases without adenovirus infection. More attention should be focused on the harm caused by adenovirus infection.
Clinical features and epidemiological analysis of respiratory human adenovirus infection in hospitalized children: a cross-sectional study in Zhejiang.
Wang Caiyun,Liu Juanjuan,Mi Yumei,Chen Jing,Bi Jing,Chen Yinghu
BACKGROUND:HAdV is one of the common pathogens in hospitalized children with acute respiratory infections (ARIs). We aim to describe the clinical and laboratory features, epidemiological characteristics, and HAdV species and/or types of inpatients with HAdV respiratory infections. METHODS:Respiratory samples were gathered from inpatients diagnosed ARIs in Children's Hospital, Zhejiang University School of Medicine, and were detected by using Direct Immunofluorescence Assay from 2018 to 2019. PCR amplification and sequencing of the hypervariable zone of hexon gene were used for genotyping. The clinical and laboratory features, and HAdV genotyping, and epidemiological characteristic analysis were retrospectively performed. RESULTS:Of 7072 samples collected, 488 were identified as HAdV-positive. The overall detection rate was 6.9%. The peaked detection rate was 14.1% in January 2019. HAdV-positive cases with ARIs mainly appeared in winter. The detection rate was highest among children between 6 months and 2 years (8.7%, 123/1408). Clinical diagnosis included pneumonia (70.3%, 343/488), bronchitis (7.0%, 34/488) and acute upper respiratory tract infection (22.7%, 111/488). The common clinical manifestations were fever (93.4%, 456/488), cough (94.7%, 462/488), wheezing (26.2%, 128/488), and shortness of breath (14.8%, 72/488). 213 (43.6%) cases had co-infection and 138 (28.3%) cases had extrapulmonary symptoms. 96(19.7%) cases had intrapulmonary and intrathoracic complications.78 (16.0%) had an underlying condition, most of which were congenital heart diseases (20.5%, 16/78). The proportions of hyperpyrexia, duration of fever > 10 days, severe pneumonia, and wheezing in the co-infection group were remarkably higher than those in HAdV single-infection group (all p < 0.05). The proportions of duration of hospitalization, duration of fever > 10 days, wheezing, shortness of breath, change in level of consciousness, serosal fluids, extrapulmonary symptoms, co-infections and underlying diseases were significantly higher in severe pneumonia group than those in the mild pneumonia group (all p < 0.05). Four HAdV species were successfully identified in 155 cases and presented by 8 genotypes. HAdV-B3 (56.1%, 87/155) and HAdV -B7 (31.0%, 48/155) were the most predominant detected types and occurred commonly in different severity groups (p = 0.000), while, HAdV-B55 was detected only in the severe group. HAdV-B7's detection rate in the severe pneumonia group was significantly higher than the non-severe pneumonia group. CONCLUSION:HAdV detection rate is related to age and season. Bronchopneumonia accounts for about 70% HAdV-positive inpatients. The common clinical manifestations include hyperpyrexia, cough, wheezing, and shortness of breath. HAdV-B3 and HAdV-B7 are the most common types in children diagnosed with respiration infections.
Association of coinfection with adenovirus pneumonia severity in children.
Wei Jinfeng,Wu Suling,Jin Xuefeng,Zhang Jie,Pan Shanshan
Allergologia et immunopathologia
Between the winter of 2018 and the end of 2019, there has been an epidemic of adenovirus infection in southern China, including Zhejiang Province. The number of children suffering from adenovirus pneumonia (AP) has significantly increased. AP can be accompanied by in children. This study aimed to investigate the association of and identify the risk factors for coinfection on hospitalized patients with AP. The patients were classified into two groups by etiologic analysis (single AP and AP with coinfection groups). The clinical manifestations, clinical medication, and laboratory and imaging findings of the two groups were compared and analyzed. The coinfection group (n = 125) had a significantly longer duration of fever than the single AP group (n = 171; P = 0.03). Shortness of breath (P = 0.023) and pulmonary imaging findings, such as pulmonary consolidation, atelectasis, pleural effusion, and multilobe lesions (P < 0.05), were more common in the coinfection group. The patients with coinfection had more severe symptoms, significantly longer hospitalization time and an increased proportion of using glucocorticoids and/or immunoglobulin needing oxygen inhalation (P < 0.05). The incidence of AP with coinfection is high. The prolonged fever duration and pulmonary imaging findings could be used as prediction factors to predict coinfection in children with AP. Patients with AP coinfected with MP may easily develop severe illness. Hence, a reasonable change in the treatment is necessary.
Adenovirus: Epidemiology, Global Spread of Novel Types, and Approach to Treatment.
Seminars in respiratory and critical care medicine
Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The vast majority of cases are self-limited. However, the clinical spectrum is broad and fatalities may occur. Dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 100 genotypes and 52 serotypes of AdV have been identified and classified into seven species designated HAdV-A through -G. Different types display different tissue tropisms that correlate with clinical manifestations of infection. The predominant types circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been done. Cidofovir has been the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States but currently are not available to civilians.
Establishment of a predictive nomogram and its validation for severe adenovirus pneumonia in children.
Shen Yang,Zhou Yao,Ma Cuian,Liu Yuqiao,Wei Botao
Annals of palliative medicine
BACKGROUND:Severe adenovirus pneumonia (SAP) of children is prone to multi-system complications, has the high mortality rate and high incidence of sequelae. Severity prediction can facilitate an adequate individualized treatment plan. Our study try to develop and evaluate a predictive nomogram for children with SAP. METHODS:An observational study was designed and performed retrospectively. The data were categorized as training and validation datasets using the method of credible random split-sample (split ratio =0.7:0.3). The predictors were selected using Lasso (least absolute shrinkage and selection operator) logistic regression and the nomogram was developed. Nomogram discrimination was assessed using the receiver operating characteristic (ROC) curve, and the prediction accuracy was evaluated using a calibration curve. The nomogram was also evaluated for clinical effectiveness by the decision curve analysis (DCA). A P value of <0.05 was deemed statistically significant. RESULTS:The identified predictors were fever duration, and interleukin-6 and CD4+ T cells and were assembled into the nomogram. The nomogram exhibited good discrimination with area under ROC curve in training dataset (0.79, 95% CI: 0.60-0.92) and test dataset (0.76, 95% CI: 0.63-0.87). The nomogram seems to be useful clinically as per DCA. CONCLUSIONS:A nomogram with a potentially effective application was developed to facilitate individualized prediction for SAP in children.
Human adenovirus infections in pediatric population - An update on clinico-pathologic correlation.
