TB and Diabetes
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Transcript of TB and Diabetes
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
Structure of the Presentation
• Background Epidemiology
• Collaborative Framework for Care
• Challenges for Care
• Conclusion
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
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]
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]
India and China [2012]
India
• 63 million DM
• 2.2 million TB per annum
China
• 92 million DM
• 1.0 million TB per annum
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
The global increase in DM
• 2012 371 million with DM
• 2030 552 million with DM
[Diabetes Atlas: International Diabetes Federation, 2012]
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
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
Recognised in Roman times that DM increases risk of TB
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
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
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
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
Expert Meeting convened in November 2009
(WHO, Union, WDF, IDF, Academia, Ministries of Health)
Collaborative Framework for Care
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
Collaborative Framework for Care and Control of TB
and Diabetes
Launched in August 2011
The recommendations
http://www.who.int/tb/publications/2011/en/index.html Document available at:
Three challenges for care
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
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
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
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
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
Back of the TB Treatment card used in India
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
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
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
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
Ways forward: i) programme integrationTB Clinic Diabetes Clinic
Peripheral clinic needs integrated DM / TB facilities
ii) better screening tools
TUBERCULOSISSputum smear microscopy
Xpert MTB/RIF
DIABETES MELLITUSFasting blood glucose
Glycated haemoglobin
iii) cohort analysis for DM for case burden and treatment outcomes
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
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
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]
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]
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
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
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]
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
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
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