Troy McCarthy

Swine workers and swine influenza virus infections.

Swine workers and their spouses are at markedly increased risk of acquiring swine influenza virus infections.

Human Metapneumovirus, Peru

We retrospectively studied 420 pharyngeal swab specimens collected from Peruvian and Argentinean patients with influenzalike illness in 2002 and 2003 for evidence of human metapneumovirus (HMPV). Twelve specimens (2.3%) were positive by multiple assays. Six specimens yielded HMPV isolates. Four of the 6 isolates were of the uncommon B1 genotype.

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 for avian influenza A infections among Iowa’s agricultural workers

Background  Identifying risk factors for zoonotic influenza transmission may aid public health officials in pandemic influenza planning.

Molecular typing of clinical adenovirus specimens by an algorithm which permits detection of adenovirus coinfections and intermediate adenovirus strains.

BACKGROUND Epidemiological data suggest that clinical outcomes of human adenovirus (HAdV) infection may be influenced by virus serotype, coinfection with multiple strains, or infection with novel intermediate strains. In this report, we propose a clinical algorithm for detecting HAdV coinfection and intermediate strains. STUDY DESIGN We PCR amplified and sequenced subregions of the hexon and fiber genes of 342 HAdV-positive clinical specimens obtained from 14 surveillance laboratories. Sequences were then compared with those from 52 HAdV prototypic strains. HAdV-positive specimens that showed nucleotide sequence identity with a corresponding prototype strain were designated as being of that strain. When hexon and fiber gene sequences disagreed, or sequence identity was low, the specimens were further characterized by viral culture, plaque purification, repeat PCR with sequencing, and genome restriction enzyme digest analysis. RESULTS Of the 342 HAdV-positive clinical specimens, 328 (95.9%) were single HAdV strain infections, 12 (3.5%) were coinfections, and 2 (0.6%) had intermediate strains. Coinfected specimens and intermediate HAdV strains considered together were more likely to be associated with severe illness compared to other HAdV-positive specimens (OR=3.8; 95% CI=1.2-11.9). CONCLUSIONS The majority of severe cases of HAdV illness cases occurred among immunocompromised patients. The analytic algorithm we describe here can be used to screen clinical specimens for evidence of HAdV coinfection and novel intermediate HAdV strains. This algorithm may be especially useful in investigating HAdV outbreaks and clusters of unusually severe HAdV disease.

Emergent US Adenovirus 3 Strains Associated with an Epidemic and Serious Disease

BACKGROUND Adenovirus type 3 (HAdV3) is one of the most prevalent serotypes detected globally. Variants of HAdV3 have been associated with outbreaks of severe disease. OBJECTIVES To better understand genetic diversity of circulating HAdV3s and examine risk factors for severe disease. STUDY DESIGN Restriction enzyme analysis for genomic characterization of clinical HAdV3 isolates detected by 15 collaborative US laboratories during the period July 2004 to May 2007. Multivariate modeling was employed for statistical analyses. RESULTS The most common HAdV3 types of 516 isolates studied were HAdV3a2 (36.9%), HAdV3a50 (27.1%), HAdV3a51 (18.0%), and HAdV3a17 (4.6%). Non-HAdV3a genome types were rare (1.2%). HAdV3a50 and HAdV3a51 are newly described variants which became more prevalent in 2006 and 2007 and have been associated with at least one epidemic. Their uniqueness was determined by specific banding profiles generated by digests with endonucleases BclI, BglII, and HindIII. Multivariable risk factor modeling demonstrated that children under 2 years of age (OR=2.7; 95%CI 1.6-4.6), persons with chronic disease (OR=5.1; 95%CI 2.6-9.8), persons infected with HAdV3a2 (OR=3.0; 95%CI 1.5-6.0), with HAdV3a50 (OR=2.5; 95%CI 1.2-5.2), or with multiple or rare strains (OR=2.8; 95%CI 1.3-6.5) were at increased risk of severe HAdV3 clinical disease. CONCLUSIONS In the study period considerable genetic diversity was found among US clinical HAdV3 strains. Novel variants emerged and became prevalent. One such emergent strain may be associated with more severe clinical disease.

Adenovirus type 3 outbreak in connecticut associated with a novel variant

An adenovirus outbreak occurred in New Haven, Connecticut in 2006–2007. Molecular typing revealed a twofold increase in adenovirus type 3 infections. Restriction enzyme analysis (REA) indicated that the CT outbreak was largely due to a marked increase in the novel Ad3a51 strain. This outbreak represents the first detection of Ad3a51 in the United States. While most infections were mild, children under 3 were at increased risk for severe disease and one patient with underlying disease died. J. Med. Virol. 81:1380–1384, 2009.

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.

Localization of Epidermal Growth Factor Receptor in Alveolar Epithelium During Human Fetal Lung Development in Vitro

Epidermal growth factor (EGF) enhances alveolar type II cell differentiation. In human fetal lung explants, EGF stimulates surfactant protein A (SP-A) synthesis. This effect may occur through a direct interaction of the ligand on EGF receptors located within distal pulmonary epithelium during alveolar type II cell differentiation. To determine if EGF receptor is present in alveolar epithelium, immunostaining for EGF receptor and in situ hybridization for EGF receptor mRNA were performed in human fetal lung explants undergoing alveolar type II cell differentiation in vitro. After 4 days in culture, EGF receptor immunostaining was present in alveolar epithelium from human fetal lung explants compared to minimal immunostaining in undifferentiated human fetal lung epithelium prior to culture. In situ hybridization revealed increased EGF receptor mRNA in differentiated type II cells from cultured explants, with minimal EGF receptor mRNA detected in undifferentiated epithelium from tissue prior to culture. Immunogold staining revealed EGF receptors on the cytoplasmic membranes of epithelial cells lining the prealveolar ducts in human fetal lung explants after 2 days in culture. Alveolar type II cell differentiation in vitro was confirmed ultrastructurally by the presence of lamellar bodies and biochemically by an increase in SP-A content. Thus, EGF receptor is found in alveolar epithelium during differentiation, which suggests an important role for EGF during human fetal lung development.

Effect of tyrosine kinase inhibition on surfactant protein A gene expression during human lung development

Epidermal growth factor (EGF) stimulates surfactant protein (SP) A synthesis in human fetal lung explants. Ligand binding to the EGF receptor stimulates an intrinsic receptor tyrosine kinase with subsequent activation of second messengers. We hypothesized that inhibition of EGF-receptor tyrosine kinase activity would block SP-A expression in spontaneously differentiating cultured human fetal lung tissue. Midtrimester fetal lung explants were exposed for 4 days to genistein (a broad-range inhibitor of tyrosine kinases) and tyrphostin AG-1478 (a specific inhibitor of EGF-receptor tyrosine kinase). Genistein significantly decreased SP-A and SP-A mRNA levels without affecting either tissue viability or the morphological differentiation of alveolar type II cells. Tyrphostin AG-1478 also decreased SP-A content and SP-A mRNA levels in cultured fetal lung explants. Treatment with EGF could not overcome the inhibitory effects of either genistein or tyrphostin on SP-A; however, only tyrphostin inhibited EGF-receptor tyrosine phosphorylation. We conclude that specific inhibition of EGF-receptor tyrosine kinase with tyrphostin AG-1478 blocks the expression of SP-A during spontaneous differentiation of cultured human fetal lung tissue. Furthermore, exposure to genistein also decreases SP-A expression and blocks the effects of EGF in human fetal lung tissue without inhibiting EGF-receptor tyrosine phosphorylation. These findings support the importance of tyrosine kinase-dependent signal transduction pathways in the regulation of SP-A during human fetal lung development.