Tuberculosis Research Institute at MUHAS (TRIM-TB)

Tuberculosis is the leading cause of death among persons with HIV infection in Tanzania. Clinical and operational research to improve prevention and treatment of both adult and pediatric HIV-TB is a defined national priority but there is no specifically designated and staffed institute to plan, coordinate and conduct such research. The objective of TRIM-TB is to provide the training to develop a premier HIV-TB clinical and operational research institute at Muhimibili University of Health and Allied Sciences (MUHAS). MUHAS leadership, the Tanzanian National Tuberculosis and Leprosy Program (NTLP) and former Fogarty trainees have all contributed to planning the new institute.

The program will consolidate the expertise of past Fogarty trainees with a new focused plan to train the requisite professionals to fully staff TRIM-TB. The institute will be based a new office complex at MUHAS with additional staffing located at the NTLP. An initial faculty core at MUHAS (Director, Associate Director) will be augmented by the addition of trainees who will complete the following degrees determined to be necessary for providing the necessary research expertise for the institute: 3 MPH degrees at Dartmouth, 3 MPH degrees at MUHAS, 1 master’s degree at BU (pharmacology) and 2 doctoral degrees at BU (epidemiology, public health).

Additional short and medium term training in ethics, good clinical practice and HIV-TB research methods will be provided for investigators. Advanced TB microbiology and TB immunology training will be provided for research microbiologists who will staff the TRIM-TB core laboratory. Pilot grant funding will be available for HIV-TB research projects and investigators will coordinate efforts thru monthly research seminars at MUHAS linked by teleconference to Dartmouth and BU. Defined performance measures focused on development of independent HIV-TB research capacity have been developed and will be monitored.

An extensive candidate pool will be recruited from health science students and at MUHAS, prior DBU AITRP trainees, Fogarty alumni, public presentations and focused advertising. Performance sites for research will include adult and pediatric DarDar Programs, NTLP clinical sites, and the Fogarty African Consortium on Tuberculosis (FACT, developed by the DBU AITRP). TRIM-TB faculty have extensive experience in HIV-TB research, actively funded research projects, and wide experience training and mentoring junior colleagues. An expert Training Advisory Committee will oversee the program. After 5 years TRIM-TB will have set HIV-TB research priorities for Tanzania and have secured independent funding for research on these priorities.

Dartmouth/Penn Research Ethics Training
and Program Development for Tanzania

The overall goal of the Dartmouth/Penn Research Ethics Training and Program Development for Tanzania (DPRET) is to establish new and strengthen existing expertise in research bioethics among research scientists, faculty, health care providers and other professionals at the Muhimbili University of Health and Allied Sciences (MUHAS) and throughout Tanzania. This goal will be achieved through graduate level degree training for Tanzanian scholars at the University of Pennsylvania (Penn), intensive practicum experiences at Dartmouth and MUHAS, and the establishment of a graduate training program in bioethics in Tanzania.

The specific aims are:

• to recruit 5 Tanzanian trainees for enrollment in Penn’s Master of Bioethics (MBE) degree program;
• to offer an intensive 3-week bioethics practicum at Dartmouth with an emphasis on institutional review board (IRB) management and human subjects protection training that will carry academic credit toward completion of the MBE degree, augmented by IRB experience at Penn during their year in residence;
• to revise and restructure the existing bioethics course at MUHAS to address the stated training needs in Tanzania and comply with graduate-level educational standards;
• to capitalize on AMANET’s on-line and other course curricula to build a foundation for a graduate-level Master of Science in Bioethics (MScB) degree program at MUHAS;
• to transfer 2 Penn and 2 Dartmouth courses to MUHAS as the genesis of the core research ethics curriculum of a new MScB degree that will be established and open for student enrollment beginning in the 3rd year of the grant;
• to establish a new Institute of Bioethics at MUHAS, whose mission will be to serve as a national resource and center of excellence for faculty, students, and visiting scholars, plus to provide ongoing leadership in the MUHAS graduate program in bioethics. The establishment of the Institute will be a major part of the DPRET sustainability plan for the future of bioethics training at MUHAS and throughout Tanzania. A Program Advisory Committee consisting of international leaders in the field of bioethics will assist in the recruitment and evaluation of trainees, monitoring of general program effectiveness, and regularly consult with the DPRET principal investigators and staff.

