John Metcalfe, MD, PhD, MPH


My research focuses on fundamental questions in the tracking and early identification of drug-resistant tuberculosis (DR-TB) to better target and evaluate control interventions. I have specialized training in clinical research methods, statistical prediction, repeated measures, and causal inference through doctoral work in the Division of Epidemiology, UC Berkeley. I have served as a consultant to the WHO, USAID, and PAHO for the development of regional and national TB management guidelines. Because of my commitment to work with critically underserved populations, I have been attracted to global health projects with strong programmatic relevance throughout my career. I have experience conducting prospective studies in challenging environments, including a one-year field assignment in eastern D.R. Congo, and in Zimbabwe, where we oversaw treatment of the first cohort of drug-resistant TB patients (2011), undertook the first modern characterization of DR-TB in the country (2014), carried out a pragmatic diagnostic RCT of GeneXpert MTB/RIF (2014), and consulted on national TB (2014) and DR-TB (2016) prevalence surveys.

Within the NIH Division of AIDS Clinical Trials Group, I lead an ACTG phase IIc trial (protocol A5362) examining the sterilizing activity of the repurposed agent clofazimine and the new rifamycin rifapentine; this trial will enroll TB patients at nine sites in seven countries. I am Industry Contact and Protocol Design Lead for molecular drug susceptibility testing for the Rapid Research for Diagnostics Development in TB Network (R2D2 TB Network). My work also focuses on determining mechanisms of M. tuberculosis clonal evolution under treatment, the longitudinal clinical significance of micro-heteroresistance, and on developing assays for non-invasive therapeutic drug monitoring. Collectively, these experiences provide distinct perspectives on keystone problems with high clinical impact, bench-to-bedside translation barriers, and scientific conduct in a variety of international settings.
Ph.D., 2012 - Division of Epidemiology, University of California, Berkely
Fellowship, 2009 - Pulmonary and Critical Care Medicine, University of California, San Francisco
Residency, 2006 - Internal Medicine, University of California, San Francisco
MPH, 2003 - Chronic Complex Emergencies, Tufts University School of Medicine
M.D., 2003 - School of Medicine, Tufts University School of Medicine
BS, 1998 - Molecular Biology, Humboldt State University
AB, 1995 - Sociology, Michigan State University
Honors and Awards
  • Clinical Scientist Development Award, Doris Duke Charitable Foundation, 2015
  • Harold Amos Scholar, Robert Wood Johnson Foundation, 2010
  • Chancellor's Fellow, University of California, Berkeley, 2008
  1. Derendinger B, de Vos M, Pillay S, Venter R, Metcalfe J, Ghebrekristos Y, Minnies S, Dolby T, Beylis N, Warren R, Theron G. Frequent suboptimal thermocycler ramp rate usage negatively impacts GenoType MTBDRsl VER 2.0 performance for second-line drug resistant tuberculosis diagnosis. 2022. PMID: 35108607

  2. Whitfield MG, Engelthaler DM, Allender C, Folkerts M, Heupink TH, Limberis J, Warren RM, Van Rie A, Metcalfe JZ. Comparative Performance of Genomic Methods for the Detection of Pyrazinamide Resistance and Heteroresistance in Mycobacterium tuberculosis. 2021. PMID: 34757831

  3. Timire C, Ngwenya M, Chirenda J, Metcalfe JZ, Kranzer K, Pedrazzoli D, Takarinda KC, Nguhiu P, Madzingaidzo G, Ndlovu K, Mapuranga T, Cornell M, Sandy C. Catastrophic costs among tuberculosis-affected households in Zimbabwe: A national health facility-based survey. 2021. PMID: 34192392

  4. Tadokera R, Huo S, Theron G, Timire C, Manyau-Makumbirofa S, Metcalfe JZ. Health care seeking patterns of rifampicin-resistant tuberculosis patients in Harare, Zimbabwe: A prospective cohort study. 2021. PMID: 34270593

