http://www.aap.org/policy/re9960t.html

 

Policy Statement

Pediatrics

Volume 106, Number 02

August 2000, pp 367-376

[Policy Statement: Recommendations for the Prevention of Pneumococcal Infections, Including the Use of Pneumococcal Conjugate Vaccine (Prevnar), Pneumococcal Polysaccharide Vaccine, and Antibiotic Prophylaxis]

Technical Report: Prevention of Pneumococcal Infections, Including the Use of Pneumococcal Conjugate and Polysaccharide Vaccines and Antibiotic Prophylaxis (RE9960)

AMERICAN ACADEMY OF PEDIATRICS

Gary D. Overturf, MD,A and the Committee on Infectious Diseases

ABSTRACT. Pneumococcal infections are the most common invasive bacterial infections in children in the United States. The incidence of invasive pneumococcal infections peaks in children younger than 2 years, reaching rates of 228/100 000 in children 6 to 12 months old. Children with functional or anatomic asplenia (including sickle cell disease [SCD]) and children with human immunodeficiency virus infection have pneumococcal infection rates 20- to 100-fold higher than those of healthy children during the first 5 years of life. Others at high risk of pneumococcal infections include children with congenital immunodeficiency; chronic cardiopulmonary disease; children receiving immunosuppressive chemotherapy; children with immunosuppressive neoplastic diseases; children with chronic renal insufficiency, including nephrotic syndrome; children with diabetes; and children with cerebrospinal fluid leaks. Children of Native American (American Indian and Alaska Native) or African American descent also have higher rates of invasive pneumococcal disease. Outbreaks of pneumococcal infection have occurred with increased frequency in children attending out-of-home care. Among these children, nasopharyngeal colonization rates of 60% have been observed, along with pneumococci resistant to multiple antibiotics. The administration of antibiotics to children involved in outbreaks of pneumococcal disease has had an inconsistent effect on nasopharyngeal carriage. In contrast, continuous penicillin prophylaxis in children younger than 5 years with SCD has been successful in reducing rates of pneumococcal disease by 84%.

Pneumococcal polysaccharide vaccines have been recommended since 1985 for children older than 2 years who are at high risk of invasive disease, but these vaccines were not recommended for younger children and infants because of poor antibody response before 2 years of age. In contrast, pneumococcal conjugate vaccines (Prevnar) induce proposed protective antibody responses (>.15 µg/mL) in >90% of infants after 3 doses given at 2, 4, and 6 months of age. After priming doses, significant booster responses (ie, immunologic memory) are apparent when additional doses are given at 12 to 15 months of age. In efficacy trials, infant immunization with Prevnar decreased invasive infections by >93% and consolidative pneumonia by 73%, and it was associated with a 7% decrease in otitis media and a 20% decrease in tympanostomy tube placement. Adverse events after the administration of Prevnar have been limited to areas of local swelling or erythema of 1 to 2 cm and some increase in the incidence of postimmunization fever when it is given with other childhood vaccines. Based on data in phase 3 efficacy and safety trials, the US Food and Drug Administration has provided an indication for the use of Prevnar in children younger than 24 months.

ABBREVIATIONS. AOM, acute otitis media; SCD, sickle cell disease; HIV, human immunodeficiency virus; OR, odds ratio; CI, confidence interval; NP, nasopharyngeal; PCV7, heptavalent pneumococcal CRM₁₉₇ conjugate vaccine; DTaP, diphtheria and tetanus toxoids and acellular pertussis; HbOC, Haemophilus influenzae type b conjugate; DTP, diphtheria and tetanus toxoids and pertussis; OPV, oral poliovirus; IPV, inactivated poliovirus; MMR, measles-mumps-rubella; MenCRM, meningococcal C conjugated to CRM₁₉₇; 23PS, 23-valent pneumococcal polysaccharide; 14PS, 14-valent pneumococcal polysaccharide vaccine.

Streptococcus pneumoniae is the most common cause of bacteremia, sepsis, meningitis, pneumonia, sinusitis, and acute otitis media (AOM) in children. Children at increased risk of pneumococcal infections include those with anatomic or functional asplenia (including sickle cell disease [SCD]); recipients of immunosuppressive chemotherapy (particularly children with hematopoietic and lymphoreticular malignancies); those with congenital and acquired immunodeficiency (including human immunodeficiency virus [HIV] infections); those with chronic renal disease (including nephrotic syndrome); and healthy Native American (American Indian and Alaska Native) and African American children. Since 1988, outbreaks of pneumococcal infection have been reported with increasing frequency in children attending out-of-home care. Children younger than 60 months in out-of-home care have a twofold to threefold higher risk of experiencing invasive pneumococcal infections than do children in home care. Many outbreaks of pneumococcal infections in out-of-home-care settings have been caused by penicillin-nonsusceptible strains of S pneumoniae.

