Martineau AR, Nhamoyebonde S, Oni T, Rangaka MX, Marais S, Bangani N, Tsekela R, Bashe L, de Azevedo V, Caldwell J, Venton TR, Timms PM, Wilkinson KA, Wilkinson RJ.
Proc Natl Acad Sci U S A. 2011 Oct 24. PMID: 22025704
25 October 2011
UCT research shows strong connection between Vitamin D deficiency and TB
Researchers at the University of Cape Town and the National Institute for Medical Research (NIMR) in the UK have found that vitamin D deficiency is extremely common in black Africans living in Cape Town and is associated with susceptibility to tuberculosis (TB) infection. The research is published in Proceedings of the National Academy of Sciences in the USA.
South Africa has the third-highest incidence of TB in the world, with 490,000 cases estimated to have arisen in 2009. Active TB can arise as a consequence of reactivation of latent MTB infection following compromise of the antimycobacterial immune response. HIV infection is a major cause of such immunocompromise, and the high prevalence of HIV infection in South Africa drives its TB epidemic. But other factors may also contribute.
The prevalence of Vitamin D deficiency in patients with TB in subtropical Africa has not previously been reported, although vitamin D deficiency is associated with susceptibility to TB in HIV-uninfected people in Europe. There is particularly good reason to investigate this question in Cape Town, because TB incidence in this city is higher than elsewhere in South Africa, and the ability of sunlight to synthesize vitamin D is compromised during the winter in Cape Town.
Professor Robert Wilkinson is associated with both UCT and NIMR's Division of Mycobacterial Research. He worked with colleagues in Cape Town and London to conduct a cross-sectional study to determine whether vitamin D deficiency was associated with susceptibility to active TB in HIV-uninfected and HIV-infected black Africans in Cape Town. He also investigated whether there was evidence of seasonal variation in vitamin D status and TB notifications in this setting over an eight-year period. The team measured vitamin D levels in the serum of HIV-infected and uninfected patients with TB and appropriate control subjects who did not have TB.
They found that vitamin D deficiency is highly prevalent among black African adults living in Cape Town. The deficiency is associated with susceptibility to active TB in both HIV-uninfected and infected persons, but the association is stronger in HIV-infected people. A seasonal pattern of notifications of TB occurs in Cape Town, with the lowest rates in the second quarter of the year, coincident with peak vitamin D serum concentrations.
Professor Wilkinson said: "A growing body of evidence suggests that vitamin D deficiency may also impair the immune response to Mycobacterium tuberculosis (MTB). We have previously reported that vitamin D deficiency is associated with susceptibility to TB in London and that this association is modified by variants in the genes for the vitamin D receptor (which senses vitamin D) and vitamin D binding protein (which carries the vitamin around the body). Adrian Martineau has also shown that vitamin D supplementation enhances immunity to mycobacteria, both in healthy people and in a genetically defined subgroup of patients with active TB. Vitamin D supplementation might be a highly cost effective, safe and simple means to reduce tuberculosis incidence."
This research is also of relevance to the UK because TB is more common among immigrants from Africa, who are more likely to be HIV infected and vitamin D deficient.
Issued by: UCT Communication and Marketing Department
Report of Freezerworks™ training
Freezer Inventory and Sample Tracking Solutions
A successful 3-day training session was run 3rd to 5th October by two trainers from DataWorks™, Seattle, US; Andrew Michels and Nate Rheaume.
Trainees were from South African TB Vaccine Initiative (SATVI) Worcester and Cape Town labs, IDM Wilkinson group, Medical Microbiology, Institute of Child Health Laboratory Red Cross Children's Hospital, Desmond Tutu HIV Centre and Virology. All attendees had FreezerWorks, but different software versions and varying degrees of skills; SATVI staff who use FreezerWorks Unlimited, were the most experienced; other groups use FreezerWorks Basics.
On day one, 10 and 13 trainees attended the morning and afternoon sessions respectively, thereafter on day two, 9 trainees attended the administrators' session and on day three, 10 trainees attended all day. The administrators' session was open to all interested for information; this covered functions recommended for restricted access as changes could affect existing data stored.
The course covered all aspects of sample inventory management. The first session dealt with the basics and there was an open session for product information over lunch for those interested in purchasing the software. This software has provision for any type of storage but most commonly it is used for freezer and liquid nitrogen storage management. Samples may be allocated specific positions on collection according to study, sample type and any other information as required eg cell counts, phlebotomist, date and time of bleed and storage. This assists towards efficient sample management and ensures ease of traceability as required for performance monitoring in Clinical Trials. The trainers have been provided with the attendance records and certificates of participation in the course will be provided.
In summary this course provided vital information for staff who are learning how to use the software and an excellent update for more experienced users on how to get the most from this very useful lab tool. I thank CIDRI for the valuable financial contribution that made this course possible.
E Jane Hughes
SATVI Lab Project Manager
Prizes for Publications by Wilkinson Group staff
Associate Professor Graeme Meintjes was awarded the best publication prize for 2011 by the Department of Medicine at Groote Schuur Hospital and the University of Cape Town. The award was presented at the 38th Annual Department of Medicine Research Day held on 6th October 2011.
The award-winning article entitled "Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome" was published in AIDS 2010 Sep 24;24(15):2381-90
Mrs Rabecca Tadokera received a "Best Publication 2010" award in the discipline of Basic Laboratory Science from the Faculty of Health Sciences at the University of Cape Town. This award is given annually for the best publication by a young and promising researcher in the Faculty. Rabecca was also the recipient of a prestigious postgraduate scholarship from the Clinical Infectious Diseases Research Initiative based at UCT, providing support during the completion of her doctoral thesis, from 2009-2011.
