Costs of tuberculosis screening among inpatients with HIV
Authors: Alice Zwerling
Journal: The Lancet Global Health (2019)

Mortality due to tuberculosis remains high among people living with HIV and accounted for 32% of AIDS-related deaths in 2017.1WHO2018 Global TB report.http://apps.who.int/iris/bitstream/handle/10665/274453/9789241565646-eng.pdfDate: Sept 18, 2018Date accessed: December 19, 2018Google Scholar Diagnosing tuberculosis remains challenging in people with HIV because they are often unable to provide sputum samples, which are required for most standard tests.1WHO2018 Global TB report.http://apps.who.int/iris/bitstream/handle/10665/274453/9789241565646-eng.pdfDate: Sept 18, 2018Date accessed: December 19, 2018Google Scholar In 2015, WHO issued conditional recommendations endorsing a urine lateral flow assay for Mycobacterium tuberculosis lipoarabinomannan (Alere Determine TB-LAM Ag test, Abbott, Waltham, MA, USA; TB-LAM) for use in adult inpatients with HIV, symptoms of tuberculosis, and CD4 counts of fewer than 100 cells per μL or serious illness.2WHOThe use of lateral flow urine lipoarabinomannan assay (LF-LAM) for the diagnosis and screening of active tuberculosis in people living with HIV: policy guidance. World Health Organization, Geneva2015Google Scholar Despite the endorsement, scale-up of TB-LAM use has been slow,3Médecins Sans FrontièresOut of step 2017. TB policies in 29 countries: a survey of prevention, testing and treatment policies and practicies.http://reliefweb.int/sites/reliefweb.int/files/resources/out_of_step_report_3rd_ed_july_2017.pdfDate: July, 2017Date accessed: December 19, 2018Google Scholar possibly because of confusion over conditional WHO policy recommendations and lack of integration between tuberculosis and HIV programmes. In The Lancet Global Health, Krishna Reddy and colleagues4Reddy KP Gupta-Wright A Fielding KL et al.Cost-effectiveness of urine-based tuberculosis screening in hospitalised patients with HIV in Africa: a microsimulation modelling study.Lancet Glob Health. 2019; 7: e200-e208Summary Full Text Full Text PDF PubMed Scopus (23) Google Scholar report a cost-effectiveness analysis in which they used a microsimulation model and data from the STAMP trial5Gupta-Wright A Corbett EL van Oosterhout JJ et al.Rapid urine-based screening for tuberculosis in HIV-positive patients admitted to hospital in Africa (STAMP): a pragmatic, multicentre, parallel-group, double-blind, randomised controlled trial.Lancet. 2018; 392: 292-301Summary Full Text Full Text PDF PubMed Scopus (118) Google Scholar to assess the cost-effectiveness of screening hospitalised HIV-positive patients irrespective of symptoms in Malawi and South Africa. They compared two strategies: the GeneXpert assay for M tuberculosis and rifampicin resistance (Cepheid, Sunnyvale, CA, USA; Xpert) to test sputum, which is the standard of care, versus sputum Xpert, TB-LAM, and concentrated urine Xpert (the intervention). Life expectancy was increased by 0·5–1·2 years by the intervention with little additional cost compared with sputum Xpert alone. Calculation of incremental cost-effectiveness ratios showed that the intervention would be cost-effective overall, with an incremental cost-effectiveness ratio of US$450 per year of life saved in Malawi and $840 per year of life saved in South Africa compared with the thresholds of $750 and $940, respectively. A modified version of the intervention that used sputum Xpert and TB-LAM without urine Xpert provided nearly equal clinical benefit and was at least as cost-effective as the intervention in both countries. Both strategies became cost-effective over time, reaching cost-effective thresholds at 4 years in Malawi and 15 years in South Africa, which reflects necessary initial investments required for implementation of a novel diagnostic or screening approach. Key drivers of cost-effectiveness included significantly lower availability of sputum samples in Malawi than in South Africa (39% vs 75%) and less use of empirical treatment based on