40 35 30 3
ELISA
2 1 0.35 µg/mL
W
The authors have no funding or conflicts of interest to disclose. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3305-0545 DOI: 10.1097/INF.0000000000000252
7F 9V 14
5 6A 6B
18 C 19 A 19 F 23 F
To The Editors: e read with interest the article by Antachopoulos et al1 describing pneumococcal pleural effusion (PPE) caused by Streptococcus pneumoniae infection in Greece after the implementation of 13-valent pneumococcal conjugate vaccine (PCV13). PPE related to S. pneumoniae serotype 3 infections developed in 5 children despite vaccination with PCV13. No child had received the complete infant series (3+1 or 2+1 immunization schedules). We describe what we believe to be the first case of vaccination failure despite a complete vaccination program, which suggests that the immune response for serotype 3 differs from that of the other PCV13 serotypes. A 3-year-old girl was admitted to our pediatric department in October 2013 because of PPE. She was born at full term and had been healthy. She had no known history of severe infections and no familial history of immunodeficiency. She presented a 15-day history of cough, 12 days of fever and 4 days of lethargy and feeding difficulties. The general practitioner had prescribed amoxicillin (75 mg/kg/d) for 4 days. At the time of admission, the respiratory rate was 40 breaths/min with intercostal retractions along with diminished air entry on the right side and crackles; the oxygen saturation value in room air was normal. The diagnosis was pneumonia with massive pleural effusion in the right lung, which was confirmed on chest radiograph. Ultrasonography confirmed the right pleural effusion. On needle thoracocentesis, 15 mL viscid purulent fluid (PF) was aspirated. The leukocyte count was 25.4 × 109/L (61% neutrophils) and C-reactive protein value 291 mg/L (normal < 5 mg/L). PF analysis revealed an exudate with elevated lactate dehydrogenase value (54 200 U/L), low pH and low glucose concentration (0.3 mmol/L). PF culture was negative for bacteria; immunochromatographic pneumococcal
4
1
0
3
Serotype 3 Pneumococcal Pleural Empyema in an Immunocompetent Child after 13-valent Pneumococcal Conjugate Vaccine
Concentration (µg/mL)
Letter to the Editor
Serotypes
FIGURE 1. Standard pneumococcal anticapsular polysaccharide ELISA of serotype-specific IgG binding antibody at 12 days after hospital admission in a child vaccinated with PCV13. antigen (Binax NOW, Portland, ME) was detected in PF and S. pneumoniae serotype 3 was found on multiplex PCR of PF.2 The initial treatment was cefotaxime (300 mg/kg/d) and rifampin (30 mg/kg/d) given intravenously. Because the condition had clinically deteriorated, with worsening fever, tachypnea and increasing oxygen requirement, a second needle thoracocentesis was performed on day 4 and 130 mL PF was obtained. Rifampin was discontinued on day 3. Therapy with cefotaxime continued 11 days followed by oral amoxicillin for a total of 4 weeks of treatment at home. The child had received 2 injections of PCV13 at 2 months, 22 days of age and again at 5 months of age, with a booster vaccination at 12 months, 23 days. PPE caused by S. pneumoniae serotype 3 occurred at 23 months after the booster injection, which suggested immune deficiency. The concentrations of immunoglobulins (IgG, IgA and IgM), complement fractions and lymphocyte subpopulations and titers of antibodies to tetanus, Haemophilus influenzae type B, diphtheria, poliovirus and pertussis vaccine antigens were within the normal range. Antibody values measured by ELISA 3 weeks after the beginning of the symptoms and 12 days after admission were greater for serotype 3 than other PCV13 serotypes (Fig. 1). Furthermore, opsonophagocytic activity assay titers for serotype 3 were high (1/17 496) suggesting a booster effect induced by the infection. Failure of serotype 3 vaccine was previously described by Antachopoulos et al,1 and our case was not surprising given the immunogenicity studies of PCV13. Indeed, the immune responses for serotype 3 differ from that for the other serotypes: lower antibody titers and no or little booster effect (but no hyporesponsiveness).3–6 Furthermore, in contrast with other vaccine serotypes, for serotype 3 vaccine, evidence of protection
The Pediatric Infectious Disease Journal • Volume 33, Number 5, May 2014
(invasive disease or carriage) is lacking. Nevertheless, the response to serotype 3 on opsonophagocytic activity assay is high with the infant series and toddler dose of PCV13.3,4 Moreover, no study has assessed the persistence of antibodies 2 years after the toddler dose of PCV13. Although PCV13 contains most serotypes of S. pneumoniae associated with PPE,7 information of vaccine failure collected by new microbiologic techniques is needed. Indeed, these clinical cases encourage the use of indirect research techniques for detecting pneumococcal strains in PF as well as multiplex PCR. Routine culture of PF or blood is usually negative for bacteria because antibiotics are often prescribed before admission to hospital.7 Monitoring S. pneumoniae serotypes may be more important with invasive pneumococcal disease, especially PPE, after PCV13 implementation than previously thought and studying the underlying mechanisms is crucial.
