Search

Influenza A(H5N1) vaccination strategies that improve the speed of the immunological response and cross-clade protection are desired. We compared the immunogenicity of a single 15-µg or 90-µg dose of A/H5N1/Indonesia/05/05 (clade 2) vaccine in adults who were previously primed with A/H5N1/Vietnam/1203/2004 (clade 1) vaccine. High-dose vaccine resulted in significantly higher titers to both clade 1 and 2 antigens. Clade 2 titers were unaffected by the previous dose of clade 1 vaccine. Low-dose priming with a mismatched pandemic influenza A(H5N1) vaccine would improve the rapidity, magnitude, and cross-reactivity of the immunological response following a single high-dose, unadjuvanted, pandemic vaccine. [ABSTRACT FROM AUTHOR]

Background. Parainfluenza virus (PIV), a common pediatric pathogen, is associated with significant morbidity in immunocompromised (IC) hosts. DAS181, a novel sialidase fusion protein inhibitor, seems to be effective against PIV in vitro and in vivo; its use in IC children has not been evaluated. Methods. Patients were diagnosed with PIV infection using a quantitative reverse transcription-polymerase chain reaction. DAS181 was obtained under emergency investigational new drug applications and was administered via aerosol chamber or nebulizer. Patients were assessed daily for their clinical condition and adverse outcomes. Results. Four pediatric hematopoietic cell transplantation (HCT) patients with PIV detected in respiratory specimens were identified and treated with DAS 181. Patients 1 and 2 were diagnosed with PIV lower respiratory tract infection (LRTI) by bronchoalveolar lavage at 9 months and 2 days after allogeneic transplantation, respectively. Patient 3 was on chemotherapy prior to planned autologous HCT at time of PIV diagnosis from a nasal swab. Patient 4 was diagnosed with PIV via nasal wash 2 days after HCT. Patients 1-3 had clinical symptoms and chest imaging consistent with LRTI. Inhaled DAS181 was administered for 5-10 days. All 4 patients tolerated therapy well. Clinical improvement in oxygen requirement and respiratory rate was observed in all patients who required oxygen at therapy initiation. Viral load decreased in all patients within 1 week of therapy and became undetectable by day 3 of therapy in patient 3. Conclusion. DAS181 was used to treat 4 severely IC pediatric patients with PIV disease. The drug was well tolerated. Improvement in both viral loads and symptoms after initiation of therapy was observed in all cases. This report supports prospective, randomized studies in IC patients with PIV infection. [ABSTRACT FROM AUTHOR]

Background Methods for the longitudinal study of respiratory virus infections are cumbersome and limit our understanding of the natural history of these infections in solid organ transplant (SOT) recipients. Objectives To assess the feasibility and patient acceptability of self-collected foam nasal swabs for detection of respiratory viruses in SOT recipients and to define the virologic and clinical course. Study design We prospectively monitored the course of symptomatic respiratory virus infection in 18 SOT patients (14 lung, 3 liver, and 1 kidney) using patient self-collected swabs. Results The initial study sample was positive in 15 patients with the following respiratory viruses: rhinovirus (6), metapneumovirus (1), coronavirus (2), respiratory syncytial virus (2), parainfluenza virus (2), and influenza A virus (2). One hundred four weekly self-collected nasal swabs were obtained, with a median of 4 samples per patient (range 1–17). Median duration of viral detection was 21 days (range 4–77 days). Additional new respiratory viruses detected during follow-up of these 15 patients included rhinovirus (3), metapneumovirus (2), coronavirus (1), respiratory syncytial virus (1), parainfluenza virus (1), and adenovirus (1). Specimen collection compliance was good; 16/18 (89%) patients collected all required specimens and 79/86 (92%) follow-up specimens were obtained within the 7 ± 3 day protocol-defined window. All participants agreed or strongly agreed that the procedure was comfortable, simple, and 13/14 (93%) were willing to participate in future studies using this procedure. Conclusion Self-collected nasal swabs provide a convenient, feasible, and patient-acceptable methodology for longitudinal monitoring of upper respiratory virus infection in SOT recipients. [ABSTRACT FROM AUTHOR]

