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Diabetes Mellitus and Tuberculosis: current status and implications for tuberculosis control __________________________

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Title: Dual Burden of Diabetes Mellitus and Tuberculosis: is there a need for an integrated policy for screening and care? Author: A. D. Harries – PowerPoint PPT presentation

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Title: Diabetes Mellitus and Tuberculosis: current status and implications for tuberculosis control __________________________


1
Diabetes Mellitus and Tuberculosiscurrent
status and implications for tuberculosis
control__________________________
  • Anthony D Harries
  • The Union
  • Paris, France

2
Global Burden of DM and TB
  • Diabetes Mellitus 2008
  • 250 million people living with DM
  • 6 million new cases each year
  • 3.5 million people died of DM during the year
  • World Diabetes Foundation 2009
  • Tuberculosis 2009
  • 14.0 million people living with TB
  • 9.4 million new cases each year
  • 1.7 million people died of TB during the year
  • WHO- Global TB Control 2010

3
Global Distribution of DM and TB
  • Diabetes Mellitus 2008
  • South East Asia 20
  • Western Pacific 23
  • Africa 5
  • 70 in LIC and MIC
  • World Diabetes Foundation 2009
  • Tuberculosis 2009
  • South East Asia 35
  • Western Pacific 20
  • Africa 30
  • 95 in LIC and MIC
  • WHO- Global TB Control 2010

4
The global increase in DM
  • 2010 285 million with DM
  • 2030 440 million with DM
  • Diabetes Atlas International
    Diabetes federation, 2009

5
THE TUBERCLE BACILLUS
TUBERCULOSIS
M.tuberculosis bacteria
2.0 billion people carry this bacteria in their
bodies
Life-time risk of active TB 5-15
6
Risk of active TB increased in
  • HIV/AIDS
  • Other causes of immune suppression (steroids)
  • Silicosis
  • Malnutrition
  • Smoke from domestic stoves and cigarettes
  • Diabetes mellitus

7
Recognised in Roman times that DM increases risk
of TB
8
Jeon CY, Murray MB. Diabetes Mellitus increases
the risk of active tuberculosis a systematic
review of 13 observational studies. PLoS
Medicine 2008 5 e152
Search of PubMed and EMBASE databases studies
reporting age-adjusted quantitative estimate of
association between DM and active TB
13 observational studies 3 cohort 8
case-control 2 other
9
RESULTS
1,786,212 participants with 17,698 TB cases
DM associated with increased risk of TB Cohort
studies RR 3.1, 95 CI 2.3 4.3 Case control
studies OR 1.2 7.8 Higher risks in young
people and communities with high background TB
incidence
10
Other global studies on DM increasing the risk of
TB
  • Stevenson et al (Chronic Illn, 2007)
  • Medline search for studies after 1995
  • Increased RR or OR of 1.5 7.8
  • Risk higher in younger people

11
India Stevenson et al BMC Public Health 2007
  • Epidemiological model constructed based on 21M
    adults with DM and 900,000 new TB cases in 2000
  • DM accounted for 15 PTB (7 - 23)
  • 20 smearve
    PTB (8 - 42)
  • Urban areas more affected than rural areas

Diabetes mellitus makes substantial contribution
to burden of new TB in India
12
Diabetes Mellitus increases the risk of TB by a
factor of 2 - 3
Dooley and Chaisson, Lancet Infectious Diseases,
2009
Ruslami et al, Tropical Medicine International
Health, 2010
Goldhaber-Fiebert et al, International Journal
Epidemiology 2011
13
Is this biologically plausible?
  • YES-
  • Animal models diabetic mice have impaired CMI
    and have higher M.TB loads than normal mice
  • Patients with DM have low levels of IFN-gamma,
    reduced white cell killing activity
  • DM impairs innate and immune responses to TB

14
ALSO-
  • Diabetes Mellitus associated with
  • Pulmonary microangiopathy
  • Renal failure
  • Micronutrient Deficiency

Increased risk of TB
15
Association between DM and TB
  • Not in doubt
  • Biologically plausible
  • BUT previous studies have limitations-
  • Most are from industrialised countries
  • Almost none from Africa
  • Many are health facility-based and are secondary
    analyses of routine data sources
  • Many critical unanswered questions

16
Expert Meeting convened in November 2009(WHO,
Union, WDF, IDF, Academia, Ministries of Health)
17
Objectives of Meeting
  1. Discuss an updated systematic review conducted by
    Harvard University between May Aug 2009, and
    identify knowledge gaps
  2. Develop a prioritised research agenda
  3. Decide on policy recommendations

18
1. Updated systematic review focus on issues
related to TB control
PUBMED, EMBASE, Bibliographies, Conference
proceedings from IUATLD in 2007 and 2008
19
1.Linkage between DM and TB
  • Strong evidence from 16 age-adjusted studies
    (summary OR 2.2)
  • Some evidence that poor DM control increases risk
    of TB (HbA1c gt7 RR 2.56)
  • USA,UK, Canada, Mexico, Russia, India,
    Taiwan, South Korea, Indonesia
  • Knowledge gaps
  • Little evidence from low-income countries,
    especially Africa
  • Need more data on the effect of DM control on
    risk of TB