Human adenoviruses can cause infections at any age but most commonly in pediatric population, especially in young children and infants. By the time of 10 years old, most children have had at least one episode of adenovirus infection. Adenoviruses can cause many symptoms similar to common cold, including rhinorrhea, fever, cough, and sore throat. Lower respiratory infections such as bronchitis, bronchiolitis, and pneumonia can be severe and even fatal. Other diseases such as conjunctivitis, gastroenteritis, cystitis, myocarditis, cardiomyopathy, and meningoencephalitis can also be associated with adenovirus infections. A variety of recent advancement of structural and molecular biology methods have revamped the taxonomy of adenoviruses and furthered our understanding of the diversity of related clinical diseases. Because of the wide spectrum and complexity of diseases associated with human adenovirus infections, the scope of this review is limited to basic virology and epidemiology of adenoviruses with a main focus on the clinico-pathologic correlation. Clinical manifestations and pathology of any infectious disease are always related; therefore, it is logical to review clinico-pathologic correlation within the specific disease entity caused by adenoviruses to better understand this common viral infection in pediatric population.
[Epidemiological characteristics of adenovirus infection in hospitalized children with acute respiratory tract infection in Kunming during 2019].
Gu Y,Huang R W,Wang M,Tang C H,Li P,Duan J,Shi L B,Li M,Fu H M
Zhonghua er ke za zhi = Chinese journal of pediatrics
To investigate the epidemiology and clinical characteristics of adenovirus (ADV)-caused acute respiratory tract infection among hospitalized children in Kunming, China. Clinical and laboratory data were collected from 467 children with adenovirus infection who were hospitalized from January 1, 2019 to December 31, 2019 in 6 grade A class Ⅲ hospitals in Kunming area. The basic characteristics, epidemiology, mixed infection and adenovirus genotypes of the patients were retrospectively analyzed. The patients diagnosed with adenovirus pneumonia (AP) were divided into two groups, severe AP (SAP) group and general AP(GAP) group according to the severity of illness. Mann-Whitney test or χ test was used for comparison between groups, while multivariate regression was applied to analyze the risk factors of SAP. Among 15 635 hospitalized children with respiratory tract infection, 467 cases were adenovirus positive, with a detection rate of 2.99%. Of the 467 patients with adenovirus infection, 284 were male and 183 female, the age was 2.4 (1.1,3.9) years, including 44 cases (9.4%) < 0.5 years, 59 cases (12.6%) of 0.5 to<1.0 years, 176 cases (37.7%) of 1.0 to <3.0 years, 150 cases (32.1%) of 3.0 to <7.0 years, and 38 cases (8.1%) of 7.0 to 14.0 years. Adenovirus infection was common in autumn and winter, and the high incidence months were October to December, which accounted for 51.6% (241/467) of the whole year cases. Co-infection was detected in 226 cases (48.4%) out of 467 patients, in which one pathogen co-infection was the most frequent form (172 cases, 76.1%). Of the 262 pathogen detected 108 (41.2%) were . In 144 of ADV-positve cases (30.8%) were taken geno-typing was done by PCR amplification, the results showed that 74 cases (51.4%) were ADV 3, 7 subtypes and 65 cases (45.1%) of ADV 1, 2,6 subtypes. Of the 467 cases of ADV infection, 320 (68.5%) were diagnosed with pneumonia, 82 (17.6%) with upper respiratory tract infection and pharyngeal tonsillitis, and 65 (13.9%) with bronchitis, laryngeal bronchitis, and asthmatic bronchitis. Among the 320 patients with AP, 56 cases were severe and 264 cases were general. Two cases (3.6%) in severe group died. Compared with the GAP group, the age was young [17 (11,42) months 24 (14,44) months, =2.222, =0.026], the fever duration was long [8 (5,14) days 6 (3,9) days, =3.380, <0.01], and the proportions of preterm birth and having underlying diseases were high [respectively 19.6% (11/56) 6.1% (16/264), 26.8% (15/56) 10.2% (27/264), χ=8.965,11.109, <0.05] in SAP group. Referring to laboratory markers, white blood cell count, C-reactive protein, creatine kinase-MB and lactate dehydrogenase were significantly increased in SAP group as compared to GAP group(all <0.05). Multivariate Logistic regression analysis showed that preterm birth (=3.284, 95% 1.079-9.993, =0.036), underlying disease (=3.284, 95% 1.079-9.993, =0.036), fever duration ≥10 d (=2.523,95% 1.195-5.328, =0.015) and C-reactive protein ≥50 mg/L (=3.156, 95% 1.324-7.524, =0.010) were positively correlated with the risk of SAP. The incidence of adenovirus infection among hospitalized children in Kunming was lower than the national level, and no outbreak occurred in 2019. Subtype 3 and 7 of ADV are the predominant strains for infection, which usually occurs in autumn and winter and mainly causes pneumonia. Premature birth, underlining diseases, long fever duration and markedly increased C-reactive protein are the risk factors for developing into severe pneumonia. This paper presents the prevalence and clinical characteristics of adenovirus infection in children at high altitude area.
Risk Factors for the Development of Hemophagocytic Lymphohistiocytosis in Children With Severe Adenovirus Pneumonia: A Single-Center Retrospective Study.
Zhang Hua-Yong,Xiao Min,Yan Fan,Zhang Mao-Rong,Zhang Yong
Frontiers in pediatrics
To investigate and analyze the relevant risk factors for hemophagocytic lymphohistiocytosis (HLH) in children with severe adenovirus pneumonia (SAP). A retrospective study of children with SAP was performed in 30 cases developing HLH and 94 cases not developing HLH from December 2018 to August 2019. The binary logistic regression analysis was used to identify risk factors that were significantly associated with the development of HLH after the univariate analysis, and the receiver operating characteristic (ROC) curve was performed to find out the cut-off value for the significant relevant factors. Two factors were associated with the development of HLH, which were the length of fever ( = 1.331, 95%: 1.002-1.769) and triglycerides (TG) ( = 17.345, 95%: 1.358-221.538). The cut-off value of the length of fever was 12.5 days, and the cut-off value of TG was 3.02 mmol/L. Children with SAP who had a duration of fever over 12.5 days and the TG level over 3.02 mmol/L are more likely to develop HLH.
Clinical features of pneumonia with adenovirus infection in children.
Peng Li,Zhong Li-Li,Huang Zhen,Li Yan,Zhang Bing
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics
OBJECTIVES:To study the clinical features of pneumonia (MPP) with adenovirus (ADV) infection in children. METHODS:A retrospective analysis was performed on the medical data of 228 children with MPP alone and 28 children with MPP and ADV infection. The two groups were compared in terms of clinical features, laboratory results, and treatment outcome. RESULTS:Compared with the MPP group, the MPP+ADV group had significantly longer duration of fever and length of hospital stay, a significantly higher proportion of patients with severe lesions (erosion and exfoliation) of the airway mucosa under bronchoscopy, a significantly higher clinical pulmonary infection score, and a significantly higher proportion of patients requiring oxygen therapy (<0.05). There were no significant differences between the two groups in white blood cell count, C-reactive protein, DNA copy number in bronchoalveolar lavage fluid, and the incidence rates of pleural effusion and extrapulmonary complications (>0.05). CONCLUSIONS:Compared with children with MPP alone, children with MPP and ADV infection tend to have more severe clinical manifestations and airway mucosal lesions and are more likely to require oxygen therapy, but most of the laboratory markers lack specificity.
