TB in special conditions

1. TUBERCULOSIS IN SPECIAL
CONDITIONS
BY NUWAGABA NORMAN :
CLINICAL OFFICER,CHEST MEDICINE SPECIALIST
DCMCH,BCMCH
HND –CHESTMEDICINE
MBA &PGD MEDICAL EDUCATION

2. SUMMARY
• Tuberculosis incidence, risk, progression and treatment may be altered in
particular patient populations such as those with comorbidities.
• Some of the common comorbidities among TB patients includes;
1. HIV
2. Diabetes
3. Renal disease
4. Hepatic disease)
5. TB in mental health and substance dependence
6. Pregnant women.
• This Chapter provides information on the unique drug-disease interactions
and drug-drug interactions and how this affect diagnosis and management
of tuberculosis in these specific groups of patients.

3. MODULES
Unit 1: TB/HIV Co-infection
Unit 2: TB and Diabetes Mellitus
Unit 3: TB in Mental Health and Substance dependence
Unit 4: TB in Pregnancy
Unit 5: TB and Liver disease
Unit 6: TB and Kidney disease
Unit 7: TB and COVID-19

4. • UNIT 2:
• MANAGEMENT OF DIABETES MELLITUS (DM) &
TUBERCULOSIS (TB)

5. LEARNING OUTCOMES/ OBJECTIVES
By the end of this session, participants will be able to:
―Explain the effects of Diabetes on TB
―Explain the effects of TB on Diabetes
―Explain the diagnosis of DM and TB
―Illustrate bi-directional screening and diagnosis of DM and TB
―Describe management of DM in TB
―Describe treatment/management of TB in DM
―Outline Anti-TB medicines adjustment in DM

6. INTRODUCTION/BACKGROUND
• Diabetes Mellitus is a serious and life-long condition characterized by
hyperglycemia as a result of defects in insulin secretion, insulin action or
both
• Diabetes and TB are both chronic diseases with high socio-economic
impact at the Individual, household, community and the health system
• The susceptibility to tuberculosis (TB) is increased by impaired host
defenses in individuals, such as those with diabetes
• Globally, 15% of tuberculosis cases are estimated to be attributable to
diabetes.
• Mortality rates among TB cases with DM are twice the rate of those
without DM

7. STATISTICS ON TB/DM
In Kenya, prevalence of DM in adult TB patients is 5%; double the burden of
general adult population which is 2%
• 2020 data:
1,757 DM cases reported among patients with TB
TSR rate for TB/DM at 78.4%
• Gaps:
Collaboration activities still in infancy
Lack of TB/DM policy framework and coordination mechanisms
• Way forward
Adopt comprehensive collaborative framework in all health care settings
Measure impact of TB/DM interventions and activities
Monitor outcomes (TSR, mortality) for TB/DM patients
Identify missed opportunities for bi-directional screening of TB/DM

8. • In Uganda, Prevalance rate of Diabetes mellitus among the admitted patients with Tuberculosis
was 8.5%.
• Only 5(1.9%) patients with TB had a known Diabetes Mellitus at enrollment. Accoeding to a cross
sectional study by Dr Davis Kibirige and the colleagues.
• Confirmed diagnosis due to presence of clinical presentation and plus either Positive Zn smear,
Positive molecular test, positive culture positive or histological diagnosis of TB on lymph nodes or
pleural specimen.
• INCLUSION CRITERIA
• was being an adult patient with a confirmed diagnosis of TB and admitted on pulmonology wards
of Mulago hospital
• Study period was from September 2011 to febuary 2012
• EXCLUSION CRITERIA
• Adults on antiTuberculosis drugs not able to offer an informed consent
• Rifampicin a very potent antiTB drug has also been shown to induce a transient early phase
hyperglycaemia owing to augmentation of intestinal absorption.