In 1985, the American Academy of Pediatrics Committee on Infectious Diseases provided recommendations for the use of pneumococcal polysaccharide vaccines in children and indications for antibiotic prophylaxis in targeted populations.¹ In 1997, updated recommendations for the prevention of pneumococcal infections were provided,² and recommendations for the management of infections caused by penicillin-nonsusceptible pneumococci were published.³ The purposes of this technical report are to provide an update on the epidemiology of pneumococcal infections in children, including the infections in high-risk populations, and to present new information on the pneumococcal conjugate vaccine, Prevnar (Lederle Laboratories, Pearl River, NY/Wyeth-Ayerst Laboratories, Marietta, PA),B and capsular polysaccharide vaccines. In addition, the rationale for the use of prophylactic antibiotics in asplenic children will be reviewed. The use of antibiotics to control pneumococcal outbreaks among children in out-of-home care also will be discussed.

Epidemiology of Pneumococcal Infections
Invasive Pneumococcal Infection in Children

Following the widespread use of Haemophilus influenzae type b vaccines, S pneumoniae has become the most common cause of invasive bacterial infection in children in the United States.^4,5 Pneumococci are the most common cause of bacteremia in young children between 2 and 36 months old who have fever without an identifiable source, accounting for >84% of recovered bacterial pathogens.⁶ Children younger than 12 months have the highest rates of pneumococcal meningitis (estimated to be 10/100 000).^5,7 Among children younger than 5 years, pneumococcal infections cause an estimated minimum of 1400 cases of meningitis, 17 000 cases of bacteremia, 71 000 cases of pneumonia, and 5 to 7 million cases of otitis media annually. Rates of pneumococcal infection among children younger than 5 years are at least twofold higher than those observed in the next highest risk group (adults older than 65 years). The highest rates of invasive pneumococcal infection are observed in children 6 to 23 months old, with rates among all racial and ethnic groups varying from 184 to 1820/100 000 (Table 1). Rates of infection decrease steadily with increasing age beyond 24 months.

Pneumococcal disease, other than sepsis and meningitis, also is associated with considerable morbidity in children. Pneumococcal infection is a common cause of community-acquired pneumonia in children, accounting for 13% to 28% of bacterial pneumonia in industrialized nations^8-10 and up to 28% in developing countries.¹¹ Pneumococci are isolated from pleural fluid in 18% of children with empyema.¹² S pneumoniae also is the most common bacterial cause of AOM and sinusitis.^13-15 AOM is responsible for >20 million visits to pediatricians annually,¹⁴ and ~30% to 50% of AOM infections are caused by pneumococci.¹⁵ In US studies, nearly two thirds of children have at least 1 episode of AOM by their first birthday, and nearly one half have 3 or more episodes before their third birthday.¹⁶

SCD and Splenectomy

A high incidence of invasive pneumococcal infection in children with SCD has been demonstrated in several epidemiologic studies throughout the past 3 decades (Table 1). Before the use of penicillin prophylaxis, pneumococcal polysaccharide vaccines, and neonatal screening for hemoglobinopathies, rates of invasive pneumococcal disease in children with SCD exceeded those in healthy children by 20- to 100-fold, with the greatest risk in children younger than 5 years.¹⁷ Rates of invasive pneumococcal infections calculated for large populations of children with SCD from 1977 through 1986 were ~5200 to 6450/100 000 in children younger than 5 years, declining to 62 to 1100/100 000 in persons older than 5 years.¹⁷ Children with sickle cell hemoglobinopathy and certain other sickle cell hemoglobinopathies (including thalassemias) have lower rates of infection than do children with SSD hemoglobinopathy, but their rates are much greater than those of other children, and deaths attributable to fulminant pneumococcal infection have been reported in these children as well.¹⁸ Despite the use of pneumococcal polysaccharide vaccines and penicillin prophylaxis, high rates of invasive pneumococcal infection have continued to be observed (3000/100 000) in some groups of children with SCD.^19,20

