Tuberculosis

Dr. SHAMI POKHREL

LECTURER
Dept. of Pediatrics, LMC
 Etiology
• Mycobacterium tuberculosis complex.
• M. bovis, M.africanum, M.microti, M.canetti.
• Non-spore forming, non-motile, weakly gram
positive, obligate aerobes, growing in
synthetic medium.
• Lipid rich cell wall.
• Acid fastness- capacity to form stable.
mycolate complexes with arylmethane dyes.
 3 clinical stages of tuberculosis
• Exposure
• Infection
• Disease
• An immunocompetent adult with untreated
TB infection has apprx. 5-10% lifetime risk of
developing disease whereas an infected child
younger than 1 yr of age has a 40% chance of
developing disease within 9 months.
 Epidemiology
• One third of worlds population is infected.
• 95% of cases occur in the developing world.
• Incident cases 8.7 million, 12 million prevalent
cases, 1.4 million deaths occurred worldwide
in 2013.
• WHO estimates there were 550,000 childhood
cases and 80,000 TB associated deaths from
TB in 2013.
 Transmission
• Inhalation of airborne droplet nuclei.
• Not common in case of children.
• Congenital infection, transmission via
umbilical vein to fetal circulation, aspiration of
infected amniotic fluid.
• However most the common route of
transmission in perinatal period is?
 Pathogenesis
• Stays Infected for life long in 90%-tuberculin
test +.
• Ghon focus.
• Primary complex.
• Hypersensitivity (2-12wks).
• Pneumonia.
• Disseminated(Lymphadenopathy, Meningitis,
Pericarditis, Milliary.
 Contd….
• Post Primary- reactivation and re infection.
• Features of Post primary: Extensive lung
destruction with cavitation, positive sputum
smear, upper lobe involvement usually no
intra-thoracic lymphadenopathy.
 Clinical manifestations
• Cough>2 wks, Sputum Production and wt.loss.
• Respiratory:- hemoptysis, chest pain,
breathless, wheeze, pleural effusion.
• Constitutional:- fever/night sweats, tiredness,
loss of appetite.
• Pericardial.
• Disseminated.
• Lymph node.
 Diagnosis
• Microscopy sputum examination.
• X- ray chest.
• Tuberculin skin test.
• Culture.
• Biopsy.
• Fluid Analysis and marker(plueral, ascities,
CSF) ADA.
• CBC,ESR.
 Continued diagnosis

. Diagnosing latent tuberculosis (TB)

– Mantoux testing.
– Interferon-gamma testing.

• Diagnosing active TB
– Posterior-anterior chest X-ray
– Multiple sputum samples for microscopy and culture.
– Site-specific investigations for non-respiratory TB (X-ray, computed
tomography, magnetic resonance imaging, ultrasound,
echocardiogram, intravenous urography, biopsies, culture)
– Use of rapid diagnostic tests, ideally sent for culture by automated
liquid methods.
 Case definition by site and result of sputum
smear
• Pulmonary TB ( Smear Positive)- 2 sputum smears
positive or 1 with x-ray abnormalities or culture positive.

• Pulmonary (Smear negative)- 3 sputum negative but x-

ray evidence consistent with active tuberculosis which
does not clear with antibiotic or culture positive.

• Extra-pulmonary TB: At least 1 positive culture from

extra pulmonary site or X-ray or histologically or clinical
evidence consistent with active TB at an extra-pulmonary
site.
 continued
• Pulmonary TB: only involved the parenchyma.

• Extra pulmonary: Commonly affected sites

are( in order of frequency) Lymph node(40%),
pleura(20%), Genitourinary(15%), Bones and
joint(10%), meningitis and tuberculoma
(10%) gastrointestinal (3.5%)Peritoneum, and
Pericardium and milliary or disseminated.
 Case definition by previous treatment

• New case:- A pt. who has never had treatment for

tuberculosis or has taken anti-tuberculosis drugs for less
than one month.

• Relapse:- A pt. previously treated for tuberculosis who has

been declared cured or treatment completed and is
diagnosed with bacteriologically +ve( at least one smear or
culture) tuberculosis.

• Treatment failure:- A pt. who remains or becomes, sputum

smear +ve 5 months or more after starting treatment.
 continued
• Treatment after default:- A pt. who returns to
treatment with +ve bacteriology following
interrupted for two months or more.

• Transfer in:- A pt. who has been transferred from

another tuberculosis register to continue
treatment in a different register area.

• Others:- All cases who do not fit the above

definitions.
 Aims of ATT
• To cure the pt. of TB.
• To prevent death from active TB or its late
affects.
• To prevent TB relapse.
• To decrease TB transmission to others.

Properly applied anti-TB drug treatment will

achieve these aims and prevent the emergence
of drug resistant Tuberculosis.
Standardized treatment categories
TB treatment categories Patients
Category 1 New sputum smear –positive
PTB, sputum Negative PTB and
Extra Pulmonary TB.
Category 2 Relapse
Treatment failure
Treatment after
default( interrupted treatment)
Weight (kg) HRZ 50/75/150 E 100 Contd phase
HR 50/75

4-7.9 1 1 1

8-11.9 2 2 2

12-15.9 3 3 3

16-24.9 4 4 4

25 Use adult prep

 Essential Anti-TB drugs
Essential Anti- Mode of Dose mg/kg Intermittent Intermittent
TB drug Action 3x/wk 2x/wk
Isoniazid(H) Bactericidal 5 10 15
Rifampicin(R) Bactericidal 10 10 10
Pyrazinamide(Z Bactericidal 25 35 50
) Bactericidal 15 30 45
Ethambutol(E) Bactericidal 15 15 15
Streptomycin(s)
 Modes of Action Of anti-TB drugs
• A-metabolically active ,continuously growing
bacilli inside cavities.
• B-bacilli inside cells eg macrophages.
• C-semi-dormant bacilli(persistent) which
undergo occasional sputs of metabolism.
• D-dormant bacilli which fade and die on their
own.
 continue
• Isoniazid:- kills 90% of the total population of bacilli
during the first few days of treatment. Most effective
in metabolically active, continuously growing bacilli.
• Rifampicin:- can kill the semi dormant bacilli which
isoniazid can’t.
• Pyrazinamide:-kill bacilli in an acid environment
inside cells, eg macrophages.
• Sterilizing action:- mean killing all the bacilli.
( rifampicin and pyrazinamide)
 TB treatment regimens
• Initial(intensive) phase and a continuous phase.

• Initial Phase(2 months):- rapid killing of TB bacilli, infectious

pts. become non-infectious within about 2wks.symptoms
improve. Sputum smear +ve TB become sputum smear –ve
within 2months.

• Directly observed therapy is essential in the initial phase to

ensure that the pt. takes every single dose. This protect
rifampicin against the development of drug resistance.
 continue
• Continuous Phase:-(4-5 months) fewer drugs are necessary,
but for a long time. Eliminate remaining TB bacilli, kill
persisted.

• Directly observed therapy is the ideal when the pt. receives

rifampicin in the continuous phase.

• Retreatment cases:- The initial phase lasts 3 months with

directly observed therapy. The continuous phase lasts 5
months with close supervision.
 Childhood Tb Regimen(0-14yrs)
Category Indication Regimen
1 New TB cases New bacteriologic Intensive Continuous
confirmed TB. Phase phase
New clinically diagnosed 2HRZE 4HR
severe TB
New severe Extra
Pulmonary TB.
Specific condition TB Meningitis 2HRZE 10 HRE
Osteoarticular TB
Milliary TB. TB pericarditis
2 Retreatment cases Sputum Smear +ve: 2HRZE 4HR
Relapse, treatment failure 6HRZE Levofloxacin
And Return after default. 6HRZE full
 Anti-TB Drugs in Special Situations.
• Pregnancy: Don’t give streptomycin in pregnancy. use
ethambutol.

• Renal failure: rifampicin, isoniazid and pyrazinamide are safe.

• Liver disease: most anti-TB drugs can cause liver damage. If

you diagnose drug-induced hepatitis, stop the anti-TB drugs.
Wait until the jaundice resolves. Jaundice pts. who develop
TB should receive t/t regimen 2SHE/10 HE. Don’t give
pyrazinamide to pt. with liver disease. ( If ALT is 3 times raise
with symptoms or isolated increased enzymes 5 times then
stop ATT till resolve the enzymes)
 Indications of Steroid in TB Pts.
• TB Meningitis(decrease consciousness, neurological defects, or
spinal block)

• TB pericarditis( with effusion or constriction).

