key: cord-0777340-24f2gvag
authors: Monteny, Miriam; Niesters, Hubert G.M.; Moll, Henriëtte A.; Berger, Marjolein Y.
title: Human Bocavirus in Febrile Children, the Netherlands
date: 2007-01-03
journal: Emerg Infect Dis
DOI: 10.3201/eid1301.060819
sha: c54608c457676be2a819a1879a14df08074082d1
doc_id: 777340
cord_uid: 24f2gvag

nan

To the Editor: Human bocavirus (HBoV) is a recently discovered virus of the family Parvoviridae, genus Bocavirus, which appears to cause widespread respiratory tract infections (RTI) in children. In selected groups of children with RTI, detection rates have varied from 2.8% to 11.3% (1) (2) (3) (4) (5) (6) (7) (8) (9) . However, the exact prevalence and pathogenic effects of this virus remain to be established.

During a prospective cohort study to evaluate the prognosis of fever at a general practice after-hours service in Rotterdam, nasopharyngeal swabs were collected from febrile children and tested for respiratory viruses, including HBoV. We report the incidence and clinical features of HBoV infection in these children.

From June 1, 2005, through January 16, 2006, all children 3 months to 6 years of age whose parents contacted the after-hours service because of fever, as reported by parents and not further defined, were eligible for inclusion in the study. Children were excluded when the parents could not communicate in Dutch (n = 77) and if the child had already been included within the past 2 weeks (n = 11). A research nurse visited the child at home within 24 hours of inclusion. The child was physically examined, and a nasopharyngeal swab and a blood sample for C-reactive protein measurement were collected. The parents subsequently recorded the child's symptoms in a diary for 7 days. The Central Committee on Research Involving Human Subjects, the Netherlands, approved this study.

Nucleic acids were isolated on a MagnaPure isolation station (Roche Applied Science, Penzberg, Germany) and subsequently analyzed by realtime assays. Detection of HBoV was performed by using a primers set and a 6%) , all boys. The characteristics of these children are shown in the Table. All 4 children reported rhinorrhea and cough. Patient 1 reported abdominal pain, diarrhea (more than twice daily, with mucus), dyspnea, and a skin rash, along with respiratory symptoms. All symptoms lasted for >1 week. At physical examination, the research nurse evaluated the children to be not ill or (slightly) ill, based on standard criteria. Patient 1 had a skin rash and palpable cervical lymph nodes. Patient 4 had palpable lymph nodes and red tonsils. Patient 1 was given amoxicillin for otitis media, and patient 4 received amoxicillin for tonsillitis, as diagnosed by the general practitioner on the basis of the patient's clinical symptoms, without bacteriologic confirmation. During a 1-week follow-up period, none of the patients sought further medical advice.

Our finding that HBoV may cause RTI is in accordance with the literature (1-6) . Our findings support those of others in suggesting a role for HBoV in systemic infection, causing gastrointestinal symptoms and skin rash (6, 8) .

Our detection rate, in general practice, is lower than the rates reported from former studies of children with RTI (3%-10%) (1) (2) (3) (4) (5) (6) (7) (8) . Coinfection of HBoV and other viruses was found among 3 (75%) of 4 children (Table) . In other studies, coinfection was found in 17.6%-55.6% (mainly adenovirus, RSV, and human metapneumovirus) (1, 2, 5, (7) (8) (9) . The other detected viruses could have caused the symptoms of patients 2-4. However, HBoV was the only detected virus in 1 child with respiratory symptoms, gastrointestinal symptoms, and rash, and therefore might be the pathogen. Considering the high amount of HBoV in patient 3, symptoms were likely caused by HBoV in this patient as well.

Our ability to analyze severity of disease in our study population was limited because all children had mild disease, and no child was hospitalized. However, all children reported a prolonged course of fever, >7 days or recurrent within 1 week. This finding is in contrast with the mean duration of fever of 2.6 days in the study of Arnold et al., which was based in a hospital setting (6) . In our study, none of the HBoV-positive children received a diagnosis of bronchiolitis, pneumonia, or bronchitis, as in previous studies. None of the 4 children in our study was born preterm, compared with 19%-44% of HBoV-positive children in previous studies (5, 6) . None had a positive history for asthma or other underlying diseases, as did up to 50% of the children in previous studies (1, 6) .

