XDR-TB transmission in London: Case management and contact tracing investigation assisted by early whole genome sequencing

Abstract Yukon Territory (YT) is a remote region in northern Canada with ongoing spread of tuberculosis (TB). To explore the utility of whole genome sequencing (WGS) for TB surveillance and monitoring in a setting with detailed contact tracing and interview data, we used a mixed-methods approach. Our analysis included all culture-confirmed cases in YT (2005–2014) and incorporated data from 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping, WGS and contact tracing. We compared field-based (contact investigation (CI) data + MIRU-VNTR) and genomic-based (WGS + MIRU-VNTR + basic case data) investigations to identify the most likely source of each person's TB and assessed the knowledge, attitudes and practices of programme personnel around genotyping and genomics using online, multiple-choice surveys (n = 4) and an in-person group interview (n = 5). Field- and genomics-based approaches agreed for 26 of 32 (81%) cases on likely location of TB acquisition. There was less agreement in the identification of specific source cases (13/22 or 59% of cases). Single-locus MIRU-VNTR variants and limited genetic diversity complicated the analysis. Qualitative data indicated that participants viewed genomic epidemiology as a useful tool to streamline investigations, particularly in differentiating latent TB reactivation from the recent transmission. Based on this, genomic data could be used to enhance CIs, focus resources, target interventions and aid in TB programme evaluation.

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Countrywide implementation of whole genome sequencing: an opportunity to improve tuberculosis management, surveillance and contact tracing in low incidence countries

European Respiratory Journal ◽

10.1183/13993003.00387-2018 ◽

2018 ◽

Vol 51 (6) ◽

pp. 1800387 ◽

Cited By ~ 14

Author(s):

Andrea Maurizio Cabibbe ◽

Alberto Trovato ◽

Maria Rosaria De Filippo ◽

Arash Ghodousi ◽

Laura Rindi ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Contact Tracing ◽

Whole Genome ◽

Low Incidence

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The largest prison outbreak of TB in Western Europe investigated using whole-genome sequencing

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.21.0033 ◽

2021 ◽

Vol 25 (6) ◽

pp. 491-497

Author(s):

E. Roycroft ◽

M. M. Fitzgibbon ◽

D. M. Kelly ◽

M. Scully ◽

A. M. McLaughlin ◽

...

Keyword(s):

Public Health ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Western Europe ◽

Education Programme ◽

Multidrug Resistant ◽

Case Finding ◽

Contact Tracing ◽

Whole Genome ◽

Nucleotide Polymorphisms

BACKGROUND: In March 2011, the Department of Public Health East in Ireland were notified of two cases of TB in two prisoners sharing a cell. We define the resulting outbreak and highlight the role of public health and laboratory-based molecular epidemiology in mapping and control of a prison outbreak.METHODS: Cases were identified through clinical presentation, contact tracing, case-finding exercise or enhanced laboratory surveillance. Mycobacterium tuberculosis isolates were genotyped and underwent whole-genome sequencing (WGS).RESULTS: Of the 34 cases of TB linked to the outbreak, 27 were prisoners (79%), 4 prison officers (12%) and 3 community cases (9%). M. tuberculosis was isolated from 31 cases (culture positivity: 91%). A maximum of six single-nucleotide polymorphisms separated the isolates, with 22 being identical, suggestive of a highly infectious ‘super-spreader´ within the prison. Isolates belonged to the Beijing sub-lineage, and were susceptible to first-line anti-TB agents. A case-finding exercise incidentally detected a prisoner with multidrug-resistant TB. Of the 143 prison officers screened, 52% had latent TB infection. Litigation costs exceeded five million euros.CONCLUSION: This constitutes the largest prison outbreak of TB in Western Europe investigated using WGS. A robust prison entry TB screening and education programme is required to effect better TB control, and prevent future outbreaks and attendant litigation.

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Whole-Genome Sequencing: The Key to Unlocking a Nosocomial Outbreak of Coronavirus Disease 2019 (COVID-19)

Antimicrobial Stewardship & Healthcare Epidemiology ◽

10.1017/ash.2021.98 ◽

2021 ◽

Vol 1 (S1) ◽

pp. s51-s51

Author(s):

Lindsey Gottlieb ◽

Emilia Sordillo ◽

Harm van Bakel ◽

Barbara Smith ◽

Bernard Camins ◽

...