9. TB as a predisposing factor for
Hyperglycemia
Studies suggest that TB can cause diabetes in those not previously known
to be diabetic: Mainly due to
• Decreased hepatic/liver glycogenesis.(formation of glycogen from sugar)
• Increased hepatic/ liver glycogenolysis (break down of glycogen into glucose and
glucose-1-phosphate) & gluconeogenesis.(formation of glucose from non
carbohydrate carbon substrates mainly in liver and sometimes cortex of kidneys)
• Lack of insulin due to impairment of pancreatic islets
• Tubercle bacilli suppress the sensitivity of tissues to insulin
• Tuberculosis causes tissue destruction
• Diabetogenic effect of INH.

10. Effect of Diabetes Mellitus on Pulmonary
TB
• On Incidence and Prevalence
• Increases Risk of TB 2-3 times
• Increases risk of MDR-TB
• On Clinical Presentation
• TB may present atypically
• TB may progress faster
• TB may present with more chest and systemic symptoms; more exudation and caseation
with subsequent cavitation and toxaemia, more frequent haemoptysis and pleural effusi
on,
• Predilection to hilar and basal regions
• Less frequent extra-pulmonary TB and fibrous adhesions
• TB may present with more frequent and higher grade smear/culture positivity; DM cause
s a delay in sputum culture conversion

11. Effect of Diabetes Mellitus on Pulmonary
TB
• On response to TB treatment
• Prolonged smear/ culture positivity
• Diabetes causes changes in oral absorption, decreased protein binding of d
rugs, and renal insufficiency or fatty liver with impaired drug clearance
• DM poses a higher risk of adverse drug reactions e.g. hepatitis, renal toxicit
y, GIT effects
• On TB treatment and outcome
• Increased risk of death
• Increased risk of treatment failure
• Increased risk of loss to follow-up
• Increased risk of relapse

12. Effect of TB on Diabetes Mellitus
• TB causes worsening of diabetic state
 induce glucose intolerance
 worsen glycemic control with increased insulin requirement and ketosis
• The endocrine function of the pancreas is adversely affected
severe tuberculosis
higher incidence of chronic calcific pancreatitis occurs in patients with
concomitant diabetes
tuberculosis leads to an absolute or relative insulin deficiency state

13. Bi-directional screening and diagnosis
of DM and TB
• All confirmed/ diagnosed TB patients should be screened for
diabetes at the time of diagnosis or registration for TB
• Additionally, all people diagnosed with Diabetes Mellitus
should be screened for Tuberculosis at each clinic appointment

14. Diagnosis of TB in Persons with DM
Any diabetic patients who suddenly develops any of the following
symptoms should be investigated for presence of tuberculosis as
per the SOPs (Ref integrated guideline)
• Cough
• Fever
• Unexplained loss of weight
• Drenching night sweats
• Abnormal chest radiograph
• Needs increasing doses of insulin to control blood glucose

15. Screening for DM in TB patients
ALL REGISTERED TB
PATIENTS
DO GLYCEMIC TEST
Do patients have FBS ≥ 126mg/dl or FBS
≥ 7.0mmol/L OR RBS (at least 2 hours
after meal) ≥ 200mg/dl or RBS ≥
11.1mmol/L?
 FOLLOW-UP: According to TB
schedule. Repeat glycemic test
every 2 months OR if DM
symptoms present
 Do patients have FBS ≥
126mg/dl or FBS ≥ 7.0mmol/L
OR RBS (at least 2 hours after
meal) ≥ 200mg/dl or RBS ≥
11.1mmol/L?
 Start/Continue TB management
according to national guideline
 Be aware of DM symptoms: Polyuria?
Polydipsia? Polyphagia? Weight loss?
Blurred vision? Numbness/tingling?
 Adherence to TB medications
Refer to DM clinic for DM
work up (Based on national
guideline)
Is DM diagnosed?
 Continue TB management:
 Stop smoking, stop alcohol drinking,
do physical exercise, healthy diet
 Be aware of DM symptoms
 Adherence to TB medications
 Start DM management according to
national guideline: Be aware of poor blood
sugar control
 Continue TB management: Be aware of
poor TB treatment outcome
 Education and counselling: TB & DM
treatment adherence and psychological
support
 Regularly and strictly follow-up
YES NO
YES
NO
YES NO

