an overview of tuberculosis and its management

1. DR.G.VENKATA RAMANA
HOD FAMILY MEDICINE
RDT HOSPITAL BATHALAPALLI
AN OVERVIEW OF TUBERCULOSIS

2. CONTENTS
 ETIOLOGY
 PATHOGENESIS
 CASE DEFINITIONS
 DIAGNOSIS OF TUBERCULOSIS
 TREATMENT AND FOLLOW UP
 MANAGEMENT OF ADVERSE EFFECTS OF ATT
 TB IN SPECIAL SITUATIONS
 TREATMENT OUTCOMES
 TB PREVENTIVE TREATMENT
 DRUG RESISTANT TB REGIMENS

3. TUBERCULOSIS
 Etiology
 Mycobaterium tuberculosis complex
 Source of Infection
• Human (e.g. cases of pulmonary tuberculosis)
• Bovine source (e.g. consumption of unpasteurized infected milk)
• Mode of Transmission
• Airborne - inhalation of aerosols, generated while coughing,
sneezing, or speaking of infected patients.
• Other modes of transmission are rare, such as –
• Inoculation – direct skin contact with an infected person is uncommon
• Consumption of unpasteurized (infected) milk
 Risk factors
 Undernourishment
 HIV infection
 Alcohol consumption
 Smoking
 Diabetes

4. PATHOGENESIS OF TUBERCULOSIS

5. NATURAL HISTORY AND SPECTRUM OF TUBERCULOSIS

6. Features Primary pulmonary TB Post primary/secondary TB
Results due to Exogenous infection with
tubercle bacilli
Exogenous reinfection,
Endogneous-reactivation of the
latent primary lesion
Age group
affected
Children Adults
Parts of the
lungs
commonly
affected
lower part of the upper lobe or
the upper part of the lower
lobe,close to the pleura
Apical and posterior segments of
the upper lobes(areas of high O2
tension)
Lesions formed
at the initial
sites
Gray-white inflammation
with consolidation known as
the Ghon focus.
Gray-white areas of caseation and
multiple areas of softening and
cavitation.
Lymphnode Gohn focus and nodal
involvement-Ghon complex
Lymph node involvement unusual
Clinical
features
Asymptomatic or Flu like
illness
Fever,cough,weight
loss,hemoptysis
Cavity formation in lungs
Fate lesions heal spontaneously,
primary complex become
calcified.Rarely in children
with impaired immunity
Caseating pneumonia
Hematogenous spread and
granuloma formation
Rarely heals spontaneously

7. CASE DEFINITIONS
Presumptive Pulmonary TB Cough for 2 weeks or more
Fever for 2 weeks or more
Significant weight loss
Hemoptysis
Any abnormality in chest radiograph
Presumptive Pediatric TB Cough for 2 weeks or more
Fever for 2 weeks or more
Loss of weight
No weight gain
History of contact with infectious TB cases
Presumptive Extra Pulmonary TB Presence of organ-specific symptoms and signs
like swelling of lymph node, pain and swelling in
joints, neck stiffness,disorientation,etc.,and/or
constitutional symptoms like significant weight
loss, persistent fever for 2 weeks or more, night
sweats.
Presumptive DR TB Refers to the patient who is eligible for
Rifampicin resistant screening at the time of
diagnosis or/and during the course of treatment
for DS TB or H mono/poly

8. Microbiologically
confirmed TB
Presumptive TB case from whom a biological
specimen is positive for acid fast bacilli,or positive for
Mycobacterium tuberculosis on culture, or positive for
tuberculosis through Rapid Diagnostic molecular test
Clinically Diagnosed TB Presumptive TB case who is not microbiologically
confirmed, but has been diagnosed with active TB
by a clinician on the basis of X-ray abnormalities,
histopathology or clinical signs with a decision to treat
the patient with a full course of Anti TB treatment.
Pulmonary Tuberculosis TB involving the lung parenchyma or the
tracheo-bronchial tree.
Extra Pulmonary
Tuberculosis
TB involving organs other than the lungs such as
pleura, lymph nodes, intestine, genitourinary tract,
joint and bones, meninges of the brain etc
Miliary Tuberculosis Miliary TB is classified as PTB because there are
lesions in the lungs.
A patient with both pulmonary and extra-pulmonary
TB should be classified as a case of Pulmonary TB

