Optimising Xpert-Ultra and culture testing to reliably measure tuberculosis prevalence in the community: findings from surveys in Zambia and South Africa
Objectives Prevalence surveys remain the best way to assess the national tuberculosis (TB) burden in many countries. Challenges with using culture (the reference standard) for TB diagnosis in prevalence surveys have led to increasing use of molecular tests (Xpert assays), but discordance between the...
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BMJ Publishing Group
2022-06-01
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| author | Richard Hayes Sarah Fidler Sian Floyd María Rupérez Helen Ayles Redwaan Vermaak Kwame Shanaube Albertus Schaap Eveline Klinkenberg Petra de Haas Barry Kosloff Thomas Gachie Pete J Dodd Chali Wapamesa Michael J Burnett Nico Kalisvaart Tila Mainga Linda Mureithi |
| author_facet | Richard Hayes Sarah Fidler Sian Floyd María Rupérez Helen Ayles Redwaan Vermaak Kwame Shanaube Albertus Schaap Eveline Klinkenberg Petra de Haas Barry Kosloff Thomas Gachie Pete J Dodd Chali Wapamesa Michael J Burnett Nico Kalisvaart Tila Mainga Linda Mureithi |
| author_sort | Richard Hayes |
| collection | DOAJ |
| description | Objectives Prevalence surveys remain the best way to assess the national tuberculosis (TB) burden in many countries. Challenges with using culture (the reference standard) for TB diagnosis in prevalence surveys have led to increasing use of molecular tests (Xpert assays), but discordance between these two tests has created problems for deciding which individuals have TB. We aimed to design an accurate diagnostic algorithm for TB prevalence surveys (TBPS) that limits the use of culture.Design TBPS in four communities, conducted during 2019.Setting Three Zambian communities and one South-African community included in the TBPS of the Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening study.Participants Randomly sampled individuals aged ≥15 years. Among those who screened positive on chest X-ray or symptoms, two sputum samples were collected for field Xpert-Ultra testing and a third for laboratory liquid-culture testing. Clinicians reviewed screening and test results; in Zambia, participants with Mycobacterium tuberculosis-positive results were followed up 6–13 months later. Among 10 984 participants, 2092 screened positive, 1852 provided two samples for Xpert-Ultra testing, and 1009 had valid culture results.Outcomes Culture and Xpert-Ultra test results.Results Among 946 culture-negative individuals, 917 were Xpert-negative, 12 Xpert-trace-positive and 17 Xpert-positive (grade very low, low, medium or high), with Xpert categorised as the highest grade of the two sample results. Among 63 culture-positive individuals, 8 were Xpert-negative, 9 Xpert-trace-positive and 46 Xpert-positive. Counting trace-positive results as positive, the sensitivity of Xpert-Ultra compared with culture was 87% (95% CI 76% to 94%) using two samples compared with 76% (95% CI 64% to 86%) using one. Specificity was 97% when trace-positive results were counted as positive and 98% when trace-positive results were counted as negative. Most Xpert-Ultra-positive/culture-negative discordance was among individuals whose Xpert-positive results were trace-positive or very low grade or they reported previous TB treatment. Among individuals with both Xpert-Ultra results grade low or above, the positive-predictive-value was 90% (27/30); 3/30 were plausibly false-negative culture results.Conclusion Using Xpert-Ultra as the primary diagnostic test in TBPS, with culture only for confirmatory testing, would identify a high proportion of TB cases while massively reducing survey culture requirements.Trial registration number NCT03739736. |
| format | Article |
| id | doaj-art-d0740d88ce524560a5f5e89e47847b3f |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-06-01 |
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| spelling | doaj-art-d0740d88ce524560a5f5e89e47847b3f2025-01-24T20:45:10ZengBMJ Publishing GroupBMJ Open2044-60552022-06-0112610.1136/bmjopen-2021-058195Optimising Xpert-Ultra and culture testing to reliably measure tuberculosis prevalence in the community: findings from surveys in Zambia and South AfricaRichard Hayes0Sarah Fidler1Sian Floyd2María Rupérez3Helen Ayles4Redwaan Vermaak5Kwame Shanaube6Albertus Schaap7Eveline Klinkenberg8Petra de Haas9Barry Kosloff10Thomas Gachie11Pete J Dodd12Chali Wapamesa13Michael J Burnett14Nico Kalisvaart15Tila Mainga16Linda Mureithi17Psychological Medicine, King`s College London, London, UK3Imperial College Healthcare NHS Trust, London, UKLondon School of Hygiene & Tropical Medicine, London, UKLondon School of Hygiene & Tropical Medicine, London, UK1 Zambart, Lusaka, ZambiaHealth Systems Trust, Cape Town, South AfricaZambart, University of Zambia School of