Positive Viral Test Research Articles

Effectiveness of Live Zoster Vaccine in Preventing Herpes Zoster Ophthalmicus (HZO)

BackgroundHerpes zoster ophthalmicus (HZO), caused by reactivation of varicella-zoster virus in or around the eye, can be severe and often results in care-seeking that may be less discretionary than for uncomplicated herpes zoster (HZ). We compared the vaccine effectiveness (VE) of live zoster vaccine against HZO with the VE against HZ overall.MethodsKaiser Permanente Northern California (KPNC) members enter the ongoing cohort study when age-eligible for zoster vaccine starting in 2007. Incident HZ was defined as a new diagnosis of HZ with an antiviral prescription or a positive varicella viral test. Among those, an HZO case was defined as having an HZO diagnosis during an ophthalmology visit within 30 days of the initial HZ diagnosis. VE by age at vaccination and time since vaccination was estimated using Cox regression adjusted for age, race, sex and time-varying measures of healthcare use, comorbidities and immunocompromise status. Average VE over the first 5 years following vaccination was calculated as a weighted average of annual VE estimates.ResultsDuring 2007–2014, ~1.3 million individuals ≥50 years of age entered the study population and 29% were vaccinated. Among 48,889 incident HZ cases, 2,858 (6%) had HZO, 87% of whom were unvaccinated. For all ages combined, VE against HZO was 72% (95% CI, 64%-79%) in year 1, similar to 68% (95% CI, 65%-70%) against HZ. VE fell in years 2, 3, 4, and 5 to 47%, 45%, 42% and 27% for HZO and to 47%, 39%, 41% and 37% for HZ. For age groups 60 – 69 and 70 – 79, where we have the most data, initial VE and waning were similar for HZO and HZ. Numbers of HZO cases for 50–59 year olds were too small to evaluate at this time. Average VE against HZO over the first 5 years following vaccination was 52% (95% CI, 42%–60%) for ages 60–69, 51% (95% CI, 39%–61%) for ages 70-79, and 39% (95% CI, 14%-57%) for ages 80+; similarly, 5-year average VE against HZ was 49%, 46%, and 44% for these 3 age groups.ConclusionVE against HZO was similar to VE against HZ regardless of age at vaccination or time since vaccination. Effectiveness of live zoster vaccine in preventing HZO was highest in year one with subsequent waning.Disclosures E. Earley, Merck & Co.: Research Contractor, Salary; M. Marks, Merck and Co. Inc.: Employee, Restricted Stock and Salary; P. Saddier, Merck & Co., Inc.: Employee, Salary; N. P. Klein, GSK: Investigator, Grant recipient; sanofi pasteur: Investigator, Grant recipient; Merck & Co.: Investigator, Grant recipient; MedImmune: Investigator, Grant recipient; Protein Science: Investigator, Grant recipient Pfizer: Investigator, Grant recipient

Integration of Next–Generation Sequencing, Viral Sequencing, and Host-Response Profiling for the Diagnosis of Acute Infections