Background The clinical presentation and management of human metapneumovirus (hMPV) infections in immunocompromised children is not well understood. Methods We performed a retrospective evaluation of pediatric patients with laboratory-confirmed hMPV infections and underlying hematologic malignancy, solid tumors, solid organ transplant, rheumatologic disease, and/or receipt of chronic immunosuppressants. Data were analyzed using t tests and Fisher's exact tests. Results Overall, 55 patients (median age: 5 years; range: 5 months–19 years) with hMPV infection documented between 2006 and 2010 were identified, including 24 (44%) with hematologic malignancy, 9 (16%) undergoing hematopoietic stem cell transplant, 9 (16%) with solid tumors, and 8 (15%) with solid organ transplants. Three (5%) presented with fever alone, 35 (64%) presented with upper respiratory tract infections, and 16 (29%) presented with lower respiratory tract infections (LRTI). Twelve (23%) patients required intensive care unit admission and/or supplemental oxygen ≥28% FiO2. Those with severe disease were more likely to be neutropenic (P = .02), but otherwise did not differ by age (P = .27), hematopoietic stem cell transplant recipient status (P = .19), or presence of lymphopenia (P = .09). Nine (16%) patients received treatment with ribavirin, intravenous immunoglobulin, or both. Three children (5%) died of hMPV pneumonia. Conclusions Immunocompromised pediatric patients with hMPV infection have high rates of LRTI and mortality. The benefits of treatment with ribavirin and intravenous immunoglobulin in this patient population require further evaluation. [ABSTRACT FROM PUBLISHER]

We propose a new definition of lower respiratory tract disease (LRTD) based on the viral detection site that correlates with clinical outcome. Monocyte count, oxygen use, and high-dose steroid use are associated with mortality after parainfluenza virus LRTD.Background. Parainfluenza virus (PIV) commonly infects patients following hematopoietic cell transplantation (HCT), frequently causing lower respiratory tract disease (LRTD). The definition of LRTD significantly differs among studies evaluating the impact of PIV after HCT.Methods. We retrospectively evaluated 544 HCT recipients with laboratory-confirmed PIV and classified LRTD into 3 groups: possible (PIV detection in upper respiratory tract with new pulmonary infiltrates with/without LRTD symptoms), probable (PIV detection in lung with LRTD symptoms without new pulmonary infiltrates), and proven (PIV detection in lung with new pulmonary infiltrates with/without LRTD symptoms).Results. Probabilities of 90-day survival after LRTD were 87%, 58%, and 45% in possible, probable, and proven cases, respectively. Patients with probable and proven LRTD had significantly worse survival than those with upper respiratory tract infection (probable: hazard ratio [HR], 5.87 [P < .001]; proven: HR, 9.23 [P < .001]), whereas possible LRTD did not (HR, 1.49 [P = .27]). Among proven/probable cases, oxygen requirement at diagnosis, low monocyte counts, and high-dose steroid use (>2 mg/kg/day) were associated with high mortality in multivariable analysis.Conclusions. PIV LRTD with viral detection in lungs (proven/probable LRTD) was associated with worse outcomes than was PIV LRTD with viral detection in upper respiratory samples alone (possible LRTD). This new classification should impact clinical trial design and permit comparability of results among centers. [ABSTRACT FROM AUTHOR]

