Clinical Management of TuberculosisDato Dr Hj Abdul Razak Muttalif MBBS, MSc, M.Med, AM, FCCP Consultant Chest Physician & Head Department of Respiratory Medicine Hospital Pulau Pinang

Diagnosis of Tuberculosis

Pulmonary Tuberculosis Symptoms & Signs Investigations

Sputum AFBs X 3, AFB C&S (egg based media, BACTEC)

Chest X-rays Mantoux test

Duration of symptoms from first visit70 60 50 40 30 20 10 0 Days Weeks Months Years Percent

Razak,Norhafizah,Norlidar,Norhashimah. C.C.HKT

2.Microbiology

Sputum AFB/AFB C+S Most cost effective method Categorization for treatment

AFB +ve AFB -ve

3. Serology Mantoux Test Antibody/antigen PCR

More than 10mm is positive

2TU in 0.1 ml, read after 72 hours

In children more than 15 mm

4.CXR Upper lobe opacity Cavity ( 1 cavity= 1 million bacilli) Miliary Effusion

Radiological classification Minimal

Slight lesion without cavitations, confined to a small part of one or both lungs. Total extent of lesions should not exceed the volume of lung which lies above the second chostosternal junction and the spine of the fourth vertebra

Radiological classification Moderately advanced

One or both lungs may be involved. Total extent of lesion should not exceed the following:

i) Not exceeding total volume of one lung ii)Dense lesions not exceeding one third lung volume Iii)Total diameter of cavity less than 4cm

Radiological classification Far advanced

Lesions more extensive than moderately advanced

Extra pulmonary TB (TB outside the lungparenchyma)

Tuberculous lymphadenitis by LN biopsy sent for DS, C&S, cytology TB effusion by pleurocentesis, pleural biopsy GUT by radiological, urine C&S TB bones/joints by x-rays, HPE Miliary TB by CXR,liver biopsy TB meningitis CSF microscopy, biochemestry C&S, PCR for TB

Tuberculosis Classification Pulmonary tuberculosis

Smear positive Smear negative

Extrapulmonary tuberculosis Pulmonary with Extrapulmonary

tuberculosis

Pulmonary Tuberculosis Smear positive

Two sputum DS positive One sputum positive with CXR changes of TB One sputum positive with culture positive Three DS negative with CXR abnormalities and decision to treat as TB Initial sputum DS negative but culture positive

Smear negative

Extra Pulmonary TB Extra-pulmonary TB

TB of organs other than lung parenchyma Based on culture, histology or strong clinical evidence and a decision to treat Tuberculosis involving lung parenchyma as well as any other part of the body

Pulmonary with extra-pulmonary

Extrapulmonary TB classification of severity Severe

Meningitis, miliary, pericarditis, peritonitis, bilateral or extensive pleural effusion, spinal, intestinal, genito-urinary Lymph node, unilateral pleural effusion, bone (excluding spine), peripheral joint, skin

Less severe

Definition of terms New case Relapse case Chronic case Cure Treatment failure Treatment after interruption Transferred in case

Definition New case Newer had TB treatment or has take treatment for less than 4 weeks in the past Relapse case

Sputum positive relapse Declared cured of any form of TB in the past by a doctor has become sputum smear positive Sputum negative relapse As above, developed active disease based on bacteriological, histological clinical and radiological assessment

Definition Chronic case

A patient who remained or becomes smear positive again after completing a fully supervised re-treatment regimen A smear positive patient has negative sputum at the end of treatment and another negative sputum one month or more prior to completion of treatment

Cure

Definition Treatment failure A patient while on treatment becomes again smear positive 5 months or later after commencing treatment A patient who was initially negative became positive after second month of treatment Treatment after interruption

A patient who interrupts treatment for 2 months or more then returns with smear positive or negative but still active TB based on clinical or radiological assessment

Definition Transferred in case

A patient transferred from another centre for continuation of treatment. The new centre undertakes the responsibility of treatment Not considered a transfer if a patient just come to centre for treatment only

Tuberculosis in children Infection from adults via coughing and

droplets From milk and food Through skin

Changes after infection in children Primary complex Pleural effusion Acute cavitation of focus Ring shadow Lymph node at root of lung Blood spread

Liver, bones, brain kidneys

?TB in children Failed to gain weight Wheezing, cough, fever, LOA, LOW Pleural effusion Ascites Joint swelling, spinal lump Lymph node, discharging sinus Headache, irritability

FAMILY HISTORY OF TB!!!!

Two Diseases - one Patient

TuberculosisT helper lymphocytesProtective Immunity

Immunopathology Stress GlucocorticoidsTh1

and disease

Th1

+

Th2

Tissue damageMacrophage activation

The immune response

Altered cytokines in HIV/TB patientsNormal CD4 INF IL-12 IL-10 TNF 231 759 7.5 0.6 Tb 569 10 12.5 424 370 TB/HIV 201 2.2 4 735 232 21 Advanced HIV 130 0.1 2.2

TH1 cytokines---IL-12,INF Inhibitory cytokines IL-10

S.swaminathan et al 2002

Effect of TB on HIV TB causes release of TNF and

stimulates multiplication of virus inside T cells TB helps in destruction of CD4 cells Helps release of new virions from HIV infected cells

Effect of HIV on TB Decrease macrophage activating

lymphokines Increase in number of CD8 cells Increase tissue destruction T4 lymphopenia HIV promotes T4 destruction and CD4 cells impairment

Effect of HIV on TB

HIV Status Negative Positive

Lifetime risk of developing TB 5-10% 50%

Chest Imaging (in HIV +ve case) Not used for screening Limited to symptomatic Variety of manifestations Normal CXR in 15%,CT scan used only

for further diagnostic procedures Gallium scan for PCP

CXR findings in HIV patients (1) Normal

PCP, MTB, Histoplasma, Kaposi PCP, MTB, bacterial, Cryptococcus,aspergillus PCP, MTB, bacterial Cryptococcus, histoplasma

Focal infiltrates

Diffuse infiltrates

CXR finding (2) Nodular PCP, Cryptococcus, Histoplasma, Norcardia, CMV, Toxo Cavitary

Bacterial, PCP, MTB, Aspergilluss

Lymphadenopathy PCP, MTB, Cryptococcus, Kaposi, lymphoma Pleural effussion

Bacterial, PCP, MTB, lymphoma

Pneumothorax PCP, MTB

Pneumococcal

Staphylococcal

Lung abscess

Acceleration of TB in HIV patientsAmong 30 residents from a housing facility for HIV infected persons, 11 patients had active TB and were noted to have the same restricted fragment length polymorphisms (RFLPs) 4 others had positive TST 6 of the 28 staff members had positive TST Conclusion: Newly acquired TB infection in HIV infected patients can spread readily and progress rapidly to active disease. Heightened surveillance for TB in facilities as this is neededCharles et al. NEJM 1992;326:231-5

PTB mini epidemic in a church Gospel Choir Five cases of TB, one index and three

secondary All three had same DNA fingerprinting All three were tenors (not sopranos) Singing, location of ventilation and exposure time were contributing factors

Bonita et al Chest 1998; 113: 234-37

PTB in early and late HIV infection

Features of PTB

Stage of HIV infectionEarly LateOften resembles primary PTB Often negative Often infiltrates with no cavities

Clinical picture Sputum smear CXR

Often resembles post primary PTB Often positive Often cavities

CD4 count and CXR 35 subjects, 26 had CD4