16. Screening for DM in persons with TB
Every patient with TB should be screened for DM:
• A fasting plasma glucose > 7mmol/L = DM
• A random plasma glucose > 11.1 mmol/L= DM.
• A Hemoglobin A1c > 6.5% = DM
• Ask about polyuria (urinate frequently) /polydipsia (increased thirst
and fluid intake) and polyphagia (increased hunger) at TB clinic
visits
• Abnormal glucose values should be repeated in patients who have
no symptoms of DM; Glucose should be repeated after 2-4 weeks
of TB Rx or if symptoms of hyperglycemia develop
• Rifampin and INH can markedly elevate glucose levels

17. Management of DM in TB
• Management of DM is aimed at controlling blood glucose as well as reducing
long and short term complications
• Management of DM mainly involves lifestyle modification:
Maintain healthy weight
Healthy Diet
Physical Activities
Smoking cessation
Reduce alcohol consumption
Administration of glucose lowering agents/medications
management of existing complications like diabetic foot, neurological and eye
problems
• Priority is to treat TB disease while at the same time controlling the blood
glucose levels

18. Treatment of TB Disease in persons
with DM (1)
• The TB treatment regimen for both DSTB and DRTB is similar in persons with or
without diabetes
• Ensure that TB treatment is appropriately adjusted in persons with diabetes; Both
PZA and EMB need adjustment for renal impairment (PZA 25mg/kg and Ethambutol
15mg/kg to be administered three times per week )
Preferred regimen
• Initial phase: 2 months isoniazid (INH), rifampin (RIF),pyrazinamide (PZA), and
ethambutol
• Continuation phase: 4 months INH and RIF
• Be aware of poor absorption of some TB meds in DM; Observe closely for treatment
failure

19. Treatment of TB Disease in persons
with DM (2)
• Consider extending treatment to 9 months for patients with cavitary pulmonary TB
with DM and positive culture results at the end of intensive phase. Upon completion
of therapy, obtain smear for AFB and culture
• Rifampicin may cause new onset of hyperglycemia or worsen glycemic control;
insulin is the preferred treatment in early stages of TB treatment in severe TB and in
renal or liver impairment. However, oral hypoglycemics can be used in mild DM
• Metformin is preferred as the OGLA for patients with TB since it is not metabolized
by cytochrome P450 enzymes
• There may be a slight increase in diabetic retinopathy in persons with DM
• Follow up the patient at 6 months and one year after TB treatment completion

20. Pharmacological issues in the Management of DM and TB
Drugs used to treat tuberculosis might:
• Have overlapping toxicities in co-managing tuberculosis and diabetes.
 Peripheral neuropathy caused by isoniazid; Give Pyridoxine (B6) to prevent
INH induced peripheral neuropathy
• Worsen glycemic control
Rifampicin directly causes early-phase hyperglycaemia with associated
hyperinsulinaemia even in non-diabetics. Or indirectly worsen glycemic control
via interactions with OAD (It lowers the serum levels of sulphonylureas and
biguanides)
Rifampicin decreases concentrations of rosiglitazone by 54–65% and of the
related drug pioglitazone by 54%
Insulin requirements might increase when on rifampicin
• Ensure you manage interactions between TB and DM drugs

21. Key Take Home Message
• All adult TB patients should be screened for diabetes at TB treatment
initiation
• Patients with diabetes should be screened for TB at every clinic visit using
TPT/ICF symptom questionnaire
• Treatment of TB in patients with diabetes is similar to that in patients without
diabetes
• Patient education on lifestyle modification for TB patients with TB is
paramount
• Insulin is the drug of choice where blood sugar control is not attained in
severe TB, renal disease or liver disease
• Closely monitor treatment response, adherence and adverse reactions to TB
and diabetes
• Align TB DM activities to achieve priority outcomes for TB NSP

22. References
• -Davidson Book of Internal medicine
• Oxford book of Medicine
• Williams Textbook of Endocrinology
• UCG 2022
• CLINICAL AND COMMUNITY TUBERCULOSIS BY LIOYD N. FRIEDMAN