Madhukar Pai

McGill University, Montréal, Quebec, Canada

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Publications (310)1777.33 Total impact

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    ABSTRACT: Both product innovation (e.g., more sensitive tests) and process innovation (e.g., a point-of-care [POC] testing programme) could improve patient outcomes. To study the respective contributions of product and process innovation in improving patient outcomes. We implemented a POC programme using Xpert(®) MTB/RIF in an out-patient clinic of a tertiary care hospital in India. We measured the impact of process innovation by comparing time to diagnosis with routine testing vs. POC testing. We measured the impact of product innovation by comparing accuracy and time to diagnosis using smear microscopy vs. POC Xpert. We enrolled 1012 patients over a 15-month period. Xpert had high accuracy, but the incremental value of one Xpert over two smears was only 6% (95%CI 3-12). Implementing Xpert as a routine laboratory test did not reduce the time to diagnosis compared to smear-based diagnosis. In contrast, the POC programme reduced the time to diagnosis by 5.5 days (95%CI 4.3-6.7), but required dedicated staff and substantial adaptation of clinic workflow. Process innovation by way of a POC Xpert programme had a greater impact on time to diagnosis than the product per se, and can yield important improvements in patient care that are complementary to those achieved by introducing innovative technologies.
    The International Journal of Tuberculosis and Lung Disease 09/2015; 19(9):1084-90. DOI:10.5588/ijtld.15.0120 · 2.76 Impact Factor
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    PLoS ONE 08/2015; · 3.23 Impact Factor
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    ABSTRACT: BACKGROUND: Existing studies of the quality of tuberculosis care have relied on recall-based patient surveys, questionnaire surveys of knowledge, and prescription or medical record analysis, and the results mostly show the health-care provider's knowledge rather than actual practice. No study has used standardised patients to assess clinical practice. Therefore we aimed to assess quality of care for tuberculosis using such patients. METHODS: We did a pilot, cross-sectional validation study of a convenience sample of consenting private health-care providers in low-income and middle-income areas of Delhi, India. We recruited standardised patients in apparently good health from the local community to present four cases (two of presumed tuberculosis and one each of confirmed tuberculosis and suspected multidrug-resistant tuberculosis) to a randomly allocated health-care provider. The key objective was to validate the standardised-patient method using three criteria: negligible risk and ability to avoid adverse events for providers and standardised patients, low detection rates of standardised patients by providers, and data accuracy across standardised patients and audio verification of standardised-patient recall. We also used medical vignettes to assess providers' knowledge of presumed tuberculosis. Correct case management was benchmarked using Standards for Tuberculosis Care in India (STCI). FINDINGS: Between Feb 2, and March 28, 2014, we recruited and trained 17 standardised patients who had 250 interactions with 100 health-care providers, 29 of whom were qualified in allopathic medicine (ie, they had a Bachelor of Medicine & Surgery [MBBS] degree), 40 of whom practised alternative medicine, and 31 of whom were informal health-care providers with few or no qualifications. The interactions took place between April 1, and April 23, 2014. The proportion of detected standardised patients was low (11 [5%] detected out of 232 interactions among providers who completed the follow-up survey), and standardised patients' recall correlated highly with audio recordings (r=0·63 [95% CI 0·53-0·79]), with no safety concerns reported. The mean consultation length was 6 min (95% CI 5·5-6·6) with a mean of 6·18 (5·72-6·64) questions or examinations completed, representing 35% (33-38) of essential checklist items. Across all cases, only 52 (21% [16-26]) of 250 were correctly managed. Correct management was higher among MBBS-qualified doctors than other types of health-care provider (adjusted odds ratio 2·41 [95% CI 1·17-4·93]; p=0·0166). Of the 69 providers who completed the vignette, knowledge in the vignettes was more consistent with STCI than their actual clinical practice-eg, 50 (73%) ordered a chest radiograph or sputum test during the vignette compared with seven (10%) during the standardised-patient interaction; OR 0·04 (95% CI 0·02-0·11); p<0·0001. INTERPRETATION: Standardised patients can be successfully implemented to assess tuberculosis care. Our data suggest a big gap between private provider knowledge and practice. Additional work is needed to substantiate our pilot data, understand the know-do gap in provider behaviour, and to identify the best approach to measure and improve the quality of tuberculosis care in India. FUNDING: Grand Challenges Canada, the Bill & Melinda Gates Foundation, Knowledge for Change Program, and the World Bank Development Research Group. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Infectious Diseases 08/2015; DOI:10.1016/S1473-3099(15)00077-8 · 19.45 Impact Factor
