O'Donnell Lab
Location and Contact Information
Principal Investigator
Dr. O'Donnell's research interests center around global health, respiratory infections, and sepsis. Current projects are in tuberculosis (TB), HIV, SARS-CoV-2, respiratory epidemiology, sepsis, and global health including ethical issues in global health research. Current research content areas include drug-resistant tuberculosis, emerging respiratory viral infections including Covid-19, global sepsis epidemiology, and global health education. Areas of methodologic expertise include clinical and molecular epidemiology, clinical trials, basic/translational research, and implementation science. Geographic areas where we work include South Africa, Uganda, Rwanda, Ethiopia, Brazil and New York City. Collaborators include the Center for Infection and Immunity, ICAP, the Centre for AIDS Programme of Research in South Africa (CAPRISA), Uganda Virus Research Institute (UVRI), University of Rwanda, East Africa Training Initiative (EATI), Instituto Nacional de Infectologia Evandro Chagas-Fiocruz, and the Larsen lab at Albert Einstein College of Medicine, among others.
Drug-resistant tuberculosis is an important global public health concern because of increasing incidence, low cure rates, and high reported mortality. Nowhere has this increased incidence generated more concern than in South Africa where interactions between TB and generalized HIV/AIDS epidemics are causing explosive increases in TB incidence and TB case-fatality rates. The most drug-resistant form of tuberculosis, extensively drug resistant tuberculosis (XDR-TB), is increasingly prevalent in South Africa.
Acute respiratory infections continue to be responsible for approximately 3.9 million deaths worldwide (apart from the COVID-19 epidemic), predominantly in children, without a substantial decrease in estimated mortality over the past two decades. In addition, outbreaks of emergent viral respiratory infections with pandemic potential and periodic outbreaks of severe acute respiratory infection caused by vaccine-preventable pathogens continue to threaten global health security.
Active Projects
Epidemiology
Our team has published describing widespread transmission of MDR-TB and XDR-TB among South African health care workers. Using spatiotemporal analytics, we have shown that influenza outbreaks in Uganda are associated with periurban slums and distinct meteorological conditions. During COVID-19 we have provided detailed longitudinal description of COVID-19 ARDS epidemiology in New York City and Uganda, including identifying latent classes with heterogenous response to therapeutics.
Clinical
Our team has described clinical treatment outcomes for patients with XDR-TB and HIV co-infection. Ongoing work includes a cohort study of later generation fluoroquinolones, and clofazamine, a leprosy drug, for XDR-TB treatment. We are prospectively studying adherence to bedaquiline and ART in drug-resistant TB/HIV treatment using a next generation cellular enabled electronic pillbox. During Covid-19 our group has led site specific clinical trials of antiviral therapeutics, anti-Covid-19 immunoglobulin, and provided overall leadership for a randomized controlled trial of convalescent plasma. Ongoing projects include prospective sepsis and COVID-19 cohorts in Uganda, continued COVID-19 serologic work in Brazil, and clinical trials of adherence support for MDR-TB and XDR-TB in South Africa.
Translational
Working with the Larsen lab, we are involved in designing clinical studies on biomarkers to quantify response to TB treatment, predict early treatment outcome, and detect worsening of drug-resistance in real-time among XDR-TB patients on treatment. We are comparing deep sequencing approaches to identify limits of detection for emergent drug-resistance in clinical isolates among patients on treatment for TB. Working with the Lipkin lab we have executed studies using oligonucleotide probe libraries to identify emerging and vaccine preventable pathogens in patients with unexplained severe respiratory infections in Uganda. Ongoing projects include novel methods to detect TB bacteremia, COVID-19 ARDS metabolomics, and novel methods for TB drug susceptibility testing.
Lab Members
Matt Cummings, MD
- Assistant Professor of Medicine at CUMC
Currently Matt is collaborating with researchers at UVRI, the Lipkin lab and the Jeff Shaman research group (both at the Mailman School of Public Health) to characterize influenza epidemiology and isolate and sequence viral genomes from clinical samples of Ugandan patients with severe acute respiratory infection of unknown etiology.
