Adenovirus pneumonia can occur in immunocompetent youths and adults. We conducted a retrospective analysis on five immunocompetent patients (aged ⩾14 years) with adenovirus pneumonia who visited our fever clinic between 1 February 2020 and 29 February 2020. The symptoms at clinical onset were fever, with cough and phlegm production either absent or appearing several days after disease onset. One patient with severe disease exhibited dyspnoea and a rapid development of respiratory failure. A subset of patients had concurrent gastrointestinal symptoms. The results of blood tests revealed normal leukocyte counts, decreased lymphocyte counts and increased C-reactive protein levels. The imaging findings resembled those of bacterial pneumonia, and pleural effusions were present in some cases. Most patients had a good prognosis with symptomatic treatment and supportive care. However, one patient with severe disease and a MuLBSTA score of >12 had a poor prognosis and ultimately died. Immunocompetent youths and adults may develop adenovirus pneumonia, and severe cases are at the risk of death. Since no effective treatments for adenovirus pneumonia are currently known, the early diagnosis and provision of symptomatic treatment and supportive care should be adopted to prevent the development and progression of severe disease.

We investigated risk factors for severe acute lower respiratory infections (ALRI) among hospitalised children <2 years, with a focus on the interactions between virus and age. Statistical interactions between age and respiratory syncytial virus (RSV), influenza, adenovirus (ADV) and rhinovirus on the risk of ALRI outcomes were investigated. Of 1780 hospitalisations, 228 (12.8%) were admitted to the intensive care unit (ICU). The median (range) length of stay (LOS) in hospital was 3 (1–27) days. An increase of 1 month of age was associated with a decreased risk of ICU admission (rate ratio (RR) 0.94; 95% confidence intervals (CI) 0.91–0.98) and with a decrease in LOS (RR 0.96; 95% CI 0.95–0.97). Associations between RSV, influenza, ADV positivity and ICU admission and LOS were significantly modified by age. Children <5 months old were at the highest risk from RSV-associated severe outcomes, while children >8 months were at greater risk from influenza-associated ICU admissions and long hospital stay. Children with ADV had increased LOS across all ages. In the first 2 years of life, the effects of different viruses on ALRI severity varies with age. Our findings help to identify specific ages that would most benefit from virus-specific interventions such as vaccines and antivirals.

The adenovirus vaccine and benzathine penicillin G (BPG) have been used by the US military to prevent acute respiratory diseases (ARD) in trainees, though these interventions have had documented manufacturing problems. We fit Poisson regression and random forest models (RF) to 26 years of weekly ARD incidence data to explore the impact of the adenovirus vaccine and BPG prophylaxis on respiratory disease burden. Adenovirus vaccine availability was among the most important predictors of ARD in the RF, while BPG was the ninth most important. BPG was a significant protective factor against ARD (incidence rate ratio (IRR) = 0.68; 95% confidence interval (CI) 0.67–0.70), but less so than either the old or new adenovirus vaccine (IRR = 0.39, 95% CI 0.38–0.39 and IRR = 0.11, 95% CI 0.11–0.11), respectively. These results suggest that BPG is moderately predictive of, and significantly protective against ARD, though to a lesser extent than either the old or new adenovirus vaccine.

For most patients, adenoviruses cause few acute health concerns and are often self-limiting. Patients who are immunocompromised or immunosuppressed, however, are at risk for disseminated adenovirus and suffer high morbidity and mortality, without well-defined treatment options. We report the case of a 9-month-old boy who was successfully treated for disseminated adenovirus infection with intravenous immunoglobulin and cidofovir 3 months post heart transplant, tailored to serum adenoviral load and clinical response. We emphasise the importance of early identification, monitoring, and a potentially novel treatment in the paediatric cardiac transplant population with disseminated adenovirus infection.

