Withdrawn Post Notification Lorne Infection and Immunity 2019

Differences in metabolic risk factors for tuberculosis in close contacts with diabetes from two ethnicities impacting M. tuberculosis growth in peripheral blood mononuclear cells (#173)

Katharina Ronacher 1 , Leanie Kleynhans 2 , Gerhard Walzl 2 , Larry S Schlesinger 3 , Blanca I Restrepo 4
  1. Mater Research Institute - The University of Queensland, Brisbane, QUEENSLAND, Australia
  2. Stellenbosch University, Cape Town, South Africa
  3. Texas Biomed, San Antonio, TX, USA
  4. University of Texas Health, Brownsville, TX, USA

Background:

Type 2 diabetes (T2D) is a highly prevalent risk factor for TB, but the effect size of this association varies across populations, which may be due to other metabolic and epidemiological factors besides hyperglycemia. The impact of these factors on containment of mycobacteria by immune cells is largely unexplored.

Methods:

We performed a prospective cross-sectional study in adult close contacts of newly diagnosed pulmonary TB patients in South Africa (n=247) and the Texas-Mexico border (n=106) and assessed metabolic and sociodemographic characteristics. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of contacts with T2D (n=36 in South Africa, n=32 in Texas-Mexico) and with normo- or intermediate glycaemia (n=52 in South Africa, n=68 in Texas-Mexico) and infected ex vivowith live M. tuberculosisH37Rvto determine mycobacterial growth.

Results:

The overall prevalence of T2D was 30.2% in Texas-Mexico and 17.4% in South Africa. Newly diagnosed T2D prevalence amongst TB contacts was high with 47% in South Africa and 34% in Texas-Mexico. Strikingly, the diabetic phenotype differed between Hispanics and South African Coloureds particularly in concentrations of triglycerides and cholesterols. In vitrogrowth of M. tuberculosiswas significantly higher in PBMCs from T2D patients compared to normo-glycemic participants across both ethnicities, but did not differ between T2D patients using metformin vs. other or no T2D drugs. Mycobacterial growth was lower in PBMCs from contacts with serum cholesterol >200mg/dL in South Africa, whereas mycobacterial growth was higher in PBMCs from smokers.

Conclusions:

Our findings suggest that expanding T2D screening from TB patients to their close contacts is effective to identify new T2D patients at risk for TB infection and disease. Our findings also demonstrate that contacts with T2D differ across ethnicities in characteristics that could further affect TB risk, including concentrations of serum lipids and smoking.