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Tuberculosis skin testing at the end of a century.

Tuberculosis remains a threat to children, particularly those in high-risk groups. This article reviews new screening protocols for tuberculosis, and appropriate methods for managing positive test results. An overview of new research related to tuberculin testing is presented.

Screening is a fundamental part of pediatric primary care. We do not, however, screen for every disease or health problem that a child might acquire. In order to justify the time and expense involved, certain characteristics of the disease must exist. Some are obvious: the disease must be "around" (prevalence); there must be a reasonable chance children will get it (incidence); the effects of the disease in children must be significant (serious morbidity or mortality); and there must be an acceptable method of treating the problem. Tuberculosis (TB) certainly fits those criteria.

At the beginning of the twentieth century, tuberculosis was a mass killer of children and adults, with no medications which would halt the course of the disease once it was established. Without a doubt, it was a serious disease. In the 1940s, however, improved public health measures and antibiotics effective against the tubercle bacillus (Mycobacterium tuberculosis) were introduced. The number of cases began to drop steadily. It seemed that in the United States this disease was no longer a threat. Then in 1986, a "blip" appeared on the incidence chart and an upward trend in tuberculosis cases began and continued through 1992. During 1993 and 1994, there were decreases in many states but the total number of cases in 1994, 24,361, represented an overall increase of 9.7% over 1985, the year with the fewest reported cases (Centers for Disease Control and Prevention [CDC], 1996c).

Tuberculosis is back and children are getting it. There has been an increase of TB of approximately 35% in children from birth to 14 years of age (American Academy of Pediatrics [AAP], 1994). In 1990 alone, there were 1,576 new cases of TB in children in that age range (American Nurses Association [ANA], 1994). However, the risk of children acquiring TB is not uniform across the United States. New York and California have the highest rates, 21.7 and 16.6 per 100,000 persons respectively. Nine other states have rates of [is greater than] 9.8 per 100,000 population. The distribution largely follows that of the human immunodeficiency virus (HIV) epidemic (CCD, 1996c).

Another characteristic of TB that makes screening for it an important public health measure, is that it has an asymptomatic stage when the child is infected but does not have active, communicable tuberculin disease. Children who are identified during this period can have prophylactic drug treatment, which is very effective in preventing progression to full-blown disease.

Who Should be Screened?

More than 80% of childhood TB occurs in minority groups (CDC, 1991a). Table 1 outlines those who are at greatest risk for contracting tuberculosis (AAP, 1994). The Committee on Infectious Diseases, 1995 to 1996, of the American Academy of Pediatrics (AAP) recommends that surveillance efforts should be concentrated on those children at high risk of acquiring the disease. At one time, annual tuberculin testing for all children in high-risk groups was recommended. Now, that idea has been modified. Table 2 describes the revised guidelines (AAP, 1996).
Table 1. Children to Screen for Tuberculosis

  * Those with HIV infection
  * Close contacts of infectious tuberculosis cases
  * Malnourished (10% or more below ideal body weight)
  * Those with medical conditions which increase the risk of TB(+)
  * Foreign-born from countries with high prevalence of TB
  * Low-income populations, including high-risk minorities
  * Intravenous drug users and alcoholics
  * Residents of prisons and institutions
  * Those with immunosuppressive conditions
  * Those with chest X-ray suggestive of TB

(+) These conditions include: diabetes mellitus, Hodgkin's disease, end-stage
renal disease, chronic malabsorption syndromes




Note: Adapted from AAP (1994).
Table 2. TB Skin Test Recommendations for Children (Revised)

IMMEDIATE skin testing is indicated
   Contacts of individuals with confirmed or suspected active TB
      (includes contact with individuals in jail in last 5 years)
   Clinical findings suggestive of tuberculosis
   Immigrants from areas with endemic TB
      (e.g., Latin America, Africa, Middle East, Asia)
   Travel history to endemic countries
   Significant contact with indigenous persons from endemic areas
ANNUAL testing
   Infected with HIV
   Incarcerated
EVERY 2-3 YEARS
   Exposed to individuals in the following categories: HIV infected,
   homeless, institutionalized in nursing homes or prisons, users
   of illicit drugs, migrant farm workers
AT 46 AND 11-16 YEARS OF AGE
   Children without specific risk factors who reside in high-risk areas
Note: Adapted from AAP (1996).




A health assessment that includes a history of exposure to tuberculosis is important for all children. However, tuberculin skin testing should be reserved for those at increased risk.

Routine screening of ALL children in the United States, through school-based programs for example, is not a good use of limited resources when low-prevalence localities are included. The American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC) concur with the American Academy of Pediatrics. They recommend that children in low-risk groups, who live in communities with a low prevalence of tuberculosis, should be tested only once during childhood and this is for epidemiological purposes (AAP, 1994).

What Test Should be Used?

