A review of 65 years of human adenovirus seroprevalence.

Introduction: Human adenovirus (HAdV)-derived vectors have been used in numerous pre-clinical and clinical trials during the last 40 years. Current research in HAdV-based vaccines focuses on improving transgene immunogenicity and safety. Because pre-existing humoral immunity against HAdV types correlate with reduced vaccine efficacy and safety, many groups are exploring the development of HAdV types vectors with lower seroprevalence. However, global seroepidemiological data are incomplete. Areas covered: The goal of this review is to centralize 65 years of research on (primarily) HAdV epidemiology. After briefly addressing adenovirus biology, we chronical HAdV seroprevalence studies and highlight major milestones. Finally, we analyze data from about 50 studies with respect to HAdVs types that are currently used in the clinic, or are in the developmental pipeline. Expert opinion: Vaccination is among the most efficient tools to prevent infectious disease. HAdV-based vaccines have undeniable potential, but optimization is needed and antivector immunity remains a challenge if the same vectors are to be administrated to different populations. Here, we identify gaps in our knowledge and the need for updated worldwide epidemiological data.

Dynamic Changes in Clinical Characteristics During an Outbreak of Human Adenovirus Serotype 55 in China.

OBJECTIVE: To determine dynamic changes in clinical characteristics by examining an outbreak of adenovirus infection that occurred from December 20, 2012, to February 25, 2013, in Tianjin, China. METHODS: Active surveillance for febrile respiratory illnesses was conducted, and medical records of patients were collected. Real-time quantitative polymerase chain reaction and sequencing were used for pathogen identification and viral genome study, respectively. Student's t-test was used to compare the mean values of normally distributed continuous variables. Mann-Whitney U or Kruskal-Wallis tests were used if continuous variables were not normally distributed. Pearson's chi-square test or Fisher's exact test was used to compare categorical variables. RESULTS: The outbreak was sourced from the index case diagnosed as the common cold on December 20, 2012; a total of 856 cases were reported in the following 66 days. The pathogen was identified as human adenovirus (HAdV) 55. The symptoms manifested differently in severe and mild cases. Routine blood examinations, liver function indexes, and heart function indexes showed different dynamic patterns over time in hospitalized patients. CONCLUSIONS: Clinical characteristics and laboratory examinations may reveal unique patterns over the course of HAdV-55 infection. (Disaster Med Public Health Preparedness. 2018;12:464-469).

Human Adenovirus 36 Infection Increased the Risk of Obesity: A Meta-Analysis Update.

Human adenovirus 36 (HAdV-36), as the key pathogen, was supposed and discussed to be associated with obesity. We searched the references on the association between HAdV-36 infection and obesity with the different epidemiological methods, to explore the relationship with a larger sample size by meta-analysis and compare the differences of epidemiological methods and population subsets by the subgroup analyses.We conducted literature search on the association between HAdV-36 infections and obesity in English or Chinese published up to July 1, 2015. The primary outcome was the HAdV-36 infection rate in the obese and lean groups; the secondary outcomes were the BMI level and BMI z-score in the HAdV-36 positive and negative groups. The pooled odds ratio (OR) was calculated for the primary outcome; the standardized mean differences (SMDs) were calculated for the secondary and third outcomes. Prediction interval (PI) was graphically presented in the forest plot of the random effect meta-analyses. Metaregression analysis and subgroup analysis were performed.Finally 24 references with 10,191 study subjects were included in the meta-analysis. The obesity subjects were more likely to be infected with HAdV-36 compared to the lean controls (OR = 2.00; 95%CI: 1.46, 2.74; PI: 0.59, 6.76; P < 0.001) with a high heterogeneity (I = 80.1%; P < 0.001) estimated by the random effect model. Subgroup analysis demonstrated that the pooled OR of HAdV-36 infection for obesity were 1.77 (95%CI: 1.19, 2.63; PI: 0.44, 7.03; P = 0.005) and 2.26 (95%CI: 1.67, 3.07; PI: 1.45, 3.54; P < 0.001) in the adults and children, respectively. Compared to the HAdV-36 negative subjects, the SMD of BMI was 0.28 (95% CI: 0.08, 0.47; PI: -0.53, 1.08; P = 0.006) in the HAdV-36 positive subjects with a high heterogeneity (I = 86.5%; P < 0.001). The BMI z-score in the children with HAdV-36 infection was higher than those without HAdV-36 infection (SMD = 0.19; 95%CI: -0.31, 0.70; PI: -2.10, 2.49), which had no significantly statistical difference (P = 0.453).HAdV-36 infection increased the risk of obesity. HAdV-36 also increased the risk of weight gain in adults, which was not observed in children.

Association of viral isolates from stool samples with intussusception in children.

BACKGROUND: Intussusception is the most common cause of intestinal obstruction in young children. The pathogenesis of intussusception is still not well understood. In this study the pathogens from stool specimens were investigated in children with intussusception. METHODS: Patients diagnosed with primary idiopathic intussusception were enrolled. Pathogenic bacteria and viruses were detected in the stool samples by routine culture, cell culture, polymerase chain reaction, reverse transcriptase-polymerase chain reaction, enzyme immunoassay, and electron microscopy examinations. RESULTS: A total of 71 samples were analyzed during the 2-year study period. The patients ranged in age from 4 to 47 months. Viruses were detected in 56 of the 71 stool samples (78.9%). Adenovirus was found in 19 of 35 cases aged <2 years, whereas it was found in 17 of 21 cases aged ≥2 years. The majority of adenovirus isolates were non-enteric organisms generally associated with respiratory tract symptoms. CONCLUSIONS: These results suggest a casual association of viral infections in children with intussusception. Adenovirus infection, especially with the primary non-enteric types, is a significant risk factor for developing intussusception in children, particularly those aged over 2 years.

Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004-2006.

BACKGROUND: Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus. METHODS: In an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during 2004-2006. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method. RESULTS: Among civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%). CONCLUSIONS: For both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age <7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease.

Human adenoviruses types associated with non-gonococcal urethritis.

BACKGROUND: Role of adenoviruses in non-gonococcal urethritis (NGU) has been reported in only a few studies. The aim of the study was to detect and type adenoviruses in men presenting with NGU. METHODS: 636 heterosexual and homosexual men presenting with NGU from Melbourne, Australia were recently evaluated for various aetiological organisms including adenovirus. We utilised methods including polymerase chain reaction for detection followed by sequence analysis to type positive samples. RESULTS: Overall, 12 samples from patients with NGU had adenovirus detected. Five types were identified: type 4 (subgenus E), type 35 (subgenus B), and types 9, 37 and 49 (subgenus D). The presence of mixed adenovirus strains was not detected in any sample. CONCLUSION: Overall, subgenus B, D and E were predominant in this patient population.

Surveillance of transcriptomes in basic military trainees with normal, febrile respiratory illness, and convalescent phenotypes.

Gene expression profiles permit analysis of host immune response at the transcriptome level. We used the Pax gene Blood RNA (PAX) System and Affymetrix microarrays (HG-U133A&B) to survey profiles in basic military trainees and to classify them as healthy, febrile respiratory illness (FRI) without adenovirus, FRI with adenovirus, and convalescent from FRI with adenovirus. We assessed quality metrics of RNA processing for microarrays. Class prediction analysis discovered nested sets of transcripts that could categorize the phenotypes with optimized accuracy of 99% (nonfebrile vs febrile, P<0.0005), 87% (healthy vs convalescent, P=0.001), and 91% (febrile without vs with adenovirus, P<0.0005). The discovered set for classification of nonfebrile vs febrile patients consisted of 40 transcripts with functions related to interferon induced genes, complement cascades, and TNF and IL1 signaling. The set of seven transcripts for distinguishing healthy vs convalescent individuals included those associated with ribosomal structure, humoral immunity, and cell adhesion. The set of 10 transcripts for distinguishing FRI without vs with adenovirus had functions related to interferon induced genes, IL1 receptor accessory protein, and cell interactions. These results are the first in vivo demonstration of classification of infectious diseases via host signature transcripts and move us towards using the transcriptome in bio-surveillance.

Enfermedad neurologica por adenovirus / Neurologic disease due to adenovirus infection

El objetivo de este trabajo fue determinar la prevalencia de adenovirus (ADV) en las infecciones del sistema nervioso central (SNC). Se analizaron 108 muestras de líquido cefalorraquídeo (LCR) provenientes de 79 casos de encefalitis, 7 meningitis y 22 de otras patologías neurológicas, recibidas en el período 2000-2002. Cuarenta y nueve (47.35%) se obtuvieron de pacientes inmunocomprometidos. La presencia de ADV se investigó mediante reacción en cadena de la polimerasa en formato anidado (Nested-PCR). La identificación del genogrupo se realizó mediante análisis filogenético de la secuencia nucleotídica parcial de la región que codifica para la proteína del hexón. Se detectó la presencia de ADV en 6 de 108 (5.5%) muestras de LCR analizadas. Todos los casos positivos pertenecieron a pacientes con encefalitis que fueron 79, (6/79, 7.6%). No se observó diferencia estadísticamente significativa entre los casos de infección por ADV en pacientes inmunocomprometidos e inmunocompetentes (p>0.05). Las cepas de ADV detectadas se agruparon en los genogrupos B1 y C. En conclusión, nuestros resultados describen el rol de los ADV en las infecciones neurológicas en Argentina. La información presentada contribuye al conocimiento de su epidemiología, en particular en casos de encefalitis.

Infección viral del tracto respiratorio inferior

Las infecciones respiratorias agudas son una de las principales causas de morbilidad y mortalidad entre los niños. Con el desarrollo de tecnologías de diagnóstico rápido para la detección de antígenos virales es posible reconocer el agente viral de la infección respiratoria en horas. El diagnóstico etiológico de infección respiratoria viral es no sólo cada vez más importante para la selección apropiada de los pacientes que deben recibir tratamiento antiviral o con antibióticos, sino también para el control de la diseminación de las infecciones respiratorias virales en salas pediátricas. En la Clínica Amparo Infantil Santa Ana de Medellín ocurrió un brote de infección respiratoria aguda del tracto respiratorio inferior en el último trimestre de 1994 producida por virus. Los virus detectados fueron virus respiratorio sincitial 41.8 por ciento, adenovirus 33,3 por ciento, parainfluenza tipo 1, en el 8.3 por ciento e infección mixta en el 16.7 por ciento. Se describe el método diagnóstico utilizado en la detección de los antígenos virales y las características de este brote.