Madhukar Pai

McGill University, Montréal, Quebec, Canada

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Publications (271)1595.91 Total impact

  • Samuel G Schumacher, Madhukar Pai
    The International Journal of Tuberculosis and Lung Disease 01/2015; 19(1):2. · 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; · 2.30 Impact Factor
  • European Respiratory Journal 10/2014; 45(2). · 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.
    International Journal of Mycobacteriology. 10/2014;
  • Claudia M Denkinger, Madhukar Pai
    European Respiratory Journal 10/2014; 44(4):1095-6. · 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.
    Annals of the American Thoracic Society. 09/2014;
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    ABSTRACT: The landscape of diagnostic testing for tuberculosis (TB) is changing rapidly, and stakeholders need urgent guidance on how to develop, deploy and optimize TB diagnostics in a way that maximizes impact and makes best use of available resources. When decisions must be made with only incomplete or preliminary data available, modelling is a useful tool for providing such guidance. Following a meeting of modelers and other key stakeholders organized by the TB Modelling and Analysis Consortium, we propose a conceptual framework for positioning models of TB diagnostics. We use that framework to describe modelling priorities in four key areas: Xpert(®) MTB/RIF scale-up, target product profiles for novel assays, drug susceptibility testing to support new drug regimens, and the improvement of future TB diagnostic models. If we are to maximize the impact and cost-effectiveness of TB diagnostics, these modelling priorities should figure prominently as targets for future research.
    The International Journal of Tuberculosis and Lung Disease 09/2014; 18(9):1012-8. · 2.76 Impact Factor
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    ABSTRACT: India has announced a goal of universal access to quality tuberculosis (TB) diagnosis and treatment. A number of novel diagnostics could help meet this important goal. The rollout of one such diagnostic, Xpert MTB/RIF (Xpert) is being considered, but if Xpert is used mainly for people with HIV or high risk of multidrug-resistant TB (MDR-TB) in the public sector, population-level impact may be limited.
    PLoS Medicine 07/2014; 11(7):e1001674. · 14.00 Impact Factor
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    Madhukar Pai, Prashant Yadav, Ravi Anupindi
    The Lancet Global Health. 07/2014; 2(7):e389.
  • Madhukar Pai
    Journal of Epidemiology and Global Health. 06/2014;
  • Claudia M Denkinger, Madhukar Pai
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 05/2014;
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    ABSTRACT: The absence of a gold standard, i.e., a diagnostic reference standard having perfect sensitivity and specificity, is a common problem in clinical practice and in diagnostic research studies. There is a need for methods to estimate the incremental value of a new, imperfect test in this context.
    BMC Medical Research Methodology 05/2014; 14(1):67. · 2.17 Impact Factor
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    ABSTRACT: Background. India has the largest global burden of tuberculosis (TB)-related morbidity and mortality as well as undernutrition. Undernutrition impairs cell-mediated immunity, is a risk factor for the development of TB, and has the largest potential impact on the incidence of TB in countries with a high burden of TB. Methods. We refined the national estimate of the population-attributable fraction (PAF) for undernutrition in India to report the first subnational estimates, and stratified these further for age, gender, residence, caste and socioeconomic status. We also compared the PAF related to undernutrition in India with that in 15 other countries with a high burden of TB. We used data on body mass index (BMI) from the National Family Health Survey-3 (NFHS-3), as well as risk estimates for a low BMI from a recently published population-based study which had controlled for several confounders. Results. The overall prevalence of undernutrition in the age group of 15-49 years was 35.6% among women and 34.2% among men. About half (55.4%; 95% CI 27.4- 75.9) of all cases of active TB among women and 54.4% (95% CI 26.5-75.2) of all cases among men were attributable to undernutrition. In the age group of 15-19 years, the PAFs for undernutrition were 62% and 67% among women and men, respectively. The PAF of undernutrition was higher in rural areas, in scheduled castes, scheduled tribes and other backward classes, and in the lower quintiles of the wealth index. The PAF of undernutrition exceeded 50% in most states, and the largest PAFs were seen among women of scheduled tribes in central India. Among countries with a high burden of TB, India had the highest PAF related to undernutrition. Conclusion. Addressing the problem of endemic undernutrition among adolescents and adults in India could complement the current TB control strategy based on case management, and help reduce the incidence of TB in India in line with global targets. Copyright 2014, NMJI.
    The National medical journal of India 05/2014; 27(3):128-133. · 0.91 Impact Factor
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    ABSTRACT: To the Editor:Globally, a third of all tuberculosis (TB) cases are not notified and many patients do not receive drug susceptibility testing (DST) (1). New diagnostics can contribute to increased case detection, shorter diagnostic delay and reduced TB transmission. While the Xpert MTB/RIF assay (Cepheid Inc., Sunnyvale, CA, USA) is a much needed breakthrough (2), it may not reach lower tiers of the healthcare system (3) and doesn't meet all needs (e.g. cannot detect resistance against multiple drugs).Several promising diagnostics are under development and companies are showing interest in TB products, inspired by the success of Xpert MTB/RIF (4). But which new TB diagnostics should they invest in, and what is the potential market size for these products? Stakeholders have expressed a need for different products, including a test for childhood TB (5), a simple point-of-care-test for active pulmonary TB (6), a molecular smear replacement test (7), DST for expected new drug regimens (8), predictive biomarkers for latent TB infection (LTBI) (9), and treatment monitoring (10).Given the variety of these needs, it is important for product developers to have access to: 1) a clearly identified list of diagnostics that are considered high priority by the TB community; 2) well developed, detailed.
