TB and Diabetes
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![Page 1: TB and Diabetes](https://reader031.fdocuments.us/reader031/viewer/2022020211/577cc3a01a28aba711969f35/html5/thumbnails/1.jpg)
The double burden of diabetes mellitus and tuberculosis:
interactions and challenges for care__________________________
Anthony D Harries“The Union”, Paris, France
London School of Hygiene and Tropical Medicine
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Structure of the Presentation
• Background Epidemiology
• Collaborative Framework for Care
• Challenges for Care
• Conclusion
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Non-communicable and communicable disease
Diabetes Mellitus (DM)• Disease of antiquity• Three main types:-
– Type 1– Type 2– Gestational DM
• Diagnosis: Blood glucose
• Treatment: diet, drugs, insulin for life
Tuberculosis (TB)• Disease of antiquity• Three main types:-
– Site of disease– Bacterially confirmed – Drug sensitive / resistant
• Diagnosis: Smear for AFB
• Treatment: 6 months of drugs
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Global Burden of DM and TBDiabetes Mellitus: 2012
• 371 million people living with DM
• 10 million new cases per annum
• 4.8 million people died of DM during the year
[IDF Diabetes Atlas 2012]
Tuberculosis: 2012
• 12.0 million people living with TB
• 8.6 million new cases in the year
• 1.3 million people died of TB during the year
[WHO- Global TB Control 2013]
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Global Distribution of DM and TBDiabetes Mellitus: 2012
• South East Asia 19%
• Western Pacific 36%
• Africa 4%
80% in LIC and MIC
[IDF Diabetes Atlas 2012]
Tuberculosis: 2012
• South East Asia 40%
• Western Pacific 19%
• Africa 27%
95% in LIC and MIC
[WHO- Global TB Control 2013]
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India and China [2012]
India
• 63 million DM
• 2.2 million TB per annum
China
• 92 million DM
• 1.0 million TB per annum
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Not diagnosed or notifiedDiabetes Mellitus 2012
• 371 M with DM
• 187 M (50%) undiagnosed
IDF Diabetes Atlas 2012
Tuberculosis 2012
• 8.6 M with TB
• 3.0 M (35%) not notified to NTPs
WHO Global Report 2013
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The global increase in DM
• 2012 371 million with DM
• 2030 552 million with DM
[Diabetes Atlas: International Diabetes Federation, 2012]
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M.tuberculosis bacteria
~ 2.0 billion people carry this bacteria in their bodies
TUBERCULOSIS
Life-time risk of active TB = 5-15%
THE TUBERCLE BACILLUS
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Risk of active TB increased in…
• Extremes of age (infants and elderly)• HIV/AIDS• Other causes of immune suppression (steroids)• Silicosis• Malnutrition• Smoke from domestic stoves or cigarettes• Alcohol and substance abuse• Diabetes mellitus
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Recognised in Roman times that DM increases risk of TB
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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
Some evidence that poor DM control increases TB risk (HbA1c >7% = RR 2.56) [USA,UK, Canada, Mexico, Russia, India, Taiwan, South Korea, Indonesia]
Stevenson et al, Chronic Illness 2007 Jeon and Murray, PLoS Medicine 2008
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Is this biologically plausible?
YES:-
• Animal models – diabetic mice have impaired cell mediated immunity and have higher M.TB loads than normal mice
• Patients with DM have impaired immunity and poor lung defences against M.TB
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WHO estimates for 2012PAF of DM for adult TB No. adults with TB and DM
World 8.3% 1,042,000
South-East Asia 7.6% 423,000
Western Pacific 9.1% 238,000
Africa 5.0% 194,000
Europe 8.5% 94,000
Eastern Mediterranean 9.4% 51,000
The Americas 9.6% 41,000
PAF = population attributable fraction Lonnroth, Lancet Diabetes Endocrinol 2014
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WHO estimates for 2012PAF of DM for adult TB No. adults with TB and DM
India 8.6% 302,000
China 9.6% 156,000
South Africa 8.3% 70,000
Indonesia 5.6% 48,000
Pakistan 6.8% 43,000
Bangladesh 5.5% 36,000
Philippines 6.0% 29,000
PAF = population attributable fractionLonnroth, Lancet Diabetes Endocrinol 2014
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Expert Meeting convened in November 2009
(WHO, Union, WDF, IDF, Academia, Ministries of Health)
Collaborative Framework for Care
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Rationale for a Framework
• Evidence of interaction between DM and TB• Need for guidance on collaborative activities• Evidence weak to support specific guidance• Thus, Provisional Framework• Launched in 2011
• To be reviewed and revised by 2015
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Collaborative Framework for Care and Control of TB
and Diabetes
Launched in August 2011
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The recommendations
http://www.who.int/tb/publications/2011/en/index.html Document available at:
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Three challenges for care
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1. Bi-directional screening
• Screening TB patients for Diabetes (DM) [DM may not be recognised clinically]
• Screening DM patients for active TB [TB may present differently]
Jeon CY et al, TMIH 2010; 15: 1300-1314
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Bi-Directional Screening of TB and Diabetes
Mellitus
China and India
World Diabetes Foundation Support
• National Stakeholders Meeting
• Training for implementers
• Implementation of screening
• Review of activities and data
• National Stakeholders Meeting
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Screen TB patients for DM
Is there is a known diagnosis of DM?
