Intensive Case Finding and Isoniazid Preventative Therapy in HIV Infected Individuals in Africa: Economic Model and Value of Information Analysis

Background: Tuberculosis (TB) accounts of much of the morbidity and mortality associated with HIV. We evaluate the costeffectiveness of different strategies to actively screen for TB disease in HIV positive individuals, where isoniazid preventative therapy (IPT) is given to those screening negative, and use value of information analysis (VOI) to identify future research priorities. Methodology / Principal Findings: We built an individual sampling model to investigate the costs (2010 US Dollars) and consequences of screening for TB, and providing TB treatment or IPT in adults testing HIV positive in Sub-Saharan Africa. A systematic review and meta-analysis was conducted to assess performance of the nine different TB screening strategies evaluated. Probabilistic sensitivity analysis was conducted to incorporate decision uncertainty, and expected value of perfect information for the entire model and for groups of parameters was calculated. Screening all HIV infected individuals with sputum microscopy was the least costly strategy, with other strategies not cost-effective at WHO recommended thresholds. Screening those with TB symptoms with sputum microscopy and CXR would be cost-effective at a threshold ICER of $7,800 per quality-adjusted life year (QALY), but associated with significant uncertainty. VOI analysis suggests further information would be of value. Conclusions / Significance: Resource-constrained countries in sub-Saharan Africa wishing to scale up TB preventativ

Trends in drug-resistant tuberculosis in a gold-mining workforce in South Africa, 2002-2008.

SETTING AND OBJECTIVE: To describe trends in drug-resistant tuberculosis (TB) in two gold-mining workforces, South Africa, 2002-2008. DESIGN: TB programme data analysis. RESULTS: TB case notification rates decreased between 2002 and 2008 from 4006 to 3018 per 100,000 and from 3192 to 2468/100,000 for Companies A and B, respectively. Human immunodeficiency virus (HIV) prevalence exceeded 80% in TB episodes with known status. The proportion of TB episodes with multidrug-resistant TB (MDR-TB) increased from 6/129 (4.7%) to 17/85 (20.0%) among previously treated cases, and from 4/38 (10.4%) to 7/28 (25.0%) in Companies A and B, respectively (tests for trend, Company A, P < 0.001; Company B, P = 0.304). Case notifications of MDR-TB increased during 2002-2008 from 39.8 to 122.9/100,000/year in Company A and from 7.8 to 96.8/100,000/year in Company B. Coverage of second-line drug susceptibility testing (DST) among MDR-TB episodes was low. Previous treatment exposure was a strong risk factor for MDR-TB (prevalence ratio 8.78, 95%CI 5.94-12.97 in previously treated vs. untreated individuals). CONCLUSION: Despite decreasing TB notifications overall, MDR-TB notifications and proportions of episodes with MDR-TB increased in the larger company. Cure must be ensured in first episodes to prevent acquired resistance. Improved coverage of culture, DST and HIV testing is required to allow treatment to be optimised

Spectrum of non-tuberculous mycobacteria identified using standard biochemical testing vs. 16S sequencing.

Non-tuberculous mycobacterial isolates from gold miners were speciated using standard biochemical testing (SBT) and 16S rDNA sequencing. Of 237 isolates tested, SBT identified 126, compared with all 237 identified using sequencing. Of 111 isolates unspeciated by SBT but identified by sequencing, 38 (34.2%) were identified as Mycobacterium gordonae and 8 (7.2%) were new species. Of 126 isolates speciated by both methods, 37 were discordant, with 14/17 M. gordonae isolates incorrectly identified as M. scrofulaceum using SBT. The majority of these were the potentially pathogenic strain D, M. gordonae. Sequencing is preferable where available to guide treatment

Raised Venous Lactate and Markers of Intestinal Translocation Are Associated With Mortality Among In-Patients With HIV-Associated TB in Rural South Africa.

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.Introduction: Case fatality among in-patients with HIV-associated tuberculosis (HIV-TB) in Africa is high. We investigated the factors associated with mortality in a rural South African hospital. Methods: This was a prospective observational study of HIV-TB in-patients, with death by 8 weeks the endpoint. Results: Of 99 patients (median CD4 count 72 cells/mm3), 32 (32%) died after median 8-day TB treatment. TB was diagnosed microbiologically in 75/99 and clinico-radiologically in 24, with no mortality difference between these groups [31% versus 38% (P = 0.53)]. Median venous lactate was 5.5 mmol/L (interquartile range 3.9-6.2) in those who died and 3.1 mmol/L (interquartile range 2.2-4.1) in survivors (P < 0.001). In multivariable analysis, lactate ≥4 mmol/L [adjusted odds ratio (aOR) 9.8, 95% confidence interval (CI): 3.0 to 32.2], Glasgow Coma Score <15 (aOR 6.6, 95% CI: 1.5 to 29.6), CD4 count <50 cells per cubic millimeter (aOR 5.5, 95% CI: 1.6 to 18.5), and age ≥50 (aOR 7.7, 95% CI: 1.2 to 46.9) independently predicted death. In a nested case-control study, comparing those who died versus CD4-matched survivors, median plasma lipopolysaccharide concentrations were 93 and 57 pg/mL (P = 0.026) and intestinal fatty acid-binding protein, 132 and 0 pg/mL (P = 0.002). Conclusions: Mortality was high and predicted by elevated lactate, likely reflecting a sepsis-syndrome secondary to TB or bacterial coinfection with intestinal barrier dysfunction appearing to contribute

Spectrum of non-tuberculous mycobacteria identified using standard biochemical testing versus 16S sequencing.

Please help populate SUNScholar with the full text of SU research output. Also - should you need this item urgently, please send us the details and we will try to get hold of the full text as quick possible. E-mail to [email protected]. Thank you.Journal Articles (subsidised)Geneeskunde en GesondheidswetenskappeMolekul�re Biologie & Mensgenetik

Incidence and risk factors for tuberculosis among people with HIV on antiretroviral therapy in the UK

OBJECTIVE: The UK has a low tuberculosis incidence and earlier combination antiretroviral therapy (cART) is expected to have reduced incidence among people with HIV. Epidemiological patterns and risk factors for active tuberculosis were analysed over a 20 year period among people accessing HIV care at sites participating in the UK CHIC observational study. DESIGN: Cohort analysis. METHODS: Data were included for individuals over 15 years old attending for HIV care between 1996 and 2017 inclusive, with at least three months follow up recorded. Incidence rates of new tuberculosis events were calculated and stratified by ethnicity (white/black/other) as a proxy for tuberculosis exposure. Poisson regression models were used to determine the associations of calendar year, ethnicity and other potential risk factors after cART initiation. RESULTS: 58,776 participants (26.3% female; 54.5% white, 32.0% black, 13.5% other/unknown ethnicity; median (interquartile range) age 34 (29-42) years) were followed for 546,617 person-years. 704 were treated for active tuberculosis (rate 1.3 [95% confidence interval (CI) 1.2-1.4]/1000 person-years). Tuberculosis incidence decreased from 1.3 [1.2-1.5] to 0.6 [0.4-0.9]/1000 person-years from pre-2004 to 2011-2017. The decline among people of black ethnicity was less steep than among those of white/other ethnicities, with incidence remaining high among black participants in the latest period (2.1 [1.4-3.1]/1000 person-years). 283 participants (191 (67%) black African) had tuberculosis with viral load < 50 copies/ml. CONCLUSIONS: Despite the known protective effect of cART against tuberculosis, a continuing disproportionately high incidence is seen among black African people. Results support further interventions to prevent tuberculosis in this group