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Tuberculosis (TB), the disease caused primarily by the pathogen Mycobacterium tuberculosis, is one of the leading causes of death due to an infectious disease. Globally, TB has infected around one quarter of the population, with approximately 10 million people developing TB in 2019 and 1.4 million succumbing to the disease.1 New Zealand has a low incidence of TB, with a case notification rate ranging from 5.9 to 6.4 per 100,000 yearly between 2012 and 2016.1,2

TB is both a preventable and curable disease. It is believed around 85% of those with the disease are treatable with a six-month long drug regime. However, drug-resistant TB (DR-TB) is a growing concern, requiring longer, more-expensive and more-complex treatment courses.1 Multidrug-resistant TB (MDR-TB) is defined as being resistant to at least rifampicin (RIF) and isoniazid (INH), the two most effective first-line antitubercular agents.1–5 It is estimated that multidrug- and rifampicin-resistant TB (MDR/RR-TB) accounted for 3.32% of new cases and 17.7% of previously treated cases in 2020. Although this represents a reduction from 2019, there was an increase in the percentage of cases that failed treatment or returned after default treatment.1 In New Zealand, MDR-TB composed an average of 1.3% of culture-positive cases between 2007 and 2016. Additionally, TB cases resistant to at least one antibiotic comprised 9.3% of total cases in New Zealand between 2011 and 2016. This, in combination with an average treatment delay of 83 days, poses a threat to public health in those with pulmonary TB.2

Whole genome sequencing (WGS) provides an alternative method of drug susceptibility testing (DST), instead of traditional phenotypic and molecular assay techniques.5,6 WGS has the ability to overcome limitations inherent to these techniques, with improved sensitivity and involvement in multiple components of management.4–6 WGS is increasingly being used overseas and is expected to become routine for molecular diagnosis of TB in New Zealand.6 The utility of WGS in a reference mycobacterium laboratory in New Zealand to supplement other molecular tests and to assist in a rapid but accurate diagnosis and appropriate management of MDR-TB has recently been reported.4 However, the lack of standardisation in the bioinformatics process to analyse WGS data and report formatting prevents the routine utility of WGS in a clinical setting.6 Although progress has been made in the standardisation of data analysis,6 a standardised reporting format tailored to New Zealand clinicians could help cross another hurdle to the implementation of WGS in TB management.

Data output from WGS is complex, and interpretation is only possible with related expertise. Reports generated from WGS highlight genomic data that identify the specific mutations present within the isolate believed to be responsible for associated drug resistance (Table 1). 4 This data has only limited use for clinicians in the clinical context. In order for this information to be utilised clinically, it must be translated into an easily understandable format that highlights important information relevant to treatment decision-making.

In this study, we propose a standardised template for clinical reporting of WGS results for Mycobacterium tuberculosis in New Zealand (Figure 1). Patient identifiers are chiefly important in clinical reporting in order to ensure the data reported are applicable to the correct patient and to avoid clinical errors. This information is placed at the top of the report to ensure it is appropriately emphasised. A brief summary of diagnostic results and the level of drug resistance (ie, multidrug-resistant [MDR] or extensively drug-resistant [XDR]) is displayed in bold. Below this, a simplified drug susceptibility profile is located. Separated into available first- and second-line antitubercular agents, resistance is identified and highlighted in red. The mutated genes and variant confidence are also included to provide further insight. A comment section is included with additional information and referral to the Ministry of Health Guidelines for Tuberculosis Control in New Zealand.3 Relevant information regarding the analysed sample is included in addition to information about the reporting laboratory. Lastly, in-depth results are located at the bottom of the report. This section summarises information reported in the simplified drug profile with some additional information pertaining to the specific mutations present.

In short, the New Zealand-specific, clinician-tailored WGS report format proposed in this study could be valuable in the implementation of WGS as a method of DST for TB to improve patient outcomes in New Zealand.

Table 1: Conventional WGS report. Adapted from Basu et al.4

Figure 1: Proposed WGS summary report to assist in making clinical decisions. View online.

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

Lars Humblestone: Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand. Brendan Arnold: Dunedin Hospital, Southern District Health Board, Dunedin, New Zealand. Htin Lin Aung: Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.

Acknowledgements

LH was funded by the Otago Medical Research Fund and Flavell Memorial. HLA. was supported by the New Zealand Health Research Council Sir Charles Hercus Health Research Fellowship.

