This publication is provided for historical reference only and the information may be out of date.
Tuberculosis (TB) continues to be a public health problem in the United States for both children and adults. Although the number of new TB cases in the United States among children younger than 15 years of age declined steadily from 1953 (when national surveillance for TB began) until 1988, the number of new cases increased 51% between 1988 and 1992 (from 1133 to 1708). Despite a drop in new TB cases in children between 1992 and 1995, 38% more new cases occurred in 1995 compared with 1988. Factors contributing to the increase in the number of TB cases include adverse social and economic conditions, the epidemic of human immunodeficiency virus (HIV) infection, immigration of individuals with Mycobacterium tuberculosis infection, and noncompliance of clinicians and patients with recommended screening and treatment regimens. The recent emergence of multiple-drug-resistant strains of M. tuberculosis has added urgency to the need for improved preventive efforts to combat the disease.
Of additional concern is that the number of TB cases among children younger than age 2 years is twice that among older children. Young children, in whom early TB disease may go unrecognized because their TB skin tests may be negative and because they may have few symptoms of disease, are more likely to develop severe disease such as meningitis or miliary tuberculosis than older children or adults. Young children are also more likely to progress from primary TB infection to active disease in a shorter time period than older children and adults.
The diagnosis of TB disease in a child is a sentinel event, signifying recent and ongoing transmission of M. tuberculosis in the community. In most states, the clinician is responsible for reporting cases of TB to the appropriate local or state health department, in order to initiate an epidemiologic investigation to identify and to treat infectious cases and contacts in the community.
Pediatric populations at high risk for TB disease include foreign born, African American, and Hispanic children. General populations at high risk of tuberculous infection include: 1) close contacts of persons known or suspected to have TB; 2) persons infected with HIV; 3) persons who inject illicit drugs or other locally identified high-risk substance abusers (eg, crack cocaine users); 4) persons who have medical risk factors known to increase the risk for TB disease if infection occurs; 5) residents and employees of high-risk congregate settings (eg, correctional institutions, nursing homes, mental institutions, other long-term residential facilities, and shelters for the homeless); 6) health-care workers who serve high-risk clients; 7) foreign-born persons, including children, who have arrived within 5 years from countries with a high incidence or prevalence of TB; and 8) some medically underserved, low-income populations.
Conditions and chronic diseases that predispose patients to development of TB disease include HIV infection, diabetes mellitus, end-stage renal disease, and hematologic and reticuloendothelial diseases; history of intestinal bypass or gastrectomy, chronic malabsorption syndromes, silicosis, cancers of the upper gastrointestinal tract or oropharynx, prolonged steroid use, and immunosuppressive therapy; and being 10% or more below desirable body weight.
Screening for TB consists of an intradermal injection of purified protein derivative (Mantoux test). A positive skin reaction (Table 9.1) necessitates additional work-up (chest x-rays, sputum smears and cultures) to differentiate between TB infection and TB disease. A drug regimen based on this evaluation will either be a prophylactic treatment of TB infection or a multi-drug treatment of TB disease (based on the organism's antibiotic sensitivities).
Isoniazid prophylaxis has been shown to be effective in preventing the progression of TB infection to clinical TB disease. When isoniazid is taken for 12 months, it reduces the occurrence of TB disease by 54% to 88%. The efficacy of isoniazid is directly related to the length of prophylaxis, the extent of patient compliance with the prophylactic regimen, and the susceptibility of the infecting organism to isoniazid.
In the United States, the use of Bacillus of Calmette and Guérin (BCG) vaccine to prevent TB infection is rarely indicated; however, new recommendations have been developed in light of two meta-analyses of BCG vaccine clinical trials, as well as the increase in TB cases and the outbreaks of multi-drug-resistant TB. The meta-analyses of BCG protective efficacy indicated that the vaccine efficacy for preventing serious forms of TB in children (meningeal and miliary) was high (>80%). (See Basics of: BCG Vaccination.)
Tuberculosis disease is currently designated as an infectious disease notifiable at the national level. Refer to Appendix C for further information on nationally notifiable diseases.
Recommendations of Major Authorities
- All major authorities, including American Academy of Pediatrics (AAP), American Academy of Family Physicians, American Medical Association, American Thoracic Society, Canadian Task Force on the Periodic Health Examination, Centers for Disease Control and Prevention, and US Preventive Service Task Force (USPSTF) --
- Tuberculin testing should be performed on children and adolescents at high risk of disease. AAP has recommended annual TB testing for infants and children with HIV and incarcerated adolescents; testing every 2 to 3 years for children exposed to individuals in certain high-risk groups (HIV infected, homeless, residents of nursing homes, institutionalized adolescents or adults, users of illicit drugs, incarcerated adolescents or adults and migrant farm workers); and testing at ages 4 to 6 years and 11 to 16 years for children without specific risk factors who reside in high prevalence areas and for children whose parents immigrated from regions with a high prevalence of TB or with continued potential exposure by travel to the endemic areas and/or household contact with persons from the endemic areas with unknown skin test status. The USPSTF has stated that the frequency of skin testing is a matter of clinical discretion.