Fouad Madhi, MD
GPIP (Groupe de Pathologie Infectieuse Pédiatrique) de la SFP (Société Française de Pédiatrie), Paris Service de pédiatrie générale Centre Hospitalier Intercommunal de Créteil, Créteil
Cécile Godot, MD
Service de pédiatrie générale Centre Hospitalier Intercommunal de Créteil, Créteil
Philippe Bidet, MD, PhD
Service de Microbiologie Hôpital Robert Debré (AP-HP) Université Denis-Diderot Paris 7
Mathilde Bahuaud, MSc Laboratoire d’Immunologie Hôpital Cochin www.pidj.com | 545
The Pediatric Infectious Disease Journal • Volume 33, Number 5, May 2014
Letters
Ralph Epaud, MD
Service de pédiatrie générale Centre Hospitalier Intercommunal de Créteil, Créteil
Robert Cohen, MD
GPIP (Groupe de Pathologie Infectieuse Pédiatrique) de la SFP (Société Française de Pédiatrie), Paris Service de Néonatologie Centre Hospitalier Intercommunal de Créteil Créteil, France REFERENCES
1. Antachopoulos C, Tsolia MN, Tzanakaki G, et al. Parapneumonic pleural effusions caused by Streptococcus pneumoniae serotype 3 in children immunized with 13-valent conjugated pneumococcal vaccine. Pediatr Infect Dis J. 2014;33:81–83. 2. Maataoui N, Bidet P, Doit C, et al. A multiplex polymerase chain reaction method for rapid pneumococcal serotype determination in childhood empyema. Diagn Microbiol Infect Dis. 2011;69:245–249. 3. Snape MD, Klinger CL, Daniels ED, et al. Immunogenicity and reactogenicity of a 13-valent-pneumococcal conjugate vaccine administered at 2, 4, and 12 months of age: a double-blind randomized active-controlled trial. Pediatr Infect Dis J. 2010;29:e80–e90. 4. Kieninger DM, Kueper K, Steul K, et al.; 006 study group. Safety, tolerability, and immunologic noninferiority of a 13-valent pneumococcal conjugate vaccine compared to a 7-valent pneumococcal conjugate vaccine given with routine pediatric vaccinations in Germany. Vaccine. 2010;28:4192–4203. 5. Esposito S, Tansey S, Thompson A, et al. Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine compared to those of a 7-valent pneumococcal conjugate vaccine given as a three-dose series with routine vaccines in healthy infants and toddlers. Clin Vaccine Immunol. 2010;17:1017–1026. 6. Vanderkooi OG, Scheifele DW, Girgenti D, et al.; Canadian PCV13 Study Group. Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine in healthy infants and toddlers given with routine pediatric vaccinations in Canada. Pediatr Infect Dis J. 2012;31:72–77. 7. Burgos J, Falcó V, Pahissa A. The increasing incidence of empyema. Curr Opin Pulm Med. 2013;19:350–356.
