John Metcalfe, MD, PhD, MPH
Professor
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.
Education
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
Websites
Publications
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
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
Ismail N, Rivière E, Limberis J, Huo S, Metcalfe JZ, Warren RM, Van Rie A. Genetic variants and their association with phenotypic resistance to bedaquiline in Mycobacterium tuberculosis: a systematic review and individual isolate data analysis. 2021. PMID: 34796339
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
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
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
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
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
Tadyanemhandu C, Chirenda J, Garvey C, Metcalfe J. Treatment success, but living with the consequences of post-tuberculosis sequelae. 2020. PMID: 32718395
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
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
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
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
Tadyanemhandu C, Garvey C, Chin A, Metcalfe J. More should be done now for patients with TB-associated chronic lung disease. 2019. PMID: 31627778
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
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
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
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
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
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
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
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
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
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
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
O'Donnell MR, Padayatchi N, Metcalfe JZ. Elucidating the role of clofazimine for the treatment of tuberculosis. 2016. PMID: 28240574
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
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
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
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
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
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
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:
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
Metcalfe JZ, O'Donnell MR, Bangsberg DR. Moving Beyond Directly Observed Therapy for Tuberculosis. Volume 12 of Issue 9. 2015. PMID: 26372602
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Brust JC, O'Donnell MR, Metcalfe JZ. TB/HIV: an orphan disease? Volume 183 of Issue 11. 2011. PMID: 21642250
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
Kato-Maeda M, Metcalfe JZ, Flores L. Genotyping of Mycobacterium tuberculosis: application in epidemiologic studies. Volume 6 of Issue 2. 2011. PMID: 21366420
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
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:
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
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
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
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
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
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: