TB and Diabetes Intersection of Two Diseases E. Jane Carter, M.D. Associate Professor of Medicine Alpert School of Medicine at Brown University Providence, Rhode Island
Disclosures No financial disclosures Board Involvement World Lung Foundation International Union Against TB and Lung Disease Committee Involvement Advisory Committee for the Elimination of TB-CDC International Health Committee ATS Expert Committee - TB Active Case Finding -WHO
Questions to examine today: Does Diabetes contribute to the global burden of Tuberculosis? Does coexistence of TB and Diabetes in the same patient affect the course of the other clinical condition? Does treatment of TB in the Diabetic Patient differ than other TB? Do opportunities in synergy exist for health care systems not for the diseases?
Does Diabetes contribute to the global burden of Tuberculosis?
Burden of TB 9.4 million new cases of TB disease per year 2 million deaths 1 infection per second Leading cause of death in PLWHA Leading cause of death in women of child bearing years globally
Target testing for TB We screen populations At risk for exposure and resultant infection At risk for development of disease if infected HIV infection 100 fold Use of biologic agents 70 fold Medical conditions that influence ability to contain infection Diabetes 3 fold
Diabetes as a contributor to the global Top 10 in TB India China Indonesia Nigeria Bangladesh Pakistan Ethiopia Philippines South Africa DRC burden of TB Top 10 in Diabetes India China USA Indonesia Japan Pakistan Russia Brazil Italy Bangladesh
The preference is that the 2 populations are mutually exclusive Diabetes 250 million 6m new annually Tuberculosis 14 million 9.4m new annually
Situation in a low TB incidence country Diabetes Tuberculosis Population where Diabetes now acts as a multipler
Situation in a High TB incidence Country Diabetes TB Population where Diabetes now acts as a
Global Distribution of DM and TB Diabetes 2008 South East Asia 20% Western Pacific 23% Africa 5% Tuberculosis 2009 South East Asia 35% Western Pacific 20% Africa 30% 70% in LIC and MIC 95% in LIC and MIC By sheer numbers, Diabetes CoMorbidity may contribute As much or more to TB Incidence burden than HIV despite being a weaker inducer
Does coexistence of TB and Diabetes in the same patient affect the course of the other clinical condition?
Presentation of Disease Some studies have demonstrated more common atypical presentations Turkey Saudi Arabia Pakistan Taiwan Some studies have suggested more cavitation
Outcome of Disease Possible delay in Sputum Culture conversion 8 studies comparing DM and Non DM RR 0.8-3.2 but 5/8 had RR >2 Possible Increase Death 23 studies comparing risk of death Pooled RR =1.85 ( 95% confidence interval;1.5-2.3) Possible Risk of Recurrent Disease 4 studies Pooled RR=3.98 ( 95% CI, 2.1-7.5)
Why might Diabetics do Worse? Drug Drug interactions Rifampin reduces levels of oral hypoglycemic Diabetes is a risk factor for hepatotoxicity from TB drugs
Why might Diabetics do Worse? TB risk seems to correlate with duration and severity of diabetes More post primary TB Higher bacterial burden Worse Immunopathology High Cytokine levels Slow response to treatment Synergy with other Co-morbidities
Does treatment of TB in the Diabetic Patient differ than other TB?
Treatment Considerations Peripheral neuropathy DM versus TB meds Diabetics should always be given B6 for prevention Drug Interactions Rifampin Oral Hypoglycemics Malabsorption Diabetics have been shown ot be at risk for malabsorption of medications Length of Therapy
Risk of Relapse (Study22) Continuation phase, Control, (I/R 2x/wk) Cavity Culture positive at 2 months Yes 21.8% 6.2% Culture negative at 2 months No 5.0% 2.1%
Treatment Implications Diabetics have prolonged culture positivity Extend by 3 months Diabetics may have more cavitary disease Extend by 3 months Whether Diabetes itself should predict longer therapy is unclear??? If neither of the above risk factors are present
Do opportunities in synergy exist for health care systems not for the diseases?
Saipan Experience Diabetes recorded in the TB clinic data base Most common co-morbidity 30% of all cases Over 70% of Pacific Island Cases Development of Diabetes Protocols for the TB Clinic
DM Guidelines Every person with TB over age 18 should be screened for Diabetes All Pacific Islanders with DM who are at risk for TB should be screened for LTBI and active TB Diabetics with LTBI should be encouraged to take INH for 9 months Ensure that TB treatment is appropriately adjusted for Diabetes B6 supplementation; Kidney function assessment ( Cr)
Ensure that TB treatment is appropriately adjusted for Diabetes B6 supplementation Kidney function assessment ( Cr) Be aware of drug interactions Be aware of poor absorption of some TB medications Be aware of the possibility of relapse in treatment not extended Repeat glucose monitoring during the course of treatment Appointments and DOT visits can be used as DM Teachable Moments
Universal TB Screening of all Diabetics? Remember- you do have to have TB infection for Diabetes to increase the risk of disease Targeted Testing In Diabetic Services who deliver care to TB risk populations All (TB) Epi is Local. Certainly represents an Opportunity for Synergy
The preference is that the 2 populations are mutually exclusive Diabetes 250 million 6m new annually Tuberculosis 14 million 9.4m new annually
Situation in a low TB incidence area Diabetes Tuberculosis Population where Diabetes now acts as a multipler
Situation in a High TB incidence Area Diabetes TB Population where Diabetes now acts as a
Summary Diabetes has been an ignored contributor to the overall TB global burden. With increasing incidence of diabetes in areas of high incidence TB, this will be a growing problem. There is no evidence to date that diabetics are at increased risk of infection if exposed. Diabetes increases the risk of progression to disease by at least 3 fold.
Summary Diabetes may influence Co-morbidities and their influence on TB may offer opportunities for synergistic care programs
Stop TB. Thank you for your attention. Questions?