Post-infectious bronchiolitis obliterans in children: a review of 42 cases.
Li Ya-Nan,Liu Li,Qiao Hong-Mei,Cheng Hang,Cheng Huan-Ji
BACKGROUND:This study aimed to describe the clinical characteristics, radiological features and outcomes of 42 children with post-infectious bronchiolitis obliterans (PIBO). METHODS:Forty-two children diagnosed with PIBO were prospectively studied at the First Hospital of Jilin University in northern China between January, 2008 and January, 2013. Their clinical characteristics, lung high resolution computed tomography (HRCT) findings and pulmonary function tests were reported. RESULTS:In children with PIBO, adenovirus was the most common etiologic agent (21/42), followed by Mycoplasma pneumoniae (M. pneumoniae). All of the patients presented with repeated wheezing and tachypnea. In addition, 22 patients required intensive management, while six patients required home oxygen therapy. HRCT findings were consistent with the PIBO diagnosis in all of the patients. Pulmonary function testing was useful in evaluating therapeutic responses. Systemic steroids combined with azithromycin were effective for PIBO treatment. CONCLUSIONS:Severe adenovirus bronchiolitis and M. pneumoniae infections have a higher risk of development for PIBO. HRCT and pulmonary function testing are useful in the diagnosis of PIBO. The degree of airway obstruction did not differ significantly between adenovirus and M. pneumoniae. A combination of steroids and azithromycin offers some benefit in treating these patients.
Community acquired respiratory virus infections in cancer patients-Guideline on diagnosis and management by the Infectious Diseases Working Party of the German Society for haematology and Medical Oncology.
von Lilienfeld-Toal Marie,Berger Annemarie,Christopeit Maximilian,Hentrich Marcus,Heussel Claus Peter,Kalkreuth Jana,Klein Michael,Kochanek Matthias,Penack Olaf,Hauf Elke,Rieger Christina,Silling Gerda,Vehreschild Maria,Weber Thomas,Wolf Hans-Heinrich,Lehners Nicola,Schalk Enrico,Mayer Karin
European journal of cancer (Oxford, England : 1990)
BACKGROUND:Community acquired viruses (CRVs) may cause severe disease in cancer patients. Thus, efforts should be made to diagnose CRV rapidly and manage CRV infections accordingly. METHODS:A panel of 18 clinicians from the Infectious Diseases Working Party of the German Society for Haematology and Medical Oncology have convened to assess the available literature and provide recommendations on the management of CRV infections including influenza, respiratory syncytial virus, parainfluenza virus, human metapneumovirus and adenovirus. RESULTS:CRV infections in cancer patients may lead to pneumonia in approximately 30% of the cases, with an associated mortality of around 25%. For diagnosis of a CRV infection, combined nasal/throat swabs or washes/aspirates give the best results and nucleic acid amplification based-techniques (NAT) should be used to detect the pathogen. Hand hygiene, contact isolation and face masks have been shown to be of benefit as general infection management. Causal treatment can be given for influenza, using a neuraminidase inhibitor, and respiratory syncytial virus, using ribavirin in addition to intravenous immunoglobulins. Ribavirin has also been used to treat parainfluenza virus and human metapneumovirus, but data are inconclusive in this setting. Cidofovir is used to treat adenovirus pneumonitis. CONCLUSIONS:CRV infections may pose a vital threat to patients with underlying malignancy. This guideline provides information on diagnosis and treatment to improve the outcome.
Adenovirus serotype 7 associated with a severe lower respiratory tract disease outbreak in infants in Shaanxi Province, China.
Tang Liuying,Wang Li,Tan Xiaojuan,Xu Wenbo
BACKGROUND:Pneumonia caused by adenovirus infection is usually severe especially with adenovirus serotype 7 commonly associated with lower respiratory tract disease outbreaks. We reported an outbreak of 70 cases of severe pneumonia with one death of infants in Shaanxi Province, China. Sampling showed adenovirus 7 (Ad7) as the primary pathogen with some co-infections. RESULTS:Two strains of adenovirus and two strains of enterovirus were isolated, the 21 pharynx swabs showed 14 positive amplifications for adenovirus; three co-infections with respiratory syncytial virus, two positive for rhinovirus, one positive for parainfluenza 3, and four negative. Adenovirus typing showed nine of the nine adenovirus positive samples were HAdV-7, three were HAdV-3 and two were too weak to perform sequencing. The entire hexon gene of adenovirus was sequenced and analyzed for the two adenovirus serotype 7 isolates, showing the nucleic acid homology was 99.8% between the two strains and 99.5% compared to the reference strain HAdV-7 (GenBank accession number AY769946). For the 21 acute phase serum samples from the 21 patients, six samples had positives results for ELISA detection of HAdV IgA, and the neutralization titers of the convalescent-phase samples were four times higher than those of the acute-phase samples in nine pairs. CONCLUSIONS:We concluded adenovirus was the viral pathogen, primarily HAdV-7, with some co-infections responsible for the outbreak. This is the first report of an infant pneumonia outbreak caused by adenovirus serotype 7 in Shaanxi Province, China.
Human adenovirus type 7 infection causes a more severe disease than type 3.
Fu Yangxi,Tang Zhengzhen,Ye Zhixu,Mo Shi,Tian Xingui,Ni Ke,Ren Luo,Liu Enmei,Zang Na
BMC infectious diseases
BACKGROUND:Human adenovirus type 3 (HAdV-3) and 7 (HAdV-7) cause significant morbidity and develop severe complications and long-term pulmonary sequelae in children. However, epidemiologic reports have suggested that nearly all highly severe or fatal adenoviral diseases in children are associated with HAdV-7 rather than HAdV-3. Here, we conduct in-depth investigations to confirm and extend these findings through a comprehensive series of assays in vitro and in vivo as well as clinical correlates. METHODS:A total of 8248 nasopharyngeal aspirate (NPA) samples were collected from hospitalized children with acute respiratory infections in Children's Hospital of Chongqing Medical University from June 2009 to May 2015. Among 289 samples that tested positive for HAdVs, clinical data of 258 cases of HAdV-3 (127) and HAdV-7 (131) infections were analyzed. All HAdV-positive samples were classified by sequencing the hexon and fiber genes, and compared with clinical data and virological assays. We also performed in vitro assays of virus quantification, viral growth kinetics, competitive fitness, cytotoxicity and C3a assay of the two strains. Mouse adenovirus model was used to evaluate acute inflammatory responses. RESULTS:Clinical characteristics revealed that HAdV-7 infection caused more severe pneumonia, toxic encephalopathy, respiratory failure, longer mean hospitalization, significantly lower white blood cell (WBC) and platelet counts, compared to those of HAdV-3. In cell culture, HAdV-7 replicated at a higher level than HAdV-3, and viral fitness showed significant differences as well. HAdV-7 also exhibited higher C3a production and cytotoxic effects, and HAdV-7-infected mice showed aggravated pathology and higher pulmonary virus loads, compared to HAdV-3-infected mice. Macrophages in BALF remained markedly high during infection, with concomitant increase in pro-inflammatory cytokines (TNF-α, IL-1β, IFN-γ, and IL-6), compared HAdV-3 infection. CONCLUSIONS:These results document that HAdV-7 replicates more robustly than HAdV-3, and promotes an exacerbated cytokine response, causing a more severe airway inflammation. The findings merit further mechanistic studies that offer the pediatricians an informed decision to proceed with early diagnosis and treatment of HAdV-7 infection.
