Resistance and Susceptibility to Infections Group (RSIG) activities –Kenya
The RSIG of the University of Manitoba is a very active group with a significant amount of work
being conducted in Nairobi, Kenya. Studies in Kenya have been ongoing for more than 25 years
in close collaboration with colleagues at the University of Nairobi. The projects worked on
cover a range of infectious diseases but the primary focus has been on HIV/AIDS and over the
years a significant amount of information and data from these studies has contributed to the
global understanding of the virus and the virus/host interaction. A basic science research team
consisting of Drs Ball, Fowke, Kimani, Luo and others under the leadership of Dr Frank Plummer
directs a significant level of work that is focused on understanding "natural" correlates of
protection against HIV infection. These factors have been identified in women from the well
characterized highly HIV exposed commercial sex worker cohort in Pumwani. These women are
known to HIV exposed but remain seronegative (HESN) and can be considered "resistant" to
HIV. Since this phenomenon of protection was first identified, a significant number of the RSIG
studies have looked at identifying, validating and characterizing the factors that play a role in
resistance, thus bringing in facets related to virology, immunology, genetics and utilizing cutting
edge technologies such as proteomics platforms to generate the data. The RSIG and its work
has been supported by a variety of grants including the CIHR, NIH and Bill and Melinda Gates
Foundation.
Based on many results generated in this cohort in Nairobi, there was an International
Symposium on Natural Immunity to HIV (ISNIH) hosted in Winnipeg in the fall of 2009, bringing
together investigators from around the globe who worked on the topic of resistance to HIV
infection. The enthusiasm generated from this first gathering was great and it was soon
followed by a workshop at the NIH with Drs Ball and Plummer as part of the leadership in the
summer of 2010 to continue the momentum and move forward. Planning for a second ISNIH
meeting in ongoing right now in conjunction with international colleagues. One of the key
outcomes of these first meetings was the identification of the need for the formation of an
international consortium - the International Natural Immunity to HIV Consortium (INIC) in order
to better coordinate results, tools and findings as a global scientific community. The University
of Manitoba group (Winnipeg/Nairobi) is heading a grant proposal with 4 different partners in
Canada, the United States and Europe for submission in early 2012 to move forward with this
exciting initiative.
In addition to the INIC proposal, there continues to be exciting and important data generated
on a variety of subjects related to resistance and susceptibility to HIV by the RSIG. Research
projects that continue to produce interesting data related to the studies on HIV resistance
include the CIHR-funded studies led by Dr Fowke on Immune Quiescence. This body of work
has yielded important results to further our understanding on protection from HIV. Dr Ball's
program has two CIHR grants focused on the role(s) of IRF-1 and serpins in HIV resistance. The
IRF-1 studies have been moving at a significant pace with exciting data on the epigenetic
regulation of IRF-1 gene expression and differences in resistance and susceptibility to HIV
infection. In addition, these studies have garnered outside interest and collaborations to
investigate these factors at a mucosal level have led to further funding from the NIH.
The collaborative projects between Dr Plummer and Dr Ofer Mandelboim of the Hebrew
University have been extremely productive and successful to date with plans to expand the
studies further. Results are being generated looking at the role of Natural Killer (NK) cells in
protection against HIV. The first paper from this collaboration was just accepted for
publication, describing altered interaction between dendritic cells and NK cells in the context of
resistance to HIV. NK cells in HIV resistance an exciting, unexplored area and the support from
the Manitoba Government and the Canadian Friends of the Hebrew University has allowed the
project to continue.
Work by the RSIG continues to explore and understand factors involved in the progression to
AIDS. The CIHR grant led by Drs Plummer and Ball is focused on characterizing immune
responses (specifically CD8 T cell responses) and how they protect against progression to AIDS.
Current studies are looking at the functional capacities of epitope-specific CD8 T cell
populations and their variant populations in HIV positive individuals by multiple approaches.
We have previously identified that T cells specific for variants of a particular CD8 T cell epitopes
in HIV envelope perform different functions, that is, CD8 T cell functional capacity is specific to
the level of T cell epitope variants. Additional studies include further analysis on other
immunodominant HIV p24 epitopes and their variants using tetramers, the key reagent to
these studies. Drs Plummer and Luo have generated exciting results on the CIHR funded project
looking at specific immune responses to HIV and how these specific results play a role in
protection and/or disease progression. Building on this information, Dr Luo's CIHR grant
funding a study in non human primates as a vaccine trial is generating extremely exciting
results. This work is ongoing and first stages of analysis are currently underway.