9. New TB patient Who has never had treatment for TB or has taken anti-TB
drugs for less than one month
Previously treated TB Who has received one month or more of anti-TB drugs from
any source in the past.
Recurrent TB patient A TB Patient previously declared as successfully treated
(cured/treatment completed) and is subsequently found to be
microbiologically confirmed TB
Treatment after failure
patients
Those who have previously been treated for TB and
whose treatment failed at the end of their most recent course
of treatment
Treatment after lost to
follow-up
A TB patient previously treated for TB for one month or
more and was declared lost to follow-up (LFU) in their most
recent course of treatment and subsequently found to be
microbiologically confirmed TB
Other previously
treated patients
Those who have previously been treated, who
cannot be classified into any of the above.

10. Isoniazid-
resistant
TB(HrTB)
A TB patient, whose biological specimen is resistance to isoniazid
and susceptibility to rifampicin has been confirmed
Mono-resistant
TB (MR TB).
A TB patient, whose biological specimen is resistant to one first-
line anti-TB drug only.
Rifampicin
resistant TB
(RR-TB).
A TB patient, whose biological specimen is resistant to R,
detected using phenotypic or genotypic methods, with or without
resistance to other anti-TB drugs.
Multidrug-
resistant TB
(MDR-TB)
A TB patient, whose biological specimen is resistant to both H
and R with or without resistance to other first-line anti-TB drugs
Poly-drug
resistant TB
(PDR-TB)
A TB patient, whose biological specimen is resistant to more than
one first-line anti-TB drug, other than both H and R
Pre-extensively
drug resistant TB
(Pre-XDRTB)
TB caused by Mycobacterium tuberculosis strains that fulfil the
definition of MDR/RR-TB and are also resistant to any
fluoroquinolone
Extensively drug
resistant TB
(XDR-TB)
TB caused by Mycobacterium tuberculosis strains that fulfil the
definition of MDR/RR-TB and are also resistant to any
fluoroquinolone (levofloxacin or moxifloxacin) and at least one
additional Group A drug (presently to either Bedaquiline or
linezolid [or both])

12. DIAGNOSIS OF TUBERCULOSIS
• SMEAR EXAMINATION
• MOLECULAR TESTS
• CULTURE
• NOTE:smear examination
and molecular tests
cannot differentiate
between live and dead
bacteria,but culture can
detect both

13. COLLECTION OF SPUTUM
 Method:The patient is instructed to inhale deeply 2–3 times with mouth
open,cough out deeply from the chest, open the container and spit out
the sputum into it, and close the container
 Two specimens are collected
 spot specimen labelled as specimen 'a'.
 early morning specimen labelled as specimen 'b'.
 Two supervised spot samples may be collected one hour apart if patient
is too sick, coming from a long distance or likelihood of not giving a
second sample is significant.
 Good quality sample
 Thick (semisolid),coughed out deeply from the lungs
 mucoid or mucopurulent
 minimum amount of oral or nasopharyngeal material
 adequate in quantity (2-5ml)
 Collected in a proprely labelled sterile container
 Send biopsy specimen in normal saline for culture not in formalin as it
will kill the bacilli

14. SMEAR EXAMINATION
 Direct smear microscopy is technique of choice
 Because it is simple,rapid,lowcost and operational feasibility
 It differentiates between active and healed TB
 1.ZN staining
 Advantages-more specificity,lesser cost and rapid
 Disadvantages-low sensitivity for HIV and childhood TB
(50%)
 Its sensitivity is increased if cavities are present in chest
xray
 2.Fluorescent (auramine)staining
 More specific and sensitive than ZN staining
 Advantages-faster screening of smears
 Doesnot require use of oil immersion
 No heat is required for staining

15. Zeihl-Neelsen and Fluorescence staining smears/ Grading
scales for ZN/FM

16. MOLECULAR TESTS
 Detect genetic
mutations with drug
resistance
 Donot distinguish
between live and
dead bacteria
 1)Xpert MTB/RIF
(CBNAAT)
 2)Line probe assay
 CBNAAT/Xpert
MTB/RIF
 Detects
Mycobacterium TB
alog with Rifampicin
resistance with in 2hrs
 For-Sputum
 FNAC (lymphnode)
 CSF
 Pleural fluid (less
sensitive)

