David R. Boulware, M.D., MPH, CTropMed
Lois & Richard King Distinguished Associate Professor
Associate Director of Global Health Programs in Internal Medicine, Division of Infectious Diseases & International Medicine, Department of Medicine
Dr. Boulware serves as the Associate Director of Global Health Programs in Internal Medicine, and his research interest is in meningitis and complications of HIV/AIDS in resource-limited settings. In particular, cryptococcal meningitis has become the focus of his research. Cryptococcus, a fungus living in the environmental, can cause meningitis in persons with a weakened immune systems, such as those receiving immunosuppressant medications or living with HIV/AIDS, Although this is relatively uncommon in the United States, cryptococcal meningitis is the most common cause of meningitis in adults in sub-Saharan Africa, accounting for 20-25% of AIDS-related deaths in Africa. This neglected tropical disease became an interest for Dr. Boulware during his first trip to Uganda in 2005 when he saw the overwhelming burden of cryptococcosis. In Uganda, Cryptococcus neoformans causes 50-60% of the meningitis at referral hospitals.
Dr. Boulware has worked to understanding the pathogenesis of HIV immune reconstitution inflammatory syndrome (IRIS), an important complication of HIV therapy that has recently emerged with the roll out of antiretroviral therapy in Africa. He has worked to define what is IRIS, biomarkers for prediction, and most importantly – what clinically one can do to decrease the risk of IRIS. In collaboration with investigators at the Infectious Diseases Institute of Makerere University and Mbarara University of Science & Technology in Uganda, and investigators at the University of Cape Town, South Africa, Dr. Boulware and colleagues conducted the Cryptococcal Optimal ART Timing (COAT) Trial to determine when is the optimal time to start HIV therapy after cryptococcal meningitis (NCT01075152). In August 2013, a new randomized clinical trial began investigating potentially better treatments for this deadly disease (ASTRO-CM Trial: NCT01802385).
Dr. Boulware also works to translate research into practical interventions and policy to improve Global Health. He has conducted a number of cost-effectiveness analysis studies which have better informed national and international policies. Principle among these is that cryptococcal antigen screening among persons with AIDS entering HIV care is cost-savings to health systems and results in better survival. In collaboration with Dr. David Meya at the Infectious Diseases Institute and Centers for Disease Control and Prevention (CDC), the operational research in cryptococcal antigen screening (ORCAS, NCT01535469).
Dr. Boulware graduated from Indiana University and then completed an internal medicine-pediatrics residency and an infectious disease fellowship at the University of Minnesota. He joined the UMN faculty in 2007. He previously has served on the 2007 DHHS/IDSA HIV Opportunistic Infections Guidelines Panel, 2011 WHO Cryptococcal Guideline Review Panel, and serves on the ASTMH CTropMed® examination committee.
Current Publication List (PubMed)
- Boulware DR. Rolfes MA, Rajasingham R, von Hohenberg M, Qin Z, Taseera K, Schutz C, Kwizera R, Butler EK, Meintjes G, Muzoora C, Bischof JC, Meya DB. Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast. Emerg. Infect Dis. 2014; In Press dx.doi.org/10.3201/eid2001.130906
- * Durski KN, Kuntz KM, Yasukawa K, Virnig BA, Meya DB, Boulware DR. Cost-effective diagnostic checklists for meningitis in resource limited settings. JAIDS 2013; 63:e101-108 PMC3683123
- Diagnostic Algorithms for CNS infections for download as editable word documents
- **Rajasingham R, Rolfes MA, Birkenkamp K, Meya DB, Boulware DR. Cryptococcal meningitis treatment strategies in resource-limited settings: a cost-effectiveness analysis. PLoS Med. 2012; 9 (9): e1001316. PMC3463510
- Rajasingham R, Meya DB, Boulware DR. Integrating cryptococcal antigen screening and pre-emptive treatment into routine HIV care. J Acquir Immune Defic Syndr. 2012;59:e85-91. PMC3311156
- Rhein J, Boulware DR. The prognosis and management of cryptococcal meningitis in HIV infected patients. Neurobehavioral HIV Med 2012; 4: 45-61.
- ** Meya DB, Manabe YC, Castelnuovo C, Cook BA, Elbireer AM, Kambugu A, Kamya MR, Bohjanen PR, Boulware DR. Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ <100 cells/mL who start HIV therapy in resource-limited settings. Clin Infect Dis. 2010; 51:448-55. PMC2946373
- ** Boulware DR, Bonham SC, Meya DB, Wiesner DL, Park GS, Kambugu A, Janoff EN, Bohjanen PR. Paucity of initial cerebrospinal fluid inflammation in cryptococcal meningitis is associated with subsequent immune reconstitution inflammatory syndrome. J Infect Dis. 2010; 202: 962-970. PMC2924457
- Boulware DR, Meya DB, Bergemann TL, Williams D, Vlasova IA, Rhein J, Staddon J, Janoff EN, Kambugu A, Bohjanen PR. Antiretroviral therapy down-regulates innate antiviral response genes in AIDS patients in Sub-Saharan Africa. JAIDS 2010; 55:428-38. PMC3159954
- Haddow LJ, Colebunders R, Meintjes G, Lawn SD, Elliott JH, Manabe YC, Bohjanen PR, Sungkanuparph S, Easterbrook PJ, French MA, Boulware DR. Cryptococcal immune reconstitution inflammatory syndrome: literature review and proposed clinical case definitions. Lancet Infect Dis. 2010; 10: 791 – 802. PMC3026057
- ** Boulware DR, Meya DB, Bergemann TL, Wiesner DL, Rhein J, Musubire A, Lee S, Kambugu A, Janoff EN, Bohjanen PR. Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study. PLoS Med. 2010; 7: e1000384. doi:10.1371/journal.pmed.1000384
- Boulware DR, Hullsiek KH, Puronen CE, Rupert A, Baker JV, French MA, Bohjanen PR, Novak RM, Neaton JD, Sereti I, for the INSIGHT Study Group. Higher levels of CRP, d-dimer, IL-6 and hyaluronic acid before initiation of antiretroviral therapy (ART) are associated with increased risk of AIDS or death. J Infect Dis. 2011; 203:1637-46. PMID:21592994
- * Wiesner DL, Boulware DR. Cryptococcus-related immune reconstitution inflammatory syndrome: pathogenesis and its clinical implications. (PDF) Curr
Fungal Infect Rep. 2011; 5(4): In Press. NIHMSID:252-261. The final
publication is available at www.springerlink.com