Brian D.W. Chow

Newly recognized bocaviruses (HBoV, HBoV2) in children and adults with gastrointestinal illness in the United States

BACKGROUND The human bocavirus (HBoV) is a newly recognized parvovirus associated with respiratory and gastrointestinal disease. Recently, two new members of the parvovirus family have been recognized, HBoV2 and HBoV3. OBJECTIVES Here we investigate stool and respiratory samples for the presence of HBoV, HBoV2 and HBoV3. STUDY DESIGN Stool samples collected from 12/1/2007 to 3/31/2008 were screened by PCR for the presence of HBoV, HBoV2, and HBoV3. Extracted DNA from respiratory specimens archived between 10/17/2005 and 3/29/2006 were screened by PCR for HBoV2 and HBoV3. Medical records for all bocavirus positive patients were reviewed. RESULTS Of 479 stool samples screened, 328 (68.5%) were from adults, and 151 (31.5%) were from children. Sixteen (3.4%) patients were positive for the presence of a bocavirus, including 10 (2.1%) HBoV and 6 (1.3%) HBoV2. No HBoV3 was detected in stool samples. Frequency of HBoV and HBoV2 in stool samples from children was 3.3% and 0.7%, and from adults was 1.5% and 1.5% respectively. Clinical findings in patients with HBoV and HBoV2 in stool include diarrhea (50% and 83.3%), abdominal pain (40%, 33.3%), and cough (10%, 50%). Of 868 respiratory samples screened, none were positive for either HBoV2 or HBoV3. CONCLUSIONS The newly recognized parvovirus HBoV2 circulates in the United States. Patients with bocaviruses in stool have evidence of gastrointestinal illness. HBoV2 was not detected in respiratory samples. HBoV3 was not detected in either stool or respiratory samples.

The human bocaviruses: a review and discussion of their role in infection.

Respiratory tract infections are a leading cause of morbidity and mortality worldwide. The human bocavirus (HBoV) is a newly recognized human parvovirus first reported in 2005. Since its discovery, this virus has been associated with upper and lower respiratory tract disease and gastroenteritis worldwide. This article is a comprehensive review of what is known about HBoV. It includes an evaluation of diagnostic modalities, symptoms occurring in affected patients, and a discussion as to whether HBoV is responsible for identified clinical manifestations. The article reviews the incidence and effect of coinfection and updates on related members (HBoV-2 and HBoV-3) recently reported. Understanding of respiratory viruses such as HBoV remains vitally important to the health of adult and pediatric patients.

Evidence of human bocavirus circulating in children and adults, Cleveland, Ohio

Abstract Background Viral respiratory illness is a major cause of morbidity and mortality. The human bocavirus (HBoV) is a recently recognized parvovirus isolated from human respiratory secretions. Objectives To define the clinical and epidemiologic characteristics in adult and pediatric patients with evidence of HBoV. Study design From October 2005 through October 2006, we screened respiratory samples from children and adults negative for common respiratory pathogens for HBoV by PCR. Demographic and clinical characteristics were obtained from medical records of HBoV positive individuals. Results Of 2075 samples screened, 1826 (88.0%) represented distinct respiratory events: 1539 (84.3%) were pediatric (<18 years), and 273 (15.0%) adult (≥18 years). Forty (2.2%) patients had HBoV: 36 (2.3%) children and 4 (1.5%) adults. HBoV positive children had history of prematurity (31.3%) and cardiac disease (18.8%). Adults had underlying pulmonary (100%) and cardiac (50%) disease. Twenty-seven children (84.4%) were hospitalized; 9 (28.1%) required intensive care. All adults were hospitalized; none required intensive care. Nosocomial acquisition likely occurred in 3 patients. Conclusions HBoV circulates in Cleveland, OH, in children and adults with similar frequencies, and can warrant hospitalization and intensive care. Further study would clarify our understanding of this newly recognized human pathogen.

Candida parapsilosis and the neonate: epidemiology, virulence and host defense in a unique patient setting

Invasive candidiasis is a common problem in premature infants that leads to high morbidity and mortality. Although Candida albicans has historically been the most prominent species involved in these infections and has therefore been the subject of the most study, Candida parapsilosis is increasing in frequency, and neonates are disproportionately affected. This article reviews unique aspects of the epidemiology of this organism as well as strategies for prophylaxis against invasive candidiasis in general. Additionally, important differences between C.parapsilosis and C.albicans are coming to light related to virulence determinants and interactions with components of host immunity. These developments are reviewed while highlighting the significant gaps in our understanding that remain to be elucidated.