Background. Respiratory syncytial virus (RSV) lower respiratory tract disease (LRD) is a life-threatening complication in hematopoietic cell transplant (HCT) recipients. Lymphopenia has been associated with an increased risk of progression from upper respiratory tract infection (URI) to LRD.Methods. This study retrospectively analyzed the significance of lymphocyte engraftment dynamics, lung function, smoking history, corticosteroids, antiviral treatment, viral subtypes, and RSV-specific neutralizing antibodies for the progression to LRD in 181 HCT recipients with RSV URI.Results. In multivariable models, smoking history, conditioning with high-dose total body irradiation, and an absolute lymphocyte count (ALC) ≤100/mm3 at the time of URI onset were significantly associated with disease progression. No progression occurred in patients with ALCs of >1000/mm3 at URI onset. Lymphocyte engraftment dynamics were similar in progressors and nonprogressors. Pre- and posttransplant donor and posttransplant recipient RSV subtype-specific neutralizing antibody levels, RSV viral subtypes, and corticosteroids also were not significantly associated with LRD progression.Conclusions. Host and transplant related factors appear to determine the risk of progression to LRD more than viral factors. Dysfunctional cell-mediated immunity appears to be important in the pathogenesis of progressive RSV disease after HCT. A characterization of RSV-specific T-cell immunity is warranted. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) RNA detection in plasma or serum may be a marker for lung injury and poor outcomes in hematopoietic cell transplant recipients with RSV lower respiratory disease. Treatment with aerosolized ribavirin appeared protective against overall and pulmonary mortality.Background. Respiratory syncytial virus (RSV) pneumonia after hematopoietic cell transplant (HCT) is associated with severe morbidity. Although RSV RNA has been detected in serum from patients with RSV lower respiratory disease (LRD) after HCT, the association with clinical outcomes has not been well established in multivariable models. Additionally, the role of antiviral treatment in HCT recipients has not been previously analyzed in multivariable models.Methods. We retrospectively identified HCT recipients with virologically confirmed RSV LRD and tested stored plasma/serum samples by quantitative reverse transcription polymerase chain reaction for RSV RNA. Risk factors for RSV RNA detection and the impact of RSV RNA in serum and antiviral therapy on outcomes were analyzed using multivariable Cox models.Results. RSV RNA was detected in plasma or serum from 28 of 92 (30%) patients at a median of 24.5 days following HCT and 2 days following LRD. In multivariable models, neutropenia, monocytopenia, thrombocytopenia, and mechanical ventilation increased the risk of plasma/serum RSV RNA detection; lymphopenia and steroid use did not. RSV RNA detection increased the risk of overall mortality in multivariable models (adjusted hazard ratio [aHR], 2.09 [P = .02]), whereas treatment with aerosolized ribavirin decreased the risk of overall mortality and pulmonary death (aHR, 0.33 [P = .001] and aHR 0.31 [P = .003], respectively).Conclusions. RSV RNA detection in plasma or serum may be a marker for lung injury and poor outcomes in HCT recipients with RSV LRD. Treatment with aerosolized ribavirin appeared to be protective against overall and pulmonary mortality. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Respiratory syncytial virus (RSV) is the most important cause of serious respiratory infections in young children. No prior studies using molecular techniques to examine RSV transmission in the community childcare setting have been performed. Objectives: We seek to characterize the molecular epidemiology of RSV transmission in childcare to evaluate the impact of RSV disease in a community-based population. Methods: We sequenced RSV-positive nasopharyngeal samples from a prospective longitudinal study of respiratory illnesses among children enrolled in childcare during three winter seasons. Phylogenetic analysis was performed to identify unique viral strains. Results: RSV was detected in 59 (11%) illnesses. Compared to RSV-negative illnesses, RSV-positive illnesses were associated with longer symptom duration and increased frequency of health care visits. Another respiratory virus was detected in 42 (71%) RSV-positive illnesses. RSV viral load did not differ between RSV-positive illnesses with and without another respiratory virus identified (P =0.38). In two childcare rooms, 50% of the children had RSV detected within six days of the first case. Five (38%) of 13 illness episodes from one childcare room were sequenced and shown to be the same viral strain, suggesting rapid child-to-child transmission within the room over a 16 day period. Conclusions: RSV is rapidly transmitted within childcare. Childcare facilities may serve as ideal sites for evaluation of new prevention strategies given the high burden of RSV disease in this population and the rapidity of RSV spread between children. [Copyright &y& Elsevier]

Background. The identification of multiple viruses during respiratory illness is increasing with advances in rapid molecular testing; however, the epidemiology of respiratory viral coinfections is not well known.Methods. In total, 225 childcare attendees were prospectively followed for up to 2 years. Nasal swabs were collected at respiratory illness onset and every 7–10 days until illness resolution. Swabs were tested by polymerase chain reaction for 15 respiratory viruses and subtypes.Results. At least 1 virus was detected in 382 (84%) of 455 new-onset illnesses with multiple viruses identified in 212 (46%). The proportion of subject swabs with multiple viruses detected changed as respiratory illnesses progressed from week to week, as did the prevalence of individual viruses. Children with multiple viruses detected at the time of illness onset had less frequent fever (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.35, 0.90), however, these children more often had illness symptoms lasting over 7 days (OR, 1.94; 95% CI, 1.20, 3.14).Conclusions. A high proportion of daycare attendees had multiple viruses detected during respiratory illnesses. Delay between onset of illness and viral detection varied by virus, indicating that some viruses may be underrepresented in studies of virus epidemiology that rely on only a single test at symptom onset. [ABSTRACT FROM AUTHOR]

Influenza RNA in blood (viremia) was detected in 9 of 79 (11.4%) hematopoietic cell transplant recipients with influenza, and was less frequently observed in patients with upper respiratory tract disease only and more frequently in patients infected with 2009 pandemic influenza A/H1N1 strain (versus seasonal strains). Viremia increased the risk of progression to lower respiratory tract disease (LRD), hypoxemia, respiratory failure, and overall and influenza-related death. Among patients with LRD, viremia was associated with increased hazards of overall and influenza-associated death (hazard ratio 3.5, 1.1–12). Thus, influenza viremia may serve as marker for overall poor outcome. [ABSTRACT FROM AUTHOR]

