TY - JOUR AB - Background: In sub-Saharan Africa, patients with advanced HIV experience high mortality during the first few months of antiretroviral therapy (ART), largely attributable to tuberculosis (TB). We evaluated the cost-effectiveness of TB diagnostic strategies to reduce this early mortality. Methods: We developed a decision analytic model to estimate the incremental cost, deaths averted, and cost-effectiveness of 3 TB diagnostic algorithms. The model base case represents current practice (symptoms screening, sputum smear, and chest radiography) in many resource-limited countries in sub-Saharan Africa. We compared the current practice with World Health Organization (WHO)-recommended practice with culture and WHO-recommended practice with the Xpert mycobacterium tuberculosis and resistance to rifampicin test and considered relevant medical costs from a health system perspective using the timeframe of the first 6 months of ART. We conducted univariate and probabilistic sensitivity analyses on all parameters in the model. Results: When considering TB diagnosis and treatment and ART costs, the cost per patient was $850 for current practice, $809 for the algorithm with Xpert test, and $879 for the algorithm with culture. Our results showed that both WHO-recommended algorithms avert more deaths among TB cases than does the current practice. The algorithm with Xpert test was least costly at reducing early mortality compared with the current practice. Sensitivity analyses indicated that cost-effectiveness findings were stable. Conclusions: Our analysis showed that culture or Xpert were cost-effective at reducing early mortality during the first 6 months of ART compared with the current practice. Thus, our findings provide support for ongoing efforts to expand TB diagnostic capacity. AU - Abimbola, Taiwo O. AU - Marston, Barbara J. AU - Date, Anand A. AU - Blandford, John M. AU - Sangrujee, Nalinee AU - Wiktor, Stefan Z. KW - HIV tuberculosis tuberculosis diagnosis cost cost-effectiveness sub-Saharan Africa 00126334-201205010-00016 M1 - 1 PY - 2012 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1525-4135 SP - e1-e7 10.1097/QAI.0b013e318246538f ST - Cost-Effectiveness of Tuberculosis Diagnostic Strategies to Reduce Early Mortality Among Persons With Advanced HIV Infection Initiating Antiretroviral Therapy T2 - JAIDS Journal of Acquired Immune Deficiency Syndromes TI - Cost-Effectiveness of Tuberculosis Diagnostic Strategies to Reduce Early Mortality Among Persons With Advanced HIV Infection Initiating Antiretroviral Therapy UR - http://journals.lww.com/jaids/Fulltext/2012/05010/Cost_Effectiveness_of_Tuberculosis_Diagnostic.16.aspx http://graphics.tx.ovid.com/ovftpdfs/FPDDNCDCLFEDDD00/fs047/ovft/live/gv024/00126334/00126334-201205010-00016.pdf VL - 60 ID - 540 ER - TY - JOUR AB - The Bill and Melinda Gates Foundation supports an ambitious portfolio of novel vaccines, drug regimens, and diagnostic tools for tuberculosis (TB). We elicited the expected efficacies and improvements of the novel interventions in discussions with the foundations managing their development. Using an age-structured mathematical model of TB, we explored the potential benefits of novel interventions under development and those not yet in the portfolio, focusing on the WHO Southeast Asia region. Neonatal vaccination with the portfolio vaccine decreases TB incidence by 39% to 52% by 2050. Drug regimens that shorten treatment duration and are efficacious against drug-resistant strains reduce incidence by 10-27%. New diagnostics reduce incidence by 13-42%. A triple combination of a portfolio vaccine, drug regimen, and diagnostics reduces incidence by 71%. A short mass vaccination catch-up campaign, not yet in the portfolio, to augment the triple combination, accelerates the decrease, preventing >30% more cases by 2050 than just the triple combination. New vaccines and drug regimens targeted at the vast reservoir of latently infected people, not in the portfolio, would reduce incidence by 37% and 82%, respectively. The combination of preventive latent therapy and a 2-month drug treatment regimen reduces incidence by 94%. Novel technologies in the pipeline would achieve substantial reductions in TB incidence, but not the Stop TB Partnership target for elimination. Elimination will require new delivery strategies, such as mass vaccination campaigns, and new products targeted at latently infected people. AD - Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. AN - 19666590 AU - Abu-Raddad, L. J. AU - Sabatelli, L. AU - Achterberg, J. T. AU - Sugimoto, J. D. AU - Longini, I. M., Jr. AU - Dye, C. AU - Halloran, M. E. C2 - 2720405 DA - Aug 18 DO - 0901720106 [pii] 10.1073/pnas.0901720106 [doi] DP - Nlm ET - 2009/08/12 KW - Antitubercular Agents/ therapeutic use Asia, Southeastern Combined Modality Therapy/methods Disease Progression Humans Immunization Programs Models, Theoretical Prevalence Public Health Reproducibility of Results Time Factors Tuberculosis/diagnosis/drug therapy/ epidemiology/prevention & control Tuberculosis Vaccines/ therapeutic use World Health LA - eng M1 - 33 N1 - Abu-Raddad, Laith J Sabatelli, Lorenzo Achterberg, Jerusha T Sugimoto, Jonathan D Longini, Ira M Jr Dye, Christopher Halloran, M Elizabeth T32 HD007543-10/HD/NICHD NIH HHS/United States Research Support, Non-U.S. Gov't United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13980-5. Epub 2009 Aug 3. PY - 2009 RN - fulltext fulltext_1208 SN - 1091-6490 (Electronic) 0027-8424 (Linking) SP - 13980-5 ST - Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics T2 - Proc Natl Acad Sci U S A TI - Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics UR - http://www.pnas.org/content/106/33/13980.full.pdf VL - 106 ID - 617 ER - TY - JOUR AB - BACKGROUND: Resistance to commonly used antituberculosis drugs is emerging worldwide. Conventional drug-susceptibility testing (DST) methods are slow and demanding. Alternative, rapid DST methods would permit the early detection of drug resistance and, in turn, arrest tuberculosis transmission. METHODS: A cost-effectiveness analysis of 5 DST methods was performed in the context of a clinical trial that compared rapid with conventional DST methods. The methods under investigation were direct phage-replication assay (FASTPlaque-Response; Biotech), direct amplification and reverse hybridization of the rpoB gene (INNO-LiPA; Innogenetics), indirect colorimetric minimum inhibitory concentration assay (MTT; ICN Biomedicals), and direct proportion method on Lowenstein-Jensen medium. These were compared with the widely used indirect proportion method on Lowenstein-Jensen medium. RESULTS: All alternative DST methods were found to be cost-effective, compared with other health care interventions. DST methods also generate substantial cost savings in settings of high prevalence of multidrug-resistant tuberculosis. Excluding the effects of transmission, the direct proportion method on Lowenstein-Jensen medium was the most cost-effective alternative DST method for patient groups with prevalences of multidrug-resistant tuberculosis of 2%, 5%, 20%, and 50% (cost in US$2004, $94, $36, $8, and $2 per disability-adjusted life year, respectively). CONCLUSION: Alternative, rapid methods for DST are cost-effective and should be considered for use by national tuberculosis programs in middle-income countries. AD - Instituto de Medicina Tropical Alexander Von Humboldt, Lima, Peru. AN - 18636955 AU - Acuna-Villaorduna, C. AU - Vassall, A. AU - Henostroza, G. AU - Seas, C. AU - Guerra, H. AU - Vasquez, L. AU - Morcillo, N. AU - Saravia, J. AU - O'Brien, R. AU - Perkins, M. D. AU - Cunningham, J. AU - Llanos-Zavalaga, L. AU - Gotuzzo, E. DA - Aug 15 DO - 10.1086/590010 ET - 2008/07/19 KW - Antitubercular Agents/*pharmacology Bacterial Proteins/genetics Colorimetry Cost-Benefit Analysis *Drug Resistance, Multiple, Bacterial Gene Amplification Humans Income/classification Microbial Sensitivity Tests/economics/methods Mycobacteriophages/physiology Mycobacterium tuberculosis/*drug effects/genetics/growth & development Nucleic Acid Hybridization Peru Quality-Adjusted Life Years Reagent Kits, Diagnostic Sensitivity and Specificity Time Factors Tuberculosis, Multidrug-Resistant/*diagnosis/epidemiology/microbiology Tuberculosis, Pulmonary/diagnosis/epidemiology/microbiology LA - eng M1 - 4 N1 - Acuna-Villaorduna, Carlos Vassall, Anna Henostroza, German Seas, Carlos Guerra, Humberto Vasquez, Lucy Morcillo, Nora Saravia, Juan O'Brien, Richard Perkins, Mark D Cunningham, Jane Llanos-Zavalaga, Luis Gotuzzo, Eduardo Clinical Trial, Phase III Research Support, Non-U.S. Gov't United States Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Clin Infect Dis. 2008 Aug 15;47(4):487-95. PY - 2008 RN - fulltext fulltext_1208 SN - 1537-6591 (Electronic) 1058-4838 (Linking) SP - 487-95 ST - Cost-effectiveness analysis of introduction of rapid, alternative methods to identify multidrug-resistant tuberculosis in middle-income countries T2 - Clin Infect Dis TI - Cost-effectiveness analysis of introduction of rapid, alternative methods to identify multidrug-resistant tuberculosis in middle-income countries UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18636955http://www.journals.uchicago.edu/doi/pdf/10.1086/590010 http://cid.oxfordjournals.org/content/47/4/487.full.pdf VL - 47 ID - 619 ER - TY - JOUR AB - OBJECTIVE: To compare the cost-effectiveness of three diagnostic algorithms incorporating a new rapid test, FASTPlaqueTB, with the current National TB Control Programme (NTCP) algorithm for diagnosis of pulmonary tuberculosis in new smear-negative suspects in South Africa. DESIGN: A model of the outcome of patients screened using each diagnostic algorithm was established using published costs and performance data for each component of the algorithm. Direct health care provider costs associated with provision of each diagnostic strategy were determined. Overall performance, total cost, speed and accuracy of diagnosis were estimated for screening 1000 new TB suspects using each algorithm. RESULTS: The use of FASTPlaqueTB and culture algorithms enabled 28% more smear-negative TB patients to be diagnosed overall and was cheaper to implement than the NTCP algorithm (18,312-18,581 US dollars compared with 20,079 dollars). Fewer clinic visits were required to establish a diagnosis, reducing clinic workload and patient costs. FASTPlaqueTB enabled rapid and specific diagnosis of at least 50% of smear-negative TB patients within 2 days. CONCLUSIONS: The use of FASTPlaqueTB can assist in improving