Margaret L. Chorazy

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.

Evidence of previous avian influenza infection among US turkey workers.

The threat of an influenza pandemic is looming, with new cases of sporadic avian influenza infections in man frequently reported. Exposure to diseased poultry is a leading risk factor for these infections. In this study, we used logistic regression to investigate serological evidence of previous infection with avian influenza subtypes H4, H5, H6, H7, H8, H9, H10, and H11 among 95 adults occupationally exposed to turkeys in the US Midwest and 82 unexposed controls. Our results indicate that farmers practising backyard, organic or free‐ranging turkey production methods are at an increased risk of infection with avian influenza. Among these farmers, the adjusted odds ratios (ORs) for elevated microneutralization assay titres against avian H4, H5, H6, H9, and H10 influenza strains ranged between 3.9 (95% CI 1.2–12.8) and 15.3 (95% CI 2.0–115.2) when compared to non‐exposed controls. The measured ORs were adjusted for antibody titres against human influenza viruses and other exposure variables. These data suggest that sometime in their lives, the workers had been exposed to low pathogenicity avian influenza viruses. These findings support calls for inclusion of agricultural workers in priority groups in pandemic influenza preparedness efforts. These data further support increasing surveillance and other preparedness efforts to include not only confinement poultry facilities, but more importantly, also small scale farms.

Human Adenovirus 14a: A New Epidemic Threat

The recent much-publicized report World at Risk [1] predicts that we are soon to experience a biological or nuclear weapons attack. This issue of the Journal contains 2 reports of outbreaks of a new human adenovirus (Ad) type 14 strain [2, 3], which serves to remind us that we are at least equally likely, if not more likely, to soon experience large-scale morbidity through epidemics of emergent pathogens. As was illustrated by the severe acute respiratory syndrome-associated coronavirus, when a ubiquitous nuisance pathogen suddenly becomes more virulent, its reign of destruction needs little help from rogue nations or terrorist cells. Humankind is quite efficient in spreading such pathogens around. It is likely that the new Ad14 strain entered Oregon in 2005 and apparently spread throughout the state by 2007 [2, 4]. In their retrospective review of clinical and laboratory data (from 1 November 2006 through 31 July 2007), Lewis et al. [2] demonstrate that the new Ad14 variant quickly became a highly prevalent strain, explaining 60% ofAd infections. Of 40 Ad14-positive patients, 76% required hospitalization, 61% merited supplemental oxygen, 47% received critical care, and 18% died. In a comprehensive contemporary epidemiological investigation in Texas, Tate et al. [3] show a similar rapid transmission of Ad14 with high morbidity. They estimate that, of 1147 otherwise healthy young military trainees with febrile respiratory illness in 2007, 551 (48%) were infected with Ad14. Of these Ad14-infected patients, 23 were hospitalized, 4 required admission to an intensive care unit, and 1 died. These transmission and morbidity statistics are consistent with those from the first report of this emergent Ad14 strain [4], when clusters totaling 140 patients with acute Ad14 respiratory disease were noted in Oregon, Texas, and Washington, with 38% being hospitalized, 17% requiring admission to an intensive care unit, and 9 dying. The 52 human Ad serotypes [5] cause a broad spectrum of clinical illnesses: pharyngoconjunctival fever, keratoconjunctivitis, pneumonia, hemorrhagic cystitis, gastroenteritis, acute respiratory disease, severe disseminated disease, cardiomyopathy, and encephalitis [6]. Populations commonly at risk for adenoviral illness include new military recruits, young children, and especially those who are immunocompromised. Ad14 (strain deWit) was first isolated from Dutch military recruits with acute respiratory disease in the 1950s and was associated with a few reported outbreaks of acute respiratory disease in Europe and Asia through the 1960s [7–13]. In the United States, Ad14 was only recently identified in military and civilian populations, has most often been associated with sporadic cases rather than outbreaks, and has not been previously associated with severe clinical illness [14, 15]. However, in 2005, Ad14 suddenly became more prevalent in the United States. In our 2004–2007 US National Surveillance for Emerging Adenovirus Infections program (3026 typed isolates in total) [14], we first detected Ad14 strains during March 2005 in Missouri and Arizona, and by April 2007 we had identified 19 Ad14 isolates from 12 different US laboratories. Similarly, Metzgar et al. [15] reported the abrupt emergence of Ad14 in US military populations in March and April 2006. Through further study, we now recognize that these recent Ad14 isolates are virtually identical to the emergent Ad14 genotype first reported to have caused serious illness among patients in New York, Oregon, Texas, and Washington during 2006–2007 [4]. As was described by both Tate et al. [3] and Lewis et al. [2], the Ad14 isolates detected in these outbreaks were identical by sequence data but were different from the Ad14 deWit strain [7]. On the basis of differences in restriction enzyme digest patterns, Louie et. al. designated the new strain Ad14a [16]. This new strain was observed to be associated with severe clinical illness more often than the prototype Ad14 deWit strain [4]. Novel Ad strains have been associated with more severe clinical disease and have seemed to have a competitive advantage in their spread [17–21]. Although the genetic differences between the Ad14 deWit and Ad14a strains may account for the observed higher rate of transmission of Ad14a and its associated more severe morbidity, one can strongly argue that these observations are confounded by a lack of individual and herd immunity to Ad14 [2, 3, 16]. However, another observer might counter that Ad epidemics are not often seen when other rare Ad strains are detected. Virulence studies using cellular and animal models may be necessary to sort this out. Fortunately, most Ad14a infections do not cause severe illness. Tate et al. [3] found that, of the trainees with serological evidence of acute Ad14a infection, 51% reported afebrile or mild disease, and 9% reported no respiratory symptoms at all. Even so, Ad14a represents an emerging threat in that it seems to cause more severe disease in some persons, has been implicated in community-based infections [2], and, in at least 1 facility, has demonstrated a propensity to infect hospital staff [22]. Data from reports on Ad14a suggest that risk factors for severe Ad14a disease may include male sex, older age, smoking, and underlying medical conditions, but more comprehensive study is needed [2, 3]. Available reports further suggest that Ad14a illness is mitigated by preexisting immunity [3, 15]. Tate et al. showed that previous natural infection with Ad7 may protect against severe Ad14a illness requiring hospitalization. This is particularly good news for military trainees, given the loss of Ad4 and Ad7 vaccines in 1999 and their expected return to availability soon [23, 24]. It is difficult to determine the geographical distribution of Ad14a infections, given that Ad surveillance is generally passive. Additionally, relatively few laboratories look for Ad, and even fewer can distinguish Ad14 from other Ad types. Through specific reports of Ad14a and our national surveillance program (for which sampling ended in 2007)[14], we know that Ad14a has been detected in Alaska, Arizona, California, Connecticut, Hawaii, Indiana, Missouri, New York, Oregon, Tennessee, Texas, Washington, and Wisconsin. With its propensity for rapid transmission, it seems likely that Ad14a is now circulating throughout the United States and may have been introduced from another country. How does our knowledge of Ad14a affect future clinical care and public health? Given its association with more-severe disease, when Ad14a is detected in a medical facility, infection-control professionals may choose to employ patient isolation and special precautions to reduce the risk of nosocomial transmission. For patients with severe infections, clinicians, like those in Oregon [2], may be more aggressive in using antiviral therapy. Confronted with Ad14a outbreaks in crowded long-term-care facilities, public health officials may decide to employ nonpharmaceutical interventions [25]. Finally, should Ad14a prove to be a frequent cause of epidemics, those persons at greatest risk might benefit from the possible cross-protection conferred by Ad7 vaccine (although previous indications have included only military personnel). Lewis et al. [2] describe polymerase chain reaction (PCR)-based methods to detect Ad14. Many other serological [5, 26], PCR-based [27], and DNA sequence-based typing methods [14, 28–30] have been used to distinguish the 52 Ad strains. If Ad14 is detected in the United States, it most likely is the new Ad14a strain. However, restriction enzyme digest analysis or targeted gene sequencing is necessary to confidently distinguish the Ad14a strain from the Ad14 deWit strain [16].

