+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Rapid Diagnosis of Tuberculosis with the Xpert MTB/RIF Assay in High Burden Countries: A Cost-Effectiveness Analysis


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          A cost-effectiveness study by Frank Cobelens and colleagues reveals that Xpert MTB/RIF is a cost-effective method of tuberculosis diagnosis that is suitable for use in low- and middle-income settings.



          Xpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings.

          Methods and Findings

          We estimate the impact of the introduction of Xpert on the costs and cost-effectiveness of TB care using decision analytic modelling, comparing the introduction of Xpert to a base case of smear microscopy and clinical diagnosis in India, South Africa, and Uganda. The introduction of Xpert increases TB case finding in all three settings; from 72%–85% to 95%–99% of the cohort of individuals with suspected TB, compared to the base case. Diagnostic costs (including the costs of testing all individuals with suspected TB) also increase: from US$28–US$49 to US$133–US$146 and US$137–US$151 per TB case detected when Xpert is used “in addition to” and “as a replacement of” smear microscopy, respectively. The incremental cost effectiveness ratios (ICERs) for using Xpert “in addition to” smear microscopy, compared to the base case, range from US$41–$110 per disability adjusted life year (DALY) averted. Likewise the ICERS for using Xpert “as a replacement of” smear microscopy range from US$52–$138 per DALY averted. These ICERs are below the World Health Organization (WHO) willingness to pay threshold.


          Our results suggest that Xpert is a cost-effective method of TB diagnosis, compared to a base case of smear microscopy and clinical diagnosis of smear-negative TB in low- and middle-income settings where, with its ability to substantially increase case finding, it has important potential for improving TB diagnosis and control. The extent of cost-effectiveness gain to TB programmes from deploying Xpert is primarily dependent on current TB diagnostic practices. Further work is required during scale-up to validate these findings.

          Please see later in the article for the Editors' Summary

          Editors' Summary


          Tuberculosis (TB) is a bacterial disease that infects one-third of the world's population. The disease is caused by Mycobacterium tuberculosis, a bacterium that most commonly infects the lungs (known as pulmonary TB) and is transmitted from person to person when an infected individual coughs, sneezes, or talks. The symptoms of TB include chest pain, weight loss, fever, and a persistent cough that sometimes contains blood. Only 5%–10% of people who are infected with TB become sick or infectious, but people with weakened immune systems, such as individuals who are HIV-positive, are more likely to develop the disease. TB is estimated to have killed 1.7 million people in 2009 and is currently the leading cause of death among people infected with HIV.

          Why Was This Study Done?

          Although TB can be treated with a six-month course of antibiotics, effectively diagnosing TB is not always straightforward and drug resistance is becoming an increasing problem. One of the most common and simple methods to diagnose TB is a technique called sputum smear microscopy, which involves examining matter from the lungs under a microscope for the presence of TB-causing bacteria. However, despite being cheap and relatively simple, the test does not always detect active TB (smear-negative) and cannot determine whether the TB-causing bacteria are resistant to antibiotics. The World Health Organization has recently endorsed a new rapid test, called Xpert MTB/RIF (referred to as Xpert), for the initial diagnosis of TB. The test uses DNA amplification methods to reliably and quickly detect TB and whether infecting bacteria are resistant to the antibiotic rifampicin. The new test is expensive so there are concerns that the test might not be cost-effective in low- and middle-income countries.

          What Did the Researchers Do and Find?

          The researchers used a technique called modeling to simulate the outcome of 10,000 individuals with suspected TB as they went through a hypothetical diagnostic and treatment pathway. The model compared the costs associated with the introduction of Xpert to a base case for two different scenarios. In the base case all individuals with suspected TB had two sputum smear microscopy examinations followed by clinical diagnosis if they were smear-negative. For the different scenarios Xpert was either used in addition to the two sputum smear microscopy examinations (if the patient was smear-negative) or Xpert was used as a replacement for sputum smear microscopy for all patients. Different input parameters, based on country-specific estimates, were applied so that the model reflected the implementation of Xpert in India, South Africa, and Uganda.

          In the researcher's model the introduction of Xpert increased the proportion of TB-infected patients who were correctly diagnosed with TB in any of the settings. However, the cost per TB case detected increased by approximately US$100 in both scenarios. Although the cost of detection increased significantly, the cost of treatment increased only moderately because the number of false-positive cases was reduced. For example, the percentage of treatment costs spent on false-positive diagnoses in India was predicted to fall from 22% to 4% when Xpert was used to replace sputum smear microscopy. The model was used to calculate incremental cost effectiveness ratios (ICERs—the additional cost of each disability-adjusted life year [DALY] averted) for the different scenarios of Xpert implementation in the different settings. In comparison to the base case, introducing Xpert in addition to sputum smear microscopy produced ICERs ranging from US$41 to US$110 per DALY averted, while introducing Xpert instead of sputum smear microscopy yielded ICERs ranging from US$52 to US$138 per DALY averted.

