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- W3127835309 abstract "Group B streptococcus (GBS) is the leading cause of invasive neonatal disease in infants aged <90 days. Screening for maternal colonization by GBS and subsequent administration of intrapartum antimicrobial prophylaxis is the primary strategy to prevent the development of invasive neonatal disease [[1]Edmond K.M. Kortsalioudaki C. Scott S. Schrag S.J. Zaidi A.K.M. Cousens S. et al.Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis.Lancet. 2012; 379: 547-556Abstract Full Text Full Text PDF PubMed Scopus (432) Google Scholar]. Enrichment culture of rectovaginal swabs is the primary means to detect colonization; however, nucleic acid amplification tests (NAATs) of rectovaginal swabs sampled at 35–37 weeks of pregnancy and enriched in culture broth or performed directly from rectovaginal swabs sampled intrapartum have substantially improved the detection of GBS [[2]Shin J.H. Pride D.T. Comparison of three nucleic acid amplification tests and culture for detection of group B Streptococcus from enrichment broth.J Clin Microbiol. 2019; 57 (e01958-18)Crossref Scopus (16) Google Scholar,[3]Church D.L. Baxter H. Lloyd T. Larios O. Gregson D.B. Evaluation of StrepB Select Chromagar and the Fast Track Diagnostics Group B Streptococcus (GBS) real-time polymerase chain reaction assay compared to routine culture for detection of GBS during antepartum screening.J Clin Microbiol. 2017; 55: 2137-2142Crossref PubMed Scopus (8) Google Scholar]. Currently, 12 NAATs are registered at the US Food and Drug Administration (FDA; www.fda.org) to detect GBS and at least eight of them use the haemolysin cfb gene region as a diagnostic target, seven of these NAATs as the sole target (Table 1).Table 1Nucleic acid amplification tests registered at the United States Food and Drug AdministrationNAATYearTestingMethodTarget (gene)Sensitivity % (95% CI)aSensitivity and specificity as declared in the US Food and Drug Administration registration documents (available at www.fda.org).Specificity % (95% CI)aSensitivity and specificity as declared in the US Food and Drug Administration registration documents (available at www.fda.org).Xpert GBS2006DirectrtPCRcfb89 (83–93)97 (95–98)Xpert GBS LB2012EnrichmentrtPCRcfb99 (96–100)92 (90–94)BD Max GBS2012EnrichmentrtPCRcfb95 (90–98)97 (95–98)Alethia GBS2012EnrichmentLAMPNA99 (97–100)93 (92–95)AmpliVue GBS2013EnrichmentHDAatoB100 (97–100)93 (91–94)Aries GBS2016EnrichmentrtPCRcfb96 (91–98)91 (89–94)Great Basin Portrait GBS2016EnrichmentrtPCRcfb98 (93–99)96 (94–98)Solana GBS2017EnrichmentHDAatoB100 (98–100)96 (94–97)GenePOC GBS LB2017EnrichmentrtPCRcfb96 (92–98)96 (94–97)NeuMoDx GBS2018EnrichmentrtPCRpcsB97 (94–98)96 (95–97)Simplexa GBS2018EnrichmentrtPCRcfb97 (92–99)96 (93–98)Panther Fusion GBS2020EnrichmentrtPCRcfb,sip100 (98–100)97 (95–98)Abbreviations: GBS, Group B streptococcus; HDA, helicase-dependent amplification; LAMP, loop-mediated isothermal amplification; NA, not available; NAAT, nucleic acid amplification test; rtPCR, real-time polymerase chain reaction.a Sensitivity and specificity as declared in the US Food and Drug Administration registration documents (available at www.fda.org). Open table in a new tab Abbreviations: GBS, Group B streptococcus; HDA, helicase-dependent amplification; LAMP, loop-mediated isothermal amplification; NA, not available; NAAT, nucleic acid amplification test; rtPCR, real-time polymerase chain reaction. We read with great concern the interesting report by Tickler et al. [[4]Tickler I.A. Tenover F.C. Dewell S. Le V.M. Blackman R.N. Goering R.V. et al.Streptococcus agalactiae strains with chromosomal deletions evade detection with molecular methods.J Clin Microbiol. 2019; 57 (e02040-18)Crossref Scopus (5) Google Scholar] of GBS isolates with four types of chromosomal deletions in the cfb region that escaped detection by one of the registered NAATs in the USA and Ireland and had a prevalence of up to 7% at one testing site (but <1% in three other geographic locations). This was especially worrying because our national programme in Slovenia is aimed to use NAATs after enrichment as part of the national neonatal sepsis prevention strategy. In a recent study, we collected and whole-genome-sequenced all available invasive GBS isolates cultured from blood and cerebrospinal fluid in Slovenia from 2001 to 2018 (n = 101) and a selection of consecutive colonizing GBS isolates cultured from screening rectovaginal swabs sampled at 35–37 weeks of pregnancy from 2018 (n = 70) [[5]Perme T. Golparian D. Bombek-Ihan M. Genomic and phenotypic characterisation of invasive