Polymicrobial acute respiratory infections in a hospital-based pediatric population.

Background: The clinical impact of polymicrobial respiratory infections remains uncertain. Previous reports are contradictory regarding an association with severe disease. Methods: Three hundred forty-six specimens from children with acute respiratory illness identified at the University of Iowa Hospitals and Clinics Clinical Microbiology Laboratory were evaluated by direct immunofluorescent assay and/or viral culture by Clinical Microbiology Laboratory and later by molecular study for the presence of influenza, parainfluenza, respiratory syncytial virus, adenovirus, human metapneumovirus, rhinovirus and human bocavirus. Demographic and clinical data were abstracted from medical records. Results: Multiple viruses were detected in 46 (21.7%) of 212 virus-positive specimens with the most frequent virus–virus combinations being HRV-respiratory syncytial virus (n = 12), HRV-human bocavirus (n = 6) and HRV-parainfluenza virus 3 (n = 4). Risk factors for coinfection included male gender (OR [odds ratio]: 1.70, 95% confidence interval [CI]: 0.83–3.46), 6 months to 1 year age (OR: 2.15, 95% CI: 0.75–6.19) and history of immunosuppression (OR: 2.05, 95% CI: 0.99–4.23). Children with viral coinfections were less likely than children with single virus infections to be admitted to an intensive care unit (OR: 0.32, 95% CI: 0.08–1.27); however, this may be explained by undetected viral–bacterial coinfections. Conclusions: HRV, respiratory syncytial virus, human bocavirus, and polymicrobial infections were prevalent in this study. Although the cross-sectional design could not easily examine polymicrobial infection and disease severity, prospective, population-based research regarding the clinical impact of such infections is warranted.