clinical assessment in Malawi, resulting in improved diagnostic yield from TB-LAM and, thus, improved cost-effectiveness in Malawi compared with South Africa. Nevertheless, results were robust across both countries and a wide range of key variables (eg, tuberculosis prevalence, test costs, and HIV costs) that were explored in a sensitivity analysis. The evidence base for the cost-effectiveness of TB-LAM is small, with only five studies reporting on the costs of this assay and only one study other than that by Reddy and colleagues set outside South Africa.6Boyles TH Griesel R Stewart A Mendelson M Maartens G Incremental yield and cost of urine Determine TB-LAM and sputum induction in seriously ill adults with HIV.Int J Infect Dis. 2018; 75: 67-73Summary Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 7Mukora R Tlali M Monkwe S et al.Cost of point-of-care lateral flow urine lipoarabinomannan antigen testing in HIV-positive adults in South Africa.Int J Tuberc Lung Dis. 2018; 22: 1082-1087Crossref PubMed Scopus (3) Google Scholar, 8Orlando S Triulzi I Ciccacci F et al.Delayed diagnosis and treatment of tuberculosis in HIV+ patients in Mozambique: a cost-effectiveness analysis of screening protocols based on four symptom screening, smear microscopy, urine LAM test and Xpert MTB/RIF.PLoS One. 2018; 13: e0200523Crossref PubMed Scopus (10) Google Scholar, 9Shah M Dowdy D Joloba M et al.Cost-effectiveness of novel algorithms for rapid diagnosis of tuberculosis in HIV-infected individuals in Uganda.AIDS. 2013; 27: 2883-2892Crossref PubMed Scopus (25) Google Scholar, 10Sun D Dorman S Shah M et al.Cost utility of lateral-flow urine lipoarabinomannan for tuberculosis diagnosis in HIV-infected African adults.Int J Tuberc Lung Dis. 2013; 17: 552-558Crossref PubMed Scopus (30) Google Scholar The findings from these studies, however, are consistent, which suggests that TB-LAM is likely to be highly cost-effective in African inpatient settings, particularly among patients with low CD4 cell counts. Reddy and colleagues additionally assessed the cost-effectiveness of TB-LAM as a screening strategy irrespective of symptoms or CD4 cell counts, whereas in previous studies cost-effectiveness has been assessed in groups of patients preselected for tuberculosis symptoms, CD4 cell counts, or both. The microsimulation model, therefore, suggests that cost-effectiveness could be further improved if tests were to be implemented more widely among HIV inpatients. Broader screening policies might be easier to implement within current health systems than more targeted approaches. Simply being cost-effective does not mean an intervention is affordable. In a budget impact assessment, Reddy and colleagues showed that the primary intervention could save 51 000 years of life in Malawi and 171 000 years of life in South Africa over 5 years, with health-care expenditure for screened individuals increasing by $37 million (10·8%) and $261 million (2·8%) million, respectively, over the same period. The increased costs associated with TB-LAM represent small proportions of total health-care expenditure in both countries, and are driven primarily by the downstream increased need for antiretroviral drugs and non-antiretroviral therapy care rather than tuberculosis diagnostic costs, which are much smaller. Previous cost-effectiveness work in this area has shown that the incremental cost of diagnosing active tuberculosis with TB-LAM is far less than the incremental cost of treating tuberculosis and HIV, such that the incremental cost-effectiveness of TB-LAM begins to approximate the incremental cost-effectiveness of tuberculosis and HIV treatment.9Shah M Dowdy D Joloba M et al.Cost-effectiveness of novel algorithms for rapid diagnosis of tuberculosis in HIV-infected individuals in Uganda.AIDS. 2013; 27: 2883-2892Crossref PubMed Scopus (25) Google Scholar, 10Sun D Dorman S Shah M et al.Cost utility of lateral-flow urine lipoarabinomannan for tuberculosis diagnosis in HIV-infected African adults.Int J Tuberc Lung Dis. 2013; 17: 552-558Crossref PubMed Scopus (30) Google Scholar Although evidence in support of TB-LAM has been consistent,6Boyles TH Griesel R Stewart A Mendelson M Maartens G Incremental yield and cost of urine Determine TB-LAM and sputum induction in seriously ill adults with HIV.Int J Infect Dis. 2018; 75: 67-73Summary Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 8Orlando S Triulzi I Ciccacci F et al.Delayed diagnosis and treatment of tuberculosis in HIV+ patients in Mozambique: a cost-effectiveness analysis of screening protocols based on four symptom screening, smear microscopy, urine LAM test and Xpert MTB/RIF.PLoS One. 2018; 13: e0200523Crossref PubMed Scopus (10) Google Scholar, 9Shah M Dowdy D Joloba M et al.Cost-effectiveness of novel algorithms for rapid diagnosis of tuberculosis in HIV-infected individuals in Uganda.AIDS. 2013; 27: 2883-2892Crossref PubMed Scopus (25) Google Scholar, 10Sun D Dorman S Shah M et al.Cost utility of lateral-flow urine lipoarabinomannan for tuberculosis diagnosis in HIV-infected African adults.Int J Tuberc Lung Dis. 2013; 17: 552-558Crossref PubMed Scopus (30) Google Scholar the STAMP trial showed only weak evidence in favour of screening by this method.5Gupta-Wright A Corbett EL van Oosterhout JJ et al.Rapid urine-based screening for tuberculosis in HIV-positive patients admitted to hospital in Africa (STAMP): a pragmatic, multicentre, parallel-group, double-blind, randomised controlled trial.Lancet. 2018; 392: 292-301Summary Full Text Full Text PDF PubMed Scopus (118) Google Scholar If the addition of TB-LAM does not truly reduce mortality, including this test in screening strategies might not be worthwhile. Novel versions of TB-LAM are under development and evaluation and might offer further improvements in diagnostic accuracy of these tests. As novel tests become available, it will be important to consider how their different characteristics will affect cost-effectiveness estimates and what the preferred screening approaches might be. Evidence obtained in a wider range of settings and populations of patients, and with various diagnostic algorithms, will be required moving forward. The need for affordable, novel, rapid, non-sputum, point-of-contact diagnostic tools for diagnosis of tuberculosis remains a "key ask" of the tuberculosis community.11Stop TB PartnershipUnited to end tuberculosis: an urgent global response to a global epidemic. Key asks from TB stakeholders and communities.http://www.stoptb.org/assets/documents/global/advocacy/KEYASKS.PDFDate: Sept 26, 2018Date accessed: December 19, 2018Google Scholar We cannot wait for the perfect tool, but the TB-LAM test used by Reddy and colleagues4Reddy KP Gupta-Wright A Fielding KL et al.Cost-effectiveness of urine-based tuberculosis screening in hospitalised patients with HIV in Africa: a microsimulation modelling study.Lancet Glob Health. 2019; 7: e200-e208Summary Full Text Full Text PDF PubMed Scopus (23) Google Scholar increases diagnostic yield over the standard of care with sputum Xpert, while being low cost and requiring little equipment, training, and infrastructure compared with more complicated sputum and PCR-based diagnostic tests. Scale-up of existing tools is a crucial step in reducing mortality due to tuberculosis, and moving towards elimination of tuberculosis. Lessons learned from such work will only serve to better inform test development and future scale-up efforts. I declare no competing interests Cost-effectiveness of urine-based tuberculosis screening in hospitalised patients with HIV in Africa: a microsimulation modelling studyUrine-based tuberculosis screening of all hospitalised patients with HIV could increase life expectancy and be cost-effective in resource-limited settings. Urine TB-LAM is especially attractive because of high incremental diagnostic yield and low additional cost compared with sputum Xpert, making a compelling case for expanding its use to all hospitalised patients with HIV in areas with high HIV burden and endemic tuberculosis. Full-Text PDF Open Access