Data are limited regarding 2 new human polyomaviruses, KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV), in immunocompromised patients. We used real-time PCR to test for these and 12 respiratory viruses in 2,732 nasal wash samples collected during the first year after allogeneic hematopoietic cell transplantation from 222 patients. Specimens were collected weekly until day 100; then at least every 3 months. One year after hematopoietic cell transplantation, the cumulative incidence estimate was 26% for KIPyV and 8% for WUPyV. Age <20 years predicted detection of KIPyV (hazard ratio [HR] 4.6) and WUPyV (HR 4.4), and detection of a respiratory virus in the previous 2 weeks predicted KIPyV detection (HR 3.4). Sputum production and wheezing were associated with detection of KIPyV in the past week and WUPyV in the past month. There were no associations with polyomavirus detection and acute graft versus host disease, cytomegalovirus reactivation, neutropenia, lymphopenia, hospitalization, or death. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Burns et al. (2011) Respiratory viruses in children with cystic fibrosis: viral detection and clinical findings. Influenza and Other Respiratory Viruses 6(3), 218-223. Background Viral detection from different respiratory sample types in children with cystic fibrosis (CF) is facilitated by available molecular methods, but optimum sampling strategies have not been identified. In addition, associations between viral detection and respiratory symptoms are not well described. Objectives Study goals were to compare molecular detection of viruses from concurrent upper airway and sputum samples in children with CF and to describe relative frequency of respiratory viral infections and identify potential clinical associations. Methods We conducted a 2-year prospective surveillance study in 44 children with CF aged 6-18 years. Upper airway and sputum samples were collected quarterly and during pulmonary exacerbations and tested for respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses types 1-4, human metapneumovirus, coronaviruses, rhinoviruses, and adenoviruses. Physical exams and symptom surveys were used to identify respiratory signs and symptoms. Results Upper airway samples were collected at 359 visits; concordance of PCR-based viral detection was examined in a subset of paired upper airway and sputum samples from 21 participants at 92 visits. Rhinovirus was the most commonly detected virus (23·1% overall), and rhinovirus detection was the same for both sample types (21·7% each). Sensitivity and specificity for the detection of rhinovirus in sputum relative to upper airway sampling were 70% and 91·7%, respectively. Respiratory symptoms associated with rhinovirus detection included increased cough, increased nasal congestion, increased sputum production, and wheezing. Conclusions A relatively high frequency of rhinovirus detection was observed by either upper airway or sputum samples, and clinical findings suggest a significant-associated symptom burden. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Martin et al. (2012) Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children. Influenza and Other Respiratory Viruses 6(1), 71-77. Background Molecular testing for viral pathogens has resulted in increasing detection of multiple viruses in respiratory secretions of ill children. The clinical impact of multiple virus infections on clinical presentation and outcome is unclear. Objectives To compare clinical characteristics and viral load between children with multiple virus versus single virus illnesses. Patients/methods Eight hundred and ninety-three residual nasal wash samples from children treated for respiratory illness at Children's Hospital, Seattle, from September 2003 to September 2004 were evaluated by quantitative PCR for respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (Flu), parainfluenza, adenoviruses, and coronaviruses (CoV). Illness severity and patient characteristics were abstracted from medical charts. Results Coinfections were identified in 103 (18%) of 566 virus-positive samples. Adenovirus was most commonly detected in coinfections (52%), followed by CoV (50%). Illnesses with a single virus had increased risk of oxygen requirement ( P = 0·02), extended hospital stays ( P = 0·002), and admissions to the inpatient ( P = 0·02) or intensive care units ( P = 0·04). For Adv and PIV-1, multiple virus illnesses had a significantly lower viral load (log10 copies/ml) than single virus illnesses (4·2 versus 5·6, P = 0·007 and 4·2 versus 6·9, P < 0·001, respectively). RSV, Flu-A, PIV-3, and hMPV viral loads were consistently high whether or not another virus was detected. Conclusions Illnesses with multiple virus detections were correlated with less severe disease. The relationship between viral load and multiple virus infections was virus specific, and this may serve as a way to differentiate viruses in multiple virus infections. [ABSTRACT FROM AUTHOR]

Adeno-associated virus (AAV) is widely considered to be nonpathogenic, but the clinical epidemiology of this virus is limited. By use of polymerase chain reaction assays, we investigated the incidence and clinical significance of AAV viremia in a population of consecutive recipients of a hematopoietic cell transplant (HCT). Four (2.8%) of 145 patients developed AAV viremia after HCT. Viremia was low level and transient in all patients. Two patients were admitted to the hospital and died in proximity to AAV viremia (<7 weeks between diagnosis and death); however, AAV was not detected in tissue specimens obtained at autopsy. Thus, AAV does not appear to play a pathogenic role in organ-specific illness, even in a highly immunocompromised population. [ABSTRACT FROM AUTHOR]