- American Academy of Pediatrics (AAP), American Thoracic Society (ATS), and Centers for Disease Control and Prevention (CDC) --
- Children with a positive Mantoux test and without active disease should receive prophylaxis with isoniazid. Certain children with a negative Mantoux test should be considered for isoniazid prophylaxis (See Basics of Prophylaxis: Indications). The AAP has also suggested prophylaxis for patients who are anergic and from a population with a high prevalence of TB. Recommendations for the duration of isoniazid prophylaxis vary among authorities. The ATS and CDC recommend a minimum of 6 months of prophylaxis; the AAP recommends a minimum of 9 months of prophylaxis. According to AAP recommendations, newborn prophylaxis may be discontinued at 3 months of age if a Mantoux test at that time is negative; if all known adult contacts have negative sputum samples and are compliant with anti-TB medications; and if a repeat Mantoux test is performed at 6 months of age. The ATS and CDC recommend maintaining newborn prophylaxis until a negative PPD test is obtained at 6 months of age. Patients who are HIV-positive or who have evidence of prior TB on chest radiograph should receive isoniazid prophylaxis for 12 months. In the latter case, a 4-month course of isoniazid combined with rifampin can also be used.
- Advisory Committee on Immunization Practices (ACIP), Advisory Council for the Elimination of Tuberculosis, American Academy of Pediatrics (AAP), Centers for Disease Control and Prevention (CDC), and US Preventive Services Task Force (USPSTF) --
- BCG vaccination should be considered for an infant or child who has a negative TB skin-test result if the following circumstances are present: the child is exposed continually to an untreated or ineffectively treated patient who has infectious pulmonary TB, and the child cannot be separated from the presence of the infectious patient or given long-term primary preventive therapy OR the child is exposed continually to a patient who had infectious pulmonary TB caused by M. tuberculosis strains resistant to isoniazid and rifampin, and the child cannot be separated from the presence of the infectious patient. The AAP and USPSTF also recommend consideration of BCG vaccination for infants and children in groups in which an excessive rate of new infections is present (eg, >1%) and the usual surveillance and treatment have failed or are not feasible (eg, in groups without a source of regular health care). In the United States, BCG vaccination is rarely indicated. Physicians considering the use of BCG vaccine for their patients are encouraged to consult the TB control programs in their area or the CDC's Division of Tuberculosis Elimination at (404)639-8120.
Basics of Tuberculosis Screening
NOTE: Persons who are not likely to be infected with M. tuberculosis generally should not undergo skin testing, because the predictive value of a positive skin test in low-risk populations is poor.
The Mantoux test is the standard method of testing. Multiple-puncture tests should not be used to determine whether a person is infected.
For the Mantoux test, use 0.1 mL of purified protein derivative (PPD) containing 5 tuberculin units. Administer PPD using a disposable tuberculin syringe, with the bevel of the needle facing upward. Administer the injection intradermally on the volar surface of the forearm to produce a pale, discrete elevation of the skin (weal) 6 to 10 mm in diameter. The weal disappears shortly after the test is administered.
Read the test 48 to 72 hours after injection by measuring the diameter of induration (not erythema) transverse to the long axis of the forearm. Record the actual millimeters of induration. Do not consider the erythema that may surround the area of induration.
The definition of a positive skin test reaction depends on the likelihood of tuberculosis infection and the risk of tuberculosis disease if infection has occurred. A positive skin reaction can be expected 2 to 10 weeks after infection with TB has occurred.
Do not retest patients who have a documented history of a positive Mantoux test; such testing has no diagnostic utility.
Live-virus vaccines, such as measles-mumps-rubella (MMR), varicella (VCV), and oral polio vaccine (OPV), may interfere with a response to a tuberculin skin test. The tuberculin skin test should either be administered on the same day as the live-virus vaccinations, or postponed until 4 to 6 weeks after the vaccinations.
Basics of Tuberculosis Prophylaxis
A child with a positive Mantoux test result but without active disease is a candidate for isoniazid prophylaxis. Active disease is excluded by a normal chest radiograph and a lack of symptoms suggesting TB disease. See Table 43.1 for more information on general indications for prophylaxis.
Special pediatric cases should be considered candidates for isoniazid prophylaxis even if they lack documentation of a positive Mantoux test:
- Newborn prophylaxis: Infants whose mothers have active disease (even if noncontagious) and infants whose mothers have a positive Mantoux test but do not have active disease (preventive therapy can be discontinued after the entire family is demonstrated to have negative tuberculin skin tests)
- Children who are both anergic or HIV-positive and from populations where the prevalence of TB infection is higher than 10% (eg, injection drug users, homeless persons, migrant laborers, and individuals from Asia, Africa, or Latin America)
- Children who have had close contact within the past 3 months with a person with infectious TB.
