TUBERCULOSISDiagnosis & treatment

Dr. Fazli WahabFCPS(Med), FCPS(Pulmonology)

Assisstant Prof Peshawar Medical College

Diagnostic ToolsMicroscopy

◦AFB smear◦Histology

AFB Culture

Radiology

Tuberculin skin test

Serological Tests

AFB smearRapid 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 MonthsContinuation 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