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

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

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

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

Number of TB Cases in U. S. -born vs Number of TB Cases in U.S.-born vs. Foreign-born Persons United States, 1993-2003 No. of Cases CDC

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

Reported TB Cases by Age Group United States, 2003 <15 yrs (6%) 65+ yrs (20%) 15 - 24 yrs (11%) 25 - 44 yrs (34%) 45 - 64 yrs (29%)

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

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

Children <15 years with TB by Site of Disease

Children <15 years with TB: Extrapulmonary Disease

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)

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

Mantoux tuberculin skin test

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

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?

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.?

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

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

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

AAP Recommendations: Tuberculin Skin Testing Children who should be considered for TST at 4-6 and 11-16 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)

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

Reading the Tuberculin Skin Test Read reaction 48-72 hours after injection Measure only induration Record reaction in millimeters

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

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

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

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

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)

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 20-40 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

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.

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

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

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)

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

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