TuberculosisDR NWOKOMA

Outline

Burden of TBThe organismTransmission and organ involvement Pathogenesis of TBClinical featuresInvestigationschemotherapy

Burden of TB

TB is found globally About a third of the world population is

infected~ 1 person is infected per secondMost are asymptomatic and only about

10% of those infected are likely to develop active disease

Burden is worse in poorer countries

Burden of TB

Untreated, Mortality ~ 50-67%Treated and well supported mortality ~ 5%Relapse rate of 2-3% amongst those

considered cured after standard therapyMajor drain on economy : loss of man-hour

and school absenteeismAbout 8 m of nearly 2 billion infected

individuals become symptomatic every year

Burden of TB

Accounts for ~ 2m deaths per year, 90% of this occurs in developing countries

Age 15-54 years mostly affected (75% of cases) WHO declared TB as an emergency in 1993

HIV/AIDS has compounded the problem of TBDrug resistance is very high ~ 20%Multiple drugs: HAART and anti TB

◦Interactions◦expense

Burden of TB

Re-emergence of TB due to: PovertyNeglect of the diseaseCollapse of health facilities in depressed

economyHIV/AIDS scourge

The organism

Causative organism: Mycobacteria spp. (tuberculosis>>>> bovis>> africanum > microti)*

An obligate aerobic organism◦Acid fast Bacilli (due to presence of mycolic

acid** in the cell wall) *others are called non tuberculous

mycobacteria e.g. M. leprae** mycolic acid is also responsible for

caseous granuloma

The organism

Organism is slow growing (division: 15-20 hours vs ~20min. in E. coli)

Discovered by Robert Koch in 1882

Genome sequenced in 1998

Transmission and organ involvement

usually by inhalation of aerosols The risk of infection of a susceptible

individual is high with close, prolonged, indoor exposure to a person with sputum smear-positive PTB.

At risk people include:◦Immuno-compromised people

HIV/AIDS, severe malnutrition, immuno-supressant, DM, leukaemia, lymphomas

◦Close contacts including health care workers

Sources of PTB infection

1. Drivers using Air Conditioned cars

2. Domestic servant, house keepers or house help

3. Gardeners4. Personal cooks5. Hostel (especially in the

universities)

Transmission and organ involvement

M. bovis usually by ingestion of un-pasteurised infected milk

Organ involvement is broadly divided into: ◦Pulmonary (75%) or ◦extra-pulmonary

Sites other than lung = Extra-pulmonary TB

Pathogenesis of TB

Primary infectionin people who have not had any previous exposure

to tubercle bacilli multiplication of tubercle bacilli in the lungs.The resulting lesion is the Ghon focus. Lymphatics drain the bacilli to the hilar lymph

nodes. Ghon focus & related hilar lymphadenopathy form

the primary complex. size of infecting dose and strength of immune

response

Pathogenesis of TB

immune response stops the multiplication of bacilli.

a few dormant bacilli may persist.A positive tuberculin skin test only

evidence of infection. In a few cases the immune response is notstrong enough to prevent multiplicationdisease occurs within a few months.

Post-primary TB

occurs after a latent period of months or years

following primary infection. either by reactivation of dormant tubercle

bacilli acquired from a primary infection or by

reinfection. Reactivation may be in response to a

trigger

Post-primary TB

extensive lung destruction with cavitation; positive sputum smear; upper lobe involvement;

usually no intrathoracic lymphadenopathy. Patients with these lesions are the main

transmitters of infection in the commmunity

Clinical features

cough for more than 2 or 3 weeks;sputum production; weight loss. Respiratory: chest pain, haemoptysis,

breathlessness.Constitutional: fever, night sweats,

tiredness, loss of appetite,

Extrapulmonary TB

Common Less common Pleural effusion Empyema Lymphadenopathy Male genital tract(usually cervical) epididymitis, orchitis) Central nervous Female genital tract(meningitis, cerebral tuberculoma) (tubo-ovarian, endometrium) Pericarditis(effusion/constrictive) Adrenal gland Gastrointestinal Kidney

(ileocaecal, peritoneal) Skin (lupus vulgaris, tuberculids, miliary) Spine, other bone and joint

Investigations

three sputum samples for microscopy Chest Xray CLASSICAL PATTERN ATYPICAL PATTERN upper lobe infiltrates interstitial infiltrates (esp

lower zones)

bilateral infiltrates

cavitation intrathoracic lymphadenopathy pulmonary fibrosis and shrinkage no cavitation no abnormalities

Investigations

culture from clinical specimens (e.g. sputum,lymph node aspirate, cerebrospinal fluid) the gold standard for the definitive diagnosis

of TB. culture can also be tested in vitro for

sensitivity to anti-TB drugsLöwenstein Jensen, liquid culture media and automated systems

