Whole-Genome Sequencing and Social-Network Analysis of a Tuberculosis Outbreak

Gardy, Jennifer L.; Johnston, James C.; Sui, Shannan Ho; Cook, Victoria; Shah, Lena; Brodkin, Elizabeth; Rempel, Shirley; Moore, Richard; Zhao, Yongjun; Holt, Robert A.; Varhol, Richard; Birol, İnanç; Lem, Marcus; Sharma, Meenu K.; Elwood, Kevin; Jones, Steven J.M.; Brinkman, Fiona S. L.; Brunham, Robert C.; Tang, Patrick

doi:10.1056/nejmoa1003176

Cited by 662 publications

(622 citation statements)

References 12 publications

(9 reference statements)

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“…Together with other recent work (17)(18)(19), this study argues strongly for multiple genome sequences to understand patterns of transmission within an outbreak. Such analyses can already be conducted in a matter of days, and technological advances will only improve our ability to perform them in real time.…”

Section: Discussionsupporting

confidence: 63%

“…Highly accurate sequencing and SNP identification can overcome the noise from sequencing error and discern phylogenetic signal, which may, as in this case, depend on a small number of nucleotides. As demonstrated by the multiple independent sequencing efforts related to this E. coli O104:H4 outbreak (9, 10, 13, 15), and also epidemiological investigations of other infectious diseases (17)(18)(19), genomic epidemiology is likely to become the standard strategy in molecular epidemiology as the cost of sequencing continues to decline and technology becomes more widely accessible.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Genomic epidemiology of the Escherichia coli O104:H4 outbreaks in Europe, 2011

Grad

Lipsitch

Feldgarden

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

253

232

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International audienceThe degree to which molecular epidemiology reveals informationabout the sources and transmission patterns of an outbreakdepends on the resolution of the technology used and the samplesstudied. Isolates of Escherichia coli O104:H4 from the outbreak centeredin Germany in May–July 2011, and the much smaller outbreakin southwest France in June 2011, were indistinguishable by standardtests. We report a molecular epidemiological analysis usingmultiplatform whole-genome sequencing and analysis of multipleisolates from the German and French outbreaks. Isolates from theGerman outbreak showed remarkably little diversity, with onlytwo single nucleotide polymorphisms (SNPs) found in isolates fromfour individuals. Surprisingly, we found much greater diversity (19SNPs) in isolates from seven individuals infected in the French outbreak.The German isolates form a clade within the more diverseFrench outbreak strains. Moreover, five isolates derived from a singleinfected individual from the French outbreak had extremelylimited diversity. The striking difference in diversity between theGerman and French outbreak samples is consistent with severalhypotheses, including a bottleneck that purged diversity in theGerman isolates, variation in mutation rates in the two E. coli outbreakpopulations, or uneven distribution of diversity in the seedpopulations that led to each outbreak

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Genomic epidemiology of the Escherichia coli O104:H4 outbreaks in Europe, 2011

Grad

Lipsitch

Feldgarden

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

253

232

View full text Add to dashboard Cite

show abstract

“…Table 1 lists four defining features of TB disease and diagnosis (latency 44 , gradual symptom onset 45,46 , reliance on sputum 47 and concentration of transmission among 'superspreaders' 48 ). These features highlight a number of potential diagnostic gaps, or elements along the TB diagnostic pathway, which, if filled by a novel diagnostic test, could generate substantial incremental value.…”

