Chapter 11: Pneumococcal

Key points

This chapter provides general guidance for vaccine-preventable disease surveillance, describing the disease background/epidemiology, case investigation and reporting/notification, disease case definitions, and activities for enhancing surveillance, case investigation, and outbreak control for pneumococcal.

Disease Description

Streptococcus pneumoniae (pneumococcus) is a gram-positive bacterium with more than 100 known serotypes. Pneumococcus is spread by airborne droplets and is a leading cause of serious illness, including sepsis, meningitis, and pneumonia among children and adults worldwide.12 Although all serotypes can cause serious disease, a relatively limited number of serotypes cause the majority of invasive pneumococcal disease (IPD).

The Centers for Disease Control and Prevention's (CDC's) Active Bacterial Core Surveillance (ABCs) has tracked IPD in selected regions of the United States since 1995.3 ABCs data indicate that younger children and older adults have the highest rates of invasive disease (Table 1).24 Approximately 10% of all patients with IPD die of their illness, but case-fatality rates are higher for older adults and patients with certain underlying illnesses.45

Table 1. Incidence of Invasive pneumococcal disease at ABCs sites in the United States, 20224

Age (years) Disease Incidence Cases/100,000 Death Rate Deaths/100,000
<1 10.8 0.5
1 7.6 0.0
2−4 6.8 0.3
5−17 2.3 0.1
18−34 3.1 0.2
35−49 7.4 0.6
50−64 13.2 1.8
65−74 15.8 1.7
75−84 16.4 2.7
≥85 27.4 7.5
Total 8.3 1.0

Each year in the United States, pneumococcal disease accounts for a substantial number of cases of invasive and non-invasive disease including meningitis, sepsis, pneumonia, sinusitis, and acute otitis media (AOM).456789 Prior to the COVID-19 pandemic, approximately 30,000 IPD cases 3,000 deaths from IPD occurred each year in the United States.4Estimating the number of non-invasive pneumococcal disease cases remains challenging due to limitations with diagnostic testing. Recent estimates suggest more than 2 million pneumococcal infections occur annually, resulting in 6,000 deaths.10

Pneumococcal disease is preceded by asymptomatic colonization of the nasopharynx which tends to be especially common in children.11 AOM is the most common clinical manifestation of pneumococcal infection among children and the most common outpatient diagnosis resulting in antibiotic prescriptions in that group.12 In adults, pneumonia is the most common clinical manifestation, causing an estimated 150,000 hospitalizations each year in the United States.10

Background

Trends in invasive pneumococcal disease

A 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in U.S. children aged <5 years in 2000. Following the introduction of PCV7, dramatic declines in IPD were reported among children aged <5 years. Rates of IPD caused by the 7 serotypes included in the vaccine declined from around 80 cases per 100,000 population in 1998-1999, to less than 1 case per 100,000 population by 2007 (Figure 1).13

Figure 1. Rates of invasive pneumococcal disease among children <5 years of age, 1998–20224

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chart for Figure 1. Rates of invasive pneumococcal disease among children <5 years of age, 1998–2022
Figure 1

The use of PCV7 in children aged <5 years also reduced the burden of IPD among older children and adults through reduced transmission of vaccine serotype pneumococci (herd protection). In 1998-99, rates of PCV7-type IPD among adults aged ≥65 years were around 40 cases per 100,000 population. After the introduction of PCV7, rates of disease due to these 7 serotypes had declined 45% by 2007 (Figure 2).1314151617

Figure 2. Rates of invasive pneumococcal disease among U.S. adults >65 years of age, 1998–2022 4

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chart for Rates of invasive pneumococcal disease among U.S. adults ≥65 years of age, 1998–2022
Figure 2

At the same time, increases in disease caused by serotypes not included in PCV7 (i.e., non-vaccine serotypes or NVT) were observed among children and adult populations, although these increases were small in magnitude compared with the overall reduction in disease.131415161718 An increase in disease caused by non-vaccine serotypes after vaccine introduction is called replacement disease.

