MUHAS Infectious Disease Initiative (MIDI)

Tuberculosis remains a leading cause of death among persons living with HIV (PLWH) in Tanzania. In 2019, of the 27,000 adult and child deaths among PLWH in Tanzania, an estimated 12,000, or 44%, were TB-related. Epidemiologic and operational research to improve prevention and treatment of both adult and pediatric HIV-TB is a defined national priority, and was confirmed as the largest training gap in our pre-proposal needs assessment, but there is no specifically designated and staffed institute to plan, coordinate and conduct such research. The objective of MIDI is to provide the training to develop a premier clinical and operational research infectious disease institute at Muhimibili University of Health and Allied Sciences (MUHAS), with a first focus on advancing research in HIV-TB. MUHAS leadership, the Tanzanian National Tuberculosis and Leprosy Programme (NTLP), National HIV/AIDS Control Programme (NACP) 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 MUHAS faculty to affiliate with MIDI. The institute is based in a newly renovated office space in the Centre for Health Professions Education (CHPE) building on the MUHAS campus. The 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 PhD candidates in biostatistics and/or epidemiology, 1 in biomedical data sciences, and 2 junior faculty with focused grant-writing training.

Additional short and medium term training in HIV-TB updates, HIV-TB monitoring and evaluation, and data analysis using R programming for infectious disease research, and HIV-TB research methods will be provided for investigators. Pilot grant funding will be available for HIV-TB research projects and investigators will coordinate efforts through regular research seminars at MUHAS linked by teleconference to Dartmouth and BU. Short-term training will also be offered to NTLP and NACP leaderhip and researchers to link MIDI and Minstry of Health research efforts and skills. Defined performance measures focused on development of independent HIV-TB research capacity have been developed and will be monitored.

A targeted candidate pool will be recruited from junior faculty and trainees at MUHAS, prior Dartmouth-BU-MUHAS/Fogarty alumni, and public presentations and focused advertising. Performance sites for research will include adult and pediatric DarDar Programs, NTLP clinical sites, and active MUHAS clinical research sites. MIDI faculty have extensive experience in HIV-TB research, actively funded research projects, and wide experience training and mentoring junior colleagues. A senior Training Advisory Committee provides expert consultation to the program. After 5 years, MIDI 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/MUHAS Research Ethics Training and Program Development for Tanzania (DMRET) is to expand existing expertise in research bioethics among all individuals engaged in the research enterprise at Muhimbili University of Health and Allied Sciences (MUHAS) and throughout Tanzania and the entire east sub-Saharan Africa region. The program has progressed from an absence of any program or individuals trained in Research Bioethics to an increasingly robust entity that includes a successful training program with several cohorts of Master in Bioethics (MBE) graduates and a vital Department of Bioethics and Professionalism at MUHAS. Program graduates have now entered the workforce and created a large community of ethics professionals at institutions across the country, who contribute to an expanding research enterprise. The program faculty now provide teaching across the institution, serving as the main source of bioethics training for all MUHAS students, and they are expanding their expertise through their own PhD education and a number of active collaborations with other programs. These developments are both an impetus for, and in many respects a result of, a strong region-specific program in Research Bioethics. Over the next five years we will expand and strengthen ethics scholarship at MUHAS, and across Tanzania and the region.

The specific aims are to:

• continue the to solidify and expand the Tanzanian training infrastructure for the Master of Bioethics (MBE) degree program at MUHAS including regional candidates and to transition primary leadership for the program;
• to transition to a regional program through collaboration with specific institutions in Tanzania and to promote and intensify the focus on building regional bioethics capacity;
• to continue to support and develop the Bioethics Society of Tanzania as a MUHAS -led Center of Excellence in Bioethics, serving as a national and regional resource and a focal point for academic excellence across the region and to support a Visiting Scholars program.

Developing the OSP at Muhimbili: A North-South Training Collaborative
(Fogarty OSP 08/01/2013-01/31/2018)

The overall goal of this collaborative training program was 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 and the University of California San Francisco (UCSF) assisted MUHAS by providing training and mentorship to its new Office of Sponsored Programs (OSP) through intensive residency internships at Dartmouth and USCF, in-country short-term training programs and distance learning.

The specific aims were to:

• to provide a comprehensive, robust and innovative training platform that complemented on-going activities amongst these universities and established MUHAS as a regional leader in managing HIV and other grant activities. The training focused 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 were employed including (a) short residency training at Dartmouth for MUHAS staff in the new OSP, (b) short-term “continuing education” programs in Dar for these individuals (and others) after they returned to Tanzania, (c) local training for administrators of smaller projects, and (d) long-term mentorship via distance learning and other methods that were led by Dartmouth and UCSF faculty and staff teamed with appropriate MUHAS collaborators;
• assist with the development of standard operating procedures (SOP) that guided all activities in the OSP;
• develop a long-term program sustainability plan to direct and support the OSP activities following the three-year term of this project; and
• 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 included 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
(09/01/2010-03/14/2012)

The overall goal of our project was 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. Building on Dartmouth’s long-standing collaboration with the MUHAS Research Ethics Committee (REC), this grant allowed 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 were to:

• Establish a new electronic IRB management, tracking and monitoring database system at MUHAS. This included a user-friendly yet powerful system to handle the necessary documentation required for an efficient IRB. Initial training was provided by Dartmouth and long-term training and support was 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 improved the competencies of both committees in order to more effectively process research protocols that were 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. The learning experiences provided by the program also supported the development of a new comprehensive IRB management program 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.

