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TUBERCULOSISDiagnosis & treatment
Dr. Fazli WahabFCPS(Med), FCPS(Pulmonology)
Assisstant Prof Peshawar Medical College
Diagnostic Tools
Microscopy◦AFB smear◦Histology
AFB Culture
Radiology
Tuberculin skin test
Serological Tests
AFB smear
Rapid and inexpensive
Granuloma
Mycobacterial Culture
Definitive diagnosis
Growth detected after 4–8 weeks.
Radiographic Procedures
The "classic" picture is that of upper-lobe disease with infiltrates and cavities,
X-ray chest appearance can be any of the followingInfiltrationCavitationsFibrosis with tractionEnlargement of hilar and mediastinal lymph node Pleural effusion/empyemaNodular/ Miliary shadows
Mantoux Tuberculin Test (MT)/ Tuberculin Skin Test (TST)
Test TB infection in adults and children
Patient status Positive Result
Healthy individuals with no exposure history
>15mm
Healthy individuals with exposure history or risk factors
>10mm
HIV +ve >5mm
Serological TestsNot routinely used
Polymerase Chain Reaction (PCR)
Interferon Gamma release assays (IGRS)
Enzyme Assays & Chromatographic assays:◦Unreliable & Ineffective methods◦No role in diagnosis in any form of TB◦Mycodot assay◦ ICT TB
Treatment
Two aims
◦Interrupt transmission
◦Prevent morbidity and death.
Anti-tuberculosis Drugs 1ST LINE DRUGS:
• Isoniazid (H) • Rifampicin (R)
• Pyrazinamide (Z) • Ethambutol (E) • Streptomycin (S)
1st line ATT Mode of Action
DailyDose (mg/kg)
Isoniazid (H) Bactericidal 5 (4-6)
Rifampicin (R) Bactericidal 10 (8-12)
Pyrazinamide (Z)
Bactericidal 25 (20-30)
Streptomycin (S)
Bactericidal 15 (12-18)
Ethambutol (E) Bacteriostatic 15 (15-20)
Regimens
Standard short course regimens 6-8 months.
An initial, intensive or bactericidal, phase and
A continuation, or sterilizing, phase.
DOTS
DOTS (directly observed treatment, short-course), the WHO-recommended TB control strategy.
New Cases
•Sputum smear positive pulmonary TB
•Sputum smear negative pulmonary TB
•Extra-pulmonary tuberculosis
Initial Intensive Phase
HRZE : 2 Months
Continuation Phase
HR: 4months OR HE: 6 Months
WHO Category I:• New SS +VE Pulmonary
TB• Severe Extra-Pulmonary• Severe SS –VE
Pulmonary TBWHO Category III:
New SS-VE Pulmonary TBExtra-Pulmonary (less severe)
RE-TREATMENT CASES/ WHOCategory II:•Relapse•Treatment Failures•Smear positive patients who have taken ATT for more than one month and defaulted
INITIAL INTENSIVE PHASE (3months)HRZES: 2MONTHS Then HRZE:1 Month
CONTINUATION PHASEHRE: 5 Months
No Treatment is better than Poor Treatment
Drug-resistant TB is caused by: ◦ Inconsistent or partial treatment, when patients do
not take all their medicines regularly for the required period.
◦ Doctors and health workers prescribe the wrong treatment regimens, or because
◦ The drug supply is unreliable.
The ultimate result is the multidrug-resistant TB (MDR-TB) or extensively-drug resistant TB (XDR-TB)
In MDR-TB the Mycobacterium Tuberculosis is resistant to Rifampacin and INH with or without resistance to other 1st ATT.
Treatment is difficult and expensive.
Prevention
The best way to prevent tuberculosis is to Treat.
Additional strategies include
◦BCG vaccination and
◦Treatment of persons with latent tuberculosis infection who are at high risk of developing active disease.
ATT in Special situationsPregnancy
Infants of T.B. mothers & Breast Feeding
Women on O.C.P
Renal Impairment
ATT Induced Hepatitis
HIV - Infected or AIDS
PregnancyH, R, Z, E : Safe
Streptomycin: OtotoxicMay cause deafness in babiesContraindicated
Infants of T.B. mothers & Breast Feeding
Mothers must continue A.T.T during feeding
Child should not be separated
Mother should cover her mouth during cough particularly if smear +ve
INH prophylaxis : 5 mg/Kg 2 months
Infants of T.B. mothers & Breast Feeding
Do T.T:If –ve
◦Stop INH, give BCGIf +ve
◦Continue INH 4 months◦Then BCG
Do not give BCG while on INH◦ INH resistant BCG
Rifampicin + INH – 3 months
Women on O.C.PRifampicin:
◦Hepatic enzyme inducer
◦O.C.P may become ineffective
Renal ImpairmentGeneral principle:
◦Standard chemotherapy◦Standard duration ◦Dose interval modification
Rifampicin and INH◦Safe and use normal dose
Pyrazinamide◦Needs dose interval adjustment
Renal ImpairmentEthambutol
◦Nephrotoxic , Renal excretion - 80% unchanged ◦Ocular toxicity – dose dependent◦Serum monitoring required
Amino glycosides – Streptomycin◦Nephrotoxic, renal excretion- 80% unchanged◦Needs dose interval adjustment in all stages
New recomandations◦Avoid Aminoglycosides
ATT Induced HepatitisUsually present early but may
present any time
Mild / transient derangement in LFTs is normal (15 – 20 %)
TYPES:◦Hepatocellular:◦Cholestatic◦Mixed
ATT Induced HepatitisRISK FACTOR
Age >35 years Female sex Oriental race (EAST ASIAN)Pre-existing liver disease Extensive tuberculosisHigh alcohol consumption Malnutrition and hypo AlbuminemiaOther hepatotoxic drugsSlow Acetylator statusHigh dosage in relation to body weight
Management↑ ALT/AST (< Twice normal)
◦ Continue ATT◦Check after 2 weeks
↑ ALT/AST (>Twice normal)◦Continue ATT◦Check LFTs weekly for 2 weeks ◦Then every 2 weeks until normal
Management↑ ALT/AST (>Thrice normal) + Symptoms
◦ Anorexia, Nausea, Vomiting, Abdominal Pain , Jaundice◦ STOP ATT
↑ ALT/AST (>5 time normal) OR ↑ Bilirubin◦ Even If Patient Asymptomatic◦ Stop ATT
If patient is smear –ve / Clinically stable◦ Wait until LFTs are normal◦ No need for alternate drugs
If patient is smear +ve / Clinically unstable◦ Start Ethambutol, Streptomycin and one of the
reserve drugs until LFT‘s are normal◦ Continue safe drugs until LFTs are normal
ManagementWhen LFT’s are normal
◦Reintroduce ATT to detect offending drugs◦Start with least hepatotoxic one by one
INH > RIF > PZAIf no reaction
◦Continue ATT◦Stop alternate drugs
If reaction has developed◦Stop offending drug◦Continue remaining drugs
Ensure adequate regimen and duration
HIV - Infected or AIDSStandard regimen – usually good
response ◦Drug reactions more common ◦Thiacetazone should be avoided ◦Prolonged treatment
Thanks