1. Prevention of tuberculosis. Targeted Tuberculin Skin Testing
Lecturer MD, Ph.D. Furdela Victoria
Assistant Professor, Pediatrics Department #2, Ternopil State Medical University, Ukraine

2. Tuberculosis in Children and Adolescents
Epidemiology
Public Health Aspects & TB Control
Targeted Tuberculin Skin Testing
Contact Investigations
BCG Vaccine
Treatment of Latent TB Infection and TB Disease

3. Global Epidemiology of TB
Tuberculosis remains the leading infectious disease in the world
More than 40% of the world’s population (>2 billion people) are infected with M. tuberculosis
In the 1990s:
90 million new cases
30 million deaths
Among children <15 years of age:
Approximately 13 million cases
5 million deaths

4. Reported TB Cases United States, 1982-2003
28,000
24,000
No. of Cases
20,000
16,000
12,000
1983
1987
1991
1995
1999
2003
Year

5. Number of TB Cases in U. S. -born vs
Number of TB Cases in U.S.-born vs. Foreign-born Persons United States,
No. of Cases
CDC

6. Trends in TB Cases in Foreign-born Persons, United States, 1986-2003
No. of Cases
Percentage 00 01 02 03
CDC

7. Reported TB Cases by Age Group United States, 2003
<15 yrs
(6%)
65+ yrs
(20%)
yrs
(11%)
yrs
(34%)
yrs
(29%)

8. Summary of Epidemiology of TB
Cases and case rates are on the decline
Foreign born persons account for more than 50% of U.S. cases
New Jersey: 70%
TB in children:
Highest risk for disease:
<5 years of age
Foreign born children
60% of cases develop within 18 months of arrival in U.S.
Most common countries of birth: Mexico, Philippines, Vietnam
Varies depending on immigration patterns, i.e., recent increases in case among children from Sub-Saharan Africa and Eastern Europe
Racial and ethnic minorities

9. Significance of Tuberculosis in Children
A case of tuberculosis in a child is considered a “sentinel healthcare event” representing recent transmission of TB within the community

10. Children <15 years with TB by Site of Disease

11. Children <15 years with TB: Extrapulmonary Disease

12. TB Control In the United States
Identification of new cases of TB
Initiation of appropriate treatment
Directly observed therapy
Contact Investigations
Identify persons at risk for infection
Targeted tuberculin testing
Identifies persons at high risk for TB who would benefit by treatment of LTBI
Treatment of latent TB infection (LTBI)

13. Mantoux Tuberculin Skin Test
Specificity of the test varies depending on the prevalence of LTBI and the frequency of cross-reactions to the PPD antigen in a given population
In a population with relatively high frequency cross-reactions the specificity of the PPD is <95%
Decreases the positive predictive value of positive test in a low risk population
If the specificity is 90% in a low risk population with a prevalence of LTBI of 1%:
Positive predictive value of TST: 8%
92% of positives are false positives
As prevalence of LTBI increases the PPV increases

14. Mantoux tuberculin skin test

15. AAP Recommendations: Targeted Tuberculin Skin Testing
Risk of exposure to TB should be assessed at routine healthcare evaluations
Only children with an increased risk of acquiring TB infection or disease should be considered for testing
Frequency of testing should be according to the degree of risk of acquiring infection
“Screening” is an inefficient way to control tuberculosis

16. Targeted Tuberculin Testing Risk-Assessment Questionnaire
Was your child born outside the United States?
Africa, Asia, Eastern Europe, Latin America
Has your child traveled outside the United States? >1 week
Has your child been exposed to anyone with TB disease? TB or LTBI, nature of contact
Does your child have close contact with a person who has a positive TB skin test?

17. Targeted Tuberculin Testing Risk-Assessment Questionnaire
Depending on local epidemiology and priorities other possible questions include:
Does your child spend time with anyone who has been in jail or a shelter, uses illegal drugs or has HIV?
Has your child had raw milk or eaten unpasteurized cheese?
Is there a household member born outside the U.S.?
Is there a household member who has traveled outside the U.S.?

18. AAP Recommendations: Tuberculin Skin Testing
Children for whom immediate TST is indicated:
Contacts of persons with confirmed or suspected infectious tuberculosis (contact investigation)
Children with CXR or clinical findings suggesting TB
Children immigrating from endemic countries (e.g., Asia, Middle East, Africa, Latin America)
Children with histories of travel to endemic countries and/or significant contact with indigenous persons from such countries

19. AAP Recommendations: Tuberculin Skin Testing
Children who should have an annual TST:
Children with HIV infection
Incarcerated adolescents

20. AAP Recommendations: Tuberculin Skin Testing
Some experts recommend that these children should be tested every 2-3 years:
Children exposed to the following persons:
HIV-infected
Homeless
Residents of nursing homes
Institutionalized or incarcerated adolescents or adults
Users of illicit drugs
Migrant farm workers
Foster children with exposure to adults in the preceding high risk groups

