30% of the world population (2 billion) are infected with tuberculosis
2.3 million deaths from tuberculosis per year
8.4 million cases of tuberculosis illness per year
1.3 million cases and 450,000 deaths from tuberculosis occur in children each year
Tuberculosis in children is increasing by 6% annually
WHO estimates 159 & 370/100,000 new smear positive pulmonary TB & all other forms of TB respectively
40% of adult tuberculosis cases are HIV positive
Tuberculosis
A neglected disease, "Orphan disease"
Tuberculosis accounts for 20% or more of the TB case-load in many countries with high TB incidence
Mycobacterium species
M.tuberculosis
M.bovis
M.africanum
M.microti
M.canetti
Mycobacterium tuberculosis
Non–spore-forming, non-motile, pleomorphic, weakly gram-positive curved rods 2-4µm long which are obligate aerobes
Acid-fast
Form stable mycolate complexes with arylmethane dyes
Resist discoloration with ethanol and hydrochloric or other acids
Grow slowly, with a generation time of 12-24 hr
Isolation of mycobacterium from clinical specimens
1. On solid synthetic media - takes 3-6 weeks
2. In selective liquid medium using radiolabeled nutrients - 1-3 weeks
Exposure
A child has had significant contact with an adult or adolescent with infectious tuberculosis but lacks proof of infection
Infection
The individual has inhaled droplet nuclei containing M. tuberculosis, which survive intracellularly within the lung and associated lymphoid tissue
Disease
Signs, symptoms or radiographic manifestations of tuberculosis become apparent
An immunocompetent adult with untreated tuberculosis infection has approximately a 5-10% lifetime risk of developing disease
An infected child under 1 year of age has a 40% chance of developing disease within 9 months
Modes of tuberculosis transmission
Inhalation of airborne mucus droplet nuclei
Ingestion of milk (M. bovis)
Skin (direct contact)
Transplacental
Factors affecting tuberculosis transmission
Environmental factors: Crowding, poverty, UV light, genetics, close contact, dark & humid area, indoors, large # of bacilli in sputum
Patient factors: Positive acid-fast smear of sputum, extensive upper lobe infiltrate or cavity, copious production of thin sputum, severe and forceful cough
Factors affecting tuberculosis disease development
Immunity status
Nutritional status
Intercurrent illness
Length of time of exposure
Number of bacteria inhaled
Age at infection
Primary infection
The initial infection, including the parenchymal pulmonary focus and the regional lymph nodes
Reactivation
Pulmonary tuberculosis which occurs after 1 year of infection, usually characterized by cavitations
Disseminated and meningeal tuberculosis are early manifestations, often occurring within 2-6 months of acquisition
Significant lymph node or endobronchial tuberculosis usually appears within 3-9 months
Lesions of the bones and joints take several years to develop, and renal lesions become evident decades after infection
Extra-pulmonary manifestations are more common in children than adults (25-35% of children vs 10% of immunocompetent adults)
The risk for dissemination of M. tuberculosis is very high in HIV-infected persons, and reinfection can also occur in persons with advanced HIV or AIDS
Diagnostic methods for tuberculosis
X-rays
Tuberculin skin test
Culture
Biopsy
PCR
DNA finger printing
Ziel Nielson stain
Flourochrome stain
T-cell based interferon-gamma assays (QuantiFERON-TB gold, T-SPOT.TB)
Sputum acid-fast bacilli (AFB) smear
Chest X-ray
No shadow is typical for tuberculosis, and 40% of patients diagnosed as having TB by X-Ray alone may not have active TB disease
Tuberculin skin test (PPD)
Based on the delayed hypersensitivity which develops after infection, measurement done after 48 to 72 hours, transient reactions within 24 hours are considered negative, results based on measurement of induration (not erythema)
Causes of false negative PPD test
Severe protein-energy malnutrition
Measles
Overwhelming tuberculosis
Wrong techniques
HIV
Steroids
Cancer
Causes of false positive PPD test
Atypical mycobacterial infections
Hypersensitivity to constituents
BCG vaccination
Criteria for tuberculosis diagnosis in children
Positive PPD
Compatible radiology
Contact history
Symptom complex
Acid-fast bacilli
Miliary pattern on chest X-ray
Biopsy
Culture
Positive PPD in unvaccinated children under 5 years of age
Common sites are cervical lymph nodes, occasionally axillary and groin lymph nodes, mostly unilateral, TST (PPD) positive in 80% of patients but chest X-ray is normal in 70% of patients
Primary pulmonary tuberculosis
The primary complex includes the parenchymal pulmonary focus and the regional lymph nodes, approximately 70% of lung foci are subpleural, all lobar segments of the lung are at equal risk for initial infection, the hallmark is the relatively large size of the regional lymphadenitis compared with the relatively small size of the initial lung focus
Symptoms of primary pulmonary tuberculosis in children
Nonproductive cough and mild dyspnea are the most common symptoms, severe symptoms like fever, cough with sputum production, weight loss, and night sweats are less common, 50% of infants and children with radiographically moderate to severe pulmonary tuberculosis have no physical findings
Progressive primary pulmonary tuberculosis
A rare but serious complication where the primary focus enlarges steadily and develops a large caseous center, characterized by high fever, severe cough with sputum production, weight loss, and night sweats
Primary complex
Includes the parenchymal pulmonary focus and the regional lymph nodes