Impact of crowding on the antibiotic resistance of carriage isolates of Streptococcus pneumoniae from healthy Peruvian children in the pre-PCV7 period Öffentlichkeit

Abstract

Background: Streptococcus pneumoniae is a highly transmissible upper respiratory pathogen that is a major contributor to child mortality, especially within developing countries. Conjugate vaccines, such as PCV7, have been effective in reducing pneumococcal burden worldwide, but vaccine-type replacement, growing antimicrobial resistance, and poor vaccine access in developing areas indicate that additional solutions are needed. Understanding how environmental factors influence pneumococcal dynamics in carriers may be useful in creating effective interventions that complement vaccination. The purpose of this study was (1) to describe molecular aspects and invasive disease potential of S. pneumoniae carriage isolates collected from healthy young children between 2007-2009 and (2) determine how exposure to crowded environments and molecular factors promote multidrug-resistant S. pneumoniae carriage in healthy young children in Peru.

Methods: This cross-sectional study utilized whole genome sequencing to describe the serotype distribution, genetic lineages, and antibiotic resistance profiles of carriage S. pneumoniae isolates (n=508) collected from healthy children aged 2-24 months in seven Peruvian cities between 2007-2009. The invasive disease potential (IDP) of each serotype was quantified using a subset of the carriage isolates from Lima (n=259) and invasive-disease isolates from a separate study conducted in Lima (n=133) [2]. Risk factors for the carriage of multidrug-resistant S. pneumoniae were assessed using logistic regression models that dichotomized the number of antibiotic classes a strain was resistant into ≥3 classes and <3 classes.

Results: Among 508 carriage isolates, 52.6% had a PCV7 serotype, 40.4% could be linked to a PMEN clonal complex, and 22.4% were resistant to at least three classes of antibiotics. Serotypes 14 and 6B were found to have an IDP>1.0 at α=0.05 and represented 21.5% (n=109) of all carriage isolates. Multivariate logistic regression determined that being a PCV7 serotype carrier (OR=11.83, p<0.0001), daycare attendance (OR=4.92, p=0.031), and living in a highly urban area (OR=2.86, p=0.008) were significant risk factors for children being carriers of multidrug-resistant S. pneumoniae.

Conclusions: S. pneumoniae carriage strains in Peruvian children before PCV7 implementation were genetically diverse and highly drug-resistant. Carriage of multidrug-resistant S. pneumoniae in young children can be partly attributable to exposure to crowded environments and carrying a vaccine-type strain.

Table of Contents

 

I. INTRODUCTION………………………………………………………………………………….1

II. METHODS…………………………………………………………………………………...........8

                Project aims……………………………………………………………………………...8

                Carriage isolate acquisition ……………………………………………………………...9

                Whole genome sequencing……………………………………………………………....10

                Antibiotic resistance determination……………………………………………………...11

                Invasive disease potential determination………………………………………………...12

                Statistical analysis…………………………………………………………………….....13

III. RESULTS………………………………………………………………………………………….14

                ST and serotype prevalence……………………………………………………………....14

                Antibiotic resistance prediction………………………………………………………......15

                Invasive disease potential………………………………………………………………...15

                Model results…………………………………………………………………………….16

IV. DISCUSSION………………………………………………………………………………….......17

                Serotypes and lineages……………………………………………………………….......17

                Antibiotic resistance……………………………………………………………………..18

                Invasive disease potential………………………………………………………………...19

                Crowded environments and molecular determinants of MDR…………………………....20

                Conclusions and future recommendations……………………………………..................22

V. REFERENCES……………………………………………………………………………..............24

VI. TABLES AND FIGURES………………………………………………………………………...28

VII. APPENDIX…………………………………………………………………………………….....39

About this Master's Thesis

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Rollins School of Public Health
Department	Environmental Health
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Environmental Health Biology, Microbiology Health Sciences, Epidemiology
Stichwort	pneumococcal carriage MDR Peru whole genome sequencing pneumococcal conjugate vaccine sequence types children Crowding Streptococcus pneumoniae PMEN PCV Invasive Disease Potential antibiotic resistance NCIRD siblings Crowded environments Daycare IDP multidrug resistance clonal complex respiratory disease invasive pneumococcal disease CDC PCV7
Committee Chair / Thesis Advisor	McGee, Lesley, CDC Levy, Karen, Emory University
Committee Members	Liu, Yang, Emory University Tolbert, Paige, Emory University
Partnering Agencies	CDC

Zuletzt geändert

Primary PDF

Thumbnail	Title	Date Uploaded	Actions
	Impact of crowding on the antibiotic resistance of carriage isolates of Streptococcus pneumoniae from healthy Peruvian children in the pre-PCV7 period ()	2018-04-23 13:35:33 -0400	Press to Select an action Download

Supplemental Files

Thumbnail	Title	Date Uploaded	Actions