Ana W. Capuano

Methicillin-Resistant Staphylococcus aureus (MRSA) Strain ST398 Is Present in Midwestern U.S. Swine and Swine Workers

Background Recent research has demonstrated that many swine and swine farmers in the Netherlands and Canada are colonized with MRSA. However, no studies to date have investigated carriage of MRSA among swine and swine farmers in the United States (U.S.). Methods We sampled the nares of 299 swine and 20 workers from two different production systems in Iowa and Illinois, comprising approximately 87,000 live animals. MRSA isolates were typed by pulsed field gel electrophoresis (PFGE) using SmaI and EagI restriction enzymes, and by multi locus sequence typing (MLST). PCR was used to determine SCCmec type and presence of the pvl gene. Results In this pilot study, overall MRSA prevalence in swine was 49% (147/299) and 45% (9/20) in workers. The prevalence of MRSA carriage among production system As swine varied by age, ranging from 36% (11/30) in adult swine to 100% (60/60) of animals aged 9 and 12 weeks. The prevalence among production system As workers was 64% (9/14). MRSA was not isolated from production system Bs swine or workers. Isolates examined were not typeable by PFGE when SmaI was used, but digestion with EagI revealed that the isolates were clonal and were not related to common human types in Iowa (USA100, USA300, and USA400). MLST documented that the isolates were ST398. Conclusions These results show that colonization of swine by MRSA was very common on one swine production system in the midwestern U.S., suggesting that agricultural animals could become an important reservoir for this bacterium. MRSA strain ST398 was the only strain documented on this farm. Further studies are examining carriage rates on additional farms.

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.

Aspirin as a Promising Agent for Decreasing Incidence of Cerebral Aneurysm Rupture

Background and Purpose— Chronic inflammation is postulated as an important phenomenon in intracranial aneurysm wall pathophysiology. This study was conducted to determine if aspirin use impacts the occurrence of intracranial aneurysm rupture. Methods— Subjects enrolled in the International Study of Unruptured Intracranial Aneurysms (ISUIA) were selected from the prospective untreated cohort (n=1691) in a nested case–control study. Cases were subjects who subsequently had a proven aneurysmal subarachnoid hemorrhage during a 5-year follow-up period. Four control subjects were matched to each case by site and size of aneurysm (58 cases, 213 control subjects). Frequency of aspirin use was determined at baseline interview. Aspirin frequency groups were analyzed for risk of aneurysmal hemorrhage. Bivariable and multivariable analyses were performed using conditional logistic regression. Results— A trend of a protective effect for risk of unruptured intracranial aneurysm rupture was observed. Patients who used aspirin 3× weekly to daily had an OR for hemorrhage of 0.40 (95% CI, 0.18–0.87); reference group, no use of aspirin), patients in the “< once a month” group had an OR of 0.80 (95% CI, 0.31–2.05), and patients in the “> once a month to 2×/week” group had an OR of 0.87 (95% CI, 0.27–2.81; P=0.025). In multivariable risk factor analyses, patients who used aspirin 3 times weekly to daily had a significantly lower odds of hemorrhage (adjusted OR, 0.27; 95% CI, 0.11–0.67; P=0.03) compared with those who never take aspirin. Conclusions— Frequent aspirin use may confer a protective effect for risk of intracranial aneurysm rupture. Future investigation in animal models and clinical studies is needed.

Testing human sera for antibodies against avian influenza viruses: Horse RBC hemagglutination inhibition vs. microneutralization assays

BACKGROUND The hemagglutination inhibition (HI) assay is a frequently used method to screen human sera for antibodies against influenza A viruses. Because HI has relatively poor sensitivity in detecting antibodies against avian influenza A strains, a more complicated microneutralization (MN) assay is often preferred. Recent research suggests that the sensitivity of the HI assay can be improved by switching from the traditionally used turkey, guinea pig, human, or chicken RBCs to horse RBCs. OBJECTIVE To evaluate the performance of the horse RBC HI when screening for human antibodies against avian influenza types H3, H4, H5, H6, H7, H9, H11, and H12. STUDY DESIGN We evaluated the reproducibility of horse RBC HI and its agreement with MN results using sera from people exposed or not exposed to wild and domestic birds. RESULTS The horse RBC HI assay had high reliability (90%-100%) and good agreement with MN assay results (52%-100%). CONCLUSION The horse RBC HI assay is reliable, less expensive, less complex, and faster than the MN assay. While MN will likely remain the gold standard serologic assay for avian viruses, the horse RBC HI assay may be very useful as a screening assay in large-scale epidemiologic studies.

Risk of ventriculostomy-related hemorrhage in patients with acutely ruptured aneurysms treated using stent-assisted coiling.