existing case detection strategies and may be cost-effectively integrated into the current diagnostic infrastructure, offering patients more rapid and reliable diagnosis whilst reducing the overall cost. AD - Biotec Laboratories Ltd., c/o National Health Laboratory Service, Cape Town, Western Cape, South Africa. alberth@mweb.co.za AN - 15139454 AU - Albert, H. DA - Feb ET - 2004/05/14 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - *Algorithms Bacteriological Techniques/*economics Cost-Benefit Analysis Humans Mycobacterium tuberculosis/classification Predictive Value of Tests South Africa Sputum/*microbiology Time Factors Tuberculosis, Pulmonary/*diagnosis LA - eng M1 - 2 M3 - Comparative Study N1 - Albert, H France Int J Tuberc Lung Dis. 2004 Feb;8(2):240-7. PY - 2004 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 240-7 ST - Economic analysis of the diagnosis of smear-negative pulmonary tuberculosis in South Africa: incorporation of a new rapid test, FASTPlaqueTB, into the diagnostic algorithm T2 - Int J Tuberc Lung Dis TI - Economic analysis of the diagnosis of smear-negative pulmonary tuberculosis in South Africa: incorporation of a new rapid test, FASTPlaqueTB, into the diagnostic algorithm UR - http://www.ncbi.nlm.nih.gov/pubmed/15139454 VL - 8 ID - 1418 ER - TY - JOUR AB - Background: In settings with high tuberculosis (TB) prevalence, 15–30% of HIV-infected individuals initiating antiretroviral therapy (ART) have undiagnosed TB. Such patients are usually screened by symptoms and sputum smear, which have poor sensitivity. Objective: To project the clinical and economic outcomes of using Xpert MTB/RIF(Xpert), a rapid TB/rifampicin-resistance diagnostic, to screen individuals initiating ART. Design: We used a microsimulation model to evaluate the clinical impact and cost-effectiveness of alternative TB screening modalities – in all patients or only symptomatic patients – for hypothetical cohorts of individuals initiating ART in South Africa (mean CD4 cell count = 171 cells/μl; TB prevalence 22%). We simulated no active screening and four diagnostic strategies, smear microscopy (sensitivity 23%); smear and culture (sensitivity, 100%); one Xpert sample (sensitivity in smear-negative TB: 43%); two Xpert samples (sensitivity in smear-negative TB: 62%). Outcomes included projected life expectancy, lifetime costs (2010 US$), and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs less than $7100 (South African gross domestic product per capita) were considered very cost-effective. Results: Compared with no screening, life expectancy in TB-infected patients increased by 1.6 months using smear in symptomatic patients and by 6.6 months with two Xpert samples in all patients. At 22% TB prevalence, the ICER of smear for all patients was $2800 per year of life saved (YLS), and of Xpert (two samples) for all patients was $5100/YLS. Strategies involving one Xpert sample or symptom screening were less efficient. Conclusion: Model-based analysis suggests that screening all individuals initiating ART in South Africa with two Xpert samples is very cost-effective. AU - Andrews, Jason R. AU - Lawn, Stephen D. AU - Rusu, Corina AU - Wood, Robin AU - Noubary, Farzad AU - Bender, Melissa A. AU - Horsburgh, C. Robert AU - Losina, Elena AU - Freedberg, Kenneth A. AU - Walensky, Rochelle P. KW - antiretroviral therapy cost-effectiveness diagnostics HIV tuberculosis 00002030-201205150-00010 M1 - 8 PY - 2012 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0269-9370 SP - 987-995 10.1097/QAD.0b013e3283522d47 ST - The cost-effectiveness of routine tuberculosis screening with Xpert MTB/RIF prior to initiation of antiretroviral therapy: a model-based analysis T2 - AIDS TI - The cost-effectiveness of routine tuberculosis screening with Xpert MTB/RIF prior to initiation of antiretroviral therapy: a model-based analysis UR - http://journals.lww.com/aidsonline/Fulltext/2012/05150/The_cost_effectiveness_of_routine_tuberculosis.10.aspx http://graphics.tx.ovid.com/ovftpdfs/FPDDNCDCLFEDDD00/fs047/ovft/live/gv024/00002030/00002030-201205150-00010.pdf VL - 26 ID - 541 ER - TY - JOUR AB - Extensively drug-resistant tuberculosis (XDR TB) has been detected in most provinces of South Africa, particularly in the KwaZulu-Natal province where several hundred cases have been reported since 2004. We analyzed the transmission dynamics of XDR TB in the region using mathematical models, and observed that nosocomial transmission clusters of XDR TB may emerge into community-based epidemics under the public health conditions of many South African communities. The effective reproductive number of XDR TB in KwaZulu-Natal may be around 2. Intensified community-based case finding and therapy appears critical to curtailing transmission. In the setting of delayed disease presentation and high system demand, improved diagnostic approaches may need to be employed in community-based programs rather than exclusively at tertiary hospitals. Using branching process mathematics, we observed that early, community-based drug-susceptibility testing and effective XDR therapy could help curtail ongoing transmission and reduce the probability of XDR TB epidemics in neighboring territories. AD - Tugela Ferry Care and Research Collaboration, Tugela Ferry, KwaZulu-Natal 3010, South Africa. sanjay.basu@yale.edu AN - 19365076 AU - Basu, S. AU - Friedland, G. H. AU - Medlock, J. AU - Andrews, J. R. AU - Shah, N. S. AU - Gandhi, N. R. AU - Moll, A. AU - Moodley, P. AU - Sturm, A. W. AU - Galvani, A. P. C2 - 2678614 DA - May 5 DO - 0812472106 [pii] 10.1073/pnas.0812472106 [doi] DP - Nlm ET - 2009/04/15 KW - Disease Outbreaks/ prevention & control Humans Models, Biological South Africa/epidemiology Tuberculosis, Multidrug-Resistant/ epidemiology/ prevention & control/transmission LA - eng M1 - 18 N1 - Basu, Sanjay Friedland, Gerald H Medlock, Jan Andrews, Jason R Shah, N Sarita Gandhi, Neel R Moll, Anthony Moodley, Prashini Sturm, A Willem Galvani, Alison P R36/PHS HHS/United States T32/PHS HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2009 May 5;106(18):7672-7. Epub 2009 Apr 13. PY - 2009 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1091-6490 (Electronic) 0027-8424 (Linking) SP - 7672-7 ST - Averting epidemics of extensively drug-resistant tuberculosis T2 - Proc Natl Acad Sci U S A TI - Averting epidemics of extensively drug-resistant tuberculosis UR - http://www.pnas.org/content/106/18/7672.full.pdf VL - 106 ID - 548 ER - TY - JOUR AB - SETTING: Bleach sedimentation is a method used to increase the diagnostic yield of sputum microscopy for countries with a high prevalence of human immunodeficiency virus (HIV) infection and limited resources. OBJECTIVES: To compare the relative cost-effectiveness of different microscopy approaches in diagnosing tuberculosis (TB) in Kenya. METHODS: An analytical decision tree model including cost and effectiveness measures of 10 combinations of direct (D) and overnight bleach (B) sedimentation microscopy was constructed. Data were drawn from the evaluation of the bleach sedimentation method on two specimens (first on the spot [1] and second morning [2]) from 644 TB suspects in a peripheral health clinic. Incremental cost per smear-positive detected case was measured. Costs included human resources and materials using a micro-costing evaluation. RESULTS: All bleach-based microscopy approaches detected significantly more cases (between 23.3% for B1 and 25.9% for B1+B2) than the conventional D1+D2 approach (21.0%). Cost per tested case ranged between respectively euro 2.7 and euro 4.5 for B1 and B1+D2+B2. B1 and B1+B2 were the most cost-effective approaches. D1+B2 and D1+B1 were good alternatives to avoid using approaches exclusively based on bleach sedimentation microscopy. CONCLUSIONS: Among several effective microscopy approaches used, including sodium hypochlorite sedimentation, only some resulted in a limited increase in the laboratory workload and would be most suitable for programmatic implementation. AD - Epicentre, Paris, France. maryline.bonnet@geneva.msf.org AN - 20392349 AU - Bonnet, M. AU - Tajahmady, A. AU - Hepple, P. AU - Ramsay, A. AU - Githui, W. AU - Gagdnidze, L. AU - Guerin, P. J. AU - Varaine, F. DA - May DP - NLM ET - 2010/04/16 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Centrifugation Cost-Benefit Analysis Decision Trees Humans Kenya/epidemiology Microscopy/economics/ methods Sodium Hypochlorite/ chemistry Sputum/ microbiology Time Factors Tuberculosis, Pulmonary/ diagnosis/epidemiology LA - eng M1 - 5 N1 - Bonnet, M Tajahmady, A Hepple, P Ramsay, A Githui, W Gagdnidze, L Guerin, P J Varaine, F Research Support, Non-U.S. Gov't France Int J Tuberc Lung Dis. 2010 May;14(5):571-7. PY - 2010 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - 571-7 ST - Added value of bleach sedimentation microscopy for diagnosis of tuberculosis: a cost-effectiveness study T2 - Int J Tuberc Lung Dis TI - Added value of bleach sedimentation microscopy for diagnosis of tuberculosis: a cost-effectiveness study VL - 14 ID - 556 ER - TY - JOUR AB - Rationale: Tuberculosis (TB) is characterized by a subclinical phase (symptoms absent or not considered abnormal); prediagnostic phase (symptoms noticed but diagnosis not pursued); and clinical phase (care actively sought). Diagnostic capacity during these phases is limited. Objectives: To estimate the population-level impact of TB case-finding strategies in the presence of subclinical and prediagnostic disease. Methods: We created a mathematical epidemic model of TB, calibrated to global incidence. We then introduced three prototypical diagnostic interventions: increased sensitivity of diagnosis in the clinical phase by 20% ("passive"); early diagnosis during the prediagnostic phase at a rate of 10% per year ("enhanced"); and population-based diagnosis of 5% of undiagnosed prevalent cases per year ("active"). Measurements and Main Results: If the subclinical phase was ignored, as in most models, the passive strategy was projected to reduce TB incidence by 18% (90% uncertainty range [UR], 11-32%) by year 10, compared with 23% (90% UR, 14-35%) for the enhanced strategy and 18% (90% UR, 11-28%) for the active strategy. After incorporating a subclinical phase into the model, consistent with population-based prevalence surveys, the active strategy still reduced 10-year TB incidence by 16% (90% UR, 11-28%), but the passive and enhanced strategies' impact was attenuated to 11% (90% UR, 8-25%) and 6% (90% UR, 4-13%), respectively. The degree of attenuation depended strongly on the transmission rate during the subclinical phase. Conclusions: Subclinical disease may limit the impact of current diagnostic strategies for TB. Active detection of undiagnosed prevalent cases may achieve greater population-level TB control than increasing passive case detection. AD - 615 North Wolfe Street, E6531, Baltimore, MD 21205. ddowdy@jhsph.edu. AN - 23262515 AU - Dowdy, D. W. AU - Basu, S. AU - Andrews, J. R. DA - Mar 1 DO - 10.1164/rccm.201207-1217OC DP - NLM ET - 2012/12/25 J2 - American journal of respiratory and critical care medicine LA - eng M1 - 5 N1 - Dowdy, David W Basu, Sanjay Andrews, Jason R United States Am J Respir Crit Care Med. 2013 Mar 1;187(5):543-51. doi: 10.1164/rccm.201207-1217OC. Epub 2012 Dec 21. PY - 2013 SN - 1535-4970 (Electronic) 1073-449X (Linking) SP - 543-51 ST - Is passive diagnosis enough?: the impact of subclinical disease on diagnostic strategies for tuberculosis T2 - Am J Respir Crit Care Med TI - Is passive diagnosis enough?: the impact of subclinical disease on diagnostic strategies for tuberculosis UR - http://ajrccm.atsjournals.org/content/187/5/543.full.pdf VL - 187 ID - 1303 ER - TY - JOUR AB - 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. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Suite W6508, Baltimore, MD 21205, USA. AN - 18695217 AU - Dowdy, D. W. AU - Chaisson, R. E. AU - Maartens, G. AU - Corbett, E. L. AU - Dorman, S. E. C2 - 2516234 DA - Aug 12 DO - 0800965105 [pii] 10.1073/pnas.0800965105 [doi] DP - Nlm ET - 2008/08/13 KW - Disease Outbreaks Drug Resistance, Multiple, Bacterial Female HIV Infections/complications/ diagnosis/ mortality/transmission Humans Male Models, Theoretical Retrospective Studies South Africa/epidemiology Time Factors Tuberculosis/complications/ diagnosis/ mortality/transmission World Health Organization LA - eng M1 - 32 N1 - Dowdy, David W Chaisson, Richard E Maartens, Gary Corbett, Elizabeth L Dorman, Susan E 074644/Wellcome Trust/United Kingdom K23 AI51528/AI/NIAID NIH HHS/United States K24 AI01637/AI/NIAID NIH HHS/United States T32 GMO7309/PHS HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11293-8. Epub 2008 Aug 11. PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1091-6490 (Electronic) 0027-8424 (Linking) SP - 11293-8 ST - Impact of enhanced tuberculosis diagnosis in South Africa: a mathematical model of expanded culture and drug susceptibility testing T2 - Proc Natl Acad Sci U S A TI - Impact of enhanced tuberculosis diagnosis in South Africa: a mathematical model of expanded culture and drug susceptibility testing UR - http://www.pnas.org/content/105/32/11293.full.pdf VL - 105 ID - 564 ER - TY - JOUR AB - OBJECTIVE: To explore the potential impact of enhanced tuberculosis (TB) diagnostic techniques as a TB control strategy in an adult population with high HIV prevalence. DESIGN: A compartmental difference-equation model of TB/HIV was developed using parameter estimates from the literature. METHODS: The impact of five TB control interventions (rapid molecular testing, mycobacterial culture, community-wide and HIV-targeted active case finding, and highly active antiretroviral therapy) on TB incidence, prevalence, and mortality was modeled in a steady-state population with an HIV prevalence of 17% and annual TB incidence of 409 per 100 000. Sensitivity analyses assessed the influence of each model parameter on the interventions' mortality impact. RESULTS: Enhanced diagnostic techniques (rapid molecular testing or culture) are each projected to reduce TB prevalence and mortality by 20% or more, an impact similar to that of active case-finding in 33% of the general community and greater than the effect achievable by case-finding or antiretroviral treatment efforts in HIV-positive patients alone. The projected impact of enhanced diagnostics on TB incidence (< 10% reduction) is smaller. The impact of TB diagnostics is sensitive to the quality of existing diagnostic standards and the level of access to diagnostic services, but is robust across a wide range of population parameters including HIV and TB incidence. CONCLUSIONS: Enhanced TB diagnostic techniques may have substantial impact on TB morbidity and mortality in HIV-endemic regions. As TB rates continue to increase in these areas, enhanced diagnostic techniques merit further consideration as TB control strategies. AD - Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland 21231, USA. AN - 16514306 AU - Dowdy, D. W. AU - Chaisson, R. E. AU - Moulton, L. H. AU - Dorman, S. E. DA - Mar 21 DO - 10.1097/01.aids.0000216376.07185.cc [doi] 00002030-200603210-00015 [pii] DP - Nlm ET - 2006/03/04 KW - AIDS-Related Opportunistic Infections/ diagnosis Adolescent Adult Anti-HIV Agents/therapeutic use Antiretroviral Therapy, Highly Active Bacterial Typing Techniques Communicable Disease Control DNA, Bacterial/analysis Developing Countries Disease Outbreaks HIV Infections/ complications/drug therapy Health Services Accessibility Humans Incidence Intervention Studies Middle Aged Models, Statistical Mycobacterium tuberculosis/genetics/isolation & purification Prevalence Tuberculosis/ diagnosis/epidemiology/virology LA - eng M1 - 5 N1 - Dowdy, David W Chaisson, Richard E Moulton, Lawrence H Dorman, Susan E 5 T32 GMO7309/PHS HHS/United States K23 AI 51528/AI/NIAID NIH HHS/United States K24 AI16137/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England AIDS (London, England) AIDS. 2006 Mar 21;20(5):751-62. PY - 2006 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 0269-9370 (Print) 0269-9370 (Linking) SP - 751-62 ST - The potential impact of enhanced diagnostic techniques for tuberculosis driven by HIV: a mathematical model T2 - AIDS TI - The potential impact of enhanced diagnostic techniques for tuberculosis driven by HIV: a mathematical model UR - http://graphics.tx.ovid.com/ovftpdfs/FPDDNCDCLFEDDD00/fs047/ovft/live/gv024/00002030/00002030-200603210-00015.pdf VL - 20 ID - 565 ER - TY - JOUR AB - BACKGROUND: Culture of Mycobacterium tuberculosis currently represents the closest "gold standard" for diagnosis of tuberculosis (TB), but operational data are scant on the impact and cost-effectiveness of TB culture for human immunodeficiency (HIV-) infected individuals in resource-limited settings. METHODOLOGY/PRINCIPAL FINDINGS: We recorded costs, laboratory results, and dates of initiating TB therapy in a centralized TB culture program for HIV-infected patients in Rio de Janeiro, Brazil, constructing a decision-analysis model to estimate the incremental cost-effectiveness of TB culture from the perspective of a public-sector TB control program. Of 217 TB suspects presenting between January 2006 and March 2008, 33 (15%) had culture-confirmed active tuberculosis; 23 (70%) were smear-negative. Among smear-negative, culture-positive patients, 6 (26%) began TB therapy before culture results were available, 11 (48%) began TB therapy after culture result availability, and 6 (26%) did not begin TB therapy within 180 days of presentation. The cost per negative culture was US$17.52 (solid media)-$23.50 (liquid media). Per 1,000 TB suspects and compared with smear alone, TB culture with solid media would avert an estimated eight TB deaths (95% simulation interval [SI]: 4, 15) and 37 disability-adjusted life years (DALYs) (95% SI: 13, 76), at a cost of $36 (95% SI: $25, $50) per TB suspect or $962 (95% SI: $469, $2642) per DALY averted. Replacing solid media with automated liquid culture would avert one further death (95% SI: -1, 4) and eight DALYs (95% SI: -4, 23) at $2751 per DALY (95% SI: $680, dominated). The cost-effectiveness of TB culture was more sensitive to characteristics of the existing TB diagnostic system than to the accuracy or cost of TB culture. CONCLUSIONS/SIGNIFICANCE: TB culture is potentially effective and cost-effective for HIV-positive patients in resource-constrained settings. Reliable transmission of culture results to patients and integration with existing systems are essential. AD - Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. AN - 19129940 AU - Dowdy, D. W. AU - Lourenco, M. C. AU - Cavalcante, S. C. AU - Saraceni, V. AU - King, B. AU - Golub, J. E. AU - Bishai, D. AU - Durovni, B. AU - Chaisson, R. E. AU - Dorman, S. E. C2 - 2614861 DO - 10.1371/journal.pone.0004057 ET - 2009/01/09 J2 - PloS one KW - AIDS-Related Opportunistic Infections/*diagnosis Bacteriological Techniques/*economics Brazil Cost-Benefit Analysis HIV Infections/*complications Humans Mycobacterium tuberculosis/*isolation & purification Tuberculosis/*diagnosis LA - eng M1 - 12 M3 - Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't N1 - Dowdy, David W Lourenco, Maria C Cavalcante, Solange C Saraceni, Valeria King, Bonnie Golub, Jonathan E Bishai, David Durovni, Betina Chaisson, Richard E Dorman, Susan E 5 T32 GMO7309/PHS HHS/ K23 AI 51528/AI/NIAID NIH HHS/ K24 AI 16137/AI/NIAID NIH HHS/ PLoS One. 2008;3(12):e4057. Epub 2008 Dec 29. PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e4057 ST - Impact and cost-effectiveness of culture for diagnosis of tuberculosis in HIV-infected Brazilian adults T2 - PLoS One TI - Impact and cost-effectiveness of culture for diagnosis of tuberculosis in HIV-infected Brazilian adults UR - http://www.ncbi.nlm.nih.gov/pubmed/19129940 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614861/pdf/pone.0004057.pdf VL - 3 ID - 566 ER - TY - JOUR AB - A decision analysis was conducted to evaluate the cost-effectiveness of programs in which the Amplified Mycobacterium Tuberculosis Direct test (MTD) (Gen-Probe) is used to rapidly exclude Mycobacterium tuberculosis complex as a cause of disease in smear-positive respiratory specimens. MTD sensitivity, specificity, and probability of inhibition for smear-positive specimens were estimated from literature reports. Costs and laboratory performance characteristics were determined from review of records and practices at an urban hospital in the mid-Atlantic United States. In the base case, 31.4% of smear-positive specimens were assumed to be culture positive for M. tuberculosis. Under these conditions, the marginal cost of the MTD testing program was estimated as $338 per smear-positive patient, or $494 per early exclusion of tuberculosis based on negative MTD results. By comparison, the cost of respiratory isolation ($27.77/day) and drugs ($5.66/day) averted by MTD testing was estimated at $201 per early tuberculosis exclusion. MTD testing was therefore not cost-effective in this scenario. Sensitivity analysis revealed that cost-effectiveness estimates are sensitive to the number of smear-positive specimens