Human adenoviruses (HAdVs) are an important cause of infections in both immunocompetent and immunocompromised individuals, and they continue to provide clinical challenges pertaining to diagnostics and treatment. The growing number of HAdV types identified by genomic analysis, as well as the improved understanding of the sites of viral persistence and reactivation, requires continuous adaptions of diagnostic approaches to facilitate timely detection and monitoring of HAdV infections. In view of the clinical relevance of life-threatening HAdV diseases in the immunocompromised setting, there is an urgent need for highly effective treatment modalities lacking major side effects. The present review summarizes the recent progress in the understanding and management of HAdV infections.

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

Viruses are the most common causes of respiratory infection. The imaging findings of viral pneumonia are diverse and overlap with those of other nonviral infectious and inflammatory conditions. However, identification of the underlying viral pathogens may not always be easy. There are a number of indicators for identifying viral pathogens on the basis of imaging patterns, which are associated with the pathogenesis of viral infections. Viruses in the same viral family share a similar pathogenesis of pneumonia, and the imaging patterns have distinguishable characteristics. Although not all cases manifest with typical patterns, most typical imaging patterns of viral pneumonia can be classified according to viral families. Although a definite diagnosis cannot be achieved on the basis of imaging features alone, recognition of viral pneumonia patterns may aid in differentiating viral pathogens, thus reducing the use of antibiotics. Recently, new viruses associated with recent outbreaks including human metapneumovirus, severe acute respiratory syndrome coronavirus, and Middle East respiratory syndrome coronavirus have been discovered. The imaging findings of these emerging pathogens have been described in a few recent studies. This review focuses on the radiographic and computed tomographic patterns of viral pneumonia caused by different pathogens, including new pathogens. Clinical characteristics that could affect imaging, such as patient age and immune status, seasonal variation and community outbreaks, and pathogenesis, are also discussed. The first goal of this review is to indicate that there are imaging features that should raise the possibility of viral infections. Second, to help radiologists differentiate viral infections, viruses in the same viridae that have similar pathogenesis and can have similar imaging characteristics are shown. By considering both the clinical and radiologic characteristics, radiologists can suggest the diagnosis of viral pneumonia. ©RSNA, 2018.

https://pubs.rsna.org/doi/pdf/10.1148/rg.2018170048

Radiographic and CT Features of Viral Pneumonia.

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 disease is more severe and 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 50 serotypes of AdV have been identified. Different serotypes display different tissue tropisms that correlate with clinical manifestations of infection. The predominant serotypes 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 conducted. Cidofovir is 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.

/pdf/adenovirus-epidemiology-global-spread-of-novel-serotypes-and-2u0jbhsjjp.pdf

Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention

The aim of this review is to describe the biology of human adenovirus (HAdV), the clinical and epidemiological characteristics of adenoviral epidemic keratoconjunctivitis and to present a practical update on its diagnosis, treatment, and prophylaxis. There are two well-defined adenoviral keratoconjunctivitis clinical syndromes: epidemic keratoconjunctivitis (EKC) and pharyngoconjunctival fever (PCF), which are caused by different HAdV serotypes. The exact incidence of adenoviral conjunctivitis is still poorly known. However, cases are more frequent during warmer months. The virus is endemic in the general population, and frequently causes severe disease in immunocompromised patients, especially the pediatric patients. Contagion is possible through direct contact or fomites, and the virus is extremely resistant to different physical and chemical agents. The clinical signs or symptoms of conjunctival infection are similar to any other conjunctivitis, with a higher incidence of pseudomembranes. In the cornea, adenoviral infection may lead to keratitis nummularis. Diagnosis is mainly clinical, but its etiology can be confirmed using cell cultures, antigen detection, polymerase chain reaction or immunochromatography. Multiple treatments have been tried for this disease, but none of them seem to be completely effective. Prevention is the most reliable and recommended strategy to control this contagious infection.

/pdf/human-adenovirus-viral-pathogen-with-increasing-importance-4apwxjw7dq.pdf

Human adenovirus: Viral pathogen with increasing importance.

Adenoviruses are DNA viruses that naturally infect many vertebrates, including humans and monkeys, and cause a wide range of clinical illnesses in humans Infection from individual strains has conventionally been thought to be species-specific Here we applied the Virochip, a pan-viral microarray, to identify a novel adenovirus (TMAdV, titi monkey adenovirus) as the cause of a deadly outbreak in a closed colony of New World monkeys (titi monkeys; Callicebus cupreus) at the California National Primate Research Center (CNPRC) Among 65 titi monkeys housed in a building, 23 (34%) developed upper respiratory symptoms that progressed to fulminant pneumonia and hepatitis, and 19 of 23 monkeys, or 83% of those infected, died or were humanely euthanized Whole-genome sequencing of TMAdV revealed that this adenovirus is a new species and highly divergent, sharing <57% pairwise nucleotide identity with other adenoviruses Cultivation of TMAdV was successful in a human A549 lung adenocarcinoma cell line, but not in primary or established monkey kidney cells At the onset of the outbreak, the researcher in closest contact with the monkeys developed an acute respiratory illness, with symptoms persisting for 4 weeks, and had a convalescent serum sample seropositive for TMAdV A clinically ill family member, despite having no contact with the CNPRC, also tested positive, and screening of a set of 81 random adult blood donors from the Western United States detected TMAdV-specific neutralizing antibodies in 2 individuals (2/81, or 25%) These findings raise the possibility of zoonotic infection by TMAdV and human-to-human transmission of the virus in the population Given the unusually high case fatality rate from the outbreak (83%), it is unlikely that titi monkeys are the native host species for TMAdV, and the natural reservoir of the virus is still unknown The discovery of TMAdV, a novel adenovirus with the capacity to infect both monkeys and humans, suggests that adenoviruses should be monitored closely as potential causes of cross-species outbreaks

/pdf/cross-species-transmission-of-a-novel-adenovirus-associated-1yvzkbd7j3.pdf

Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony

Background Human adenoviruses (Ads) typically cause mild illnesses in otherwise healthy hosts. We investigated a community-based outbreak that had substantial morbidity caused primarily by Ad14, an uncommon serotype. Methods We retrospectively reviewed the medical records of all patients with confirmed cases of Ad infection from 1 November 2006 through 31 July 2007 in Oregon. Isolates were typed by sequencing. We analyzed clinical and laboratory variables to identify risk factors for severe Ad14 disease. Results Ad14 first emerged in Oregon in 2005. Of 67 cases of Ad infection detected during the study period, 40 (60%) involved Ad14. Most of the 38 Ad14-infected patients who had medical records available for review presented with fever and cough; 29 (76%) required hospitalization, 23 (61%) required supplemental oxygen, 18 (47%) required critical care, 9 (24%) required vasopressors, and 7 (18%) died. Lobar infiltrates on chest radiographs suggestive of bacterial pneumonia were common among those needing hospitalization. Older age, chronic underlying condition, low absolute lymphocyte counts, and elevated creatinine levels were associated with severe illness. Except for 1 case of possible hospital transmission, we identified no epidemiological links among patients. Conclusion Ad14 emerged in Oregon in 2005 and became the predominant circulating type by 2007. Infection with this uncommon virus was primarily associated with a community-acquired pneumonia syndrome and caused substantial morbidity and mortality.

/pdf/a-community-based-outbreak-of-severe-respiratory-illness-r6l5b5ra0s.pdf

A community-based outbreak of severe respiratory illness caused by human adenovirus serotype 14.

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A community-based outbreak of severe respiratory illness caused by human adenovirus serotype 14.