In 2010, a new 13-valent conjugate vaccine (PCV13) was introduced in children aged <5 years. This vaccine included the original 7 serotypes in PCV7 plus 6 additional serotypes (Table 2). After the introduction of PCV13, cases of invasive disease due to the six additional serotypes covered by the vaccine (PCV13 non-PCV7) declined substantially.17 In 2007-08 (pre-PCV13), rates of PCV13-type IPD among children aged <5 years were around 14 cases per 100,000 population. In 2014-15 (post-PCV13), rates of PCV13-type disease had decreased by 87%. Declines plateaued after 2015 and remained stable through 2019 (Figure 1).4

After introduction of PCV13 in children, older adults also saw reductions in IPD through herd protection. In 2007-08, rates of PCV13-type IPD among adults aged ≥65 years were around 17 cases per 100,000 population. In 2014-15, rates of PCV13-type disease had decreased by 70% (Figure 2). No significant increases in non-PCV13-type IPD have been observed in any age group since the introduction of PCV13. In late 2014, PCV13 was approved for routine use among adults aged ≥65 years. No additional declines in PCV13-type IPD were observed in adults aged ≥65 years after introduction of PCV13 in 2014. In 2020, during the COVID-19 pandemic, rates of IPD declined sharply in all age groups.19 However, in 2021–2022 rates of IPD rebounded in both children and adults (Figures 1&2).

New higher valency PCVs (PCV15, PCV20) were recommended for adults in 2021.20 PCV15 and PCV20 were also recommended for children in 2022 and 2023, respectively.2122 Additionally, in 2024, PCV21 was recommended for adults.23 With the impact of the recent COVID-19 pandemic and rapid introduction of several new vaccines in both children and adults, it is vital to continue monitoring IPD trends in the U.S. to determine the impact of these new vaccines. Up-to-date trends for U.S. IPD cases can be found on ABCs Bact Facts Interactive Data Dashboard.

Antimicrobial resistance trends

Before 1990, S. pneumoniae was almost uniformly susceptible to penicillin, allowing most clinicians to treat persons with severe infections with penicillin alone. However, during the 1990's, resistance to penicillin and to multiple classes of antibiotics spread rapidly in the United States with an increasing trend of invasive pneumococci resistant to three or more antibiotic classes (defined as S. pneumoniae isolates that are either intermediate or fully resistant to three antibiotics tested).24252627 As of 2018, CDC estimated there were 900,000 infections and 3,600 deaths associated with drug-resistant Streptococcus pneumoniae (DRSP) infections.10 Up-to-date estimates of the burden of DRSP are published as part of CDC's Antibiotic Resistance Threats Report.

Following the introduction of PCV7 into the routine childhood immunization program in 2000, the incidence of antibiotic-resistant invasive disease declined substantially among both young children and older persons due to reductions in resistant infections caused by vaccine serotypes.1628293031 Between 1998–99 and 2008, penicillin-resistant IPD rates declined 64% for children aged <5 years of age and 45% for adults aged ≥65 years.31 An increase in penicillin-resistant disease caused by serotypes not included in PCV7 was also identified during the same time period, although the magnitude of this effect remained small.28 PCVs are not expected to reduce the incidence of DRSP caused by non-vaccine type (NVT) serotypes. The prevalence of antibiotic resistance varied by geographic area both before and after PCV7 introduction, with higher prevalence noted in the southeastern United States.2425262728

During 2007–08, PCV13 non-PCV7 serotypes caused 78–97% of penicillin-resistant IPD, depending on age.31 Serotype 19A, a PCV13 non-PCV7 serotype, accounted for more than 30% of DRSP during 2005–2009 prior to PCV13 introduction.32 The introduction of PCV13 in 2010 led to further reductions in antibiotic-resistant IPD rates, particularly among serotype 19A. From 2009-2013 rates of antibiotic-resistant IPD caused by PCV13 non-PCV7 serotypes decreased by 97% among children aged <5 years, and 64% among adults aged ≥65 years.33 In 2008, the Clinical and Laboratory Standards Institute (CLSI) established new, higher minimum inhibitory concentration (MIC) breakpoints for defining pneumococcal susceptibility to parenterally administered penicillin when treating pneumococcal disease other than meningitis.34 Regardless of whether the old or new parenteral penicillin breakpoints are used, penicillin-resistant IPD caused by PCV13 serotypes has decreased substantially for all age groups.3133 However, during this period, rates of antibiotic-resistant IPD due to non-PCV13-type increased in all age groups.

Introduction of higher valency PCVs that contain additional pneumococcal serotypes (PCV15, PCV20, PCV21) is expected to further reduce the incidence of antibiotic resistant IPD. During 2014-2018, additional serotypes included in PCV15 and PCV20 (but not included in PCV13) contributed to 19% and 24% of all antibiotic-resistant IPD cases, respectively.32 Introduction of these higher valency vaccines is expected to further avert antibiotic use for outpatient bacterial respiratory infections and therefore the burden of DRSP.35

Because of a lack of rapid, sensitive, and specific diagnostic tests, acute respiratory tract infections treated in outpatient settings remains empiric. Inappropriate antibiotic use contributes to the development of DRSP. Principles have been developed to avoid unnecessary antibiotic use and emphasize appropriate selection and duration of antibiotic therapy when indicated for adults and children with upper respiratory infections.36373839 Groups of experts have provided national guidance for treating infections commonly caused by pneumococcus, such as AOM and pneumonia, considering emergence of DRSP.36373839

Importance of Surveillance

Surveillance for IPD has four main goals:

  • Characterization of national and local trends of IPD,
  • Detection of geographic and temporal changes in the prevalence of DRSP,
  • Monitoring impact of vaccines on IPD, and
  • Informing future vaccine development.

Surveillance for IPD in persons aged ≥5 years is useful to monitor the impact of the herd effects of pediatric PCV use and replacement disease. Following the introduction of new PCVs since 2021, monitoring disease trends in both children and adults is important to assess the impact of the updated vaccine recommendations.20212223

Serotyping of pneumococcal isolates can improve understanding of the vaccine impact. However, serotyping is expensive and requires specialized reagents and extensive technical training; therefore, serotyping capacity is not widely available. The use of polymerase chain reaction (PCR) or whole genome sequencing to identify pneumococcal capsular genes specific for individual capsular serotypes may be feasible for some state public health and academic research centers.4041 CDC's Streptococcus Laboratory has developed a protocol to identify pneumococcal serotypes using PCR.

Pneumococcal surveillance enables recognition of new or rare resistance patterns.42 Surveillance information can be used on the national level for research and policy development and at the state or local level to raise awareness of DRSP among healthcare providers and the general public. Surveillance data also may be useful for tracking the impact of interventions aimed at reducing unnecessary use of antimicrobial agents.

CDC's Antibiotic Resistance Laboratory Network (ARLN) program can assist state and local health departments with Clinical Laboratory Improvement Amendments (CLIA) approved serotyping and antimicrobial susceptibility testing for IPD isolates that meet certain criteria. For additional information on serotyping requests, contact ARLN@cdc.gov.

Disease Reduction Goals

Continuous surveillance is important to evaluate the impact of PCVs on the incidence of IPD, DRSP infections, and to monitor disease caused by pneumococcal serotypes not included in PCVs (i.e., replacement disease).

Disease reduction goals also focus on minimizing complications of DRSP infections through prevention and control measures. Geographic differences in antibiotic prescribing practices have been described.43 In sites where antibiotic prescribing is high, the proportion of IPD resistant to antibiotics is also high, suggesting that local prescribing practices may contribute to local resistance patterns.43

In 2003, CDC launched a national educational campaign now known as Be Antibiotics Aware: Smart Use, Best Care. The campaign provides resources to healthcare providers and the public about antibiotic resistance and how to optimize antibiotic prescribing and use. In 2014, CDC released the Core Elements of Antibiotic Stewardship to provide a set of key principles for healthcare facility leaders and healthcare providers to facilitate efforts to improve the quality of antibiotic use. The Core Elements framework has been adapted for several healthcare settings, including outpatient settings, and emphasizes the importance of appropriate management of respiratory infections.

Case Definition

Beginning in 2017, a new "probable" case classification was added to capture cases diagnosed using culture-independent diagnostic tests (CIDTs) and replaced the "suspected" case definition. The following definitions are in use for national notification of IPD in the United States.

Confirmed: Isolation of S. pneumoniae from a normally sterile site (e.g., blood, cerebrospinal fluid, or, less commonly, joint, pleural or pericardial fluid). (Event code 11723)

Probable: Identification of S. pneumoniae from a normally sterile body site by a CIDT without isolation of the bacteria.44

Confirmed and suspected cases of IPD should be reported to public health authorities within 1 week of diagnosis. CSTE also recommends certain clinical and epidemiological information be collected, including date of illness onset, clinical syndrome (e.g., pneumonia, meningitis), underlying medical conditions, type of diagnostic test used, and pneumococcal vaccination history. DRSP is no longer collected in national surveillance as a separate event from IPD.45

Laboratory Testing

Refer to Chapter 22: Laboratory Support for Surveillance of Vaccine-Preventable Diseases | Manual for the Surveillance of Vaccine-Preventable Diseases | CDC for detailed information on laboratory testing for IPD and for specific information on specimen collection and shipment.

Specimen collection

Specimen collection and shipping are important steps in obtaining laboratory diagnosis or disease confirmation. Guidelines have been published for specimen collection and handling for viral and microbiologic agents. Information is also available on using CDC laboratories as support for reference and disease surveillance; resources include:

Reporting and Case Notification

Case reporting within a jurisdiction

Each state and territory (jurisdiction) has regulations and laws governing the reporting of diseases and conditions of public health importance.46 These regulations and laws list the diseases that are to be reported, and describe those persons or institutions responsible for reporting, such as healthcare providers, hospitals, laboratories, schools, daycare and childcare facilities, and other institutions. Detailed information on reportable conditions in each jurisdiction is available through CSTE.47

Most jurisdictions currently require IPD to be reported to local or state/jurisdiction health authorities, regardless of the age of the patient or presence of drug resistance. Additional jurisdictions require reporting in limited populations, such as children <5 years of age. In jurisdictions with reporting requirements, confirmed and probable cases of IPD should be reported to state/jurisdiction or local health departments by healthcare providers, which may include clinicians, laboratories, hospitals, and pharmacies.4748 Healthcare providers should identify cases through microbiology laboratories, death certificates, hospital discharge or outpatient records, and electronic medical records. The following data are recommended for case investigation and reporting: patient's date of birth or age, the anatomic site of specimen collection, and type of infection. Other epidemiological information that is preferred includes the patient's demographic information (i.e., sex, race, and ethnicity), specimen collection date, whether the patient was hospitalized, clinical syndrome, antibiotic susceptibility, details of pneumococcal vaccination history, underlying medical conditions, outcome, and any serotyping results available (if an isolate was tested). Additional information may be collected at the direction of the state or local health department. The S. pneumoniae Surveillance Worksheet is included as Appendix 13 to serve as a guide for data collection during investigation of reported cases.

Case notification to CDC

Notifications for confirmed cases of IPD should be sent to CDC using event code 11723 in the National Notifiable Diseases Surveillance System (NNDSS).4549 The S. pneumoniae Surveillance Worksheet is included as Appendix 13, to serve as a guide for data collection to be included in case investigations and case notification to CDC. Case notification should not be delayed because of incomplete information or lack of confirmation. The jurisdiction in which the patient resides at the time of diagnosis should submit the case notification to CDC.