  5. Bisimwa BC, Nachega JB, Warren RM, Theron G, Metcalfe JZ, Shah M, Diacon AH, Sam-Agudu NA, Yotebieng M, Bulabula ANH, Katoto PDMC, Chirambiza JP, Nyota R, Birembano FM, Musafiri EM, Byadunia S, Bahizire E, Kaswa MK, Callens S, Kashongwe ZM. Xpert MTB/RIF-detected Rifampicin Resistance is a Sub-Optimal Surrogate for Multidrug Resistant Tuberculosis in Eastern Democratic Republic of the Congo: Diagnostic and Clinical Implications. 2020. PMID: 32590841

  6. Metcalfe J, Bacchetti P, Esmail A, Reckers A, Aguilar D, Wen A, Huo S, Muyindike WR, Hahn JA, Dheda K, Gandhi M, Gerona R. Diagnostic accuracy of a liquid chromatography-tandem mass spectrometry assay in small hair samples for rifampin-resistant tuberculosis drug concentrations in a routine care setting. 2021. PMID: 33482745

  7. Reckers A, Huo S, Esmail A, Dheda K, Bacchetti P, Gandhi M, Metcalfe J, Gerona R. Development and validation of a liquid chromatography-tandem mass spectrometry method for quantifying delamanid and its metabolite in small hair samples. 2020. PMID: 33713954

  8. Tadyanemhandu C, Chirenda J, Garvey C, Metcalfe J. Treatment success, but living with the consequences of post-tuberculosis sequelae. 2020. PMID: 32718395

  9. Reckers A, Wen A, Aguilar D, Bacchetti P, Gandhi M, Metcalfe J, Gerona R. Validated LC-MS/MS Panel for Quantifying 11 Drug-Resistant TB Medications in Small Hair Samples. 2020. PMID: 32510502

  10. Chaka W, Berger C, Huo S, Robertson V, Tachiona C, Magwenzi M, Magombei T, Mpamhanga C, Katzenstein D, Metcalfe J. Presentation and outcome of suspected sepsis in a high-HIV burden, high antiretroviral coverage setting. 2020. PMID: 32289564

  11. Wasserman S, Huo S, Ky K, Malig YN, Esmail A, Dheda K, Bacchetti P, Gerona R, Maartens G, Gandhi M, Metcalfe J. CORRELATION OF LINEZOLID HAIR CONCENTRATIONS WITH PLASMA EXPOSURE IN PATIENTS WITH DRUG-RESISTANT TB. 2020. PMID: 31932382

  12. Engelthaler DM, Streicher EM, Kelley EJ, Allender CJ, Wiggins K, Jimenez D, Lemmer D, Vittinghoff E, Theron G, Sirgel FA, Warren RM, Metcalfe JZ. Minority Mycobacterium tuberculosis Genotypic Populations as an Indicator of Subsequent Phenotypic Resistance. 2019. PMID: 31774334

  13. Tadyanemhandu C, Garvey C, Chin A, Metcalfe J. More should be done now for patients with TB-associated chronic lung disease. 2019. PMID: 31627778

  14. Timire C, Metcalfe JZ, Chirenda J, Scholten JN, Manyame-Murwira B, Ngwenya M, Matambo R, Charambira K, Mutunzi H, Kalisvaart N, Sandy C. Prevalence of drug-resistant tuberculosis in Zimbabwe: a health facility-based cross-sectional survey. 2019. PMID: 31357057

  15. Gerona R, Wen A, Aguilar D, Shum J, Reckers A, Bacchetti P, Gandhi M, Metcalfe J. Simultaneous analysis of 11 medications for drug resistant TB in small hair samples to quantify adherence and exposure using a validated LC-MS/MS panel. 2019. PMID: 31369929

  16. Pooran A, Theron G, Zijenah L, Chanda D, Clowes P, Mwenge L, Mutenherwa F, Lecesse P, Metcalfe J, Sohn H, Hoelscher M, Pym A, Peter J, Dowdy D, Dheda K. Point of care Xpert MTB/RIF versus smear microscopy for tuberculosis diagnosis in southern African primary care clinics: a multicentre economic evaluation. 2019. PMID: 31097281

  17. de Vos M, Ley SD, Wiggins KB, Derendinger B, Dippenaar A, Grobbelaar M, Reuter A, Dolby T, Burns S, Schito M, Engelthaler DM, Metcalfe J, Theron G, van Rie A, Posey J, Warren R, Cox H. Bedaquiline Microheteroresistance after Cessation of Tuberculosis Treatment. 2019. PMID: 31141643

  18. Metcalfe J, Bacchetti P, Gerona R, Esmail A, Dheda K, Gandhi M. Association of anti-tuberculosis drug concentrations in hair and treatment outcomes in MDR- and XDR-TB. 2019. PMID: 31041318

  19. Chin AT, Rylance J, Makumbirofa S, Meffert S, Vu T, Clayton J, Mason P, Woodruff P, Metcalfe J. Chronic lung disease in adult recurrent tuberculosis survivors in Zimbabwe: a cohort study. 2019. PMID: 30808453

  20. Di Tanna GL, Raza Khaki A, Theron G, McCarthy K, Cox H, Mupfumi L, Trajman A, Sodai Zijenah L, Mason P, Bandason T, Durovni B, Bara W, Hoelscher M, Clowes P, Mangu C, Chanda D, Pym A, Mwaba P, Cobelens F, Nicol MP, Dheda K, Churchyard G, Fielding K, Metcalfe JZ. Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis. 2019. PMID: 30683238

  21. Kühnert D, Coscolla M, Brites D, Stucki D, Metcalfe J, Fenner L, Gagneux S, Stadler T. Tuberculosis outbreak investigation using phylodynamic analysis. 2018. PMID: 29880306

  22. Metcalfe JZ, Streicher E, Theron G, Colman RE, Allender C, Lemmer D, Warren R, Engelthaler DM. Cryptic Microheteroresistance Explains Mycobacterium tuberculosis Phenotypic Resistance. Volume 196 of Issue 9. 2017. PMID: 28614668

  23. Metcalfe JZ, Streicher E, Theron G, Colman RE, Penaloza R, Allender C, Lemmer D, Warren RM, Engelthaler DM. Mycobacterium tuberculosis Subculture Results in Loss of Potentially Clinically Relevant Heteroresistance. Volume 61 of Issue 11. 2017. PMID: 28893776

  24. Metcalfe J, Gerona R, Wen A, Bacchetti P, Gandhi M. An LC-MS/MS-based method to analyze the anti-tuberculosis drug bedaquiline in hair. Volume 21 of Issue 9. 2017. PMID: 28826458

  25. O'Donnell MR, Padayatchi N, Metcalfe JZ. Elucidating the role of clofazimine for the treatment of tuberculosis. 2016. PMID: 28240574

  26. Rylance J, Mchugh G, Metcalfe J, Mujuru H, Nathoo K, Wilmore S, Rowland-Jones S, Majonga E, Kranzer K, Ferrand RA. Chronic lung disease in HIV-infected children established on antiretroviral therapy. Volume 30 of Issue 18. 2016. PMID: 27662546

  27. Blount RJ, Tran MC, Everett CK, Cattamanchi A, Metcalfe JZ, Connor D, Miller CR, Grinsdale J, Higashi J, Nahid P. Tuberculosis progression rates in U.S. Immigrants following screening with interferon-gamma release assays. Volume 16 of Issue 1. 2016. PMID: 27558397

  28. Moses MW, Zwerling A, Cattamanchi A, Denkinger CM, Banaei N, Kik SV, Metcalfe J, Pai M, Dowdy D. Serial testing for latent tuberculosis using QuantiFERON-TB Gold In-Tube: A Markov model. Volume 6. 2016. PMID: 27469388

  29. Gerona R, Wen A, Koss C, Bacchetti P, Gandhi M, Metcalfe J. A multi-analyte panel for non-invasive pharmacokinetic monitoring of second-line anti-tuberculosis drugs. Volume 20 of Issue 7. 2016. PMID: 27287660

  30. Metcalfe JZ, Makumbirofa S, Makamure B, Sandy C, Bara W, Mason P, Hopewell PC. Xpert(®) MTB/RIF detection of rifampin resistance and time to treatment initiation in Harare, Zimbabwe. Volume 20 of Issue 7. 2016. PMID: 27287639

  31. Gerona R, Wen A, Chin AT, Koss CA, Bacchetti P, Metcalfe J, Gandhi M. Quantifying Isoniazid Levels in Small Hair Samples: A Novel Method for Assessing Adherence during the Treatment of Latent and Active Tuberculosis. Volume 11 of Issue 5. 2016. PMID: 27191185

  32. S Rylance, J Rylance, G McHugh, H Mujuru, S Munyati, T Bandason, J Metcalfe, K Kranzer, R Ferrand. G276(P) Chronic respiratory morbidity among HIV-infected children in Zimbabwe; a comparison of ART naïve and treated cohorts. 2016. PMID:

  33. O'Donnell MR, Daftary A, Frick M, Hirsch-Moverman Y, Amico KR, Senthilingam M, Wolf A, Metcalfe JZ, Isaakidis P, Davis JL, Zelnick JR, Brust JC, Naidu N, Garretson M, Bangsberg DR, Padayatchi N, Friedland G. Re-inventing adherence: toward a patient-centered model of care for drug-resistant tuberculosis and HIV. Volume 20 of Issue 4. 2016. PMID: 26970149

  34. Metcalfe JZ, O'Donnell MR, Bangsberg DR. Moving Beyond Directly Observed Therapy for Tuberculosis. Volume 12 of Issue 9. 2015. PMID: 26372602

  35. Metcalfe JZ, Makumbirofa S, Makamure B, Mutetwa R, Peñaloza RA, Sandy C, Bara W, Mungofa S, Hopewell PC, Mason P. Suboptimal specificity of Xpert MTB/RIF among treatment-experienced patients. Volume 45 of Issue 5. 2015. PMID: 25792637

  36. Coscolla M, Barry PM, Oeltmann JE, Koshinsky H, Shaw T, Cilnis M, Posey J, Rose J, Weber T, Fofanov VY, Gagneux S, Kato-Maeda M, Metcalfe JZ. Genomic epidemiology of multidrug-resistant Mycobacterium tuberculosis during transcontinental spread. Volume 212 of Issue 2. 2015. PMID: 25601940

  37. Metcalfe JZ, Vittinghoff E, Hopewell PC. Analysis of Green Light Committee implementation and acquisition of second-line drug resistance. Volume 60 of Issue 6. 2014. PMID: 25527651

  38. Kelly JD, Grace Lin SY, Barry PM, Keh C, Higashi J, Metcalfe JZ. Xpert MTB/RIF false detection of rifampin-resistant tuberculosis from prior infection. Volume 190 of Issue 11. 2014. PMID: 25436783

  39. Tagmouti S, Slater M, Benedetti A, Kik SV, Banaei N, Cattamanchi A, Metcalfe J, Dowdy D, van Zyl Smit R, Dendukuri N, Pai M, Denkinger C. Reproducibility of interferon gamma (IFN-?) release Assays. A systematic review. Volume 11 of Issue 8. 2014. PMID: 25188809

  40. Metcalfe JZ, Mason P, Mungofa S, Sandy C, Hopewell PC. Empiric tuberculosis treatment in retreatment patients in high HIV/tuberculosis-burden settings. Volume 14 of Issue 9. 2014. PMID: 25164190

  41. Mupfumi L, Makamure B, Chirehwa M, Sagonda T, Zinyowera S, Mason P, Metcalfe JZ, Mutetwa R. Impact of Xpert MTB/RIF on Antiretroviral Therapy-Associated Tuberculosis and Mortality: A Pragmatic Randomized Controlled Trial. Volume 1 of Issue 1. 2014. PMID: 25734106