17. CBNAAT FORM

18. CBNAAT/GENE XPERT MTB/RIF TEST PROCEDURE

19. LINE PROBE ASSAY
 Fast (2 days)
 Good sensitivity and
specificity
 Done only in sputum
AFB positive patients
 PCR based technique
 Detects Rifampicin and
Isoniazid resistance
 Detects resistance to
FQs and 2nd line
injectable drugs
LINE PROBE
ASSAY
CBNAAT
Done only in smear
positive
Can be done in
both smear +ve or -
ve
Less automated More automated
Done only at state
level
At sub-district level
Less value in
HIV/EPTB
More value
2 days 2hrs
RIF/INH resistance RIF resistance

24. LAB INVESTIGATIONS BEFORE STARTING
TREATMENT
 HIV
 RBS
 LFT
 S.CREATININE
 CHEST XRAY
 CBC
 SPUTUM TB CULTURE
 LPA
 VISUAL ACUITY AND COLOUR VISION

25. TREATMENT REGIMEN
 Regimen for Drug-Sensitive TB (DSTB) cases: 2HRZE/4HRE
 This regimen is for H & R sensitive TB cases and cases with unknown sensitivity
pattern
 Treatment is given in two phases
 Intensive phase (IP) consists of 8 weeks (56 doses) of isoniazid (H), rifampicin
(R),pyrazinamide (Z) and ethambutol (E) given under direct observation in daily
dosages as per weight band categories
 Continuation phase (CP) consists of 16 weeks (112 doses) of isoniazid,
rifampicin and ethambutol in daily dosages
 The CP may be extended by 12-24 weeks in certain forms of TB like CNS
TB,Skeletal TB, Disseminated TB etc. based on clinical decision of the treating
physician on case to case basis
 Extension beyond 12 weeks should only be on recommendation of specialists.
 Steroids as an adjunctive therapy is useful in patients with TB pericarditis and
meningeal TB, with an initial high dose tapered downwards gradually over 6 - 8
weeks

27. FOLLOW UP OF TREATMENT
Clinical follow up Follow up lab
investigation
Long term follow up
Should be at least
monthly
Can be in clinical
facility/patient’s house
To observe
improvement of Chest
symptoms, weight gain
Control the comorbid
conditions such as HIV
and diabetes
To monitor any adverse
reaction of ATT
For PTB cases Sputum
smear examination at
the end of IP and at the
end of treatment
In case of clinical
deterioration,consider
repeat sputum smear
even during CP
At the completion of
treatment sputum
smear and culture
CXR whenever required
and available
After completion of
treatment,the patient
should be followed up
at the end of
6,12,18&24 months

28. Management of adverse effects of ATT
Symptom Drug Action to be taken
Gastrointestinal
(vomiting or
epigastric
discomfort)
Any oral
medication
Maintain hydration
Consider treatment with anti-emetics
(e.g.domperidone) and proton pump
inhibitors (e.g.Omeprazole)
Itching/Rashes Isoniazid (and
other
drugs also)
Itching without rash or a mild rash
• Continue treatment and
giveAntihistamines
Itching with moderateto severe rash
• Stop all drugs till symptoms subside
• Treat with antihistamines
• Patients withmucosal involvement, fever
and hypotensionwill require
treatment with corticosteroids
• When the reactionSubsides reintroduce
drugs one by one in thisorderINH.
Rifampicin Pyrazinamide Ethambutol

29. Management of adverse effects of ATT
Tingling/burning
/numbness in the
hands and feet
Isoniazid Give pyridoxine100 mg/day orally
orparenterally until
symptoms subside.
Patients not responding to
pyridoxine will require treatment with
amitryptiline
Joint pains Pyrazinamide Give NSAIDs like paracetamol,Aspirin
or ibuprofen and in severe
casesIndomethacin for aweek to 10
days
• In severe cases estimate serum
uricacid levels If uric acid levels
are significantlyraised treat withNSAIDs
and colchicine.
Allopurinol is not Effective
In severe cases with normal or slightly
elevated uric acid
consider reduction of the dose of
Pyrazinamide.

