Investigation of Respiratory Syncytial Virus Outbreak on an Adult Stem Cell Transplant Unit by Use of Whole-Genome Sequencing

ABSTRACTA viral whole-genome sequencing (WGS) strategy, based on PCR amplification followed by next-generation sequencing, was used to investigate a nosocomial respiratory syncytial virus-B (RSV-B) outbreak in a hematology-oncology and stem cell transplant unit. RSV-B genomes from 16 patients and health care workers (HCWs) suspected to be involved in the outbreak were compared to RSV-B genomes that were acquired from outpatients during the same time period but epidemiologically unrelated to the outbreak. Phylogenetic analysis of the whole genome identified a cluster of 11 patients and HCWs who had an identical RSV-B strain which was clearly distinct from strains recovered from individuals unrelated to the outbreak. Sequence variation of the glycoprotein (G) gene alone was insufficient to distinguish the outbreak strains from the outbreak-unrelated strains, thereby demonstrating that WGS is valuable for local outbreak investigation.

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Use of whole-genome sequencing in the molecular investigation of care-associated HCoV-OC43 infections in a hematopoietic stem cell transplant unit

Journal of Clinical Virology ◽

10.1016/j.jcv.2019.104206 ◽

2020 ◽

Vol 122 ◽

pp. 104206 ◽

Cited By ~ 3

Author(s):

Delphine Beury ◽

Léa Fléchon ◽

Florence Maurier ◽

Ségolène Caboche ◽

Jean-Stéphane Varré ◽

...

Keyword(s):

Stem Cell ◽

Whole Genome Sequencing ◽

Hematopoietic Stem Cell ◽

Genome Sequencing ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Whole Genome ◽

Hematopoietic Stem ◽

Molecular Investigation

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Respiratory syncytial virus outbreak on an adult stem cell transplant unit

American Journal of Infection Control ◽

10.1016/j.ajic.2016.03.075 ◽

2016 ◽

Vol 44 (9) ◽

pp. 1022-1026 ◽

Cited By ~ 13

Author(s):

Sean G. Kelly ◽

Kristen Metzger ◽

Maureen K. Bolon ◽

Christina Silkaitis ◽

Mary Mielnicki ◽

...

Keyword(s):

Stem Cell ◽

Respiratory Syncytial Virus ◽

Stem Cell Transplant ◽

Adult Stem Cell ◽

Cell Transplant ◽

Syncytial Virus

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Using Whole Genome Sequences to Investigate Adenovirus Outbreaks, Including Five Deaths in a Haematopoietic Stem Cell Transplant Unit

10.1101/2020.11.26.20239111 ◽

2020 ◽

Author(s):

Chloe E. Myers ◽

Charlotte J. Houldcroft ◽

Sunando Roy ◽

Ben K. Margetts ◽

Timothy Best ◽

...

Keyword(s):

Stem Cell ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Stem Cell Transplant ◽

Haematopoietic Stem Cell Transplant ◽

Haematopoietic Stem Cell ◽

Infection Prevention And Control ◽

Clinical Samples ◽

Cell Transplant ◽

Whole Genome

AbstractBackgroundHuman mastadenoviruses (HAdV) are associated with significant morbidity and mortality amongst the immunocompromised population. A recent surge in HAdV cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate.MethodsTo gain a complete transmission picture, we compared outbreak and non-outbreak sequences (54 sequences from 37 patients) with GenBank sequences and our own database of previously sequenced HAdVs (132 sequences from 37 patients). An improved bait set for WGS was used. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships paired with epidemiological data from routine Infection, Prevention and Control (IPC) activity.ResultsNine monophyletic clusters were identified, seven of which were corroborated by epidemiological evidence and by comparison of single nucleotide polymorphisms. Two incomplete patient clusters were identified by IPC over the same time period. Of the five patients who died, one had a mixed HAdV infection and two were the source of transmission events.ConclusionsThe clinical consequences of unmitigated HAdV transmission events are high. Focusing on two high risk wards using WGS we identified six transmission events, over prolonged periods, that would have gone unnoticed using traditional polymerase chain reaction and epidemiology. Mixed infection is frequent (10% of patients), providing a sentinel source of recombination and superinfection. Immunosuppressed patients harbouring a high rate of HAdV positivity require comprehensive surveillance. As a consequence of these findings, HAdV WGS is being incorporated routinely into a clinical algorithm to prevent transmission and influence IPC policy in real-time.SummaryWhole genome sequencing of adenovirus, direct from clinical samples, can be used to identify cryptic health care associated transmission events, and to resolve transmission suspected by traditional epidemiology. It can also identify mixed genotype infections in immunocompromised patient populations.

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Carbapenem-resistant Klebsiella pneumoniae colonization and infection is associated with lower overall survival in a cohort of haematopoietic stem-cell transplantation patients: mechanism of resistance and virulence by whole-genome sequencing

Journal of Medical Microbiology ◽

10.1099/jmm.0.001422 ◽

2021 ◽

Vol 70 (10) ◽

Author(s):

Hermes Ryoiti Higashino ◽

Ana Paula Marchi ◽

Roberta Cristina Ruedas Martins ◽

Laina Bubach Carvalho ◽

Lauro Vieira Perdigão Neto ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Klebsiella Pneumoniae ◽

Genome Sequencing ◽

Stem Cell Transplant ◽

Haematopoietic Stem Cell ◽

Cell Transplant ◽

Whole Genome ◽

Carbapenem Resistant ◽

Overall Mortality

Carbapenem-resistant Klebsiella pneumoniae (CRK) infections are a growing concern in immunocompromised patients. The aim of the present study was to evaluate the impact of CRK colonization and infection in overall mortality for haematopoietic stem-cell transplant (HSCT) patients. We also aimed to investigate resistance and virulence profiles of CRK isolates and assess their epidemiological and genetic relatedness. Patients in the HSCT unit were screened for colonization with CRK with weekly rectal swab or stool cultures and placed under contact precautions. We defined CRK colonization as positive culture from a swab or stool sample grown in MacConkey agar with meropenem at 1 µg ml−1. Demographic and clinical data were retrieved from the patients’ charts and electronic records. According to resistance mechanisms and pulsed field gel electrophoresis profile, isolates were selected based on whole-genome sequencing (WGS) using MiSeq Illumina. Outcomes were defined as overall mortality (death up to D+100), and infection-related death (within 14 days of infection). We report a retrospective cohort of 569 haematopoietic stem-cell transplant patients with 105 (18.4 %) CRK colonizations and 30 (5.3 %) infections. blaKPC was the most frequent carbapenemase in our cohort with three isolates co-harbouring blaKPC and blaNDM. We found no difference in virulence profiles from the CRK isolates. There were also no significant differences in virulence profiles among colonization and infection isolates regarding genes encoding for type 1 and 3 fimbriae, siderophores, lipopolysaccharide and colibactin. In clonality analysis by PFGE and WGS, isolates were polyclonal and ST340 was the most prevalent. Overall survival at D+100 was 75.4 % in in CRK-colonized (P=0.02) and 35.7 % in infected patients and significantly lower than non-colonized patients (85.8 %; P<0.001). We found a higher overall mortality associated with colonization and infection; KPC was the main resistance mechanism for carbapenems. The polyclonal distribution of isolates and findings of CRK infection in patients not previously colonized suggest the need to reinforce antibiotic stewardship.

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