1. Tuberculosis in Children and Young Adults
Good Morning and welcome. It gives me great pleasure to begin our conference on research priorities in pediatric TB with a discussion on the global epidemiology of childhood tuberculosis.
FARHAD SALEHZADEH MD.
2009 ARUMS

2. TB in PEDIATRIC

3. TB in PEDIATRIC

4. Transmission and Pathogenesis

5. TB

7. TB in PEDIATRIC Primary infection Reactivated TB
Progressive post primary TB
Miliary TB
Lymphohematogenesis TB

8. Tuberculosis is one of the great imitator.
Evaluation for TB
Medical history
Physical examination
Mantoux tuberculin skin test
Chest radiograph
Bacteriologic or histologic exam
“Clinical judgement”
Tuberculosis is one of the great imitator.

9. Common Sites of TB Disease
Lungs
Pleura
Central nervous system
Lymphatic system
Genitourinary systems
Bones and joints
Disseminated (miliary TB)

10. Conditions That Increase the Risk of Progression to TB Disease
HIV infection
Substance abuse
Recent infection
Chest radiograph findings suggestive of previous
Diabetes mellitus
Immunosuppressed
End-stage renal disease
Chronic malabsorption syndromes
Low body weight (10% or more below the ideal)

11. Systemic Symptoms of TB
Fever
Chills
Night sweats
Appetite loss
Weight loss
Easy fatigability

12. Bone and Joint TB, Miliary TB, or TB Meningitis in Children
Extrapulmonary TB
In most cases, treat with same regimens
used for pulmonary TB
Bone and Joint TB, Miliary TB,
or TB Meningitis in Children
Treat for a minimum of 12 months

13. TB in Children WHO estimate of TB in children 1.3 million annual cases
450,000 deaths
15% of TB in low-income countries children vs. 6% in United States
In 1989, the World Health Organization, or WHO, estimated that there were 1.3 million annual cases, and 450,000 deaths due to tuberculosis among children less than 15 years of age. Unfortunately, these estimates have not been revised more recently. It is estimated that 15% of all TB in low-income countries occurs among children less that 15 years of age compared with only 6% in the United States, and even lower percentages in some European countries.

14. Risk of Progression to Disease
Age
43% in infants (children < 1year)
25% in children aged one to five years
15% in adolescents
10% in adults
Recent Infection
Malnutrition
Immunosuppression, particularly HIV
Once infected, certain risk factors increase the risk of progression to TB disease. A strong risk factor for disease is age of infection, with infants having a 43% risk of disease progress, children aged 1 to 5 a 25% risk of progress, and adolescents a 15% risk of disease progress. Adults, by contrast, have a 10% lifetime risk once infected. Recent infection, including among adults, is another risk factor for disease progression, as is malnutrition and immunosuppression. Immunosuppression due to the human immunodeficiency virus, or HIV, is the most potent risk factor for disease progression now known among adults.
In the remainder of this talk, I will focus on TB DISEASE in children
Miller, 1963

15. Childhood TB diagnosed by:
Combination of :
Contact with infectious adult case
Symptoms and signs
Positive tuberculin skin test
Suspicious CXR
Bacteriological confirmation
Serology

16. Childhood TB
Retrospective study of 43 hospitals using National TB Data from 1998
2739 cases in children (11.9%)
1.3% smear-positive, 21.3% smear-negative, 15.9% extrapulmonary
Poor outcomes
45% completed treatment
17% died
13% default
21% unknown
A recent study published this year is an excellent example of the possibilities of using surveillance data. In a study in Malawi, a retrospective study was performed using records at all 43 public hospitals which treat TB in Malawi in 1998 and National TB program records. This study found 2739 cases of TB in children, representing nearly 12% of all TB in TB in children accounted for 1.3% of all smear-positive cases, 21.3% of smear-negative cases, and 15.9% of all extrapulmonary cases during This analysis also revealed poor outcomes among children: only 45% completed treatment, 17% died, 13% defaulted, and in 21%, the treatment outcome was unknown.
Harries AD et al. Int J Tuberc Lung Dis ; 6:

17. TB and BCG Vaccination
Efficacy for adult pulmonary TB 0-80% in randomized clinical trials
Best efficacy against serious childhood disease
64% protection against TB meningitis
78% protection effect against disseminated TB
BCG important for young children, inadequate as single strategy
Finally, in the next section, I would like to briefly mention a few topics of importance in understanding the epidemiology of childhood TB: BCG vaccination, TB/HIV coinfection, and drug resistance. BCG has an important, but limited role in the control of TB, particularly childhood TB. While the efficacy of BCG in preventing adult pulmonary TB has varied from 0 to 80% in randomized clinical trials, it has shown the best efficacy against serious forms of childhood disease. In a published meta-analysis of BCG efficacy, it had a 64% protective effect in preventing TB meningitis in children and a 78% protective effect in preventing disseminated TB among children. Clearly, BCG has an important role in preventing serious disease in young children. However, BCG alone is insufficient to prevent children from TB.
Colditz GA et al. JAMA 1994; 271:

21. TB PEDIATRIC

22. In older children and adults the distinction between
TB infection and disease is usually clear and often
separated by a period of years before the onset of
reactivation-type disease. A major reason for making
the distinction between infection and disease is because
each is treated differently. Infection is treated
with one medication, whereas disease is treated with at
least three or more anti-TB drugs.

23. A diagnosis of latent TB infection (LTBI) can be made solely on clinical grounds and a positive TST or INF--releasing assay (IGRA).

25. The IGRAs results are unaffected by prior BCG vaccination.
IGRAs are highly
specific and correlate well with known exposure history.
IGRAs appear to be sensitive, at least in children
over 2 years of age. It is reasonable to hold off on
treatment in a TST, IGRA asymptomatic child
who is over age 2 years and has a normal CXR.

27. TB disease are a chronic cough for more than 21 days,
Worldwide the most common symptoms of pediatric
TB disease are a chronic cough for more than 21 days,
a fever 38°C for 14 days (after common causes such
as malaria and pneumonia have been excluded), and
weight loss or failure to thrive.1 Any child with any of
these symptoms for a shorter duration than described
above and a history of contact to an index case should
have a TST planted and diagnostic workup for TB,