20
2. Diagnosis of TB and DM
  • Two main problems-
  • In patients with TB, DM is not suspected or
    recognised
  • In patients with DM, TB may present differently
    and may not be diagnosed

21
(2.1.) Is DM under-diagnosed in TB patients?
  • Tanzania 506 consecutive PTB patients
  • 9 known to have DM
  • Other patients given a 75G OGTT 11 had
  • sustained high blood glucose levels DM
  • DM missed in over half the patients

Mugusi et al, Tubercle 1990
22
(2.2.) Does TB present differently in patients
with DM?
  • Most consistent difference is
  • infiltrates more common in lower lung fields
  • Turkey Bacakoglu et al, 2001
  • Saudi Arabia Shaikh et al, 2003
  • Pakistan Jabbar et al 2006
  • Taiwan Wang et al, 2008

23
TYPICAL CHEST X-RAY
ATYPICAL CHEST X-RAY
24
3. Effect of DM on treatment outcomes of TB
  • DM associated with-
  • possible delay in sputum culture conversion
  • increased risk of death
  • increased risk of recurrent TB
  • BUT many limitations to these studies

25
3.1. Delay in sputum culture conversion at 2-3
months
  • 8 studies comparing DM with non-DM
  • Relative risks from 0.8 3.2
  • Five of eight studies had RR gt 2

26
Risk of remaining sputum culture positive after
2-3 months of treatment for DM patients with TB
versus non-DM patients with TB
27
3.2. Increased risk of death
  • 23 studies comparing risk of death in DM and
    non-DM patients
  • Pooled RR 1.85 (95 CI, 1.5 2.3)
  • 4 studies adjusted for age /other confounders
    pooled OR 4.95 (95 CI, 2.7 9.1)

28
Risk of death for DM patients with TB compared to
non-DM patients with TB
29
Adjusted odds of death for diabetic patients with
TB compared to non-diabetic patients with
TB adjusted for age and other confounders
30
3.3. Increased risk of recurrent TB
  • 5 studies assessed risk of relapse or
    drug-resistant recurrent TB
  • For Relapse, pooled RR 3.89 (95
    CI, 2.1 7.5)
  • For drug-resistant recurrent disease, there was
    no evidence of any association (pooled OR
    1.24, 95 CI 0.7 2.2)

31
Risk of TB relapse for DM patients with TB
compared to non-DM patients with TB
Population with DM Relapse/
Total
Population without DM Relapse/ Total
32
Why an increased risk of adverse outcomes?
  • Drug-drug interactions between oral hypoglycaemic
    drugs and rifampicin (decreased RF
    concentrations and poor glycaemic control)
  • DM is a risk factor for hepatic toxicity with TB
    drugs
  • Immune-suppressive effects of DM

33
4. Preventing TB in DM
  • Two observational studies in 1958 and 1969
    showing that isoniazid prophylaxis in DM patients
    reduces risk of TB
  • Knowledge gaps
  • Very poorly conducted studies and therefore
    evidence base still weak

34
Summary DM-TB is similar to HIV-TB
  • HIV-TB
  • Increased TB cases
  • More difficult to diagnose TB cases
  • Increased death
  • Increased recurrent TB
  • DM-TB
  • Increased TB cases
  • More difficult to diagnose TB cases
  • Increased death
  • Increased recurrent TB

Int J Tuberc Lung Dis 2011 6 September epub
ahead of print
35
Proportion of TB burden attributable to some
major risk factors in high TB burden countries
Relative risk for active TB disease Weighted prevalence (adults 22 HBCs) Population Attributable Fraction (adults)
HIV infection 20.6/26.7 0.8 16
Malnutrition 3.2 16.7 27
Diabetes 3.1 5.4 10
Alcohol use (gt40g / d) 2.9 8.1 13
Active smoking 2.0 26 21
Indoor Air Pollution 1.4 71.2 22
Sources Lönnroth K, Castro K, Chakaya JM,
Chauhan LS, Floyd K, Glaziou P, Raviglione M.
Tuberculosis control 2010 2050 cure, care and
social change. Lancet 2010 DOI10.1016/s0140-6736(
10)60483-7.
36
2. Prioritised research agenda
Tropical Medicine International Health 2010
15 659-663
37
Highly prioritised Research
  • Bi-directional screening active TB in DM
    patients and DM in TB patients
  • Treatment outcomes in DM patients (focus on
    mortality and strategies to reduce mortality
  • Use of the DOTS model to manage DM
  • POC diagnostic and monitoring tests for DM
    (glycosylated haemoglobin HbA1c)

38
3. Policy Recommendations
39
Collaborative Framework for Care and Control of
TB and Diabetes
40
The recommendations
http//www.who.int/tb/publications/2011/en/index.h
tml
Document available at
41
SummaryDiabetes and Tuberculosis
  • Rapidly growing pandemic of diabetes
  • This could threaten tuberculosis control by-
    increasing the number of cases
  • increasing the case fatality
  • increasing the risk of relapse after
    treatment
  • We have a framework for action and now need to
    implement
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