Keyword(s):

New York ◽

High Risk ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Positive Test ◽

Contact Tracing ◽

Whole Genome ◽

Nosocomial Outbreak ◽

Primary Case ◽

Eye Protection

Background: Accurately tracing nosocomial transmission of coronavirus disease 2019 (COVID-19) is critical to developing effective infection prevention policies. Given the high prevalence and variable incubation period of SARS-CoV-2 infection, the utility of traditional contact tracing is limited. We describe a nosocomial outbreak in which whole-genome sequencing (WGS) was pivotal to identifying the primary case. Methods: This study was conducted at a New York City academic hospital. The index case was identified on August 13, 2020, and the last case on September 9, 2020. Hospital policy required all inpatients to be screened for COVID-19 on admission by SARS-CoV-2 molecular amplification testing. All healthcare workers (HCWs) were required to wear masks and eye protection for patient care. After a patient (patient 1), who tested SARS-CoV-2 negative on admission, was positive on preprocedure screening on hospital day 9, contact tracing was initiated. Two patients (patients 2 and 3) and 13 HCWs with high-risk exposures (HREs) to patient 1 were quarantined and referred for testing. Additional surveillance testing was performed on 18 inpatients and 84 HCWs on the affected unit. Patients 2 and 3 and 3 HCWs (HCW-1, -2, and -3), only 1 of whom had a high-risk exposure to patient 1, tested positive. WGS was performed to further investigate this outbreak. Results: The outbreak variant (clade 20A) was found in samples from 6 patients and 2 HCWs. Patients 2 and 3 were roommates of patient 1 in the 2 days before patient 1’s positive test, and they did not consistently wear masks in the room. HCW-1 placed a peripheral IV in patient 1 the day before patient 1’s positive test without wearing eye protection. Four additional cases in this cluster (patients 4–6 and HCW-4) were identified by surveillance WGS of positive tests. A review indicated that patient 1 was located ~3 m (~10 feet) away from patient 4 in the emergency department (ED) for 6 hours on hospital day 1, when the admission SARS-CoV-2 test from patient 4 was not positive. No epidemiologic link was found to patient 5 or 6 or HCW-4. The specimen from HCW-2 was inadequate for WGS. The specimen from HCW-3 was not linked to this cluster. Conclusions: This complex nosocomial outbreak highlights the importance of WGS in understanding transmission events. Patient 4 was not identified by traditional contact tracing but was linked to patient 1 and was recognized as the primary case through WGS, having likely infected patient 1 in the ED. Based on these findings, we focused our corrective actions on more promptly isolating suspected COVID-19 cases in the ED, increasing inpatient masking, and improving HCW adherence to universal eye protection.Funding: NoDisclosures: None

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Propagation of a hospital-associated cluster of COVID-19 in Malaysia

BMC Infectious Diseases ◽

10.1186/s12879-021-06894-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Diane Woei-Quan Chong ◽

Vivek Jason Jayaraj ◽

Chiu-Wan Ng ◽

I-Ching Sam ◽

Mas Ayu Said ◽

...

Keyword(s):

Risk Assessment ◽

Whole Genome Sequencing ◽

Healthcare Worker ◽

Genome Sequencing ◽

Control Measures ◽

Contact Tracing ◽

Infection Prevention And Control ◽

Whole Genome ◽

Epidemiological Investigation ◽

Hospital Population

Abstract Background Hospitals are vulnerable to COVID-19 outbreaks. Intrahospital transmission of the disease is a threat to the healthcare systems as it increases morbidity and mortality among patients. It is imperative to deepen our understanding of transmission events in hospital-associated cases of COVID-19 for timely implementation of infection prevention and control measures in the hospital in avoiding future outbreaks. We examined the use of epidemiological case investigation combined with whole genome sequencing of cases to investigate and manage a hospital-associated cluster of COVID-19 cases. Methods An epidemiological investigation was conducted in a University Hospital in Malaysia from 23 March to 22 April 2020. Contact tracing, risk assessment, testing, symptom surveillance, and outbreak management were conducted following the diagnosis of a healthcare worker with SARS-CoV-2 by real-time PCR. These findings were complemented by whole genome sequencing analysis of a subset of positive cases. Results The index case was symptomatic but did not fulfill the initial epidemiological criteria for routine screening. Contact tracing suggested epidemiological linkages of 38 cases with COVID-19. Phylogenetic analysis excluded four of these cases. This cluster included 34 cases comprising ten healthcare worker-cases, nine patient-cases, and 15 community-cases. The epidemic curve demonstrated initial intrahospital transmission that propagated into the community. The estimated median incubation period was 4.7 days (95% CI: 3.5–6.4), and the serial interval was 5.3 days (95% CI: 4.3–6.5). Conclusion The study demonstrated the contribution of integrating epidemiological investigation and whole genome sequencing in understanding disease transmission in the hospital setting. Contact tracing, risk assessment, testing, and symptom surveillance remain imperative in resource-limited settings to identify and isolate cases, thereby controlling COVID-19 outbreaks. The use of whole genome sequencing complements field investigation findings in clarifying transmission networks. The safety of a hospital population during this COVID-19 pandemic may be secured with a multidisciplinary approach, good infection control measures, effective preparedness and response plan, and individual-level compliance among the hospital population.

