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CHILDHOOD EMPYEMA: LIMITED POTENTIAL IMPACT OF 7-VALENT PNEUMOCOCCAL CONJUGATE VACCINE

Fletcher, Margaret PhD, FRCPCH*; Leeming, John PhD; Cartwright, Keith FRCPath; Finn, Adam PhD, FRCP on behalf of the South West of England Invasive Community Acquired Infection Study Group

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The Pediatric Infectious Disease Journal: June 2006 - Volume 25 - Issue 6 - p 559-560
doi: 10.1097/01.inf.0000219535.14201.1b
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Abstract

Pneumonia remains a cause of considerable morbidity in childhood with either sustained or increased rates of complicated pneumonia, including empyema, being reported.1–3 During the winter of 2003–2004, a marked increase in the number of children presenting with empyema at our institution, a tertiary referral facility, was observed compared with the previous year. For the 12 months from August 1, 2002, 10 children were coded as having a primary diagnosis of empyema, whereas 31 were so coded for the same period in 2003–2004. Although this may have reflected unknown changes in practice, there were no internal system changes to suggest that this reflected variation in coding procedures rather than in morbidity and no changes in service delivery or referral patterns were recorded.

Data from the United States has confirmed that the conjugate pneumococcal vaccine has had a significant impact on invasive pneumococcal infection4 with evidence of herd immunity in unimmunized age groups. However, severe cases of disease caused by serotypes not included in the current 7-valent conjugate vaccine continue to occur as documented by Byington et al,5 who also noted an increase in childhood empyema coincident with the introduction of PCV7.

In view of the apparent increased rates of complicated pneumonia and the expected imminent introduction of pneumococcal conjugate vaccine into the U.K. primary schedule, a detailed examination of the pathology of all cases presenting to our hospital with complex effusion or for surgical drainage after failure of conservative treatment was undertaken. Enhanced diagnostic procedures were used to determine the proportion of cases in which the etiology was Streptococcus pneumoniae and, in these cases, the proportions caused by serotypes included in the 7-valent conjugate vaccine.

MATERIALS AND METHODS

During the 12 months from August 2003, all empyema cases were prospectively ascertained in our secondary/tertiary pediatric center by daily review of admissions. All cases were confirmed by chest radiograph and ultrasound examination and, from the history, were attributable to community-acquired infection in previously well children.

Informed signed consent was obtained to record clinical details and analyze empyema fluid (pus in all cases) for evidence of pneumococcal infection, as detailed subsequently. Parents were also interviewed to ascertain recent antibiotic use. The study was reviewed and approved by the institutional ethics committee.

All samples were subjected to pneumococcal capsular polysaccharide enzyme-linked immunosorbent assay (ELISA) (PCPE) for 13 serotypes and C polysaccharide ELISA (CPE) analysis. All ELISAs were solid-phase assays in which antigen was captured by polyclonal rabbit group or C polysaccharide-specific antiserum (Statens Serum Institut, Denmark) and mouse monoclonal antibodies (donated by Wyeth, NY) were used to detect captured antigen as previously described.3,6,7

RESULTS

Of 37 eligible cases ascertained, we obtained consent from 34 children and/or their parents for inclusion in the study. The majority of the children (28 of 34) were transferred from their local hospitals for surgical review and pleural drainage. The median age was 6.3 years (range = 0.8–14.8 years) on admission; 12 were girls, 2 of whom were siblings presenting during the same week (case nos. 13 and 14). Another child was treated for empyema at the same time as his mother presented with community-acquired pneumonia and pleural effusion.

Although cases presented throughout the year, 26 (70%) were recruited during the 6 months from November to April.

In 5 children, no pleural empyema fluid was available for ELISA analysis. Of these 5, positive nonpneumococcal empyema fluid cultures were obtained in 2 (one Staphylococcus aureus and one group A Streptococcus), Gram-positive cocci were seen, but cultures were negative in a third and all investigations, including routine empyema fluid culture, were negative in 2. Of the remaining 29 empyema fluid samples, 26 were positive for pneumococcus by PCPE; 18 serotype 1, one serotype 7F, 2 serotype 3, 3 serotype 4, one serotype 9V and one for both serotypes 4 and 23F. Of the 3 PCPE-negative cases, one was CPE positive, suggesting pneumococcal infection with a serotype not in the PCPE panel and 2 had positive empyema fluid cultures for group A Streptococcus. Positive cultures were also obtained for 8 of the children with positive PCPE results; 2 from empyema fluid (S. pneumoniae and coagulase-negative Staphylococcus spp., respectively) and 6 from blood (all S. pneumoniae, one also H. influenzae).

DISCUSSION

More children were identified by active prospective surveillance than by retrospective review of International Classification of Diseases, 10th Revision codings, but most were identified by both approaches, suggesting that coding is broadly reliable in our center. The apparent increase in the number of cases of empyema presenting at this hospital during the winter of 2003–2004 could reflect either a rise in incidence or changes in referral patterns, although there have been no significant service changes to suggest the latter.

Lack of culture-proven diagnosis remains common in pediatric empyema.2,7 Our data show that in children with this condition in whom all cultures are negative, the causative organism is usually the pneumococcus and most often serotype 1. Microbiologic proof is valuable to the clinician in determining the optimal antibiotic regimen. Our data, the largest series published using diagnosis by pneumococcal antigen analysis (PCPE and PCE) of empyema fluid, strongly suggests that this is a sensitive and clinically useful diagnostic test in this setting.

Antigen analysis resulted in a microbiologic diagnosis for all 29 cases when fluid was available and a serotype assigned in all but one pneumococcal infection.

A predominance of serotype 1 among cases of pneumococcal empyema has recently been reported in the United Kingdom3,7 and the United States2 and is reconfirmed in this study. This contrasts with the low reported proportion of cases of pneumococcal invasive disease overall8 and very low rates of colonization9 caused by this serotype. The reason for this high invasive potential and predilection for the pleural space is unknown. Certainly, the relative importance of this serotype in empyema undermines the notion that serotypes not included in the current conjugate vaccine are not only rarer, but also less virulent.10 Serotype 1 was more prevalent in the early 20th century both in Northern Europe and North America11,12 and there is no reason, in principle, why this pattern should not recur in the future based on our observations and those of Byington et al.5 Immunization with the 7-valent pneumococcal conjugate vaccine significantly reduces invasive pneumococcal disease in children4; however, a vaccine that includes serotype 1 would be needed to reduce the morbidity reported here. Further studies to characterize serotype 1 isolates could help elucidate their apparent predilection to cause pleural empyema in our population.

REFERENCES

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Keywords:

empyema; capsular polysaccharide; ELISA; diagnosis

© 2006 Lippincott Williams & Wilkins, Inc.