Severe Necrotizing Pneumonia in Children, Houston, Texas, USA

To the Editor: Routine vaccination of children with the 7-valent pneumococcal conjugate vaccine (PCV-7; Wyeth Pharmaceuticals, Collegeville, PA, USA), initiated in the United States in 2000, was followed within 2 years by an extensive and rapid decline in invasive pneumococcal disease (IPD) (1). During the past few years, increasing frequency of invasive disease including necrotizing pneumonia caused by serotypes not included in the vaccine has been reported (2). We show an expanded pattern of the changing spectrum of the disease associated with nonvaccine serotypes through this report of 4 cases of necrotizing pneumonia in children, caused by Streptococcus pneumoniae serotype 19A. 
 
Over a 6-month period ending in March 2008, 4 children (median age 3.6 years, 1 with asthma) (Table) were brought to our hospital with signs of respiratory distress and a 4- to 7-day history of fever and cough. All had decreased breath sounds or crackles, and radiologic studies showed evidence of complicated pneumonia, which led to hospital admission (3 to an intensive care unit [ICU]). S. pneumoniae 19A was isolated from normally sterile sites with each child. All received intravenous antimicrobial drugs followed by an oral antimicrobial drug regimen and were discharged in good health. By reviewing immunization records, we confirmed that all had completed the PCV-7 series before becoming ill. 
 
 
 
Table 
 
Characteristics of patients in study of severe necrotizing pneumonia in children, Houston, Texas, USA, 2007–2008* 
 
 
 
During the same period, complicated pneumonia was identified in 7 other inpatients by using the International Classification of Diseases, 9th revision, codes for necrotizing pneumonia and empyema and Current Procedural Terminology codes for thoracoscopic surgery (median age 4.3 years); 2 had asthma, 1 had congenital diaphragmatic hernia with resultant left lung hypoplasia. No causative organism was identified for any of these cases. 
 
As illustrated by our 4 cases, serotype 19A is emerging as an increasing cause of severe disease such as complicated pneumonia. Although the incidence of IPD in general has decreased since the introduction of PCV-7, the emergence of nonvaccine serotypes as a cause of severe disease is becoming more prevalent. Among 8 geographic areas in the United States, the incidence of IPD caused by nonvaccine serotypes in children <5 years of age increased from 16.3 cases/100,000 population to 19.9 cases/100,000 population, respectively, from prevaccine years 1998–1999 to in 2004 (3). 
 
Because organisms were not isolated from the 7 other patients with necrotizing pneumonia during the same period, we are unable to comment on whether S. pneumoniae 19A was the predominant cause of necrotizing pneumonia in our study. However, in comparing our patients with these 7 patients, those with S. pneumoniae 19A appear to have had a more complicated course of illness, longer hospital stays (mean 19 days vs. 13 days), and a longer course of intravenous antimicrobial drugs (mean 19.2 days vs. 17 days). Although these 7 patients required more video-assisted thoracoscopic surgery than did our 4 patients (100% vs. 75%), those with S. pneumoniae 19A necrotizing pneumonia had a more severe clinical course of illness resulting in more ICU admissions (75% vs. 29%) and intubations (75% vs. 14%). 
 
All 4 of our patients had completed the PCV-7 series before becoming ill. The emergence of nonvaccine serotypes as a cause of severe disease may be caused by serotype replacement and increased nasopharyngeal carriage of nonvaccine serotypes after receiving PCV-7 (4). Our report supports the theory of serotype replacement. The increasing incidence of invasive disease caused by nonvaccine serotypes has prompted development of an expanded pneumococcal vaccine to include serotypes 1, 3, 5, 6A, 7F, and 19A in addition to those covered by PCV-7 (5). The need for this expanded vaccine is becoming more evident as the number of children with severe pneumococcal disease increases due to current nonvaccine serotypes.

