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Journal of Clinical Microbiology, December 2008, p. 4104-4105, Vol. 46, No. 12
0095-1137/08/$08.00+0     doi:10.1128/JCM.01288-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

CASE REPORT

Hepatitis and Human Bocavirus Primary Infection in a Child with T-Cell Deficiency{triangledown}

Leena Kainulainen,1* Matti Waris,2 Maria Söderlund-Venermo,3 Tobias Allander,4 Klaus Hedman,5 and Olli Ruuskanen1

Department of Pediatrics, Turku University Hospital, Box 52, 20521 Turku, Finland,1 Department of Virology, University of Turku, Kiinamyllynkatu 13, 20520 Turku, Finland,2 Department of Virology, Haartman Institute, Box 21, 00014 University of Helsinki, Helsinki, Finland,3 Department of Clinical Microbiology, Karolinska University Hospital, SE-17176 Stockholm, Sweden,4 Department of Virology, Haartman Institute, Box 21, 00014 University of Helsinki and Helsinki University Hospital, Helsinki, Finland5

Received 8 July 2008/ Returned for modification 15 August 2008/ Accepted 28 September 2008


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ABSTRACT
 
Human bocavirus (HBoV) is one of the recently identified respiratory viruses. The clinical features of HBoV infection have not yet been fully elucidated. We report an invasive HBoV infection and hepatitis in a boy with cartilage-hair hypoplasia and severe T-cell immunodeficiency.


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CASE REPORT
 
Cartilage-hair hypoplasia and a homozygous A70G mutation were diagnosed in a boy at the age of 2 months. A severe immunodeficiency was found at the age of 3 months. The boy was lymphopenic (1.8 x 109/liter) and showed a marked reduction in CD3+ T cells (22%; 0.400 x 109/liter; normal range, 2.2 x 109 to 6.5 x 109/liter). The T-cell function was severely impaired, as shown by low lymphocyte proliferation responses (10% of control responses) to phytohemagglutinin, concanavalin A, and pokeweed mitogens. Immunoglobulin M (IgM) and IgG antibody formations in vitro measured by an enzyme-linked immunospot assay were normal. Upon receiving a pertussis-diphtheria-tetanus vaccination, the patient showed good antibody responses against tetanus and diphtheria. At the age of 4 months, rhinovirus was detected by PCR in nasopharyngeal aspirate (NPA) and remained detectable for 2 weeks. At 5 months, the patient was hospitalized for rotavirus gastroenteritis, with antigen in feces shown for 5 days. At the age of 6 months, palivizumab prophylaxis for respiratory syncytial virus was given for 3 months because of an ongoing epidemic. At 7 months of age, on 9 March 2008, the boy was admitted to the hospital because of fever, skin blisters, and a painful perianal ulceration. He had no respiratory symptoms. At the time of admission, his white blood cell count was 13.0 x 109/liter and his serum C-reactive protein level was 31 mg/liter. Intravenous cloxacillin, ceftazidime, and acyclovir were started. Blood culture results remained negative. The chest X ray done at admission was unremarkable. Herpes simplex cultures as well as PCR tests for adenovirus, human herpesvirus 6, parvovirus, cytomegalovirus, and enteroviruses of the blister fluid and perianal ulceration were negative. Serum IgM antibodies for Epstein-Barr virus remained undetectable. Hepatomegaly was observed. Serum alanine aminotransferase and gamma-glutamyltransferase levels were elevated: 474 U/liter and 178 U/liter, respectively. Serum prealbumin was low (0.08 g/liter), confirming liver dysfunction. The patient received a single dose (800 mg/kg of body weight) of intravenous immunoglobulin (IVIG) on 14 March 2008. Amphotericin B was added to the treatment. After 10 days of illness, liver function normalized and the patient was discharged. At the time of hepatitis, human bocavirus (HBoV) was detected in consecutive NPA, feces, urine, and serum samples. The highest copy numbers were found in NPA and feces. For serological diagnosis, an IgG enzyme immunoassay (EIA) and IgM mu capture EIA were used, with recombinant virus-like particles applied as an antigen (M. Söderlund-Venermo, unpublished data). Significant rises in serum IgM and IgG HBoV antibodies were demonstrable, confirming acute infection.