In conclusion, HBoV was detected in nasopharyngeal swabs of 4 (1.6%) of 257 children <6 years of age whose parents contacted a general practice after-hours service. Our results suggest that HBoV might cause mild disease with respiratory and gastrointestinal symptoms and skin rash. Further research, not restricted to susceptible or hospitalized patients, is needed to clarify the prevalence and pathogenicity of this new virus in the general population.

Cloning of a human parvovirus by molecular screening of respiratory tract samples

Evidence of human coronavirus HKU1 and human bocavirus in Australian children

Detection of human bocavirus in Japanese children with lower respiratory tract infections

Human bocavirus infection

Human bocavirus in children

Human bocavirus: prevalence and clinical spectrum at a children's hospital

Frequent detection of bocavirus DNA in German children with respiratory tract infections

Bocavirus infection in hospitalized children

The association of newly identified respiratory viruses with lower respiratory tract infections in Korean children

We thank Ann Vossen for the analysis of the swabs.

To the Editor: The global prevalence of dengue fever (DF) has grown dramatically in recent decades; DF is now endemic to >100 countries (1) . Dengue hemorrhagic fever (DHF), a potentially lethal complication of dengue virus infection, was first recognized in Asia in the 1950s and is now a leading cause of hospitalization and death among children (1) . During the past decade, DHF epidemics have occurred in China, Sri Lanka, India, the Maldives, Bangladesh, and Pakistan (2) (3) (4) .In Pakistan, an outbreak of DHF was first reported in Karachi in 1994 (4) . Through mid-2005, 15-20 patients with DF or DHF were admitted each year to the Aga Khan University Hospital (AKUH), a tertiary care referral center in Karachi. Many more cases, however, may have gone unrecognized. Ours is the first report of dengue virus serotype 3 in Pakistan.From September through December 2005, at least 3 major hospitals in Karachi, including AKUH, had a sudden increase in the number of patients with signs consistent with the World Health Organization definition of DHF: high fever, rash, epistaxis, gum bleeding, liver dysfunction, and thrombocytopenia (platelets <100,000/mm 3 ); most had evidence of capillary leakage in the form of raised hematocrit and pleural effusion with or without ascites (5) . Because in Pakistan, Crimean-Congo hemorrhagic fever (CCHF) is an important differential diagnosis for hemorrhagic fever, most patients seen at AKUH received care in strict isolation and were empirically treated with ribavirin. At time of admission, blood samples were collected for serologic testing for dengue virus and reverse transcription (RT)-PCR testing for CCHF virus. The first 5 samples, collected during the initial 2 weeks of the outbreak, were also sent to the Special Pathogens Reference Unit, Centre for Emergency Preparedness and Response, Health Protection Agency, Salisbury, United Kingdom, for diagnostic confirmation. In the absence of a local surveillance and disease notification system, the number of patients with suspected DHF at different hospitals in Karachi could not be ascertained.Of the 106 patients who had a clinical diagnosis compatible with DHF (5), 9 (8.5%) died and 97 (91.5%) recovered. Patients with possible DF (fever, mild thrombocytopenia with platelets >100,000/mm 3 ) were not admitted and were treated as outpatients. Dengue virus infection was confirmed for 42 of the 106 patients. Serum samples from 39 patients contained anti-dengue virus immunoglobulin M (IgM) antibody (Chemicon, Temecula, CA, USA). Diagnosis for 6 of these patients was confirmed by using immunoblot tests (Dengue IgM Blot and Dengue IgG Blot, Genelabs Diagnostics, Singapore). Of the 9 patients who died, 6 had dengue IgM and IgG according to immunoblot testing, and 3 had dengue IgM according to ELISA. Diagnoses for 3 additional patients were confirmed by RT-PCR.An RT-PCR assay specific for dengue viruses (6) was used to amplify the C/PrM/M region of the genome and produced PCR products of the expected size in 3 patient samples: 2 (K1 and 2) from Karachi and 1 (B) from Balochistan. The PCR products were sequenced, and data were subsequently placed in GenBank under accession numbers DQ469827 for D3418-05 (patient K1), DQ469828 for D3419-05 (patient K2), and DQ469826 for D3417-05 (patient B). These data were compared with those in databases by using the basic local alignment search tool for nucleotides (blastn), with default settings (7) . For