BackgroundTo guide treatment of infectious diseases, clinicians need sensitive, specific, and rapid diagnostics. We aim to incorporate complementary methods of microbial sequencing and host-response profiling to improve the diagnosis of patients at risk for acute infections.MethodsWe enrolled 200 adult patients with systemic inflammatory response syndrome (SIRS) at the Stanford Emergency Department. Physicians with specialty training in infectious diseases conducted retrospective two-physician chart review to establish likely admission diagnoses. Blood samples were tested with a previously described 18-gene host-response integrated antibiotics decision model (IADM) that distinguishes noninfectious SIRS, bacterial infections and viral infections. Plasma samples were tested with shotgun metagenomic next-generation sequencing (NGS) and viral sequencing with VirCapSeq. A novel statistical algorithm was developed to identify contaminant organism sequences in NGS data.ResultsThe physician chart review classified 99 patients (49%) as infected, 69 (35%) possibly infected and 32 (16%) non-infected. Compared with chart review, the IADM distinguished bacterial from viral infections with an area under curve of 0.85 (95% confidence interval 0.77–0.93). NGS results to date confirmed positive blood cultures in seven of nine patients, with two of four blood culture-positive E. coli patients turning up negative on NGS due to E. coli contamination. NGS also confirmed positive cultures from other sites in two of six patients with negative blood cultures. Preliminary VirCapSeq data from 23 patients confirmed positive viral tests in five of six patients with Hepatitis C, BK Virus, Cytomegalovirus and Epstein–Barr Virus infections. VirCapSeq did not identify a causative agent in the plasma of 11 patients with confirmed respiratory viral infection and intestinal Norovirus infection, and six patients with idiopathic illness. Interestingly, VirCapSeq found viral reactivation in 8 of 12 immunocompromised patients.ConclusionThe diagnosis of suspected infections may be enhanced by integrating host-response and microbial data alongside clinical judgment. Our results and large cohort lay the foundation to demonstrate the utility of this approach and in which patients these tools may be most useful.Disclosures T. E. Sweeney, Inflammatix, Inc: Employee and Shareholder, Salary; T. Briese, Roche: Columbia University has licensed VirCapSeq to Roche, Licensing agreement or royalty; W. I. Lipkin, Roche: Columbia University has licensed VirCapSeq to Roche., Licensing agreement or royalty; P. Khatri, Inflammatix, Inc.: Co-founder, Scientific Advisor and Shareholder, Licensing agreement or royalty and ownership stock; D. A. Relman, Karius: Consultant, Stock options; Arc Bio LLC: Consultant, Stock options

Promoting notification and linkage of HBs antigen and anti-HCV antibody-positive patients through hospital alert system

BackgroundIn Japan, approximately 0.9% and 1% of the whole population are infected with HBV and HCV, respectively. Doctors from departments other than gastroenterology often order viral hepatitis tests before an invasive examination or an operation. However, the notification of positive results to the patients and linkage to care is not appropriately performed. The in-hospital alert system was constructed to promote the notification and referral to gastroenterologists for patients with positive viral hepatitis tests, and its efficacy was evaluated.MethodsThe patients who tested HBsAg and anti-HCV antibody by chemiluminescent enzyme immunoassays and chemiluminescent immunoassays were investigated for whether they were notified of the positive results and if they were referred to gastroenterologists at our hospital. The notification and referral rate was compared before (from January to December 2014) and after the introduction of the alert system (from February to September 2016).ResultsHBsAg-positive rate was 1.1% (69/6543) before the introduction of the alert system and 0.8% (41/5403) after it. The notification rate has significantly improved from 46% to 73% (p = 0.0061) and the referral rate has improved from 16% to 27%, while not significant. Positive rate of anti-HCV antibody was 2.1% (139/6481) before the introduction of the alert system and 2.4% (128/5322) after it. The rate of notification and referral has significantly improved from 35% to 62% (p < 0.0001) and from 6% to 23% (p < 0.0001), respectively.ConclusionsThe in-hospital alert system increased the rates of notification and referral of the patients with positive viral hepatitis tests. Enlightenment of doctors other than gastroenterologists on viral hepatitis and cooperation of medical staffs would be helpful to improve the notification and referral rates.

Respiratory viral detection in the paranasal sinuses of patients with cystic fibrosis.

Pulmonary colonization with antibiotic-resistant organisms in patients with cystic fibrosis (CF) is often preceded by upper-airway infections. Although there is a well-described relationship between pulmonary respiratory viral infections and overall disease progression of CF, the pathogenicity of respiratory viral infections in the paranasal sinuses of patients with CF remains unknown. With recent advances in respiratory virus detection techniques, this study sought to detect the presence of respiratory viruses in the paranasal sinuses of patients with CF in comparison with healthy controls and to correlate the viral presence with clinical measures of sinonasal disease. This prospective individual cohort study compared 24 patients with CF with 14 healthy controls. Basic demographics, clinical measures of disease and respiratory viral screens (commercial multiplex) obtained directly from the paranasal sinuses were compared between the two groups. Respiratory viruses were detected in 33% of patients with CF (8/24) compared with 0% of the healthy controls (0/14) (p = 0.017). Respiratory viruses were only detected during the winter months, and the most commonly identified were influenza A and human rhinovirus strains. There was no statistical difference in the 22-Item Sino-Nasal Outcome Test (SNOT-22) scores (p = 0.93) or modified Lund-Kennedy scores (p = 0.74) between patients with CF with a positive viral test and those without a positive result. Respiratory viral detection is more commonly detected in the paranasal sinuses of patients with CF compared with healthy controls. Although respiratory viral presence did not correlate with a worse clinical severity of sinonasal disease, these findings may provide insight into the pathophysiology of CF and open new avenues for potential targeted therapy.

Concurrent Respiratory Viruses and Kawasaki Disease.

The diagnosis of Kawasaki disease (KD) remains challenging without a definitive diagnostic test and currently is guided by using clinical patient characteristics and supported by laboratory data. The role of respiratory viruses in the pathogenesis of KD is not fully understood. Charts of patients with KD admitted to Children's Hospital Colorado from January 2009 to May 2013 were retrospectively reviewed. Patients with KD who had a nasopharyngeal wash submitted for multiplex polymerase chain reaction (PCR) viral testing were included. Clinical characteristics, laboratory data, and outcomes of patients with and without positive respiratory viral PCR results were compared. Of 222 patients with KD admitted to the hospital, 192 (86%) had a respiratory viral PCR test performed on or shortly after admission. Ninety-three (41.9%) of the 192 patients with KD had a positive respiratory viral PCR, and the majority were positive for rhinovirus/enterovirus. No statistically significant differences were found in the clinical characteristics and laboratory values between the groups with and without positive respiratory viral PCR findings. Both groups had the same frequency of upper respiratory and gastrointestinal symptoms and had the same incidence of admission to the PICU, intravenous immunoglobulin-resistant disease, and coronary artery lesions. No differences in clinical presentations or outcomes in children with KD stratified according to positive or negative respiratory viral PCR testing were observed. A positive respiratory viral PCR or presence of respiratory symptoms at the time of presentation should not be used to exclude a diagnosis of KD.

Analysis of viral testing in nonacetaminophen pediatric acute liver failure.

Viral infections are often suspected to cause pediatric acute liver failure (PALF), but large-scale studies have not been performed. We analyzed the results of viral testing among nonacetaminophen PALF study participants. Participants were enrolled in the PALF registry. Diagnostic evaluation and final diagnosis were determined by the site investigator and methods for viral testing by local standard of care. Viruses were classified as either causative viruses (CVs) or associated viruses (AVs). Supplemental testing for CV was performed if not done clinically and serum was available. Final diagnoses included "viral," "indeterminate," and "other." Of 860 participants, 820 had at least 1 test result for a CV or AV. A positive viral test was found in 166/820 (20.2%) participants and distributed among "viral" (66/80 [82.5%]), "indeterminate" (52/420 [12.4%]), and "other" (48/320 [15.0%]) diagnoses. CVs accounted for 81/166 (48.8%) positive tests. Herpes simplex virus (HSV) was positive in 39/335 (11.6%) who were tested 26/103 (25.2%) and 13/232 (5.6%) among infants 0 to 6 and >6 months, respectively. HSV was not tested in 61.0% and 53% of the overall cohort and those 0 to 6 months, respectively. Supplemental testing yielded 17 positive, including 5 HSV. Viral testing in PALF occurs frequently but is often incomplete. The evidence for acute viral infection was found in 20.2% of those tested for viruses. HSV is an important viral cause for PALF in all age groups. The etiopathogenic role of CV and AV in PALF requires further investigation.

Investigation of rotavirus and adenovirus antigens in patients with acute gastroenteritis

Objective: Nowadays, viruses are the most common agents of acute gastroenteritis all over the world. Acute gastroenteritis, especially in children, is an important cause of mortality and morbidity. Both the lack of effective treatments as well as due to the unnecessary use of antibiotics, detection of viral agents in stool is important in terms of the epidemiology and monitoring of the disease. The purpose of this study is to determine the frequency of rotavirus and adenovirus in patients with acute gastroenteritis admitted to our hospital. Methods: Rotavirus and adenovirus 40/41 antigens were investigated by immunochromatographic method in stool samples of 2795 patients admitted to our hospital with the diagnosis of acute gastroenteritis between January 2010- December 2013. Results: Viral antigens were detected in 338 (12,1%) of the total 2795 samples. Rotavirus antigen was detected in 273 (9.8%), adenovirus in 36 (1.3%), both rotavirus and adenovirus in 29 (1.0%) of the patients. Of the cases who have positive viral antigen test, 154 (45.6%) were female, 184 (54.4%) were male and 198 (58.6%) were in the 0-2 age group. Total antigen positivity was more common in the late summer and autumn. Conclusion: Rotavirus is the most important agent in acute gastroenteritis in our hospital. More than half of patients were in the 0-2 years old group. Detection of viral agents in patients with acute gastroenteritis will allow early diagnosis and symptomatic treatment as well as will prevent empirically the use of antibiotics. J Clin Exp Invest 2014; 5 (2): 256-260