Historically, two types of skin tests have been used in TB screening programs: multiple-puncture tests (MPT) such as the Tine test and the Mantoux (PPD) intradermal test. The MPTs were widely used because they could be administered by individuals without extensive training. The MPTs have significant drawbacks, however. They have poor sensitivity, meaning that a large number of people who have TB will test negative. MPTs also have poor specificity, which means that individuals who are free of TB will test positive. MPTs, therefore, lack predictive value in identifying persons who actually have tuberculosis infection. This is because the amount of antigen on the metal prongs cannot be standardized by the manufacturers. Also, with any positive reaction using an MPT, the Mantoux (PPD) test must be used to confirm the results. This adds expense and may lead to the booster phenomenon. This phenomenon occurs when there is an increase in reaction size when repetitive tests are given to an individual infected with mycobacteria. Because of the low. predictive value, CDC, ATS, and AAP all agree that use of MPTs should be eliminated or greatly restricted to low-risk situations. The Mantoux (PPD) is the test recommended in any circumstances, except those of lowest risk, because it has much better predictive power in correctly identifying children who actually have TB infection (AAP, 1994).

Using the Mantoux Skin Test

Five tuberculin units of purified protein derivative (PPD) tuberculin are injected intradermally with the bevel of the needle pointing upward to form a wheel of 6 to 10 mm. The volar or dorsal surface of the forearm is the usual site. In 48 to 72 hours, the size of the transverse diameter of induration, not erythema, is measured. The diameter transverse to the long axis of the forearm is the only one standardized for measurement purposes (CDC, 1991a).

Interpretation of the Mantoux

In the past, a reaction of 10 mm or more was considered a positive test for TB infection. Now, there are three categories of "positive" based or the person's degree of risk for developing active tuberculosis disease. Table 3 describes these classifications. A negative skin test (0-4 mm), however, is not a guarantee that an individual is free of tuberculosis. Some diseases, infections (HIV in particular), or drugs may suppress cellular hypersensitivity mediated by t-lymphocytes and reduce a person's ability to mount a delayed-type hypersensitivity (DTH) reaction. This is known as energy. With energy, a person can have a negative Mantoux test and still have active tuberculosis. Clinical signs and symptoms, as well as a history of TB exposure, need to be taken into account. In people with a high probability of TB and DTH energy, companion testing of PPD and another antigen should be done. Although studies indicate that several antigens could be useful in this evaluation, mumps antigen is the only product standardized at this time for DHT to which a large proportion of Americans would be expected to react (CDC, 1991b).
Table 3. Positive Tuberculin Skin Test Reactions

Tuberculin reaction of 5 mm is positive for:
   Children with close recent contact with adults with active TB
   Children with chest x-rays suggestive of TB
   Children with known or suspected HIV infection

Tuberculin reaction of 10 mm is positive for:
   Children in medically underserved, low-income populations,
      including high-risk minorities especially African Americans,
      Hispanics, and Native Americans
   Children born in high-prevalence areas
   Children with selected medical risk factors (see Table 1)
   Children who use intravenous drugs
   Children in long-term care facilities or prisons

Tuberculin reaction of 15 mm is positive for:
   All those not covered above

Note: Adapted from National Tuberculosis Training Initiative (1991).




What About . . .

No shows? If the patient does not return within the recommended time frame, it may be possible to get an accurate measure for up to 1 week after the test has been placed. In situations where it is known that there is a high likelihood that the person will not return, such as with a transient homeless population, screening directly for the disease with a chest x-ray may be more appropriate than skin testing (CDC, 1991a).

Recent skin test converters? Many people have "converted" from PPD negative to PPD positive in the past. A recent converter, however, is one whose test has become positive in the last 2 years. These individuals are of concern because the risk for miliary (disseminated) TB or TB meningitis is greatest in the first months after infection. Recent converters are also at increased risk of developing active TB and in most cases will need to take preventive therapy (CDC, 1991a).

Measles vaccine &r TB skin testing? Since having the disease rubeola was shown to reactivate dormant Mycobacterium tuberculosis, it was theorized that administration of the measles vaccine could have the same effect. Therefore, there was a recommendation by AAP that children be skin tested for TB before (usually at the 12 month visit) or at the same time they are being given the MMR vaccine. Data have not supported this concept and routine testing of infants is no longer thought to be warranted (AAP, 1996).

Children of health care workers? These children are not at increased risk of acquiring tuberculosis unless the parent is a converter or develops tuberculosis disease (AAP, 1996).