processed annually, the relative prevalence of M. tuberculosis in smear-positive specimens, and the marginal daily cost of respiratory isolation. A decision tool is therefore presented for assessing the cost-effectiveness of MTD under various combinations of those three variables. While routine MTD testing of smear-positive specimens is not expected to be cost-saving for most individual hospitals, centralized reference laboratories may be able to implement MTD in a cost-effective manner across a wide range of situations. AD - Johns Hopkins Bloomberg School of Public Health. Johns Hopkins Hospital. Johns Hopkins University School of Medicine, Baltimore, Maryland. AN - 12624014 AU - Dowdy, D. W. AU - Maters, A. AU - Parrish, N. AU - Beyrer, C. AU - Dorman, S. E. DA - Mar N1 - 22511020 0095-1137 Journal Article PY - 2003 RN - fulltext fulltext_1208 SP - 948-953 ST - Cost-effectiveness analysis of the gen-probe amplified mycobacterium tuberculosis direct test as used routinely on smear-positive respiratory specimens T2 - Journal of clinical microbiology TI - Cost-effectiveness analysis of the gen-probe amplified mycobacterium tuberculosis direct test as used routinely on smear-positive respiratory specimens UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12624014file://C:\literature_pdf\rm11132.pdf VL - 41 ID - 735 ER - TY - JOUR AB - SETTING: The potential cost-effectiveness of improved diagnostic tests for tuberculosis (TB) in resource-limited settings is unknown. OBJECTIVE: To estimate the incremental cost-effectiveness of a hypothetical new point-of-care TB diagnostic test in South Africa, Brazil and Kenya. DESIGN: Decision-analysis model, adding four diagnostic interventions (sputum smear microscopy, new test, smear plus new test and smear plus TB culture) to a baseline of existing infrastructure without smear. RESULTS: Adding sputum smear was estimated to be more cost-effective (incremental cost per disability-adjusted life year [DALY] of $86 [South Africa], $131 [Brazil], $38 (Kenya]) than a new TB diagnostic with 70% sensitivity, 95% specificity and price of $20 per test ($198 [South Africa], $275 [Brazil], $84 [Kenya]). However, compared to sputum smear, smear plus new test averted 46-49% more DALYs per 1000 TB suspects (321 vs. 215 [South Africa], 243 vs. 166 [Brazil], 790 vs. 531 [Kenya]), at an incremental cost of $170 (Kenya) to $625 (Brazil) per DALY averted. Cost-effectiveness was most sensitive to the specificity and price of the new test, the baseline TB case detection rate and the discount rate. CONCLUSION: Novel diagnostic tests for TB are potentially highly cost-effective. Cost-effectiveness is maximized by high-specificity, low-cost tests deployed to regions with poor infrastructure. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. david.w.dowdy@gmail.com AN - 18713499 AU - Dowdy, D. W. AU - O'Brien, M. A. AU - Bishai, D. DA - Sep ET - 2008/08/21 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Brazil Cost-Benefit Analysis Decision Support Techniques Diagnostic Tests, Routine/*economics/methods Humans Kenya Models, Economic Sensitivity and Specificity South Africa Tuberculosis/*diagnosis/drug therapy/economics LA - eng M1 - 9 M3 - Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't N1 - Dowdy, D W O'Brien, M A Bishai, D 5 T32 GM07309/GM/NIGMS NIH HHS/ France Int J Tuberc Lung Dis. 2008 Sep;12(9):1021-9. PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1027-3719 (Print) 1027-3719 (Linking) SP - 1021-9 ST - Cost-effectiveness of novel diagnostic tools for the diagnosis of tuberculosis T2 - Int J Tuberc Lung Dis TI - Cost-effectiveness of novel diagnostic tools for the diagnosis of tuberculosis UR - http://www.ncbi.nlm.nih.gov/pubmed/18713499 VL - 12 ID - 567 ER - TY - JOUR AB - BACKGROUND: Undiagnosed and misdiagnosed tuberculosis (TB) drives the epidemic in India. Serological (antibody detection) TB tests are not recommended by any agency, but widely used in many countries, including the Indian private sector. The cost and impact of using serology compared with other diagnostic techniques is unknown. METHODS AND FINDINGS: Taking a patient cohort conservatively equal to the annual number of serological tests done in India (1.5 million adults suspected of having active TB), we used decision analysis to estimate costs and effectiveness of sputum smear microscopy (US$3.62 for two smears), microscopy plus automated liquid culture (mycobacterium growth indicator tube [MGIT], US$20/test), and serological testing (anda-tb ELISA, US$20/test). Data on test accuracy and costs were obtained from published literature. We adopted the perspective of the Indian TB control sector and an analysis frame of 1 year. Our primary outcome was the incremental cost per disability-adjusted life year (DALY) averted. We performed one-way sensitivity analysis on all model parameters, with multiway sensitivity analysis on variables to which the model was most sensitive. If used instead of sputum microscopy, serology generated an estimated 14,000 more TB diagnoses, but also 121,000 more false-positive diagnoses, 102,000 fewer DALYs averted, and 32,000 more secondary TB cases than microscopy, at approximately four times the incremental cost (US$47.5 million versus US$11.9 million). When added to high-quality sputum smears, MGIT culture was estimated to avert 130,000 incremental DALYs at an incremental cost of US$213 per DALY averted. Serology was dominated by (i.e., more costly and less effective than) MGIT culture and remained less economically favorable than sputum smear or TB culture in one-way and multiway sensitivity analyses. CONCLUSIONS: In India, sputum smear microscopy remains the most cost-effective diagnostic test available for active TB; efforts to increase access to quality-assured microscopy should take priority. In areas where high-quality microscopy exists and resources are sufficient, MGIT culture is more cost-effective than serology as an additional diagnostic test for TB. These data informed a recently published World Health Organization policy statement against serological tests. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. AN - 21857810 AU - Dowdy, D. W. AU - Steingart, K. R. AU - Pai, M. C2 - 3153451 DA - Aug DO - 10.1371/journal.pmed.1001074 ET - 2011/08/23 J2 - PLoS medicine KW - Adult Antibodies, Bacterial/*blood Bacteriological Techniques/*economics Bias (Epidemiology) Cost-Benefit Analysis Decision Support Techniques Enzyme-Linked Immunosorbent Assay Humans India Microscopy/economics Mycobacterium/immunology/pathogenicity Sensitivity and Specificity Serologic Tests/*economics Sputum/*microbiology Tuberculosis/*diagnosis/microbiology LA - eng M1 - 8 M3 - Comparative Study Research Support, Non-U.S. Gov't N1 - Dowdy, David W Steingart, Karen R Pai, Madhukar Canadian Institutes of Health Research/Canada PLoS Med. 2011 Aug;8(8):e1001074. Epub 2011 Aug 9. PY - 2011 RN - fulltext fulltext_1208 SN - 1549-1676 (Electronic) 1549-1277 (Linking) SP - e1001074 ST - Serological testing versus other strategies for diagnosis of active tuberculosis in India: a cost-effectiveness analysis T2 - PLoS Med TI - Serological testing versus other strategies for diagnosis of active tuberculosis in India: a cost-effectiveness analysis UR - http://www.ncbi.nlm.nih.gov/pubmed/21857810 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153451/pdf/pmed.1001074.pdf VL - 8 ID - 737 ER - TY - JOUR AB - Background & objectives: New diagnostic tests for tuberculosis, especially those based on nucleic acid amplification, offer the possibility of early and accurate diagnosis of active TB. In this study we use mathematical modelling to explore the potential epidemiological impact of these new tests, with particular reference to India. Methods: A behavioural model of patient-doctor interactions embedded in an epidemiological model of Mycobacterium tuberculosis transmission, linked to field data, was used to investigate the effects of early diagnosis in preventing future TB cases. Results: New diagnostic tests for active TB will have a bigger impact sooner where: disease incidence is high and most cases are due to recent infection; advances in test technology (test sensitivity, specificity, etc.) are combined with early diagnosis; new tests have not only better technical specifications than current tests, but also compensate for the misuse of existing tests; health system delays are long compared with patient delays, assuming the former are more amenable to change. Interpretation & conclusions: New diagnostic tests will certainly improve TB control, but the highest impact will be obtained by applying tests with higher sensitivity and specificity early in the infectious period. Refined behavioural and epidemiological models should be able to investigate the mechanisms by which early diagnosis could be achieved, in addition to the consequent epidemiological effects. AD - HIV/AIDS, Tuberculosis, Malaria & Neglected Tropical Diseases Cluster, World Health Organization, Geneva, Switzerland. AN - 22771607 AU - Dye, C. C2 - 3401708 DA - May DO - IndianJMedRes_2012_135_5_737_97762 [pii] DP - Nlm ET - 2012/07/10 LA - eng M1 - 5 N1 - Dye, Christopher India The Indian journal of medical research Indian J Med Res. 2012 May;135(5):737-44. PY - 2012 RN - fulltext fulltext_1208 SN - 0971-5916 (Print) SP - 737-44 ST - The potential impact of new diagnostic tests on tuberculosis epidemics T2 - Indian J Med Res TI - The potential impact of new diagnostic tests on tuberculosis epidemics UR - http://www.ijmr.org.in/article.asp?issn=0971-5916;year=2012;volume=135;issue=5;spage=737;epage=744;aulast=Dye VL - 135 ID - 740 ER - TY - JOUR AB - We conducted a decision analysis to assess and compare four algorithms for amplified Mycobacterium tuberculosis direct (MTD) testing of respiratory specimens in terms of cost-effectiveness. The most cost-effective strategy was one in which smear-positive specimens but not smear-negative specimens were diluted prior to MTD testing. AD - Johns Hopkins University Center for Tuberculosis Research, 1550 Orleans Street, Room 1M-06, Baltimore, MD 21231, USA. AN - 18799694 AU - Guerra, R. L. AU - Hooper, N. M. AU - Baker, J. F. AU - Alborz, R. AU - Armstrong, D. T. AU - Kiehlbauch, J. A. AU - Conde, M. B. AU - Dorman, S. E. DA - Nov DO - JCM.01682-08 [pii] 10.1128/JCM.01682-08 ET - 2008/09/19 KW - Cost-Benefit Analysis Humans Mycobacterium tuberculosis/genetics/*isolation & purification Nucleic Acid Amplification Techniques/*economics/*methods Tuberculosis, Pulmonary/*diagnosis/microbiology LA - eng M1 - 11 N1 - Guerra, Renata L Hooper, Nancy M Baker, James F Alborz, Roya Armstrong, Derek T Kiehlbauch, Julia A Conde, Marcus B Dorman, Susan E D43 TW05574-01/TW/FIC NIH HHS/United States K23AI51528/AI/NIAID NIH HHS/United States U19AI45432/AI/NIAID NIH HHS/United States U2R TW006883/TW/FIC NIH HHS/United States Research Support, N.I.H., Extramural United States Journal of clinical microbiology J Clin Microbiol. 2008 Nov;46(11):3811-2. Epub 2008 Sep 17. PY - 2008 RN - fulltext fulltext_1208 SN - 1098-660X (Electronic) 0095-1137 (Linking) SP - 3811-2 ST - Cost-effectiveness of different strategies for amplified Mycobacterium tuberculosis direct testing for cases of pulmonary tuberculosis T2 - J Clin Microbiol TI - Cost-effectiveness of different strategies for amplified Mycobacterium tuberculosis direct testing for cases of pulmonary tuberculosis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18799694http://jcm.asm.org/cgi/reprint/46/11/3811.pdf http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2576624/pdf/1682-08.pdf VL - 46 ID - 791 ER - TY - JOUR AB - BACKGROUND: There is wide variation in the techniques deployed to diagnose tuberculosis in the UK, with little agreement on which tools or strategies are cost effective. This analysis therefore comprehensively evaluated the cost effectiveness of currently available diagnostic strategies for routine diagnosis of TB in the NHS. METHODS: The analysis compared strategies consisting of Nucleic Acid Amplification Techniques, culture and microscopy. A decision tree was used to estimate costs and Quality-Adjusted Life Years (QALYs) from a UK health service perspective. The sensitivity and specificity of each test determined the true and false positive and negative results in patients suspected of having active tuberculosis. These results led to either early, correct diagnosis or delayed diagnosis and the associated costs and QALYs. The presence of active tuberculosis combined with the side effects of treatment was associated with reduction in quality of life. Costs included were test costs, drug costs and the management of tuberculosis. Drug costs were based on generic UK list prices. Uncertainty in the model was explored through probabilistic and deterministic sensitivity analyses. RESULTS/CONCLUSIONS: The cost effective strategy at threshold of pound20,000 per QALY was a strategy using only sputum microscopy and culture routinely, meaning Nucleic Acid Amplification Techniques are not cost effective at baseline. When the prevalence of tuberculosis was increased, however, nucleic acid amplification became cost effective at the same threshold. Aside from the prevalence, the results were shown to be robust. At low tuberculosis prevalence, Nucleic Acid Amplification Techniques may not be cost effective but their potential in higher prevalence situations is considerable. AD - National Clinical Guidelines Centre, 180 Great Portland Street, London W1W 5QZ, UK. Ralph.hughes@rcplondon.ac.uk AN - 22137190 AU - Hughes, R. AU - Wonderling, D. AU - Li, B. AU - Higgins, B. DO - S0954-6111(11)00345-3 [pii] 10.1016/j.rmed.2011.10.005 KW - Cost-Benefit Analysis Decision Trees *Direct Service Costs Female Great Britain/epidemiology Humans Male *Microscopy/economics/methods National Health Programs/economics Nucleic Acid Amplification Techniques/*economics/methods Prevalence Quality-Adjusted Life Years Sensitivity and Specificity Tuberculosis/*diagnosis/*economics/genetics LA - eng N1 - Hughes, Ralph Wonderling, David Li, Bernadette Higgins, Bernard Comparative Study Review England Respiratory medicine Respir Med. 2012 Feb;106(2):300-7. Epub 2011 Dec 1. PY - 2012 RN - fulltext fulltext_1208 SN - 1532-3064 (Electronic) 0954-6111 (Linking) SP - 300-307 ST - The cost effectiveness of Nucleic Acid Amplification Techniques for the diagnosis of tuberculosis T2 - Respiratory medicine TI - The cost effectiveness of Nucleic Acid Amplification Techniques for the diagnosis of tuberculosis UR - http://www.ncbi.nlm.nih.gov/pubmed/22137190 http://ac.els-cdn.com/S0954611111003453/1-s2.0-S0954611111003453-main.pdf?_tid=f0fb9cfc-6b2f-11e2-85ca-00000aacb35e&acdnat=1359586622_4d20eeb6452ae11ec466e6aa649b2371 VL - 106 ID - 811 ER - TY - JOUR AB - The introduction and scale-up of new tools for the diagnosis of Tuberculosis (TB) in developing countries has the potential to make a huge difference to the lives of millions of people living in poverty. To achieve this, policy makers need the information to make the right decisions about which new tools to implement and where in the diagnostic algorithm to apply them most effectively. These decisions are difficult as the new tools are often expensive to implement and use, and the health system and patient impacts uncertain, particularly in developing countries where there is a high burden of TB. The authors demonstrate that a discrete event simulation model could play a significant part in improving and informing these decisions. The feasibility of linking the discrete event simulation to a dynamic epidemiology model is also explored in order to take account of longer term impacts on the incidence of TB. Results from two diagnostic districts in Tanzania are used to illustrate how the approach could be used to improve decisions. AD - Clinical Group, Liverpool School of Tropical Medicine, Liverpool, UK, ivorlang@liv.ac.uk. AN - 22674467 AU - Langley, I. AU - Doulla, B. AU - Lin, H. H. AU - Millington, K. AU - Squire, B. DA - Sep DO - 10.1007/s10729-012-9201-3 [doi] DP - Nlm ET - 2012/06/08 LA - eng M1 - 3 N1 - Langley, Ivor Doulla, Basra Lin, Hsien-Ho Millington, Kerry Squire, Bertie Netherlands Health care management science Health Care Manag Sci. 2012 Sep;15(3):239-53. Epub 2012 Jun 7. PY - 2012 RN - fulltext fulltext_1208 SN - 1386-9620 (Print) 1386-9620 (Linking) SP - 239-53 ST - Modelling the impacts of new diagnostic tools for tuberculosis in developing countries to enhance policy decisions T2 - Health Care Manag Sci TI - Modelling the impacts of new diagnostic tools for tuberculosis in developing countries to enhance policy decisions UR - http://www.springerlink.com/content/u768lr018r04t135/fulltext.pdf VL - 15 ID - 831 ER - TY - JOUR AB - OBJECTIVE: The prompt diagnosis of smear-negative pulmonary tuberculosis (PTB) is a clinical challenge. It may be achieved by a number of tests which have varying accuracies, costs and degrees of invasiveness. The objective of this study was to compare the cost-effectiveness of clinical judgement (empirical), the Roche Cobas amplicor assay for Mycobacterium tuberculosis (amplicor), acid-fast staining of bronchoalveolar lavage specimens (BAL), nucleic acid amplification tests of bronchoalveloar lavage specimens for M. tuberculosis (BAL + NAA), computed tomography (CT) and amplicor assay followed by BAL. METHODOLOGY: The range of predictive values of the various strategies were derived from published data and a new study of 441 consecutive adult patients with suspected smear-negative PTB prospectively stratified into three pretest risk groups: low, intermediate and high. The cost-effectiveness was evaluated with a decision tree model (DATA software). RESULTS: The incidence of PTB was 5.7% (4% culture positive) for the whole group, 95% in the high-risk group, 0.9% in the low-risk group and 3.4% in the intermediate-risk group. The sensitivity of the empirical approach was 49% and of the amplicor assay was 44%. Patient outcomes were expressed as life expectancy for the base case of a 58-year-old man with a pretest probability of 5.7%. At this low pretest risk the differences in life expectancies between tests was < 0.1 years and the empirical approach incurred the lowest cost. Sensitivity analysis at increasing pretest risks showed better life expectancies (approximately 1 years) for CT scan and test combinations than empirical and amplicor for additional costs of US$243-US$309. Bronchoalveolar lavage had the worst overall cost-effectiveness. CONCLUSIONS: We conclude that the pretest risk of active PTB was a key determinant of test utility; that the AMPLICOR assay was comparable to clinical judgement; that BAL was the least useful test; and that with increasing risks, CT scan and test combinations performed better. Further studies are needed to better define patients with intermediate risk for PTB and to directly compare the cost-effectiveness of more sensitive nucleic acid amplification tests such as the enhanced Gen Probe, CT scan and test combinations/sequences in these patients. AD - Department of Medicine, National University of Singapore, Singapore. mdclimtk@nus.edu.sg AN - 11192555 AU - Lim, T. K. AU - Cherian, J. AU - Poh, K. L. AU - Leong, T. Y. DA - Dec ET - 2001/02/24 KW - Bacteriological Techniques/economics/*standards *Bronchoalveolar Lavage Fluid Bronchoscopy/economics/*standards Cost-Benefit Analysis Decision Trees Humans Life Expectancy Male Middle Aged Nucleic Acid Amplification Techniques/economics/*standards Patient Selection Risk Factors Sensitivity and Specificity Sputum/*microbiology Tomography, X-Ray Computed/economics/*standards Tuberculosis, Pulmonary/*diagnosis/microbiology LA - eng M1 - 4 N1 - Lim, T K Cherian, J Poh, K L Leong, T Y Case Reports Comparative Study Validation Studies Australia Respirology (Carlton, Vic.) Respirology. 2000 Dec;5(4):403-9. PY - 2000 RN - fulltext fulltext_1208 SN - 1323-7799 (Print) 1323-7799 (Linking) SP - 403-9 ST - The rapid diagnosis of smear-negative pulmonary tuberculosis: a cost-effectiveness analysis T2 - Respirology TI - The rapid diagnosis of smear-negative pulmonary tuberculosis: a cost-effectiveness analysis UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11192555 VL - 5 ID - 841 ER - TY - JOUR AB - OBJECTIVE: To estimate the impact of new tuberculosis diagnostics on tuberculosis transmission given the complex contextual factors that can lead to patient loss before diagnosis or treatment. METHODS: An epidemic model of tuberculosis specifying discrete steps along the tuberculosis diagnostic pathway was constructed. The model was calibrated to the epidemiology of tuberculosis and human immunodeficiency virus (HIV) infection in the United Republic of Tanzania and was used to assess the impact of a new diagnostic tool with 70% sensitivity for smear-negative pulmonary tuberculosis. The influence of contextual factors on the projected epidemic impact of the new diagnostic tool over the decade following introduction was explored. FINDINGS: With the use of smear microscopy, the incidence of tuberculosis will decline by an average of 3.94% per year. If the new tool is added, incidence will decline by an annual 4.25%. This represents an absolute change of 0.31 percentage points (95% confidence interval: 0.04-0.42). However, the annual decline in transmission with use of the new tool is less when existing strategies for the diagnosis of smear-negative cases have high sensitivity and when symptomatic individuals delay in seeking care. Other influential contextual factors include access to tuberculosis care, patient loss before diagnosis, initial patient default after diagnosis and treatment success rate. CONCLUSION: When implementing and scaling up the use of a new diagnostic tool, the operational context in which diagnosis and treatment take place needs to be considered. AD - Institute of Epidemiology and Preventive Medicine, National Taiwan University, 17 Xuzhou Road, 100 Taipei, Taiwan, China. AN - 23109741 AU - Lin, H. H. AU - Dowdy, D. AU - Dye, C. AU - Murray, M. AU - Cohen, T. C2 - 3471051 DA - Oct 1 DO - 10.2471/blt.11.101436 DP - NLM ET - 2012/10/31 J2 - Bulletin of the World Health Organization LA - eng M1 - 10 N1 - Lin, Hsien-Ho Dowdy, David Dye, Christopher Murray, Megan Cohen, Ted Research Support, Non-U.S. Gov't Switzerland Bull World Health Organ. 