Cost Savings From a Policy to Diagnose and Prevent Transmission of Adenoviral Conjunctivitis in Employees of a Large Academic Medical Center.

IMPORTANCE: Adenoviral conjunctivitis is highly contagious, can be associated with systemic infections, and can cause chronic visual impairment. It accounts for a large proportion of acute conjunctivitis. Outbreaks of epidemic keratoconjunctivitis (EKC) are costly in terms of productivity loss from work furloughs and spread to patients and have resulted in clinic and departmental closures. OBJECTIVE: To examine the institutional cost savings of a policy to diagnose adenoviral conjunctivitis and triage and furlough medical center employees with this condition to prevent outbreaks. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study assessed Johns Hopkins Medicine employees with red eye from November 1, 2011, through October 31, 2018, who were triaged at the occupational health clinic whose conditions were diagnosed using polymerase chain reaction (PCR) validated for adenoviral conjunctivitis. INTERVENTIONS: Only employees with positive PCR test results were furloughed, with furlough length tailored to subtype (a minimum of 2 weeks for EKC and 1 week otherwise). MAIN OUTCOMES AND MEASURES: Total number of furloughs avoided and cost savings associated with reducing unnecessary furloughs. RESULTS: Of 2142 employees with red eye, 1520 (71.0%) underwent PCR testing; 130 (8.6%) had positive adenoviral PCR test results, of whom 41 (31.5%) had EKC. Furloughing 130 employees with positive PCR test results vs furloughing all 1520 employees clinically suspected of having adenoviral conjunctivitis represented an estimated annual savings of $442 073, or $3 094 511 during 7 years. The cost of performing PCR on employees suspected of having adenoviral conjunctivitis was 5.0% of the cost associated with furloughing all employees with red eye. No outbreaks occurred. CONCLUSIONS AND RELEVANCE: In this quality improvement study, this policy, notable for development and use of PCR for adenoviral conjunctivitis on a large scale, resulted in substantial cost savings from fewer work furloughs compared with the number of employees who would have been furloughed based on clinical diagnosis. These results may provide impetus for policy adoption by other institutions and for development of a rapid, sensitive, and specific diagnostic test for adenoviral conjunctivitis.

Assessment of clinical signs associated with adenoviral epidemic keratoconjunctivitis cases in southern Japan between 2011 and 2014.

Adenoviral epidemic keratoconjunctivitis (EKC) is a major cause of ocular morbidity worldwide and specific antiviral therapies are not available. EKC is primarily caused by Human adenovirus D (HAdV-D) types 8, 37, 53, 54, 56 and 64. Considering the genomic variation in HAdV-D, we hypothesized that clinical signs could be differentiated by virus type. The hypothesis was retrospectively tested with clinical signs recorded from 250 patients with ocular infections visiting an ophthalmological clinic in southern Japan between 2011 and 2014. The results showed that conjunctival opacity, corneal epithelial disorders and pre-auricular lymphadenopathy, were more frequently associated with EKC than other ocular infections. Furthermore, HAdV types 8, 37 and 54, caused corneal complications and longer infections significantly more frequently than infections by types 53 and 56 (P < 0.05). Our descriptive results supported that symptoms severity vary with the infecting type, however, further research is needed to improve diagnosis of EKC.

Adenoviral keratitis: a review of the epidemiology, pathophysiology, clinical features, diagnosis, and management.

PURPOSE OF REVIEW: Adenoviral keratitis is a common and bothersome ocular infection that produces a lot of burden on healthcare systems and patients. The goal of this article is to provide a review of the topic, with an emphasis on current attempts at advancing strategies in diagnosis and management. RECENT FINDINGS: Sixty-eight articles and one textbook published on adenoviral keratitis were reviewed. The findings on the epidemiology, pathophysiology, clinical features, diagnosis, and management were summarized. Any contradicting opinions for which the literature was unclear were either omitted or recorded as lacking strong evidence. SUMMARY: Although significant effort has been made to develop new methods for diagnosis and management, adenoviral keratitis is predominantly diagnosed clinically with prevention being the mainstay of management. The use of newer DNA analysis techniques and topical anti-inflammatory agents for treatment of corneal infiltrates show promising results, but a better understanding of the pathogenesis and clinical features can lead to more targeted methods of diagnosis and therapy.

Assessment of the risks for human health of adenoviruses, hepatitis A virus, rotaviruses and enteroviruses in the Buffalo River and three source water dams in the Eastern Cape.