To the Editor: Routine vaccination of children with the 7-valent pneumococcal conjugate vaccine (PCV-7; Wyeth Pharmaceuticals, Collegeville, PA, USA), initiated in the United States in 2000, was followed within 2 years by an extensive and rapid decline in invasive pneumococcal disease (IPD) (1). During the past few years, increasing frequency of invasive disease including necrotizing pneumonia caused by serotypes not included in the vaccine has been reported (2). We show an expanded pattern of the changing spectrum of the disease associated with nonvaccine serotypes through this report of 4 cases of necrotizing pneumonia in children, caused by Streptococcus pneumoniae serotype 19A.
Over a 6-month period ending in March 2008, 4 children (median age 3.6 years, 1 with asthma) (Table) were brought to our hospital with signs of respiratory distress and a 4-to 7-day history of fever and cough. All had decreased breath sounds or crackles, and radiologic studies showed evidence of complicated pneumonia, which led to hospital admission (3 to an intensive care unit [ICU]). S. pneumoniae 19A was isolated from normally sterile sites with each child. All received intravenous antimicrobial drugs followed by an oral antimicrobial drug regimen and were discharged in good health. By reviewing immunization records, we confirmed that all had completed the PCV-7 series before becoming ill.
During the same period, complicated pneumonia was identified in 7 other inpatients by using the International Classification of Diseases, 9th revision, codes for necrotizing pneumonia and empyema and Current Procedural Terminology codes for thoracoscopic surgery (median age 4.3 years); 2 had asthma, 1 had congenital diaphragmatic hernia with resultant left lung hypoplasia. No causative organism was identified for any of these cases.
As illustrated by our 4 cases, serotype 19A is emerging as an increasing cause of severe disease such as complicated pneumonia. Although the incidence of IPD in general has decreased since the introduction of PCV-7, the emergence of nonvaccine serotypes as a cause of severe disease is becoming more prevalent. Among 8 geographic areas in the United States, the incidence of IPD caused by nonvaccine serotypes in children <5 years of age increased from 16.3 cases/100,000 population to 19.9 cases/100,000 population, respectively, from prevaccine years 1998-1999 to 2004 (3).
Because organisms were not isolated from the 7 other patients with ne-crotizing pneumonia during the same period, we are unable to comment on whether S. pneumoniae 19A was the predominant cause of necrotizing pneumonia in our study. However, in comparing our patients with these 7 patients, those with S. pneumoniae 19A appear to have had a more complicated course of illness, longer hospital stays (mean 19 days vs. 13 days), and a longer course of intravenous antimicrobial drugs (mean 19.2 days vs. 17 days). Although these 7 patients required more video-assisted thoracoscopic surgery than did our 4 patients (100% vs. 75%), those with S. pneumoniae 19A necrotizing pneumonia had a more severe clinical course of illness resulting in more ICU admissions (75% vs. 29%) and intubations (75% vs. 14%).
All 4 of our patients had completed the PCV-7 series before becoming ill. The emergence of nonvaccine se-rotypes as a cause of severe disease may be caused by serotype replacement and increased nasopharyngeal carriage of nonvaccine serotypes after receiving PCV-7 (4). Our report supports the theory of serotype replacement. The increasing incidence of invasive disease caused by nonvaccine serotypes has prompted development of an expanded pneumococcal vaccine to include serotypes 1, 3, 5, 6A, 7F, and 19A in addition to those covered by PCV-7 (5). The need for this expanded vaccine is becoming more evident as the number of children with severe pneumococcal disease due to current nonvaccine serotypes increases.   (HBoV-2), in fecal samples (1,2). HBoV-1 had been discovered in 2005 (3), and reports indicate its possible role in respiratory diseases such as upper respiratory tract infections, lower respiratory tract infections (LRTIs), and in exacerbation of asthma (4); in these diseases, the virus co-infects with other respiratory viruses (5). Systemic infection with HBoV-1 and possible association of this virus with other diseases such as gastroenteritis, Kawasaki disease, and hepatitis have been reported (6-8).

Anupama S. Kalaskar
We looked for HBoV-2 in clinical samples from children with various diseases, including acute LRTIs, Kawasaki disease, Henoch-Schönlein purpura, and hepatitis.
During September 2008-January 2009, a total of 212 nasopharyngeal aspirates were collected from 212 children (median age 8 months, range 1-59 months) hospitalized with acute LRTIs at Sanggyepaik Hospital in Seoul, South Korea. Previously, during January 2002-June 2006, a total of 173 serum samples had been obtained from children (age range 1 month-15 years) with hepatitis (hepatitis B, 20 samples; hepatitis C, 11 samples; unknown hepatitis, 31 samples), Kawasaki disease (12 samples), and Henoch-Schönlein purpura (18 samples) and from healthy children (same age range, 81 samples) (9). The study was approved by the internal review board of Sanggyepaik Hospital.
DNA was extracted from serum samples, and RNA and DNA were extracted from nasopharyngeal aspirates by using a QIAamp Viral RNA Mini Kit (QIAGEN, Hilden, Germany) and a QIAamp DNA Blood Mini Kit (QIAGEN GmbH), respectively. All nasopharyngeal aspirates were tested by PCR for common respiratory viruses such as respiratory syncytial virus, influenza viruses A and B, parainfluenza virus, and adenovirus, as described previously (10). PCRs to detect HBoV-1 were performed by using primers for the nonstructural (NS) 1 and nucleocapsid protein (NP) 1 genes, as described previously (10). Additional PCRs for rhinovirus, human metapneumovirus, human coronavirus (hCoV)-NL63, hCoV-OC43, hCoV-229E, hCoV HKU-1, WU polyomavirus, and KU polyomavirus were performed, as described, for HBoV-2 -positive samples (10).
Of the 212 samples tested, the following viruses were detected: human respiratory syncytial virus ( HBoV-1 was not detected in the study population. HBoV-2 DNA was found in 5 (2.3%) of the 212 samples collected; all positive samples had been obtained in October 2008. The age range of the children with HBoV-2-positive samples was 4-34 months (median 24 months), and all were male. The diagnoses were bronchiolitis for 3 children and bronchopneumonia for 2. The most frequently codetected virus was human respiratory syncytial virus, found in 4 (80%) of 5 samples. One