Developing the OSP at Muhimbili:
A North-South Training Collaborative (Fogarty OSP)

The overall goal of this collaborative training program is to strengthen and expand the capacity of Muhimbili University of Health and Allied Sciences (MUHAS) to better manage their portfolio of existing and future research grants. Dartmouth College (DC) and the University of California San Francisco (UCSF) will assist MUHAS in this goal by providing training and mentorship to its new Office of Sponsored Programs (OSP) through intensive residency internships at DC and USCF, in-country short-term training programs and distance learning.

The specific aims are:

• to provide a comprehensive, robust and innovative training platform that will complement on-going activities amongst these universities to establish MUHAS as a regional leader in managing HIV and other grant activities. The training will focus on the research support needs identified at MUHAS via the MUHAS-UCSF Academic Learning Program (ALP), including grant application preparation and submission, pre- and post-award management, financial management, handling conflicts of interest in research, and issues related to the responsible conduct of research. A variety of methodologies will be employed including (a) short residency training at DC for MUHAS staff in the new OSP, (b) short-term “continuing education” programs in Dar for these individuals (and others) after they return to Tanzania, (c) local training for administrators of smaller projects, and (d) long-term mentorship via distance learning and other methods lead by DC and UCSF faculty and staff teamed with appropriate MUHAS collaborators;
• (2) to assist with the development of standard operating procedures (SOP) that will guide all activities in the OSP;
• (3) to develop a long-term program sustainability plan that will direct and support the OSP activities following the three-year term of this project; and (4)
• to develop a monitoring and evaluation (M&E) plan using a logic model listing short and long-term goals as the basis for this activity.

Fogarty Africa Consortium on Tuberculosis (FACT)

Fogarty Africa Consortium on Tuberculosis (FACT) was created in 2010 as a collaboration between the Dartmouth-BU AITRP (Tanzania) and the Georgia-Case Western Reserve AITRP (Uganda). The goal of FACT is to connect current and former Fogarty trainees from East Africa in a south-south research network and to develop priorities for clinical, epidemiologic and programmatic tuberculosis research in the region.

The first annual one day research meeting was held in Dar es Salaam in 2010 and the second annual meeting in 2011 in Kampala. The program includes research lectures, study design discussions and a poster session. Annual meetings alternate between Dar and Kampala, and since 2012 has expanded to include other East African Fogarty trainees.

Dartmouth/MUHAS IRB Training Collaboration

The overall goal of our project is to establish new and strengthen existing expertise in IRB management and training among research scientists, faculty, health care providers and other professionals at MUHAS and throughout Tanzania. Dartmouth has a long-standing collaboration with the MUHAS Research Ethics Committee (REC) and this grant will allow us to assist the REC to the next step in development. Further, Dartmouth has established research and training collaborations in Tanzania on which to build innovative IRB support programs.

The specific aims are to:

• Establish a new electronic IRB management, tracking and monitoring database system at MUHAS. This will be a user-friendly yet powerful system that can handle the necessary documentation required for an efficient IRB. Initial training will be provided by Dartmouth and long-term training and support will be built into the sustainability plan.
• Develop a series of joint videoconference review sessions and training workshops for the Dartmouth IRB and the MUHAS REC. These sessions will improve the competencies of both committees in order to more effectively process research protocols that are being undertaken by both universities.
• Organize a short-term training program at Dartmouth for the MUHAS REC administrator on use of the new electronic IRB database. This program will be held the week before the 2010 PRIM&R conference that she will also attend as part of the training exchange. The learning experiences provided by the program and conference will also support the development of a new comprehensive IRB management program to be used in Tanzania for the benefit of faculty, staff, and researchers.
• Create a novel rapid-review sub-committee for collaborative review and monitoring of new and significant modifications of research protocols being conducted at Dartmouth and MUHAS.
• Leverage opportunities to sustain the new innovative systems put into place at the MUHAS REC.
• Cultivate and grow the on-going partnership between the Dartmouth IRB and MUHAS REC through sustainable and interactive program development.