Inhaled Corticosteroids Not Able to Prevent Post-bronchiolitis Asthma To The Editors: omer-Kooijker et al1 published in the journal their interesting findings on the lack of association of inhaled high-dose beclomethasone administered during hospitalization for bronchiolitis with asthma
Z
546 | www.pidj.com
and lung function at 6 years of age. During 2004–2006, 243 previously healthy infants aged
ELISA
2 1 0.35 µg/mL
W
The authors have no funding or conflicts of interest to disclose. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3305-0545 DOI: 10.1097/INF.0000000000000252
7F 9V 14
5 6A 6B
18 C 19 A 19 F 23 F
To The Editors: e read with interest the article by Antachopoulos et al1 describing pneumococcal pleural effusion (PPE) caused by Streptococcus pneumoniae infection in Greece after the implementation of 13-valent pneumococcal conjugate vaccine (PCV13). PPE related to S. pneumoniae serotype 3 infections developed in 5 children despite vaccination with PCV13. No child had received the complete infant series (3+1 or 2+1 immunization schedules). We describe what we believe to be the first case of vaccination failure despite a complete vaccination program, which suggests that the immune response for serotype 3 differs from that of the other PCV13 serotypes. A 3-year-old girl was admitted to our pediatric department in October 2013 because of PPE. She was born at full term and had been healthy. She had no known history of severe infections and no familial history of immunodeficiency. She presented a 15-day history of cough, 12 days of fever and 4 days of lethargy and feeding difficulties. The general practitioner had prescribed amoxicillin (75 mg/kg/d) for 4 days. At the time of admission, the respiratory rate was 40 breaths/min with intercostal retractions along with diminished air entry on the right side and crackles; the oxygen saturation value in room air was normal. The diagnosis was pneumonia with massive pleural effusion in the right lung, which was confirmed on chest radiograph. Ultrasonography confirmed the right pleural effusion. On needle thoracocentesis, 15 mL viscid purulent fluid (PF) was aspirated. The leukocyte count was 25.4 × 109/L (61% neutrophils) and C-reactive protein value 291 mg/L (normal < 5 mg/L). PF analysis revealed an exudate with elevated lactate dehydrogenase value (54 200 U/L), low pH and low glucose concentration (0.3 mmol/L). PF culture was negative for bacteria; immunochromatographic pneumococcal
4
1
0
3
Serotype 3 Pneumococcal Pleural Empyema in an Immunocompetent Child after 13-valent Pneumococcal Conjugate Vaccine
Concentration (µg/mL)
Letter to the Editor
Serotypes
FIGURE 1. Standard pneumococcal anticapsular polysaccharide ELISA of serotype-specific IgG binding antibody at 12 days after hospital admission in a child vaccinated with PCV13. antigen (Binax NOW, Portland, ME) was detected in PF and S. pneumoniae serotype 3 was found on multiplex PCR of PF.2 The initial treatment was cefotaxime (300 mg/kg/d) and rifampin (30 mg/kg/d) given intravenously. Because the condition had clinically deteriorated, with worsening fever, tachypnea and increasing oxygen requirement, a second needle thoracocentesis was performed on day 4 and 130 mL PF was obtained. Rifampin was discontinued on day 3. Therapy with cefotaxime continued 11 days followed by oral amoxicillin for a total of 4 weeks of treatment at home. The child had received 2 injections of PCV13 at 2 months, 22 days of age and again at 5 months of age, with a booster vaccination at 12 months, 23 days. PPE caused by S. pneumoniae serotype 3 occurred at 23 months after the booster injection, which suggested immune deficiency. The concentrations of immunoglobulins (IgG, IgA and IgM), complement fractions and lymphocyte subpopulations and titers of antibodies to tetanus, Haemophilus influenzae type B, diphtheria, poliovirus and pertussis vaccine antigens were within the normal range. Antibody values measured by ELISA 3 weeks after the beginning of the symptoms and 12 days after admission were greater for serotype 3 than other PCV13 serotypes (Fig. 1). Furthermore, opsonophagocytic activity assay titers for serotype 3 were high (1/17 496) suggesting a booster effect induced by the infection. Failure of serotype 3 vaccine was previously described by Antachopoulos et al,1 and our case was not surprising given the immunogenicity studies of PCV13. Indeed, the immune responses for serotype 3 differ from that for the other serotypes: lower antibody titers and no or little booster effect (but no hyporesponsiveness).3–6 Furthermore, in contrast with other vaccine serotypes, for serotype 3 vaccine, evidence of protection
The Pediatric Infectious Disease Journal • Volume 33, Number 5, May 2014
(invasive disease or carriage) is lacking. Nevertheless, the response to serotype 3 on opsonophagocytic activity assay is high with the infant series and toddler dose of PCV13.3,4 Moreover, no study has assessed the persistence of antibodies 2 years after the toddler dose of PCV13. Although PCV13 contains most serotypes of S. pneumoniae associated with PPE,7 information of vaccine failure collected by new microbiologic techniques is needed. Indeed, these clinical cases encourage the use of indirect research techniques for detecting pneumococcal strains in PF as well as multiplex PCR. Routine culture of PF or blood is usually negative for bacteria because antibiotics are often prescribed before admission to hospital.7 Monitoring S. pneumoniae serotypes may be more important with invasive pneumococcal disease, especially PPE, after PCV13 implementation than previously thought and studying the underlying mechanisms is crucial.