MicroRNA Expression Profile of Whole Blood Is Altered in Adenovirus-Infected Pneumonia Children.
Huang Feng,Zhang Junsong,Yang Diyuan,Zhang Yuelan,Huang Jinxiang,Yuan Yaochang,Li Xuefeng,Lu Gen
Mediators of inflammation
Human adenovirus (Adv) infection is responsible for most community-acquired pneumonia in infants and children, which results in significant morbidity and mortality in children every year. MicroRNAs (miRNAs) are associated with viral replication and host immune response. Knowing the miRNA expression profile will help understand the role of miRNAs in modulating the host response to adenovirus infection and possibly improve the diagnosis of adenovirus-infected pneumonia. In our study, total RNA extracted from whole blood of adenovirus-infected pneumonia children and healthy controls were analyzed by small RNA deep sequencing. Expression profiles of whole blood microRNAs were altered and distinctly different in adenovirus-infected children. The top 3 upregulated miRNA (hsa-miR-127-3p, hsa-miR-493-5p, and hsa-miR-409-3p) were identified in adenovirus-infected children and provided a clear distinction between infected and healthy individuals. Potential host target genes were predicated and validated by qRT-PCR to study the impact of microRNAs on the host genes. Most of the target genes were involved in the MAPK signaling pathway and innate immune response. These highly upregulated microRNAs may have crucial roles in Adv pathogenesis and are potential biomarkers for adenovirus-infected pneumonia.
Clinical characteristics and factors predicting respiratory failure in adenovirus pneumonia.
Yoon Hee,Jhun Byung Woo,Kim Se Jin,Kim Kang
Respirology (Carlton, Vic.)
BACKGROUND AND OBJECTIVE:Limited data exist regarding factors predicting respiratory failure (RF) in non-immunocompromised patients with adenovirus (AdV) pneumonia. METHODS:We described characteristics of AdV pneumonia (n = 91) versus non-AdV pneumonia (n = 55) and compared clinico-laboratory and radiological characteristics in patient groups categorized by RF. RESULTS:All 91 AdV pneumonia patients presented with acute respiratory symptoms and radiological infiltrations and had significantly lower levels of white blood cell counts and platelet counts compared with non-AdV pneumonia. Of them, 67 patients had mild pneumonia without RF (non-RF), 14 patients had no RF at admission but progressed to RF during hospitalization (progressed to RF) and 10 patients had RF at admission (initial RF). Initial monocyte percentage and absolute monocyte counts in RF patient groups (progressed to RF and initial RF) were significantly lower than those of non-RF patients (both P < 0.001), and the differences among progressed to RF and initial RF patients were not significant. Chest computed tomography findings such as dominant pattern or distribution, clinical symptoms, and bacterial or viral co-infections other than AdV were not discriminable between patients who had RF and those who did not. On univariate analysis, initial monocytopenia, multilobar infiltrations and pleural effusion were associated with RF. However, on multivariable analysis, only initial monocytopenia remained significant (P = 0.004) for predicting RF. CONCLUSION:Our data suggest that initial monocytopenia may help to predict RF during the course of AdV pneumonia in non-immunocompromised patients.
Epidemiology, clinical presentation and respiratory sequelae of adenovirus pneumonia in children in Kuala Lumpur, Malaysia.
Li Limin,Woo Yen Yen,de Bruyne Jessie Anne,Nathan Anna Marie,Kee Sze Ying,Chan Yoke Fun,Chiam Chun Wei,Eg Kah Peng,Thavagnanam Surendran,Sam I-Ching
OBJECTIVES:To describe the severity, human adenovirus (HAdV) type and respiratory morbidity following adenovirus pneumonia in children. METHODOLOGY:Retrospective review of children under 12 years of age, admitted with HAdV pneumonia, between January 2011 and July 2013, in a single centre in Malaysia. HAdV isolated from nasopharyngeal secretions were typed by sequencing hypervariable regions 1-6 of the hexon gene. Patients were reviewed for respiratory complications. RESULTS:HAdV was detected in 131 children of whom 92 fulfilled inclusion criteria. Median (range) age was 1.1 (0.1-8.0) years with 80% under 2 years. Twenty percent had severe disease with a case-fatality rate of 5.4%. Duration of admission (p = 0.02) was independently associated with severe illness. Twenty-two percent developed respiratory complications, the commonest being bronchiolitis obliterans (15.2%) and recurrent wheeze (5.4%). The predominant type shifted from HAdV1 and HAdV3 in 2011 to HAdV7 in 2013. The commonest types identified were types 7 (54.4%), 1(17.7%) and 3 (12.6%). Four out of the five patients who died were positive for HAdV7. Infection with type 7 (OR 8.90, 95% CI 1.32, 59.89), family history of asthma (OR 14.80, 95% CI 2.12-103.21) and need for invasive or non-invasive ventilation (OR 151.84, 95% CI 9.93-2.32E) were independent predictors of respiratory complications. CONCLUSIONS:One in five children admitted with HAdV pneumonia had severe disease and 22% developed respiratory complications. Type 7 was commonly isolated in children with severe disease. Family history of asthma need for invasive or non-invasive ventilation and HAdV 7 were independent predictors of respiratory complications.
Acute febrile respiratory illness in the ICU: reducing disease transmission.
Sandrock Christian,Stollenwerk Nicholas
Acute febrile respiratory illness (FRI) leading to respiratory failure is a common reason for admission to the ICU. Viral pneumonia constitutes a portion of these cases, and often the viral etiology goes undiagnosed. Emerging viral infectious diseases such as severe acute respiratory syndrome and avian influenza present with acute FRIs progressing to respiratory failure and ARDS. Therefore, early recognition of a viral cause of acute FRI leading to ARDS becomes important for protection of health-care workers (HCWs), lessening spread to other patients, and notification of public health officials. These patients often have longer courses of viral shedding and undergo higher-risk procedures that may potentially generate aerosols, such as intubation, bronchoscopy, bag-valve mask ventilation, noninvasive positive pressure ventilation, and medication nebulization, further illustrating the importance of early detection and isolation. A small number of viral agents lead to acute FRI, respiratory failure, and ARDS: seasonal influenza, avian influenza, coronavirus associated with severe ARDS, respiratory syncytial virus, adenovirus, varicella, human metapneumovirus, and hantavirus. A systematic approach to early isolation, testing for these agents, and public health involvement becomes important in dealing with acute FRI. Ultimately, this approach will lead to improved HCW protection, reduction of transmission to other patients, and prevention of transmission in the community.