Incidence and Outcomes Associated With Infections Caused by Vancomycin-Resistant Enterococci in the United States: Systematic Literature Review and Meta-Analysis.

BACKGROUND Information about the health and economic impact of infections caused by vancomycin-resistant enterococci (VRE) can inform investments in infection prevention and development of novel therapeutics. OBJECTIVE To systematically review the incidence of VRE infection in the United States and the clinical and economic outcomes. METHODS We searched various databases for US studies published from January 1, 2000, through June 8, 2015, that evaluated incidence, mortality, length of stay, discharge to a long-term care facility, readmission, recurrence, or costs attributable to VRE infections. We included multicenter studies that evaluated incidence and single-center and multicenter studies that evaluated outcomes. We kept studies that did not have a denominator or uninfected controls only if they assessed postinfection length of stay, costs, or recurrence. We performed meta-analysis to pool the mortality data. RESULTS Five studies provided incidence data and 13 studies evaluated outcomes or costs. The incidence of VRE infections increased in Atlanta and Detroit but did not increase in national samples. Compared with uninfected controls, VRE infection was associated with increased mortality (pooled odds ratio, 2.55), longer length of stay (3-4.6 days longer or 1.4 times longer), increased risk of discharge to a long-term care facility (2.8- to 6.5-fold) or readmission (2.9-fold), and higher costs (

Serologic Evidence of Avian Metapneumovirus Infection Among Adults Occupationally Exposed to Turkeys

9,949 higher or 1.6-fold more). CONCLUSIONS VRE infection is associated with large attributable burdens, including excess mortality, prolonged in-hospital stay, and increased treatment costs. Multicenter studies that use suitable controls and adjust for time at risk or confounders are needed to estimate the burden of VRE infections. Infect Control Hosp Epidemiol. 2017;38:203-215.

Lack of Evidence of Avian Adenovirus Infection Among Turkey Workers

Genetically similar, the avian metapneumovirus (aMPV) and the human MPV (hMPV) are the only viruses in the Metapneumovirus genus. Previous research demonstrated the ability of hMPV to cause clinical disease in turkeys. In this controlled, cross-sectional, seroepidemiological study, we examined the hypothesis that aMPV might infect humans. We enrolled 95 adults occupationally exposed to turkeys and 82 nonexposed controls. Sera from study participants were examined for antibodies against aMPV and hMPV. Both in bivariate (OR=3.2; 95% CI: 1.1-9.2) and in multivariate modelling adjusting for antibody to hMPV (OR=4.1; 95% CI: 1.3-13.1), meat-processing workers were found to have an increased odds of previous infection with aMPV compared to controls. While hMPV antibody cross-reactivity is evident, these data suggest that occupational exposure to turkeys is a risk factor for human infection with aMPV. More studies are needed to validate these findings, to identify modes of aMPV transmission, and to determine risk factors associated with infection.

Costs and Mortality Associated With Multidrug-Resistant Healthcare-Associated Acinetobacter Infections.

ABSTRACT Zoonotic infections constitute a major public health concern. Outbreaks of the SARS (severe acute respiratory syndrome) and avian influenza viruses are but recent examples. Although there are many animal-specific adenoviruses and occasionally they have been noted to infect man, rarely have they been studied as potential zoonotic pathogens. In this study, the authors hypothesized that the hemorrhagic enteritis virus (HEV), an avian adenovirus that causes illness among turkeys, might infect humans. Using an enzyme immunosorbent assay, the authors compared sera from 95 turkey-exposed individuals with sera from 82 nonexposed controls for serologic evidence of infection with HEV. Multivariate modeling revealed no statistical difference in elevated antibody titers against HEV between the two groups. These data do not support the hypothesis that avian adenoviruses cross the species barrier to infect humans.

Prevalence and molecular characterization of Staphylococcus aureus from human stool samples

BACKGROUND Our objective was to estimate the per-infection and cumulative mortality and cost burden of multidrug-resistant (MDR) Acinetobacter healthcare-associated infections (HAIs) in the United States using data from published studies. METHODS We identified studies that estimated the excess cost, length of stay (LOS), or mortality attributable to MDR Acinetobacter HAIs. We generated estimates of the cost per HAI using 3 methods: (1) overall cost estimates, (2) multiplying LOS estimates by a cost per inpatient-day (

A systematic review of the epidemiology of carbapenem-resistant Enterobacteriaceae in the United States

4,350) from the payer perspective, and (3) multiplying LOS estimates by a cost per inpatient-day from the hospital (