Medicine, Lusaka, ZambiaDepartment of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UKIndependent consultant, Connect TB, Den Haag, The NetherlandsTechnical Division, KNCV Tuberculosis Foundation, Den Haag, The Netherlands7 Longhorn Vaccines & Diagnostics, Bethesda, Maryland, USALondon School of Hygiene & Tropical Medicine, London, UKSchool of Health and Related Research, The University of Sheffield, Sheffield, UKZambart, University of Zambia School of Medicine, Lusaka, ZambiaHealth Systems Trust, Cape Town, South AfricaKNCV Tuberculosis Foundation, Den Haag, The NetherlandsZambart, University of Zambia School of Medicine, Lusaka, ZambiaHealth Systems Trust, Cape Town, South AfricaObjectives Prevalence surveys remain the best way to assess the national tuberculosis (TB) burden in many countries. Challenges with using culture (the reference standard) for TB diagnosis in prevalence surveys have led to increasing use of molecular tests (Xpert assays), but discordance between these two tests has created problems for deciding which individuals have TB. We aimed to design an accurate diagnostic algorithm for TB prevalence surveys (TBPS) that limits the use of culture.Design TBPS in four communities, conducted during 2019.Setting Three Zambian communities and one South-African community included in the TBPS of the Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening study.Participants Randomly sampled individuals aged ≥15 years. Among those who screened positive on chest X-ray or symptoms, two sputum samples were collected for field Xpert-Ultra testing and a third for laboratory liquid-culture testing. Clinicians reviewed screening and test results; in Zambia, participants with Mycobacterium tuberculosis-positive results were followed up 6–13 months later. Among 10 984 participants, 2092 screened positive, 1852 provided two samples for Xpert-Ultra testing, and 1009 had valid culture results.Outcomes Culture and Xpert-Ultra test results.Results Among 946 culture-negative individuals, 917 were Xpert-negative, 12 Xpert-trace-positive and 17 Xpert-positive (grade very low, low, medium or high), with Xpert categorised as the highest grade of the two sample results. Among 63 culture-positive individuals, 8 were Xpert-negative, 9 Xpert-trace-positive and 46 Xpert-positive. Counting trace-positive results as positive, the sensitivity of Xpert-Ultra compared with culture was 87% (95% CI 76% to 94%) using two samples compared with 76% (95% CI 64% to 86%) using one. Specificity was 97% when trace-positive results were counted as positive and 98% when trace-positive results were counted as negative. Most Xpert-Ultra-positive/culture-negative discordance was among individuals whose Xpert-positive results were trace-positive or very low grade or they reported previous TB treatment. Among individuals with both Xpert-Ultra results grade low or above, the positive-predictive-value was 90% (27/30); 3/30 were plausibly false-negative culture results.Conclusion Using Xpert-Ultra as the primary diagnostic test in TBPS, with culture only for confirmatory testing, would identify a high proportion of TB cases while massively reducing survey culture requirements.Trial registration number NCT03739736.https://bmjopen.bmj.com/content/12/6/e058195.full |
| spellingShingle | Richard Hayes Sarah Fidler Sian Floyd María Rupérez Helen Ayles Redwaan Vermaak Kwame Shanaube Albertus Schaap Eveline Klinkenberg Petra de Haas Barry Kosloff Thomas Gachie Pete J Dodd Chali Wapamesa Michael J Burnett Nico Kalisvaart Tila Mainga Linda Mureithi Optimising Xpert-Ultra and culture testing to reliably measure tuberculosis prevalence in the community: findings from surveys in Zambia and South Africa BMJ Open |
| title | Optimising Xpert-Ultra and culture testing to reliably measure tuberculosis prevalence in the community: findings from surveys in Zambia and South Africa |
| title_full | Optimising Xpert-Ultra and culture testing to reliably measure tuberculosis prevalence in the community: findings from surveys in Zambia and South Africa |
| title_fullStr | Optimising Xpert-Ultra and culture testing to reliably measure tuberculosis prevalence in the community: findings from surveys in Zambia and South Africa |
| title_full_unstemmed | Optimising Xpert-Ultra and culture testing to reliably measure tuberculosis prevalence in the community: findings from surveys in Zambia and South Africa |
| title_short | Optimising Xpert-Ultra and culture testing to reliably measure tuberculosis prevalence in the community: findings from surveys in Zambia and South Africa |
| title_sort | optimising xpert ultra and culture testing to reliably measure tuberculosis prevalence in the community findings from surveys in zambia and south africa |
| url | https://bmjopen.bmj.com/content/12/6/e058195.full |
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