Pulmonary tuberculosis primary infection

progressive primary infection

Chronic pulmonary TB

multidrug resistant pulmonary tuberculosis

miliary tuberculosis

TB: Airborne infection

TRANSMISSION

person to person, generally from adult to child and not vice-versa nor from child to child

Transmission rarely occurs by direct contact with an infected discharge or a contaminated fomite

The lung is the portal of entry in >98% of cases.

Factors that would ENHANCE transmission

1. when the patient has a positive acid-fast smear of sputum

2. an extensive upper lobe infiltrate or cavity

3. copious production of thin sputum

4. severe and forceful cough

5. Environmental factors such as poor air circulation

Stages of Tuberculosis

1. Primary infection

2. Progressive primary TB

3. chronic pulmonary TB

Primary Infection

First infection with tubercle bacilli

Found in children

Clinical course depends on the childs health status

If malnourished widespread (post primary or progressive primary stage)

Pathogenesis

Inhaled Tb bacilli reaches alveoli nonspecific inflammatory reaction Ghons tubercle or primary focus(initial tissue infection)

GHONS COMPLEX (Primary complex)

1.Ghons focus subpleural focus in the upper part of lower lobe/ lower part of upper lobe

2. lymphangitis

3. regional (hilar) lymphadenopathy

Develops within 2-8 weeks from onset of infection

PRIMARY INFECTION

Insiduous onset

Incubation period: 2-10 wks

No symptoms as a rule

But if (+) : Easy fatigability, low grade fever

NOT contagious

Cell mediated immunity is responsible

Primary Pulmonary TB

BUT if the immune system is weak , there can be disseminated TB

In 3-6 months , it can reach the brain (meningitis, tuberculoma, TB abscess)

In 1 year: bones

In 5-25 yrs : kidneys

Only Adults Transmit TB

Number of bacilli in sputum

Adult Child

108 104

Need about 105 organisms/ml for positive smear

Key features suggestive of TB

The presence of three or more of the following should strongly suggest a diagnosis of TB:

Chronic symptoms suggestive of TB

Physical signs highly of suggestive of TB

A positive tuberculin skin test

Chest X-ray suggestive of TB

History of contact with a source

RISK for DISSEMINATION

Conditions that adversely affect cell-mediated immunity predispose to progression from tuberculosis infection to disease (HIV, AIDS)

BCG VACCINE

Used as a diagnostic test for TB

If the child is previously sensitized to tuberculo protein accelerated local response

BCG VACCINE

Dose: 0.05ml for NB up to 1 month

0.1ml for >1month

Route: intradermal

Within 2-3 weeks induration

4-6 weeks pustule

Healing in 8-12 weeks time

Efficacy: >50-80%

BCG VACCINE

Cannot prevent people from getting primary TB

BUT it can prevent people from getting extrapulmonary TB ( meningitis, diseminated TB, etc)

Tuberculin Skin Test (Mantoux test)

Intradermal injection of 0.1ml of PPD

amount of induration is measured in 72 hr

Once positive, a PPD will always be positive.

Mantoux test

Sensitized lymphocytes (CD4 and CD8) recognize the antigen local inflammation

False positive results

Prevalence of non-tuberculous mycobacteria

Prior BCG vaccination

Repeated TST resulting in sensitization

Incorrect interpretation of the result

False negative results

Severe tuberculosis

Previous viral disease

Very young age (

Interpretation of TST size of induration interpretation

(regardless of BCG status)

>15 mm strongly POSITIVE

> 10mm POSITIVE

> 5mm Positive if any of the ff is present: immunocompromised state, history of

contact with source-case, signs and symptoms suggestive of TB, CXR

findings suggestive of TB

LAB

Sputum exam

traditional culture specimen in young children is the early morning gastric acid obtained before the child has arisen and peristalsis has emptied the stomach of the pooled secretions that have been swallowed overnight.

Interferon Gamma Release Assay (IGRA)

Involves measurement of interferon-gamma (IFN-) released by T cells that have been sensitized by a prior exposure to M. tuberculosis

Response is measured after 1-24 hrs of incubation using ELISA or enzyme-linked immunospot (ELISPOT)

Interferon Gamma Release Assay (IGRA)

Expensive

Excellent specificity and good sensitivity

Do not distinguish LTBI from active TB disease

Nucleic acid amplification methods (NAATs)

Uses polymerase chain reaction

Positive NAATs support the diagnosis of TB but a negative result does not rule it out

Hence, they are not a replacement for conventional lab methods like AFB smear and culture

How is TB cured?