The similarities and differences of epidemic cycles of chronic obstructive pulmonary disease and asthma exacerbations.
Johnston Neil W
Proceedings of the American Thoracic Society
The majority of chronic obstructive pulmonary disease (COPD) and asthma exacerbations in both children and adults are associated with respiratory viral infections and are cyclic in nature. Some variation in these cycles is associated with the timing of the appearance of respiratory viruses, particularly influenza and respiratory syncytial virus. Much more, however, is associated with signal events that are of either fixed or predictable timing. In children, asthma exacerbations reach epidemic levels following school return after the summer vacation and these are predominantly associated with rhinovirus infections. Although younger adults experience a rise in asthma exacerbations at this time, these are secondary to the epidemic in children. Older adults with either COPD or asthma experience only a slightly elevated risk of exacerbations after school return, and hospital presentations for pneumonia in any age group show only marginal increases at that time. Exacerbations of both COPD and adult asthma, with increasing risk with age, are at their highest average annual levels during the Christmas period. This effect appears to be independent of the timing of above average levels of influenza, RSV, parainfluenza, or adenovirus detections; however, hospitalization for respiratory tract infections in all age groups reaches high levels at the same time. Both the post-summer vacation asthma epidemic and the Christmas epidemic of COPD, asthma, and pneumonia are synchronous with the timing of signal events, the day of school return for the former and Christmas Day for the latter, and have been for several years. The agents responsible for the Christmas epidemic of respiratory diseases have not yet been identified. The differences between age and disease exacerbation patterns after school return and at Christmas suggest that either different agents are involved or that the response to a common agent is different between the two signal events.
Bronchiolitis obliterans in children.
Moonnumakal Siby P,Fan Leland L
Current opinion in pediatrics
PURPOSE OF REVIEW:In this review, we discuss recent advances in our understanding of the etiology, pathology and pathogenesis, clinical presentation, diagnosis, treatment, and outcome of bronchiolitis obliterans in the nontransplant, pediatric population. RECENT FINDINGS:The diagnosis of bronchiolitis obliterans in children can be made with confidence based on clinical presentation, particularly with a history of adenovirus bronchiolitis or pneumonia, fixed obstructive lung disease on pulmonary function testing, and characteristic changes of mosaic perfusion, vascular attenuation, and central bronchiectasis on chest high-resolution computed tomography, thus avoiding the need for lung biopsy in most patients. Patients with postinfectious bronchiolitis obliterans generally have chronic, nonprogressive disease; in contrast, patients with bronchiolitis obliterans from Stevens-Johnson syndrome often have progressive disease that may require lung transplantation. SUMMARY:Bronchiolitis obliterans is a rare form of chronic obstructive lung disease that follows a severe insult to the lower respiratory tract, resulting in fibrosis of the small airways. In the nontransplant pediatric population, adenovirus infection is the most common cause. Treatment is largely supportive and prognosis is mainly related to the underlying cause and to the severity of the initial insult.
The role of secretory leukocyte proteinase inhibitor and elafin (elastase-specific inhibitor/skin-derived antileukoprotease) as alarm antiproteinases in inflammatory lung disease.
Sallenave J M
Secretory leukocyte proteinase inhibitor and elafin are two low-molecular-mass elastase inhibitors that are mainly synthesized locally at mucosal sites. It is thought that their physicochemical properties allow them to efficiently inhibit target enzymes, such as neutrophil elastase, released into the interstitium. Historically, in the lung, these inhibitors were first purified from secretions of patients with chronic obstructive pulmonary disease and cystic fibrosis. This suggested that they might be important in controlling excessive neutrophil elastase release in these pathologies. They are upregulated by 'alarm signals' such as bacterial lipopolysaccharides, and cytokines such as interleukin-1 and tumor necrosis factor and have been shown to be active against Gram-positive and Gram-negative bacteria, so that they have joined the growing list of antimicrobial 'defensin-like' peptides produced by the lung. Their site of synthesis and presumed functions make them very attractive candidates as potential therapeutic agents under conditions in which the excessive release of elastase by neutrophils might be detrimental. Because of its natural tropism for the lung, the use of adenovirus-mediated gene transfer is extremely promising in such applications.
Histone acetylation and deacetylation: importance in inflammatory lung diseases.
Barnes P J,Adcock I M,Ito K
The European respiratory journal
Inflammatory lung diseases are characterised by increased expression of multiple inflammatory genes that are regulated by proinflammatory transcription factors, such as nuclear factor-kappa B. Gene expression is regulated by acetylation of core histones through the action of coactivators, such as CREB-binding protein, with intrinsic histone acetyltransferase (HAT) activity. Conversely, gene repression is mediated via histone deacetylases (HDACs) and other corepressors. In asthma, there is an increase in HAT activity and some reduction in HDAC activity, which is restored by corticosteroid therapy. Corticosteroids switch off inflammatory genes in asthma through the inhibition of HAT activity and by the recruitment of HDAC2 to the activated inflammatory gene complex. In chronic obstructive pulmonary disease, there is a reduction in HDAC2 activity and expression, which may account for the amplified inflammation and resistance to the actions of corticosteroids. The reduction in HDAC2 may be secondary to oxidative and nitrative stress as a result of cigarette smoking and severe inflammation, and may also occur in severe asthma, smoking asthmatic patients and cystic fibrosis. Similar mechanisms may also account for the steroid resistance seen with latent adenovirus infections. The reduction in histone deacetylase activity can be restored by theophylline, which may be able to reverse steroid resistance in chronic obstructive pulmonary disease and other inflammatory diseases.
Other Community Respiratory Viruses.
Wunderink Richard G
Clinics in chest medicine
Polymerase chain reaction-based diagnosis has become the standard for viral pneumonia and other respiratory tract infections. Expansion of respiratory viral panels (RVPs) outside of influenza and, possibly, respiratory syncytial virus has led to the ability to diagnose viral infections for which no approved specific antiviral treatment exists. Careful clinical evaluation of the patient with a positive RVP is, therefore, critical given the limited repertoire of treatments. Generic treatments with intravenous immunoglobulin, ribavirin, and interferons may benefit select severe viral pneumonia patients, whereas cidofovir has activity for severe adenoviral pneumonia.
Viral pneumonias in adults: radiologic and pathologic findings.