Effect of Statin Use on Influenza Vaccine Effectiveness

Background. Recent studies suggest that statin use may reduce influenza vaccine effectiveness (VE), but laboratory-confirmed influenza was not assessed. Methods. Patients ≥45 years old presenting with acute respiratory illness were prospectively enrolled during the 2004–2005 through 2014–2015 influenza seasons. Vaccination and statin use were extracted from electronic records. Respiratory samples were tested for influenza virus. Results. The analysis included 3285 adults: 1217 statin nonusers (37%), 903 unvaccinated statin nonusers (27%), 847 vaccinated statin users (26%), and 318 unvaccinated statin users (10%). Statin use modified VE and the risk of influenza A(H3N2) virus infection (P = .002) but not 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) or influenza B virus infection (P = .2 and .4, respectively). VE against influenza A(H3N2) was 45% (95% confidence interval [CI], 27%–59%) among statin nonusers and −21% (95% CI, −84% to 20%) among statin users. Vaccinated statin users had significant protection against influenza A(H1N1)pdm09 (VE, 68%; 95% CI, 19%–87%) and influenza B (VE, 48%; 95% CI, 1%–73%). Statin use did not significantly modify VE when stratified by prior season vaccination. In validation analyses, the use of other cardiovascular medications did not modify influenza VE. Conclusions. Statin use was associated with reduced VE against influenza A(H3N2) but not influenza A(H1N1)pdm09 or influenza B. Further research is needed to assess biologic plausibility and confirm these results.

Improving Human Papillomavirus Vaccine Use in an Integrated Health System: Impact of a Provider and Staff Intervention

Purpose: Acceptance and coverage of the human papillomavirus (HPV) vaccine in the United States has been suboptimal. We implemented a multifaceted provider and staff intervention over a 1-year period to promote HPV vaccination in a regional health care system. Methods: The intervention was conducted in nine clinical departments from February 2015 to March 2016; 34 other departments served as controls. The intervention included in-person provider and staff education, quarterly feedback of vaccine coverage, and system-wide changes to patient reminder and recall notifications. Change in first-dose HPV vaccine coverage and series completion were estimated among 11- to 12-year-olds using generalized estimating equations adjusted for age and sex. Results: HPV vaccine coverage in the intervention departments increased from 41% to 59%, and the increase was significantly greater than that seen in the control departments (32%—45%, p = .0002). The largest increase occurred in the quarter after completion of the provider and staff education and a patient reminder and recall postcard mailing (p = .004). Series completion also increased significantly system wide among adolescents aged 11—12 years following mailing of HPV vaccine reminder letters to parents of adolescents aged 12 years rather than 16 years. Conclusions: HPV vaccine uptake can be improved through a multifaceted approach that includes provider and staff education and patient reminder/recall. System-level change to optimize reminder and recall notices can have substantial impact on HPV vaccine utilization.

Prolonged Pyrexia and Hepatitis: Q fever

PRESENTATION Despite an ever-expanding spectrum of available tests, fever of unknown origin remains a diagnostic dilemma. A 40-year-old Nepalese man living in Rhode Island presented with a 1-week history of nausea, vomiting, fevers, and frontal headache. He denied neck stiffness, abdominal pain, diarrhea, rash, or urinary symptoms. In the emergency department, he had a temperature of 100.4 F (38.0 C) and was tachycardic to 108 beats per minute. His physical examination was otherwise normal. Lumbar puncture demonstrated no pleocytosis. Polymerase chain reaction testing of cerebrospinal fluid was negative for herpes simplex virus and enterovirus; a western blot was negative for Lyme IgM and IgG. Whole-body computed tomography was unrevealing. The patient was discharged but returned 4 days later with persistent headaches and fever, so he was admitted for further workup. His past medical history was notable for hypertension, for which he took chlorthalidone, and anxiety, for which he was prescribed paroxetine. Three years earlier, he had completed a 9-month course of isoniazid for latent tuberculosis infection. He lived with his wife and denied new sexual contacts, as well as use of any alcohol, tobacco, or illicit drugs. The patient had not travelled outside of New England following his emigration from Nepal 3 years before. He lived in an urban area and worked as a maintenance worker at a suburban warehouse where he had rodent contact and cut the grass but he denied tick bites. He had visited a farm

