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    High-Resolution Single Nucleotide Polymorphism Analysis Distinguishes Recrudescence and Reinfection in Recurrent Invasive Nontyphoidal Salmonella Typhimurium Disease

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    Author
    Okoro, CK; Kingsley, RA; Quail, MA; Kankwatira, AM; Feasey, NA; Parkhill, J; Dougan, G; Gordon, MA
    Date
    2012-04-01
    Source Title
    Clinical Infectious Diseases
    Publisher
    OXFORD UNIV PRESS INC
    University of Melbourne Author/s
    Dougan, Gordon
    Affiliation
    Microbiology and Immunology
    Metadata
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    Document Type
    Journal Article
    Citations
    Okoro, C. K., Kingsley, R. A., Quail, M. A., Kankwatira, A. M., Feasey, N. A., Parkhill, J., Dougan, G. & Gordon, M. A. (2012). High-Resolution Single Nucleotide Polymorphism Analysis Distinguishes Recrudescence and Reinfection in Recurrent Invasive Nontyphoidal Salmonella Typhimurium Disease. CLINICAL INFECTIOUS DISEASES, 54 (7), pp.955-963. https://doi.org/10.1093/cid/cir1032.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/260635
    DOI
    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.

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