Correspondence

Dr Htin Lin Aung, Sir Charles Hercus Health Research Fellow, Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand, +64 3 4795091 (phone); +64 3 4798540 (fax)

Correspondence Email

htin.aung@otago.ac.nz

Competing Interests

Nil.

1. Global tuberculosis report 2020. Geneva: World Health Organization; 2020.

2. Tuberculosis in New Zealand Annual Report 2016. Porirua, New Zealand: The Institute of Environmental Science and Research Ltd (ESR); 2019.

3. Guidelines for Tuberculosis Control in New Zealand, 2019. Wellington: Ministry of Health 2019.

4. Basu I, Bower JE, Roberts SA, Henderson G, Aung HL, Cook G, et al. Utility of whole genome sequencing for multidrug resistant Mycobacterium tuberculosis isolates in a reference TB laboratory in New Zealand. NZMJ. 2018 131(1487):15-22.

5. Witney AA, Gould KA, Arnold A, Coleman D, Delgado R, Dhillon J, et al. Clinical Application of Whole-Genome Sequencing To Inform Treatment for Multidrug-Resistant Tuberculosis Cases. Journal of Clinical Microbiology. 2015;53(5):1473-83.

6. Meehan CJ, Goig GA, Kohl TA, Verboven L, Dippenaar A, Ezewudo M, et al. Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues. Nature Reviews Microbiology. 2019;17:533-45.

For the PDF of this article,
contact nzmj@nzma.org.nz

View Article PDF

Tuberculosis (TB), the disease caused primarily by the pathogen Mycobacterium tuberculosis, is one of the leading causes of death due to an infectious disease. Globally, TB has infected around one quarter of the population, with approximately 10 million people developing TB in 2019 and 1.4 million succumbing to the disease.1 New Zealand has a low incidence of TB, with a case notification rate ranging from 5.9 to 6.4 per 100,000 yearly between 2012 and 2016.1,2

TB is both a preventable and curable disease. It is believed around 85% of those with the disease are treatable with a six-month long drug regime. However, drug-resistant TB (DR-TB) is a growing concern, requiring longer, more-expensive and more-complex treatment courses.1 Multidrug-resistant TB (MDR-TB) is defined as being resistant to at least rifampicin (RIF) and isoniazid (INH), the two most effective first-line antitubercular agents.1–5 It is estimated that multidrug- and rifampicin-resistant TB (MDR/RR-TB) accounted for 3.32% of new cases and 17.7% of previously treated cases in 2020. Although this represents a reduction from 2019, there was an increase in the percentage of cases that failed treatment or returned after default treatment.1 In New Zealand, MDR-TB composed an average of 1.3% of culture-positive cases between 2007 and 2016. Additionally, TB cases resistant to at least one antibiotic comprised 9.3% of total cases in New Zealand between 2011 and 2016. This, in combination with an average treatment delay of 83 days, poses a threat to public health in those with pulmonary TB.2

Whole genome sequencing (WGS) provides an alternative method of drug susceptibility testing (DST), instead of traditional phenotypic and molecular assay techniques.5,6 WGS has the ability to overcome limitations inherent to these techniques, with improved sensitivity and involvement in multiple components of management.4–6 WGS is increasingly being used overseas and is expected to become routine for molecular diagnosis of TB in New Zealand.6 The utility of WGS in a reference mycobacterium laboratory in New Zealand to supplement other molecular tests and to assist in a rapid but accurate diagnosis and appropriate management of MDR-TB has recently been reported.4 However, the lack of standardisation in the bioinformatics process to analyse WGS data and report formatting prevents the routine utility of WGS in a clinical setting.6 Although progress has been made in the standardisation of data analysis,6 a standardised reporting format tailored to New Zealand clinicians could help cross another hurdle to the implementation of WGS in TB management.

Data output from WGS is complex, and interpretation is only possible with related expertise. Reports generated from WGS highlight genomic data that identify the specific mutations present within the isolate believed to be responsible for associated drug resistance (Table 1). 4 This data has only limited use for clinicians in the clinical context. In order for this information to be utilised clinically, it must be translated into an easily understandable format that highlights important information relevant to treatment decision-making.