Buffalo River is an important water resource in the Eastern Cape Province of South Africa. The potential risks of infection constituted by exposure to human enteric viruses in the Buffalo River and three source water dams along its course were assessed using mean values and static quantitative microbial risk assessment (QMRA). The daily risks of infection determined by the exponential model [for human adenovirus (HAdV) and enterovirus (EnV)] and the beta-Poisson model (for hepatitis A virus (HAV) and rotavirus (RoV)) varied with sites and exposure scenario. The estimated daily risks of infection values at the sites where the respective viruses were detected, ranged from 7.31 × 10(-3) to 1 (for HAdV), 4.23 × 10(-2) to 6.54 × 10(-1) (RoV), 2.32 × 10(-4) to 1.73 × 10(-1) (HAV) and 1.32 × 10(-4) to 5.70 × 10(-2) (EnV). The yearly risks of infection in individuals exposed to the river/dam water via drinking, recreational, domestic or irrigational activities were unacceptably high, exceeding the acceptable risk of 0.01% (10(-4) infection/person/year), and the guideline value used as by several nations for drinking water. The risks of illness and death from infection ranged from 6.58 × 10(-5) to 5.0 × 10(-1) and 6.58 × 10(-9) to 5.0 × 10(-5), respectively. The threats here are heightened by the high mortality rates for HAV, and its endemicity in South Africa. Therefore, we conclude that the Buffalo River and its source water dams are a public health hazard. The QMRA presented here is the first of its kinds in the Eastern Cape Province and provides the building block for a quantitatively oriented local guideline for water quality management in the Province.

Incidence and treatment strategy for disseminated adenovirus disease after haploidentical stem cell transplantation.

Adenovirus (AdV) infection is an emerging complication in patients undergoing allogeneic stem cell transplantation (SCT) and is closely associated with delayed immune reconstitution. In particular, disseminated AdV disease accompanies a high mortality. We retrospectively examined the incidence of AdV infection in patients undergoing unmanipulated haploidentical SCT. Following 121 transplantations in 110 patients, three had asymptomatic AdV viremia, three had localized AdV disease (hemorrhagic cystitis, HC), and seven had disseminated AdV disease (HC + viremia). The median time from transplantation to the onset of AdV-associated HC was 15 days (range 4-39), and the median time to the onset of disseminated AdV disease was 23 days (range 7-38). The cumulative incidence of AdV-associated HC was 8.3 %, and that of disseminated AdV disease was 5.8 %. AdV group B (type 11, type 34, or type 35) was detected in plasma samples from all the patients with disseminated AdV disease. Among them, three patients who received either cidofovir or donor lymphocyte infusion (DLI) alone progressed to pneumonia and died. The remaining four patients were treated with the combination of cidofovir and low-dose unmanipulated DLI, and all survived. We showed that disseminated AdV disease is a significant complication after haplo-SCT and that the combination of cidofovir and DLI is a promising treatment option.

Initial assessment of impact of adenovirus type 4 and type 7 vaccine on febrile respiratory illness and virus transmission in military basic trainees, March 2012.

After a 12-year hiatus, military recruit training centers resumed administration of adenovirus type 4 and type 7 vaccine, live, oral (adenovirus vaccine) to trainees beginning in October of 2011. Subsequently, rates of febrile respiratory illnesses (FRI) and adenovirus isolations markedly declined. These findings are consistent with those of a placebo-controlled efficacy trial conducted prior to the vaccine's licensure by the U.S. Food and Drug Administration. Continued surveillance will clarify the longer term impact of vaccine use.

Incidence assessment of rotavirus and adenovirus associated acute gastroenteritis cases in early childhood.

This study was undertaken to give an insight into the incidence of acute gastroenteritis cases of rotaviral/adenoviral aetiology in patients presenting to the emergency room of an inner-city government teaching hospital. Group A rotavirus and adenovirus serotype 40-41 antigen results were obtained via immunochromatography. In 2007, there were 1543 patients with gastroenteritis between 0-5 years of age whose stool samples were tested for rota and adenovirus, of whom 386 (25%) had positive stool samples for rotavirus, and 133 (8.6%) for adenovirus serotype 40-41. The majority of rotavirus (74.6%) and adenovirus (73%) cases were between 0-2 years of age. The peak season for rotavirus gastroenteritis was January (44%) and February (50.6%), whereas July (9.7%) and August (9%) were months of low incidence. For enteric adenoviral infections summer was the peak season, with August (20.9%) and July (17.3%) being the foremost months. Among the viral gastroenteritis cases, rotavirus infections were in the majority. A seasonal trend emerges for viral gastroenteritis: Rota virus infections are most frequently seen in winter whereas adenoviral infections prefer summer months. Both viruses mostly affect children up to 2 years.