AIDS International Training and Research Program (AITRP)

The Dartmouth-Boston University Fogarty AIDS International Training and Research Program (AITRP) was established in 2003 to provide HIV and tuberculosis research training to physicians, scientists and other health care professionals from Tanzania.

The principal collaborating partner in Tanzania has been the Muhmibili University of Health and Allied Sciences (MUHAS), and additional collaborations have been established with the National Institute for Medical Research and the Ministry of Health. Geisel School of Medicine at Dartmouth, The Dartmouth Institute, and the Boston University School of Public Health offer masters and doctoral level degree training in basic science research, epidemiology, health sciences research, and pharmacology.

In Tanzania the Dartmouth-BU Fogarty program sponsors selected degree programs at MUHAS and offers 1-3 day conferences and workshops on issues on HIV and tuberculosis. Short term training in a variety of HIV- and TB-related topics is also offered. A south-south research collaboration known as the Fogarty Africa Consortium on Tuberculosis (FACT) was established in 2010 in collaboration with the Georgia-Case Western Reserve AITRP in Uganda.

Fellows & Publications

Geisel School of Medicine at Dartmouth

Masters Degrees

• Johnson Lyimo, MD (MPH, June 2005)
• Patricia Munseri, MD (MPH, June 2006)
  • Munseri, P.J., Talbot, E.A., Mtei, L., Fordham von Reyn, C. Completion of isoniazid preventive therapy among HIV- infected patients in Tanzania. The International Journal of Tuberculosis and Lung Disease, 2008, 12(9): 1037-1041.
  • Munseri P.J, Talbot E.A, Bakari M, Matee M, Teixeira JP, von Reyn C.F. The bacteremia of disseminated tuberculosis among HIV-infected patients with prolonged fever in Tanzania. Journal: Scand J Infect Dis. 2011 May 12
  • Munseri P, Talbot E, Tvaroha S, Kimambo S, Bakari M, Pallangyo K, von Reyn CF. "Acceptance of Isoniazid Preventive Therapy by Persons living with HIV in Tanzania 2001-2005. XVI International AIDS Conference, Toronto, Canada. 13-18 August 2006. (Poster MOPEO 173).
• Sajida Kimambo, MD (MPH, June 2007)
  • Sajida J Kimambo, Lillian Mtei, Johnson Lyimo, Mecky Matee, C Fordham von Reyn. Deaths from unrecognized disseminated tuberculosis (dTB) in HIV infection. (Cape town SA 2007 )
• Helga Naburi, MD (MPH, June 2009)
  • Helga Naburi, Lisa Adams, Paul Palumbo Increasing Pediatric Diagnosis and Treatment: Implications of the 2008 WHO Pediatric HIV Treatment Recommendations UCSF Center for HIV Information. August 2009.
  • Helga Naburi, MD,J Maseghe, F Cyprian,S Kaplan, N Todd-Zebell, Lisa V. Adams, MD, and Paul Palumbo, MD; Challenges to Initiating Treatment for HIV Infection in Children; August 2008, Mexico city (Poster presentation)
• Isaac Maro, MD (MPH June 2009)
  • Patient education on type 2 Diabetes mellitus in Tanzania Clinics at the 2nd International Conference on Advanced Technologies and Treatments for Diabetes. Athens, Greece, February 25-28, 2009.
• Andreas Nshala, MD (MPH, June 2010)
  • Drug Abuse among Secondary School Students in Dar es Salaam (with Anna Mukandagara). Dar es Salaam Medical Students Journal DMSJ, Vol. 13 No.1.2005
  • Paediatric AIDS: A Changing Case Presentation Pattern? DMSJ, Vol.12 No.1, April 2004
  • Internet Use for Learning in Medical School. DMSJ, Vol.12 No.1, April 2004
• Peter Pallangyo, MD (MPH, June 2011)
• Peter Maro, MD (MPH, June 2011)