OBJECT Intracranial stenting has improved the ability to treat wide-neck aneurysms via endovascular techniques. However, stent placement necessitates the use of antiplatelet agents, and the latter may complicate the treatment of patients with acutely ruptured aneurysms who demonstrate hydrocephalus and require ventriculostomy. Antiplatelet agents in this setting could increase the incidence of ventriculostomy-related hemorrhagic complications, but there are insufficient data in the medical literature to quantify this potential risk. The aim of this study was to directly quantify the risk of ventriculostomy-related hemorrhage in patients with acute aneurysmal subarachnoid hemorrhage treated with stent-assisted coiling. METHODS The authors retrospectively identified 131 patients who underwent endovascular treatment for an acutely ruptured aneurysm as well as ventriculostomy or ventriculoperitoneal (VP) shunt placement. The rate of hemorrhagic complications associated with ventriculostomy or VP shunt insertion was compared between patients who underwent coiling without a stent (Group 1) and those who underwent stent-assisted coiling and dual antiplatelet therapy (Group 2). RESULTS One hundred nine ventriculostomies or VP shunt placement procedures were performed in 91 patients in Group 1, and 50 procedures were undertaken in 40 patients in Group 2. The rates of radiographic hemorrhage and symptomatic hemorrhage were significantly higher in Group 2 (32% vs 14.7%, p = 0.02; and 8% vs 0.9%, p = 0.03, respectively). On multivariate analyses, Group 2 had 3.42 times the odds of a radiographic hemorrhage (95% CI 1.46-8.04, p = 0.0048) after adjusting for antiplatelet use prior to admission. CONCLUSIONS The application of dual antiplatelet therapy in stent-assisted coiling of acutely ruptured aneurysms is associated with an increase in the risk of hemorrhagic complications following ventriculostomy or VP shunt placement, as compared with its use in a coiling procedure without a stent.

Relation of cerebral vessel disease to Alzheimer's disease dementia and cognitive function in elderly people: a cross-sectional study

Background Few pathologic data are available on cerebral vessel disease, dementia, and cognition. This cross-sectional study examined associations of cerebral atherosclerosis and arteriolosclerosis neuropathology with probable and possible Alzheimer’s disease (AD) dementia and level of cognitive function, in a large group of older persons who came to autopsy. Methods 1,143 older women or men (median age-at-death = 88.8 years; 42% with AD dementia) underwent annual clinical evaluations and agreed to brain autopsy at time-of-death, as part of one of two cohort studies of aging. Neuropsychological data proximate-to-death were used to create summary measures of global cognition and cognitive domains. Data across all years were used to determine presence of the clinical syndrome of AD dementia. Systematic neuropathologic evaluations documented severity of cerebral large (atherosclerosis) and small vessel disease (arteriolosclerosis). Using regression analyses adjusted for demographics, gross and micro-infarcts and AD pathology, we examined associations of vessel disease severity with odds of probable and possible AD dementia and level of cognition. Findings Moderate-to-severe atherosclerosis was present in 445 (39%) subjects, and arteriolosclerosis in 401 (35%). The odds of AD dementia was higher with moderate-to-severe atherosclerosis (OR=1.33; 95%CI:1.11–1.58) and arteriolosclerosis (OR=1.20; 95%CI:1.04–1.40). Atherosclerosis was associated with lower scores for global cognition (estimate= −0.10, SE=0.04; p=0.00096) and four cognitive domains (episodic memory, semantic memory, perceptual speed and visuospatial abilities; all p<0.019) but not working memory (p=0.21). Arteriolosclerosis was associated with lower scores for global cognition (estimate= −0.10, SE=0.03; p=0.0015) and four domains (all p<0.046), and a borderline/non-significant association was noted for visuospatial abilities (p=0.052). Findings were unchanged in analyses controlling for APOEε4 and vascular risk factors. Interpretation Cerebral atherosclerosis and arteriolosclerosis each contribute to the odds of AD dementia by 20–30% per level increase in severity, and are associated with lower scores in most cognitive domains. Associations remain after taking into account AD and infarct pathologies, and vascular factors. Cerebral vessel pathology may be an under-recognized risk factor for AD dementia. Funding United States National Institutes of Health.

Hippocampal sclerosis and TDP‐43 pathology in aging and Alzheimer disease

To investigate the association of hippocampal sclerosis (HS) with TAR‐DNA binding protein of 43kDa (TDP‐43) and other common age‐related pathologies, dementia, probable Alzheimer disease (AD), mild cognitive impairment (MCI), and cognitive domains in community‐dwelling older subjects.

Preventing Zoonotic Influenza Virus Infection

We evaluated 49 swine industry workers and 79 nonexposed controls for antibodies to swine influenza viruses. Multivariate modeling showed that workers who seldom used gloves (odds ratio [OR] 30.3) or who smoked (OR 18.7) most frequently had evidence of previous H1N1 swine virus. These findings may be valuable in planning for pandemic influenza.