The study of etiology of respiratory infection and antibiotics employment in pediatric patients

Objective To research the pathogenies' types and analyze the antibacterial drug' s using rationality from the children with acute respiratory infection,our study were generated by pediatric department from the hospital lasting 2 years.Methods A total of 93 pediatric patients with acute respiratory infection admitted from December 1,2010 through November 30,2012 were enrolled into study.The throat swabs from 93 patients were sent to the Beijing Center for Disease and Prevention (CDC) to identify the influenza virus,syncytial virus and mycoplasma with rapid nucleic acid test.The specimens of sputum from hospitalized patients were sent to the hospital bacterial laboratory for bacteria culture.With the Children Drug Utilization Index (cDUI),the rationality of using antibiotics was estimated.The database was established by using SPSS version 18.0 software and the data were analyzed to determine the statistical distinction among the percentage by the Chi square test (P ＜ 0.05).Results Of them,70.96％ pediatric patients were below 3 years old (excluding newborns).Of them,62.36％ patients had positive findings of viral infection.The predominant viruses of respiratory infection were syncytial virus accounting for 30.43％,the influenza viruses 24.63％ and the para-influenza virus 10.14％.The patients with positive results in vital test were more vulnerable to lower respiratory infection than those with negative results.The pneumonia patients with positive finding of syncytial virus accounted for 85.71％ (18 patients) in which the median cDUI was 1.30.The antibiotics were given to 28 pneumonia patients with positive virus test,in which the median cDUI was 1.05.Of 28 pneumonia patients,4 (16％) had positive bacteria growth in sputum cultures,and 4 cases (16％) had positive bacteria growth in blood cultures.Conclusions In the district of hospital,the lower respiratory infection was usually caused by viruses.Therefore,antibiotics should not be given in patients without evidence of bacterial infection.It is a irrational strategy to use antibiotics in those patients when the Children Drug Utilization Index is high (＞ 1.0).It is paramount important to notice that the percentage of positive bacteria growth in sputum cultures is usually not high because the antibiotics are given by OPD physicians before hospitalization of patients with bacterial infections in the acute respiratory illness. Key words: Pneumonia; Children ; Infection ; Drug utilization index; Antimicrobial agents

Bacterial Complications of Respiratory Tract Viral Illness: A Comprehensive Evaluation

Background. Respiratory tract infection is one of the most common reasons for hospitalization among adults, and recent evidence suggests that many of these illnesses are associated with viruses. Although bacterial infection is known to complicate viral infections, the frequency and impact of mixed viral-bacterial infections has not been well studied. Methods. Adults hospitalized with respiratory illness during 3 winters underwent comprehensive viral and bacterial testing. This assessment was augmented by measuring the serum level of procalcitonin (PCT) as a marker of bacterial infection. Mixed viral-bacterial infection was defined as a positive viral test result plus a positive bacterial assay result or a serum PCT level of ≥ 0.25 ng/mL on admission or day 2 of hospitalization. Results. Of 842 hospitalizations (771 patients) evaluated, 348 (41%) had evidence of viral infection. A total of 212 hospitalizations (61%) involved patients with viral infection alone. Of the remaining 136 hospitalizations (39%) involving viral infection, results of bacterial tests were positive in 64 (18%), and PCT analysis identified bacterial infection in an additional 72 (21%). Subjects hospitalized with mixed viral-bacterial infections were older and more commonly received a diagnosis of pneumonia. Over 90% of hospitalizations in both groups involved subjects who received antibiotics. Notably, 4 of 10 deaths among subjects hospitalized with viral infection alone were secondary to complications of Clostridium difficile colitis. Conclusions. Bacterial coinfection is associated with approximately 40% of viral respiratory tract infections requiring hospitalization. Patients with positive results of viral tests should be carefully evaluated for concomitant bacterial infection. Early empirical antibiotic therapy for patients with an unstable condition is appropriate but is not without risk.