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Genomic investigation of the coronavirus disease-2019 outbreak in the Republic of Korea

Scientific Reports ◽

10.1038/s41598-021-85623-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jeong-Min Kim ◽

Sung Yong Park ◽

Daesang Lee ◽

Jun-Sub Kim ◽

Youngjoon Park ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Close Contact ◽

Religious Group ◽

Contact Tracing ◽

Whole Genome ◽

Genome Sequences ◽

South Korean Government ◽

South Korean ◽

The Republic

AbstractThe South Korean government effectively contained the coronavirus disease-2019 (COVID-19) outbreak primarily associated with a religious group. We conducted SARS-CoV-2 whole genome sequencing of 66 cases to investigate connections among the initial South Korean cases and the religious group outbreak. We assessed the accuracy of genomic investigation by comparing the whole genome sequences with comprehensive contact tracing records. Five transmission clusters were estimated among the 15 initial cases. The six close-contact cases and two potential exposure pairs identified by contact tracing showed two or fewer nucleotide base differences. Additionally, we identified two transmission clusters that were phylogenetically distinct from the initial clusters, sharing common G11083T, G26144T, and C14805T markers. The strain closest to the two additional clusters was identified from a pair of identical sequences isolated from individuals who traveled from Wuhan to Italy. Our findings provide insights into the origins of community spread of COVID-19.

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179. Identification and Whole Genome Sequencing Analysis of an Oxacillinase (OXA)-48-like-producing Acinetobacter baumannii Outbreak in California, January-May 2021

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.179 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S109-S110

Author(s):

Diana Holden ◽

Matthew Sylvester ◽

John Crandall ◽

Fengfeng Xu ◽

Emily C Schneider ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Acinetobacter Baumannii ◽

Genome Sequencing ◽

The United States ◽

Contact Tracing ◽

Resistant Organism ◽

Sentinel Site ◽

Whole Genome ◽

Sequencing Analysis ◽

Care Hospital

Abstract Background In January 2021, a California acute care hospital (ACH A), a sentinel site for Acinetobacter baumannii (AB) surveillance, identified OXA-48-like-carbapenemase producing (CP) AB in a patient admitted from a ventilator-equipped skilled nursing facility (vSNF A); OXA-48-like AB had not been previously reported in the United States. Methods Our investigation included onsite infection control (IC) assessments, contact tracing, and point prevalence surveys (PPS) at vSNF A. The Antibiotic Resistance (AR) Laboratory Network performed carbapenemase testing on AB isolates (including those from ACH A) and PPS swabs. A case was defined as a patient with an OXA-48-like AB isolate, or an epidemiologically-linked patient with an OXA-48-like gene detected via screening. We performed whole genome sequencing (WGS) of OXA-48-like AB and other CP organisms on the Illumina MiSeq and Oxford Nanopore MinION for short and long read sequencing, respectively. Results Since January 2021, we have identified five OXA-48-like AB cases (including the index), six OXA-48-like cases (no organism recovered), and six patients with other CP organisms at ACH A and vSNF A. Since August 2019, vSNF A has concurrently been experiencing an OXA-109 AB outbreak. A second vSNF A patient, Patient 2, who overlapped with the index patient, had OXA-48-like Klebsiella pneumoniae (KP) (November 2019) and OXA-109 AB (May 2020) isolates. WGS of the index patient’s AB and Patient 2’s KP isolates identified a rare OXA-48-like gene located on the AB chromosome and a KP plasmid. The OXA-48-like AB was also carrying an OXA-109 gene, and hqSNP analysis indicated it varied by 9-44 single-nucleotide polymorphisms (SNPs) from 14 OXA-109 AB isolates linked to that outbreak, and 0-3 SNPs from the other OXA-48-like AB case isolates. Figure 1. Phylogenetic Tree Comparison of OXA-109 AB and OXA-48-like AB Isolates Figure 2. Epidemic Curve of OXA-109 AB, OXA-48-like AB, and Other CP Organism Cases, 2019-2021 Conclusion The first reported case of OXA-48-like AB in the US was identified through public health sentinel laboratory surveillance, allowing prompt response to contain spread of a novel multidrug-resistant organism (MDRO). WGS detected a rare OXA-48-like gene in AB and KP and provides evidence for possible interspecies transfer of this gene from KP to AB through plasmid transfer followed by chromosomal integration. Disclosures All Authors: No reported disclosures

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Sequencing SARS-CoV-2 from Antigen Tests

10.1101/2021.07.14.21260291 ◽

2021 ◽

Author(s):

Ashley E Nazario-Toole ◽

Holly M Nguyen ◽

Hui Xia ◽

Dianne N Frankel ◽

John W Kieffer ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Diagnostic Testing ◽

Whole Genome Sequence ◽

Contact Tracing ◽

Whole Genome ◽

Rt Pcr ◽

Surveillance Strategy ◽

Viral Transport ◽

Antigen Tests

Genomic surveillance empowers agile responses to SARS-CoV-2 by enabling scientists and public health analysts to issue recommendations aimed at slowing transmission, prioritizing contact tracing, and building a robust genomic sequencing surveillance strategy. Since the start of the pandemic, real time RT-PCR diagnostic testing from upper respiratory specimens, such as nasopharyngeal (NP) swabs, has been the standard. Moreover, respiratory samples in viral transport media are the ideal specimen for SARS-CoV-2 whole-genome sequencing (WGS). In early 2021, many clinicians transitioned to antigen-based SARS-CoV-2 detection tests, which use anterior nasal swabs for SARS-CoV-2 antigen detection. Despite this shift in testing methods, the need for whole-genome sequence surveillance remains. Thus, we developed a workflow for whole-genome sequencing with antigen test-derived swabs as an input rather than nasopharyngeal swabs. In this study, we use excess clinical specimens processed using the BinaxNOW COVID-19 Ag Card. We demonstrate that whole-genome sequencing from antigen tests is feasible and yields similar results from RT-PCR-based assays utilizing a swab in viral transport media.

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Genomic Investigation of the Coronavirus Disease-2019 Outbreak in the Republic of Korea

10.21203/rs.3.rs-65856/v1 ◽

2020 ◽

Author(s):

Jeong-Min Kim ◽

Sung Yong Park ◽

Daesang Lee ◽

Jun-Sub Kim ◽

Youngjoon Park ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Close Contact ◽

Contact Tracing ◽

Whole Genome ◽

Genome Sequences ◽

South Korean Government ◽

South Korean ◽

Nucleotide Base ◽

The Republic

Abstract The South Korean government effectively contained the coronavirus disease-2019 (COVID-19) outbreak primarily associated with the Shincheonji religious group. We conducted SARS-CoV-2 whole genome sequencing of 66 cases to investigate connections among the initial South Korean cases and the Shincheonji outbreak. We assessed the accuracy of genomic investigation by comparing the whole genome sequences with comprehensive contact tracing records. Five transmission clusters were estimated among the 15 initial cases. The six close-contact cases and two potential exposure pairs identified by contact tracing showed two or fewer nucleotide base differences. Additionally, we identified two transmission clusters from the Shincheonji outbreak that were phylogenetically distinct from the initial clusters, sharing common G11083T, G26144T, and C14805T markers. The strain closest to the two Shincheonji clusters was identified from a pair of identical sequences isolated from a couple who traveled from Wuhan to Milano. Our findings provide insights into the origins of community spread of COVID-19.

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Genomic Investigation of the Coronavirus Disease-2019 Outbreak in the Republic of Korea

10.21203/rs.3.rs-65856/v2 ◽

2020 ◽

Author(s):

Jeong-Min Kim ◽

Sung Yong Park ◽

Daesang Lee ◽

Jun-Sub Kim ◽

Youngjoon Park ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Close Contact ◽

Religious Group ◽

Contact Tracing ◽

Whole Genome ◽

Genome Sequences ◽

South Korean Government ◽

South Korean ◽

The Republic

Abstract The South Korean government effectively contained the coronavirus disease-2019 (COVID-19) outbreak primarily associated with a religious group. We conducted SARS-CoV-2 whole genome sequencing of 66 cases to investigate connections among the initial South Korean cases and the religious group outbreak. We assessed the accuracy of genomic investigation by comparing the whole genome sequences with comprehensive contact tracing records. Five transmission clusters were estimated among the 15 initial cases. The six close-contact cases and two potential exposure pairs identified by contact tracing showed two or fewer nucleotide base differences. Additionally, we identified two transmission clusters from the religious group outbreak that were phylogenetically distinct from the initial clusters, sharing common G11083T, G26144T, and C14805T markers. The strain closest to the two religious group clusters was identified from a pair of identical sequences isolated from individuals who traveled from Wuhan to Italy. Our findings provide insights into the origins of community spread of COVID-19.

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