Host Defense Proteins in Breast Milk and Neonatal Yeast Colonization

Background: Colonization increases risk for invasive candidiasis in neonates. Breast milk host defense proteins may affect yeast colonization of infants. Objective: This study aimed to evaluate breast milk host defense proteins relative to yeast colonization in infants. Methods: Infants admitted for longer than 72 hours to the neonatal intensive care unit at Women & Infants Hospital in Providence, Rhode Island, were eligible. After consent, expressed breast milk and swabs from oral, rectal, and inguinal sites from infants were cultured weekly for 12 weeks, or until discharge, transfer, or death. Breast milk was tested for levels of human lactoferrin, lysozyme, apolipoprotein J, mucin-1, dermcidin, and soluble CD14 using commercial ELISA. Concentrations of these components were compared in breast milk received by infants who were colonized or not colonized with yeast. Results: From an original cohort of 130, 61 infants had samples available for this subanalysis. A convenience sample of stored breast milk was analyzed. Median lactoferrin, apolipoprotein J, and mucin-1 did not differ between colonized and uncolonized groups. Soluble CD14 was higher in the surface-colonized group (1.8 μg/mL, n = 12) compared with the surface-uncolonized group (1.6 μg/mL, n = 12, P = .02). Median lysozyme levels were higher in the surface-uncolonized group (483.0 ng/mL, n = 12) versus the surface-colonized group (298.3 ng/mL, n = 12, P = .04). Median dermcidin levels were higher in the surface-uncolonized group (19.4 ng/mL, n = 12) versus the surface-colonized group (8.7 ng/mL, n = 12, P = .04). Conclusion: This study shows an association between colonization with Candida in neonates and lower levels of lysozyme and dermcidin in received breast milk. Further study is needed to confirm these findings.

Expressed Breast Milk as a Predictor of Neonatal Yeast Colonization in an Intensive Care Setting

BACKGROUND Yeast colonization is a predictor for invasive infection in neonates. Candida albicans and Candida parapsilosis are leading causes of invasive fungal infection (IFI) in this population. This study examines maternal breast milk as a predictor of colonization of infants with yeast. METHODS Inclusion criteria were admission longer than 72 hours to the neonatal intensive care unit and parental consent. Cultures of expressed breast milk, when available, and swabs from oral, rectal, and inguinal sites were obtained weekly for 12 weeks, or until discharge, transfer, or death. Cultures were analyzed using standard laboratory methods. Clinical information was extracted from medical records. RESULTS One hundred thirty infants were enrolled from February 2011 to November 2012. Cultures were obtained in 129 patients. The median (interquartile range [IQR]) gestational age was 34.4 weeks (33.1-37.1 weeks). The median (IQR) birth weight was 2157.5 g (1740-3060 g). No infants developed IFIs. Twenty-nine (22%) infants were colonized with yeast. Potential correlates for colonization in univariate analysis included exposure to antenatal steroids, postnatal antibiotics, and receipt of breast milk containing yeast. Potential correlates that remained after multivariable logistic regression included exposure to antenatal steroids and receipt of breast milk containing yeast. In cases in which yeast was recovered from an individual infant and from the breast milk received by that infant, there was only 30% concordance between yeast species. DISCUSSION Recovery of yeast from breast milk is associated with colonization with yeast in the neonate. Because Candida transmission via breast milk had a 30% concordance, breast milk is only one of several ways colonization occurs. Further study is needed on mechanisms of colonization.

Differential modulation of human beta-defensin-3 expression in human oral epithelial cells by HPV oncoproteins E6 and E7: potential implication in oral cancer

Background Human papillomaviruses (HPVs) are small, non-enveloped DNA viruses that infect stratified squamous mucosal and cutaneous epithelia, causing diseases ranging from benign warts to invasive tumors. Failure of the immune system to detect and clear persistent HPV infections frequently leads to the development of oral warts and cancer. HPV infection has been etiologically linked with oral warts and a subset of oral squamous cell carcinoma, particularly in HIV infected patients. The incidence of HPV-related oral lesions is increased in HIV+ subjects on highly active antiretroviral therapy (HAART). We previously showed that tumor cells in oral carcinoma in situ (CIS) lesions overexpress human beta-defensin-3 (hBD-3), an antimicrobial peptide with immunomodulatory capabilities. Expression of hBD-3 in CIS contributes to the local pro-tumor immune response by selectively chemoattracting tumorassociated macrophages and by enhancing tumor development and progression.