Tuberculosis
Tuberculosis: Excerpt from The 5-Minute Pediatric Consult
Barbara M. Watson, MB, CHB, DCH, MRCP
Tuberculosis - BASICS
Tuberculosis - description
Pediatric tuberculosis (TB) is the disease state caused by Mycobacterium tuberculosis, an acid-fast bacillus (AFB). Pediatric TB should be regarded as a spectrum of exposure through infection to disease, because progression from an infected person (exposure) to infection and subsequently disease can occur much faster (within 3–6 months) in children <2 years of age (occurring within the incubation of the disease stated below).
Progression through this spectrum depends on age; such disease progression being 40–50% for children up to 2 years old, ~20% for 2–4-year-olds, and 10–15% for those ≥5 years old, the 5–10-year-old children being the most protected age group. Adolescence is another vulnerable age group.
Tuberculosis - general prevention
- Prevention of disease by using isonicotinic acid hydrazide (INH), 10 mg/kg/d PO for 9 months, or if compliance is not anticipated, 2 times a week as direct observed therapy at 20 mg/kg, with a maximum dose of 900 mg usually administered by a school nurse, child care worker, or the local TB control program, ideally without breaks in treatment, although the patient has 12 months to complete the course. If a break occurs near the end of treatment, it need not be restarted, because such treatment is ~90% effective against development of active TB for 20 years in nonimmunosuppressed children. This recommendation prevents disease in the treated patient and, as a public health measure, interrupts transmission to contacts of that infected person with 90% efficacy. Other drugs for latent TB include 4 months of rifampicin if a child cannot tolerate INH, 4 months of INH and rifampin in case of granulomas or fibrosis consistent with latent TB infection (LTBI), and finally 6 months of INH by direct observed therapy is the last resort (for a total of 72 doses).
- Calmette–Guérin bacillus vaccine is recommended only for infants and children who test negative to purified protein derivative, who are continually and intimately exposed to contagious adults or to adults with TB that is resistant to both INH and rifampin, and who cannot take long-term preventive medication or be kept away from the contagious adult. These recommendations are currently under review.
Tuberculosis - epidemiology
- The most common route of infection is via the respiratory tract. TB is spread from a person with disease by droplet nuclei that are inhaled by other people. A child becomes infected with TB after close and prolonged contact with an adult or adolescent who has active untreated infectious disease, usually pulmonary TB, in a poorly ventilated space. But there are people who develop TB without knowledge of an infectious contact.
- Congenital infection occurs, although rarely, in the setting of an untreated mother in the last trimester of pregnancy.
- Infection with the tubercle bacillus needs to be differentiated from disease (i.e., TB).
- The interval between onset of infection and disease is 10–12 weeks (details later in this chapter).
- The greatest chance of disease occurring (that is, of developing a positive result in tests using purified protein derivative [PPD], now renamed tuberculin skin test [TST]) is within the 1st 2 years after infection. However, for infants and children younger than 5 years, progression through the spectrum of pediatric TB (exposure–infection–disease) is age dependent (see “Definition”).
- Postpubertal adolescents and immunosuppressed people, including people with diabetes, with chronic renal failure, the malnourished, and those taking steroids for any reason (including pulse doses), have higher risks of progression of infection to disease.
- Nationwide, the early 1990s had a documented increase in TB in children <2 years of age in the US states where TB is more common; this trend had been reversed owing to adherence to the recommendations for treatment of the American Thoracic Society/US Centers for Disease Control and Prevention/Infectious Disease Society of America updated 2003 (see “Bibliography”). However, now an increase is being seen related to the increasing proportion of foreign-born parents of children in the US.
Tuberculosis - etiology
Direct contact with a person with active TB through transmission of air-borne droplets
Tuberculosis - associated conditions
The following diseases are associated with progression of infection to disease:
- HIV infection: Factor in the increase in TB, because 1 in 240 US residents is infected with HIV, and the bacillus grows stronger, evades detection (chest radiographs may appear normal), and is more highly contagious.
- Lymphoma
- Diabetes
- Chronic renal failure
- Malnutrition
- Immunosuppression, including chronic daily steroid use, high-dose steroid use or tumor necrosis factor-α (TNF-α) agonists, cancer chemotherapy
- Social issues: Incarcerated adolescents, infants and children in homeless shelters
Tuberculosis - DIAGNOSIS
Tuberculosis - signs & symptoms
- Failure to thrive
- Cervical or axillary lymphadenopathy without any other cause or that is prolonged
- Cough
- Weight loss
- Change in sensorium
- Fever in infants and adolescents, rarely in children 5–10 years of age
Tuberculosis - history
Inquire about the factors that are associated with TB infection at 1st encounter with the child and at every visit, since trust may develop over time and parents will share risk factor for those <2 years of age.
