Madhukar Pai

McGill University, Montréal, Quebec, Canada

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Publications (319)1887.44 Total impact

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    ABSTRACT: Background: Effective infectious disease control requires early diagnosis and treatment initiation. Point-of-care testing offers rapid turn-around-times, facilitating same day clinical management decisions. To maximize the benefits of such POC testing programs, we need to understand how rapid tests are used in everyday clinical practice. Methods: In this cross-sectional survey study, 400 primary healthcare providers in two cities in South Africa were interviewed on their use of rapid tests in general, and tuberculosis diagnostic practices, between September 2012 and June 2013. Public healthcare facilities were selected using probability-sampling techniques and private healthcare providers were randomly selected from the Health Professional Council of South Africa list. To ascertain differences between the two healthcare sectors 2-sample z-tests were used to compare sample proportions. Results: The numbers of providers interviewed were equally distributed between the public (n = 200) and private sector (n = 200). The most frequently reported tests in the private sector include blood pressure (99.5%), glucose finger prick (89.5%) and urine dipstick (38.5%); and in the public sector were pregnancy (100%), urine dipstick (100%), blood pressure (100%), glucose finger prick (99%) and HIV rapid test (98%). The majority of TB testing occurs in the public sector, where significantly more providers prefer Xpert MTB/RIF assay, the designated clinical TB diagnostic tool by the national TB program, as compared to the private sector (87% versus 71%, p-value >0.0001). Challenges with regard to TB diagnosis included the long laboratory turn-around-time, difficulty in obtaining sputum samples and lost results. All providers indicated that a new POC test for TB should be rapid and cheap, have good sensitivity and specificity, ease of sample acquisition, detect drug-resistance and work in HIV-infected persons. Conclusion/significance: The existing centralized laboratory services, poor quality assurance, and lack of staff capacity deter the use of more rapid tests at POC. Further research into the practices and choices of these providers is necessary to aid the development of new POC tests.
    PLoS ONE 10/2015; 10(10):e0141453. DOI:10.1371/journal.pone.0141453 · 3.23 Impact Factor
  • Tripti Pande · Madhukar Pai · Claudia Denkinger ·

    Chest 10/2015; 148(4_MeetingAbstracts):141A. DOI:10.1378/chest.2250163 · 7.48 Impact Factor
  • Tripti Pande · Chad Cohen · Madhukar Pai · Faiz Ahmad Khan ·

    Chest 10/2015; 148(4_MeetingAbstracts):135A. DOI:10.1378/chest.2268765 · 7.48 Impact Factor
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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 · 2.32 Impact Factor
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    ABSTRACT: Background: Successful point-of-care testing, namely ensuring the completion of the test and treat cycle in the same encounter, has immense potential to reduce diagnostic and treatment delays, and impact patient outcomes. However, having rapid tests is not enough, as many barriers may prevent their successful implementation in point-of-care testing programs. Qualitative research on diagnostic practices may help identify such barriers across different points of care in health systems. Methods: In this exploratory qualitative study, we conducted 78 semi-structured interviews and 13 focus group discussions in an urban and rural area of Karnataka, India, with healthcare providers (doctors, nurses, specialists, traditional healers, and informal providers), patients, community health workers, test manufacturers, laboratory technicians, program managers and policy-makers. Participants were purposively sampled to represent settings of hospitals, peripheral labs, clinics, communities and homes, in both the public and private sectors. Results: In the Indian context, the onus is on the patient to ensure successful point-of-care testing across homes, clinics, labs and hospitals, amidst uncoordinated providers with divergent and often competing practices, in settings lacking material, money and human resources. We identified three overarching themes affecting point-of-care testing: the main theme is 'relationships' among providers and between providers and patients, influenced by the cross-cutting theme of 'infrastructure'. Challenges with both result in 'modified practices' often favouring empirical (symptomatic) treatment over treatment guided by testing. Conclusions: Even if tests can be conducted on the spot and infrastructure challenges have been resolved, relationships among providers and between patients and providers are crucial for successful point-of-care testing. Furthermore, these barriers do not act in isolation, but are interlinked and need to be examined as such. Also, a test alone has only limited power to overcome those difficulties. Test developers, policy-makers, healthcare providers and funders need to use these insights in overcoming barriers to point-of-care testing programs.
    PLoS ONE 08/2015; 10(8):e0135112. DOI:10.1371/journal.pone.0135112 · 3.23 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 · 22.43 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 · 2.32 Impact Factor
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    Tripti Pande · Madhukar Pai · Claudia M Denkinger ·

    European Respiratory Journal 08/2015; DOI:10.1183/13993003.01064-2015 · 7.64 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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    William Arnold Wells · Mukund Uplekar · Madhukar Pai ·
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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 · 14.43 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
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    Kristen M. Little · Madhukar Pai · David W. Dowdy ·
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    ABSTRACT: Background: There is growing concern that interferon-γ release assays (IGRAs) are being used off-label for the diagnosis of active tuberculosis (TB) disease in many high-burden settings, including India, where the background prevalence of latent TB infection is high. We analyzed the costs and consequences of using IGRAs for the diagnosis of active TB in India from the perspective of the Indian TB control sector. Methods and findings: We constructed a decision analytic model to estimate the incremental cost and effectiveness of IGRAs for the diagnosis of active TB in India. We compared a reference scenario of clinical examination and non-microbiological tests against scenarios in which clinical diagnosis was augmented by the addition of either sputum smear microscopy, IGRA, or Xpert MTB/RIF. We examined costs (in 2013 US dollars) and consequences from the perspective of the Indian healthcare sector. Relative to sputum smear microscopy, use of IGRA for active TB resulted in 23,700 (95% uncertainty range, UR: 3,800 - 38,300) additional true-positive diagnoses, but at the expense of 315,700 (95% UR: 118,300 - 388,400) additional false-positive diagnoses and an incremental cost of US$49.3 million (95% UR: $34.9 - $58.0 million) (2.9 billion Indian Rupees). Relative to Xpert MTB/RIF (including the cost of treatment for drug resistant TB), use of IGRA led to 400 additional TB cases treated (95% UR: [-8,000] - 16,200), 370,600 (95% UR: 252,200 - 441,700) more false-positive diagnoses, 70,400 (95% UR: [-7,900] - 247,200) fewer disability-adjusted life years averted, and US$14.6 million (95%UR: [-$7.2] - $28.7 million) (854 million Indian Rupees) in additional costs. Conclusion: Using IGRAs for diagnosis of active TB in a setting like India results in tremendous overtreatment of people without TB, and substantial incremental cost with little gain in health. These results support the policies by WHO and Standards for TB Care in India, which discourage the use of IGRAs for the diagnosis of active TB in India and similar settings.
    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 · 2.32 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 · 6.00 Impact Factor
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    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 · 6.00 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 · 6.00 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 · 6.00 Impact Factor

Publication Stats

13k Citations
1,887.44 Total Impact Points


  • 2006-2015
    • McGill University
      • Department of Epidemiology, Biostatistics and Occupational Health
      Montréal, Quebec, Canada
    • 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
    • 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
  • 2003-2009
    • University of California, Berkeley
      • • Division of Epidemiology
      • • School of Public Health
      Berkeley, California, United States
  • 2004-2006
    • Mahatma Gandhi Institute of Medical Sciences
      • Department of Medicine
      Вардха, Mahārāshtra, India