Madhukar Pai

McGill University, Montréal, Quebec, Canada

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Publications (295)1719.17 Total impact

  • 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
  • PLoS ONE 04/2015; 10(4):e0124525. DOI:10.1371/journal.pone.0124525 · 3.53 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
  • 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
  • Madhukar Pai
    The Indian journal of tuberculosis 01/2015; 62(1):1-3. DOI:10.1016/j.ijtb.2015.02.001
  • Madhukar Pai
    01/2015; 7(3). DOI:10.1016/j.ebiom.2015.01.018
  • Samuel G Schumacher, Madhukar Pai
    The International Journal of Tuberculosis and Lung Disease 01/2015; 19(1):2. DOI:10.5588/ijtld.14.0850 · 2.76 Impact Factor
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    ABSTRACT: Objectives Successful point-of-care (POC) testing (completion of test and treat cycle in one patient encounter) has immense potential to reduce diagnostic and treatment delays, and improve patient and public health outcomes. We explored what tests are done and how in public/private, rural/urban hospitals and clinics in South Africa and whether they can ensure successful POC testing.Methods This qualitative research study examined POC testing across major diseases in Cape Town, Durban and Eastern Cape. We conducted 101 semi-structured interviews and 7 focus group discussions with doctors, nurses, community health workers, patients, lab technicians, policymakers, hospital managers and diagnostic manufacturers.ResultsIn South Africa diagnostics are characterized by a centralized system. Most tests conducted on the spot can be made to work successfully as POC tests. The majority of public/private clinics and smaller hospitals send samples via couriers to centralized labs and retrieve results back the same way, via internet, fax, or phone. The main challenge to POC testing lies in transporting samples and results, while delays risk patient loss from diagnostic/treatment pathways. Strategies to deal with associated delays create new problems, such as artificially prolonged turn-around-times, strains on human resources and quality of testing, compounding additional diagnostic and treatment delays.Conclusions For POC testing to succeed, particular characteristics of diagnostic eco-systems and adaptations of professional practices to overcome associated challenges must be taken into account.This article is protected by copyright. All rights reserved.
    Tropical Medicine & International Health 12/2014; 20(4). DOI:10.1111/tmi.12450 · 2.30 Impact Factor
  • European Respiratory Journal 10/2014; 45(2). DOI:10.1183/09031936.00147714 · 7.13 Impact Factor
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    ABSTRACT: Health care workers (HCW) in low and middle income countries are at high risk of nosocomial tuberculosis infection. Periodic screening of health workers for both TB disease and infection can play a critical role in TB infection control. Occupational health programs that implement serial tuberculin skin testing (TST) are advised to use a two-step baseline TST. This helps to ensure that boosting of waned immune response is not mistaken as new TB infection (i.e. conversion). However, there are no data on safety of the two-step TST in the Indian context where HCWs are repeatedly exposed.Materials and methodsNursing students were recruited from 2007 to 2009 at the Christian Medical College and Hospital, Vellore, India. Consenting nursing students were screened with a baseline two-step TST at the time of recruitment. From 2007 to 2008 adverse events were recorded when reported during the TST reading (Cohort A). Nurses recruited in the final study year (2009) answered an investigator administered questionnaire assessing all likely side-effects Cohort B). This information was extracted from the case report forms and analysed.ResultsBetween 2007 and 09, 800 trainees consented to participate in the annual TB screening study and 779 did not have a past history of TB or recall a positive TST and were selected to administer TST. Of these, 755 returned for reading the result and had complete data and were included for the final analysis – 623 subjects in (cohort A) and 132 in (cohort B). These were included for the final analysis. In cohort A only 1.3% reported adverse events. In cohort B, as per the investigator administered questionnaire; 25% reported minor side effects. Itching and local pain were the most common side effects encountered. There were no major adverse events reported. In particular, the adverse events were similar in the second step of the test and not more severe.Conclusion Screening of HCWs with two-step TST for LTBI is simple and safe, and hence suitable for wide scale implementation in high-burden settings such as India.
    10/2014; 3(4). DOI:10.1016/j.ijmyco.2014.10.004
  • Claudia M Denkinger, Madhukar Pai
    European Respiratory Journal 10/2014; 44(4):1095-6. DOI:10.1183/09031936.00106914 · 7.13 Impact Factor
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    ABSTRACT: Rationale: Interferon-gamma release assays for latent tuberculosis infection result in a larger than expected number of conversions and reversions in occupational screening programs and reproducibility of test results is a concern. Objectives: Knowledge of the relative contribution and extent of the individual sources of variability (immunological, pre-analytical, or analytical) could help optimize testing protocols. Methods: We performed a systematic review of studies published by October 2013 on all potential sources of variability of commercial Interferon-gamma release assays (QuantiFERON-TB Gold In-Tube and T-SPOT.TB). The included studies assessed test variability under identical conditions and under different conditions (the latter both overall and stratified by individual sources of variability). Linear mixed effects models were used to estimate within-subject standard deviation. Measurements and Main Results: We identified a total of 26 articles, including 7 studies analyzing variability under the same conditions, 10 studies analyzing variability with repeat testing over time under different conditions and 19 studies reporting individual sources of variability. Most data were on QuantiFERON (only 3 studies on T-SPOT.TB). A considerable number of conversions and reversions were seen around the manufacturer-recommended cut-point. The estimated range of variability of interferon-gamma response in QuantiFERON under identical conditions was +/-0.47 IU/mL (coefficient of variation 13%) and +/- 0.26 IU/mL (30%) for individuals with an initial interferon-gamma response in the borderline range (0.25-0.80 IU/mL). The estimated range of variability in non-controlled settings was substantially larger (+/- 1.4 IU/mL; 60%). Blood volume inoculated into QuantiFERON tubes and pre-analytic delay were identified as other key sources of variability. Conclusion: This systematic review shows substantial variability with repeat Interferon-gamma release assays testing even under identical conditions suggesting that reversions and conversions around the existing cut-point should be interpreted with caution.
    09/2014; DOI:10.1513/AnnalsATS.201405-188OC

Publication Stats

11k Citations
1,719.17 Total Impact Points


  • 2007–2015
    • McGill University
      • • Department of Epidemiology, Biostatistics and Occupational Health
      • • Department of Pediatrics
      Montréal, Quebec, Canada
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 2012–2013
    • Maastricht University
      • Department of Health, Ethics & Society
      Maastricht, Provincie Limburg, Netherlands
  • 2010–2012
    • University of Alberta
      • Department of Medical Microbiology and Immunology
      Edmonton, Alberta, Canada
    • King Saud medical city
      Ar Riyāḑ, Ar Riyāḑ, Saudi Arabia
  • 2007–2012
    • Montreal Heart Institute
      Montréal, Quebec, Canada
  • 2007–2009
    • Christian Medical College Vellore
      • Department of Medicine
      Vellore, State of Tamil Nadu, India
  • 2002–2009
    • University of California, Berkeley
      • • Division of Epidemiology
      • • School of Public Health
      Berkeley, California, United States
  • 2005–2007
    • Mahatma Gandhi Institute of Medical Sciences
      • Department of Medicine
      Вардха, Maharashtra, India
    • Francis J. Curry National Tuberculosis Center
      San Francisco, California, United States
  • 2006
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, California, United States