• TB pleural effusion(when large with severe symptoms).

• Hypoadrenalism(TB of adrenal glands).

• TB laryngitis(with life threatening airway obstruction).

• Severe hypersensitivity rx to anti-TB drugs.

• Renal tract TB( to prevent ureteric scarring).

• Massive lymph node enlargement with pressure effects.
 Monitoring TB Pts. During t/t

• Smear +ve pulmonary TB:- At the end of initial phase, if still

+ve give 4 drugs for 4 wks, then go for continuation phase
( even smear +ve after extra 4wks of initial phase t/t).

• Sputum smear in continuation phase:- In 6 months or 8

months regimens a +ve sputum smear at 5 months or any
time after 5 months means treatment failure. Change t/t
category 2 and starts retreatment regimen.
 continue
• Sputum smear on completion of treatment: 6 months or 8
months t/t regimen , Negative sputum smear at 5 and 7or 8
months –bacteriological cure. Don’t give more than
recommended period.

• Sputum Smear Negative PTB: X-ray at the end of 1st month

smokers and above 40 yrs to r/o possibility of malignancy.
Sputum examination at 2 months.
 continue
• Extra pulmonary: Sputum examination at the end of second
month if earlier chest x- ray has not already been done .

• Recording t/t outcome in PTB pts.( Cured, T/t completed.t/t

failure, died, defaulted/t/ interrupted and transferred out.)
 Drugs side effects
• Minor : gastro-intestinal,jt.pains---opd mange.

• Major: jaundice, severe rash-refer to central hsp.

• When to stop anti-TB drugs: Hearing loss or disturbance

balance– streptomycin.
2) visual disturbance( poor vision and color perception)-
ethambutol.
3) renal failure,shock or thrombocytopenia—rifampicin.
 HIV related TB
• 11.5million HIV infection people world wide were co-infection
with Tuberculosis.

• HIV –ve 5-10% risk of developing TB.

• HIV +ve 50% risk of TB.

• Increased susceptibility to infection and progression of

Tuberculosis.
• Wt.loss and fever are more common in HIV PTB pts. Than who
are HIV negative.
 continue
• The case fatality of TB/HIV pts of 1yr after
starting TB treatment is about 20%. Greater
than HIV negative.
• Case fatality is less with SCC than with the old
standard regimen(2SHTor SHE /10 HT or HE).
• The recurrence rate is similar in HIV +ve and
HIV –ve TB pts who complete t/t.
 Prevention
• Environmental control
• Face mask
• Education
• BCG.
• PTB suspects.
 Drug resistant
• At present the NTP in Nepal is not in a position to supply
treatment to MDR TB pts.
• Drug resistant tuberculosis: tuberculosis excreting bacilli
resistant to one or more drugs.
• Failure of t/t: Excreting bacilli after 5 months of
chemotherapy.
• Chronic case: Received 2 or in some situation more course
of chemotherapy and usually but not always Excreting
MDR bacilli.
• MDR:bacilli are resistant to at least isoniazid and rifampicin.
 MDR TB new treatment regimen
Intensive phase Continuation phase
(8-12 months) (12 months)

Kanamycin(Km) Pyrazinamide(Z)
Pyrazinamide(Z) Levofloxacin(Ofx)
Levofloxacin(Ofx) Ethionamide(Eto)
Ethionamide(Eto) Cycloserine(Cs)
Cycloserine(Cs)
 Extensive drug resistant t/t regimen
First phase Second phase
12 months 12 months
(Intensive phase) ( Continuation phase)
Inj.Capreomycin (Cm) (1g vial) Clofazimine (Cm) 100mg
Clofazimine(Cfz) (100mg) Moxifloxacin(Mfx) 400mg
Moxifloxacin (mfx) (400mg) Linezolide
Linezolide Cycloserine(cs)250mg
Cycloserine(cs) (250mg) • Amoxicllin ( 500mg).Clavulate(125mg)
*Amoxicillin(500mg)/Clavulate( 125mg) (Amx/cla)
(Amx/Cla) • PAS (4g sachets)
PAS(4g sachets) • Pyrazinamide(Z) 400mg.
Pyrazinamide(z) 400mg.
 surgery
• Indications: Patient with bacilli resistant or
probably resistant. If the pt. has a large
localized cavity with little other disease,
reasonable lung function and only 2 or
3( weak) drugs available .