High-Resolution Single Nucleotide Polymorphism Analysis Distinguishes Recrudescence and Reinfection in Recurrent Invasive Nontyphoidal Salmonella Typhimurium Disease
Open Access
- 7 February 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical Infectious Diseases
- Vol. 54 (7), 955-963
- https://doi.org/10.1093/cid/cir1032
Abstract
Background. Bloodstream infection with invasive nontyphoidal Salmonella (iNTS) is common and severe among human immunodeficiency virus (HIV)–infected adults throughout sub-Saharan Africa. The epidemiology of iNTS is poorly understood. Survivors frequently experience multiply recurrent iNTS disease, despite appropriate antimicrobial therapy, but recrudescence and reinfection have previously been difficult to distinguish. Methods. We used high-resolution single nucleotide polymorphism (SNP) typing and whole-genome phylogenetics to investigate 47 iNTS isolates from 14 patients with multiple recurrences following an index presentation with iNTS disease in Blantyre, Malawi. We isolated nontyphoidal salmonellae organisms from blood (n = 35), bone marrow (n = 8), stool (n = 2), urine (n = 1), and throat (n = 1) samples; these isolates comprised serotypes Typhimurium (n = 43) and Enteritidis (n = 4). Results. Recrudescence with identical or highly phylogenetically related isolates accounted for 78% of recurrences, and reinfection with phylogenetically distinct isolates accounted for 22% of recurrences. Both recrudescence and reinfection could occur in the same individual, and reinfection could either precede or follow recrudescence. The number of days to recurrence (23–486 d) was not different for recrudescence or reinfection. The number of days to recrudescence was unrelated to the number of SNPs accumulated by recrudescent organisms, suggesting that there was little genetic change during persistence in the host, despite exposure to multiple courses of antibiotics. Of Salmonella Typhimurium isolates, 42 of 43 were pathovar ST313. Conclusions. High-resolution whole-genome phylogenetics successfully discriminated recrudescent iNTS from reinfection, despite a high level of clonality within and among individuals, giving insights into pathogenesis and management. These methods also have adequate resolution to investigate the epidemiology and transmission of this important African pathogen.Keywords
This publication has 36 references indexed in Scilit:
- Rapid Pneumococcal Evolution in Response to Clinical InterventionsScience, 2011
- Community-acquired bloodstream infections in Africa: a systematic review and meta-analysisThe Lancet Infectious Diseases, 2010
- Evolutionary dynamics of Clostridium difficile over short and long time scalesProceedings of the National Academy of Sciences, 2010
- Evolution of MRSA During Hospital Transmission and Intercontinental SpreadScience, 2010
- Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotypeGenome Research, 2009
- Invasive Non‐TyphiSalmonellaDisease in AfricaClinical Infectious Diseases, 2009
- Enhanced Bayesian modelling in BAPS software for learning genetic structures of populationsBMC Bioinformatics, 2008
- Accurate whole human genome sequencing using reversible terminator chemistryNature, 2008
- High-throughput sequencing provides insights into genome variation and evolution in Salmonella TyphiNature Genetics, 2008
- RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed modelsBioinformatics, 2006