No known diagnosis - screen first with RBG
If RBG ≥ 6.1 mmol/l, screen with FBG
If FBG ≥ 7.0 mmol/l, then diagnose DM and refer to DM care
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Screening TB patients for DM in India
Indicator TOTAL
Number of patients with TB registered and enrolled 8269
Number (%) with known diagnosis of DM 682 (8)
Number needing to be screened with RBG 7587
Number (%) actually screened with RBG 7467 (98)
Number with RBG >110 mg/dl and needing to be screened with FBG 2838
Number (%) screened with FBG 2703 (95)
Number (%) with FBG ≥ 126 mg/dl (newly diagnosed with DM) 402 (5)
Number (%) with known and newly diagnosed DM 1084 (13)
Number (%) with known / newly diagnosed DM referred to DM care 1033 (95)
India TB-DM study group TMIH 2013: 18: 636-45
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Screening TB patients for DM in
India • directive from India TB Programme to screen TB patients for DM and link them to diabetes care
• directive from India NCD programme to use glucometers to screen TB patients for DM
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Back of the TB Treatment card used in India
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Simple parameters added for routine recording in quarterly TB reports
• Number of TB patients registered
• Number of TB patients screened for DM
• Number of TB patients diagnosed with DM
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Screen DM patients for TB
Screen once a quarter when DM patients come to clinic
Ask: “Has TB been diagnosed during the quarter”
If no, screen for positive symptoms of TB
Refer those with positive symptoms for TB diagnosis and care
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DM patients Q2-2012
Number seen in the quarter 12237
Number diagnosed with TB in the quarter from elsewhere 74
Screened for TB symptoms in the DM clinic in the quarter 6393 (52%)
Positive TB symptom screen 135 (2%)
Referred for TB investigations 128 (95%)
Diagnosed with a new episode of TB 11
Total number with new TB and TB from elsewhere 85
Known to have started or to be on anti-TB Treatment 80
TB cases per 100,000 DM patients seen per quarter 695
Screening of DM Patients for TB in India
India DM-TB study group TMIH 2013; 18: 646-654
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Challenges in screening DM patients for TB
• Diabetes doctors not interested – extra work
• No structured recording systems in DM clinics
• No cohort analysis or public health approach
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Ways forward: i) programme integrationTB Clinic Diabetes Clinic
Peripheral clinic needs integrated DM / TB facilities
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ii) better screening tools
TUBERCULOSISSputum smear microscopy
Xpert MTB/RIF
DIABETES MELLITUSFasting blood glucose
Glycated haemoglobin
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iii) cohort analysis for DM for case burden and treatment outcomes
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2. DM and TB treatment outcomes
• Previous studies in TB patients show that DM is associated with:-– possible delay in sputum culture conversion– increased risk of death– increased risk of recurrent TB
• BUT many limitations to these studies
Baker MA et al, BMC Medicine 2011; 9: 81
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Risk of remaining sputum culture positive after 2-3 months of treatment for DM patients with TB versus non-DM patients with TB
8 studies: RR 0.8 – 3.2
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Risk of death for DM patients with TB compared to non-DM patients with TB
23 studies: Pooled RR 1.85 [1.5-2.4]
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Weights are from random effects analysis
Summary
Heterogeneity I-squared = 0% (0,79)
Wada, 2000
Singla, 2006
Zhang, 2009
Study
Mboussa, 2003
Maalej, 2009
Japan
Saudi Arabia
China
Country
Congo
Tunisia
7/61 (11%)
2/130 (2%)
33/165 (20%)
6/17 (35%)
4/55 (7%)
4/284 (1%)
3/367 (1%)
9/170 (5%)
9/77 (12%)
1/82 (1%)
3.89 (2.43, 6.23)
8.15 (2.46, 26.97)
1.88 (0.32, 11.14)
3.78 (1.87, 7.65)
RR (95% CI)
3.02 (1.24, 7.35)
5.96 (0.68, 51.95)
3.89 (2.43, 6.23)
8.15 (2.46, 26.97)
1.88 (0.32, 11.14)
3.78 (1.87, 7.65)
RR (95% CI)
3.02 (1.24, 7.35)
5.96 (0.68, 51.95)
1.3 1 3.89 15 60
Population with DM Relapse/ Total
Population without DM Relapse/ Total
Risk of TB relapse for DM patients with TB compared to non-DM patients with TB
5 Studies: Pooled RR 3.89 [2.4 – 6.2]
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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 liver toxicity with TB drugs
• Immune-suppressive effects of DM
• Possible exposure to TB in DM clinics
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But many questions….
• DM control and TB treatment outcomes• 6-months anti-TB treatment – adequate?• Timing of death in DM-TB patients• Reasons for death • Strategies to prevent death• Recurrent TB – reactivation or re-infection?• Integration of DM and TB care
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3. 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
Pfaffenberg et al, 1958 [Germany]
Lesnichii et al, 1969 [Russia]
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Summary: DM-TB is “similar” to HIV-TB
HIV-TB• Increased TB cases• More difficult to
diagnose TB cases• Increased death• Increased recurrent TB• Increased failure
DM-TB• Increased TB cases• More difficult to
diagnose TB cases• Increased death• Increased recurrent TB• Increased failure
Harries AD et al, Int J Tuberc Lung Dis 2011; 15: 1436 - 1444
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Need to tackle the upstream issues
HIV prevention/control• Behaviour• Condoms• Male circumcision• Early use of ART• ART as HIV prevention
DM prevention/control:• Healthy diets• Exercise• Obesity• Early detection of
impaired glucose tolerance
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Summary:Diabetes and Tuberculosis
• Rapidly growing pandemic of diabetes
• This could threaten tuberculosis control by:- increasing the number of cases
increasing case fatality increasing the risk of failure or relapse
• Global framework for collaborative activities exists but we need country-level action