Abstract: The emergence of oseltamivir resistance in seasonal and pandemic influenza A/H1N1 has created challenges for diagnosis and clinical management. This review discusses how clinical virology laboratories have handled diagnosis of oseltamivir-resistant H1N1 and what we have learned from clinical studies and case series. Immunocompetent patients infected with oseltamivir-resistant H1N1 have similar outcomes as patients infected with oseltamivir-susceptible H1N1. However, immunocompromised patients infected with oseltamivir-resistant H1N1 experience potentially more risks of complication and transmissibility with few therapeutic options. [Copyright &y& Elsevier]

Abstract: Background: Although data documenting the severity and frequency of human parechovirus (HPeV) infections have been published, detection of HPeV is not routinely performed in most clinical virology laboratories. Objective: To describe diagnostic yield, epidemiology and clinical characteristics of patients infected with HPeV during the first year using a new HPeV reverse transcription (RT)-PCR. Study design: We introduced an HPeV RT-PCR for the routine testing of cerebrospinal fluid (CSF) and blood samples submitted to our clinical laboratory for detection of human enteroviruses (HEV). Prospective testing of samples with retrospective analysis of medical charts was performed. Results: Of the 499 clinical samples received between May, 2009 and May, 2010, 9.6% (46 patients) had HEV detected and 3.4% (15 patients) had HPeV detected. All patients infected by HPeV were <3 months old, hospitalized between June and October 2009, and all typed viruses were HPeV3. Clinical characteristics of HPeV and HEV infected infants were similar. However, patients infected with HPeV were more likely to have a normal leukocyte count in their CSF (p <0.001). One HPeV3-infected infant developed encephalitis and another developed hepatitis. Conclusion: In our institution, the HPeV RT-PCR was useful to diagnose a novel pathogen in infants with sepsis-like disease. [Copyright &y& Elsevier]

Most oseltamivir-resistant pandemic (H1N1) 2009 viruses have been isolated from immunocompromised patients. To describe the clinical features, treatment, outcomes, and virologic data associated with infection from pandemic (H1N1) 2009 virus with H275Y mutation in immunocompromised patients, we retrospectively identified 49 hematology--oncology patients infected with pandemic (H1N1) 2009 virus. Samples from 33 of those patients were tested for H275Y genotype by allele-specific real-time PCR. Of the 8 patients in whom H275Y mutations was identified, 1 had severe pneumonia; 3 had mild pneumonia with prolonged virus shedding; and 4 had upper respiratory tract infection, of whom 3 had prolonged virus shedding. All patients had received oseltamivir before the H275Y mutation was detected; 1 had received antiviral prophylaxis. Three patients excreted resistant virus for >60 days. Emergence of oseltamivir resistance is frequent in immunocompromised patients infected with pandemic (H1N1) 2009 virus and can be associated with a wide range of clinical disease and viral kinetics. [ABSTRACT FROM AUTHOR]

The Centers for Disease Control and Prevention (CDC) recommends that health care personnel (HCP) infected with pandemic influenza (H1N1) 2009 virus not work until 24 hours after fever subsides without the use of antipyretics. During an influenza outbreak, we examined the association between viral shedding and fever among infected HCP. Participants recorded temperatures daily and provided nasal wash specimens for 2 weeks after symptom onset. Specimens were tested by using PCR and culture. When they met CDC criteria for returning to work, 12 of 16 HCP (75%) (95% confidence interval 48%-93%) had virus detected by PCR, and 9 (56%) (95% confidence interval 30%-80%) had virus detected by culture. Fever was not associated with shedding duration (p = 0.65). HCP might shed virus even when meeting CDC exclusion guidelines. Further research is needed to clarify the association between viral sheddinq, symptoms, and infectiousness. [ABSTRACT FROM AUTHOR]

Background. Little is known about human bocavirus (HBoV) persistence and shedding and the association between HBoV detection and the onset and resolution of respiratory symptoms. Methods. We performed HBoV testing on nasal swab samples from a prospective, longitudinal study of respiratory illness in 119 children who attended daycare. Results. HBoV was detected in 70 children (59%) and in 106 (33%) of the 318 cases of illness. Another virus was detected in 76 (72%) of 106 HBoV-positive cases. Extended and intermittent shedding was observed, with consistent HBoV detection documented for up to 75 days. HBoV was detected in 20 (44%) of 45 asymptomatic enrollment samples, and HBoV prevalence and viral load did not differ significantly between children with and children without symptoms at enrollment. HBoV-positive illnesses were longer than HBoV-negative illnesses (odds ratio for duration of symptoms 17 days, 2.44; 95% confidence interval, 1.41-4.22), and illnesses with HBoV load ≥4 log10 copies/mL required a visit to a health care provider more often than did HBoV-negative illnesses (odds ratio, 1.64; 95% confidence interval, 1.02-2.64). Conclusion. HBoV was more common in illnesses with greater severity. However, detection of HBoV was not associated with the presence of respiratory illness or with specific respiratory symptoms in this prospective study of infants and toddlers attending daycare centers. [ABSTRACT FROM AUTHOR]