21. AAP Recommendations: Tuberculin Skin Testing
Children who should be considered for TST at 4-6 and years of age:
Children whose parents immigrated (with unknown TST status) from regions of the world with high prevalence of tuberculosis
Children with continued potential exposure by travel to endemic areas and/or household contact with persons from endemic areas (with unknown TST status)

22. Administering the Tuberculin Skin Test
Inject intradermally 0.1 ml of 5 TU PPD tuberculin
Produce wheal 6mm to 10mm in diameter
Placed and read by experienced health professionals

23. Reading the Tuberculin Skin Test
Read reaction hours after injection
Measure only induration
Record reaction in millimeters

24. Positive TST in Children: Definitions
Takes into account the following:
Risk of infection (exposure)
Risk of progression to disease
Immune status
Age

25. Positive TST Results: Infants, Children, and Adolescents
TST considered positive at >5 mm induration when:
In close contact with known or suspected contagious cases of tuberculosis
Suspected to have tuberculosis disease:
CXR consistent with active or previously active tuberculosis
Clinical evidence of tuberculosis
Receiving immunosuppressive therapy
With immunosuppressive conditions
With HIV infection

26. Positive TST Results: Infants, Children, and Adolescents
TST considered positive at >10 mm induration in children:
At increased risk of disseminated disease:
Young age: <4 years of age
Other medical conditions: Hodgkin disease, lymphoma, diabetes mellitus, chronic renal failure, malnutrition
With increased exposure to tuberculosis disease
Born or whose parents were born in high-prevalence regions of the world
Frequently exposed to adults who are HIV-infected, homeless, users of illicit drugs, residents of nursing homes, incarcerated or institutionalized persons, migrant farm workers
Travel and exposure to high-prevalence regions of the world

27. Positive TST Results: Infants, Children, and Adolescents
TST considered positive at >15 mm induration:
In children >4 years of age without any risk factors

28. Evaluation of the Child with a Positive TST
Evaluation of all children with a positive TST should include:
A careful history
Household investigation
Physical examination
Chest radiographs (PA & lateral)

29. Treatment of Latent Tuberculosis Infection in Children
INH 10 mg/kg (max., 300 mg) PO daily for 270 doses
Alternative: Twice weekly directly observed (DOT) INH mg/kg (max., 900 mg) PO for 72 doses
Monitor index case isolate sensitivities
Hepatotoxicity from INH is rare in children:
A monthly assessment for clinical evidence of hepatotoxicity should be made: loss of appetite or weight, nausea, vomiting, abdominal pain, jaundice
Routine monitoring of LFTs is not indicated

30. Tuberculosis Control in the United States
Contact Investigations
“The most reliable TB control program is based upon aggressive and expedient contact investigations, rather than routine screening of large populations with low risk.”
Can be complex, require experience and often a lot of detective work.

31. Tuberculosis Exposure in Children
History, PE, TST, CXR done
CXR is done regardless of TST result
IF:
Asymptomatic and physical examination is normal
TST is negative
Chest X-ray is normal
AND IF <4 years of age START: Isoniazid (INH) 10 mg/kg (max., 300 mg) PO once daily

32. Tuberculosis Exposure in Children
Why is INH given even if there is no evidence of infection or disease at initial visit:
May already be infected
Infection more likely to progress to disease
Infants and younger children are more likely to have disseminated disease or meningitis
TST repeated 12 weeks after contact broken with infectious adult:
If TST (-), discontinue INH
If TST (+), re-evaluate child and treat accordingly

33. Prevention of Tuberculosis in Children: Missed Opportunities
Failure to find and appropriately manage adult source cases (Case finding)
Delay in reporting the initial diagnosis of TB
Contact investigation interview failure
Delay in evaluation of exposed children
Failure to completely evaluate exposed children
Failure to prescribe prophylactic INH
Failure to maintain a contact under surveillance
LTBI diagnosed; treatment not prescribed
Failure to complete treatment for LTBI (Adherence)

34. BCG Vaccine and Tuberculin Skin Testing
History of a BCG is never a contraindication to tuberculin skin testing
No reliable method of distinguishing (+) TSTs due to BCG from those caused by infection with M. tuberculosis
Therefore, management of children with a history of BCG and a (+) PPD includes:
Diagnostic evaluation including a chest radiograph
Appropriate treatment

35. BCG – Fantasy and Fact FANTASY FACT
BCG protects against getting TB infection
BCG provides lifetime protection against developing active TB
BCG causes the tuberculin skin test (TST) to be positive for life
In a BCG-vaccinated person, a positive TST is most likely due to BCG
A positive TST in a person of any age from any country is most likely due to BCG, not TB infection
There is no need for a BCG-vaccinated person with a positive TST to be treated
BCG will not protect against becoming infected with TB
BCG protects against severe complications of TB disease in young children, but provides little or no protection in adolescents and adults
BCG causes the TST to be positive for a few years and then the TST reaction becomes much weaker. Generally, no reaction is present after 5 years.
There is no way to tell whether a positive TST is due to BCG or to TB infection
A positive TST in an adolescent or adult from a TB high-burden country is almost always due to TB infection, not BCG
Persons with a positive TST from TB high-burden countries are at high risk of developing active TB and should be treated