TB can be cured. DOTS (Directly-Observed Treatment Short

Course) is the recommended strategy to cure TB.

It ensures the right combination and dosage of anti-TB drugs.

It ensures regular and complete intake of anti-TB drugs.

Patient takes drugs every day with the help of a treatment partner.

CHEMOPROPHYLAXIS

Primary chemoprophylaxis

Given to tuberculin negative neonates, infants and children

TREATMENT

6 month regimen of Isoniazid (H), rifampicin (R) and 2 months of pyrazinamide (Z)

Ethambutol used in children with life- threatening TB or who are at risk for drug resistant tuberculosis

Streptomycin used to replace Ethambutol for children below 6 yrs and in the treatment of TB meningitis; reserved for multi-drug resistant TB

2 Phases of treatment: The intensive phase usually covers the first 2 months of

treatment. During this phase, most of the bacilli will be

killed. The sputum converts from positive to

negative in more than 80 % of the new patients within the first 2 months of treatment.

Phases of treatment: The continuation phase usually lasts 4-6 months, depending on the

treatment regimen. intended to eliminate the remaining dormant

bacilli. Since it is not possible to identify which

patients still have dormant bacilli, all patients should continue their treatment until the end of the prescribed period, to limit the number of relapses.

Common side effects:

Ethambutol : optic neuritis

INH : peripheral neuropathy

Rifampicin : Hepatotoxicity

Streptomycin: ototoxicity and vestibular dysfunction

Pyrazinamide - hepatotoxicity

Evaluation of response to TB

(-) Anorexia 3-6 months

(-) pulmonary infiltrates 2-9 months

(-) Hilar adenopathy 2-3 years

(-) Pleural effusion 6-12 wks

2. Progressive Primary Pulmonary Disease

A rare but serious complication of TB in a child occurs when the primary focus enlarges steadily and develops a large caseous center.

Liquefaction can cause formation of a primary cavity associated with large numbers of tubercle bacilli.

2. Progressive Primary Pulmonary Disease

s/s: child looks ill; distressing cough

sputum positive

Dx: CXR bronchopneumonic foci

3. Chronic Pulmonary TB

Aka Reactivation TB, Phthisis

usually represents endogenous reactivation of a site of tuberculosis infection established previously in the body.

Occurs in older children >10 years of age

Children with a healed tuberculosis infection acquired at 7 yr of age.

Usually happens in malnourished children

3. Chronic Pulmonary TB

3. Chronic Pulmonary TB

Now with the apical seedings (Simon foci) established during the hematogenous phase of the early infection.

usually remains localized to the lungs, because the established immune response prevents further extrapulmonary spread.

CXR: infiltrates or thick-walled cavities in the apex of the upper lobes, where oxygen tension is high and poor lymphatic drainage

Miliary Tuberculosis

A serious post primary complication due to massive invasion of the blood stream by tubercle bacilli

result in dissemination of the bacilli and a miliary pattern, with small nodules evenly distributed on the chest radiograph

Involves 2 or more non-contiguous anatomic sites (disseminated)

Miliary Tuberculosis

3 clinical forms of Miliary TB

1. typhoidal

2. pulmonary

3. meningeal

Extrapulmonary Tuberculosis

Disease involving anatomic structures other than the lung parenchyma

Most common form Tuberculous lymphadenitis (scrofula)

Results from lymphohematogenous spread

Drug - resistant TB

is a laboratory diagnosis

Features of a child suspected of having drug-resistant TB:

contact with a known case of drug-resistant TB

not responding to the anti-TB treatment regimen

recurrence of TB after adherence to treatment

All mono-therapeutic regimens (real or masked by combination with drugs to which bacilli are resistant) lead to treatment failure and to the development of resistance.

When three or more drugs are administered, the risk of resistance is practically zero.

spectrum of childhood TB

TB exposure: child with close contact a source case, no s/sx, (-) TST, no radiologic or lab findings for TB

TB infection: child with (+) TST, no radiologic or lab findings for TB

TB disease: child is TB symptomatic, (+) TST and/or positive radiologic or lab findings suggestive of TB

TUBERCULOSIS Clinical manifestations in pediatric TB may be

non-specific

TB is much more difficult to diagnose in children

Undiagnosed or untreated TB in a child is potentially serious,

More likely to develop severe or disseminated disease

Knowing how to administer and read PPDs, and to contextually interpret PPDs and CXRs is vital