The collaborative project in Kenya looking at the immunobiology of tuberculosis and HIV coinfection is underway. Together with partners at the University of Nairobi, we are working on
a pilot project to introduce and evaluate the Quantiferon test for TB into a small outpatient
health clinic at Mbugathi Provincial Hospital in Nairobi, Kenya. This clinic sees over 40 patients a
day, with an estimated 50-60% being HIV positive. There is still a great need to examine the
utility of these new TB diagnostic assays in high TB/HIV burden settings such as this. Currently
we have tested about 200 patients and their household contacts with the quantiferon test.
Currently, there are 2 masters students at the University of Nairobi working on these projects.
Additionally, we are currently seeking funding to expand on this cohort and follow HIV patients
with both active and latent TB infection longitudinally. As HIV is a strong predictor of
developing active TB disease, understanding immune responses to TB in these individuals and
potentially ones associated with TB reactivation may allow for the development of new and
more sensitive diagnostics for this patient population. This will help to inform policy/program
direction for targeting TB therapy among those at highest risk of developing active TB, curbing
TB spread.
Zoonotic viral infections and emerging pathogens are also areas of ongoing discussion and
investigation together with scientists at the National Microbiology Laboratory and the
Department of Medical Microbiology at the University of Manitoba.
In addition to the multidisciplinary studies described above that the RSIG is investigating on the
topic of resistance and susceptibility to HIV infection and HIV pathogenesis, we have ongoing
work that has been extremely critical with clinical benefit to Kenyans living with HIV. This is
work led by Dr Kimani and Drs Gelmon, Avery and others together with the University of
Manitoba continue their work in providing HIV care, treatment and prevention services to
Kenyans in Nairobi. This work is supported by CDC-PEPFAR and has been going on since 2005.
This work began in the Majengo and Pumwani clinics in Nairobi but has expanded and is now
providing services to most at risk populations (MARPS) through outreach activities at 8 clinics.
Efforts to mobilize and enumerate commercial sex workers in Nairobi with the aim to better
predict needs for care and treatment have resulted in approximately 37,000 individuals being
mobilized, and over 16,000 people being enrolled at the clinics. Of these, approximately 11,000
have been tested and as of August 2011, more than 9,000 people have been on palliative care
since the program's inception and over 4,000 receiving anti-retroviral therapy (ART).
An enumeration of sex workers was carried out in Nairobi’s Central Business using traditional
mapping techniques and GPS technology in 2010. Over 122 “hotspots” were identified and
almost 7,000 sex workers were contacted. The methodology was found to be successful, and
could be replicated in other neighborhoods in Nairobi. Based on this success a countrywide
enumeration of MARPS is set for the first quarter of 2012.
Through PEPFAR funding, a randomized controlled trial has been conducted, investigating the
use of mobile phone SMS messages to increase adherence to ART. The final results have not
yet been analyzed, but indications are that the use of mobile phone messages increased
adherence, improved the communication between clients and clinics, and reduced the number
of untreated side effects. This has lead to funding by the IDRC of Canada to Drs Avery and
Kimani to assess the effects of SMS on prevention of mother- to-child-transmission of HIV.
Our activities are having an impact on Kenya’s national HIV policy framework. Kenya lacks a
national strategy on HIV prevention targeting sex workers and during the past year, the
University of Manitoba team facilitated the development of national guidelines on HIV
prevention involving sex workers, with the support and cooperation of the National AIDS and
STDs Control Programme (NASCOP), Ministry of Health (MOH) and technical assistance from
Global AIDS Program, CDC, and Atlanta.
Following these successes, the University of Manitoba and University of Nairobi collaboration
was recently awarded several grants to provide prevention services to in Kenya. The team, led
by Drs Gelmon and Kimani were successful in securing 3 out of 5 MARPS proposals totaling 23
million dollars Canadian for Kenya over the next five years. These are primarily prevention
programs that will provide service to at risk populations throughout the majority of Kenya,
although it is hoped that supplementary funding will also be awarded to continue the
treatment and care activities as well.
This represents a brief summary of ongoing RSIG activities in Kenya.
On behalf of the RSIG, Adrienne Meyers