Background. Few data exist on respiratory virus quantitation in lower respiratory samples and detection in serum from hematopoietic cell transplant (HCT) recipients with respiratory virus-associated pneumonia. Methods. We retrospectively identified HCT recipients with respiratory syncytial virus (RSV), parainfluenza virus, influenza virus, metapneumovirus (MPV), and coronavirus (CoV) detected in bronchoalveolar lavage (BAL) samples, and we tested stored BAL and/or serum samples by quantitative polymerase chain reaction. Results. In 85 BAL samples from 82 patients, median viral loads were as follows: for RSV (n=35), 2.6 × 106 copies/mL; for parainfluenza virus (n=35), 4.9×107 copies/mL; for influenza virus (n=9), 6.8×105copies/mL; for MPV (n=7), 3.9×107copies/mL; and for CoV (n=4), 1.8×105 copies/mL. Quantitative viral load was not associated with mechanical ventilation or death. Viral RNA was detected in serum samples from 6 of 66 patients: 4 of 41 with RSV pneumonia, 1 with influenza B, and 1 with MPV/influenza A virus/CoV coinfection (influenza A virus and MPV RNA detected). RSV detection in serum was associated with high viral load in BAL samples (P=.05), and viral RNA detection in serum was significantly associated with death (adjusted rate ratio, 1.8; P=.02). Conclusion. Quantitative polymerase chain reaction detects high viral loads in BAL samples from HCT recipients with respiratory virus pneumonia. Viral RNA is also detectable in the serum of patients with RSV, influenza, and MPV pneumonia and may correlate with the severity of disease. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to describe the frequency of viral pathogens and relative frequency of co-infections in nasal specimens obtained from young children with bronchiolitis receiving care at a children's hospital. Methods: We conducted a study of nasal wash specimens using real-time PCR and fluorescent-antibody assay results from children less than two with an ICD-9-CM code for bronchiolitis. All specimens were collected for clinical care at Children's Hospital in Seattle, WA, USA, during the respiratory season from October 2003 to April 2004. Results: Viruses were detected in 168 (93%) of the 180 children with bronchiolitis. A single virus was identified in 127 (71%) children and multiple viruses in 41 (23%). Respiratory syncytial virus (RSV) was the most common virus detected (77%), followed by adenovirus (15%), human metapneumovirus (11%), coronavirus (8%), parainfluenza (6%) and influenza (1%). Of the 139 samples with RSV detected, 34 (24%) were co-infected with another viral pathogen. Conclusion: Molecular diagnostic techniques identified a high frequency of viruses and viral co-infections among children evaluated for bronchiolitis. Further study of the role of viral pathogens other than RSV and co-infections with RSV in children with bronchiolitis appears warranted. [ABSTRACT FROM AUTHOR]