Section: Methodsmentioning

confidence: 99%

Understanding the incremental value of novel diagnostic tests for tuberculosis

Arinaminpathy

Dowdy

2015

Nature

109

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Tuberculosis is a major source of global mortality caused by infection, partly because of a tremendous ongoing burden of undiagnosed disease. Improved diagnostic technology may play an increasingly crucial part in global efforts to end tuberculosis, but the ability of diagnostic tests to curb tuberculosis transmission is dependent on multiple factors, including the time taken by a patient to seek health care, the patient's symptoms, and the patterns of transmission before diagnosis. Novel diagnostic assays for tuberculosis have conventionally been evaluated on the basis of characteristics such as sensitivity and specificity, using assumptions that probably overestimate the impact of diagnostic tests on transmission. We argue for a shift in focus to the evaluation of such tests' incremental value, defining outcomes that reflect each test's purpose (for example, transmissions averted) and comparing systems with the test against those without, in terms of those outcomes. Incremental value can also be measured in units of outcome per incremental unit of resource (for example, money or human capacity). Using a novel, simplified model of tuberculosis transmission that addresses some of the limitations of earlier tuberculosis diagnostic models, we demonstrate that the incremental value of any novel test depends not just on its accuracy, but also on elements such as patient behaviour, tuberculosis natural history and health systems. By integrating these factors into a single unified framework, we advance an approach to the evaluation of new diagnostic tests for tuberculosis that considers the incremental value at the population level and demonstrates how additional data could inform more-effective implementation of tuberculosis diagnostic tests under various conditions

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“…These are important considerations given that social factors such as lack of transportation or resources and communal living may play a greater role in contributing to an outbreak than organism virulence or ethnicity. 17,18 Follow-up completion and preventive therapy acceptance rates were lowest for contacts of Indigenous cases living off-reserve. In spite of both presumed and reported barriers to access of health services on-reserve, time to assessment was better on-reserve than off.…”

Section: Discussionmentioning

confidence: 99%

Contact investigation outcomes of Canadian-born adults with tuberculosis in Indigenous and non-Indigenous populations in Alberta

Eisenbeis

Gao

Heffernan

et al. 2016

Can J Public Health

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OBJECTIVES: Contact investigations are a critical component of tuberculosis control in high-income countries. However, the relative success of conventional methods by population group and place of residence is unknown. This study compares outcomes of contact investigations of Canadian-born Indigenous tuberculosis cases living on-and off-reserve with other Canadian-born cases. METHODS:In a retrospective analysis, Canadian-born adult culture-positive pulmonary TB cases (2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010) were identified. Characteristics of source cases and their contacts were compared by population group. Outcomes of contact investigations, including completion of recommended investigations and preventive therapy, were compared in multivariable analysis. RESULTS:Of 171 cases of tuberculosis identified, 49 (29%) were Indigenous on-reserve, 62 (36%) Indigenous off-reserve, and 60 (35%) non-Indigenous or Canadian-born, "other". Indigenous people had more contacts identified per case compared to non-Indigenous patients. Case population group and smear status were the main predictors of the success of contact investigations. Of those recommended preventive therapy, close contacts of Indigenous cases onreserve had the highest rate of completion, at 54%, vs. 41% and 37% for close contacts of Indigenous living off-reserve and Canadian-born "other" respectively (p = 0.02). Contacts of Indigenous cases living off-reserve had the greatest delay in assessment and the lowest rates of completion of assessment and preventive therapy. In multivariable analysis, population group, smear status of source case and proximity of contact were predictors of preventive therapy acceptance and/or completion.CONCLUSIONS: Significant differences in outcomes of contact investigations were observed between population groups. The higher priority of contacts of smear-positive cases appears to influence efficiency of service delivery, regardless of population group. Jurisdictional differences in program delivery, resource availability and perceived risk of transmission likely influence outcomes of contact investigations.KEY WORDS: Tuberculosis in Canada; tuberculosis in Indigenous peoples; contact investigations La traduction du résumé se trouve à la fin de l'article.

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Whole-Genome Sequencing and Social-Network Analysis of a Tuberculosis Outbreak

Cited by 662 publications

References 12 publications

Genomic epidemiology of the Escherichia coli O104:H4 outbreaks in Europe, 2011

Genomic epidemiology of the Escherichia coli O104:H4 outbreaks in Europe, 2011

Understanding the incremental value of novel diagnostic tests for tuberculosis

Contact investigation outcomes of Canadian-born adults with tuberculosis in Indigenous and non-Indigenous populations in Alberta

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