Kim Eun A,Lee Kyung Soo,Primack Steven L,Yoon Hye Kyung,Byun Hong Sik,Kim Tae Sung,Suh Gee Young,Kwon O Jung,Han Joungho
Radiographics : a review publication of the Radiological Society of North America, Inc
Numerous viruses, including influenza virus, measles virus, Hantavirus, adenovirus, herpesviruses, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus, can cause lower respiratory tract infection in adults. Viral pneumonia in adults can be classified into two clinical groups: so-called atypical pneumonia in otherwise healthy hosts and viral pneumonia in immunocompromised hosts. Influenza virus types A and B cause most cases of viral pneumonia in immunocompetent adults. Immunocompromised hosts are susceptible to pneumonias caused by cytomegalovirus, herpesviruses, measles virus, and adenovirus. The radiographic findings, which consist mainly of patchy or diffuse ground-glass opacity with or without consolidation and reticular areas of increased opacity, are variable and overlapping. Computed tomographic findings, which are also overlapping, consist of poorly defined centrilobular nodules, ground-glass attenuation with a lobular distribution, segmental consolidation, or diffuse ground-glass attenuation with thickened interlobular septa. The radiologic findings reflect the variable extents of the histopathologic features: diffuse alveolar damage (intraalveolar edema, fibrin, and variable cellular infiltrates with a hyaline membrane), intraalveolar hemorrhage, and interstitial (intrapulmonary or airway) inflammatory cell infiltration. Clinical information such as patient age, immune status, community outbreaks, symptom onset and duration, and presence of a rash remain important aids in diagnosis of viral causes.
Severe Respiratory Viral Infections: New Evidence and Changing Paradigms.
Walter James M,Wunderink Richard G
Infectious disease clinics of North America
Lower respiratory tract infection is a leading cause of death in the United States. Advances in diagnostic testing have improved our ability to detect pathogens. Viral pathogens are important causal pathogens in immunocompetent patients. As the number of elderly adults and those with chronic medical conditions increases, the burden of viral respiratory infections will increase. Clinicians must be familiar with the characteristics of rhinovirus, human adenoviruses, respiratory syncytial virus, and human metapneumovirus. Major challenges include distinguishing true infection from asymptomatic carriage and characterizing patients admitted with severe lower respiratory tract infection who do not have a causative pathogen identified.
Marcos Maria Angeles,Esperatti Mariano,Torres Antoni
Current opinion in infectious diseases
PURPOSE OF REVIEW:Community-acquired pneumonia (CAP) has traditionally focused little on viral causes, and few studies have done an extensive and appropriate evaluation for viral cause. The purpose of the present article is to review several issues of viral infection in CAP in light of recent studies that included exhaustive evaluation of viruses. RECENT FINDINGS:The introduction of better quality diagnostic tests, such as nucleic acid amplification techniques, have markedly improved our ability to detect multiple viral pathogens. With these diagnostic tools, a viral cause can be established in more than half of patients with CAP. Influenza A and respiratory syncytial virus are the most frequent causes of viral pneumonia followed by adenovirus, parainfluenza virus types 1, 2, and 3, and influenza. Although some clinical findings have been more frequent with viral infection, no clear-cut clinical signs have been shown to be predictive of specific cause. Of more interest is the association of mixed virus-bacteria infection with poorer severity scores found in some studies. The diagnostic approach with new techniques should be taken for a true estimation of viral infection in epidemiologic studies.Unfortunately, there are no other licensed antivirals or vaccines against the large variety of clinically important respiratory viruses with the notable exception of influenza. SUMMARY:Given the high rate of viral infection in CAP and its probable association with poorer prognosis in mixed virus-bacteria infection, an extensive evaluation for virus in some populations seems appropriate. These findings can be useful for a more appropriate management of these patients.
Viral pneumonia: epidemiological, clinical, pathophysiological and therapeutic aspects.
Figueiredo Luiz Tadeu Moraes
Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia
In humans, the most common types of infection are respiratory tract infections, among which viral infections predominate. Viruses can also infect the low respiratory tract, causing bronchiolitis, bronchitis and pneumonia. The objective of this review article was to show epidemiological, pathophysiological, clinical and therapeutic aspects of viral community-acquired pneumonia. These types of pneumonia are commonly caused by influenza A and B; parainfluenza 1, 2 and 3; respiratory syncytial virus; or adenovirus. We also address the types of pneumonia caused by hantaviruses, metapneumoviruses and rhinoviruses.
Influenza and endemic viral pneumonia.
Ramsey Clare D,Kumar Anand
Critical care clinics
Viruses are a common and important cause of severe community-acquired pneumonia, and may lead to severe respiratory disease and admission to the intensive care unit. Influenza is the most common virus associated with severe viral pneumonia, although other important causes include respiratory syncytial virus, adenovirus, metapneumonia virus, and coronaviruses. Viral pneumonias tend to have a seasonal predilection and are often preceded by a typical viral prodrome. This article focuses on severe influenza pneumonia, including the 2009 H1N1 pandemic, and briefly discusses other causes of severe respiratory disease of viral etiology.
Epidemic viral pneumonia and other emerging pathogens.
Radigan Kathryn A,Wunderink Richard G
Clinics in chest medicine
Viruses cause a high percentage of community-acquired pneumonias. The advent of polymerase chain reaction and other molecular techniques has been associated with the detection of a higher prevalence of common respiratory viruses than previously suspected. Better diagnostics have shown new viral pathogens regularly in epidemics, immunocompromised patients, and occasionally children. Despite better diagnostics, treatment for all but influenza is still very limited.
Treatment of Adenoviral Acute Respiratory Distress Syndrome Using Cidofovir With Extracorporeal Membrane Oxygenation.
Lee Minhyeok,Kim Seulgi,Kwon Oh Jung,Kim Ji Hye,Jeong Inbeom,Son Ji Woong,Na Moon Jun,Yoon Yoo Sang,Park Hyun Woong,Kwon Sun Jung
Journal of intensive care medicine
Adenovirus infections are associated with respiratory (especially upper respiratory) infection and gastrointestinal disease and occur primarily in infants and children. Although rare in adults, severe lower respiratory adenovirus infections including pneumonia are reported in specific populations, such as military recruits and immunocompromised patients. Antiviral treatment is challenging due to limited clinical experience and lack of well-controlled randomized trials. Several previously reported cases of adenoviral pneumonia showed promising efficacy of cidofovir. However, few reports discussed the efficacy of cidofovir in acute respiratory distress syndrome (ARDS). We experienced 3 cases of adenoviral pneumonia associated with ARDS and treated with cidofovir and respiratory support, including extracorporeal membrane oxygenation (ECMO). All 3 patients showed a positive clinical response to cidofovir and survival at 28 days. Cidofovir with early ECMO therapy may be a therapeutic option in adenoviral ARDS. A literature review identified 15 cases of adenovirus pneumonia associated with ARDS.
Viral infections of the lower respiratory tract: old viruses, new viruses, and the role of diagnosis.