Viral Infections in Children with Community-Acquired Pneumonia

Viral pathogens are commonly isolated from children with community-acquired pneumonia (CAP). Viruses like respiratory syncytial virus, human rhinovirus, human metapneumovirus, parainfluenza viruses, and influenza may act as sole pathogens or may predispose to bacterial pneumonia by a variety of mechanisms. New, emerging, or reemerging viral pathogens occasionally cause outbreaks of severe respiratory tract infection in children. The 2009–2010 H1N1 influenza virus pandemic resulted in increased rates of influenza-related hospitalizations and deaths in children. Rapid viral diagnostic tests based on antigen detection or nucleic acid amplification are increasingly available for clinical use and confirm the importance of viral infection in children hospitalized with CAP. Recently published guidelines for the management of CAP in children note that positive viral test results can modify clinical decision making in children with suspected pneumonia by allowing antibacterial therapy to be withheld in the absence of clinical, laboratory, or radiographic findings that suggest bacterial coinfection.

Hepatitis B virus-related post-infectious glomerulonephritis: a case report

Hepatitis B virus infection is an uncommon cause of acute glomerulonephritis. We present a case of acute glomerulonephritis revealing a chronic viral hepatitis B. A 45 year-old man was admitted in the nephrology department of Hassan II university hospital (Fez, Morocco) for nephritic syndrome with advanced acute kidney injury. The investigations have revealed viral hepatitis B with a positive HBV-DNA and Others viral serology tests were negative. Renal biopsy showed a diffuse and global endocapillary proliferation without extra-capillary proliferation; and global deposits of C3 and Ig G On immunofluorescence. There wasn't any other infectious cause. We thus retained the diagnosis of hepatitis B virus-associated acute glomerulonephritis. He was given entecavir and corticosteroids. Three months later, the evolution was marked by the normalization of renal function, negativity of proteinuria and HBV DNA became undetectable. There was no relapse of glomerulonephritis and HBV viral load was still negative after one year follow-up.

Which patients should be tested for viruses on bronchoalveolar lavage fluid?

Bronchoalveolar lavage (BAL) is a major diagnostic tool in lung diseases, including viral respiratory infections. We aimed to better define the situations where viral tests should be performed on BAL fluid (BALF). We retrospectively studied all cases where viral tests [immunofluorescence, immunocytochemistry, viral culture, and/or polymerase chain reaction (PCR)] were performed on BALF during a period of 1 year (2008) in our institution. We compared the characteristics of patients with virus-positive versus virus-negative BALF. Of the 636 BALF samples sent to the microbiology laboratory, 232 underwent viral tests. Of these, 70 (30 %) were positive and identified 85 viruses: herpes simplex virus (HSV)-1 (n = 27), cytomegalovirus (CMV, n = 23), Epstein–Barr virus (EBV, n = 18), human herpesvirus (HHV)-6 (n = 12), respiratory syncytial virus (RSV, n = 3), rhinovirus (n = 1), and adenovirus (n = 1). The variables associated with positive viral tests on univariate analysis were immunosuppression [human immunodeficiency virus (HIV), corticosteroids >10 mg/day for ≥3 weeks, or other immunosuppressive therapy], ground-glass attenuations on computed tomography (CT) scanning, late-onset ventilator-associated pneumonia (VAP), and durations of (i) hospital stay, (ii) intensive care unit (ICU) stay, and (iii) mechanical ventilation before BAL (p < 0.01 for each comparison). On multivariate analysis, only immunosuppression [odds ratio (OR) 6.4, 95 % confidence interval (CI) [2.8–14.3], p < 0.0001] and ground-glass attenuations (OR 3.7, 95 % CI [1.8–7.7], p = 0.0004) remained associated with virus-positive BAL. None of the viral tests performed on BALF for the initial assessment of diffuse infiltrative lung disease (n = 15) was positive. PCR improved the diagnostic yield of viral tests on BALF by 50 %. Testing for viruses on BALF should be mostly restricted to immunocompromised patients with acute respiratory diseases and/or patients with unexplained ground-glass attenuations on CT scanning.