BCG (Bacille Calmette-Guerin)? BCG is a vaccine against TB that is not used widely in the United States, but is used in other parts of the world with high rates of tuberculosis. Studies of the effectiveness of BCG vaccine in preventing TB range from 0% to 76%. Theoretically, if a person has received BCG, he should have a positive reaction with TB skin testing. However, many people who have been given the vaccine never react. In those who do develop a reaction, it wanes after 1 to 5 years. "Prior BCG vaccination is never a contraindication to tuberculin testing" (AAP, 1994, p. 132). A careful evaluation needs to be done to determine if the person has risk factors for developing TB regardless of previous BCG vaccination. The probability that a positive reaction is caused by infection with Mycobacterium tuberculosis rather than the BCG vaccine should be suspected when: the reaction is very large, the time since vaccination is long (certainly if it is greater than 3 years), and there is known exposure to communicable TB disease (CDC, 1996a).

If the PPD Is Positive

Children with a positive skin test need to be evaluated for infectious tuberculin disease. This evaluation includes: a thorough health history with emphasis on exposure to TB, previous TB, or signs/symptoms such as chronic cough, weight loss, and night sweats; a thorough physical examination by a pediatric clinician; a chest x-ray; and bacteriologic and histologic examinations of sputum or lesions (AAP, 1996). A positive culture for Mycobacterium tuberculosis is needed to confirm tuberculosis disease. Those who do not have active TB disease should be placed on a preventive therapy regimen of isoniazid (INH) and every attempt should be made to identify the source case of TB. For children, this is usually someone with whom they have regular contact (CDC, 1996b).

New Research in TB Testing

New research on TB testing being conducted in other countries may affect U.S. practices in the future. For example, in France, a study of 31 children was done to see the value of enzyme-linked immunosorbent assay (ELISHA) in differentiating between tuberculosis infection and disease. ELISHA was superior in making the discrimination, especially in those children with extrapulmonary disease (Delacourt et al., 1993).

Researchers in Turkey used BCG vaccine as the antigen and compared it to PPD testing. They found that more cases of pulmonary and extrapulmonary disease were identified by the BCG vaccine. They postulated that malnourishment of many of the children may have accounted for these results. They suggest that studies be done in other developing countries, where more sophisticated methods are not available, to confirm this (Gocmen, Kiper, Ertan, Kalayci, Ozcelik, 1994).

Conclusion

At the end of the 20th century, there are increased rates of TB in some groups of children in the United States. Primarily affected are those with HIV infection and minority children living in poverty. The American Academy of Pediatrics, the Centers for Disease Control and Prevention, and the American Thoracic Society all agree that screening efforts should be directed toward children in those high-risk groups. The Mantoux (PPD) intradermal skin test should be used rather than one of the multiple-puncture tests. New definitions for a positive Mantoux test have been defined and they may continue to evolve because of the problem of energy seen primarily in children with HIV infection.

References

American Academy of Pediatrics, Committee on Infectious Diseases. (1994). Screening for tuberculosis in infants and children. Pediatrics, 93, 131-134.

American Academy of Pediatrics, Committee on Infectious Diseases. (1996). Update on tuberculosis skin testing of children. Pediatrics, 97, 282284.

American Nurses Association. (1994). Clinician's handbook of preventive services, put prevention into practice. Waldorf, MD: American Nurses Publishing.

Centers for Disease Control. (1991a). Core curriculum on tuberculosis. Atlanta, GA: U.S. Department of Health & Human Services, Public Health Service.

Centers for Disease Control and Prevention. (1991b). Purified protein derivative (PPD)-tuberculin, energy and HIV infection: Guidelines for energy testing and management of anergic persons at risk of tuberculosis. Morbidity and Mortality Weekly Report, 40, No. RR-5, 27-33.

Centers for Disease Control and Prevention. (1996a). Tuberculosis information, BCG vaccine (Document # 250120). Atlanta, GA: Author.

Centers for Disease Control and Prevention. (1996b). Tuberculosis Information, screening for tuberculosis (Document # 250140). Atlanta, GA: Author.

Centers for Disease Control and Prevention. (1996c). Tuberculosis information, tuberculosis morbidity--United States, 1994 (Document # 250150). Atlanta, GA: Author.

Delacourt, C., Gobin, J., Gaillard, J.L., de Blic, J., Veron, M., Scheinmann, R (1993). Value of ELISHA using antigen 60 for the diagnosis of tuberculosis in children. Chest, 104, 393-398.

Gocmen, A., Kiper, N., Ertan, U., Kalayci, O., & Ozcelik, U. (1994).1s the BCG test of diagnostic value in tuberculosis7 Tubercle & Lung Disease, 75, 54-57.

The Primary Care Approaches section focuses on physical and developmental assessment and other topics specific to children and their families. If you are interested in author guidelines and/or assistance, contact Judith Vessey, PhD, RNC, DPNP; Johns Hopkins University College of Nursing; 1830 East Monument Street; Baltimore, MD 20215; (410) 614-1684.

Maureen C. Maguire, MSN, RN, PNP, is Coordinator, Nursing for Child Health, at Johns Hopkins University School of Nursing in Baltimore, MD.
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Author:Maguire, Maureen C.
Publication:Pediatric Nursing
Date:Mar 1, 1997
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