Allison Wolf, MPH, MS
Allison has current projects in the molecular epidemiology of tuberculosis transmission. She also has an active role in the PRAXIS study characterizing and designing interventions to improve adherence for drug-resistant TB and HIV working with collaborators at CAPRISA and the Department of Epidemiology.
Select Publications
MR O'Donnell, B Grinsztejn, MJ Cummings, JE Justman, MR Lamb, ...et al. A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19. J Clin Invest. 2021;131(13):e150646.
Matthew J Cummings, Barnabas Bakamutumaho, Nicholas Owor, John Kayiwa, Joyce Namulondo, Timothy Byaruhanga, Moses Muwanga, Christopher Nsereko, Matthew R Baldwin, Julius J Lutwama, Max R O'Donnell Stratifying Sepsis in Uganda Using Rapid Pathogen Diagnostics and Clinical Data: A Prospective Cohort Study. Amer J Trop Med Hygiene. 2021. Jun. DOI: 10.4269/ajtmh.21-0138. PMID: 34125696
Amrita Daftary, Shinjini Mondal, Jennifer Zelnick, Gerald Friedland, Boitumelo Seepamore, Resha Boodhram, K Rivet Amico, Nesri Padayatchi, Max R O'Donnell. Dynamic needs and challenges of people with drug-resistant tuberculosis and HIV in South Africa: a qualitative study. Lancet Global Health, Volume 9, Issue 4, 2021, Pages e479-e488
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. Int J Tuberc Lung Dis. 2016 Apr;20(4):430-4. PMID: 26970149 PMCID: PMC4863995
Desjardins CA, Cohen KA, Abeel T, Manson McGuire A, Munsamy V, Shea TP, Walker BJ, Bantubani N, Almeida DV, Alvarado L, Chapman SB, Mvelase NR, Duffy EY, Fitzgerald MG, Govender P, Gujja S, Hamilton S, Howarth C, Larimer JD, Maharaj K, Pearson MD, Priest ME, Zeng Q, Padayatchi N, Grosset J, Young SK, Wortman J, Mlisana KP, O'Donnell MR, Birren BW, Bishai WR, Earl AM, Pym AS. Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance. Nature Genetics. 2016. PMID: 27064254 [PubMed - in process] PMCID: PMC4848111 [Available on 2016-11-01]
Cohen KA, Abeel T, Manson McGuire A, Desjardins CA, Munsamy V, Shea TP, Walker BJ, Bantubani N, Almeida DV, Alvarado L, Chapman SB, Mvelase NR, Duffy EY, Fitzgerald MG, Govender P, Gujja S, Hamilton S, Howarth C, Larimer JD, Maharaj K, Pearson MD, Priest ME, Zeng Q, Padayatchi N, Grosset J, Young SK, Wortman J, Mlisana KP, O'Donnell MR, Birren BW, Bishai WR, Pym AS, Earl AM. Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from KwaZulu-Natal. PLoS Med. 2015 12(9):e1001880. PMID: 26418737 PMCID: PMC4587932
O'Donnell MR, Pillay M, Pillay M, Werner L, Master I, Wolf A, et al. Primary Capreomycin Resistance Is Common and Associated With Early Mortality in Patients With Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa. Journal of acquired immune deficiency syndromes. 2015;69(5):536-43. PMID: 25886924 PMCID: PMC4501864
O'Donnell MR, Pym A, Jain P, Munsamy V, Wolf A, Karim F, et al. A Novel Reporter Phage To Detect Tuberculosis and Rifampin Resistance in a High-HIV-Burden Population. Journal of clinical microbiology. 2015;53(7):2188-94. PMID: 25926493 PMCID: PMC4473227.
Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, Aaron JG, Claassen J, Rabbani LE, Hastie J, Hochman BR, Salazar-Schicchi J, Yip NH, Brodie D, O'Donnell MR. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395:1763-1770.
Cummings MJ, Tokarz R, Bakamutumaho B, Kayiwa J, Byaruhanga T, Owor N, Namagambo B, Wolf A, Mathema B, Lutwama JJ, Schluger NW, Lipkin WI, O'Donnell MR. Precision surveillance for viral respiratory pathogens: virome capture sequencing for the detection and genomic characterization of severe acute respiratory infection in Uganda. Clin Infect Dis. 2019; 68:1118-1125.