Understanding Post-Vaccine Pneumococcal Evolution and Antimicrobial Resistance in the United States Pubblico

Abstract

Purpose: S. pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia in children under five years of age worldwide and is responsible for an estimated 1.6 million deaths per year in all ages. Two serotype-specific pneumococcal vaccines, PCV7 and PCV13, were introduced in the United States for routine immunization in children under two years of age in 2000 and 2010, respectively. The purpose of this study was to examine changes in invasive pneumococci following the introduction of these vaccines in the US.

Methods: We used laboratory and demographic data of 13,383 cases of IPD collected by the Active Bacterial Core surveillance program from eight surveillance areas in 1998-1999, 2009, and 2012 to estimate rates and antimicrobial resistance in IPD

Results: The overall rates of invasive disease fell from 21.9 to 12.8 cases per 100,000 persons following PCV7 and continued to drop to 9.2 cases per 100,000 persons following PCV13. These declines in rate were due to substantial drops in IPD caused by vaccine-type serotypes and were observed across all age groups. PCV7-serotype IPD dropped from 13.8 to 0.5 cases per 100,000 persons post-PCV7 and PCV13-serotype IPD dropped from 6.5 to 2.6 cases per 100,000 persons post-PCV13. A noticeable increase from 8.2 to 12.3 cases per 100,000 persons was observed in non-PCV7-serotype IPD following PCV7 with 19A as the predominant serotype. No significant increase was seen in non-PCV13-serotype IPD following PCV13. Though overall incidence decreased, the proportion of strains showing antimicrobial resistance to 7 antimicrobial drugs rose dramatically by 9 years following PCV7 but dropped or remained the same for 13 antimicrobial drugs following PCV13. MDR proportion followed a similar pattern.

Conclusions: PCV7 led to a substantial reduction in IPD both in young children and non-vaccinated children. However, we saw indications of serotype replacement following PCV7, characterized by increased drug-resistance largely due to the expansion of highly-resistant strains, particularly within serotype 19A. Targeting of these serotypes by PCV13 has led to a continued decline in invasive disease and antimicrobial resistance. Though serotype replacement was not detected following PCV13, a longer follow-up may reveal the expansion of non-PCV13 serotypes.

Table of Contents

LIST OF TABLES

1

LIST OF FIGURES

4

ABBREVIATIONS

5

BACKGROUND AND SIGNIFICANCE

6

METHODS

9

RESULTS

12

DISCUSSION

24

STRENGTHS & WEAKNESSES

27

PUBLIC HEALTH IMPLICATIONS

28

FUTURE DIRECTION

28

TABLES

30

FIGURES

53

REFERENCES

61

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Global Epidemiology - MPH & MSPH
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Biology, Microbiology
Parola chiave	Streptococcus pneumoniae antimicrobial resistance vaccine pneumococcal
Committee Chair / Thesis Advisor	Klugman, Keith P, Emory University
Committee Members	McGee, Lesley, Emory University
Partnering Agencies	CDC

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