Pavia Andrew T
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Viral infections of the lower respiratory tract cause an enormous disease burden in children, and the role of respiratory viruses in serious lower respiratory tract infections (LRTIs) in older adults is increasingly appreciated. Although viruses are responsible for a large proportion LRTIs, antibiotics are often prescribed. New diagnostic platforms have the potential to detect a wider range of established and newly discovered viruses with greater sensitivity. This will create additional challenges. Although it is clear that influenza, parainfluenza, respiratory syncytial virus, human metapneumovirus, and adenovirus are important causes of pneumonia, the role of rhinoviruses and some of the newly described viruses, including human coronaviruses and bocavirus, is harder to determine. Better diagnostic tests that establish the cause of LRTIs in children have the potential to both reduce overall antibiotic use and to improve the targeted use of antibiotics. In addition, rapid identification of viral infections can help control nosocomial transmission.
[Post-infectious bronchiolitis obliterans].
de Blic J,Deschildre A,Chinet T
Revue des maladies respiratoires
Post-infectious bronchiolitis obliterans (BO) is characterized by inflammatory and fibrotic lesions of small airways following a pulmonary infection and leading to some degree of airway obstruction. It represents a rare cause of chronic obstructive pulmonary disease, and is probably underestimated, especially when the lesions affect small areas of the lungs. The clinical features differ between children and adults. In children, adenovirus is the most frequently involved infectious agent, especially the more virulent serotypes 3, 7 and 21. The clinical and radiological signs vary widely and the functional outcome depends on the extent of the lung injury. The diagnosis is based on the medical history, the CT-scan and functional data. The treatment is symptomatic. The most severe forms may result in chronic respiratory insufficiency. In adults, the frequency of obstructive injuries of the small airways in the context of lung infection is unclear. Parenchymal lesions are often present, resulting in BO with organizing pneumonia. These lesions alter the clinical presentation and the radiographic features of the initial infectious disease and often prove difficult to diagnose and manage. Several authors have published clinical cases describing presumed efficacy of systemic corticosteroids but the data are scarce.
Long term sequelae from childhood pneumonia; systematic review and meta-analysis.
Edmond Karen,Scott Susana,Korczak Viola,Ward Catherine,Sanderson Colin,Theodoratou Evropi,Clark Andrew,Griffiths Ulla,Rudan Igor,Campbell Harry
BACKGROUND:The risks of long term sequelae from childhood pneumonia have not been systematically assessed. The aims of this study were to: (i) estimate the risks of respiratory sequelae after pneumonia in children under five years; (ii) estimate the distribution of the different types of respiratory sequelae; and (iii) compare sequelae risk by hospitalisation status and pathogen. METHODS:We systematically reviewed published papers from 1970 to 2011. Standard global burden of disease categories (restrictive lung disease, obstructive lung disease, bronchiectasis) were labelled as major sequelae. 'Minor' sequelae (chronic bronchitis, asthma, other abnormal pulmonary function, other respiratory disease), and multiple impairments were also included. Thirteen papers were selected for inclusion. Synthesis was by random effects meta-analysis and meta-regression. RESULTS:Risk of at least one major sequelae was 5.5% (95% confidence interval [95% CI] 2.8-8.3%) in non hospitalised children and 13.6% [6.2-21.1%]) in hospitalised children. Adenovirus pneumonia was associated with the highest sequelae risk (54.8% [39.2-70.5%]) but children hospitalised with no pathogen isolated also had high risk (17.6% [10.9-24.3%]). The most common type of major sequela was restrictive lung disease (5.4% [2.5-10.2%]) . Potential confounders such as loss to follow up and median age at infection were not associated with sequelae risk in the final models. CONCLUSIONS:All children with pneumonia diagnosed by a health professional should be considered at risk of long term sequelae. Evaluation of childhood pneumonia interventions should include potential impact on long term respiratory sequelae.
Viruses associated with pneumonia in adults.
Cesario Thomas C
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Viral pneumonia, which is typically associated with disease in childhood, is increasingly recognized as causing problems in adults. Certain viruses, such as influenza virus, can attack fully immunocompetent adults, but many viruses take advantage of more-vulnerable patients. The latter include patients receiving immunosuppressive therapy and elderly subjects, particularly those residing in long-term care facilities. The range of viruses producing pneumonia in adults includes common agents, such as varicella-zoster virus and influenza virus, as well as respiratory syncytial virus, human metapneumovirus, adenoviruses, picornaviruses, and coronaviruses. The roles played by other agents, such as rhinoviruses and human bocaviruses, in pneumonia are still under study. While therapy for most of theses agents, at least in adults, has not yet been fully clarified, it is reasonable to assume antivirals may work in certain situations if they are introduced early enough in the course of infection.
Viral etiology of hospitalized acute lower respiratory infections in children under 5 years of age -- a systematic review and meta-analysis.
Lukšić Ivana,Kearns Patrick K,Scott Fiona,Rudan Igor,Campbell Harry,Nair Harish
Croatian medical journal
AIM:To estimate the proportional contribution of influenza viruses (IV), parainfluenza viruses (PIV), adenoviruses (AV), and coronaviruses (CV) to the burden of severe acute lower respiratory infections (ALRI). METHODS:The review of the literature followed PRISMA guidelines. We included studies of hospitalized children aged 0-4 years with confirmed ALRI published between 1995 and 2011. A total of 51 studies were included in the final review, comprising 56091 hospitalized ALRI episodes. RESULTS:IV was detected in 3.0% (2.2%-4.0%) of all hospitalized ALRI cases, PIV in 2.7% (1.9%-3.7%), and AV in 5.8% (3.4%-9.1%). CV are technically difficult to culture, and they were detected in 4.8% of all hospitalized ALRI patients in one study. When respiratory syncytial virus (RSV) and less common viruses were included, at least one virus was detected in 50.4% (40.0%-60.7%) of all hospitalized severe ALRI episodes. Moreover, 21.9% (17.7%-26.4%) of these viral ALRI were mixed, including more than one viral pathogen. Among all severe ALRI with confirmed viral etiology, IV accounted for 7.0% (5.5%-8.7%), PIV for 5.8% (4.1%-7.7%), and AV for 8.8% (5.3%-13.0%). CV was found in 10.6% of virus-positive pneumonia patients in one study. CONCLUSIONS:This article provides the most comprehensive analysis of the contribution of four viral causes to severe ALRI to date. Our results can be used in further cost-effectiveness analyses of vaccine development and implementation for a number of respiratory viruses.
Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children.