The risk of invasive pneumococcal disease in children with congenital or surgical asplenia has not been defined precisely.^21,22 Asplenic children younger than 2 years are assumed to have high risks similar to young patients with SSE hemoglobinopathy who are functionally asplenic (autosplenectomized) by 18 months of age. For example, children with congenital heart disease and associated congenital asplenia have high rates of invasive pneumococcal disease that parallel those of children with SCD.²³

HIV Infection

Children with HIV infection have high rates of morbidity and mortality attributable in part to high rates of infection caused by encapsulated bacteria (Table 1). S pneumoniae is the most common cause of invasive bacterial infection in these children, accounting for 35% to 50% of such episodes, with relative risks of pneumococcal disease 3- to 22-fold higher than those of children without HIV infection.^24,25 Rates of invasive pneumococcal infection for children with HIV infection through 7 years of age have been calculated to be 6100/100 000, with rates as high as 11 300/100 000 during the first 3 years of life.²⁶ Children infected with HIV and with acquired immunodeficiency syndrome or those with increased levels of immunoglobulin G or immunoglobulin M are at greatest risk for invasive pneumococcal disease.²⁷

Specific Populations of Children With High Risk of Pneumococcal Infection

Certain groups of children of Native American descent have moderate risks ( >20/100 000) of pneumococcal infection, compared with other healthy children. Most groups of Native American children who are at high risk of invasive pneumococcal infection (>150/100 000) are younger than 2 years (Table 1). The degree of risk may vary by factors other than age, including tribal affiliation and residence on or off reservation sites. For many groups, the precise risk of pneumococcal infection remains to be defined. Annual incidence rates for pneumococcal infection among White Mountain Apache children are 1820, 227, and 54/100 000 for children younger than 2, 2 to 4, and 5 to 9 years old, respectively.²⁸ Rates of pneumococcal infection in Navajo children in Arizona and New Mexico have been estimated to be 664, 453, and 163/100 000 per year in children 12 months or younger, 12 to 23 months old, and 24 to 35 months old, respectively, with rates declining to ~50% of this level by 3 to 5 years of age (O'Brien K, personal communication, 1999). Alaska Natives have an incidence of invasive pneumococcal disease of 624/100 000 in children younger than 2 years.²⁹ Children of African American descent have rates of invasive pneumococcal infection that are twofold to threefold higher at all ages from birth to 59 months of age, compared with all US children (Table 1).

Infants and Children in Out-of-Home Care

Pneumococcal disease among children in out-of-home care has been reported more often throughout the last decade in the United States and other developed countries. In Finland, an increased risk for invasive pneumococcal disease among children younger than 2 years has been associated with attendance at out-of-home care (odds ratio [OR]: 36; 95% confidence interval [CI]: 5.7-233) or family home care (OR: 4.4; 95% CI: 1.7-12).³⁰ A history of frequent episodes of otitis media was a risk factor independent of out-of-home care. Attendance in out-of-home care also has been shown to increase the risk of respiratory tract infections and otitis media in US children.^31,32 In the United States, out-of-home care (defined as >4 hours/week outside the home) increases the risk for invasive pneumococcal infection (2.63-fold risk in children 2-11 months old, 2.29-fold risk in children 12-23 months old, and 3.28-fold risk in children 24-59 months old).³³

Among children in out-of-home care, outbreaks of invasive pneumococcal disease and respiratory tract infections, along with high rates of pneumococcal colonization, have been reported for several pneumococcal serotypes, particularly 14, 23F, and 12F.^34-37 Pneumococcal infections in such outbreaks have included sepsis, meningitis, purulent conjunctivitis, recurrent otitis media, and sinusitis. In one center, 3 cases of meningitis attributable to multiply resistant serotype 14 S pneumoniae occurred during a 5-day period, and nasopharyngeal (NP) carrier rates with the same pulsed-field genotype of multiply resistant pneumococcus varied from 44% to 65% at 2 other out-of-home care centers and 1 pediatric practice in the same community.³⁷ In another center, presumptive serogroup 19 pneumococcal disease, identified by serologic and polymerase chain reaction, caused hemorrhagic shock and resulted in the deaths of 2 children who were 4 and 7 months old.³⁸

ALL INFORMATION, DATA, AND MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR LEGAL ADVICE.  THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH YOUR HEALTH CARE PROVIDER.