Print version ISSN 0325-0075
Arch. argent. pediatr. vol.111 no.3 Buenos Aires June 2013
Invasive infections caused by Streptococcus pneumoniae in a tertiary-level children´s hospital before the introduction of the conjugate vaccine. Clinical characteristics and serotypes involved
Guadalupe M. Pérez, M.D.a, Adriana Parra, M.D.a, Lidia Casimir, M.D.b, Alejandra Mastroianni, Biochemistb, Vanesa Reijtman, Biochemistb, Horacio Lopardo, M.D.b and Rosa Bologna,M.D.a
a. Department of
b. Department of Microbiology. Hospital Nacional de Pediatría "Prof. Dr. Juan P. Garrahan".
E-mail adress: Guadalupe M. Pérez, M.D.: email@example.com Conflict of interest: None
Invasive pneumococcal diseases are the main
cause of morbidity and mortality in children.
In the Hospital "Prof. Dr. Juan P. Garrahan",
between October 1st
, 2008 and September 30th,
2011 all invasive pneumococcal diseases with
positive blood cultures were retrospectively
studied before the implementation of the
universal immunization schedule with the
13-valent pneumococcal conjugate vaccine. A
total of 124 patients were identified, and their
mean age was 48.3 months (range: 1-216). In this
population, 58.9% (n: 73) were OVER 2 years
old and 89% (n: 65) of them had an underlying
disease. The most frequent clinical presentation
was pneumonia. The most frequent S. pneumoniae
serotypes identified were: 14 (22.5%, n: 25), 6
(14.4%, n: 16), 19 (8.1%, n: 9), 23 (7.2%, n: 8),
1 (6.3%, n: 7), 5 (4.5%, n: 5), and 7 (7.2%, n: 8).
Of the S. pneumoniae serotypes in this series, 82.2% is included in the 13-valent pneumococcal conjugate vaccine. Continuous epidemiological surveillance is essential to further identify the epidemiology and study the evolution of invasive pneumococcal disease in Argentina.
Key words: Pneumococcal disease; Streptococcus pneumoniae; Pneumococcal serotypes; Pneumonia; Bacteremia.
Invasive pneumococcal diseases are the main cause of morbidity and mortality in children. S. pneumoniae is the main etiologic agent in children with bacterial pneumonia, meningitis, sepsis, and bacteremia in Argentina.1 The implementation of universal immunization against pneumococcus in children in countries like the United States,2 Brazil and Uruguay3,4 has proven to be an effective strategy to reduce the incidence of this invasive disease, both in children and in adults.5 In Argentina, the 13-valent pneumococcal conjugate vaccine was added to the national immunization schedule.6 This study describes the clinical characteristics and serotypes involved in pneumococcal invasive diseases confirmed by blood cultures in Hospital de Pediatría"Prof. Dr. Juan P. Garrahan" over the three years previous to adding this vaccine to the immunization program.
MATERIAL AND METHODS
Invasive infections caused by
S. pneumoniae were retrospectively
studied from October 2008 to
September 2011 in Hospital "Prof.
Dr. Juan P. Garrahan", a children's
tertiary care hospital with 620 beds
and 4 intensive care units where
children from all over the country
are referred to. All children with a
clinical condition compatible with S. pneumoniae and positive blood
cultures recorded in the hospital
during the study period were
included. Patients with blood cultures
tested at a different hospital were
Medical records were reviewed to document each patient´s history as well as the characteristics of the clinical course and evolution. Results were submitted for publication after ensuring that patients' identity would be kept confidential. The study was conducted in accordance with the Declaration of Helsinki ethical principles. Serotyping of the 111 pneumococcal isolates available at the time of the study was performed in the Infectious Disease National Institute of the National Administration of Labs and Health Institutions (INEI-ANLIS) "Dr. Carlos G. Malbrán" using the Quellung reaction with the antisera provided by the Statens Serum Institut, Copenhagen, Denmark.
Between October 2008 and September 2011,
124 patients with blood cultures positive for S.
pneumoniae and symptomatology compatible with
invasive pneumococcal disease were identified.
Out of them, 50.8% (n: 63) were male. The mean
age was 48.3 months (range: 1-216). Of them, 67.7%
(n: 84) had an underlying disease. Predominant
comorbidities were: hematooncological disease
(44.4%, n: 36), nephrotic syndrome (9.9%, n: 8),
immunodeficiencies (12.8%, n: 10), and congenital
heart defects (6.2%, n: 5). Only 10 patients (8.1%)
had received a pneumococcal vaccine. Mortality
rate was 9.7% (n: 12).
Patients' characteristics were analyzed depending on whether they were older or younger than 2 years old (Table 1). Patients older than 2 years old accounted for 58.9% of the population (n: 73), and 89% (n: 65) of them had an underlying disease. The presence of an underlying disease was predominant in the older than 2 year old group ( <0.01).
Table 1. Demographic, clinical outcomes characteristics of the population by age
The most frequent presentation of the invasive
disease caused by S. pneumoniae was pneumonia:
60.8% (n: 31) in patients younger than 2 years old
and 49.3% (n: 36) in patients older than 2 years
old. Considering both groups, 30% had sepsis.
Primary peritonitis was present in 5.9% (n: 3)
of the patients younger than 2 years old and in
13.7% (n: 10) of children older than 2 years old.
The most frequent serotypes of S. pneumoniae were: 14 (22.5%, n: 25), 6 (14.4%, n: 16), 19 (8.1%, n: 9), 23 (7.2%, n: 8), 1 (6.3%, n: 7), 5 (4.5%, n: 5), and 7 (7.2%, n: 8) (Figure 1).
Figure 1. Frequency of serotypes identified in patients younger and older than 2 years old
Invasive infection caused by S. pneumoniae is
still the main cause of severe disease in children
worldwide.1 It is the most common cause of
community-acquired bacterial pneumonia
among non-vaccinated populations7 and the
etiologic agent of community-acquired sepsis and
meningitis. In Argentina, population studies have
estimated an annual incidence of invasive disease
similar to that found in other countries before the
implementation of the universal immunization
The incidence of invasive disease caused by S. pneumoniae, reported in the bibliography, is higher among patients under 2 years old and immunocompromised patients.1 However, in the series run at Hospital Garrahan, the incidence was higher in children older than 2 years old, a finding which is probably related to the characteristics of the hospital population (patients with chronic conditions, hematooncological disease, immunodeficiencies, and heart disease).
In this series, pneumonia, with or without pleural empyema, was the most predominant clinical presentation, followed by sepsis and fever without a source. This is consistent with the bibliography, which describes pneumonia, followed by occult bacteremia and sepsis, as prevalent syndromes.9 Given the association with the nephrotic syndrome and the characteristics of the underlying disease in the studied population, primary peritonitis was also found to be a frequent presentation in this series. Mortality in this study was higher than the rate described in specialized literature.10 It should be noted that 67.7% of children had associated comorbidities, which favor the occurrence of more serious infections.
The recent incorporation of the 13-valent pneumococcal conjugate vaccine for children younger than 2 years old in Argentina's immunization schedule is an effective strategy evaluated in other countries for the decrease of invasive disease11 and nasopharyngeal carriage of S. pneumoniae.12
The 13-valent pneumococcal conjugate vaccine includes capsular antigens of serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.5 Of the serotypes found in this series, 82.8% is included in the vaccine. If only children younger than 2 years old are studied, 85.6% of the serotypes identified in this study are covered by the 13-valent pneumococcal conjugate vaccine.
In countries where universal immunization has been performed with the 7-valent conjugate vaccine for years, non vaccine serotypes have emerged13,14 and the clinical characteristics of the invasive infection caused by S. pneumoniae have changed.15 In Argentina, universal immunization in children younger than 2 years old with the 13-valent pneumococcal conjugate vaccine has been in place since 2012. It is necessary to maintain a careful epidemiological surveillance and to continuously study incidence, evolution and clinical presentations of the invasive pneumococcal disease and its predominant serotypes.
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