Table. Positive Purified Protein Derivative Results (Pediatrics In Review Apr 2008)

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1 PPD and TB Sreening COMPETENCY- The resident should know the risk factors for TB exposure, when to screen, and the appropriate criteria for recognizing a positive PPD in children of different age groups and exposure/infection to different risk factors. CASE- A mother and her 5 year old daughter, Mya present for an initial visit to your clinic for a well child check. The mother states that they have just moved from Chile and now reside in Chicago. She has never had a BCG vaccination. Mya seems to be doing well. You decide to screen for TB risk factors during this visit. QUESTIONS- 1. What is Tuberculosis and what is a PPD test? 2. How does Tuberculosis exposure/infection occur? 3. When is a PPD test considered positive in children? 4. When should children be screened for Tuberculosis? 5. What should be done if a patient s PPD test is positive, but the patient is asymptomatic? 6. What should be done if a patient s PPD test is negative but you highly suspect infection? 7. Can you place a PPD and give live viral vaccinations at the same time? References: Mayers, Marguerite M. Tuberculosis In Brief. Pediatrics in Review. Vol 29.No.4.April CDC.gov The Red Book Harriet Lane Book

2 1. What is Tuberculosis and what is a PPD test? Tuberculosis is a disease caused most commonly by Mycobacterium tuberculosis and Mycobacterium bovis that the World Heath Organization estimates to affect 2 billion people worldwilde, most with latent disease. Although less prominent in the United States, in 2005 there were 863 cases of active TB in children, with 480 of those children younger than 5 years of age and 383 in those between 5 and 15 years of age, for a rate of 1.4/100,000 children. Primary pulmonary disease is the most common presentation of active TB, although extrapulmonary infections are seen: lymphadenitis, meningitis, osteomyelitis, and peritoneal and renal TB. Symptoms usually are nonspecific and consist of fever, anorexia, and weight loss. Occasionally, a nonproductive cough, headache, and vague abdominal pain are seen. The intradermal Mantoux test is the most reliable TST (Tuberculin Skin Test) screen for TB. The test consists of 0.1mL of 5 tuberculin units of purified protein derivative (PPD) injected intradermally on the volar aspect of the forearm, forming a 6- to 10- mm wheal. The area is inspected at 48 to 72 hours; induration, not erythema, is measured transfersely to the long axis of the forearm and the results recorded in millimeters. The determination of a positive PPD depends on the clinical and epidemiologic circumstances of the child, and size does not differentiate between active or latent infection (see question 3). 2. How does Tuberculosis exposure/infection occur? All of the Mycobacterium organisms including atypicals are aerobic, nonmotile bacilli characterized by their ability to absorb a carbol-fuchsin stain (Ziehl-Neelsen) when heated and resist decolorization by acid alcohol, thus requiring the name acidfast bacilli (AFB). The air droplet nuclei containing the tubercle bacilli are inhaled, entering the respiratory tract and initiating infection in the lungs. Rarely there is GI or cutaneous acquisition. The infection spreads from there to regional lymph nodes and subsequently throughout the body via the systemic circulation, preferring the vascular areas. This is usually unrecognized and asymptomatic in all affected people. Once the affected individual mobilized cell-mediated immunity 6 to 10 weeks later, the progress of the infection is stopped, many of the bacilli are eliminated and those that remain enter a latent state. Ninety percent of those infected have latent TB infection (LTBI) and a lifetime risk of reactivation. The highest incidence of active disease is found in children younger than 4 years of age and in those recently infected. Symptomatic illness peaks within the first year or two after infection and decreases substantially after 5 years, although a small ongoing risk of reactivation exists for the lifetime of the individual. This risk increases if the individual acquires HIV infection, certain chronic disease, or is on immunosuppressive therapy.

3 3. When is a PPD test considered positive in children? Table. Positive Purified Protein Derivative Results (Pediatrics In Review Apr 2008) 5-mm Reaction Exposure to active tuberculosis (TB) Human immunodeficiency virus (HIV) infection or immunosuppression Chest radiograph or clinical presentation consistent with TB 10-mm Reaction High risk of disseminated TB (<4 y; lymphoma, diabetes, renal failure, malnutrition, or other predisposing condition) High risk of exposure to TB (birth in or frequent visits to a high prevalence area; exposure to adults who are infected with HIV, homeless, incarcerated, illicit drug users, residents of nursing homes or institutions, or migrant workers) 15-mm Reaction More than 4 years of age with no identifiable risk factor Of note, this community (Chicago, Illinois) should be considered a high prevalence area so a 10-mm reaction would be considered positive in a well child. 4. When should children be screened for Tuberculosis? Routine screening for TB no longer is recommended. However, children always should be tested if active disease is suspected, and in certain identifiable groups, the prevalence of disease is high enough that a TST is recommended. In fact the CDC recommends screening for Tuberculosis by asking about risk factors during Well Child Checkups. BCG vaccination is not a contraindication to TST nor does it change the interpretation of results. Immediate TST: -Contacts of people with confirmed or suspected contagious tuberculosis -Children with radiographic or clinical findings suggesting tuberculosis disease -Children immigrating from countries with endemic infection (eg Asia, Middle East, Africa, Latin America, countries of the former Soviet Union) including international adoptees