Prevalence and Clinical Course of Viral Upper Respiratory Tract Infections in Immunocompromised Pediatric Patients With Malignancies or After Hematopoietic Stem Cell Transplantation

Respiratory tract infections (RTI) in immunosuppressed pediatric patients with malignancies or after hematopoietic stem cell transplantation (HSCT) are associated with significant morbidity and mortality. Prospective data on the incidence and clinical role of infections by respiratory viruses in this population have been lacking. In this prospective study, 191 children between 0 and 18 years of age were investigated by real-time polymerase chain reaction for the presence of 8 common respiratory virus types in transnasal aspirations. The study included 110 children with leukemia, lymphoma, or solid tumors (subgroup 1); 31 children after HSCT (subgroup 2); and 50 immunocompetent control patients. In comparison with the control group, immunocompromised children showed a significantly higher incidence of positive virus tests (subgroup 1: 53%; subgroup 2: 81%; controls: 24%; P<0.0001), and more frequently experienced ensuing viral infections in the lower respiratory tract (subgroup 1: 74%; subgroup 2: 88%; controls: 25%; P<0.0001). Sixteen percent of these children had coinfections by 2 or more viruses and revealed more severe respiratory illness. The present epidemiologic study on viral upper RTI in immunocompromised children revealed a high virus-associated morbidity which was particularly prominent in HSCT recipients. In these children, detection of viral coinfections was identified as a risk factor for a severe course of lower RTI.

Pneumococcal Pneumonia in Preschool Children

To the Editors: We read with interest the article by Techasaensiri et al,1 which analyzed the effect of viral coinfection on the clinical and laboratory characteristics, and outcome of 129 patients with invasive pneumococcal disease. It is believed that viral infections in pneumococcal pneumonia appear to be associated with more severe clinical disease.2 Between December 2006 and December 2008, we performed a prospective study on hospitalized children at the Hospital Infantil Niño Jesus of Madrid, who had acute community-acquired pneumonia. Previously healthy, children aged 2 to 6 years were considered eligible for inclusion. Etiologic studies included blood culture; pneumococcal DNA detection in blood samples by real-time polymerase chain reaction (RT-PCR), as described by Tarrago et al3; and viral serologic conversion in paired serum samples. Three RT-nested PCR assays were performed in nasopharyngeal samples to detect a total of 16 respiratory viruses: influenza virus A, B, and C were detected using previously described primer sets only to amplify influenza viruses4; a second multiplex PCR was used to detect parainfluenza viruses 1 to 4, human coronaviruses 229E and OC43, enteroviruses, and rhinoviruses5; the presence of respiratory syncytial virus-A and B types, hMPV, HBoV, and adenoviruses was investigated by a third multiplex RT-nested PCR.6 Patients who needed thoracocentesis were admitted to the pediatric intensive care unit. The study of the pleural fluid included microbiologic cultures, Gram staining, antigen testing (Binax Now), and RT-PCR for Streptococcus pneumoniae. This study was approved by the ethical committee of our institution, and signed consent forms were obtained from informed parents. Pneumococcal pneumonia was diagnosed in 83 patients, on the basis of blood cultures (11), RT-PCR (71), or pleural liquid studies (16). Quantitative procalcitonin samples were obtained in 74 cases, and serology paired samples were done in 62 cases. Viral coinfections were found in 49 patients (59%): 25 patients with 1 virus, 18 patients with 2 viruses, and 6 patients with 3 viruses. The most common viruses identified were rhinovirus (28), respiratory syncytial virus (11), and adenovirus (11). As Techasaensiri et al reported, we did not find significant differences when comparing the clinical and laboratory characteristics of patients with positive versus negative viral tests (Table, Supplemental Digital Content 1, https://links.lww.com/INF/A672). Length of stay, pediatric intensive care unit admission, and development of pleural effusion were not influenced by the presence of viral coinfection. It is remarkable that none of the patients with respiratory syncytial virus developed pleural effusion. There were no deaths among our patients. In contrast to the study of Techasaensiri et al,1 we included only patients with pneumonia, preschool age, and without any known underlying medical condition. Our results indicate that viral coinfection in pneumococcal pneumonia had no influence on clinical manifestations, laboratory characteristics, and patient outcome. Javier Alvarez-Coca Gonzalez, MD, PhD Jorge Martinez Perez, MD Seccion de Pediatria, Hospital Infantil Niño Jesus David Tarrago Asensio, MD, PhD Inmaculada Casas Flecha, MD, PhD Centro Nacional de Microbiología, ISCIII Almudena Alonso Ojembarrena, MD Seccion de Pediatria, Hospital Infantil Niño Jesus Madrid, Spain Giovanni Fedele, MD, PhD Centro Nacional de Microbiología, ISCIII Madrid, Spain

