Figure

Figure. . Chest radiograph of the index patient, a 16-month-old boy in Finland with human bocavirus 1 pneumonia, on day 2 of hospitalization. Bilateral pulmonary infiltrations and atelectasis of the upper right...

The index patient was a male twin who was born prematurely at 26 weeks’ gestation. He weighed 1,540 g at birth and had severe bronchopulmonary dysplasia. He was not administered pneumococcal vaccine. At the age of 16 months, he was admitted to the hospital for evaluation and treatment of wheezing. Rhinorrhea and cough had been present for 12 days. No fever was recorded at admission. The child had a heart rate of 170 beats/min (reference range 75–130 beats/min) and a respiratory rate of 50 breaths/min (reference range 25–30 breaths/min). He experienced severe respiratory distress and was transferred to the intensive care unit. A chest radiograph showed bilateral pulmonary infiltrations and atelectasis of the upper right lobe (Figure). His serum C-reactive protein level was 1 mg/L, and his leukocyte count was 19.6 ×10⁹/L. He was treated with intravenous cefuroxime, clarithromycin, and methylprednisolone. Tracheal intubation and bronchoalveolar lavage (BAL) were performed. Cultures of blood and BAL sample did not grow bacteria.

After a week, ventilator-associated pneumonia developed in the child. His serum C-reactive protein level rose to 68 mg/L; intravenous vancomycin and meropenem treatment were initiated. Pseudomonas aeruginosa was identified in a second BAL culture. The child was extubated after 3 weeks, and after 5 weeks of hospitalization, he recovered completely.

The patient’s twin brother had recovered from a common cold, which had started 2 weeks before the patient was hospitalized. Two days after the patient was admitted, his brother contracted another mild respiratory infection lasting 4 days. The 34-year-old mother remained asymptomatic, but the 58-year-old grandmother, who stayed in the household daily for many hours, had rhinitis. All family members were tested for respiratory viruses.

Nasopharyngeal aspirate (NPA) collected from the index patient was negative by PCR for influenza A and B, parainfluenza type 1–3 viruses, adenovirus, human metapneumovirus, respiratory syncytial virus, enteroviruses, and coronavirus types 229E, OC 43, NL63, and HKU1. PCR revealed a low load of human rhinovirus (HRV) RNA and a much higher load of HBoV1 DNA (Table). The index patient had an HBoV1 infection proven by detection of HBoV1 DNA in high copy numbers in NPA and BAL samples, as well as in serum. The DNA levels gradually decreased until they were not detectable (Table). PCR showed the index patient’s serum samples to be HBoV1-positive for 4 weeks and nasal mucus samples to be positive for at least 3 months. All samples were negative for HBoV2–4 DNA. The child had an HBoV1-specific IgM response and a >4-fold increase in HBoV1 IgG. The avidity of the IgG was initially low and then matured, but IgM declined and were undetectable by the end of the 3-month follow-up period.

The twin brother’s NPA was positive for HBoV1 DNA for 6 weeks. Two months later, his test results were HBoV1 IgM–negative but exhibited HBoV1 IgG at a high level and of high avidity. The children’s mother, who was asymptomatic, lacked HBoV1–4 DNA in serum but had intermittent low HBoV1 DNA loads in NPA. She had neither HBoV1-specific IgM nor IgG but exhibited a stable level of HBoV2-specific IgG of high avidity. NPA collected from the grandmother was intermittently HBoV1 DNA–positive twice during the first 9 days and twice thereafter. On day 13 of her grandson’s hospitalization, her serum was HBoV1 DNA–positive; on follow-up, she had an increase of high-avidity HBoV1 IgG but no IgM response.

The index patient was tested for HRV RNA 8 times during hospitalization. His results were positive (1.5 × 10⁵ copies/mL) once, on day 4 after admission. His mother’s test result was positive (1.9 × 10⁴ copies/mL) on day 5. The twin brother's test results were positive (5.4 × 10⁷ – 1,500 copies/mL) on days 5, 14, and 29, indicating he had an acute HRV infection. Three months after this episode of HBoV1 infection, all 4 family members had symptomatic parainfluenza type 1 virus infections, and clinical samples for the twin brother were again positive for HBoV1 DNA. Four months later, both brothers had an adenovirus infection, and the twin brother’s test result was again positive for HBoV1.

For each family member tested, quantitative PCR for HBoV1 in NPA was performed as described (9). HBoV1–4 DNA in serum was measured by multiplex and singleplex PCRs (6). For other respiratory viruses, qualitative multiplex PCR (SeeplexRV12, Seegene, Seoul, South Korea) and quantitative PCR methods were used (10). Biotinylated HBoV1–3 VP2 virus-like particles were applied as antigens in enzyme immunoassays for measurement of HBoV-specific IgM, IgG, and IgG avidity (8,11). For removal of cross-reacting heterologous HBoV antibodies, virus-like particle–based competition assays were used (7).