Background. Respiratory syncytial virus infection of the upper airways may progress to fatal pneumonia in hematopoietic cell transplant recipients. The safety and efficacy of aerosolized ribavirin in preventing disease progression is unknown. Methods. In a multicenter prospective trial, hematopoietic cell transplant recipients with respiratory syncytial virus infection of the upper airways were randomized to receive ribavirin (2 g 3 times daily) or supportive care for 10 days. The primary end point was progression to radiographically proven pneumonia. Secondary end points included virologically proven respiratory syncytial virus pneumonia, viral load changes, and safety. Results. Fourteen patients were randomized to 1 of 2 treatment arms. The trial was discontinued after 5 years because of slow accrual. Pneumonia at 1 month after randomization occurred in 1 of 9 patients who received ribavirin and in 2 of 5 patients who received supportive care (P = 51); virologically proven respiratory syncytial virus pneumonia occurred in 0 of 9 and 2 of 5 patients, respectively (P= 11). At 10 days after randomization, the average viral load decreased by 0.75 log10 copies/mL in ribavirin recipients, compared with a viral load increase of 1.26 log10 copies/mL in untreated patients (P = 7). No discontinuations of ribavirin therapy because of adverse effects occurred during 84 drug administrations. Rates of adverse events were similar in both groups. Conclusions. Preemptive aerosolized ribavirin treatment appeared to be safe, and trends of decreasing viral load over time were observed. However, proof of efficacy remains elusive in hematopoietic cell transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Human metapneumovirus (hMPV), a recently discovered respiratory virus, is associated with clinical disease in young and elderly persons. Objective: To determine the importance of hMPV in hematopoietic stem-cell transplant recipients. Design: Retrospective survey of patients with consecutive residual bronchoalveolar lavage (BAL) samples. Setting: Referral cancer center. Patients: Hematopoietic stem-cell transplant recipients who underwent BAL because of lower respiratory tract disease. Measurements: Bronchoalveolar lavage specimens were assayed by quantitative real-time polymerase chain reaction methods. Results: Human metapneumovirus was detected in BAL specimens from 5 of 163 patients (3.0%). Persistent viral infection was noted in 3 patients with several samples, and hMPV was detected in 1 of 2 lung specimens tested. Infected patients became symptomatic within the first 40 days after transplantation. Initial symptoms included fever, cough, nasal congestion, and sore throat. Clinical findings included respiratory failure, pulmonary hemorrhage, and culture-negative septic shock. Four of 5 patients died with acute respiratory failure. Limitations: This retrospective study did not evaluate asymptomatic patients or those with mild disease. Conclusion: Human metapneumovirus infection in the lower respiratory tract is associated with respiratory failure in immunocompromised adults who were previously considered to have ‘idiopathic pneumonia.’ The infection may result in fulminant respiratory decompensation and shock after transplantation. [ABSTRACT FROM AUTHOR]

Background: Women infected with human immunodeficiency virus type 1 (HIV-1) and -2 may be at higher risk of developing cervical cancer than uninfected women. We assessed the relationships among human papillomavirus (HPV) types and persistence, HIV-1 and/or HIV-2 infection, and the development of high-grade cervical squamous intraepithelial lesions (HSILs) in a prospective study. Methods: We studied 627 women with and without HIV-1 and/or HIV-2 infection and high-risk HPV infection in Senegal, West Africa, who were assessed every 4 months for HSIL and HPV DNA over a mean follow-up of 2.2 years. Cox regression modeling was used to assess risks associated with development of HSIL. Results: During follow-up, 71 (11%) of 627 women developed HSIL as detected by cytology. HIV-infected women with high-risk HPV types were at greatest risk for development of HSIL. In multivariable modeling, infection with oncogenic HPV types--both persistent (hazard ratio [HR] = 47.1, 95% confidence interval [CI] = 16.3 to 136) and transient (HR = 14.0, 95% CI = 3.7 to 54)—was strongly associated with HSIL risk. In univariate analyses, HIV-positive women infected with HIV-2 were less likely to develop HSIL (HR = 0.3, 95% CI = 0.1 to 0.9) than HIV-positive women infected with HIV-1. HIV-positive women with CD4+ cell counts between 200 and 500 cells per microliter (HR = 2.2, 95% CI = 0.8 to 6.3) or fewer than 200 cells per milliliter (HR = 5.5, 95% CI = 2.0 to 15.2) were at greater risk of HSIL than HIV-positive women with CD4 counts of more than 500 cells per milliliter. High plasma HIV RNA levels were associated with increased HSIL risk (HR for each order of magnitude increase in the level of plasma HIV RNA = 1.4, 95% CI = 1.1 to 1.7; P = .005). After adjustment for HPV types and persistence, however, HIV type, plasma HIV RNA level, and CD4 count were no longer statistically significantly associated with increased risk of HSIL. Conclusions: HIV-1 and HIV-2 are associated with increased risk for development of HSIL. This risk appears to be associated primarily with increased HPV persistence that may result from immunosuppression related to HIV-1 and/or HIV-2 infection. [ABSTRACT FROM AUTHOR]

Abstract: Background:: Human metapneumovirus (hMPV), a recently identified virus, causes respiratory illness in children. Objectives:: A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was developed and used to detect and quantify hMPV in respiratory specimens. Study design:: The quantitative RT-PCR assay amplified an approximately 70 base pair fragment from the hMPV fusion protein gene. The assay was validated and used to test respiratory specimens obtained from children seen at a hospital in Seattle, Washington, from December 2002 through May 2003. Results:: The assay detected 1000hMPV copies/mL of specimen, did not detect 19 other respiratory viruses, and was able to detect and accurately quantify isolates from the four known hMPV genetic lineages in a proficiency panel of 20 previously tested samples. hMPV was detected in 52 (7.2%) of 719 pediatric respiratory specimens. The mean log10copies/mL of hMPV in the 52 positive specimens was 7.67 (range=4.59–10.60). Children aged 7–12 months had a significantly higher hMPV prevalence (12.4%) than did children younger than 7 months (4.7%) (P &#60;0.005). Children in this age group also had significantly higher levels of hMPV in their respiratory specimens (mean log8.43 copies/mL) than did the younger children (mean log6.93copies/mL) (P =0.0025). Conclusions:: The rapid real-time RT-PCR assay described here is a sensitive test for clarifying the epidemiology of and diseases associated with hMPV. [Copyright &y& Elsevier]