2012 Oct 1;90(10):739-747A. doi: 10.2471/BLT.11.101436. Epub 2012 Jul 16. PY - 2012 SN - 1564-0604 (Electronic) 0042-9686 (Linking) SP - 739-747A ST - The impact of new tuberculosis diagnostics on transmission: why context matters T2 - Bull World Health Organ TI - The impact of new tuberculosis diagnostics on transmission: why context matters UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471051/pdf/BLT.11.101436.pdf VL - 90 ID - 1329 ER - TY - JOUR AB - Efforts to stimulate technological innovation in the diagnosis of tuberculosis (TB) have resulted in the recent introduction of several novel diagnostic tools. As these products come to market, policy makers must make difficult decisions about which of the available tools to implement. This choice should depend not only on the test characteristics (e.g., sensitivity and specificity) of the tools, but also on how they will be used within the existing health care infrastructure. Accordingly, policy makers choosing between diagnostic strategies must decide: 1) What is the best combination of tools to select? 2)Who should be tested with the new tools? and 3)Will these tools complement or replace existing diagnostics? The best choice of diagnostic strategy will likely vary between settings with different epidemiology (e.g., levels of TB incidence, human immunodeficiency virus co-infection and drug-resistant TB) and structural and resource constraints (e.g., existing diagnostic pathways, human resources and laboratory capacity). We propose a joint modelling framework that includes a tuberculosis (TB) transmission component (a dynamic epidemiological model) and a health system component (an operational systems model) to support diagnostic strategy decisions. This modelling approach captures the complex feedback loops in this system: new diagnostic strategies alter the demands on and performance of health systems that impact TB transmission dynamics which, in turn, result in further changes to demands on the health system. We demonstrate the use of a simplified model to support the rational choice of a diagnostic strategy based on health systems requirements, patient outcomes and population-level TB impact. AD - Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan. AN - 21740663 AU - Lin, H. H. AU - Langley, I. AU - Mwenda, R. AU - Doulla, B. AU - Egwaga, S. AU - Millington, K. A. AU - Mann, G. H. AU - Murray, M. AU - Squire, S. B. AU - Cohen, T. DA - Aug DO - 10.5588/ijtld.11.0062 ET - 2011/07/12 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease KW - Antitubercular Agents/therapeutic use *Bacteriological Techniques/economics Computer Simulation *Decision Support Techniques Feedback Health Care Costs Health Policy Health Resources/economics/utilization Humans Policy Making Predictive Value of Tests Prognosis Sensitivity and Specificity Sputum/microbiology Time Factors Tuberculosis/*diagnosis/drug therapy/economics/epidemiology/transmission LA - eng M1 - 8 M3 - Research Support, Non-U.S. Gov't N1 - Lin, H-H Langley, I Mwenda, R Doulla, B Egwaga, S Millington, K A Mann, G H Murray, M Squire, S B Cohen, T France Int J Tuberc Lung Dis. 2011 Aug;15(8):996-1004. PY - 2011 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - 996-1004 ST - A modelling framework to support the selection and implementation of new tuberculosis diagnostic tools T2 - Int J Tuberc Lung Dis TI - A modelling framework to support the selection and implementation of new tuberculosis diagnostic tools UR - http://www.ncbi.nlm.nih.gov/pubmed/21740663 VL - 15 ID - 577 ER - TY - JOUR AB - BACKGROUND: The Xpert MTB/RIF test enables rapid detection of tuberculosis (TB) and rifampicin resistance. The World Health Organization recommends Xpert for initial diagnosis in individuals suspected of having multidrug-resistant TB (MDR-TB) or HIV-associated TB, and many countries are moving quickly toward adopting Xpert. As roll-out proceeds, it is essential to understand the potential health impact and cost-effectiveness of diagnostic strategies based on Xpert. METHODS AND FINDINGS: We evaluated potential health and economic consequences of implementing Xpert in five southern African countries--Botswana, Lesotho, Namibia, South Africa, and Swaziland--where drug resistance and TB-HIV coinfection are prevalent. Using a calibrated, dynamic mathematical model, we compared the status quo diagnostic algorithm, emphasizing sputum smear, against an algorithm incorporating Xpert for initial diagnosis. Results were projected over 10- and 20-y time periods starting from 2012. Compared to status quo, implementation of Xpert would avert 132,000 (95% CI: 55,000-284,000) TB cases and 182,000 (97,000-302,000) TB deaths in southern Africa over the 10 y following introduction, and would reduce prevalence by 28% (14%-40%) by 2022, with more modest reductions in incidence. Health system costs are projected to increase substantially with Xpert, by US$460 million (294-699 million) over 10 y. Antiretroviral therapy for HIV represents a substantial fraction of these additional costs, because of improved survival in TB/HIV-infected populations through better TB case-finding and treatment. Costs for treating MDR-TB are also expected to rise significantly with Xpert scale-up. Relative to status quo, Xpert has an estimated cost-effectiveness of US$959 (633-1,485) per disability-adjusted life-year averted over 10 y. Across countries, cost-effectiveness ratios ranged from US$792 (482-1,785) in Swaziland to US$1,257 (767-2,276) in Botswana. Assessing outcomes over a 10-y period focuses on the near-term consequences of Xpert adoption, but the cost-effectiveness results are conservative, with cost-effectiveness ratios assessed over a 20-y time horizon approximately 20% lower than the 10-y values. CONCLUSIONS: Introduction of Xpert could substantially change TB morbidity and mortality through improved case-finding and treatment, with more limited impact on long-term transmission dynamics. Despite extant uncertainty about TB natural history and intervention impact in southern Africa, adoption of Xpert evidently offers reasonable value for its cost, based on conventional benchmarks for cost-effectiveness. However, the additional financial burden would be substantial, including significant increases in costs for treating HIV and MDR-TB. Given the fundamental influence of HIV on TB dynamics and intervention costs, care should be taken when interpreting the results of this analysis outside of settings with high HIV prevalence. AD - Center for Health Decision Sciences, Harvard School of Public Health, Boston, Massachusetts, United States of America. nmenzies@fas.harvard.edu AN - 23185139 AU - Menzies, N. A. AU - Cohen, T. AU - Lin, H. H. AU - Murray, M. AU - Salomon, J. A. C2 - 3502465 DO - 10.1371/journal.pmed.1001347 DP - NLM ET - 2012/11/28 J2 - PLoS medicine LA - eng M1 - 11 N1 - Menzies, Nicolas A Cohen, Ted Lin, Hsien-Ho Murray, Megan Salomon, Joshua A R25 CA092203/CA/NCI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States PLoS Med. 2012;9(11):e1001347. doi: 10.1371/journal.pmed.1001347. Epub 2012 Nov 20. PY - 2012 SN - 1549-1676 (Electronic) 1549-1277 (Linking) SP - e1001347 ST - Population health impact and cost-effectiveness of tuberculosis diagnosis with Xpert MTB/RIF: a dynamic simulation and economic evaluation T2 - PLoS Med TI - Population health impact and cost-effectiveness of tuberculosis diagnosis with Xpert MTB/RIF: a dynamic simulation and economic evaluation UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502465/pdf/pmed.1001347.pdf VL - 9 ID - 1316 ER - TY - JOUR AB - OBJECTIVE: We estimated the incremental cost and impact on diagnosis and treatment uptake of national rollout of Xpert MTB/RIF technology (Xpert) for the diagnosis of pulmonary TB above the cost of current guidelines for the years 2011 to 2016 in South Africa. METHODS: We parameterised a population-level decision model with data from national-level TB databases (n = 199,511) and implementation studies. The model follows cohorts of TB suspects from diagnosis to treatment under current diagnostic guidelines or an algorithm that includes Xpert. Assumptions include the number of TB suspects, symptom prevalence of 5.5%, annual suspect growth rate of 10%, and 2010 public-sector salaries and drug and service delivery costs. Xpert test costs are based on data from an in-country pilot evaluation and assumptions about when global volumes allowing cartridge discounts will be reached. RESULTS: At full scale, Xpert will increase the number of TB cases diagnosed per year by 30%-37% and the number of MDR-TB cases diagnosed by 69%-71%. It will diagnose 81% of patients after the first visit, compared to 46% currently. The cost of TB diagnosis per suspect will increase by 55% to USD 60-61 and the cost of diagnosis and treatment per TB case treated by 8% to USD 797-873. The incremental capital cost of the Xpert scale-up will be USD 22 million and the incremental recurrent cost USD 287-316 million over six years. CONCLUSION: Xpert will increase both the number of TB cases diagnosed and treated and the cost of TB diagnosis. These results do not include savings due to reduced transmission of TB as a result of earlier diagnosis and treatment initiation. AD - Health Economics and Epidemiology Research Office (HE2RO), Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. AN - 22693561 AU - Meyer-Rath, G. AU - Schnippel, K. AU - Long, L. AU - Macleod, W. AU - Sanne, I. AU - Stevens, W. AU - Pillay, S. AU - Pillay, Y. AU - Rosen, S. DO - 10.1371/journal.pone.0036966 PONE-D-11-25103 [pii] LA - eng N1 - Meyer-Rath, Gesine Schnippel, Kathryn Long, Lawrence Macleod, William Sanne, Ian Stevens, Wendy Pillay, Sagie Pillay, Yogan Rosen, Sydney United States PloS one PLoS One. 2012;7(5):e36966. Epub 2012 May 31. PY - 2012 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e36966 ST - The Impact and Cost of Scaling up GeneXpert MTB/RIF in South Africa T2 - PLoS One TI - The Impact and Cost of Scaling up GeneXpert MTB/RIF in South Africa UR - http://www.ncbi.nlm.nih.gov/pubmed/22693561 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365041/pdf/pone.0036966.pdf VL - 7 ID - 585 ER - TY - JOUR AB - BACKGROUND: Numerous patient and healthcare system-related delays contribute to the overall delay experienced by patients from onset of TB symptoms to diagnosis and treatment. Such delays are critical as infected individuals remain untreated in the community, providing more opportunities for transmission of the disease and adversely affecting the epidemic. METHODOLOGY/PRINCIPAL FINDINGS: We present an analysis of the factors that contribute to the overall delay in TB diagnosis and treatment, in a resource-poor setting. Impact on the distribution of diagnostic delay times was assessed for various factors, the sensitivity of the diagnostic method being found to be the most significant. A linear relationship was found between the sensitivity of the test and the predicted mean delay time, with an increase in test sensitivity resulting in a reduced mean delay time and a reduction in the drop-out rate. CONCLUSIONS/SIGNIFICANCE: The results show that in a developing country a number of delay factors, particularly the low sensitivity of the initial sputum smear microscopy test, potentially increase total diagnostic delay times experienced by TB patients significantly. The results reinforce the urgent need for novel diagnostic methods, both for smear positive and negative TB, that are highly sensitive, accessible and point of care, in order to reduce mean delay times. AD - DST/NRF Centre of Excellence for Epidemiological Modelling and Analysis (SACEMA), Stellenbosch University, Western Cape, Republic of South Africa. AN - 18398459 AU - Millen, S. J. AU - Uys, P. W. AU - Hargrove, J. AU - van Helden, P. D. AU - Williams, B. G. C2 - 2276686 DO - 10.1371/journal.pone.0001933 [doi] DP - Nlm ET - 2008/04/10 KW - Antitubercular Agents/therapeutic use Community Health Services/organization & administration Computer Simulation Developing Countries Health Services Accessibility Humans Patient Acceptance of Health Care Probability Risk Factors Sensitivity and Specificity Time Factors Tuberculosis/ diagnosis/ transmission LA - eng M1 - 4 N1 - Millen, Stephen J Uys, Pieter W Hargrove, John van Helden, Paul D Williams, Brian G Research Support, Non-U.S. Gov't United States PloS one PLoS One. 2008 Apr 9;3(4):e1933. PY - 2008 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e1933 ST - The effect of diagnostic delays on the drop-out rate and the total delay to diagnosis of tuberculosis T2 - PLoS One TI - The effect of diagnostic delays on the drop-out rate and the total delay to diagnosis of tuberculosis UR - http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0001933&representation=PDF VL - 3 ID - 586 ER - TY - JOUR AB - To determine whether polymerase chain reaction (PCR) testing in the initial diagnosis of pulmonary tuberculosis (TB) is cost-effective in a low-prevalence population, an economic evaluation was carried out between the smear and culture (NOPCR) and smear, culture and PCR (+PCR) strategies. A decision tree model based on retrospective laboratory data was developed to assess the strategies of testing patients with suspicion of TB. Direct healthcare costs prior to confirmation of TB or nontuberculous mycobacteria by PCR or culture were included. Effectiveness was measured by the probability of correct treatment and isolation decisions. In the baseline situation NOPCR costs Euro 29.50 less than the +PCR strategy per patient tested. According to sensitivity analyses, reducing PCR test price, shortening test performance time or increasing the proportion of smear-positive patients in the tested population would contribute to cost savings with the +PCR strategy. Routine polymerase chain reaction testing of all specimens from suspected tuberculosis patients in a low-prevalence population was not cost-saving. When the polymerase chain reaction assay was applied only to smear-positive sputum specimens, the smear and culture strategy was clearly dominated by it, i.e. the polymerase chain reaction smear-positive sputum strategy was less costly and more effective in producing correct treatment decisions and isolations. AD - Dept of Pulmonary Diseases, Tampere University Hospital, Tampere, Finland. iiris.rajalahti@kolumbus.fi AN - 15065837 AU - Rajalahti, I. AU - Ruokonen, E. L. AU - Kotomaki, T. AU - Sintonen, H. AU - Nieminen, M. M. DA - Mar DP - NLM ET - 2004/04/07 J2 - The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology KW - Cost-Benefit Analysis Decision Trees Finland/epidemiology Health Care Costs/statistics & numerical data Humans Incidence Polymerase Chain Reaction/ economics Prevalence Specimen Handling Sputum/microbiology Tuberculosis, Pulmonary/ diagnosis/economics/epidemiology LA - eng M1 - 3 N1 - Rajalahti, I Ruokonen, E L Kotomaki, T Sintonen, H Nieminen, M M Research Support, Non-U.S. Gov't Denmark Eur Respir J. 2004 Mar;23(3):446-51. PY - 2004 RN - fulltext fulltext_1208 SN - 0903-1936 (Print) 0903-1936 (Linking) SP - 446-51 ST - Economic evaluation of the use of PCR assay in diagnosing pulmonary TB in a low-incidence area T2 - Eur Respir J TI - Economic evaluation of the use of PCR assay in diagnosing pulmonary TB in a low-incidence area UR - http://erj.ersjournals.com/content/23/3/446.full.pdf VL - 23 ID - 918 ER - TY - JOUR AB - BACKGROUND: Use of Xpert MTB/RIF is being scaled up throughout South Africa for improved diagnosis of tuberculosis (TB). A large proportion of HIV-infected patients with possible TB are Xpert-negative on their initial test, and the existing diagnostic algorithm calls for these patients to have sputum culture (Xpert followed by culture (X/C)). We modelled the costs and impact of an alternative diagnostic algorithm in which these cultures are replaced with a second Xpert test (Xpert followed by Xpert (X/X)). METHODS: An existing population-level decision model was used. Costs were estimated from Xpert implementation studies and public sector price and salary data. The number of patients requiring diagnosis was estimated from the literature, as were rates of TB treatment uptake and loss to follow-up. TB and HIV positivity rates were estimated from the national TB register and laboratory databases. RESULTS: At national programme scale in 2014, X/X (R969 million/year) is less expensive than X/C R1 095 million/year), potentially saving R126 million/year (US$17.4 million). However, because Xpert is less sensitive than culture, X/X diagnoses 2% fewer TB cases. This is partly offset by higher expected treatment uptake with X/X due to the faster availability of results, resulting in 1% more patients initiating treatment under X/X than X/C. The cost per TB patient initiated on treatment under X/X is R2 682, which is 12% less than under X/C (R3 046). CONCLUSIONS: Modifying the diagnostic algorithm from X/C to X/X could provide rapid results, simplify diagnostic processes, improve HIV/TB treatment outcomes, and generate cost savings. AD - Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa. kschnippel@heroza.org AN - 23374320 AU - Schnippel, K. AU - Meyer-Rath, G. AU - Long, L. AU - Stevens, W. S. AU - Sanne, I. AU - Rosen, S. DA - Feb DO - 10.7196/samj.6182 DP - NLM ET - 2013/02/05 J2 - South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde LA - eng M1 - 2 N1 - Schnippel, K Meyer-Rath, G Long, L Stevens, W S Sanne, I Rosen, S U2RTW007373/PHS HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't South Africa S Afr Med J. 2013 Jan 14;103(2):101-6. doi: 10.7196/samj.6182. PY - 2013 SN - 0256-9574 (Print) 0256-9574 (Linking) SP - 101-6 ST - Diagnosing Xpert MTB/RIF negative TB: impact and cost of alternative algorithms for South Africa T2 - S Afr Med J TI - Diagnosing Xpert MTB/RIF negative TB: impact and cost of alternative algorithms for South Africa UR - http://www.samj.org.za/index.php/samj/article/view/6182 VL - 103 ID - 1281 ER - TY - JOUR AB - SETTING: In-patient hospitals in South Africa and Uganda. OBJECTIVE: To evaluate the cost-effectiveness of a lateral-flow urine lipoarabinomannan (LAM) test when added to existing strategies for tuberculosis (TB) diagnosis in human immunodeficiency virus infected adults (CD4(+) T-cell counts < 100 cells/l) with symptoms of active TB. DESIGN: Decision-analytic cost-utility model, with the primary outcome being the incremental cost-effectiveness ratio, expressed in 2010 US dollars per disability-adjusted life year (DALY) averted from the perspective of a public sector TB control program. RESULTS AND CONCLUSION: For every 1000 patients tested, adding lateral-flow urine LAM generated 80 incremental appropriate anti-tuberculosis treatments and averted 224 DALYs. Estimated cost utility was US$353 per DALY averted (95% uncertainty range $192$1161) in South Africa and $86 per DALY averted (95% uncertainty range $49$239) in Uganda, reflecting the lower treatment costs in Uganda. Cost utility was most sensitive to assay specificity, cost of anti-tuberculosis treatment, life expectancy after TB cure and cohort TB prevalence, but did not rise above $1500 per DALY averted in South Africa under any one-way sensitivity analysis. The probability of acceptability was >99.8% at a per-DALY willingness-to-pay threshold equal to the per capita gross domestic product in South Africa ($7275) and Uganda ($509). AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. AN - 23485389 AU - Sun, D. AU - Dorman, S. AU - Shah, M. AU - Manabe, Y. C. AU - Moodley, V. M. AU - Nicol, M. P. AU - Dowdy, D. W. DA - Apr DO - 10.5588/ijtld.12.0627 ET - 2013/03/15 J2 - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease LA - eng M1 - 4 N1 - Sun, D Dorman, S Shah, M Manabe, Y C Moodley, V M Nicol, M P Dowdy, D W France Int J Tuberc Lung Dis. 2013 Apr;17(4):552-8. doi: 10.5588/ijtld.12.0627. PY - 2013 SN - 1815-7920 (Electronic) 1027-3719 (Linking) SP - 552-8 ST - Cost utility of lateral-flow urine