Frank Esper

A 1-Year Experience with Human Metapneumovirus in Children Aged <5 Years

Abstract Human metapneumovirus (hMPV) is a recently discovered respiratory pathogen. We tested respiratory specimens for the presence of hMPV by reverse-transcription polymerase chain reaction. These specimens were obtained over a 1-year period from children aged <5 years and had negative results by the direct fluorescent antibody test for respiratory syncytial virus, influenza A and B, parainfluenza viruses 1–3, and adenovirus. Overall, 54 (8.1%) of 668 individuals tested positive for hMPV. During March and April of the study period, hMPV was detected in 17.6% and 25.0% of specimens tested, respectively. At least 2 distinct genotypes of hMPV circulated during the study period. Fever, tachypnea, cough, rhinorrhea, retractions of the chest wall, and wheezing were common findings. Of hMPV-positive children, 60.4% were aged <12 months. hMPV accounted for a small but significant proportion of respiratory-tract disease in infants and children.

Association between a Novel Human Coronavirus and Kawasaki Disease

Abstract Kawasaki disease is a systemic vasculitis of childhood; its etiology is unknown. We identified evidence of a novel human coronavirus, designated “New Haven coronavirus” (HCoVNH), in respiratory secretions from a 6-month-old infant with classic Kawasaki disease. To further investigate the possible association between HCoV-NH infection and Kawasaki disease, we conducted a case-control study. Specimens of respiratory secretions from 8 (72.7%) of 11 children with Kawasaki disease and from 1 (4.5%) of 22 control subjects (children without Kawasaki disease matched by age and the time the specimens were obtained) tested positive for HCoVNH by reverse-transcriptase polymerase chain reaction (Mantel-Haenszel matched odds ratio, 16.0 [95% confidence interval, 3.4–74.4]; P = .0015). These data suggest that HCoV-NH infection is associated with Kawasaki disease.

Evidence of a novel human coronavirus that is associated with respiratory tract disease in infants and young children.

Abstract Background. The etiological agents responsible for a substantial proportion of respiratory tract diseases have not been identified. We sought to determine whether novel human coronaviruses (HCoVs) are circulating in New Haven, Connecticut, and, if so, whether they are associated with respiratory tract disease in infants and young children. Methods. We developed a polymerase chain reaction (PCR)-based approach for screening specimens from the respiratory tracts of symptomatic children. PCR probes that target regions of the replicase 1a gene that are conserved among genetically diverse animal CoVs and HCoVs were designed. Using these probes, we identified genomic sequences of a novel HCoV, designated “New Haven coronavirus” (HCoV-NH). Thereafter, we designed specific probes to screen respiratory specimens from children <5 years old for this novel HCoV. Clinical features associated with HCoV-NH infection were identified. Results. Seventy-nine (8.8%) of 895 children tested positive for HCoV-NH. Cough, rhinorrhea, tachypnea, fever, abnormal breath sounds, and hypoxia were the most common findings associated with HCoV-NH infection. Sequence analysis revealed that HCoV-NH is closely related to a novel HCoV recently reported in The Netherlands. Conclusions. The novel HCoVs identified in New Haven and The Netherlands are similar and likely represent the same species. This newly discovered virus may have worldwide distribution and may account for a significant proportion of respiratory tract disease in infants and young children.

Seroepidemiology of human metapneumovirus (hMPV) on the basis of a novel enzyme-linked immunosorbent assay utilizing hMPV fusion protein expressed in recombinant vesicular stomatitis virus.

ABSTRACT Human metapneumovirus (hMPV) is a newly identified human respiratory virus now recognized as a major respiratory pathogen of infants and children. To define the seroepidemiology of hMPV, we developed a novel enzyme-linked immunosorbent assay (ELISA) based on expression of the fusion protein of hMPV (hMPV F) in recombinant vesicular stomatitis virus (VSV). Western blot analysis using an hMPV F-specific antiserum confirmed the expression of hMPV in recombinant VSV. The ELISA is specific for hMPV F; antibody specific for the most closely related human paramyxovirus, respiratory syncytial virus, does not bind to hMPV F. Overall, 216 serum specimens were tested. The percentages of seropositive individuals were 89.1% in children ≤5 months old, 55.0% in children 6 to 11 months old, 36.0% in children 12 to 23 months old, 45.0% in children 24 to 47 months old, 77.3% in children 48 to 59 months old, 91.3% in children 5 to 10 years old, and 95.5% for individuals 11 to 20 years old. This is the first seroepidemiological survey of hMPV in the United States and the first analysis to determine the prevalence of antibody to a specific hMPV protein. The data suggest that exposure to hMPV is common in childhood and that hMPV F is an antigenic determinant of hMPV.

Coronavirus HKU1 infection in the United States.

Virus is associated with respiratory tract disease in children <5 years of age.

Human metapneumovirus and exacerbations of chronic obstructive pulmonary disease

Summary Objective Respiratory viruses are a common trigger for exacerbations of chronic obstructive pulmonary disease (COPD). Human metapneumovirus (hMPV) is a paramyxovirus associated with respiratory tract infections and wheezing. Our aim was to determine whether hMPV was associated with exacerbations of COPD. Methods The study was designed as an observational cohort study carried out in a 944-bed urban teaching hospital located in New Haven, Connecticut. Between December 2002 and May 2003, patients hospitalized due to an exacerbation of COPD were identified. Nasopharyngeal specimens obtained from these patients were tested for human metapneumovirus by RT–PCR and for respiratory syncytial virus, influenza A and B, parainfluenza-1, -2, and -3 and adenovirus by a cytospin-enhanced direct immunofluorescence assay and/or viral culture. Results Fifty individuals met enrollment criteria and hMPV was identified in 6 (12%), respiratory syncytial virus in 4 (8%), influenza A in 2 (4%) and parainfluenza type 3 in 1 (2%) patients. Both A and B hMPV genotypes were identified in patients hospitalized due to exacerbations of COPD. Conclusion hMPV was frequently identified in patients hospitalized due to an exacerbation of COPD. Further studies are necessary to determine the epidemiology and the impact of hMPV in COPD patients.

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.

Rate and influence of respiratory virus co-infection on pandemic (H1N1) influenza disease

Summary Objectives Many patients with influenza have more than one viral agent with co-infection frequencies reported as high as 20%. The impact of respiratory virus copathogens on influenza disease is unclear. We sought to determine if respiratory virus co-infection with pandemic H1N1 altered clinical disease. Methods Respiratory samples from 229 and 267 patients identified with and without H1N1 influenza respectively were screened for the presence of 13 seasonal respiratory viruses by multiplex RT-PCR. Disease severity between coinfected and monoinfected H1N1 patients were quantified using a standardized clinical severity scale. Influenza viral load was calculated by quantitative RT-PCR. Results Thirty (13.1%) influenza samples screened positive for the presence of 31 viral copathogens. The most prominent copathogens included rhinovirus (61.3%), and coronaviruses (16.1%). Median clinical severity of both monoinfected and coinfected groups were 1. Patients coinfected with rhinovirus tended to have lower clinical severity (median 0), whereas non-rhinovirus co-infections had substantially higher clinical severity (median 2). No difference in H1N1 viral load was observed between coinfected and monoinfected groups. Conclusions Respiratory viruses co-infect patients with influenza disease. Patients coinfected with rhinovirus had less severe disease while non-rhinovirus co-infections were associated with substantially higher severity without changes in influenza viral titer.

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.