- Exposure: Family member with TB or positive skin test
- Migrant farm workers
- Immigration from a TB-endemic geographic area (e.g., Haiti, Southeast Asia, Africa, South and Central America, Russia, and elsewhere in Eastern Europe, where greater concern about drug-resistant strains ought to be exercised); visit by individuals from those countries; or visited the above countries
- Higher incidence in Native Americans
- Contact with adults who have active TB
- HIV-positive people
- Immunosuppressed state
- Incarcerated adolescents and their relatives who visit
- Homeless people
- Poor people in urban areas
- Exposure to milk from untested herds
- Malnutrition
- Long-term steroid usage
Tuberculosis - physical exam
- Cervical and axillary adenopathy
- May reflect underlying disease or state (e.g., HIV, malnutrition, long-term steroid use)
- Pulmonary rales
- Enlarged liver or spleen
Tuberculosis - tests
- Skin testing: Tuberculin Skin Test (TST)
- The Mantoux test comprises five tuberculin units with purified protein derivative administered intradermally. The video and booklets on administration and interpretation of the TST are available from http://www.cdc.gov/tb.
- The US Centers for Disease Control and Prevention do not recommend routine skin testing in low-risk groups in communities with low prevalence of TB.
- Children at high risk should be tested annually:
- High-risk children include those in contact with adults from regions of the world with high TB prevalence; children who spend time in homeless shelters, those in contact with adults with TB, HIV, and other disease-producing immunosuppressed states; those with Hodgkin disease, lymphoma, diabetes, chronic renal failure, or malnutrition; incarcerated adolescents; and those with exposure to any high-risk adults.
- A skin test result may become positive 3–6 weeks after exposure, however most commonly do not turn positive for 3 months. Hence, the rationale for treating an exposed child with INH and retesting with a purified protein derivative in 3 months
- A positive TST is a SENTINEL public health event indicating TB transmission in a community even if all other tests and examinations are negative
- Other tests:
- Culture sputum, gastric washings (early morning) performed with tube down over night pleural fluid, CSF, urine
- Culture may take 2–3 weeks by the radiometric method.
- Positive culture results are found in <50% of children.
Tuberculosis - imaging
Chest radiographs may show hilar adenopathy with or without atelectasis. However, any infiltrate, pleural effusion in a child with a positive TST result, and a risk factor for TB should be considered a TB suspect until proven otherwise. Infiltrates from bacterial or viral pathogens generally clear within 6–8 weeks; TB infiltrates tend not to clear so rapidly.
Tuberculosis - differencial diagnosis
TB can do anything malignancy can do:
- Cervical or axillary adenopathy
- Pulmonary infiltrate: Other chronic organisms, disorders, and conditions (e.g., Nocardia, histoplasmosis). Infiltrates owing to bacterial or viral pathogens resolve faster than TB; thus, re-evaluation of a suspect in 8–12 weeks clarifies this differential.
- Hilar adenopathy: In TB it is usually unilateral, but Epstein–Barr virus, adenovirus, pertussis, and malignancy may possibly mimic symptoms.
- Miliary disease: Pulmonary effects, hepatosplenomegaly with or without CNS involvement
- GI disease: Most common differential diagnosis is Crohn disease.
- Meningitis: Fungal meningitis, partially treated bacterial meningitis (rarely)
Tuberculosis - TREATMENT
Tuberculosis - general measures
- Hospitalization (if the patient has disease):
- Hospitalization reinforces the importance of disease and allows time for education and enrollment in TB control programs. If this is not feasible, direct linkage of the patient to the local TB control program of the health department and provision of direct observed therapy may avert the need to hospitalize to initiate therapy.
- In cases of extensive disease (e.g., miliary TB or meningitis), and when an adult source case is not known, aggressive attempts should be made to obtain an organism from gastric aspirates, bronchoalveolar lavage, CSF, pleural or joint aspirate, bone aspirate, liver or tissue biopsy, and, in some cases, blood cultures.
