John C. Arnold

Human Bocavirus: Prevalence and Clinical Spectrum at a Children's Hospital

Abstract Background. Molecular methods of pathogen discovery have recently led to the description of several new respiratory viruses. Human bocavirus (HBoV), a proposed member of the family Parvoviridae, is one of the most recently described respiratory viruses. Initial reports indicate that HBoV is a common cause of respiratory tract infection in children. Methods. A total of 1474 nasal scraping specimens collected over a 20-month period were screened by polymerase chain reaction for the presence of HBoV nucleic acid. Positive results were confirmed with a second polymerase chain reaction assay from a different genomic region. The medical records of patients with positive results were reviewed for demographic and clinical data. Results. HBoV DNA was identified in 82 samples (5.6%). The peak rate of HBoV infection occurred during the period of March through May in both 2004 and 2005. Sixty-three percent of infected patients were <12 months of age. The most common symptoms were cough, rhinorrhea, and fever. Other symptoms of interest included diarrhea and a “paroxysmal” cough that was clinically suspected to be caused by Bordetella pertussis. Conclusions. HBoV DNA is commonly present in children with upper and lower respiratory tract infections. The presence of a pertussis-like cough and diarrhea in association with HBoV infection merits further investigation.

Undiagnosed Respiratory Viruses in Children

OBJECTIVE. An estimated 12 to 32 million upper respiratory infections occur in young children each year. In addition, 20% to 53% of infants will have ≥1 episode of lower respiratory infection in the first year of life. The current methods of diagnosing respiratory viruses are limited in scope and sensitivity. Polymerase chain reaction is a more sensitive method than antigen detection and is often used for newly discovered viruses. Using polymerase chain reaction, we sought to diagnose adenoviruses, human bocavirus, and human metapneumovirus at our childrens hospital. METHODS. Nasal-swab specimens submitted for antigen detection of respiratory viruses were collected and processed by using polymerase chain reaction to detect adenoviruses, human bocavirus, and human metapneumovirus. Inpatient and emergency department records were reviewed for clinical and demographic data. RESULTS. Approximately 1500 specimens were collected over 21 months; they contained adenoviruses, human bocavirus, and human metapneumovirus in 5.9%, 5.6%, and 5.2% of children, respectively. Using polymerase chain reaction and antigen detection, a viral agent was identified in as many as 62% of the specimens. Lower respiratory tract disease was present most frequently in patients infected with human metapneumovirus (63%) and least frequently in those infected with adenoviruses (45%). We detected adenoviruses by polymerase chain reaction in 59 patients for whom the antigen-detection test results were negative. A paroxysmal cough led to clinical suspicion of Bordetella pertussis infection in 19% of patients infected with human bocavirus. CONCLUSIONS. Adenoviruses, human bocavirus, and human metapneumovirus were each present in ∼5% of specimens submitted for respiratory virus rapid testing. The lower respiratory tract was more commonly affected in patients with human bocavirus and human metapneumovirus infections. Adenovirus was often undiagnosed by antigen detection. Other findings included the presence of a pertussis-like illness associated with human bocavirus.

Acute Bacterial Osteoarticular Infections: Eight-Year Analysis of C-Reactive Protein for Oral Step-Down Therapy

BACKGROUND: One of the most important decisions in the treatment of osteoarticular infections is the time at which parenteral therapy can be changed to oral therapy. C-reactive protein (CRP) is an acute inflammatory indicator with a half-life of 19 hours and thus can be helpful in assessing the adequacy of therapy for bacterial infections. At our institution, a combination of CRP and clinical findings is used to determine the transition to oral therapy. METHODS: A search of 8 years of electronic records identified children with osteoarticular infections. Only children with culture-positive acute bacterial arthritis (ABA) or acute bacterial osteomyelitis (ABO) were studied further. A primary chart review of demographic and clinical data was conducted, and a secondary chart review of complicated outcomes was performed. RESULTS: Of 194 total patients, complicated outcomes occurred in 40, of which 35 were prolonged therapy. Only 1 microbiologic failure occurred, presumably due to a retained intra-articular fragment of infected bone. CRP was highest initially among patients with simultaneous ABO + ABA and among those with complicated outcomes, and was lower at the transition to oral therapy in the complicated outcome group (1.5 vs 2.1 mg/dL; P = .012). CONCLUSIONS: The combination of clinical findings and CRP is a useful tool to transition children with osteoarticular infections to oral therapy. Complicated outcomes were associated with higher early CRP at diagnosis and lower CRP at the end of parenteral therapy, suggesting that clinicians were more conservative with prolonged initial parenteral therapy in this group.