In this study, we propose a standardised template for clinical reporting of WGS results for Mycobacterium tuberculosis in New Zealand (Figure 1). Patient identifiers are chiefly important in clinical reporting in order to ensure the data reported are applicable to the correct patient and to avoid clinical errors. This information is placed at the top of the report to ensure it is appropriately emphasised. A brief summary of diagnostic results and the level of drug resistance (ie, multidrug-resistant [MDR] or extensively drug-resistant [XDR]) is displayed in bold. Below this, a simplified drug susceptibility profile is located. Separated into available first- and second-line antitubercular agents, resistance is identified and highlighted in red. The mutated genes and variant confidence are also included to provide further insight. A comment section is included with additional information and referral to the Ministry of Health Guidelines for Tuberculosis Control in New Zealand.3 Relevant information regarding the analysed sample is included in addition to information about the reporting laboratory. Lastly, in-depth results are located at the bottom of the report. This section summarises information reported in the simplified drug profile with some additional information pertaining to the specific mutations present.

In short, the New Zealand-specific, clinician-tailored WGS report format proposed in this study could be valuable in the implementation of WGS as a method of DST for TB to improve patient outcomes in New Zealand.

Table 1: Conventional WGS report. Adapted from Basu et al.4

Figure 1: Proposed WGS summary report to assist in making clinical decisions. View online.

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

Lars Humblestone: Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand. Brendan Arnold: Dunedin Hospital, Southern District Health Board, Dunedin, New Zealand. Htin Lin Aung: Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.

Acknowledgements

LH was funded by the Otago Medical Research Fund and Flavell Memorial. HLA. was supported by the New Zealand Health Research Council Sir Charles Hercus Health Research Fellowship.

Correspondence

Dr Htin Lin Aung, Sir Charles Hercus Health Research Fellow, Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand, +64 3 4795091 (phone); +64 3 4798540 (fax)

Correspondence Email

htin.aung@otago.ac.nz

Competing Interests

Nil.

1. Global tuberculosis report 2020. Geneva: World Health Organization; 2020.

2. Tuberculosis in New Zealand Annual Report 2016. Porirua, New Zealand: The Institute of Environmental Science and Research Ltd (ESR); 2019.

3. Guidelines for Tuberculosis Control in New Zealand, 2019. Wellington: Ministry of Health 2019.

4. Basu I, Bower JE, Roberts SA, Henderson G, Aung HL, Cook G, et al. Utility of whole genome sequencing for multidrug resistant Mycobacterium tuberculosis isolates in a reference TB laboratory in New Zealand. NZMJ. 2018 131(1487):15-22.

5. Witney AA, Gould KA, Arnold A, Coleman D, Delgado R, Dhillon J, et al. Clinical Application of Whole-Genome Sequencing To Inform Treatment for Multidrug-Resistant Tuberculosis Cases. Journal of Clinical Microbiology. 2015;53(5):1473-83.

6. Meehan CJ, Goig GA, Kohl TA, Verboven L, Dippenaar A, Ezewudo M, et al. Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues. Nature Reviews Microbiology. 2019;17:533-45.

For the PDF of this article,
contact nzmj@nzma.org.nz

View Article PDF

Tuberculosis (TB), the disease caused primarily by the pathogen Mycobacterium tuberculosis, is one of the leading causes of death due to an infectious disease. Globally, TB has infected around one quarter of the population, with approximately 10 million people developing TB in 2019 and 1.4 million succumbing to the disease.1 New Zealand has a low incidence of TB, with a case notification rate ranging from 5.9 to 6.4 per 100,000 yearly between 2012 and 2016.1,2

TB is both a preventable and curable disease. It is believed around 85% of those with the disease are treatable with a six-month long drug regime. However, drug-resistant TB (DR-TB) is a growing concern, requiring longer, more-expensive and more-complex treatment courses.1 Multidrug-resistant TB (MDR-TB) is defined as being resistant to at least rifampicin (RIF) and isoniazid (INH), the two most effective first-line antitubercular agents.1–5 It is estimated that multidrug- and rifampicin-resistant TB (MDR/RR-TB) accounted for 3.32% of new cases and 17.7% of previously treated cases in 2020. Although this represents a reduction from 2019, there was an increase in the percentage of cases that failed treatment or returned after default treatment.1 In New Zealand, MDR-TB composed an average of 1.3% of culture-positive cases between 2007 and 2016. Additionally, TB cases resistant to at least one antibiotic comprised 9.3% of total cases in New Zealand between 2011 and 2016. This, in combination with an average treatment delay of 83 days, poses a threat to public health in those with pulmonary TB.2