          What Do These Findings Mean?

          The findings suggest that the implementation of Xpert in addition to, or instead of, sputum smear microscopy will be cost-effective in low- and middle-income countries. The calculated ICERs are below the World Health Organization's “willingness to pay threshold” for all settings. That is the incremental cost of each DALY averted by introduction of Xpert is below the gross domestic product per capita for each country ($1,134 for India, $5,786 South Africa, and $490 for Uganda in 2010). However, the authors note that achieving ICERs below the “willingness to pay threshold” does not necessarily mean that countries have the resources to implement the test. The researchers also note that there are limitations to their study; additional unknown costs associated with the scale-up of Xpert and some parameters, such as patient costs, were not included in the model. Although the model strongly suggests that Xpert will be cost-effective, the researchers caution that initial roll-out of Xpert should be carefully monitored and evaluated before full scale-up.

          Additional Information

          Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001120.

          Related collections

          Most cited references26

          • Record: found
          • Abstract: found
          • Article: not found

          HIV infection and multidrug-resistant tuberculosis: the perfect storm.

          Multidrug-resistant (MDR) tuberculosis (TB) has emerged as a global epidemic, with ~425,000 new cases estimated to occur annually. The global human immunodeficiency virus (HIV) infection epidemic has caused explosive increases in TB incidence and may be contributing to increases in MDR-TB prevalence. We reviewed published studies and available surveillance data evaluating links between HIV infection and MDR-TB to quantify convergence of these 2 epidemics, evaluate the consequences, and determine essential steps to address these epidemics. Institutional outbreaks of MDR-TB have primarily affected HIV-infected persons. Delayed diagnosis, inadequate initial treatment, and prolonged infectiousness led to extraordinary attack rates and case-fatality rates among HIV-infected persons. Whether this sequence occurs in communities is less clear. MDR-TB appears not to cause infection or disease more readily than drug-susceptible TB in HIV-infected persons. HIV infection may lead to malabsorption of anti-TB drugs and acquired rifamycin resistance. HIV-infected patients with MDR-TB have unacceptably high mortality; both antiretroviral and antimycobacterial treatment are necessary. Simultaneous treatment requires 6-10 different drugs. In HIV-prevalent countries, TB programs struggle with increased caseloads, which increase the risk of acquired MDR-TB. Surveillance data suggest that HIV infection and MDR-TB may converge in several countries. Institutional outbreaks, overwhelmed public health programs, and complex clinical management issues may contribute to the convergence of the MDR-TB and HIV infection epidemics. To forestall disastrous consequences, infection control, rapid case detection, effective treatment, and expanded program capacity are needed urgently.
            • Record: found
            • Abstract: found
            • Article: not found

            Cost effectiveness in low- and middle-income countries: a review of the debates surrounding decision rules.

            Cost-effectiveness analysis (CEA) is increasingly important in public health decision making, including in low- and middle-income countries. The decision makers' valuation of a unit of health gain, or ceiling ratio (lambda), is important in CEA as the relative value against which acceptability is defined, although values are usually chosen arbitrarily in practice. Reference case estimates for lambda are useful to promote consistency, facilitate new developments in decision analysis, compare estimates against benefit-cost ratios from other economic sectors, and explicitly inform decisions about equity in global health budgets. The aim of this article is to discuss values for lambda used in practice, including derivation based on affordability expectations (such as $US150 per disability-adjusted life-year [DALY]), some multiple of gross national income or gross domestic product, and preference-elicitation methods, and explore the implications associated with each approach. The background to the debate is introduced, the theoretical bases of current values are reviewed, and examples are given of their application in practice. Advantages and disadvantages of each method for defining lambda are outlined, followed by an exploration of methodological and policy implications.
              • Record: found
              • Abstract: found
              • Article: not found

              Standard short-course chemotherapy for drug-resistant tuberculosis: treatment outcomes in 6 countries.