[Public health surveillance and assessment of emerging infectious threats: method and criteria for risk analysis]. / Veille sanitaire et appréciation du risque infectieux émergent: méthode et critères d'analyse du risque.

One of the objectives of the surveillance systems implemented by the French National Institute for Public Health Surveillance is to detect communicable diseases and to reduce their impact. For emerging infections, the detection and risk analysis pose specific challenges due to lack of documented criteria for the event. The surveillance systems detect a variety of events, or "signals" which represent a potential risk, such as a novel germ, a pathogen which may disseminate in a non-endemic area, or an abnormal number of cases for a well-known disease. These signals are first verified and analyzed, then classified as: potential public health threat, event to follow-up, or absence of threat. Through various examples, we illustrate the method and criteria which are used to analyze and classify these events considered to be emerging. The examples highlight the importance of host characteristics and exposure in groups at particular risk, such as professionals in veterinarian services, health care workers, travelers, immunodepressed patients, etc. The described method should allow us to identify future needs in terms of surveillance and to improve timeliness, quality of expertise, and feedback information regarding the public health risk posed by events which are insufficiently documented.

Evaluation of a surveillance strategy for early detection of adenovirus by PCR of peripheral blood in hematopoietic SCT recipients: incidence and outcome.

Adenoviruses (AdV) have emerged as important causes of morbidity and mortality in patients after hematopoietic SCT (HSCT). Early diagnosis of the infection by detection of viral DNA may improve the prognosis. A surveillance strategy was evaluated for detection of AdV DNA by PCR in a prospective study of unselected allogeneic HSCT recipients. In parallel with a routine CMV surveillance program, plasma from 20 children and 77 adults was analyzed by quantitative PCR for detection of AdV DNA. In addition, in 12 unselected patients, the presence of AdV-specific T cells were analyzed by enzyme-linked immunosorbent spot (ELISPOT) at 1 to 3 months after transplantation. A total of 5 of 97 (5%) patients had detectable AdV DNA in peripheral blood. Only one patient had high titers and none developed AdV disease. BM as a source of stem cells and myelodysplastic syndrome as the indication for transplantation were independently associated with higher risk of acquiring AdV infection. AdV-specific T cells were detected in 7 (58%) of 12 patients. Although AdV DNA was found in peripheral blood by quantitative PCR in 5% of patients undergoing allogeneic HSCT, the present surveillance program did not have a significant effect on the clinical outcome.

[Adenovirus infection in hospitalized children with pneumonia in Guangzhou from 2005 to 2007].

OBJECTIVE: To understand the characteristics of adenovirus infection in hospitalized children with pneumonia in Guangzhou area. METHODS: The infection rate, hospitalization time and hospitalization expenses of adenovirus-infected hospitalized children with pneumonia in Guangzhou area from 2005 to 2007 were analyzed. RESULTS: The total adenovirus infection rate was 6.04% in these children, with a male to female ratio of 1.47:1, showing significantly higher infection rate in female (7.92%) than in male patients (5.21%, P<0.05). The hospital stay and hospitalization costs between male and female children showed no significant difference (P>0.05). Adenovirus-infected children from birth to six years old accounted for 90.50% of the total adenovirus-infected children, and the infection rate in 0 to 1-year-old children (3.71%) was significantly lower than that in elder children (P<0.05). Although the infection rate in winter (8.44%) was significantly higher than that in the other seasons (P<0.05), the cases from March to August accounted for 60.11% of the total infected cases. Furthermore, the infection rate in 2007 (4.31%) was significantly lower than that in 2005 and 2006 (7.11% and 6.71%, respectively, P<0.05). CONCLUSION: Adenovirus infection is an important pathogen in hospitalized children with pneumonia in Guangzhou area, and the infection rates differed between gender, age, season and the years.

Cost effectiveness of a point-of-care test for adenoviral conjunctivitis.