After 1 month, the PCR was negative with NPA, feces, urine, and serum samples but again turned positive after 4 weeks with NPA and feces samples with low copy numbers. At the same time, the patient had skin blisters but was otherwise well. A skin biopsy was taken of a blister, and it was negative for parvovirus and for HBoV by PCR. Before the onset of hepatitis, we searched for HBoV by PCR in preceding NPA and serum samples, with negative results (Table 1) . Two months after the onset of HBoV infection, the patient's immunological status showed transient recovery. The lymphocyte proliferation response to phytohemagglutinin increased from 1,538 cpm to 8,950 cpm but deteriorated again at the same time that HBoV PCR results returned positive.


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  		TABLE 1. HBoV PCR results for various samples and levels of serum HBoV antibodies in a patient with cartilage-hair hypoplasiaa

HBoV is one of the recently identified respiratory viruses. The prevalence of HBoV in respiratory specimens from young children with acute respiratory illnesses has ranged from 2% to 19%. HBoV is commonly detected in association with other respiratory viruses, raising the question of whether it is a passenger or a genuine respiratory pathogen (2, 4, 9). Acute expiratory wheezing and pneumonia are the clinical features typically associated with HBoV (1, 3, 4, 9). When it is a sole viral finding in the respiratory tract, HBoV usually occurs in high DNA levels and is often accompanied by the detection of HBoV DNA in serum as well as the appearance of specific IgM and IgG antibodies (1, 5).

HBoV is a ubiquitous virus. However, the clinical features of HBoV infection have not yet been fully elucidated, especially for immunosuppressed subjects (4, 9). Schenk and coworkers (8) reported disseminated (NPA, serum, and feces) HBoV infection in a child after stem cell transplantation. Fecal shedding of HBoV continued for 2 months. We have earlier reported a child with acute lymphoblastic leukemia who was NPA positive for HBoV for 3 months in five consecutive febrile episodes (6). Kupfer et al. described an adult patient with malignant B-cell lymphoma and a severe infection with long-lasting fever and pneumonia, in whom HBoV was the sole pathogen found in NPA (7). We describe a hereditably immunodeficient child with disseminated HBoV infection with clinical hepatitis and skin manifestations but without respiratory symptoms and without other concomitant viruses. A high HBoV DNA load in NPA, viremia, detection of IgM in serum, and a diagnostic elevation of IgG in paired serum samples confirmed acute primary HBoV infection. The administrated IVIG probably affected HBoV IgG levels. However, IVIG contains only IgG and does not confound IgM responses. In addition, IVIG has a half-life of 28 days. The cause of hepatitis was not specifically identified because no liver biopsies were done. However, our observations strongly suggest that HBoV was the causative agent. Recent studies in Denmark have shown that 70% of infants shed HBoV for less than a month and 26% for 2 months (10). In our patient, the virus turned transitorily negative but appeared positive on 6 June 2008 in NPA and feces about 3 months after the onset of infection, suggesting chronic HBoV infection in a child with T-cell deficiency. The true HBoV pathogenesis is not yet fully understood, and perhaps the results seen here show a more exaggerated form of the normal infection in an immunocompromised patient.


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ACKNOWLEDGMENTS
 
This study was supported by the Academy of Finland (grant 1122539), the Sigrid Jusélius Foundation, and the Helsinki University Central Hospital Research and Education Fund.


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FOOTNOTES
 
* Corresponding author. Mailing address: Department of Pediatrics, Turku University Hospital, Box 52, 20521 Turku, Finland. Phone: 358-2-3130000. Fax: 358-2-3131460. E-mail: leena.kainulainen{at}tyks.fi Back

{triangledown} Published ahead of print on 8 October 2008. Back


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Journal of Clinical Microbiology, December 2008, p. 4104-4105, Vol. 46, No. 12
0095-1137/08/$08.00+0     doi:10.1128/JCM.01288-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • de Vries, J. J. C., Bredius, R. G. M., van Rheenen, P. F., Smiers, F. J. W., Scholvinck, E. H., Vossen, A. C. T. M., Claas, E. C. J., Niesters, H. G. M. (2009). Human Bocavirus in an Immunocompromised Child Presenting with Severe Diarrhea. J. Clin. Microbiol. 47: 1241-1243 [Abstract] [Full Text]  

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