The award-winning article entitled "Hypercytokinaemia accompanies HIV-tuberculosis immune reconstitution inflammatory syndrome" was published in the European Respiratory Journal 2011: Vol 37:1248-1259
NIH Director visits IDM in the Faculty of Health Sciences
It was a whirlwind visit for Dr Francis Collins, Director of the National Institutes of Health (NIH) and several of his colleagues as they embarked on a one-day fact-finding visit to the Faculty on Thursday, 3 March 2011.
The visit included a brief meeting with members of the Deanery, where there was intense discussion on Faculty structure, methodologies and funding. This was followed by a brief, but informative sojourn with members of the Institute of Infectious Disease and Molecular Medicine, where researchers took the opportunity to speak about their work, some of it funded by agencies of the NIH.
Deputy Dean: Research, Professor Gregory Hussey, then accompanied the group and Professor Robert J. Wilkinson to the Khayelitsha Site B Community Health Care Centre, which is also the site of several Clinical Infectious Diseases Research Initiative (CIDRI) research projects. The delegation paid a visit to the isoniazid Preventive plus antiretroviral therapy study, whereby patients who are on antiretroviral therapy, or are about to begin ARV treatment, join a randomized control study to test the effectiveness of isoniazid in preventing TB disease. The group met Dr Molebogeng Rangaka, a member of the Centre for Infectious Disease and Epidemiology Research (CIDER) in the School of Public Health, who is the lead investigator of this study. She explained the reasons for the study, the method, and the follow-up, which is still being carried out. “We are very excited about this study, which is probably the only one to have evaluated isoniazid in this fashion, and we are confident that it will influence public health policy in South Africa,” said Dr Rangaka.
From there, it was short walk to the new prefabricated building that will house the Phase IIb TB vaccine trial, which is due to begin later in 2011. Dr Hanif Esmail, a Wellcome Trust Fellow who is based at UCT, addressed the group, speaking of his PhD research project, entitled “How inactive is "inactive" tuberculosis? PET/CT benchmarking of latent tuberculosis infection”, which will be embedded in the TB vaccine trial. The building forms part of an existing refurbishment to the premises, funded by the European Developing Countries Training Programme (EDCTP).
At GF Jooste Hospital in Manenberg, Dr Collins and his team met with Dr Rosie Burton, who took the group through the infectious diseases ward and clinic. They also paid a visit to the casualty unit, which is currently being refurbished. Dr Charlotte Schutz spent a few minutes explaining the COAT study, which aims to decrease the mortality rate in cryptococcal meningitis in HIV-positive people. This is a recently initiated project, which is funded by NIH.
The Red Cross War Memorial Children’s Hospital was the second-last stop on their itinerary, and this included a walk-through of emergency admitting ward and the paediatric intensive care unit and then up to the Institute of Child Health, to meet with Heather Zar, the Head of the School of Child and Adolescent Health, Lelsey Henley, Colleen Adnams, Antony Figaji, Jo Wilmshurst, head of paediatric neurology, Ernesta Meintjies, where NIH-funded projects were discussed, among others. “I was really impressed by them, they were very insightful and asked pertinent questions of the researchers,” said Assoc Prof Wilmshurst.
The collaborative Centre of Excellence, Chronic Diseases Initiative in Africa includes the Universities of Cape Town, Stellenbosch and Western Cape, the SA Medical Research Council, the Western Cape provincial government and Shree Hindu Mandal Hospital and Ministry of Health and Social Welfare in Tanzania and Harvard University, USA. It was the final element of the NIH visit and it was clear that the visitors were impressed by the initiative and what it proposes to do.
Professor Dinky Levitt, Director of the Initiative, explained that it will serve as a regional hub for developing and evaluating models for chronic disease care and prevention of their risk factors.
“The Initiative aims to reduce the burden of chronic diseases in Africa – we realize this is very ambitious, but what are we without ambition?” she said.
Dr Collins went on to speak at the first Vice-Chancellor’s Lecture of 2011 later in the day, with Sir Mark Walport, Director of the Wellcome Trust.
Dr Francis Collins, Dr Molebogeng Rangaka
and Dr Rene Goliath (behind)
Professor Valerie Mizrahi now on CIDRI steering committee
|We are very pleased that Professor Valerie Mizrahi has agreed to serve on the Steering Committee of the Clinical Infectious Diseases Research Initiative.
Professor Mizrahi took over the directorship of the Institute of Infectious Disease and Molecular Medicine from Professor Gregory Hussey, on 1st January 2011.
After a PhD in Chemistry at UCT and a postdoctoral fellowship in the United States, she settled in South Africa and launched the Molecular Biology Unit at the South African Institute for Medical Research. Her recognition of TB as an important area of research led to the establishment of the Molecular Mycobacteriology Research Unit in 2000, jointly funded by the South African Medical Research Council, the National Health Laboratory Service and Wits. She also served as the co-director of the Centre of Excellence for the Biomedical TB Research, jointly funded by the Department of Science and Technology and National Research Foundation.
Now at UCT’s IDM, Professor Mizrahi not only takes on the role of institute director but is also the head of the UCT node of the partnership with Wits and Stellenbosch in the Centre of Excellence for Biomedical TB research and director of the Molecular Mycobacteriology Research Unit, now based at UCT.