(e.g. Bactec)

Ziehl-Nelsen stain of M. tuberculosis

Drug classes

Drugs are grouped as first-line or second line based on:

Availability e.g. Fluoroquolones Toxicity e.g cycloserineEfficacy e.g PAS

chemotherapy

Prolonged therapy is the rule!Hitherto,INH + PAS for 18-24 monthsEven short course lasts 6 months!Short course consists of 4 initial drugs for

the first 2 months

First line drugs

INHEthambutolRifampicinPyrazinamide

INH (H)

RIF (R)

EMB (E)

PZA (Z)

Multi-drug Resistant TB (MDR-TB)First-line

• Resistant to the most effective first-line drugs (INH and RIF)

• Need aggressive management of side effects

• Requires 18 to 24 months of treatment given under direct observation and with assistance

Other 2nd-line

Injectable

Quinolone

OFX

LFX

MFX

SM

KM

AMK

CMETH

CS

PAS

Second-line Third-line

Other agentsAMX/CLV

ClofazamineClarithromycin

Second line drugs

Amikacin, Kanamycin, CapreomycinViomycinEthionamideCiprofloxacin, MoxifloxacinPara-aminosalicylic Acid

Standardised therapyRegimen Intensive

phaseDuration (months)

INH, Rif, PZM, Etham

2 months all drugs

4 months of INH & Rif

INH, Rif. - 9 months

INH, Rif, PZM, Strept.

2 months all drugs

4 months of INH & Rif.

PRINCIPLES OF CHEMOTHERAPY

I. 4 drug combination therapy is advocated for newly diagnosed cases of PTB while 5 drug therapy is used for resistant cases during the intensive phase therapy.

II. The use of short course chemotherapy (SCC

III.Drugs should be given in correct dosage based on age and weight.

IV.Instruct and ensure that drugs are taken regularly preferably by directly observed treatment short- course (DOTS).

V. Patient should be duly informed about the range and common side-effect of the drugs in use and should be sought for by the attending physician while patient is on treatments

PRINCIPLES OF CHEMOTHERAPY

I. Drugs should be given for the required duration of the regimen in use.

II. Drugs should be given once on an empty stomach using DOTS

III. The role of TB supervisors cannot be over-emphasized.

IV. All TB cases should have HIV -serological tests done .

V. There is a role for counselling in TB management.

VI. There are clear indications for adjuvant steriod use in TB managements.

VII.Treatment should be given to all TB patients free of charge since majority of TB cases cannot afford to buy the drugs

DOTS IN TB MANAGEMENT

DOTS (Directly Observed Treatment, Short-course) is the WHO- recommended strategy for the detection and cure of TB.

DOTS combines five elements: political commitment, microscopy services, drug supplies, monitoring systems, and direct observation of treatment.

TB can be readily and inexpensively cured with DOTS.

TB cost of the drugs and their administration is very small.

Every infectious patients cured reduces the risk to everyone of contracting TB

.

DOTS IN TB MANAGEMENT

DOTS can successfully and permanently cure more than nine in every 10 TB patients who complete the treatment.

DOTS can produce cure rates of 95 percent even in the poorest countries.

DOTS prevents new infections and the development of MDR-TB.

DOTS can add years of life to an HIV- positive person:

TB drug treatment can be as effective in curing TB in HIV- positive as in HIV-negative TB patients.

ADJUVANT STEROLD USE IN TB

INDICATIONS:

1. Tb pericarditis

2. Tb pleural effusion

3. Tb meningitis

4. Tb laryngitis

5. Tb of the adrenal gland

6. Renal tract tb

7. Severe hypersensitivity to anti-tb drugs.

8. Massive lymph node enlargement with pressure effect.

REFERENCE: E. A DOSUMU. TUBERCULOSIS (2001)

INDICATION FOR SURGERY IN TB 1. Patient with PTB, cured or on treatment, has recurrent severe

haemoptysis as a result of an Aspergilloma.

2. Surgical drainage of a tuberculous empyema or massive tuberculous pleural effusion has failed to clear with chemotherapy.

3. Rarely, there is surgery to relieve intestinal obstruction secondary to adhesions from treated abdominal tuberculosis.

4. Rarely, pericardiectomy is considered due to constrictive pericardities that could have developed years after TB pericarditis.

5. Rarely, there is removal of mediastinal glands in children causing compression of the trachea or large bronchi or biospy of a mass for histological diagnosis of EPTB.

REFERENCE: E. A DOSUMU. TUBERCULOSIS (2001)