Doctoral Degrees

• Teddy Mselle, MD (PhD, Molecular and Cellular Biology, September 2009)
  • Mikael Eriksson, Sarah K. Meadows, Satarupa Basu, Teddy F. Mselle, Charles R. Wira, Charles L. Sentman. TLRs Mediate IFN-? Production by Human Uterine NK Cells in Endometrium. The Journal of Immunology, 2006, 176: 6219-6224
  • Teddy F. Mselle, Sarah K. Meadows, Mikael Eriksson, Jennifer M. Smith, Lilian Shen, Charles R. Wira, Charles L. Sentman, Unique characteristics of NK cells throughout the human female reproductive tract. Clinical Immunology (2007) 124, 69-76
  • Charles L. Sentman, Teddy F. Mselle, Satarupa Basu. Human mucosal NK cells. in "Everything You Always Wanted to Know About NK Cells But were Afraid to Ask". Laurent Brossay (Ed). 2007 ISBN81-7895-251-3
  • Basu S, Eriksson M, Pioli PA, Conejo-Garcia J, Mselle TF, Yamamoto S, Wira CR, Sentman CL. Human uterine NK cells interact with uterine macrophages via NKG2D upon stimulation with PAMPs. Am J Reprod Immunol 2009; 61: 52­61
  • Kalkunte SS, Mselle TF, Norris WE, Wira CR, Sentman CL, Sharma S. Vascular endothelial growth factor C facilitates immune tolerance and endovascular activity of human uterine NK cells at the maternal-fetal interface.J Immunol. 2009 Apr 1;182(7):4085-92
  • Teddy F. Mselle, Alexandra L. Howell, Mimi Ghosh, Charles R. Wira, and Charles L. Sentman. Human Uterine Natural Killer Cells but not blood NK cells Inhibit HIV-1 Infection by Secretion of CXCL12. J. Virology. 2009 Nov;83(21):11188-95.
  • Kopcow HD, Eriksson M, Mselle TF, Damrauer SM, Wira CR, Sentman CL, Strominger JL. Human decidual NK cells from gravid uteri and NK cells from cycling endometrium are distinct NK cell subsets Placenta. 2010 Apr;31(4):334-8. 2010 Feb 20
  Teddy F. Mselle, Sarah K. Meadows, Mikael Eriksson, Jennifer M. Smith, Lilian Shen, Charles R. Wira, Charles L. Sentman. Unique characteristics of NK cells throughout the human female reproductive tract. New England Immunology Conference, 2006. Woods Hole, MA, US
  • Teddy F. Mselle, Alexandra L. Howell, Mimi Ghosh, Charles R. Wira, Charles L. Sentman. Soluble Factors Secreted by Human Uterine NK Cells Can Inhibit HIV-1 Infection. Presented at the Keystone Symposia on HIV Pathogenesis. March 26-April 1, 2008 Banff Springs, Alberta, Canada.
• Magdalena Lyimo, MD (PhD, Molecular, Cellular & Systems Physiology, June 2010)
  • Gisela Soboll, Mardi A.Crane-Godreau, Magdalena A.Lyimo and Charles R. Wira. Effect of oestradiol on PAMP-mediated CCL20/MIP-3? production by mouse uterine epithelial cells in culture. Immunology (2006), 118, 185 194
  • Human Breast Milk Inhibits Cell-free but not Cell-associated HIV-1 Infection of CD4+ Cells. Presented at 16th Conference on Retroviruses and Opportunistic Infections (CROI). Feb 8-11, 2009 Montreal, Canada
• Emmanuel Balandya, MD (PhD, Experimental & Molecular Medicine, 2008 -)
  • E. Balandya, W. Wieland-Alter, T. Lahey. Seminal plasma inhibits HIV-1 infection of target cells. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19-22, 2009, Capetown, South Africa.