neonatal and colonising group B Streptococcus isolates from Slovenia, 2001–2018.BMC Infect Dis. 2020; 20: 958Crossref PubMed Scopus (4) Google Scholar]. Subsequently, we performed in silico analyses from draft genomes of the cfb gene and a 1.5-kbp region downstream. Extracted sequences were aligned with MUSCLE and checked for the deletions described in cfb. All our Slovenian isolates (n = 171) contained the complete cfb gene with a conserved sequence, i.e. containing only eight sites with single nucleotide polymorphisms (six synonymous and two non-synonymous) and no deletions. Furthermore, no deletions in cfb were detected in the 1.5-kbp downstream region in any of the isolates. Strains of GBS with diagnostic-escape cfb deletions were not found in Slovenia and these strains may still be rare in many countries. However, diagnostic selective pressures may favour such mutations and potentially contribute to the selection and emergence of mutated strains, especially when the majority of the available NAATs target the same chromosomal gene (cfb). Additionally, Tickler et al. [[4]Tickler I.A. Tenover F.C. Dewell S. Le V.M. Blackman R.N. Goering R.V. et al.Streptococcus agalactiae strains with chromosomal deletions evade detection with molecular methods.J Clin Microbiol. 2019; 57 (e02040-18)Crossref Scopus (5) Google Scholar] found that the diagnostic-escape deletions in cfb appeared in several different GBS strains that appeared in geographically distinct locations, indicating that the deletion events had occurred independently of each other and in different genomic backgrounds. It cannot be excluded that these deletions affect, especially decrease, the fitness of the strains and/or impact the virulence of GBS. Notably, Tickler et al. [[4]Tickler I.A. Tenover F.C. Dewell S. Le V.M. Blackman R.N. Goering R.V. et al.Streptococcus agalactiae strains with chromosomal deletions evade detection with molecular methods.J Clin Microbiol. 2019; 57 (e02040-18)Crossref Scopus (5) Google Scholar] mainly assessed colonizing GBS isolates, whereas the majority of our examined GBS isolates were invasive [[5]Perme T. Golparian D. Bombek-Ihan M. Genomic and phenotypic characterisation of invasive neonatal and colonising group B Streptococcus isolates from Slovenia, 2001–2018.BMC Infect Dis. 2020; 20: 958Crossref PubMed Scopus (4) Google Scholar]. Furthermore, many (n = 91) of our isolates belonged to the hypervirulent multilocus sequence typing clonal complex 17 (CC-17), which was exceedingly conserved genomically with few recombination prone regions that may indicate that CC-17 has experienced an evolutionary selection to optimize its genome and increase its fitness. CC-17 isolates were largely absent in the report by Tickler et al. [[4]Tickler I.A. Tenover F.C. Dewell S. Le V.M. Blackman R.N. Goering R.V. et al.Streptococcus agalactiae strains with chromosomal deletions evade detection with molecular methods.J Clin Microbiol. 2019; 57 (e02040-18)Crossref Scopus (5) Google Scholar]. Consequently, it cannot be excluded that the cfb mutants are more associated with carriage than invasive disease. Even though isolates with cfb mutations that could potentially escape detection with commercially available NAATs were absent in our Slovenian survey, it is essential to be vigilant for the possible emergence of such strains in Slovenia and other countries. Additional studies in other geographic regions are imperative. In Slovenia, to ensure the most sensitive GBS screening, we will use a combination of direct plating on a selective chromogenic agar with high sensitivity and NAAT detection from enrichment broth. Furthermore, international surveillance of diagnostic-escape GBS strains is crucial and quality controls and external quality assessments should be sufficiently robust to detect these strains. Finally, all GBS diagnostic NAATs may need to consider two gene targets, as currently used in one of the NAATs registered by the US Food and Drug Administration (Table 1), to overcome diagnostic escape in GBS screening, in particular when NAATs are used as the sole diagnostic technique in replacement of GBS culture, which is already the case in numerous centres in Europe. All authors report no conflicts of interest relevant to this article. The study was supported by the Örebro County Council Research Committee and the Foundation for Medical Research at Örebro University Hospital, Örebro, Sweden." @default.
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- W3127835309 title "Lack of diagnostic-escape mutants of group B streptococcus in Slovenia" @default.
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