Swine Outbreak of Pandemic Influenza A Virus on a Canadian Research Farm Supports Human-to-Swine Transmission

Swine outbreaks of pandemic influenza A (pH1N1) suggest human introduction of the virus into herds. This study investigates a pH1N1 outbreak occurring on a swine research farm with 37 humans and 1300 swine in Alberta, Canada, from 12 June through 4 July 2009. The staff was surveyed about symptoms, vaccinations, and livestock exposures. Clinical findings were recorded, and viral testing and molecular characterization of isolates from humans and swine were performed. Human serological testing and performance of the human influenza-like illness (ILI) case definition were also studied. Humans were infected before swine. Seven of 37 humans developed ILI, and 2 (including the index case) were positive for pH1N1 by reverse-transcriptase polymerase chain reaction (RT-PCR). Swine were positive for pH1N1 by RT-PCR 6 days after contact with the human index case and developed symptoms within 24 h of their positive viral test results. Molecular characterization of the entire viral genomes from both species showed minor nucleotide heterogeneity, with 1 amino acid change each in the hemagglutinin and nucleoprotein genes. Sixty-seven percent of humans with positive serological test results and 94% of swine with positive swab specimens had few or no symptoms. Compared with serological testing, the human ILI case definition had a specificity of 100% and sensitivity of 33.3%. The only factor associated with seropositivity was working in the swine nursery. Epidemiologic data support human-to-swine transmission, and molecular characterization confirms that virtually identical viruses infected humans and swine in this outbreak. Both species had mild illness and recovered without sequelae.

HCV-positive intended parents may be safely used for gestational carrier cycles using RT-PCR testing and extended embryo culture

OBJECTIVE: To minimize a gestational carrier's risk of contracting hepatitis C virus (HCV) from a Hepatitis C-positive intended mother. DESIGN: Case report. MATERIALS AND METHODS: A 30-year old nulligravida woman was referred for a gestational carrier cycle. FDA screening revealed she was Hepatitis C antibody positive and plasma viral load testing showed 3.5 million copies of HCV/ml. A gastroenterologist recommended a 48-week course of Interferon/Ribavirin. Due to diminished ovarian reserve the patient desired to proceed with IVF prior to initiating treatment. On the day of TVOR, follicular fluid was tested for HCV by RT-PCR. Maternal plasma and collection/culture media served as the positive and negative controls, respectively. Routine insemination was undertaken and each oocyte was cultured separately. Every morning the zygote's surrounding media was collected and tested for virus. The zygote(s) were then washed and cultured in fresh media. Zygote(s) cultured in media testing HCV negative (<50 IU/ml) on day 3 were cryopreserved. RESULTS: Three oocytes were retrieved following a microdose-flare protocol. Follicular fluid collected on the day of oocyte retrieval tested positive for HCV RNA. Subsequent flushes of the collection tubing from each ovary also tested positive but with a decreased viral load (88,600 IU/ml and 13,350 IU/ml). Of the 3 oocytes obtained, 1 fertilized normally and was cultured further. The media surrounding this zygote showed decreasing amounts of HCV RNA with days of culture. On culture day 3, the media tested negative for HCV and the embryo was cryopreserved at the 8-cell stage.Tabled 1Days of CultureHepatitis C Viral RNA (IU/ml)Day 0 (follicular fluid)284,000Day 1 (2PN stage)7Day 2 (cleavage stage)<50Day 3 (cleavage stage)<50 Open table in a new tab CONCLUSION: The number of HCV RNA copies decreases with the number of zygote rinses and days of embryo culture. Thus, extended culture and testing by RT-PCR may help reduce the theoretical risk of viral transmission to a gestational carrier.