              No large-scale study has investigated the impact of multidrug-resistant tuberculosis (TB) on the outcome of standard short-course chemotherapy under routine countrywide TB control program conditions in the World Health Organization's (WHO) directly observed treatment short-course strategy for TB control. To assess the results of treatment with first-line drugs for patients enrolled in the WHO and the International Union Against Tuberculosis and Lung Disease's global project on drug-resistance surveillance. Retrospective cohort study of patients with TB in the Dominican Republic, Hong Kong Special Administrative Region (People's Republic of China), Italy, Ivanovo Oblast (Russian Federation), the Republic of Korea, and Peru. New and retreatment TB cases who received short-course chemotherapy with isoniazid, rifampicin, pyrazinamide, and either ethambutol or streptomycin between 1994 and 1996. Treatment response according to WHO treatment outcome categories (cured; died; completed, defaulted, or failed treatment; or transferred). Of the 6402 culture-positive TB cases evaluated, 5526 (86%) were new cases and 876 (14%) were retreatment cases. A total of 1148 (20.8%) new cases and 390 (44.5%) retreatment cases were drug resistant, including 184 and 169 cases of multidrug-resistant TB, respectively. Of the new cases 4585 (83%) were treated successfully, 138 (2%) died, and 151 (3%) experienced short-course chemotherapy failure. Overall, treatment failure (relative risk [RR], 15.4; 95% confidence interval [CI], 10.6-22.4; P<.001) and mortality (RR, 3.73; 95% CI, 2.13-6.53; P<.001) were higher among new multidrug-resistant TB cases than among new susceptible cases. Even in settings using 100% direct observation, cases with multidrug resistance had a significantly higher failure rate than those who were susceptible (9/94 [10%] vs 8/1410 [0.7%]; RR, 16.9; 95% CI, 6.6-42.7; P<.001). Treatment failure was also higher among patients with any rifampicin resistance (n=115) other than multidrug resistance (RR, 5.48; 95% CI, 3.04-9.87; P<.001), any isoniazid resistance (n=457) other than multidrug resistance (RR, 3. 06; 95% CI, 1.85-5.05; P<.001), and among patients with TB resistant to rifampicin only (n=76) (RR, 5.47; 95% CI, 2.68-11.2; P<.001). Of the retreatment cases, 497 (57%) were treated successfully, 51 (6%) died, and 124 (14%) failed short-course chemotherapy treatment. Failure rates among retreatment cases were higher in those with multidrug-resistant TB, with any isoniazid resistance other than multidrug resistance, and in cases with TB resistant to isoniazid only. These data suggest that standard short-course chemotherapy, based on first-line drugs, is an inadequate treatment for some patients with drug-resistant TB. Although the directly observed treatment short-course strategy is the basis of good TB control, the strategy should be modified in some settings to identify drug-resistant cases sooner, and to make use of second-line drugs in appropriate treatment regimens. JAMA. 2000;283:2537-2545

                Author and article information

                Role: Academic Editor
                PLoS Med
                PLoS Medicine
                Public Library of Science (San Francisco, USA )
                November 2011
                November 2011
                8 November 2011
                : 8
                : 11
                [1 ]Department of Global Health, and Amsterdam Institute of Global Health and Development, Academic Medical Center, Amsterdam, The Netherlands
                [2 ]Department of Global Health and Development, London School of Hygiene & Tropical Medicine, London, United Kingdom
                [3 ]Department of Epidemiology and Biostatistics, McGill University, Canada
                [4 ]Christian Medical College, Vellore, India
                [5 ]National TB Program, Vellore, India
                [6 ]Makerere University - University of California, San Francisco (MU-UCSF) Research Collaboration, Kampala, Uganda
                [7 ]Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California, San Francisco, United States of America
                [8 ]National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa
                [9 ]Division of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa
                [10 ]Tropical Disease Foundation, Manila, Philippines
                [11 ]Special Treatment Institution, Baku, Azerbaijan
                [12 ]Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru
                [13 ]Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland
                Edendale Hospital, South Africa
                Author notes

                Conceived and designed the experiments: AV Svk FC. Analyzed the data: AV Svk FC. Wrote the first draft of the manuscript: AV Svk FC. Contributed to the writing of the manuscript: AV SvK HS JSM KRJ SdB JLD AW MPN MTG AK CZ MDP CCB FC. ICMJE criteria for authorship read and met: AV SvK HS JSM KRJ SdB JLD AW MPN MTG AK CZ MDP CCB FC. Agree with manuscript results and conclusions: AV SvK HS JSM KRJ SdB JLD AW MPN MTG AK CZ MDP CCB FC. AV, Svk, and FC designed the overall study and the decision analytic model. SvK constructed the model. AV, SvK, and HS designed and carried out cost data collection. AV, SvK, and FC analyzed the final data and developed the first manuscript draft. JSM, KRJ, SdB, JLD, AW, MPN, MTG, AK, CZ, CCB, and MDP contributed to collecting and analyzing the diagnostic field data on which the decision models were based. All authors contributed to data collection, interpretation of data and revision of the article.

                Vassall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 14
                Research Article



                Comment on this article