Whole genome sequencing (WGS) provides an alternative method of drug susceptibility testing (DST), instead of traditional phenotypic and molecular assay techniques.5,6 WGS has the ability to overcome limitations inherent to these techniques, with improved sensitivity and involvement in multiple components of management.4–6 WGS is increasingly being used overseas and is expected to become routine for molecular diagnosis of TB in New Zealand.6 The utility of WGS in a reference mycobacterium laboratory in New Zealand to supplement other molecular tests and to assist in a rapid but accurate diagnosis and appropriate management of MDR-TB has recently been reported.4 However, the lack of standardisation in the bioinformatics process to analyse WGS data and report formatting prevents the routine utility of WGS in a clinical setting.6 Although progress has been made in the standardisation of data analysis,6 a standardised reporting format tailored to New Zealand clinicians could help cross another hurdle to the implementation of WGS in TB management.

Data output from WGS is complex, and interpretation is only possible with related expertise. Reports generated from WGS highlight genomic data that identify the specific mutations present within the isolate believed to be responsible for associated drug resistance (Table 1). 4 This data has only limited use for clinicians in the clinical context. In order for this information to be utilised clinically, it must be translated into an easily understandable format that highlights important information relevant to treatment decision-making.

In this study, we propose a standardised template for clinical reporting of WGS results for Mycobacterium tuberculosis in New Zealand (Figure 1). Patient identifiers are chiefly important in clinical reporting in order to ensure the data reported are applicable to the correct patient and to avoid clinical errors. This information is placed at the top of the report to ensure it is appropriately emphasised. A brief summary of diagnostic results and the level of drug resistance (ie, multidrug-resistant [MDR] or extensively drug-resistant [XDR]) is displayed in bold. Below this, a simplified drug susceptibility profile is located. Separated into available first- and second-line antitubercular agents, resistance is identified and highlighted in red. The mutated genes and variant confidence are also included to provide further insight. A comment section is included with additional information and referral to the Ministry of Health Guidelines for Tuberculosis Control in New Zealand.3 Relevant information regarding the analysed sample is included in addition to information about the reporting laboratory. Lastly, in-depth results are located at the bottom of the report. This section summarises information reported in the simplified drug profile with some additional information pertaining to the specific mutations present.

In short, the New Zealand-specific, clinician-tailored WGS report format proposed in this study could be valuable in the implementation of WGS as a method of DST for TB to improve patient outcomes in New Zealand.

Table 1: Conventional WGS report. Adapted from Basu et al.4

Figure 1: Proposed WGS summary report to assist in making clinical decisions. View online.

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

Lars Humblestone: Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand. Brendan Arnold: Dunedin Hospital, Southern District Health Board, Dunedin, New Zealand. Htin Lin Aung: Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.

Acknowledgements

LH was funded by the Otago Medical Research Fund and Flavell Memorial. HLA. was supported by the New Zealand Health Research Council Sir Charles Hercus Health Research Fellowship.

Correspondence

Dr Htin Lin Aung, Sir Charles Hercus Health Research Fellow, Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand, +64 3 4795091 (phone); +64 3 4798540 (fax)

Correspondence Email

htin.aung@otago.ac.nz

Competing Interests

Nil.

1. Global tuberculosis report 2020. Geneva: World Health Organization; 2020.

2. Tuberculosis in New Zealand Annual Report 2016. Porirua, New Zealand: The Institute of Environmental Science and Research Ltd (ESR); 2019.

3. Guidelines for Tuberculosis Control in New Zealand, 2019. Wellington: Ministry of Health 2019.

4. Basu I, Bower JE, Roberts SA, Henderson G, Aung HL, Cook G, et al. Utility of whole genome sequencing for multidrug resistant Mycobacterium tuberculosis isolates in a reference TB laboratory in New Zealand. NZMJ. 2018 131(1487):15-22.

5. Witney AA, Gould KA, Arnold A, Coleman D, Delgado R, Dhillon J, et al. Clinical Application of Whole-Genome Sequencing To Inform Treatment for Multidrug-Resistant Tuberculosis Cases. Journal of Clinical Microbiology. 2015;53(5):1473-83.

6. Meehan CJ, Goig GA, Kohl TA, Verboven L, Dippenaar A, Ezewudo M, et al. Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues. Nature Reviews Microbiology. 2019;17:533-45.

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