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Impact of enhanced tuberculosis diagnosis in South Africa: a mathematical model of expanded culture and drug susceptibility testing.

ABSTRACT: South Africa has high rates of tuberculosis (TB), including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Expanding access to culture and drug susceptibility testing (DST) for TB diagnosis may help control this epidemic, but the potential impact of existing and novel TB diagnostics is uncertain. By fitting to World Health Organization epidemiological estimates, we developed a compartmental difference-equation model of the TB/HIV epidemic among South African adults. Performing culture and DST in 37% of new cases and 85% of previously treated cases was projected to save 47,955 lives (17.2% reduction in TB mortality, 95% simulation interval (S.I.) 8.9-24.4%), avert 7,721 MDR-TB cases (14.1% reduction, 95% S.I. 5.3-23.8%), and prevent 46.6% of MDR-TB deaths (95% S.I. 32.6-56.0%) in South Africa over 10 years. Used alone, expanded culture and DST did not reduce XDR-TB incidence, but they enhanced the impact of transmission-reduction strategies, such as respiratory isolation. In South Africa, expanding TB culture and DST could substantially reduce TB, and particularly MDR-TB, mortality. Control of XDR-TB will require additional interventions, the impact of which may be enhanced by improved TB diagnosis.

SUBMITTER: Dowdy DW

PROVIDER: S-EPMC2516234 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Impact of enhanced tuberculosis diagnosis in South Africa: a mathematical model of expanded culture and drug susceptibility testing.

Dowdy David W DW Chaisson Richard E RE Maartens Gary G Corbett Elizabeth L EL Dorman Susan E SE

Proceedings of the National Academy of Sciences of the United States of America 20080811 32

South Africa has high rates of tuberculosis (TB), including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Expanding access to culture and drug susceptibility testing (DST) for TB diagnosis may help control this epidemic, but the potential impact of existing and novel TB diagnostics is uncertain. By fitting to World Health Organization epidemiological estimates, we developed a compartmental difference-equation model of the TB/HIV epidemic among South African adults. Perf ...[more]

PMID: 18695217

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Project description:ObjectivesPrevalence 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.DesignTBPS in four communities, conducted during 2019.SettingThree Zambian communities and one South-African community included in the TBPS of the Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening study.ParticipantsRandomly 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.OutcomesCulture and Xpert-Ultra test results.ResultsAmong 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.ConclusionUsing 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 numberNCT03739736.

Project description:BackgroundSouth Africa has one of the world's worst tuberculosis (TB) (520 per 100 000 population) and TB-human immunodeficiency virus (HIV) epidemics (~?56% TB/HIV co-infected). While individual- and system-level factors influencing progression along the TB cascade have been identified, the impact of stigma is underexplored and underappreciated. We conducted an exploratory study to 1) describe differences in perceived community-level TB stigma among community members, TB presumptives, and TB patients, and 2) identify factors associated with TB stigma levels among these groups.MethodsA cross sectional study was conducted in November 2017 at public health care facilities in Buffalo City Metro (BCM) and Zululand health districts, South Africa. Community members, TB presumptives, and TB patients were recruited. Data were collected on sociodemographic characteristics, TB knowledge, health and clinical history, social support, and both HIV and TB stigma. A validated scale assessing perceived community TB stigma was used. Univariate and multivariate linear regression models were used to describe differences in perceived community TB stigma by participant type and to identify factors associated with TB stigma.ResultsWe enrolled 397 participants. On a scale of zero to 24, the mean stigma score for TB presumptives (14.7?±?4.4) was statistically higher than community members (13.6?±?4.8) and TB patients (13.3?±?5.1). Community members from Zululand (??=?5.73; 95% CI 2.19, 9.72) had higher TB stigma compared to those from BCM. Previously having TB (??=?-?2.19; 95% CI -?4.37, 0.0064) was associated with reduced TB stigma among community members. Understanding the relationship between HIV and TB disease (??=?2.48; 95% CI 0.020, 4.94), and having low social support (??=?-?0.077; 95% CI -?0.14, 0.010) were associated with increased TB stigma among TB presumptives. Among TB Patients, identifying as Black African (??=?-?2.90; 95% CI -?4.74, -?1.04) and knowing the correct causes of TB (??=?-?2.93; 95% CI -?4.92, -?0.94) were associated with decreased TB stigma, while understanding the relationship between HIV and TB disease (??=?2.48; 95% CI 1.05, 3.90) and higher HIV stigma (??=?0.32; 95% CI 0.21, 0.42) were associated with increased TB stigma.ConclusionsTB stigma interventions should be developed for TB presumptives, as stigma may increase initial-loss-to-follow up. Given that stigma may be driven by numerous factors throughout the TB cascade, adaptive stigma reduction interventions may be required.

Dataset Information

Impact of enhanced tuberculosis diagnosis in South Africa: a mathematical model of expanded culture and drug susceptibility testing.

Publications

Impact of enhanced tuberculosis diagnosis in South Africa: a mathematical model of expanded culture and drug susceptibility testing.

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