Prevalence of transfusion-transmissible viral infections in first-time US blood donors by donation site.

Understanding the donor base, infectious disease prevalence, and donation loss at various blood donation sites will help maximize blood collection efforts and blood availability. Using donation data collected at five US blood centers, the prevalence of HIV, HTLV, HBsAg, and HCV in first-time whole-blood donations at 10 donation sites was evaluated: military, education, religious, professional, industry, services, community, health care, government, and fixed sites. Donation loss from screening test reactivity at each donation site was also evaluated. During the study, 1.2 million first-time whole-blood donations were collected. Military and education sites had a low prevalence of all viral markers, except for HBsAg, which was highest at education sites. Variations in viral marker prevalence among donation sites were partially explained by donor demographic differences. Donation loss varied by donation site, ranging from 3.3 percent at education sites to 6.4 percent at industry sites, indicating differential efficiency of blood collection efforts. Different rates of positive viral test results and donation loss in first-time whole-blood donors were observed at various types of donation sites. This information may be useful in estimating the yield of usable units from specific blood drives and in allocating resources to meet blood center collection goals.

Laboratory Acquired Infection with Recombinant Vaccinia Virus Containing an Immunomodulating Construct

Handling of Vaccinia virus represents a risk for laboratory-acquired infections, especially in individuals without completed vaccination. We report the case of a Vaccinia infection in a previously vaccinated researcher working with various genetically modified strains. We could confirm the infection by electron microscopy, positive cell culture, virus-specific PCR, sequence analysis, and viral neutralization test. The isolated virus carried a functionally inactivated cytohesin-1 gene of human origin, which had been shown to impair leukocyte adhesion by interacting with the LFA/ICAM-1 axis. The immunomodulating nature of the inserted construct might thus have added to the infectivity of the virus. We emphasize on the necessity of Vaccinia vaccination in laboratory staff working in the field.

Review article: indicators and predictors of response to anti-viral therapy in chronic hepatitis C.

The complications of chronic hepatitis C, including cirrhosis and hepatocellular carcinoma, are expected to increase dramatically world-wide over the next 10-20 years. Immunomodulatory/anti-viral therapy, employing interferon alfa both alone and in combination with ribavirin, affords the only effective treatment for hepatitis C. Accurate early prediction of response to interferon therapy may decrease or eliminate unnecessary or ineffective treatment, permit greater flexibility in tailoring therapy on an individual basis, and enhance the cost-effectiveness of treatment. Liver biopsy provides valuable information about the baseline severity and subsequent progression of hepatitis C. Severe fibrosis or cirrhosis on the pre-treatment liver biopsy is associated with decreased response rates. The measurement of viral RNA levels and genotyping may be used to optimize individual patient treatment. Genotype non-1 and a low viral load are the most significant pre-treatment indicators of sustained virological response. The most reliable predictor of a poor virological response is continued seropositivity for viral RNA during therapy. Therefore, a decision to stop or continue treatment can be based on a positive viral RNA test at 12 weeks for interferon-naive patients receiving interferon or pegylated interferon therapy.

Viral studies in the cerebrospinal fluid in subacute sclerosing panencephalitis.

The pathogenesis of subacute sclerosing panencephalitis (SSPE), and particularly, the cause of measles virus (MV) reactivation following a latent period after primary measles infection is unknown. The hypothesis of other viruses contributing to the pathogenesis of SSPE by affecting the in vivo state of MV was investigated. We examined the cerebrospinal fluid of SSPE patients (n=43) for DNA or RNA and antibodies against HSV type 1 and 2, EBV, CMV, VZV, Hepatitis B, Hepatitis C, JC virus, human herpesvirus (HHV)-6, HHV-7, HHV-8, HTLV-1, and HTLV-2. We compared the findings with those of patients with other neurological disorders (n=39). CMV DNA and HSV type 1 IgG were found more frequently in SSPE patients. Other positive results were at similar incidence in SSPE and control groups. The clinical features of SSPE cases with and without positive viral tests did not differ from each other. These data do not support a specific role for these agents in SSPE, but imply that the passage of some viruses to the CNS and local antibody synthesis may be facilitated by inflammation. The persistence or reactivation of MV in SSPE may be related to other factors pertaining to the host or environment.