Vaccination

For specific information about pneumococcal vaccination, refer to the CDC website, which provides general recommendations, including vaccine use and scheduling, immunization strategies for providers, vaccine content, adverse events and reactions, vaccine storage and handling, and contraindications and precautions. A free mobile app is available to help determine patient-specific pneumococcal vaccine recommendations.

Enhancing Surveillance

Several surveillance activities may improve the detection and reporting of pneumococcal disease and the quality of the reports.

Enhancing reporting of antibiotic susceptibility results

Concern over rising resistance to antibiotics has prompted many state or local health departments to increase their focus on reporting susceptibility results. CDC has worked with jurisdiction health departments to evaluate different surveillance methods to determine which methods would enhance the reliability of surveillance data, given certain goals and resource limitations.50 Use of aggregated antibiogram data collected from all hospital laboratories within a specific area has been shown to give a relatively accurate description of the proportion of isolates that are resistant to penicillin and a limited number of other drugs.51 Such data, however, typically cannot be analyzed by age group or other factors of interest. Sentinel systems, which may collect individual reports with more details from a limited number of laboratories, can give an accurate view of resistance if designed well.52

Encouraging provider reporting

Most jurisdictions' infectious disease surveillance systems depend upon the receipt of case reports from healthcare providers and laboratories. These data are often incomplete and may not be representative of certain populations.46 It is important for healthcare providers to understand which events should be reported, and how critical accurate reporting is for control of communicable diseases. Increasing provider awareness of local rates of IPD and local reporting requirements may enhance surveillance.

Improving detection of DRSP in laboratories

Universal adoption of optimal testing methods and testing for resistance to recommended antibiotics would improve our ability to detect and monitor resistant pathogens.34

Recommended antibiotics to test for include53

  • Erythromycin
  • Penicillin
  • Trimethoprim-sulfamethoxazole
  • Cefotaxime
  • Ceftriaxone
  • Meropenem
  • Clindamycin
  • Doxycycline
  • Tetracycline
  • Levofloxacin
  • Moxifloxacin
  • Vancomycin

Streamlining reporting using electronic methods

Use of data from sources such as electronic medical records, electronic case reporting, and laboratory information management systems can significantly improve reporting speed, enhance data quality, and reduce workload.

Case Investigation

As with many respiratory pathogens, rapid, sensitive, and specific diagnostic tests are not widely available for pneumococcal disease. An assay to detect pneumococcal antigen in urine can be used to rapidly diagnose pneumococcal pneumonia and invasive pneumococcal disease like meningitis in adults. In addition, a multiplex PCR diagnostic test that detects S. pneumoniae in lower respiratory specimens is now available. Regardless, early in the course of illnesses such as pneumonia, diagnosis of S. pneumoniae infection is often presumptive and the choice of antimicrobial therapy is nearly always empiric. However, once S. pneumoniae is isolated from a normally sterile body site, antibiotic susceptibility testing results could help guide patient management. Case investigations are not usually warranted, except in outbreaks or as determined by the state health department. CDC is available during outbreaks to assist with epidemiologic and laboratory investigations. Contact pneumococcus@cdc.gov for additional information.

Resources

Authors and Suggested Citation

Ryan Gierke, MPH; Sopio Chochua, PhD, Kristin Andrejko, PhD; Lesley McGee, PhD; Miwako Kobayashi, MD, MPH

Suggested citation:

Given the variations in the timing for when chapter updates are made, a Manual edition number is no longer used. Therefore, it is recommended that the date at the top right of the web page be used in references/citations.

Content source:
National Center for Immunization and Respiratory Diseases

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Content Source:
National Center for Immunization and Respiratory Diseases (NCIRD)
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