    European Respiratory Journal 04/2014; · 7.13 Impact Factor
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    ABSTRACT: Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is endorsed for the detection of pulmonary tuberculosis (TB). We performed a systematic review and meta-analysis to assess the accuracy of Xpert for the detection of extrapulmonary TB.We searched multiple databases to October 15, 2013. We determined the accuracy of Xpert compared with culture and a composite reference standard (CRS). We grouped data by sample type and performed meta-analyses using a bivariate random-effects model. We assessed sources of heterogeneity using meta-regression for predefined covariates.We identified 18 studies involving 4461 samples. Sample processing varied greatly among the studies. Xpert sensitivity differed substantially between sample types. In lymph node tissues or aspirates, Xpert pooled sensitivity was 83.1% (95% CI 71.4-90.7%) versus culture and 81.2% (95% CI 72.4-87.7%) versus CRS. In cerebrospinal fluid, Xpert pooled sensitivity was 80.5% (95% CI 59.0-92.2%) against culture and 62.8% (95% CI 47.7-75.8%) against CRS. In pleural fluid, pooled sensitivity was 46.4% (95% CI 26.3-67.8%) against culture and 21.4% (95% CI 8.8-33.9%) against CRS. Xpert pooled specificity was consistently >98.7% against CRS across different sample types.Based on this systematic review, the World Health Organization now recommends Xpert over conventional tests for diagnosis of TB in lymph nodes and other tissues, and as the preferred initial test for diagnosis of TB meningitis.
    European Respiratory Journal 04/2014; · 7.13 Impact Factor
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    ABSTRACT: To the Editor:We have previously shown that Indian healthcare workers have higher prevalence of latent tuberculosis infection (LTBI) and are at increased risk for new infection (1-4). Interferon-γ release assays (IGRAs) have been introduced as an alternative to the tuberculin skin test (TST) for diagnosing LTBI in healthcare workers and other high-risk groups. They have logistical advantages over the TST and will not cross-react with the bacille Calmette Guérin vaccine. IGRAs are now being widely used for screening healthcare workers (5), yet recent reports indicate that switching from TST to IGRAs for the serial testing of healthcare workers may result in increased rates of test conversions and reversions (3, 6-8). Most of these studies are from low tuberculosis (TB) incidence settings, with limited opportunity for nosocomial TB exposure; as a result, the increased conversion rates are considered false-positive test conversions, making it difficult for clinicians to interpret IGRA test conversions in these settings (9). It remains unclear whether IGRA conversions are associated with TB exposure in high TB incidence settings where unprotected exposure to infectious TB patients is more common among healthcare workers.To evaluate whether IGRA conversions may represent new cases of LTBI, in a high TB incidence setting, in the.
    European Respiratory Journal 04/2014; · 7.13 Impact Factor
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    Madhukar Pai, Prashant Yadav, Ravi Anupindi
    The Lancet Global Health. 04/2014; 2(4):e189–e190.
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    ABSTRACT: To systematically review Indian literature on delays in tuberculosis (TB) diagnosis and treatment. We searched multiple sources for studies on delays in patients with pulmonary TB and those with chest symptoms. Studies were included if numeric data on any delay were reported. Patient delay was defined as the interval between onset of symptoms and the patient's first contact with a health care provider. Diagnostic delay was defined as the interval between the first consultation with a health care provider and diagnosis. Treatment delay was defined as the interval between diagnosis and initiation of anti-tuberculosis treatment. Total delay was defined as time interval from the onset of symptoms until treatment initiation. Among 541 potential citations identified, 23 studies met the inclusion criteria. Included studies used a variety of definitions for onset of symptoms and delays. Median estimates of patient, diagnostic and treatment delay were respectively 18.4 (IQR 14.3-27.0), 31.0 (IQR 24.5-35.4) and 2.5 days (IQR 1.9-3.6) for patients with TB and those with chest symptoms combined. The median total delay was 55.3 days (IQR 46.5-61.5). About 48% of all patients first consulted private providers; an average of 2.7 health care providers were consulted before diagnosis. Number and type of provider first consulted were the most important risk factors for delay. These findings underscore the need to develop novel strategies for reducing patient and diagnostic delays and engaging first-contact health care providers.
    The International Journal of Tuberculosis and Lung Disease 03/2014; 18(3):255-66. · 2.76 Impact Factor
  • Madhukar Pai, Sandra V Kik, Niaz Banaei
    Annals of the American Thoracic Society. 03/2014; 11(3):399-401.
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    ABSTRACT: To the Editor:Sputum smear microscopy (SSM) has been the cornerstone of tuberculosis (TB) diagnosis, and is mainly performed in peripheral microscopy centres attached to primary health centres where TB therapy can be administered. Although SSM is inexpensive and easy to perform with a limited infrastructure, the shortcomings are its relatively low sensitivity and its inability to detect drug-resistance. Thus, there is a need for a more sensitive technology that can replace microscopy (1, 2).Several next-generation molecular diagnostics are under development with the specific intention of use in microscopy centres (3-5). In a recent survey of 22 high-burden countries (HBCs), we showed that the conditions, equipment and expertise present in microscopy centres are challenging and need to be considered by product developers (6). While the Xpert MTB/RIF (Cepheid Inc., Sunnyvale, CA, USA) assay is accurate, endorsed by the World Health Organization and is being implemented in many countries, it was not designed for use in peripheral microscopy centres (7, 8). To assist product developers working on tests for use in microscopy centres, we have outlined the desirable test characteristics (1).For companies to take on the challenge and invest in new diagnostics, an understanding of the potential market size is paramount (9). A.
    European Respiratory Journal 02/2014; · 7.13 Impact Factor