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    Ramnath Subbaraman · Madhukar Pai
    The International Journal of Tuberculosis and Lung Disease 08/2015; 19(8):877-8. DOI:10.5588/ijtld.15.0458 · 2.76 Impact Factor
  • Tripti Pande · Madhukar Pai · Claudia Denkinger
    European Respiratory Journal 08/2015; · 7.13 Impact Factor
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    ABSTRACT: The successful cure of tuberculosis (TB) is dependent on adherence to treatment. Various factors influence adherence, however, few are easily modifiable. There are limited data regarding correlates of psychological distress and their association with non-adherence to anti-TB treatment. In a trial of a new TB test, we measured psychological distress (K-10 score), TB-related health literacy, and morbidity (TBscore), prior to diagnosis in 1502 patients with symptoms of pulmonary TB recruited from clinics in Cape Town (n = 419), Harare (n = 400), Lusaka (n = 400), Durban (n = 200), and Mbeya (n = 83). Socioeconomic, demographic, and alcohol usage-related data were captured. Patients initiated on treatment had their DOTS cards reviewed at two-and six-months. 22 %(95 % CI: 20 %, 25 %) of patients had severe psychological distress (K-10 ≥ 30). In a multivariable linear regression model, increased K-10 score was independently associated with previous TB [estimate (95 % CI) 0.98(0.09-1.87); p = 0.0304], increased TBscore [1(0.80, 1.20); p <0.0001], and heavy alcohol use [3.08(1.26, 4.91); p = 0.0010], whereas male gender was protective [-1.47(-2.28, -0.62); p = 0.0007]. 26 % (95 % CI: 21 %, 32 %) of 261 patients with culture-confirmed TB were non-adherent. In a multivariable logistic regression model for non-adherence, reduced TBscore [OR (95 % CI) 0.639 (0.497, 0.797); p = 0.0001], health literacy score [0.798(0.696, 0.906); p = 0.0008], and increased K-10 [1.082(1.033, 1.137); p = 0.0012], and heavy alcohol usage [14.83(2.083, 122.9); p = 0.0002], were independently associated. Culture-positive patients with a K-10 score ≥ 30 were more-likely to be non-adherent (OR = 2.290(1.033-5.126); p = 0.0416]. Severe psychological distress is frequent amongst TB patients in Southern Africa. Targeted interventions to alleviate psychological distress, alcohol use, and improve health literacy in newly-diagnosed TB patients could reduce non-adherence to treatment.
    BMC Infectious Diseases 07/2015; 15:253. DOI:10.1186/s12879-015-0964-2 · 2.61 Impact Factor
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    ABSTRACT: Tuberculosis (TB) is a major public health threat. But worldwide, the majority of people with symptoms consistent with TB start their care seeking in the private or informal sector. These numbers are particularly high in Asia. Public-private mix (PPM) efforts have been introduced to reach these individuals, as soon as possible, with quality-assured diagnosis and treatment. Systematic approaches have been designed to reach all provider types. However, PPM schemes struggle to manage the scale of a fragmented and under-regulated private sector. Opportunities are arising to introduce more systemic, scalable, and innovative approaches, including social businesses, insurance-based initiatives, intermediary agencies, regulatory regimes, and provider consolidation, with a heavy emphasis on the use of new information technologies. These approaches combine the previous work on TB private sector engagement with structural solutions that make health systems function for all patients, regardless of the disease or whether patients seek care in the public or the private sector.
    PLoS Medicine 06/2015; 12(6):e1001842. DOI:10.1371/journal.pmed.1001842 · 14.00 Impact Factor
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    Marzieh Ghiasi · Tripti Pande · Madhukar Pai
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    ABSTRACT: Accurate and timely diagnosis is the first step for initiating effective treatment for tuberculosis (TB) and interrupting transmission. Worldwide, nearly one third of all TB cases go undetected or unreported each year. The emergence of extensively drug-resistant TB, in addition to challenges in detecting TB among children and people living with HIV has created an urgent need for better technologies. In the past 5 years, Xpert MTB/RIF has proved to be pathfinder for improved diagnosis. However, gaps remain. Currently, there is no molecular replacement for sputum smear microscopy at the level of peripheral laboratories. There is no simple, non-sputum-based biomarker test that can detect all forms of TB at the primary care level. There is also a need to align emerging TB drug regimens with appropriate companion diagnostics. This review describes advances in non-molecular and molecular diagnostics and their potential to fill the gaps in TB case detection.