This article outlines the evolution of a rescue team in responding to adenovirus prevention with a deployable field hospital. The local governments mobilized a shelter hospital and a rescue team consisting of 59 members to assist with rescue and response efforts after an epidemic outbreak of adenovirus. We describe and evaluate the challenges of preparing for deployment, field hospital maintenance, treatment mode, and primary treatment methods. The field hospital established at the rescue scene consisted of a medical command vehicle, a computed tomography shelter, an X-ray shelter, a special laboratory shelter, an oxygen and electricity supply vehicle, and epidemic prevention and protection equipment. The rescue team comprised paramedics, physicians, X-ray technicians, respiratory therapists, and logistical personnel. In 22 days, more than 3000 patients with suspected adenovirus infection underwent initial examinations. All patients were properly treated, and no deaths occurred. After emergency measures were implemented, the spread of adenovirus was eventually controlled. An emergency involving infectious diseases in less-developed regions demands the rapid development of a field facility with specialized medical personnel when local hospital facilities are either unavailable or unusable. An appropriate and detailed prearranged action plan is important for infectious diseases prevention. (Disaster Med Public Health Preparedness. 2018;12:109–114)

This study aimed to compare the virology and epidemiology of epidemic keratoconjunctivitis (EKC), pharyngoconjunctival fever (PCF) and acute haemorrhagic conjunctivitis (AHC) outbreaks worldwide caused by the human adenovirus (HAdV) from 1953 to 2013. Eighty-three hexon sequences from 76 conjunctivitis outbreaks were analysed and subtyped using Mega 5.05, Clustal X and SimPlot software. Epidemiology was performed for the area, age and seasonal distribution. A phylogenetic analysis indicated that all the isolates could be divided into three subgenetic lineages, without a common ancestor. The major causes of the outbreaks were Ad8, Ad7 and Ad2 co-infection with enterovirus 70 (EV70) in EKC, PCF and AHC, respectively. The epidemiological findings suggested that EKC and AHC were circulating predominantly in Asia during the early winter and spring, whereas PCF was circulating mainly in China, Australia and the United States during the summer. This study suggests that EKC, AHC and PCF outbreaks have different circulating patterns throughout the world and are caused by different adenovirus serotypes. A global surveillance system should be established to monitor conjunctivitis outbreaks in the future.

Laboratory tests in adult outpatients with longer lasting coughs to identify a potential causal pathogen are rarely performed, and there is no gold standard for these diagnostic tests. While the diagnostic validity of serological tests for pertussis is well established their potential contribution for diagnosing adenovirus and influenza virus A and B infections is unclear. A sentinel study into the population-based incidence of longer lasting coughs in adults was done in Rostock (former East Germany) and Krefeld (former West Germany). A total of 971 outpatients who consulted general practitioners or internists were included. Inclusion criteria were coughing for ⩾1 week and no chronic respiratory diseases. We evaluated the performance of polymerase chain reaction (PCR) as well as IgG and IgA serology, applying a latent class model for diagnosing infections with adenovirus, B. pertussis, and influenza virus A and B. The adult outpatients first sought medical attention when they had been coughing for a median of 3 weeks. In this situation, direct detection of infectious agents by PCR had a low sensitivity. Modelling showed that additional serological tests equally improved sensitivity and specificity for diagnosis for adenovirus, B. pertussis and influenza virus A and B infections. The combination of serology and PCR may improve the overall performance of diagnostic tests for B. pertussis and also for adenovirus, and influenza virus A and B infections.

Objective: The First Water Responder B package water treatment device was evaluated for its ability to reduce the levels of spiked indicators and pathogens (Escherichia coli, MS2 coliphage, murine adenovirus, and Cryptosporidium oocysts) in a surface water to partially evaluate its appropriateness to be used to provide safe drinking water to hospitals during emergency situations.

Methods: Lake water was collected in 50-L carboys and spiked with selected indicators and pathogens (E coli, MS2 coliphage, murine adenovirus, and Cryptosporidium oocysts) at 2 different spike levels (low and high). This water was treated using the First Water Responder B, and the microorganisms were enumerated before and after treatment using US Environmental Protection Agency and Standard Methods. Microbial removal efficiencies were compared with Environmental Protection Agency guidelines.

Results:E coli spikes ranged from 2.9 to 1059 colony-forming units (CFU)/100 mL with removals to below detection limits (1 CFU/100 mL) to 2.8 CFU/100 mL or 0.98 to 3.5 log10 reductions. MS2 coliphage spikes ranged from 3 plaque-forming units (PFU) to 837 PFU/100 mL with removals to below detection limits (1 PFU/100 mL) to 11.7 PFU/100 mL or 0.65 to 1.9 log10 reductions. Murine adenovirus spikes ranged from 203 to 8410 most probable number (MPN) of infectious units/100 mL with removals to below detection limits (23 MPN infectious units/100 mL) to 1370 MPN infectious units/100 mL or 0.79 to >1.2 log10 reductions. Cryptosporidium parvum oocyst spikes ranged from 52 to 853 oocysts per liter with removals to below detection limits (<1 oocyst per liter) to 0.3 oocysts per liter or >2.2 to 3.4 log10 reductions.

Conclusions: Although the First Water system could remove a significant portion of the spiked organisms, it is recommended that this point-of-use system be coupled with chemical disinfection in a multiple-barrier approach to provide water of the highest reasonably achievable quality for hospital use in emergency situations.

(Disaster Med Public Health Preparedness. 2011;5:29-36)

A total of 7185 faecal specimens collected from infants and children with gastroenteritis in seven different regions of Japan during 1995–2009 were examined for adenovirus by polymerase chain reaction. Adenovirus was detected in 568 (7·9%) patients. The adenovirus activity peak was in winter and spring seasons (December–March) during the study period in the Japanese paediatric population. During the last 15 years, adenovirus 41 was the most predominant strain in Japan.

This target article describes the current state of global gene replacement in the brain using viral vectors and assesses possible solutions to some of the many problems inherent in gene therapy of the central nervous system (CNS). Gene replacement therapy in the CNS is a potential means of producing a stable expression of normal human proteins in deficient cells and thus curing certain genetically inherited enzyme deficiencies and metabolic diseases as well as cancers. The two major issues to be addressed in CNS gene replacement are the delivery of genetic material to the brain and the expression of recombinant genetic material in target cells within the CNS. Focal inoculation of recombinant virions or other genetic vectors has limitations in global CNS disease. A new approach is the blood-brain barrier (BBB) disruption technique developed in this laboratory, in which hypertonic mannitol transiently shrinks the BBB endothelium, allowing passage of high molecular weight compounds and even viruses. Gene therapy of the CNS will require a viral vector system that allows long-term, nontoxic gene expression in neurons or glial cells. Retroviral vectors have limitations in CNS gene replacement, although they are suitable for expressing recombinant genes in intracerebral grafts, or toxic genes in brain tumors. Using mutant neurotropic viruses with reduced neurotoxicity (such as defective herpes simplex virus type I [HSV-1], the HSV-1 amplicon vector system we have developed, or adenovirus mutants) has potential for direct treatment of neurons. Injecting these vectors into rodent brains can lead to stable expression of foreign genetic material in postmitotic neuronal cells. We discuss our BBB disruption delivery technique, our defective HSV-1 amplicon vector system, and our feline model for the neuronal lysosomal storage disorder Gm2-gangliosidosis (Sandhoff disease), which may prove to be a useful model system for CNS gene therapy.

The unsatisfactory outcome of patients who receive intensive multimodality treatment for advanced squamous cell carcinoma of the head and neck (SCCHN) has motivated investigators to seek novel treatments to improve survival. Advances in molecular biology has led to the development of cancer gene therapy (CGT) and revived interest in viral vectors as a mechanism. SCCHN is an ideal model for CGT as disease remains locoregional and is amenable to injection of viruses. Adenovirus and Herpes Simplex Virus Type-1 (HSV) are the most studied Oncolytic Viruses (OVs). Both viruses have been shown to select and replicate in tumour cells and demonstrate anti-tumour effect in laboratory studies and clinical trials. Toxicity from OVs is minor and manageable. Different adenoviral mutants have been investigated with mixed responses. One vector, H101, has now been licensed after showing significant tumour regression in conjunction with chemotherapy. HSV has a larger capacity to carry genetic material and with the addition of the granulocyte–macrophage colony–stimulating factor, has the potential to stimulate an immune response systemically and at the site of disease. OVs are limited by the distribution of virus beyond injection site and by pre-existing or rapidly established immune response. Phase III studies are required.