Although the grant has concluded, Dartmouth continues to support the trainings of MUHAS REC and MUHAS faculty regarding bioethics issues through two annual, onsite training programs that are supported by the DMRET grant.

HIV Research Training Program (formerly the AIDS International Training and Research Program, AITRP)

The Dartmouth-Boston University HIV training research collaboration was established in 2003 with support through HIV training grants from the Fogarty International Center at the National Institutes for Health to provide advanced 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 advanced 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

Master's 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)
• Maryam Amour (MPH, June 2015)
  • Munseri P, Said J, Amour M, Magohe A, Matee M, Rees CA, Mackenzie T, Tvaroha S, Bailey-Kellogg C, Maro I, Wieland-Alter W, Adams LV, Horsburgh CR, Nakamura K, Arbeit RD, Pallangyo K, von Reyn CF. DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled, double-blind phase 2b trial. Vaccine. 2020 Oct 27;38(46):7239-7245. doi: 10.1016/j.vaccine.2020.09.055. Epub 2020 Sep 29. PMID: 33004239.
  • G Pancras, M Amour, T Mwakyandile, B Morris, BF Sunguya, B Mmbaga. How do community advisory boards fulfil their ethical role in HIV clinical trials? A protocol for a systematic review of qualitative evidence. BMJ open 10 (4), e035368.
• Cecilia Makafu, MD (MPH, June 2015)
• Kyare Ndesi (MPH, June 2016)
• Furaha Kyesi, MD (MPH, June 2017)
  • Adams, L. V., O. Hunter, F. Kyesi, A. Ahluwalia, Z. N. Daffé, P. Munseri, and Reyn CFv. "Successful Implementation of Isoniazid Preventive Therapy at a Pediatric HIV Clinic in Tanzania." (2019)
• Kim Mwamelo (MPH, June 2017)
• Jacqueline Klhwele (MPH, June 2018)

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.

Boston University School of Public Health

• Conrad Kabali, MS (MPH, PhD, May 2010)
  • Kabali C, von Reyn CF, Brooks DR, Waddell R, Mtei L, Bakari M, Matee M, Pallangyo K, Arbeit RD, Horsburgh CR. Completion of isoniazid preventive therapy and survival in HIV-infected, TST positive adults in Tanzania. Accepted in Int J Tuber Lung Dis.
  • Kabali C, Cheng DM, Brooks DR, Bridden C, Horsburgh CR, Samet JH. Recent cigarette smoking and HIV disease progression: No evidence of an association. AIDS Care. 2011;1-10.
  • Kabali C, Werler MM. Pre-pregnant body mass index, weight gain and the risk of delivering large babies among non-diabetic mothers. Int J Gynaecol Obstet 2007;97:100-4.
  • Submitted an abstract titled 'Effect of Isoniazid Preventive Therapy on mortality among HIV infected subjects in Tanzania' to the forthcoming CROI meeting
  • Kabali C, Mtei L, von Reyn F, Pallangyo K, Waddell R, Horsburgh R. Decreased Mortality Associated with Latent Tuberculosis Treatment among HIV Infected Persons in Tanzania. Presented in the CROI 15th Conference, February 3-February 6, 2008, Hynes Convention Center, Boston, MA, USA.
• Mucho Mizunduko (MPH, June 2013)
• Albert Magohe, MD (MSc Epi, January 2017)

Muhimbili University of Health & Allied Sciences

• Elimina Swai, RN (MPH, 2012)
• Rose Olotu, MD (MPH, 2013)
• Amelda Urasa, RN (MPH, 2013)
• Festo Komba (MPH, 2017)
• Samuel Likindikoki, MD, MMed (PhD, 2020)
• D, Kerrigan, TS, Karver, C. Barrington, Y Donastorg, M Perez, H Gomez, J, Mbwambo, S, Likindikoki, W, Davis, S, Wilson Beckham, A, Mantsios, N, Galai, E, Sibinga Mindfulness, Mental Health and HIV Outcomes Among Female Sex Workers in the Dominican Republic and Tanzania AIDS and Behavior, 1-10.
• Haneefa T Saleem, Samuel Likindikoki, Claire Silberg, Jessie Mbwambo, Carl Latkin Time-space constraints to HIV treatment engagement among women who use heroin in Dar es Salaam, Tanzania: A time geography perspective. Social Science & Medicine 268, 11337.
• SL Likindikoki, EJ Mmbaga, GH Leyna, K Moen, N Makyao, M Mizinduko, ... Prevalence and risk factors associated with HIV-1 infection among people who inject drugs in Dar es Salaam, Tanzania: a sign of successful intervention? Harm reduction journal 17, 1-10.