    06/2015; 2(2). DOI:10.1007/s40475-015-0043-1
  • Madhukar Pai · Camilla Rodrigues
    Lung India 05/2015; 32(3):205. DOI:10.4103/0970-2113.156210
  • Kristen M. Little · Madhukar Pai · David W. Dowdy
    PLoS ONE 04/2015; 10(4):e0124525. DOI:10.1371/journal.pone.0124525 · 3.23 Impact Factor
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    ABSTRACT: While Indian studies have assessed care providers' knowledge and practices, there is no systematic review on the quality of tuberculosis (TB) care. We searched multiple sources to identify studies (2000-2014) on providers' knowledge and practices. We used the International Standards for TB Care to benchmark quality of care. Of the 47 studies included, 35 were questionnaire surveys and 12 used chart abstraction. None assessed actual practice using standardised patients. Heterogeneity in the findings precluded meta-analysis. Of 22 studies evaluating provider knowledge about using sputum smears for diagnosis, 10 found that less than half of providers had correct knowledge; 3 of 4 studies assessing self-reported practices by providers found that less than a quarter reported ordering smears for patients with chest symptoms. In 11 of 14 studies that assessed treatment, less than one third of providers knew the standard regimen for drug-susceptible TB. Adherence to standards in practice was generally lower than correct knowledge of those standards. Eleven studies with both public and private providers found higher levels of appropriate knowledge/practice in the public sector. Available evidence suggests suboptimal quality of TB care, particularly in the private sector. Improvement of quality of care should be a priority for India.
    The International Journal of Tuberculosis and Lung Disease 04/2015; DOI:10.5588/ijtld.15.0186 · 2.76 Impact Factor
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    ABSTRACT: Background. Current phenotypic testing for drug resistance in patients with tuberculosis is inadequate primarily with respect to turnaround time. Molecular tests hold the promise of an improved time to diagnosis. Methods. A target product profile for a molecular drug-susceptibility test (DST) was developed on the basis of a collaborative effort that included opinions gathered from researchers, clinicians, policy makers, and test developers on optimal clinical and operational characteristics in settings of intended use. In addition, the current diagnostic ecosystem and the diagnostic development landscape were mapped. Results. Molecular DSTs for detecting tuberculosis in microscopy centers should ideally evaluate for resistance to rifampin, fluoroquinolones, isoniazid, and pyrazinamide and enable the selection of the most appropriate treatment regimen. Performance characteristics of DSTs need to be optimized, but compromises can be made that depend on the trade-off between a false-positive result and a false-negative result. The operational requirements of a test will vary depending on the site of implementation. However, the most-important considerations pertain to quality control, maintenance and calibration, and the ability to export data. Conclusion. This target product profile defines the needs as perceived by the tuberculosis stakeholder community and attempts to provide a means of communication with test developers to ensure that fit-for-purpose DSTs are being developed.