BACKGROUND: Conjunctivitis is a relatively common condition of the eye that can be caused by a number of different pathogens including bacteria and viruses. Clinical differentiation between adenoviral and bacterial conjunctivitis is difficult, often resulting in misdiagnosis and the provision of inappropriate treatment. METHODS: A cost-effectiveness analysis was performed from a societal perspective using primary, secondary, published literature, and expert opinion data sources. The incremental costs and effects (cases of unnecessary antibiotic treatment avoided) for a rapid point-of-care test for adenoviral conjunctivitis (RPS Adeno Detector) were modeled. RESULTS: Using base case values, the incremental cost of using no point-of-care test compared with the point-of-care test is $71.30 with 0.1786 cases of unnecessary antibiotic treatment. Extrapolating these costs to the entire U.S. population per annum, society could potentially save nearly $430 million currently spent on unnecessary medical care and avoid over 1 million cases of unnecessary antibiotic treatment. The no-point-of-care test strategy is both more costly and less effective; indicating that the point-of-care test strategy is the most cost-effective option. The results were robust to variation in key model parameters. CONCLUSIONS: Through the use of a rapid point-of-care test for adenovirus, much of the cost to society caused by acute conjunctivitis can be avoided through more timely and accurate diagnosis.

Clinical assessment of a generic DNA amplification assay for the identification of respiratory adenovirus infections.

BACKGROUND: respiratory adenoviruses are common, often resulting in serious sporadic and epidemic infections and impaired immunity can dramatically increase their severity. They are now thought capable of establishing latency. Diagnosis by culture is slow while direct antigen detection by immunofluorescence lacks sensitivity. Molecular diagnosis can be both rapid and sensitive but the genetic heterogeneity of adenoviruses poses problems. OBJECTIVES: to design a generic adenovirus nested polymerase chain amplification assay designed to be capable of detecting all respiratory adenoviruses. This was achieved through optimised thermal cycling and the development of a generic degenerate primer set targeting the adenovirus hexon gene. STUDY DESIGN: this was a cross-sectional study on 172 respiratory specimens from hospital-based patients, and one from a general practice, in Northern Ireland. A comparison was made between the amplification assay, virus culture and immunofluorescence. RESULTS: the nested polymerase chain reaction (nPCR) assay had a generic capacity for adenovirus detection and an analytical sensitivity of 6.4x10(2) copies/ml. Using an expanded gold standard (defined as a true positive or a true negative where a specimen was positive or negative by at least two of the study assays, respectively), PCR had a clinical sensitivity and specificity of 46/46 (100%) and 15/126 (91.3%), respectively. Patients with acute respiratory adenovirus infections were more likely to be male (chi(2), p=0.005) and to present with a fever (chi(2), p=0.02) than patients diagnosed with another respiratory virus. Co-infection was identified in 12/172 patients. CONCLUSIONS: the nested amplification assay proved highly sensitive in both the analytical and clinical settings for the detection of respiratory adenovirus infections.

Adult adenovirus infections: loss of orphaned vaccines precipitates military respiratory disease epidemics. For the Adenovirus Surveillance Group.

Adenovirus vaccines have greatly reduced military respiratory disease morbidity since the 1970s. However, in 1995, for economic reasons, the sole manufacturer of these vaccines ceased production. A population-based adenovirus surveillance was established among trainees with acute respiratory illness at 4 US military training centers as the last stores of vaccines were depleted. From October 1996 to June 1998, 1814 (53.1%) of 3413 throat cultures for symptomatic trainees (78% men) yielded adenovirus. Adenovirus types 4, 7, 3, and 21 accounted for 57%, 25%, 9%, and 7% of the isolates, respectively. Unvaccinated trainees were much more likely than vaccinated trainees to be positive for types 4 or 7 (odds ratio [OR] = 28.1; 95% CI, 20.2-39.2). Two training centers experienced epidemics of respiratory disease affecting thousands of trainees when vaccines were not available. Until a new manufacturer is identified, the loss of orphaned adenovirus vaccines will result in thousands of additional preventable adenovirus infections.

Cost-effectiveness analysis of reacquiring and using adenovirus types 4 and 7 vaccines in naval recruits.

Adenovirus vaccines have controlled acute respiratory disease (ARD) in military recruits since 1971. Vaccine production, however, ceased and new facilities are required. We assessed whether reacquiring and using vaccines in naval recruits is cost-effective. Three policy options were evaluated: no vaccination, seasonal vaccination, and year-round vaccination. Morbidity (outpatient and inpatient), illness costs (medical and lost training), and vaccine program costs (start-up, acquisition, and distribution) were modeled using a decision-analytic method. Results were based on a cohort of 49,079 annual trainees, a winter vaccine-preventable ARD rate of 2.6 cases per 100 person-weeks, a summer incidence rate at 10% of the winter rate, a hospitalization rate of 7.6%, and a production facility costing US$12 million. Compared to no vaccination, seasonal vaccination prevented 4,015 cases and saved $2.8 million per year. Year-round vaccination prevented 4,555 cases and saved $2.6 million. Reacquiring and using adenovirus vaccines seasonally or year-round saves money and averts suffering.