Human metapneumovirus associated with central nervous system infection in children.

Background: Human metapneumovirus (hMPV) is an established pathogen of the respiratory tract of children and adults. hMPV is related to other paramyxoviruses known to cause encephalitis. Reports suggest that hMPV may cause disease of the central nervous system (CNS). Methods: Two groups of patients were studied. The first group consisted of children between birth and 18 years from whom nasal scrapings were obtained between January 2004 and October 2005. hMPV RNA amplification by PCR was done and records were reviewed for clinical and demographic data. The second group consisted of patients with encephalitis referred to the California Encephalitis Project (CEP) for comprehensive diagnostic testing between November 2004 and June 2006. Results: In group 1, 1474 specimens were examined for hMPV RNA. Sixty-three evaluable patients were infected with hMPV of whom 4 (6.3%) had seizures, compared with 145 patients infected with RSV of whom 1 had seizures (0.7%, P = 0.031). Comparing respiratory syncytial virus (RSV) and hMPV infections, there was no significant difference in the occurrence of fever. All children with hMPV infections and seizures were hospitalized and 3 were intubated because of status epilepticus. Group 2 consisted of 205 pediatric cases referred to CEP between November 2004 and June 2006 who had hMPV testing done. hMPV was detected in nasopharyngeal swabs of 5 patients. Neither hMPV RNA nor antihMPV specific IgM were detectable in the CSF from the 5 patients for whom CSF was available. Conclusion: Nine cases of CNS illness temporally associated with the presence of hMPV nucleic acid in the upper airway are described. Compared with children infected with RSV, children with hMPV were significantly more likely to have had a seizure. Our data, in conjunction with previously reported cases suggest that hMPV may be associated with a spectrum of CNS disease ranging from febrile seizures to severe, fatal encephalitis.

Head and Neck Manifestations of Disseminated Coccidioidomycosis

Objectives/Hypothesis Coccidioidomycosis is a fungal disease endemic to semiarid regions in the southwestern United States, northern Mexico, and parts of South America. Although this is primarily a pulmonary disease, approximately 0.5% to 1.0% of infected individuals develop disseminated disease affecting skin, subcutaneous tissue, bone, joints, and meninges. The objectives of the study were to present three cases of head and neck manifestations of disseminated coccidioidomycosis and to review the literature of head and neck presentations, diagnosis, and treatment of this potentially life‐threatening disease.

Osteoarticular Infections in Children

For a child with a suspected bone or joint infection, knowledge of the workup and initial therapy is important to provide quality care. Fever and pain are hallmarks of a pediatric osteoarticular infection, although occasionally the signs and symptoms can be more subtle. The use of C-reactive protein to diagnose and validate effective management of treatment has become standard. Multiple reports confirm the success of much shorter intravenous (IV) courses than traditionally taught. The ideal IV and oral antibiotic duration, as well as defining the markers indicating need for surgical intervention, are questions yet to be answered.