Publication Stats

9k Citations
1,595.91 Total Impact Points


  • 2006–2014
    • McGill University
      • • Department of Epidemiology, Biostatistics and Occupational Health
      • • Department of Pediatrics
      Montréal, Quebec, Canada
  • 2013
    • Himalayan Institute of Medical Sciences
      Dehra, Uttarakhand, India
    • Stanford Medicine
      • Department of Pathology
      Stanford, CA, United States
  • 2012–2013
    • Maastricht University
      • Department of Health, Ethics & Society
      Maastricht, Provincie Limburg, Netherlands
    • University of Washington Seattle
      • Department of Health Services
      Seattle, WA, United States
    • Institute of Bioinformatics and Applied Biotechnology
      Bengalūru, Karnātaka, India
    • Université du Québec à Montréal
      Montréal, Quebec, Canada
  • 2011–2013
    • Beth Israel Deaconess Medical Center
      • Department of Medicine
      Boston, Massachusetts, United States
    • Johns Hopkins Bloomberg School of Public Health
      • Department of Epidemiology
      Baltimore, MD, United States
    • Groote Schuur Hospital
      Kaapstad, Western Cape, South Africa
  • 2009–2013
    • University of Cape Town
      • • Lung Infection and Immunity Unit
      • • Department of Medicine
      Kaapstad, Western Cape, South Africa
  • 2007–2013
    • Christian Medical College Vellore
      • Department of Medicine
      Velluru, Tamil Nādu, India
  • 2011–2012
    • University of Alberta
      • Department of Medical Microbiology and Immunology
      Edmonton, Alberta, Canada
  • 2007–2011
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 2006–2011
    • University of California, San Francisco
      • • Division of Hospital Medicine
      • • Division of HIV/AIDS
      San Francisco, CA, United States
  • 2010
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
    • Foundation for Innovative New Diagnostics
      Genève, Geneva, Switzerland
    • McGill University Health Centre
      Montréal, Quebec, 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
  • 2008
    • Universidade Gama Filho
      Rio de Janeiro, Rio de Janeiro, Brazil
  • 2003–2008
    • Mahatma Gandhi Institute of Medical Sciences
      • • Department of Biochemistry
      • • Department of Medicine
      Wardha, State of Maharashtra, India
  • 2005–2007
    • Francis J. Curry National Tuberculosis Center
      San Francisco, California, United States