4 Children who should have annual TST: -Children infected with HIV -Incarcerated adolescents Children at increased risk of progression of LTBI to active disease: Children with Diabetes mellitus, chronic renal failure, malnutrition, and congenital or acquired immunodeficiencies need special consideration. In addition, a TST should be performed in all children who will begin immunosuppressive therapy. A positive TST result in a child or adolescent should be regarded as a marker for active disease within that community and should serve as a call to investigate contacts and to find and treat cases of latent TB infection. 5. What should be a done if a patient s PPD test is positive, but the patient is asymptomatic? Prompt clinical and radiographic evaluation of all children and adolescents with a positive TST reaction is recommended. Latent tuberculosis infection (LTBI) is defined as M tuberculosis or M bovis infection in a person who has a positive TST result, no physical findings of disease, and chest radiograph findings that are normal or reveal evidence of healed infection (eg granuloma or calcification in the lung, hilar lymph nodes, or both). Isoniazid given to adults who have LTBI (no clinical or radiographic evidence to suggest active disease) provides a substantial protection (54-88%) against development of tuberculosis disease for at least 20 years. Among children, efficacy approaches 100% with appropriate adherence to therapy. All infants, children, and adolescents who have a positive TST result but no evidence of active disease and who never have received antituberculosis therapy should receive isoniazid unless resistance to isoniazid is suspected (known exposure to a person with isoniazidresistant TB) or a specific contraindication exists. Radiograph should be done once prior to treatment and if the individual remains asymptomatic after treatment is completed it should not be repeated. For infants, children and adolescents the recommended duration of isoniazid therapy is 9 months. Isoniazid is given daily in a single dose. When adherence with daily therapy with isoniazid cannot be ensured, twce-a-weel DPT cam be considered. 6. What should be done if a patient s PPD test is negative but you highly suspect infection? Approximately 10% to 15% of immunocompetent children with culture-documented disease do not react initially to a TST. Host factors, such as a young age, poor nutrition, immunosuppression, other viral infections, recent tuberculosis infection, and disseminated tuberculosis disease can decrease TST reactivity. Many children and adults coinfected with HIV and M tuberculosis do not react to a TST. Control skin test to assess cutaneous anergy are not recommended routinely. A child who is suspected of having active TB should be hospitalized to obtain an organism for culture and sensitivity. Chest radiography can show an infiltrate and hilar lymph adenopathy (a Ghon complex), a disseminated or millet seed pulmonary appearance, a pleural effusion (a progressive primary infection), or apical abnormalities

5 or a cavity in the adolescent who has reactivated disease. In small children, the highest yield for positive AFB smears and culture is from an early morning gastric aspirate when the volume collected exceeds 50 ml of fluid. In the adolescent who has a productive cough, sputum should be obtained by expectoration or saline induction. Bronchoscopy can be useful in obtaining a specimen. If tuberculous meningitis is suspected, the cerebrospinal fluid (CSF) examination can show a pleocytosis with a lymphocytic predominance, a low glucose concentration, and a high protein concentration. The CSF should be centrifuged and the resultant pellicle examined for AFB. Biopsies of the lymph nodes, bone marrow, and liver can be evaluated by the pathologist for caseating granulomas and sent for culture. 7. Can you place a PPD and give live viral vaccinations at the same time? The measles vaccine (part of MMR) can temporarily suppress tuberculin reactivity. If necessary, you can place the PPD on the same day as giving the MMR vaccine but it is not recommended to place a PPD within 4-6 weeks after receiving an MMR vaccination. There is no official evidence regarding other live attenuated vaccines, but it is recommended that you follow the guidelines for MMR. Additional information: Since risk of active disease is higher in children age 4 or younger, pediatricians are often conservative regarding beginning treatment (prophylaxis) for these patients who have risk factors and have LTBI. Please see references for additional information on treatment of active tuberculosis disease. Alanna Nzoma M.D. Reviewed by Kyran Quinlan M.D.