    The Journal of Infectious Diseases 04/2015; 211(suppl 2):S39-S49. DOI:10.1093/infdis/jiu682 · 5.78 Impact Factor
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    ABSTRACT: To accelerate the fight against tuberculosis, major diagnostic challenges need to be addressed urgently. Post-2015 targets are unlikely to be met without the use of novel diagnostics that are more accurate and can be used closer to where patients first seek care in affordable diagnostic algorithms. This article describes the efforts by the stakeholder community that led to the identification of the high-priority diagnostic needs in tuberculosis. Subsequently target product profiles for the high-priority diagnostic needs were developed and reviewed in a World Health Organization (WHO)-led consensus meeting. The high-priority diagnostic needs included (1) a sputum-based replacement test for smear-microscopy; (2) a non-sputum-based biomarker test for all forms of tuberculosis, ideally suitable for use at levels below microscopy centers; (3) a simple, low cost triage test for use by first-contact care providers as a rule-out test, ideally suitable for use by community health workers; and (4) a rapid drug susceptibility test for use at the microscopy center level. The developed target product profiles, along with complimentary work presented in this supplement, will help to facilitate the interaction between the tuberculosis community and the diagnostics industry with the goal to lead the way toward the post-2015 global tuberculosis targets. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail:
    The Journal of Infectious Diseases 04/2015; 211(suppl 2):S29-S38. DOI:10.1093/infdis/jiu821 · 5.78 Impact Factor
  • Madhukar Pai · Marco Schito
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    ABSTRACT: In 2015, tuberculosis remains a major global health problem, and drug-resistant tuberculosis is a growing threat. Although tuberculosis diagnosis in many countries is still reliant on older tools, new diagnostics are changing the landscape. Stimulated, in part, by the success and roll out of Xpert MTB/RIF, there is now considerable interest in new technologies. The landscape looks promising, with a robust pipeline of new tools, particularly molecular diagnostics, and well over 50 companies actively engaged in product development. However, new diagnostics are yet to reach scale, and there needs to be greater convergence between diagnostics development and development of shorter-duration tuberculosis drug regimens. Another concern is the relative absence of non-sputum-based diagnostics in the pipeline for children and of biomarker tests for triage, cure, and progression of latent Mycobacterium tuberculosis infection. Several initiatives, described in this supplement, have been launched to further stimulate product development and policy, including assessment of needs and priorities, development of target product profiles, compilation of data on resistance-associated mutations, and assessment of market size and potential for new diagnostics. Advocacy is needed to increase funding for tuberculosis research and development, and governments in high-burden countries must invest more in tuberculosis control to meet post-2015 targets for care, control, and prevention. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail:
    The Journal of Infectious Diseases 04/2015; 211(suppl 2):S21-S28. DOI:10.1093/infdis/jiu803 · 5.78 Impact Factor
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    ABSTRACT: Background. The potential available market (PAM) for new diagnostics for tuberculosis that meet the specifications of the high-priority target product profiles (TPPs) is currently unknown. Methods. We estimated the PAM in 2020 in 4 high-burden countries (South Africa, Brazil, China, and India) for tests that meet the specifications outlined in the TPPs. The yearly PAM was estimated for the most likely application of each TPP. Results. In 2020 the PAM for all 4 countries together was estimated to be (1) 12M tests/year with a value of 48M-71M USD for a sputum smear-replacement test; (2) 16M tests/year with a value of 65M-97M USD for a biomarker test; (3) 18M tests/year with a value of 18M-35M USD for a triage test; (4) 12M tests/year with a value of 59M-2238M USD for a tuberculosis detection plus drug susceptibility test (DST) all-in-one or 1.5M tests/year for a DST that follows a positive tuberculosis detection test with a corresponding value of 75M-121M for both tuberculosis detection and DST. Conclusions. Although there is a considerable potential market for novel tuberculosis diagnostics that fit the specification of the TPPs in the 4 high-burden countries, the actual market for an individual product remains uncertain.
    The Journal of Infectious Diseases 04/2015; 211(suppl 2):S58-S66. DOI:10.1093/infdis/jiu817 · 5.78 Impact Factor
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    ABSTRACT: Xpert MTB/RIF testing is being used extensively in countries with a high burden of TB. However recent evidence suggests that it may not have the same accuracy or impact in high-income, low-burden TB countries. A prospective, pragmatic study was done between March 2012 and March 2014 to determine the feasibility, test accuracy, and impact on TB disease management provided by the Xpert test in a remote, medically underserved, predominantly Inuit population in Iqaluit, Nunavut, Canada. A total of 453 Xpert tests were run on sputum samples from 344 patients with suspected TB. Twenty seven patients were identified as having active TB disease by culture. There were no cases of drug resistant TB. Using culture as the gold standard, one Xpert test compared to 1,2 or 3 sputum samples cultured per patient, had a sensitivity of 85% (66-95, CI 95%) and a specificity = 99% (97-100, CI 95%) for detection of MTB. The indeterminate rate was 4.4% of all samples run. Treatment initiation was significantly shortened using Xpert versus the national standard of three smears (1.8 vs 7.7 days, p <0.007), and particularly shorter in smear-negative, culture-positive cases (1.8 vs 37.1 days, p value< 0.008). In a predominantly Inuit population in a remote region of Canada where the burden of TB is high and no TB testing facilities are available, on-site Xpert was feasible, accurate and shortened time to TB treatment initiation.