The developing heart increases its mass predominantly by increasing the number of contained cells through proliferation. We hypothesized that addition of fibroblast growth factor-2, a factor previously shown to stimulate division of the embryonic myocytes, to the left ventricular myocardium in an experimental model of left heart hypoplasia created in the chicken would attenuate phenotypic severity by increasing cellular proliferation. We have established an effective mode of delivery of fibroblast growth factor-2 to the chick embryonic left ventricular myocardium by using adenovirus vectors, which was more efficient and better tolerated than direct injection of recombinant fibroblast growth factor-2 protein. Injection of control adenovirus expressing green fluorescent protein did not result in significant alterations in myocytic proliferation or cell death compared with intact, uninjected, controls. Co-injection of adenoviruses expressing green fluorescent protein and fibroblast growth factor-2 was used for verification of positive injection, and induction of proliferation, respectively. Treatment of both normal and hypoplastic left ventricles with fibroblast growth factor-2 expressing adenovirus resulted in to 2 to 3-fold overexpression of fibroblast growth factor-2, as verified by immunostaining. An increase by 45% in myocytic proliferation was observed following injection of normal hearts, and an increase of 39% was observed in hypoplastic hearts. There was a significant increase in anti-myosin immunostaining in the hypoplastic, but not the normal hearts. We have shown, therefore, that expression of exogenous fibroblast growth factor-2 in the late embryonic heart can exert direct effects on cardiac myocytes, inducing both their proliferation and differentiation. These data suggest potential for a novel therapeutic option in selected cases of congenital cardiac disease, such as hypoplastic left heart syndrome.

First-generation adenovirus can be engineered with powerful promoters to drive expression of therapeutic transgenes. Numerous clinical trials for glioblastoma multiforme using first generation adenoviral vectors have either been performed or are ongoing, including an ongoing, Phase III, multicenter trial in Europe and Israel (Ark Therapeutics, Inc.). Although in the absence of anti-adenovirus immune responses expression in the brain lasts 6–18 months, systemic infection with adenovirus induces immune responses that inhibit dramatically therapeutic transgene expression from first generation adenoviral vectors, thus, potentially compromising therapeutic efficacy. Here, we show evidence of an immunization threshold for the dose that generates an immune response strong enough to eliminate transgene expression from the CNS. For the systemic immunization to eliminate transgene expression from the brain, ≥1×107 infectious units (iu) of adenovirus need to be used as immunogen. Furthermore, this immune response eliminates >90% of transgene expression from 1×107–1×103 iu of vector injected into the striatum 60 days earlier. Importantly, elimination of transgene expression is independent of the nature of the promoter that drives transgene expression and is accompanied by brain infiltration of CD8+ T cells and macrophages. In conclusion, once the threshold for systemic immunization (i.e. 1×107 iu) is crossed, the immune response eliminates transgene expression by >90% even from brains that receive as little as 1000 iu of adenoviral vectors, independently of the type of promoter that drives expression.

Hydropericardium syndrome has caused huge economic losses to the poultry industry in Pakistan. The disease was reported for the first time in 1987 at Angara Goth, a broiler producing area near Karachi and given the name Angara disease. The disease is prevalent in 3–7 week old broilers and characterized by its sudden onset, accumulation of a jelly like fluid in the pericardial sac, inflamed liver with basophilic intranuclear inclusion bodies, congested kidneys and up to 70% mortality rates. Fowl adenovirus 4 has been found to be the causative agent. In Pakistan, the status of scientific research on various aspects of hydropericardium syndrome is quite unsatisfactory. There is an extensive use of formalin inactivated liver homogenate vaccines for the prevention and control of disease. Moreover, the gross lesions seen in post mortem examination are only the criteria for the clinical diagnosis of disease. Keeping in view the economic significance of hydropericardium syndrome, the need for additional scientific research on proper diagnosis and control of disease is suggested.

Delivery methods for commercial scale applications must be simple, inexpensive and cost-effective. The use of live vectors such as fowl adenoviruses (FAV) has previously been proven successful for the effective oral delivery of chicken interferon gamma to broilers under commercial growing conditions. FAV can be delivered via food or water or can be used as a spray. The ability of cytokines to modulate immune responses to vaccines and their therapeutic and growth promoting capability makes them an important component in future health management strategies for poultry. In this report, we describe the development of recombinant FAV vectors expressing chicken interleukin-2 (ChIL-2) and chicken myelomonocytic growth factor(cMGF). The ChIL-2 and cMGF genes were cloned into the right hand terminal region of FAV serotype 8, under the control of the adenovirus major late promoter. The in vitro biological activity of FAV-ChIL-2 and FAV-cMGF was comparable to that of the corresponding recombinant proteins expressed in prokaryotic (E. coli) and eukaryotic (COS cell) systems. These constructs may be particularly useful as therapeutics formucosal infections.