1. Latent TB Infection among Diabetic patients
Soe Thiha, Ne Myo Aung, Zaw Myint, Tin Tin Mar, Mar Mar Kyi, Myo Lwin Nyein and Mon Mon Aung

2. Funding
Departmental Research Conducted with the grant from Department of Medical Research Myanmar

3. Background
Treatment of latent tuberculosis – measure to reduce TB burden
High risk population should be targeted
Diabetes Mellitus is associated with impaired immune function
So, latent TB can easily be converted to active TB
Burden of latent TB among diabetes??
Nathella PK and Babu S, Immunology, 2017

4. Method
Aim – to determine the proportion of latent TB infection in diabetic patients and their characteristics
Study Area – Medical ward of Insein General Hospital

5. Inclusion Criteria
Exclusion Criteria –
all patients who provided consent.
Having previous Mantoux testing
Having active TB infection or previous known TB infection
Receiving immunoglobulin or corticosteroid or immunosuppressant
Having chemotherapy for cancer
Having HIV infection
Pregnancy

6. The participants were asked with preformed questionnaire for their risk of tuberculosis and state of diabetic control and treatment
The clinical characteristics (socio-demographic characteristics, medical history, diabetic control) of these patients were determined
All the participants were done blood test to measure HbA1C level.
If HbA1C ≥ 6.5% or there was history of diabetes, the participants were collected as diabetes group
If HbA1C < 6.5% and there was no history of treating diabetes, these participants were collected as control group.

7. Tuberculin was injected intradermally at the fore-arm of all participants and read the result (induration) after hours
If the reaction (induration) was more than or equal to 10 mm, it was defined as latent TB
The possible TB risk factors were statistically analysed for any association for latent TB

8. All hospitalized patients who meet inclusion criteria
Exclude by exclusion criteria
History taking and Physical Examination
HbA1C level
DM group
Control group
Tuberculin skin test
Tuberculin skin test
LTBI present
LTBI present
LTBI not present
LTBI not present
Compare clinical and socio-demographic profiles

11. Results
134 cases of diabetic cases and 194 cases of non-diabetic cases (as control) were tested for tuberculin test after screening for active TB

12. In diabetes group New diagnosed diabetes comprised for 43% (58/134)
The mean duration of disease in previously diagnosed diabetes mellitus was 7 years
Among the diabetes, cases with controlled diabetes (HbA1c less than 7) accounted for 12% (16/134)

13. Fifty four percent (73/134) of diabetic cases were found to have latent TB infection.

14. Diabetes mellitus increased the risk of latent TB infection by an odd ratio of 2.6 (95% CI 1.6 to 4.1)
Diabetes mellitus
(n=134)
No diabetes
(n= 194)
LTBI (positive tuberculin) 73 61
No LTBI
133
54% vs 31%
p value <

15. In Diabetic Cases LTBI N = 73 No LTBI N = 62 p value Household member
Mean (number)
6.5 (SD 2)
4.7 (SD 1.5)
0.011
TB Contact (percent) 68 15
<
Family member with high risk of TB (percent) 60 8
Active Smoking (percent) 64 34

16. In Diabetic Cases LTBI N = 73 No LTBI N = 62 p value
Recently Diagnosed DM
(percent) 51 65
0.08
DM Duration (mean) (in years)
3.5 (SD 5.3)
4.6 (SD 5.7)
0.7
HbA1c (mean)
9.4 (SD 1.6)
8.8 (SD 1.6)
0.5
Presence of BCG Scar (percent) 78 85
0.2

17. In Diabetic Cases LTBI N = 73 No LTBI N = 62 p value
Low BMI (< 18.5)
(percent) 4 5
0.8
High BMI (> 30) 57 43
0.08
Waist circumference (cm) (mean)
88.5 (SD 17.2)
81.4 (SD 16.3)
0.3

18. Discussion Diabetes mellitus predisposes to tuberculosis
Early clearance (immediate removal of Mycobacterium tuberculosis soon after infection) was impaired in diabetic due to hypo-reactive alveolar macrophages, which causes persistent infection
So, diabetes are more likely to get latent TB infection.
Nathella PK and Babu S, Immunology, 2017

19. T-helper cell response and subsequent cytokines responses are impaired in diabetics resulting in more conversion of latent TB to active TB infection
So, diabetes is high risk not only for getting latent tuberculosis but also for conversion of latent to active tuberculosis
Nathella PK and Babu S, Immunology, 2017

20. These cases were increased risk of developing active TB
In a study in Indonesia, the prevalence of latent TB in diabetics was 38.9%
These cases were increased risk of developing active TB
In this study the incidence of latent TB in diabetes was 54%
Therefore it was significantly higher incidence of latent TB in the study area than in Bandung, Indonesia
Koseomadinata RC, McAllister AM, Soetejoe NNM, et., al, Transaction Royal Society of Tropical Medicine and Hygiene, 2017

21. The risk is the same for acquisition of TB
In a meta-analysis involving 13 studies, it was found that diabetes mellitus was significantly associated with risk of latent TB
The risk is amplified if the patient resided or came from the community with high burden of TB
There was an increased risk of latent TB infection among smokers and those with contact history of tuberculosis
The risk is the same for acquisition of TB
Lee MR, Huang YP, Kuo YT, et. al. Clinical Infectious Diseases, 2017

22. It also supported the concept that diabetic patients had impaired early clearance of tuberculosis
It is also found that diabetes mellitus increased the risk of latent TB infection by an odd ratio of 2.6 (95% CI 1.6 to 4.1) than non-diabetes (control group) in this study
So, diabetes patients are more susceptible to get latent tuberculosis.

23. The duration of diabetes did not have significant effect on the increased risk of latent TB
Glycemic control did not have significant effect on latent TB
However it should be interpreted cautiously because the proportion of controlled diabetes was as low as 12%.

24. Conclusion
This study points out that diabetic patients should be tested for latent TB infection particularly in those with contact history of TB and diabetic smokers

25. Recommendation
As diabetes is high risk for getting latent tuberculosis, all diabetes patients should be screened and treated for latent tuberculosis
In particularly,
diabetes smokers,
diabetes with TB contact,
diabetes living with high risk person for getting TB
Are very high risk for latent tuberculosis
These diabetes should be screened and treated for latent tuberculosis

26. Acknowledgement Special thank to
Department of Medical Research Myanmar
National Tuberculosis Programme

27. References
1. Nathella PK and Babu S (2017) Influence of diabetes mellitus on immunity to human tuberculosis, Immunology, 152; Koseomadinata RC, McAllister AM, Soetejoe NNM, et. al. (2017) Latent TB infection and pulmonary TB disease among patients with diabetes mellitus in Bandung, Indonesia, Transaction Royal Society of Tropical Medicine and Hygiene; 111(2): Lee MR, Huang YP, Kuo YT, et. al. (2017) Diabetes mellitus and latent TB infection: A systematic review and Meta-analysis; 64(6):

28. THANK YOU