  42. Davis JL, Kawamura LM, Chaisson LH, Grinsdale J, Benhammou J, Ho C, Babst A, Banouvong H, Metcalfe JZ, Pandori M, Hopewell PC, Cattamanchi A. Impact of GeneXpert MTB/RIF on patients and tuberculosis programs in a low-burden setting. a hypothetical trial. Volume 189 of Issue 12. 2014. PMID: 24869625

  43. Metcalfe JZ, Makumbirofa S, Makamure B, Sandy C, Bara W, Mungofa S, Hopewell PC, Mason P. Drug-resistant tuberculosis in high-risk groups, Zimbabwe. Volume 20 of Issue 1. 2014. PMID: 24377879

  44. Pai M, Denkinger CM, Kik SV, Rangaka MX, Zwerling A, Oxlade O, Metcalfe JZ, Cattamanchi A, Dowdy DW, Dheda K, Banaei N. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Volume 27 of Issue 1. 2014. PMID: 24396134

  45. Millman AJ, Dowdy DW, Miller CR, Brownell R, Metcalfe JZ, Cattamanchi A, Davis JL. Rapid molecular testing for TB to guide respiratory isolation in the U.S.: a cost-benefit analysis. Volume 8 of Issue 11. 2013. PMID: 24278155

  46. Prach LM, Pascopella L, Barry PM, Flood J, Porco TC, Hopewell PC, Metcalfe JZ. Rifampin monoresistant tuberculosis and HIV comorbidity in California, 1993-2008: a retrospective cohort study. Volume 27 of Issue 16. 2013. PMID: 23842135

  47. Cattamanchi A, Walter ND, Metcalfe JZ, Davis JL. A transcriptional signature for active TB: have we found the needle in the haystack? Volume 10 of Issue 10. 2013. PMID: 24167454

  48. Gopal M, Padayatchi N, Metcalfe JZ, O'Donnell MR. Systematic review of clofazimine for the treatment of drug-resistant tuberculosis. Volume 17 of Issue 8. 2013. PMID: 23541151

  49. Metcalfe JZ, Porco TC, Westenhouse J, Damesyn M, Facer M, Hill J, Xia Q, Watt JP, Hopewell PC, Flood J. Tuberculosis and HIV co-infection, California, USA, 1993–2008. Volume 19 of Issue 3. 2013. PMID: 23745218

  50. Makamure B, Mhaka J, Makumbirofa S, Mutetwa R, Mupfumi L, Mason P, Metcalfe JZ. Microscopic-observation drug-susceptibility assay for the diagnosis of drug-resistant tuberculosis in Harare, Zimbabwe. Volume 8 of Issue 2. 2013. PMID: 23409072

  51. Metcalfe JZ, Cattamanchi A, McCulloch CE, Lew JD, Ha NP, Graviss EA. Test variability of the QuantiFERON-TB gold in-tube assay in clinical practice. Volume 187 of Issue 2. 2012. PMID: 23103734

  52. Dantes R, Metcalfe J, Kim E, Kato-Maeda M, Hopewell PC, Kawamura M, Nahid P, Cattamanchi A. Impact of isoniazid resistance-conferring mutations on the clinical presentation of isoniazid monoresistant tuberculosis. Volume 7 of Issue 5. 2012. PMID: 22649569

  53. Geng EH, Glidden DV, Bangsberg DR, Bwana MB, Musinguzi N, Nash D, Metcalfe JZ, Yiannoutsos CT, Martin JN, Petersen ML. A causal framework for understanding the effect of losses to follow-up on epidemiologic analyses in clinic-based cohorts: the case of HIV-infected patients on antiretroviral therapy in Africa. Volume 175 of Issue 10. 2012. PMID: 22306557

  54. Metcalfe JZ, Everett CK, Steingart KR, Cattamanchi A, Huang L, Hopewell PC, Pai M. Interferon-? release assays for active pulmonary tuberculosis diagnosis in adults in low- and middle-income countries: systematic review and meta-analysis. Volume 204 Suppl 4. 2011. PMID: 21996694

  55. Brust JC, O'Donnell MR, Metcalfe JZ. TB/HIV: an orphan disease? Volume 183 of Issue 11. 2011. PMID: 21642250

  56. Cattamanchi A, Smith R, Steingart KR, Metcalfe JZ, Date A, Coleman C, Marston BJ, Huang L, Hopewell PC, Pai M. Interferon-gamma release assays for the diagnosis of latent tuberculosis infection in HIV-infected individuals: a systematic review and meta-analysis. Volume 56 of Issue 3. 2011. PMID: 21239993

  57. Kato-Maeda M, Metcalfe JZ, Flores L. Genotyping of Mycobacterium tuberculosis: application in epidemiologic studies. Volume 6 of Issue 2. 2011. PMID: 21366420

  58. Metcalfe JZ, Kim EY, Lin SY, Cattamanchi A, Oh P, Flood J, Hopewell PC, Kato-Maeda M. Determinants of multidrug-resistant tuberculosis clusters, California, USA, 2004-2007. Volume 16 of Issue 9. 2010. PMID: 20735924

  59. John Metcalfe, Matt Facer, Mark Damesyn, Qiang Xia, James Watt, Julia Hill, Philip Hopewell, Janice Westenhouse, Jennifer Flood. Evolution of tuberculosis/HIV co-infection in California during the HAART Era, 1996-2007. 2010. PMID:

  60. Davis JL, Worodria W, Kisembo H, Metcalfe JZ, Cattamanchi A, Kawooya M, Kyeyune R, den Boon S, Powell K, Okello R, Yoo S, Huang L. Clinical and radiographic factors do not accurately diagnose smear-negative tuberculosis in HIV-infected inpatients in Uganda: a cross-sectional study. Volume 5 of Issue 3. 2010. PMID: 20361038

  61. Metcalfe JZ, Cattamanchi A, Vittinghoff E, Ho C, Grinsdale J, Hopewell PC, Kawamura LM, Nahid P. Evaluation of quantitative IFN-gamma response for risk stratification of active tuberculosis suspects. Volume 181 of Issue 1. 2009. PMID: 19797760

  62. Cattamanchi A, Dantes RB, Metcalfe JZ, Jarlsberg LG, Grinsdale J, Kawamura LM, Osmond D, Hopewell PC, Nahid P. Clinical characteristics and treatment outcomes of patients with isoniazid-monoresistant tuberculosis. Volume 48 of Issue 2. 2009. PMID: 19086909

  63. Gouveia EL, Metcalfe J, de Carvalho AL, Aires TS, Villasboas-Bisneto JC, Queirroz A, Santos AC, Salgado K, Reis MG, Ko AI. Leptospirosis-associated severe pulmonary hemorrhagic syndrome, Salvador, Brazil. Volume 14 of Issue 3. 2008. PMID: 18325275

  64. Roshanravan B, Kari E, Gilman RH, Cabrera L, Lee E, Metcalfe J, Calderon M, Lescano AG, Montenegro SH, Calampa C, Vinetz JM. Endemic malaria in the Peruvian Amazon region of Iquitos. Volume 69 of Issue 1. 2003. PMID: 12932096

  65. Stephanie Margaret Selike Wilmore, MRCP, MSc; Katharina Kranzer; Alan Williams; Beauty Makamure; Agness Nhdiza; Justin Mayini; Tsitsi Bandason; John Metcalfe; Mark Nicol; Indran Balakrishnan; Matthew Ellington; Neil Woodford; Susan Hopkins; Tim D McHugh; Rashida Ferrand.. Carriage of Extended-Spectrum Beta-Lactamase-producing Enterobacteriaceae in HIV-infected children in Zimbabwe . PMID: