Project

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Co-occurence of tuberculosis and diabetes mellitus in Tanzania

Applicant Boillat Blanco Noémie
Number 145866
Funding scheme Fellowships for prospective researchers
Research institution Ifakara Health Research and Development Center
Institution of higher education Institution abroad - IACH
Main discipline Tropical Medicine
Start/End 01.02.2013 - 31.07.2013
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All Disciplines (2)

Discipline
Tropical Medicine
Immunology, Immunopathology

Keywords (5)

Diabetes mellitus; Tuberculosis; Sub-Saharan Africa; Immune response; Cytokines

Lay Summary (French)

Lead
La tuberculose (Tb) touche un tiers de la population mondiale. Le diabète mellitus (DM) est un facteur de risque pour la réactivation de la Tb ainsi que pour une mauvaise évolution de cette infection sous traitement. Les bases immunologiques de cette relation sont peu connues. L’association entre Tb et DM est peu étudiée en Afrique où l’incidence de la Tb est élevée et où une augmentation importante du DM est observée.
Lay summary

Objectifs et contenu du travail de recherche

Le DM induit une réactivation de la Tb ainsi qu'une mauvaise évolution de cette infection . Cette association est peu étudiée en Afrique sub-saharienne où l’épidémie de la Tb est principalement liée au virus d’immunodéficience humaine (VIH).

L’objectif de notre étude est d’analyser la relation entre la Tb, le DM et le VIH en Tanzanie. Il s’agit aussi d’étudier la réponse immunitaire fonctionnelle et phénotypique des cellules T CD4+ spécifiques pour la Tb chez les diabétiques.

Les patients avec Tb sont prospectivement inclus dans un hôpital de Dar es Salaam en Tanzanie, où Ils auront un dépistage du DM et du VIH. Pour chaque inclusion, un contrôle sain aura un dépistage du DM et du VIH. Pour la partie immunologique, 4 groupes de patients seront étudiés: patients avec Tb active avec et sans DM ainsi que patients avec Tb latente avec et sans DM. Le profil de cytokines ainsi qu'une collection de marqueurs de surface des cellules T seront analysés par cytométrie polychromatique de flux.

Contexte scientifique du projet de recherche

Cette étude améliore la compréhension de l’interaction entre 2 problèmes majeurs de santé publique. La caractérisation de l’épidémiologie et de l’immunologie de la Tb chez les diabétiques va permettre le développement de stratégies spécifiques pour améliorer la prise en charge de la Tb dans cette population.

Direct link to Lay Summary Last update: 08.01.2013

Responsible applicant and co-applicants

Publications

Publication
Transient hyperglycemia in patients with tuberculosis in Tanzania: Implications for diabetes screening algorithms
Boillat-Blanco Noémie (2016), Transient hyperglycemia in patients with tuberculosis in Tanzania: Implications for diabetes screening algorithms, in Journal of Infectious Diseases, 213(7), 1163-1172.
Association between Tuberculosis, Diabetes and 25 Hydroxyvitamin D in Tanzania: a longitudinal case control study
Boillat-Blanco Noémie, Association between Tuberculosis, Diabetes and 25 Hydroxyvitamin D in Tanzania: a longitudinal case control study, in BMC Infectious Diseases, 16(1), 626-634.

Collaboration

Group / person Country
Types of collaboration
Centre Hospitalier Vaudois Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Swiss Tropical and Public Health Institute Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
9th European Congress on Tropical Medicine and International Health (ECTMIH) Talk given at a conference Longitudinal evolution of diabetes during tuberculosis in Dar es Salaam, Tanzania 06.09.2015 Bâle, Switzerland Boillat Blanco Noémie;
45th Union World Conference on Lung Health Talk given at a conference Alcohol use is a strong independent risk factor for tuberculosis in urban Tanzania 28.10.2014 Barcelone, Spain Boillat Blanco Noémie;
44th Union World Conference on Lung Health Talk given at a conference Association of tuberculosis and diabetes mellitus in urban Tanzania 30.10.2013 Paris, France Boillat Blanco Noémie;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Dissemination meeting: association between tuberculosis and diabetes in urban Tanzania Talk 20.10.2014 Dar es Salaam, Tanzania Boillat Blanco Noémie;


Associated projects

Number Title Start Funding scheme
139981 Co-occurrence of tuberculosis and diabetes mellitus in Sub-Saharan Africa: epidemiological and immunological study 01.02.2012 Fellowships for prospective researchers

Abstract

BackgroundTuberculosis (TB) remains a major public health problem as it is estimated that this infection affects one-third of the world population. Several studies, mostly performed in high-income countries, suggest that diabetes mellitus (DM) is a risk factor for TB reactivation and relapse post-treatment. DM appears to increase susceptibility to TB infection through reduced innate and adaptive immune responses. Data from previous studies examining the immunological response to Mycobacterium tuberculosis (Mtb) between diabetic and non-diabetic patients showed conflicting results. Of note, no comprehensive studies on the relationship between TB and DM have been conducted in Sub-Saharan Africa, where the high incidence of TB is associated with HIV infection and where sharp rises in the incidence DM have been observed over the last decade. ObjectivesThe present proposal aims to analyze the relationship between TB, DM and HIV infection in Tanzania. It also aims to determine the optimal method and timing of DM screening in TB patients. The last aim would study the functional and phenotypic profile of Mtb-specific CD4+ T-cell responses in a subset of diabetic patients with either active or latent TB infection.HypothesisWe hypothesize that DM is overrepresented in patients with active TB compared to the general population without active TB and particularly in the HIV positive population. Inversely, we think that TB prevalence is higher in people with DM than in the general population without DM. We theorize that DM testing at the time of TB diagnosis could overestimate DM and that the glycated haemoglobin (HbA1c) test for DM screening may be more reliable in a period of acute illness. We also hypothesize that DM is associated with an altered cellular immune response to Mtb in active and latent TB cases that is manifested by a significant difference in the cytokine production (lower Th1:Th2 cytokine ratio, increase of IL-17a and MIP-1ß [CCL4]), and also by changes in the T cell subset distribution in the peripheral blood including regulatory T cells (Tregs).Study designThe study will be conducted in Dar es Salaam in Mwananyamala Hospital. All consecutive patients with TB diagnosed in Mwananyamala Hospital in Dar es Salaam will be prospectively included in the study. Patients will be screened for HIV infection using a rapid immuno-chromatographic test for the detection of antibodies specific to HIV-1 and HIV-2 and for DM using fasting plasma glucose, oral glucose tolerance test (OGTT) as well as glycated haemoglobin (HbA1c). Each patient with TB will be matched with a control individual without TB, who will also be screened for DM and HIV. It is expected to recruit 1000 patients with TB and 1000 controls without TB.In the same way, all consecutive DM patients with a medical follow-up at the clinic of the Tanzanian Diabetes Association (TDA) in Mwananyamala Hospital will be prospectively included in the study. Patients will have a clinical TB screening using a short questionnaire. Each patient with DM will be matched with a control individual without DM, who will also be clinically screened for TB. It is expected to recruit 2000 patients with DM and 1000 controls without DM.For the immunological part of the study, four groups of patients would be studied: patients with active TB with and without DM, and patients with latent TB with and without DM. Intracellular cytokine profile (interferon-? (IFN-?), interleukin-17a (IL-17a), IL-2, tumor necrosis factor-alpha (TNF-a), IL-4 and macrophage inflammatory protein (MIP-1beta/CCL4)) would be assessed by polychromatic flow cytometry after antigen stimulation using Mtb related antigens including ESAT-6, CFP10 and Rv3615c . A set of T cell surface markers and Tregs characterization would be performed by polychromatic flow cytometry using un-stimulated peripheral blood mononuclear cells (PBMCs).Expected outcomeThis study advances research in the understanding of the relationship between two of the most prevalent public health problems worldwide. The characterization of the epidemiology of TB in diabetic patients as well as the setting up of an optimal method and timing of DM screening in TB patients are of primary importance in order to develop specific strategies to improve the management of TB in this population. Furthermore the study of the immunology of TB in diabetic patients could lead to the discovery of novel disease biomarkers and potential therapeutic target.
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