lipoarabinomannan for tuberculosis diagnosis in HIV-infected African adults T2 - Int J Tuberc Lung Dis TI - Cost utility of lateral-flow urine lipoarabinomannan for tuberculosis diagnosis in HIV-infected African adults UR - http://www.ncbi.nlm.nih.gov/pubmed/23485389 VL - 17 ID - 1422 ER - TY - JOUR AB - The long-term persistence of Mycobacterium tuberculosis in communities with high tuberculosis prevalence is a serious problem aggravated by the presence of drug-resistant tuberculosis strains. Drug resistance in an individual patient is often discovered only after a long delay, particularly if the diagnosis is based on current culture-based drug sensitivity testing methods. During such delays, the patient may transmit tuberculosis to his or her contacts. Rapid diagnosis of drug resistance would be expected to reduce this transmission and hence to decrease the prevalence of drug-resistant strains. To investigate this quantitatively, a mathematical model was constructed, assuming a homogeneous population structure typical of communities in South Africa where tuberculosis incidence is high. Computer simulations performed with this model showed that current control strategies will not halt the spread of multidrug-resistant tuberculosis in such communities. The simulations showed that the rapid diagnosis of drug resistance can be expected to reduce the incidence of drug-resistant cases provided the additional measure of screening within the community is implemented. AD - Faculty of Health Sciences, MRC Center for Molecular and Cellular Biology, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Stellenbosch University, Tygerberg, South Africa. pieter@edserve.co.za AN - 19297604 AU - Uys, P. W. AU - Warren, R. AU - van Helden, P. D. AU - Murray, M. AU - Victor, T. C. C2 - 2681859 DA - May DO - JCM.02289-08 [pii] 10.1128/JCM.02289-08 [doi] DP - Nlm ET - 2009/03/20 KW - Computer Simulation Drug Resistance, Multiple, Bacterial Humans Microbial Sensitivity Tests Models, Theoretical Mycobacterium tuberculosis/ drug effects/genetics/ isolation & purification South Africa Time Factors Tuberculosis, Multidrug-Resistant/ diagnosis/ microbiology/transmission LA - eng M1 - 5 N1 - Uys, Pieter W Warren, Robin van Helden, Paul D Murray, Megan Victor, Thomas C Research Support, Non-U.S. Gov't United States Journal of clinical microbiology J Clin Microbiol. 2009 May;47(5):1484-90. Epub 2009 Mar 18. PY - 2009 RN - fulltext fulltext_1208 SN - 1098-660X (Electronic) 0095-1137 (Linking) SP - 1484-90 ST - Potential of rapid diagnosis for controlling drug-susceptible and drug-resistant tuberculosis in communities where Mycobacterium tuberculosis infections are highly prevalent T2 - J Clin Microbiol TI - Potential of rapid diagnosis for controlling drug-susceptible and drug-resistant tuberculosis in communities where Mycobacterium tuberculosis infections are highly prevalent UR - http://jcm.asm.org/content/47/5/1484.full.pdf VL - 47 ID - 988 ER - TY - JOUR AB - BACKGROUND: In many communities where TB occurs at high incidence, the major force driving the epidemic is transmission. It is plausible that the typical long delay from the onset of infectious disease to diagnosis and commencement of treatment is almost certainly the major factor contributing to the high rate of transmission. METHODOLOGY/PRINCIPAL FINDINGS: This study is confined to communities which are epidemiologically relatively isolated and which have low HIV incidence. The consequences of delays to diagnosis are analyzed and the existence of a threshold delay value is demonstrated. It is shown that unless a sufficient number of cases are detected before this threshold, the epidemic will escalate. The method used for the analysis avoids the standard computer integration of systems of differential equations since the intention is to present a line of reasoning that reveals the essential dynamics of an epidemic in an intuitively clear way that is nevertheless quantitatively realistic. CONCLUSIONS/SIGNIFICANCE: The analysis presented here shows that typical delays to diagnosis present a major obstacle to the control of a TB epidemic. Control can be achieved by optimizing the rapid identification of TB cases together with measures to increase the threshold value. A calculated and aggressive program is therefore necessary in order to bring about a reduction in the prevalence of TB in a community by decreasing the time to diagnosis in all its ramifications. Intervention strategies to increase the threshold value relative to the time to diagnosis and which thereby decrease disease incidence are discussed. AD - Division of Molecular Biology and Human Genetics, MRC Center for Molecular and Cellular Biology, Faculty of Health Sciences, Stellenbosch University, Cape Town, Western Cape, Republic of South Africa. AN - 17712405 AU - Uys, P. W. AU - Warren, R. M. AU - van Helden, P. D. C2 - 1942086 DO - 10.1371/journal.pone.0000757 ET - 2007/08/23 J2 - PloS one KW - Disease Susceptibility HIV Infections/epidemiology Humans Mycobacterium tuberculosis/pathogenicity South Africa/epidemiology Time Factors Tuberculosis, Pulmonary/*diagnosis/*epidemiology/transmission LA - eng M1 - 8 M3 - Research Support, Non-U.S. Gov't N1 - Uys, Pieter W Warren, Robin M van Helden, Paul D PLoS One. 2007 Aug 22;2(8):e757. PY - 2007 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e757 ST - A threshold value for the time delay to TB diagnosis T2 - PLoS One TI - A threshold value for the time delay to TB diagnosis UR - http://www.ncbi.nlm.nih.gov/pubmed/17712405 VL - 2 ID - 1273 ER - TY - JOUR AB - BACKGROUND: 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. CONCLUSIONS: 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. AD - Department of Global Health, Amsterdam Institute of Global Health and Development, Academic Medical Center, Amsterdam, The Netherlands. AN - 22087078 AU - Vassall, A. AU - van Kampen, S. AU - Sohn, H. AU - Michael, J. S. AU - John, K. R. AU - den Boon, S. AU - Davis, J. L. AU - Whitelaw, A. AU - Nicol, M. P. AU - Gler, M. T. AU - Khaliqov, A. AU - Zamudio, C. AU - Perkins, M. D. AU - Boehme, C. C. AU - Cobelens, F. C2 - 3210757 DA - Nov DO - 10.1371/journal.pmed.1001120 [doi] PMEDICINE-D-11-00805 [pii] DP - Nlm ET - 2011/11/17 KW - Clinical Laboratory Techniques/ economics/methods Cohort Studies Cost-Benefit Analysis Humans India South Africa Tuberculosis, Pulmonary/ diagnosis/economics Uganda LA - eng M1 - 11 N1 - Vassall, Anna van Kampen, Sanne Sohn, Hojoon Michael, Joy S John, K R den Boon, Saskia Davis, J Lucian Whitelaw, Andrew Nicol, Mark P Gler, Maria Tarcela Khaliqov, Anar Zamudio, Carlos Perkins, Mark D Boehme, Catharina C Cobelens, Frank Research Support, Non-U.S. Gov't United States PLoS medicine PLoS Med. 2011 Nov;8(11):e1001120. Epub 2011 Nov 8. PY - 2011 RN - hiv_tb_Sep2012 fulltext fulltext_1208 SN - 1549-1676 (Electronic) 1549-1277 (Linking) SP - e1001120 ST - Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis T2 - PLoS Med TI - Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis UR - http://www.plosmedicine.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.1001120&representation=PDF VL - 8 ID - 608 ER - TY - JOUR AB - BACKGROUND: Prisons of the former Soviet Union (FSU) have high rates of multidrug-resistant tuberculosis (MDR-TB) and are thought to drive general population tuberculosis (TB) epidemics. Effective prison case detection, though employing more expensive technologies, may reduce long-term treatment costs and slow MDR-TB transmission. METHODS AND FINDINGS: We developed a dynamic transmission model of TB and drug resistance matched to the epidemiology and costs in FSU prisons. We evaluated eight strategies for TB screening and diagnosis involving, alone or in combination, self-referral, symptom screening, mass miniature radiography (MMR), and sputum PCR with probes for rifampin resistance (Xpert MTB/RIF). Over a 10-y horizon, we projected costs, quality-adjusted life years (QALYs), and TB and MDR-TB prevalence. Using sputum PCR as an annual primary screening tool among the general prison population most effectively reduced overall TB prevalence (from 2.78% to 2.31%) and MDR-TB prevalence (from 0.74% to 0.63%), and cost US$543/QALY for additional QALYs gained compared to MMR screening with sputum PCR reserved for rapid detection of MDR-TB. Adding sputum PCR to the currently used strategy of annual MMR screening was cost-saving over 10 y compared to MMR screening alone, but produced only a modest reduction in MDR-TB prevalence (from 0.74% to 0.69%) and had minimal effect on overall TB prevalence (from 2.78% to 2.74%). Strategies based on symptom screening alone were less effective and more expensive than MMR-based strategies. Study limitations included scarce primary TB time-series data in FSU prisons and uncertainties regarding screening test characteristics. CONCLUSIONS: In prisons of the FSU, annual screening of the general inmate population with sputum PCR most effectively reduces TB and MDR-TB prevalence, doing so cost-effectively. If this approach is not feasible, the current strategy of annual MMR is both more effective and less expensive than strategies using self-referral or symptom screening alone, and the addition of sputum PCR for rapid MDR-TB detection may be cost-saving over time. AD - Stanford University School of Medicine, California, United States of America. AN - 23209384 AU - Winetsky, D. E. AU - Negoescu, D. M. AU - DeMarchis, E. H. AU - Almukhamedova, O. AU - Dooronbekova, A. AU - Pulatov, D. AU - Vezhnina, N. AU - Owens, D. K. AU - Goldhaber-Fiebert, J. D. C2 - 3507963 DO - 10.1371/journal.pmed.1001348 DP - NLM ET - 2012/12/05 J2 - PLoS medicine LA - eng M1 - 11 N1 - Winetsky, Daniel E Negoescu, Diana M DeMarchis, Emilia H Almukhamedova, Olga Dooronbekova, Aizhan Pulatov, Dilshod Vezhnina, Natalia Owens, Douglas K Goldhaber-Fiebert, Jeremy D K01 AG037593/AG/NIA NIH HHS/United States K01 AG037593-01A1/AG/NIA NIH HHS/United States R01DA015612/DA/NIDA NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States PLoS Med. 2012;9(11):e1001348. doi: 10.1371/journal.pmed.1001348. Epub 2012 Nov 27. PY - 2012 SN - 1549-1676 (Electronic) 1549-1277 (Linking) SP - e1001348 ST - Screening and rapid molecular diagnosis of tuberculosis in prisons in Russia and Eastern Europe: a cost-effectiveness analysis T2 - PLoS Med TI - Screening and rapid molecular diagnosis of tuberculosis in prisons in Russia and Eastern Europe: a cost-effectiveness analysis UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507963/pdf/pmed.1001348.pdf VL - 9 ID - 1312 ER -