    Chest 03/2015; DOI:10.1378/chest.14-2948 · 7.13 Impact Factor
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    Madhukar Pai · Puneet Dewan
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    ABSTRACT: In a Guest Editorial on World TB Day, Madhukar Pai and Puneet Dewan identify programmatic and policy changes needed to end TB by 2035.
    PLoS Medicine 03/2015; 12(3):e1001805. DOI:10.1371/journal.pmed.1001805 · 14.00 Impact Factor
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    Madhukar Pai · Ziad A Memish
    03/2015; 5(1):1-2. DOI:10.1016/j.jegh.2015.01.001
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    Madhukar Pai
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    ABSTRACT: Interview with Professor Madhukar Pai, MD, PhD by Claire Raison (Commissioning Editor) Professor Madhukar Pai did his medical training and community medicine residency in Vellore, India. He completed his PhD in epidemiology at the University of California, Berkeley (CA, USA) and a postdoctoral fellowship at the University of California, San Francisco (CA, USA). He is currently an associate professor of epidemiology at McGill University in Montreal (Canada). He serves as the Director of Global Health Programs, and as an Associate Director of the McGill International Tuberculosis Centre. In addition, he serves as a Consultant for the Bill & Melinda Gates Foundation. He also serves on the Scientific Advisory Committee of the Foundation for Innovative New Diagnostics, Geneva, Switzerland. His research is focused on improving the diagnosis and treatment of tuberculosis, especially in high-burden countries such as India and South Africa. His research is supported by grant funding from the Gates Foundation, Grand Challenges Canada and Canadian Institutes of Health Research. He has more than 200 peer-reviewed publications. He is recipient of the Union Scientific Prize, Chanchlani Global Health Research Award and Stars in Global Health award from Grand Challenges Canada, and is a member of the Royal Society of Canada.
    Expert Review of Molecular Diagnostics 02/2015; 15(3):1-4. DOI:10.1586/14737159.2015.1010806 · 4.27 Impact Factor
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    ABSTRACT: OBJECTIVE: To assess the current served available market of tuberculosis (TB) diagnostics in South Africa in the public and private sectors.DESIGN: Public and private sector test volumes and unit costs were collected for tuberculin skin tests, interferon-gamma release assays, smear microscopy, culture, speciation, Xpert® MTB/RIF, other nucleic acid amplification tests, drug susceptibility testing and adenosine deaminase tests.RESULTS: In 2012, during Xpert scale-up, the public and private sectors performed a total of 9.2 million TB diagnostic tests, at an estimated total value of US$98 million. The public sector accounted for 93% of the overall test volume and value. There were no major differences in the types of tests performed in both sectors, with microscopy and culture accounting for the majority of tests performed (72%). In 2013, the public sector market value increased to US$101 million (a 10% increase over 2012): Xpert volumes increased by 166%, while total TB test volumes decreased by 12% compared to 2012.CONCLUSION: South Africa has a substantial TB diagnostic market in terms of both volume and value. The roll-out of Xpert provides insights into how markets change in volume and value with the introduction of new tools.
    The International Journal of Tuberculosis and Lung Disease 02/2015; 19(2). DOI:10.5588/ijtld.14.0565 · 2.76 Impact Factor

Publication Stats

11k Citations
1,777.33 Total Impact Points


  • 2006–2015
    • McGill University
      • • Department of Epidemiology, Biostatistics and Occupational Health
      • • Department of Pediatrics
      Montréal, Quebec, Canada
    • Mahatma Gandhi Institute of Medical Sciences
      • Department of Medicine
      Вардха, Mahārāshtra, India
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, California, United States
  • 2013
    • Liverpool School of Tropical Medicine
      Liverpool, England, United Kingdom
  • 2012–2013
    • Maastricht University
      • Department of Health, Ethics & Society
      Maastricht, Provincie Limburg, Netherlands
    • Montreal Heart Institute
      Montréal, Quebec, Canada
  • 2010–2012
    • University of Alberta
      • Department of Medical Microbiology and Immunology
      Edmonton, Alberta, Canada
    • King Saud medical city
      Ar Riyāḑ, Ar Riyāḑ, Saudi Arabia
  • 2002–2009
    • University of California, Berkeley
      • • Division of Epidemiology
      • • School of Public Health
      Berkeley, California, United States
  • 2005
    • Francis J. Curry National Tuberculosis Center
      San Francisco, California, United States