Postal address: Centrum för Infektionsmedicin (CIM), Karolinska Institutet, Karolinska Universitetssjukhuset Huddinge, SE-141 86 Stockholm, Sweden
Visiting address: Entrance F 59, Hälsovägen, Flemingsberg
Web page CIM: http://ki.se/ki/jsp/polopoly.jsp?d=13664&l=en
Contact person: Professor Anna Norrby-Teglund, CIM Deputy Director, phoe: +46 (0)8 585 832 97
The research at the Center for Infectious Medicine, CIM, is focused around studies of the human immune system and infection-immunity in humans. The Center operates within the Department of Medicine, Karolinska Institutet at the Karolinska University Hospital in Huddinge. CIM has since its inauguration in 2002 rapidly grown and gained national and international recognition. The vision is to become one of the leading translational research centers within immunity and infectious diseases in Europe.
Since many years, the Division of Infectious Diseases – connected to CIM – has been responsible for courses in Tropical Medicine, Vaccinology, etc. It has also been involved in collaboration on Shigella projects at ICDDR,B in Dhaka.
Research connected to South Asia
New methods of treatment of tuberculosis and HIV infection
Professor Jan Andersson, professor in Infectious Diseases at the Department of Medicine, Huddinge, has led a CIM research group focusing on ”Pathogenesis and development of new methods of treatment of tuberculosis and HIV infection”.
The research has involved collaboration with several International institutes, among them the International Centre for Diarrheal Diseases Research, Bangladesh (ICDDR,B) in Dhaka.
The research group is now led by Susanna Brighenti, Associate Professor of Immunology (photo). On 4 November 2014, Susanna Brighenti’s research group is one of the few in the whole of Sweden that work with clinical immunology with tuberculosis (TB) infection. Around 600 people are infected with TB in Sweden each year. Today, it is an infectious disease that is increasing in the country, but which is not easily diagnosed. It often requires a set of different methods, both clinical and laboratory diagnosis to detect the bacteria. As a result, Susanna Brighenti’s research group has been working together with a team in Bangladesh to develop immune diagnostics for TB. Studies are now underway at Karolinska Huddinge to see if the method will have the same positive effect on TB patients recruited in Sweden. Read more.
Susanna Brighenti and her research group was granted a development research grant from the Swedish Research Council (total amount SEK 4.4 m in four years, 2015-18) for a project entitled ”The role of diabetes-associated pathology in the development of clinical tuberculosis: a collaborative project between Sweden and Bangladesh”. The project will be carried out in collaboration with researchers and clinics in Bangladesh.
Project abstract: Tuberkulos (TB) hör tillsammans med HIV och malaria till världens största infektionssjukdomar som dödar många miljoner människor varje år, fram för allt i utvecklingsländer i Afrika och Asien. På sistone har också andra sjukdomar som främst betraktas som välfärdssjuksomar ökat markant i många av dessa utvecklingsländer. Dit hör diabetes som är en metabolisk sjukdom som resulterar i en minskad insulinkänslighet. Diabetes är en viktig riskfaktor för att drabbas av lungtuberkulos och diabetes patienter har en tre gånger så hög risk att utveckla aktiv TB jämfört med friska individer. Det är troligt att diabetes leder till ett försvagat immunsvar, men få studier görs för att bringa klarhet i de patogena mekanismerna som leder till denna ökning. För att kunna förbättra diagnos och behandling av TB också hos patienter med diabetes, måste vi först lära oss om mekanismerna kring uppkomst och utveckling av infektion och sjukdom för att försöka hjälpa patienterna till ett bättre liv. Vårt projekt syftar till studera immunsvaret vid TB/diabetes infektion samt att utveckla ny diagnostik och behandling av TB/diabetes patienter. Vår forskargrupp har etablerat ett starkt forskningsnätverk kring TB genom att vi samarbetar med forskare och kliniker i Bangladesh, där förekomsten av både TB och diabetes är mycket vanlig.
More information about Swedish Research Council grants to South Asia related projects 2014.
The research group includes Dr. P. Venkata Ramana Rao, with a PhD in Biochemistry and Immunology from the Tuberculosis Research Center in India in 2010; and a former PhD candidate from Bangladesh, Sayma Rahman. Dr. Rao is also connected to Medical Microbiology & Molecular Medicine at Linköping University. Sayma Rahman defended her doctoral dissertation in April 2013, with a thesis entitled ”Local immune responses in tuberculosis: Cytolytic effector functions at the site of Mycobacterium tuberculosis infection”.
Dr. Rubhana Raqib is a Scientist at the Immunology Unit within the Laboratory Sciences Division (LSD), ICDDR,B. She completed her PhD degree in October 1995 in a sandwich program between ICDDR,B and Karolinska Institutet, with SAREC/Sida funds and under PhD supervision from Professor Jan Andersson. She joined ICDDR,B immediately thereafter.
Dr. Raqib has been actively collaborating with Prof. Andersson in a number of Sida/SAREC funded studies. She has also become involved in new collaborations with other Swedish scientists in diverse fields, especially with Prof. Lars-Åke Persson, International Maternal and Child Health (IMCH), Department of Women’s and Children’s Health, Uppsala University. Her current research interests involve (i) alternative therapeutic strategies in combating infectious diseases, (ii) rapid diagnostic methods of tuberculosis, (iii) effects of maternal nutritional interventions on the immune function outcome of infants and children, (iv) effect of maternal exposure to toxic elements on the immune functions of infants. The research in tuberculosis diagnostics has resulted in a Patent for an immunodiagnostic method of pulmonary tuberculosis. She is involved in two ongoing research projects run by CIM:
• Studies of novel immunodiagnosis in human tuberculosis (TB), a project focusing on M. tuberculosis-specific antibody producing cells, that will only be present in peripheral blood from patients with ongoing active disease as compared to latent TB, old TB infection or uninfected individuals. It is funded by Swedish Research Council (VR), Swedish International Development Cooperation Agency (SIDA), Sida/Swedish Civil Contingencies Agency (Sida/MSB).
• Studies of novel immunotherapy in human tuberculosis (TB), a project focusing on Enhanced expression of antimicrobial peptides in immune cells and epithelial cells, that may be used as an alternative strategy to strengthen innate mucosal immunity and prevent microbial replication at the site of infection. In a placebo controlled clinical trial, we aim to test if novel inducers of antimicrobial peptides will enhance clearance of TB infection and improve clinical outcome in patients with active pulmonary TB. In addition, we will investigate if these novel inducers can reduce microbial translocation and chronic inflammation in the gut of TB/HIV co-infected patients, which may strengthen the intestinal epithelium and reduce HIV viral replication. This trial is performed at the Black Lion University Hospital in Ethiopia and also involves a network of collaborators in Ethiopia, Sweden and Bangladesh. Funding by Swedish Research Council (VR), Swedish International Development Cooperation Agency (SIDA), Sida/Swedish Civil Contingencies Agency (Sida/MSB).
Rubhana Raqib was invited as a key-note speaker in the SASNET workshop on ”The role of South Asia in the internationalisation of higher education in Sweden” held at Nobel Forum, Karolinska Institutet, Solna, 28-29 November 2006. Read Dr. Raqib’s presentation at the workshop (as a pdf-file)
PhD candidate Jagadees Rao Muvva is also part of the research group. Hailing from Guntur in South India, and with an experience of being a Resident Physician in Emergency & General practice in both India and Botswana 2010, he received an MSc in Biomedicine from Örebro University in 2013.
Disease mechanisms in severe acute bacterial infections
Professor Anna Norrby-Teglund leads a research group at CIM working on Disease mechanisms in severe acute bacterial infections. Streptococcus pyogenes is an important cause of severe invasive infections, such as toxic shock syndrome and necrotizing fasciitis, which are associated with high mortality rates despite adequate antimicrobial therapy. The research group includes one PhD candidate from India, Srikanth Mairpady Shambat, MSc in biomedical Genetics at Vellore Institute of Technology University.
In November 2008 Anna Norrby-Teglund received a Swedish Research Links (Asian–Swedish research partnership programme) one-year planning grant on 75 000 SEK for a new collaboration project with Indian colleagues, and in December 2009 she was awarded SEK 750 000 as a three-years grant. See the full list of South Asia related projects given Swedish Research Links gants 2009.
The project was titled ”Pathogenic mechanisms of meticillin-resistant Staphylococcus aureus”, and was carried out in collaboration with Dr. Mattias Svensson, also at CIM, and Dr. Gayathri Arakere, Sir Dorabji Tata Centre for Research in Tropical Diseases, Bangalore, India.
Abstract: The project aims to define the pathogenic mechanisms of meticillin-resistant Staphylococcus aureus (MRSA) with focus on the action of specific toxins, such as Panton Valentine leucocidin, superantigens and hemolysins. MRSA represent a significant health threat in both developing and developed countries. The incidences of these infections are rising, and unusually severe pathological signs have been associated with certain MRSA types, including necrotizing fasciitis and necrotizing pneumonia. There is a controversy within the field as to which toxins are the major players in the pathogenesis of these severe infections. Previous studies have used various murine infection models to compare virulence properties of isogenic toxin-deficient strains. Here the researcchers propose to use clinical isolates with the same genetic background, but with varying toxin profiles, in clinically relevant human cell and tissue model systems. The proposal is based on collaboration between India and Sweden. A large cohort of MRSA isolates collected in India will be used for studies of MRSA induced cell damage and inflammatory responses in in vitro human cell and tissue models. The project is likely to advance our understanding of the defined role of specific toxins in the destructive infections associated with MRSA. Such insight should promote identification of potential targets for intervention and thus promote development of novel therapeutic or prophylactic strategies.
The research collaboration has continued. Professor Anna Norrby-Teglund her colleagues in India have arrived at some interesting results by studying Staphylococcus aureus that, in the worst of cases, can cause aggressive, often fatal tissue death in the lungs and other organs. Using a large collection of bacterial strains from infected Indian patients, the researchers have managed to identify two staphylococcal toxins that kill the cells in the lung. “This we’ve achieved by building an artificial model of a lung in a laboratory environment for studying the infections,” says Anna Norrby-Teglund. “We’re now testing different treatments for the toxins and hope to find a suitable medicine.” (News from KI seminar 28 May 2013, more info.)
Pathogenesis of Toxoplasma gondii infections (e.g. malaria)
Dr. Antonio Barragan (photo to the left) leads a group focusing on Pathogenesis of Toxoplasma gondii infections, integrating immunology with molecular parasitology to understand how obligate intracellular parasites evade and direct host immune systems to their own advantage. Their research aims to define the pathogenic mechanisms utilized by the opportunistic human pathogen Toxoplasma gondii and related apicomplexan parasites (malaria, cryptosporidium) to promote colonization and transmission of infection.
In November 2012 Dr. Antonio Barragan together with collaboration partner Md. Shahiduzzaman, Bangladesh Agricultural University, received a Swedish Research Links (Asian–Swedish research partnership programme) grant on SEK 600 000 for their project “Detection and characterization of the waterborne parasite Cryptosporidium in Bangladesh and Sweden”. See the full list of South Asia related projects given Swedish Research Links gants 2012.
Project abstract: Cryptosporidium is a zoonotic pathogen posing a significant public health threat globally. It is an important cause of water and sanitation-related diarrheal disease worldwide. Despite major knowledge gaps in this area, the prevalence of cryptosporidiosis is generally considered higher in developing countries than in developed countries. Previous studies indicate that cryptosporidiosis may be a significant cause of diarrheal illness in Bangladesh, especially in young children. Outbreaks may also occur in developed countries, exemplified by two major outbreaks in Sweden in 2010-11. There is an overall need for improved epidemiological and diagnostic tools employed for the environmental/water survey and laboratory diagnosis of this parasitic disease. The proposed study will contribute to the elucidation of the prevalence of Cryptosporidium in water in Bangladesh. Molecular differentiation of Cryptosporidium species commonly found in animal faces or human feces will provide important epidemiological data and improved sensitivity and accuracy for human diagnostics. The execution of the project builds on reciprocal exchange at the methodological and educational levels. The results will provide important information to Health Authorities of both countries in respect of prevalence and spreading potential of this parasite. Furthermore, the establishment of methodologies for diagnostics and genetic characterizations of the parasite will aid in actions to be taken in outbreak situations.