Fouad Madhi, MD
GPIP (Groupe de Pathologie Infectieuse Pédiatrique) de la SFP (Société Française de Pédiatrie), Paris Service de pédiatrie générale Centre Hospitalier Intercommunal de Créteil, Créteil
Cécile Godot, MD
Service de pédiatrie générale Centre Hospitalier Intercommunal de Créteil, Créteil
Philippe Bidet, MD, PhD
Service de Microbiologie Hôpital Robert Debré (AP-HP) Université Denis-Diderot Paris 7
Mathilde Bahuaud, MSc Laboratoire d’Immunologie Hôpital Cochin www.pidj.com | 545
The Pediatric Infectious Disease Journal • Volume 33, Number 5, May 2014
Letters
Ralph Epaud, MD
Service de pédiatrie générale Centre Hospitalier Intercommunal de Créteil, Créteil
Robert Cohen, MD
GPIP (Groupe de Pathologie Infectieuse Pédiatrique) de la SFP (Société Française de Pédiatrie), Paris Service de Néonatologie Centre Hospitalier Intercommunal de Créteil Créteil, France REFERENCES
1. Antachopoulos C, Tsolia MN, Tzanakaki G, et al. Parapneumonic pleural effusions caused by Streptococcus pneumoniae serotype 3 in children immunized with 13-valent conjugated pneumococcal vaccine. Pediatr Infect Dis J. 2014;33:81–83. 2. Maataoui N, Bidet P, Doit C, et al. A multiplex polymerase chain reaction method for rapid pneumococcal serotype determination in childhood empyema. Diagn Microbiol Infect Dis. 2011;69:245–249. 3. Snape MD, Klinger CL, Daniels ED, et al. Immunogenicity and reactogenicity of a 13-valent-pneumococcal conjugate vaccine administered at 2, 4, and 12 months of age: a double-blind randomized active-controlled trial. Pediatr Infect Dis J. 2010;29:e80–e90. 4. Kieninger DM, Kueper K, Steul K, et al.; 006 study group. Safety, tolerability, and immunologic noninferiority of a 13-valent pneumococcal conjugate vaccine compared to a 7-valent pneumococcal conjugate vaccine given with routine pediatric vaccinations in Germany. Vaccine. 2010;28:4192–4203. 5. Esposito S, Tansey S, Thompson A, et al. Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine compared to those of a 7-valent pneumococcal conjugate vaccine given as a three-dose series with routine vaccines in healthy infants and toddlers. Clin Vaccine Immunol. 2010;17:1017–1026. 6. Vanderkooi OG, Scheifele DW, Girgenti D, et al.; Canadian PCV13 Study Group. Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine in healthy infants and toddlers given with routine pediatric vaccinations in Canada. Pediatr Infect Dis J. 2012;31:72–77. 7. Burgos J, Falcó V, Pahissa A. The increasing incidence of empyema. Curr Opin Pulm Med. 2013;19:350–356.
Inhaled Corticosteroids Not Able to Prevent Post-bronchiolitis Asthma To The Editors: omer-Kooijker et al1 published in the journal their interesting findings on the lack of association of inhaled high-dose beclomethasone administered during hospitalization for bronchiolitis with asthma
Z
546 | www.pidj.com
and lung function at 6 years of age. During 2004–2006, 243 previously healthy infants aged
