WORK UPS AND MANAGEMENT. Traditional and New Diagnostic Approaches DIAGNOSTICSAPPLICATIONS Traditional approaches - Symptom-based -TST -TB Culture --

WORK UPS AND MANAGEMENT

Traditional and New Diagnostic Approaches

DIAGNOSTICS APPLICATIONS

Traditional approaches

- Symptom-based-TST-TB Culture-- AFB smear-- Chest radiograph

Probable active TBEvidence of MTB InfectionBacteriologic Confirmation of active TB

Probable Active TB

New Diagnostic Approaches

ORGANISM BASED-Colorimetric cultures systems-- phage based test

-- Microscopic- based observation drug susceptibility (MODs) assay

Bacteriological confirmation of active TBProbable active Tb and detection of rifampin resistanceProbable active TB and detection of resistance

Traditional and New Diagnostic Approaches

DIAGNOSTICS APPLICATIONS

New Diagnostic Approaches

ANTIGEN BASED ASSAYS-LAM detection assayIMMUNE BASED ASSAY-Antibody based assay--MPB-64 skin test-- T- Cell assaysSYMPTON BASED-Symptom based screening-Refined symptom based Diagnosis

Probable active TB

Probable active TBProbable active TBDiagnosis of Latent TB infection

Screening child contacts of adult TB casesProbable Active TB

Diagnosis of TB

• A positive culture with or without a positive smear for M. Tuberculosis is the gold standard for the diagnosis of TB

In the absence of bacteriologic evidence , a child is presumed to have active TB if > 3 crteria are present:

• Exposure to an adult/Adolescence with active TB (EPIDEMIOLOGIC)

• Signs and symptoms suggestive of TB (CLINICAL)• Positive tuberculin test (IMMUNOLOGIC)• Abnormal chest radiograph suggestive of TB (RADIOLOGIC)• Other lab findings suggestive of TB (LABORATORY)

OUR PATIENT

• TST – 12 mm induration• Chest X –ray showed evidence of primary

infection• Signs and symptoms of TB

Chest X- ray of the patient 11/24/10

The heart is not enlarged. There is slight haziness over the right lung base and the retrocardiac region, with nodular densities over the retrocardiac region, which may be due to lymph nodes. This may represent primary infection.Both hemidiaphragm and sinuses are normal. The visualized osseous structures are unremarkable. 11/24/2010

Management of Tuberculosis

Objectives of Drug Therapy in TB:

1. Cure the patient of TB2. Prevent death from active TB 3. Prevent relapse of TB4. Prevent the development of drug resistance5. Decrease transmission

Phases of Treatment

• Intensive Phase - efficient killing of actively dividing organisms- relief of symptoms- terminates transmision- prevents emergence of drug resistance

• Continuation Phase - kills irregularly dividing bacilli- sterilizes lesions and prevent relapse

Drug Administartion

• The optimal dosing frequency for new patients with pulmonary TB is daily throughout the course of therapy.

Alternative Regimens:(1)A daily intensive phase followed by tree times

weekly continuation phase [2HRZE/4H3R3] , provided that each dose is directly observed

(2)Three times weekly dosing throughout the therapy [2H3R3Z3E3/4H3R3] , provided that every dose is directly observed.

Essential Anti-Tuberculosis DrugsDRUG MOA DOSE RANGE

Single daily dose mkd

3X weekly mkd

INH -Bactericidal agent--Acts on extracellular and intracellular bacillary populations-- presumed to inhibit biosynthesis of mycolic acid (cell wall component ) and effects glycolysis , nucleic acid synthesis

10 -15 Max 300 mg

20-30Max 900 mg

Rifampicin -Bactericidal agent--Acts on extracellular and intracellular bacillary populations-- inhibits nucleic acid synthesis

10-20Max 600 mg

10-20Max 600 mg

Essential Anti-Tuberculosis DrugsDRUG MOA DOSE RANGE

Single daily dose mkd

3X weekly mkd

Pyrazinamide -- weak bactericidal but with potent sterilizing activity within macrophages, areas of acute inflammation

20-40Max 2 g

50 mgMax 2 g

Streptomycin - Bactericidal 20-40 max 1 g

Ethambutol -Bacteriostatic, but with some bactericidal action at higher doses -- acts on intra and extracellular bacillary populations-- presumed to inhibit synthesis of mycolic acid (cell wall component)

15- 25 Max 1.2 g

30-50Max 2.5 g

Essential Anti-Tuberculosis Drugs

DRUG ADVERSE REACTIONS

INH -- peripheral neuropathy-Other neurological disturbance, optic neuritis, toxic psychosis, generalized convulsions-- systematic or cutaneous hypersensitivity reactions during the first week of treatment-- hepatotoxicity

Rifampicin -Gastrointestinal intolerance-- if intermittent adminidtration: rash , fever, thrombocytopenia, flu like symptoms-- increases risk of hepatotoxicity if used with INH

Pyrazinamide -- hypersensitivity reactions--moderate rise in trasaminase levels -- Hyperuricemia-- arthralgia, particularly of shoulders

Essential Anti-Tuberculosis Drugs

DRUG ADVERSE REACTIONS

Streptomycin

-- sterile abscess-- vestibular, auditory function impairment-- hemolytic anemia

Ethambutol

-- retrobulbar neuritis ( reduced visual acuity, contraction of visual fields, green red color blindness)

TREATMENT

21 kgIsoniazid 200 mg/5mL (10 mkd) – 5.5 mLRifampicin 200mg/5mL (10 mkd)- 5.5 mLPyrazinamide 500 mg/5mL (20 mkd) – 4.5 mLEthambutol 400 mg/tab (20 mkd) - 1 tab