2. Dosage and Administration
The recommended dosage of isoniazid is 10 to 15 mg/kg (up to a maximum of 300 mg) given orally once daily. For noncompliant patients, 15 mg/kg (to a maximum of 900 mg) may be given twice weekly under the direct observation of a health professional.
Continue isoniazid prophylaxis for 6 to 12 months. Recommendations regarding the duration of isoniazid prophylaxis vary (See Recommendations of Major Authorities: Prophylaxis).
Patients receiving isoniazid prophylaxis must be monitored monthly for signs and symptoms of hepatotoxicity, including loss of appetite, nausea, vomiting, persistent dark urine, jaundice, fever, and abdominal tenderness (especially in the right upper quadrant). Isoniazid should be discontinued at the first sign of hepatotoxicity, and the patient evaluated for the cause of hepatitis. If isoniazid is not the cause of hepatotoxicity, consider reinstating isoniazid preventive therapy once the patient is clinically stable. In otherwise healthy children, the incidence of hepatitis during isoniazid therapy is low enough that routine screening with liver function testing is not required. Peripheral neuritis and convulsions caused by inhibition of pyridoxine metabolism by isoniazid have rarely occurred. When neuritis or convulsions occur during isoniazid treatment, consider accidental overdosage as a possible cause. Pyridoxine supplementation may be considered on an individual basis for breast-feeding children, children with deficient diets (particularly those low in meat and milk), and pregnant women.
Basics of BCG Vaccination
Recommendations differ slightly among authorities. (See Recommendations of Major Authorities.)
2. Vaccine Types
One BCG vaccine (Tice®) is available in the United States. Other BCG preparations that are available for the treatment of bladder cancer are not intended for use as vaccines. Other vaccines are in use in Canada and Mexico.
3. Dose and Administration
> 30 days old: Drop 0.3 mL of the vaccine on the cleansed surface of the skin in the lower deltoid area. Administer the vaccine percutaneously by applying a multiple-puncture disc through the vaccine; the vaccine should flow into the puncture wounds and dry. A dressing is not required, but advise the patient to keep the site dry for 24 hours.
<30 days old: Administer only half the usual dose to infants younger than 30 days old. If an infant's indications for vaccination persist (ie, the TB skin test result is <5 mm induration), administer a full dose of vaccine at 1year of age.
Until the risks and benefits of BCG vaccination in immunocompromised populations are defined, BCG vaccination should not be administered to persons with impaired immune responses (ie, HIV infection, congenital immunodeficiency, leukemia, lymphoma, or generalized malignancy) or suppressed immune responses (from steroids, alkylating agents, antimetabolites, or radiation.) Although no harmful effects to the fetus have been associated with BCG vaccination, its use is not recommended during pregnancy.
5. Adverse reactions
A bluish-red pustule usually forms at the site within 2 to 3 weeks. After 6 weeks, the pustule ulcerates and forms a lesion approximately 5 mm in diameter. Healing is usually complete within 3 months, but a permanent scar usually occurs at the site. Keep draining lesions clean and bandaged. Hypertrophic scars occur in 28% to 33% of vaccinated persons, and keloid scars occur in 2% to 4% of vaccinees.
Although BCG vaccination often results in local adverse effects, serious or long-term complications are rare. Moderate axillary or cervical lymphadenopathy, induration and subsequent pustule formation at the injection site can be expected. More severe local reactions include ulceration at the site and regional suppurative lymphadenitis. Disseminated BCG infection is a rare occurrence, but it is the most serious complication of the vaccine, and can occur from 4 months to 2 years after the vaccination.
BCG vaccination can cause false-positive Mantoux reactions, but these tuberculin skin test reactions decrease with time after vaccination, and reactions of 15 mm induration or larger are rare. The presence or size of a post-vaccination tuberculin skin-test reaction does not predict whether BCG will provide any protection against TB disease. In general, consider BCG-vaccinated individuals with positive Mantoux test results to have true infection with M. tuberculosis.
Perform tuberculin skin testing 3 months after BCG vaccination; record test results, in millimeters of induration, in the patient's medical record. The vaccinated person may continue to participate in ongoing skin-testing programs if results remain negative (<5 mm induration). Vaccinees who have positive skin-test results ( > 5 mm induration) after vaccination should not be retested unless exposed to a person with infectious TB. A diagnosis of TB infection and the use of preventive therapy should be considered for any BCG-vaccinated person who has a tuberculin skin-test reaction of 10 mm of induration, particularly if any of the following circumstances are present:
- The vaccinated person is a contact of another person who has infectious TB, particularly if the infectious person has transmitted TB to others
- The vaccinated person was born or has resided in a country in which the prevalence of TB is high
- The vaccinated person is exposed continually to populations in which the prevalence of TB is high
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