Cost-effectiveness of Xpert MTB/RIF and investing in health care in Africa
Authors: Keertan Dheda, Grant Theron, Alex Welte
Journal: The Lancet Global Health (2014)

The Xpert MTB/RIF assay is an accurate test for the diagnosis of tuberculosis when an adequate sputum sample can be obtained; even in smear-negative tuberculosis the sensitivity is about 67%.1Steingart KR Sohn H Schiller I et al.Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults.Cochrane Database Syst Rev. 2014; : 1Google Scholar, 2Theron G Peter J van Zyl-Smit R et al.Evaluation of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in a high HIV prevalence setting.Am J Respir Crit Care Med. 2011; 184: 132-140Crossref PubMed Scopus (242) Google Scholar Although the assay turnaround time is under 2 h, depending on the health-care setting, time to tuberculosis treatment can be 2 weeks or more in a substantial number of patients.3Cohen GM Drain PK Noubary F Cloete C Bassett IV Diagnostic delays and clinical decision-making with centralized Xpert MTB/RIF testing in Durban, South Africa.J Acquir Imm Defic Syndr. 2014; (Published online August 12.)http://dx.doi.org/10.1097/QAI.0000000000000309Google Scholar The technology has now been endorsed by WHO as a frontline test for tuberculosis in populations where there is a high incidence of HIV.4WHOAutomated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB / RIF system for the diagnosis of pulmonary and extrapulmonary tuberculosis in adults and children.http://apps.who.int/iris/handle/10665/112472Google Scholar Indeed, several countries in Africa are rolling out Xpert MTB/RIF.5Scully T Tuberculosis.Nature. 2013; 502: S1-SSCrossref PubMed Scopus (6) Google Scholar However, for expanded and sustained uptake, governments and policy makers require information about the cost-effectiveness of the technology to allow for appropriate planning and allocation of health-care resources. Cost-effectiveness must be balanced against affordability and sustainability. Thus, although the diagnostic accuracy of the technique is not in doubt, questions remain about the cost-effectiveness of the technology given that the overall number of patients treated for tuberculosis can remain unchanged6Theron G Zijenah L Chanda D et al.Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial.Lancet. 2014; 383: 424-435Summary Full Text Full Text PDF PubMed Scopus (326) Google Scholar and given the high rates of empirical treatment in resource-poor health-care settings.7Theron G Peter J Dowdy D Langley I Squire SB Dheda K Do high rates of empirical treatment undermine the potential effect of new diagnostic tests for tuberculosis in high-burden settings?.Lancet Infect Dis. 2014; 14: 527-532Summary Full Text Full Text PDF PubMed Scopus (121) Google Scholar Modelling studies have estimated that the implementation of Xpert MTB/RIF, either in addition to or as a replacement to smear microscopy, will be cost-effective for the diagnosis of tuberculosis and mutidrug-resistant (MDR) tuberculosis in countries with a high burden.8Theron G Pooran A Peter J et al.Do adjunct tuberculosis tests, when combined with Xpert MTB/RIF, improve accuracy and the cost of diagnosis in a resource-poor setting?.Eur Respir J. 2012; 40: 161-168Crossref PubMed Scopus (55) Google Scholar, 9Pantoja A Fitzpatrick C Vassall A Weyer K Floyd K Xpert MTB/RIF for diagnosis of tuberculosis and drug-resistant tuberculosis: a cost and affordability analysis.Eur Respir J. 2013; 42: 708-720Crossref PubMed Scopus (71) Google Scholar, 10Vassall A van Kampen S Sohn H et al.Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis.PLoS Med. 2011; 8: e1001120Crossref PubMed Scopus (238) Google Scholar, 11Menzies NA Cohen T Lin H-H Murray M Salomon JA Population health impact and cost-effectiveness of tuberculosis diagnosis with Xpert MTB/RIF: a dynamic simulation and economic evaluation.PLoS Med. 2012; 9: e1001347Crossref PubMed Scopus (152) Google Scholar The incremental cost of each disability-associated life-year averted by Xpert implementation (the incremental cost-effectiveness ratio [ICER]) is below the WHO-defined "willingness to pay" threshold for all settings modelled by Vassal and colleagues,10Vassall A van Kampen S Sohn H et al.Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis.PLoS Med. 2011; 8: e1001120Crossref PubMed Scopus (238) Google Scholar and the findings of Menzies and colleagues suggest that Xpert implementation could, through improved case-finding and treatment, substantially reduce tuberculosis illness and death.11Menzies NA Cohen T Lin H-H Murray M Salomon JA Population health impact and cost-effectiveness of tuberculosis diagnosis with Xpert MTB/RIF: a dynamic simulation and economic evaluation.PLoS Med. 2012; 9: e1001347Crossref PubMed Scopus (152) Google Scholar However, these studies differed in their assumptions about disease transmission, rates of MDR tuberculosis, duration and effect of future disease burden, downstream effects of antiretroviral therapy, and how the relevant health-care system models were constructed. Thus, further data are required about the cost-effectiveness of different algorithmic strategies on health-care systems in Africa. In this issue of The Lancet Global Health, Ivor Langley and colleagues12Langley I Lin H-H Egwaga S et al.Assessment of the patient, health system, and population effects of Xpert MTB/RIF and alternative diagnostics for tuberculosis in Tanzania: an integrated modelling approach.Lancet Glob Health. 2014; 2: e581-e591Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar assess the cost-effectiveness of different diagnostic strategies on cost-effectiveness within the context of the Tanzanian health-care system. These strategies included a combination of conventional smear microscopy (Ziehl Nielson staining), LED microscopy (conventional versus same day), full roll-out of Xpert MTB/RIF, and LED microscopy followed by targeted Xpert in smear-negative cases (the latter two strategies in either all HIV-infected persons or only those known be HIV-infected). They found, using an integrated modelling approach, that full roll-out of Xpert MTB/RIF was the most cost-effective option with the potential to substantially reduce national tuberculosis burden, and that targeted use of Xpert MTB/RIF after microscopy in HIV-infected people was a less cost-effective approach. The latter was less cost-effective because of the reduced likelihood of preventing death and reduction in the potential gain in life-years owing to the shortened lifespan in HIV-infected people. However, there are several limitations to these findings. Current diagnostic practice, especially the frequency, timing, and accuracy of clinical diagnoses or empirical tuberculosis treatment, is highly setting-specific, dependent on adherence to the WHO algorithm for smear-negative tuberculosis,13Getahun H Harrington M O'Brien R Nunn P Diagnosis of smear-negative pulmonary tuberculosis in people with HIV infection or AIDS in resource-constrained settings: informing urgent policy changes.Lancet. 2007; 369: 2042-2049Summary Full Text Full Text PDF PubMed Scopus (412) Google Scholar and can reduce the cost-effectiveness of diagnostic interventions.7Theron G Peter J Dowdy D Langley I Squire SB Dheda K Do high rates of empirical treatment undermine the potential effect of new diagnostic tests for tuberculosis in high-burden settings?.Lancet Infect Dis. 2014; 14: 527-532Summary Full Text Full Text PDF PubMed Scopus (121) Google Scholar, 14Lin H-H Dowdy D Dye C Murray M Cohen T The impact of new tuberculosis diagnostics on transmission: why context matters.Bull World Health Organ. 2012; 90: 739-747Crossref PubMed Scopus (42) Google Scholar Langley and colleagues' estimated sensitivity of smear-negative tuberculosis in Tanzania (52%)15Swai HF Mugusi FM Mbwambo JK Sputum smear negative pulmonary tuberculosis: sensitivity and specificity of diagnostic algorithm.BMC Res Notes. 2011; 4: 475Crossref PubMed Scopus (55) Google Scholar is lower than that from a recent meta-analysis,16Walusimbi S Bwanga F De Costa A Haile M Joloba M Hoffner S Meta-analysis to compare the accuracy of GeneXpert, MODS and the WHO 2007 algorithm for diagnosis of smear-negative pulmonary tuberculosis.BMC Infect Dis. 2013; 13: 507Crossref PubMed Scopus (67) Google Scholar and the authors also assumed excellent specificity (95%). In South Africa, for example, most smear-negative patients seem to be "detected" through empirical treatment, and, as seen in Uganda and Kenya,17Nakiyingi L Bwanika JM Kirenga B et al.Clinical predictors and accuracy of empiric tuberculosis treatment among sputum smear-negative HIV-infected adult tuberculosis suspects in Uganda.PLOS One. 2013; 8: e74023Crossref PubMed Scopus (26) Google Scholar, 18Huerga H Varaine F Okwaro E et al.Performance of the 2007 WHO algorithm to diagnose smear-negative pulmonary tuberculosis in a HIV prevalent setting.PLoS One. 2012; 7: e51336Crossref PubMed Scopus (27) Google Scholar less than half of notified cases are microbiologically confirmed, suggesting that significant overtreatment is occurring.6Theron G Zijenah L Chanda D et al.Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial.Lancet. 2014; 383: 424-435Summary Full Text Full Text PDF PubMed Scopus (326) Google Scholar Furthermore, patient-level costs were not included and these are known to be substantial and influence default, particular in tuberculosis-endemic countries.19Barter D Agboola S Murray M Barnighausen T Tuberculosis and poverty: the contribution of patient costs in sub-Saharan Africa–a systematic review.BMC Public Health. 