Epidemiologic, clinical, and virologic characteristics of human rhinovirus infection among otherwise healthy children and adults: Rhinovirus among adults and children

Abstract Background human rhinovirus (HRV) is a major cause of influenza-like illness (ILI) in adults and children. Differences in disease severity by HRV species have been described among hospitalized patients with underlying illness. Less is known about the clinical and virologic characteristics of HRV infection among otherwise healthy populations, particularly adults. Objectives to characterize molecular epidemiology of HRV and association between HRV species and clinical presentation and viral shedding. Study design observational, prospective, facility-based study of ILI was conducted from February 2010 to April 2012. Collection of nasopharyngeal specimens, patient symptoms, and clinical information occurred on days 0, 3, 7, and 28. Patients recorded symptom severity daily for the first 7 days of illness in a symptom diary. HRV was identified by RT-PCR and genotyped for species determination. Cases who were co-infected with other viral respiratory pathogens were excluded from the analysis. We evaluated the associations between HRV species, clinical severity, and patterns of viral shedding. Results eighty-four HRV cases were identified and their isolates genotyped. Of these, 62 (74%) were >18 years. Fifty-four were HRV-A, 11HRV-B, and 19HRV-C. HRV-C infection was more common among children than adults (59% vs. 10%, P <0.001). Among adults, HRV-A was associated with higher severity of upper respiratory symptoms compared to HRV-B (P =0.02), but no such association was found in children. In addition, adults shed HRV-A significantly longer than HRV-C (P trend=0.01). Conclusions among otherwise healthy adults with HRV infection, we observed species-specific differences in respiratory symptom severity and duration of viral shedding.

Human metapneumovirus and human bocavirus in children.

Several new viruses have recently been described in children, including human metapneumovirus (hMPV) and human bocavirus (HBoV). hMPV has been established as a common cause of upper and lower respiratory tract infections in children, often second only to respiratory syncytial virus as a cause of bronchiolitis in infants. Diagnostic tools have been developed for the clinician and effective treatment and prevention strategies are being investigated. HBoV was more recently identified. Although it was initially identified in the airway of children, high rates of codetection of other viral pathogens and detection of the virus in the stool have raised questions about the true role of HBoV as a cause of respiratory infections. A focus on epidemiology, pathogenesis, clinical features, and diagnostic techniques for hMPV and HBoV is presented.

Comparative analysis of hemagglutination inhibition titers generated using temporally matched serum and plasma samples.

Influenza-specific hemaggluitination inhibition (HAI) antibody titer, an indicator of immunity to influenza, is often used to measure exposure to influenza in surveillance and immunogenicity studies. Traditionally, serum has been the specimen of choice for HAI assays, but a desire to reduce the amount of blood collected during studies and the availability of plasma in archived sample collections warrant the evaluation of plasma for HAI titer. Therefore, the relationship between serum and plasma HAI titer values is of great interest. Here, we compare HAI titers determined on temporally matched serum and plasma (citrated and heparinized) using influenza A and B viruses. Bland-Altman plots, McNemars test, and geometric coefficient of variation were used respectively for evaluating agreement, correlation and variability in the serum-plasma titer results. We observed a high degree of agreement (80.5%–98.8%) and correlation (r = 0.796–0.964) in the serum and matched plasma titer values although plasma titers were generally lower than corresponding serum titers. Calculated seropositive (HAI ≥40) rates were higher using serum titers than with plasma titers, but seroconversion rates were unaffected by sample type. Stronger agreement and decreased variability in titers were seen between serum and citrated plasma than between serum and heparinized plasma. Overall, these data suggest that serum or plasma can be used in serodiagnostic HAI assays, but seropositive rates may be underestimated using plasma HAI titers. The type of anticoagulant present in plasma may affect HAI titer values and warrants further investigation.

Human bocavirus in children.

Human bocavirus (HBoV) was first detected using nonspecific gene sequencing of specimens from human subjects with respiratory illness. Viral, bacterial, and human genetic sequences were identified in 2 libraries of specimens collected at different times of year. Among the genetic sequences of many known pathogens was a parvovirus clone, which was not parvovirus B19. Bovine parvovirus and canine minute virus were the closest genetic relatives to the newly discovered parvovirus, and thus, it was called “human bocavirus” (bo for bovine and ca for canine). Although HBoV was initially described with a single genotype, 2 closely related variants have subsequently been identified and designated as “HBoV2” and “HBoV3.”