Background. To determine the potential value of human papillomavirus (HPV) vaccines, information concerning the incidence and duration of clinically important lesions is needed. Methods. A total of 603 female university students were followed for a mean duration of 38.8 months. Triannual gynecologic examinations included cervical and vulvovaginal specimen collection for Pap and HPV DNA testing. Women with cytologic evidence of a high-grade squamous intraepithelial lesion (SIL) were referred for colposcopically directed biopsy. Results. Among women with incident HPV infection, the 36-month cumulative incidence of cervical SILs found by cytologic testing (47.2%; 95% confidence interval [CI], 38.9%-56.4%) was higher than that of vaginal SILs (28.8%; 95% CI, 21.3%-38.2%). The median time to clearance of cervical and vaginal SILs was 5.5 and 4.7 months, respectively. Among women with incident HPV-16 or HPV-18 infection, the 36-month cumulative in- cidence of cervical intraepithelial neoplasia (GIN) grade 2 was 20.0% (95% CI, 10.8%-35.1%), and that of GIN grade 3 was 6.7% (95% CI, 2.5%-17.O%). The 36-month cumulative incidence of clinically ascertained genital warts among women with incident HPV-6 or HPV- 11 infection was 64.2% (95% CI, 50.7%-77.4%). Conclusions. Intraepithelial lesions are common early events among women with incident HPV infection, and the interval between incident HPV-16 or HPV-18 infection and biopsy-confirmed GIN grade 2-3 appears to be relatively short. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract morbidity in young children and immunosuppressed patients. Objectives: To rapidly and accurately quantify and subtype RSV in respiratory samples, we developed and evaluated two real-time RT-PCR assays. Study design: A quantitative assay was designed using primers for a consensus region of the matrix protein gene and a subtype-specific assay for RSV-A and RSV-B detection was designed using primers for the polymerase gene. Quantitative RSV RT-PCR results of pediatric nasal wash samples submitted to the University of Washington Virology Laboratory from December 2002, through May 2003, were compared to those of an indirect fluorescent antibody RSV antigen detection assay (FA). Results: Specificity of the RT-PCR assay was high, with no amplification of eleven common respiratory viruses and eight herpes viruses. Among 751 samples, RSV was detected in 267 (35.6%) by FA and in 286 (38.1%) by RT-PCR. Median RSV copy number in nasal wash samples that were positive by both FA and RT-PCR was 2.5×107 copies/mL versus a median of 3.0×104 copies/mL for samples positive by RT-PCR only (P<0.001). The detection and quantity of RSV in respiratory specimens was associated with younger age, but not with gender or hospitalization. Among positive samples from this Seattle cohort, 52% were subtype A and 48% were subtype B. Both subtypes were detected with similar viral loads among all patient groups (stratified by age, gender, and hospitalization), and throughout the specimen collection period. Conclusions: These real-time RT-PCR assays provide a rapid, specific, and highly sensitive alternative for detecting, quantifying, and subtyping RSV in clinical specimens. [Copyright &y& Elsevier]

To assess the risk of prevalent high-grade cervical squamous intraepithelial lesions (HSILs) or invasive cervical cancer (ICC) associated with human immunodeficiency virus (HIV) type 1, HIV-2, and human papillomavirus (HPV) infections, HIV load, and CD4 cell count, we studied 4119 women attending an outpatient clinic in Senegal. HIV infection was associated with increased rates of cervical infection with high-risk HPVs. Among women infected with high-risk HPVs, those with HIV-1 (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.0-4.8), HIV-2 (OR, 6.0; 95% CI, 2.1-17.1), or dual HIV infection (OR, 8.0; 95% CI, 2.0-31.5) were more likely to have HSILs or ICC diagnosed than were HIV-negative women; this association was not observed among women not infected with high-risk HPVs. Among women with HIV, higher HIV plasma RNA loads and lower CD4 cell counts were associated with high-risk HPV infection and degree of cervical abnormality. Furthermore, HIV-2-positive women were more likely to have HSILs (OR, 3.3; 95% CI, 0.9-12.4) or ICC (OR, 7.9; 95% CI, 1.1-57) than were HIV-1-positive women. [ABSTRACT FROM AUTHOR]