2012; 12: 980Crossref PubMed Scopus (102) Google Scholar The targeted use of Xpert MTB/RIF after smear microscopy was only explored in HIV-infected participants and not HIV-uninfected people. The ICER also differed substantially from other studies.10Vassall A van Kampen S Sohn H et al.Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis.PLoS Med. 2011; 8: e1001120Crossref PubMed Scopus (238) Google Scholar However, this must be understood within the context of different assumptions about transmission, future disease burden, and antiretroviral therapy, among other factors. MDR tuberculosis was not considered in the transmission component and therefore one wonders about applicability to other settings with high rates of MDR tuberculosis, such as South Africa. However, the higher rates of MDR tuberculosis would probably have made the Xpert MTB/RIF strategy even more cost-effective in this context. One could further debate many nuances of the internal workings of the models and their external validity in replicating or predicting outcomes in the priority areas for tuberculosis intervention, but perhaps it is not reasonable to ask too much of a single study. We would argue that sensitivities of the model to particular assumptions warrant further discussion, and be interpreted not just as limitations but as flags that inform programmatic implementation. Despite these limitations, several of which are acknowledged by Langley and colleagues,12Langley I Lin H-H Egwaga S et al.Assessment of the patient, health system, and population effects of Xpert MTB/RIF and alternative diagnostics for tuberculosis in Tanzania: an integrated modelling approach.Lancet Glob Health. 2014; 2: e581-e591Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar the study adds important information to the current knowledge base, and not only confirms but quantifies the cost-effectiveness of Xpert MTB/RIF in the Tanzanian setting. It further provides crucial information about the magnitude of investment that must be made by African governments for full roll-out of Xpert MTB/RIF. Tuberculosis is now the commonest cause of death in many African countries and has a significant effect on national gross domestic products (GDPs). It therefore makes economic sense to invest in health-care systems and to roll out technologies such as nucleic acid amplification tests. However, knowledge translation is now required to affect the decision making process at programmatic level, and thereafter monitor post-implementation operational and epidemiological indicators. However, the potential gains of Xpert MTB/RIF can only be realised if several other operational and logistic aspects of the health-care system, as a whole, are addressed including communication and transport infrastructure, capacity of the national treatment programme, and investing in efficient reporting systems, among others, so that the impact of Xpert MTB/RIF can be realised on the ground. Most importantly, however, it is time for governments and policy makers to invest in health care so that the potential gains of newer technologies such as Xpert MTB/RIF can be translated into reduced morbidity and mortality, and positively affect the GDPs of African economies. There are several indications that Africa is entering a golden age of economic prosperity and it is hoped that investment in health-care systems and infrastructure will parallel this boom. The data by Langley and colleagues inform this agenda. We declare no competing interests. Assessment of the patient, health system, and population effects of Xpert MTB/RIF and alternative diagnostics for tuberculosis in Tanzania: an integrated modelling approachFor Tanzania, this integrated modelling approach predicts that full rollout of Xpert is a cost-effective option for tuberculosis diagnosis and has the potential to substantially reduce the national tuberculosis burden. It also estimates the substantial level of funding that will need to be mobilised to translate this into clinical practice. This approach could be adapted and replicated in other developing countries to inform rational health policy formulation. Full-Text PDF Open AccessCost-effectiveness of Xpert MTB/RIF and investing in health care in AfricaWe welcome the Comment by Keertan Dheda and colleagues (October issue)1 about our modelling study2 that assessed the effects and cost-effectiveness of several new tuberculosis diagnostic algorithms for adult pulmonary tuberculosis in Tanzania. However, we would argue that some key points about the importance of the work have been omitted. Full-Text PDF Open Access