Gavin Patrick J,Katz Ben Z
BACKGROUND:Adenovirus is an important cause of morbidity and mortality in the immunocompromised host. The incidence of severe adenovirus disease in pediatrics is increasing in association with growing numbers of immunocompromised children, where case fatality rates as high as 50% to 80% have been reported. There are no approved antiviral agents with proven efficacy for the treatment of severe adenovirus disease, nor are there any prospective randomized, controlled trials of potentially useful anti-adenovirus therapies. Apparent clinical success in the treatment of severe adenovirus disease is limited to a few case reports and small series. Experience is greatest with intravenous ribavirin and cidofovir. Ribavirin, a guanosine analogue, has broad antiviral activity against both RNA and DNA viruses, including documented activity against adenovirus in vitro. Ribavirin is licensed in aerosol form for the treatment of respiratory syncytial virus infection, and orally in combination with interferon to treat hepatitis C. Intravenous ribavirin is the treatment of choice for infection with hemorrhagic fever viruses. The most common adverse effect of intravenous ribavirin is reversible mild anemia. The use of cidofovir in severe adenovirus infection has been limited by adverse effects, the most significant of which is nephrotoxicity. OBJECTIVE:We report our experience with intravenous ribavirin therapy for severe adenovirus disease in a series of immunocompromised children and review the literature. DESIGN/METHODS:We retrospectively reviewed the medical records of 5 children treated with intravenous ribavirin for documented severe adenovirus disease. Two patients developed adenovirus hemorrhagic cystitis after cardiac and bone marrow transplants, respectively. The bone marrow transplant patient also received intravenous cidofovir for progressive disseminated disease. An additional 3 children developed adenovirus pneumonia; 2 were neonates, 1 of whom had partial DiGeorge syndrome. The remaining infant had recently undergone a cardiac transplant. Intravenous ribavirin was administered on a compassionate-use protocol. RESULTS:Complete clinical recovery followed later by viral clearance was observed in 2 children: the cardiac transplant recipient with adenovirus hemorrhagic cystitis and the immunocompetent neonate with adenovirus pneumonia. The remaining 3 children died of adenovirus disease. Intravenous ribavirin therapy was well tolerated. Use of cidofovir in 1 child was associated with progressive renal failure and neutropenia. DISCUSSION:Our series of patients is representative of the spectrum of immunocompromised children at greatest risk for severe adenovirus disease, namely solid-organ and bone marrow transplant recipients, neonates, and children with immunodeficiency. Although intravenous ribavirin was not effective for all children with severe adenovirus disease in this series or in the literature, therapy is unlikely to be of benefit if begun late in the course of the infection. Early identification, eg by polymerase chain reaction of those patients at risk of disseminated adenovirus disease may permit earlier antiviral treatment and better evaluation of therapeutic response. CONCLUSIONS:Two of 5 children with severe adenovirus disease treated with intravenous ribavirin recovered. The availability of newer rapid diagnostic techniques, such as polymerase chain reaction, may make earlier, more effective treatment of adenovirus infection possible. Given the seriousness and increasing prevalence of adenovirus disease in certain hosts, especially children, a large, multicenter clinical trial of potentially useful anti-adenoviral therapies, such as intravenous ribavirin, is clearly required to demonstrate the most effective and least toxic therapy.
Clinical manifestations and risk factors of adenovirus respiratory infection in hospitalized children in Guangzhou, China during the 2011-2014 period.
Wu Pei-Qiong,Zeng Sen-Qiang,Yin Gen-Quan,Huang Jian-Jun,Xie Zhi-Wei,Lu Gen,Jiang Wen-Hui
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.
Clinical features of community acquired adenovirus pneumonia during the 2011 community outbreak in Southern Taiwan: role of host immune response.
Shen Ching-Fen,Wang Shih-Min,Ho Tzong-Shiann,Liu Ching-Chuan
BMC infectious diseases
BACKGROUND:Human adenovirus 7 (HAdV-7) was responsible for a significant number of fatalities during the 2011 community outbreak in Taiwan. The mechanisms underlying the pathogenesis of severe adenovirus infections in non-immunocompromised individuals remain unclear. Adenovirus pneumonia was associated with pleural effusion in a number of patients from the 2011 outbreak suggesting that similar to bacterial pneumonia, patients diagnosed with adenovirus pneumonia who have pleural effusion are more severely and systemically infected, and may have a more protracted disease course. We hypothesized that the host immunological response determines the severity of adenoviral infection. METHODS:This retrospective case series study included patients diagnosed with severe lower respiratory tract infections at the National Cheng Kung University Hospital in southern Taiwan between December 2010 and October 2011. The main inclusion criteria were 1) presence of multifocal patchy infiltrates, lobar consolidation or reticular interstitial opacities in chest X-rays, and 2) presence of adenovirus isolated from respiratory specimens. All patients had adenovirus isolated from respiratory specimens, and were negative for other viruses. Pleural effusion was confirmed in all patients using chest echography. Clinical features and laboratory data were compared in patients with (n = 12) and without (n = 15) parapneumonic effusion. RESULTS:Presence of parapneumonic effusion was significantly associated with a longer febrile duration, more complicated clinical management, and a greater risk of extrapulmonary involvement, notably hepatitis. Patients without pleural effusion had significantly higher numbers of WBCs, platelets, and absolute segment cell counts (ASCs) compared to patients with pleural effusion (all p < 0.05). Patients without pleural effusion had significantly higher counts of CD4+, CD8+, and CD20+ T cells (all p < 0.05) compared to patients with pleural effusion. CONCLUSION:Our data indicated that presence of parapneumonic effusion in adenoviral pneumonia was associated with longer febrile duration, more complicated clinical management, a greater risk of hepatitis, and suppression of host cellular immunity. Further prospective, large-scale studies are needed to validate our results.
Ison Michael G,Hayden Randall T
Adenoviruses are a highly prevalent infection that can cause a range of clinical syndromes in immunocompromised patients, ranging from localized disease of the respiratory tract, gastrointestinal tract, or urinary tract to disseminated disease. Adenovirus infections may develop in this unique population as the result of primary infection or reactivation of latent virus. Disease can be potentially progressive with high rates of mortality in patients with pneumonia and disseminated disease. Fortunately, cidofovir and its lipid ester, brincidofovir, appear to be effective for the treatment of adenovirus, although neither is specifically approved for this indication. Adenovirus should always be considered when immunocompromised patients present with any clinical syndrome that could be compatible with adenoviral infection. Once disease is suspected, cultures or molecular testing of appropriate specimens should be obtained and blood should be sent for adenovirus polymerase chain reaction (PCR) whenever adenovirus is suspected. Monitoring of quantitative viral loads in blood is helpful in predicting response to therapy with a significant drop (>1 log) associated with a higher probability of clinical response.
Lynch Joseph P,Fishbein Michael,Echavarria Marcela
Seminars in respiratory and critical care medicine
Adenoviruses (AdV) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal (GI) tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or encephalitis. Adenovirus infections are more common in young children, owing to lack of humoral immunity. Epidemics of AdV infections may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The disease is more severe, and dissemination is more likely in patients with impaired immunity (eg, organ transplant recipients, human immunodeficiency virus infection, congenital immunodeficiency syndromes). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 50 serotypes of AdV have been identified. Different serotypes display different tissue trophisms and correlate with clinical manifestations of infection. The predominant serotypes differ among countries or regions and change over time. Transmission of novel strains between countries or across continents and replacement of dominant serotypes by new strains may occur. Treatment of AdV infections is controversial because prospective, randomized therapeutic trials have not been done. Cidofovir is considered the drug of choice for severe AdV infections, but not all patients require treatment. Vaccines have been shown to be highly efficacious in reducing the risk of respiratory AdV infection but are currently not available.