30. Management of adverse effects of ATT
Impaired vision Ethambutol Refer to ophthalmologist for
evaluation
• Impaired vision may, within a
few weeks, or may not
return to normal after stopping
ethambutol.
Don’t restart ethambutol
Ringing in the
ears Loss of
hearing
Dizziness and
loss of balance
Streptomycin Refer to oto-rhinolaryngologist
For opinion
• As hearing loss is usually not
reversible do not restart
Streptomycin

31. Management of adverse effects of ATT
Hepatitis:
Anorexia /
Nausea /
vomiting /
Jaundice
Isoniazid,
Rifampicin
or Pyrazinamide
• Rule out other causes of
hepatitis
• Do not restart treatment till
symptoms resolve and liver
enzymes return to baseline
Levels
• If liver enzymes cannot be
performed wait for2 weeks after
jaundice has disappeared to
restart treatment
• Restart treatment with one drug
at a time starting with
Rifampicin,INH,Pyrazinamide.
• In patients with severe disease
in whom treatment cannot be
stopped use a non hepatotoxic
regimen consisting of
Levofloxacin, Streptomycin and
Ethambutol

35. MANAGEMENT OF TB IN PATIENTS WITH LIVER DISORDERS
 Patients with hepatitis virus carriage, a past history of acute hepatitis, current
excessive alcohol consumption can receive the usual TB regimens provided that
there is no clinical evidence of chronic liver disease
 If the serum alanine aminotransferase level is more than 3 times normal before
the initiation of treatment, the following regimens should be considered:
 Containing two hepatotoxic drugs:
 9 months of isoniazid and rifampicin, plus ethambutol - 9HRE
 2 months of isoniazid, rifampicin, streptomycin and ethambutol, followed by 7
months of isoniazid and rifampicin-2SHR/ 7HR
 6–9 months of rifampicin, pyrazinamide and ethambutol-(6-9 RZE)
 Containing one hepatotoxic drug:
 2 months of isoniazid, ethambutol and streptomycin, followed by 10 months of
isoniazid and ethambutol (2SHE/10 HE)
 Containing no hepatotoxic drugs:
 18–24 months of streptomycin, ethambutol and a fluoroquinolone. (18-24 SLE)

36. TB PATIENT WITH RENAL FAILURE AND SEVERE RENAL
INSUFFICIENCY
 Patients suffering from Chronic Kidney diseases (CKD) are at an
increased risk of developing Tuberculosis
 Isoniazid and rifampicin are eliminated by biliary excretion, so no change
in dosing is necessary
 There is significant renal excretion of ethambutol and metabolites of
pyrazinamide, and doses should therefore be adjusted for patients with
stages 4 and 5 Chronic renal disease and on haemodialysis
 Dosing intervals should be increased to three times weekly for
ethambutol, pyrazinamide and the aminoglycosides.
 Treatment can be given immediately after hemodialysis to avoid
premature drug removal.
 With this strategy there is a possible risk of raised drug levels of
ethambutol and pyrazinamide between dialysis sessions.

38. TB IN PATIENTS WITH SEIZURE DISORDER
 The use of isoniazid and rifampicin may interfere
with many of the anti-seizure medications.
 High dose isoniazid also carries a high risk of
seizure and should be avoided in patients with
active seizure disorders.
 The prophylactic use of oral pyridoxine (vitamin
B6) can be used in patients with seizure disorders
to protect against the neurological adverse effects
of isoniazid.
 Suggested prophylactic dose
for at-risk patients on isoniazid is 25-50 mg/day

39. TB AND CONTRACEPTIVE PILLS USAGE
 Efficacy of oral contraceptive pills may be decreased due to
Rifampicin is a potent inducer of hepatic enzyme
Due to vomiting
Drug interactions with second line anti-TB drugs
 Hence, women suffering from TB and using contraceptive pills
should be advised to use alternative contraception method
 Barrier methods (Condoms/ diaphragms)
 IUDs (CuT)
 Depot medroxy-progesterone (Depo-provera)
 Use of an oral contraceptive pill containing a higher dose of
estrogen (50 /g)

40. DRUG SENSITIVE TB AND PREGNANCY
 Women in child baring age should ask
about current or plan pregnancy
 All first line drugs are safe except
streptomycin
 Should continue breastfeeding
 Take all measure to prevent transmission
of TB
 After ruling out TB in infants,should
receive IPT
 Mother receiving H,Infant should get

41. TB and HIV
 The primary impact of HIV on TB is that the risk of developing TB becomes
higher in patients withHIV.
 HIV Testing for TB Patients / Presumptive TB Cases
 TB Screening among HIV patients
 Three “I” s to reduce burden of TB among PLHIV
 ICF: Intensified (TB) case finding (ICF)
 IC-AIC: Air-borne infection control measures for prevention of TB transmission
 IPT: Implementation of Isoniazid preventive treatment (IPT) for all PLHIV
 Provision of ART for HIV infected TB patients
 Treatment of TB is same as that in the HIV-negative TB patients.
 If drug sensitive TB patient and on second line ART, Rifampicin should be
replaced with Rifabutin 300 mg three times a week or 150 mg daily.
 Anti-retroviral therapy and co-trimoxazole prophylactic therapy in HIV infected
TB Patients irrespective of CD4 cell-count, as early as possible (after 2 weeks

42. TB AND HIV
 Immune reconstitution inflammatory syndrome (IRIS) may
occur in up to one-third of patients who have been
diagnosed with TB and who have started ART.
 It typically presents within three months of the initiation of
ART but can occur as early as five days.
 Patients with TB-associated IRIS most commonly present
with fever and worsening of pre-existing
lymphadenopathy or respiratory disease.
 The symptoms are similar to the paradoxical reactions
seen in immunocompetent patients on ATT, but occur
more frequently.
 Most cases resolve without any intervention and ART can
be safely continued.
 Serious reactions, such as tracheal compression caused
by massive adenopathy or respiratory difficulty, may
occur. Therapy may require the use of corticosteroid

43. TB &DIABETES
 All TB patients who have been diagnosed and registered under NTEP
will be referred for screening for Diabetes
 good glycaemic control in TB patients can improve treatment outcomes
TB & TOBACCO
 Increase the risk of tuberculous infection and the risk of developing TB
 Affect clinical manifestations and increase risk of relapse among TB
patients
 Affect microbiological conversion (sputum smear or culture) and
outcome of treatment in TB patients
 • Increase tuberculosis mortality and drug resistance to anti–tubercular
drugs
 Brief Advice’ to quit
 tobacco used based on 5As and 5 Rs model
TB & SILICOSIS increase risk for tuberculosis

44. TB AND NUTRITION
 TB & NUTRITION
 Undernutrition is considered as one of the
risk factors in the development of TB

45. LATENT TUBERCULOSIS INFECTION (LTBI)
 Latent tuberculosis infection (LTBI) is the presence of
Mycobacterium tuberculosis in the body.No symptoms or
physical findings suggestive of TB disease.
 TST or IGRA result usually positive.
 Chest radiograph is typically normal.
 If done, respiratory specimens are smear and culture
negative.
 Cannot spread TB bacteria to others.
 Should consider treatment for LTBI to prevent TB disease
in those receiving long term corticosteroids,
immunosuppressants, HIV-infected and juvenile contacts
of sputum-positive index cases
 Isoniazid (INH) taken for at least 6 months or R for
4months or HR for 3months

46. TREATMENT OUTCOMES
Treatment
outcome
Definition
cured Microbiologically confirmed TB patients at the beginning of
treatment who was smear or culture negative at the end of the
complete treatment
Treatment
completed
A TB patient who has completed treatment without evidence of
failure or clinical deterioration BUT with no record to show that
the smear or culture results of biological specimen in the last
month of treatment was negative
Treatment
success
TB patients either cured or treatment completed
Treatment failed TB patient whose biological specimen is positive by smear or
culture at end of treatment.
Lost to follow up A TB patient whose treatment was interrupted continuously for
ONE month or more.
Not evaluated A TB Patient for whom no treatment outcome is assigned. This
includes former “transfer-out”
Died A patient who has died during the course of anti-TB treatment
Treatment A TB patient who is on first line regimen and has been

49. TB PREVENTIVE TREATMENT

50. DOSAGE SCHEDULE