- Isolation policies:
- Unless the clinician can verify that the parent or any adult visitors are not themselves contagious, many infection control units require isolation of the child because the family members’ state of contagion remains unknown at admission.
- Nonpulmonary TB (e.g., GI TB, meningitis, bone, and TB with joint involvement) also do not require isolation.
- Children >8 years of age and adolescents should be isolated until they have completed 10 days of therapy.
Tuberculosis - medication
- Initial treatment in areas with multidrug-resistant TB >4%: Until sensitivities are known, a 4-drug regimen should be started: INH, 10–15 mg/kg/d; rifampin, 10–20 mg/kg/d; pyrazinamide (PZA), 15–30 mg/kg/d; and either ethambutol, 15–20 mg/kg/d or streptomycin, 20 mg/kg/d (depending on whether diagnosis is meningitis or miliary TB, for which a bactericide is desired); however, many cases in children of foreign-born parents are increasingly streptomycin resistant, making ethambutol a better choice.
- If the organism is sensitive to therapy, treatment with the initial 4 primary drugs should continue for the 1st 2 months; by then all sputum specimens should have a negative result on culture, followed by 4 months of INH and rifampin. When this regimen is adhered to, prognosis and a complete cure are achieved in 97–98% of patients.
- If a cavity is seen in chest radiograph or sputum specimens continue to test positive, or the TB is milary, disseminated, or meningeal, the duration of treatment needs to be longer (9–12 months).
Tuberculosis - FOLLOW UP
Tuberculosis - prognosis
- Mortality for untreated TB is 40% over 4 years.
- For miliary TB and meningeal TB, prognosis depends on the stage of presentation as already discussed.
- For outbreaks of multidrug-resistant TB, death rates range from 70–90% within 4 months of diagnosis.
Tuberculosis - complications
- Missed diagnosis: Failure to consider TB in a child who is failing to thrive and whose TST is negative
- TB meningitis: Outcome depends on the stage at which anti-TB medication starts:
- If pharmacotherapy is started at stage I, complete recovery occurs in 94%, with neurologic sequelae in 6%.
- If delayed until stage II, complete recovery occurs in 51%, with neurologic sequelae in 40% and death in 7%.
- If delayed until stage III, complete recovery occurs in 18%, with neurologic sequelae in 61% and death in 20%.
- Miliary TB
- Bony TB: Most commonly spinal manifestation
- Renal TB: Presents as a fever of undetermined origin (FUO), with or without urinary symptoms
- Congenital TB manifests with hepatosplenomegaly; may have CSF abnormalities and abnormalities on CSF testing and chest radiograph: Patients too young for TST to be useful
- Drug toxicity: Pediatric patients are much more tolerant of anti-TB medications than adults are; thus regular monitoring of liver function test results is not routinely required, although clinical monitoring for symptoms such as abdominal pain and loss of appetite on a monthly basis remains the cornerstone for identifying any toxicity.
- Hepatitis with INH, rifampin, and PZA; neurologic and hematological complications with INH; skin rashes predominantly with Rifompin, INH but reports have occurred with all anti-TB medications; ototoxicity with streptomycin; but ocular toxicity with ethambutol in the pediatric age group has not been documented, and therefore it is a safe drug to use. Management of common side effects and drug interactions may be found in the 2003 American Thoracic Society/US Centers for Disease Control and Prevention/Infectious Disease Society of America (see “Bibliography”).
Tuberculosis - patient monitoring
Follow-up and contact tracing are key to making TB preventable.
Tuberculosis - bibliography
- American Thoracic Society/US Centers for Disease Control and Prevention/Infectious Disease Society of America: Treatment of tuberculosis recommendations. Am J Respir Crit Care Med. 2003;167:603–662.
- Garcia-de-Lomas J, Navarro D. New directions in diagnostics. Pediatr Infect Dis J. 1997;16(3 Suppl):S43–S48.
- Heymann SJ, Brewer TF, Wilson ME, et al. Pediatric tuberculosis: What needs to be done to decrease morbidity and mortality. Pediatrics. 2000;106:E1.
- Inselman LS. Tuberculosis in children: An update. Pediatr Pulmonol. 1996;21:101–120.
- MMWR Targeted Tuberculin testing & treatment of LTBI. 2000;June 9:49(RR-6):1–51.
- MMWR trends in TB 2004. Global incidence of multidrug-resistant tuberculosis. 2004;53(10):1–24.
- MMWR report: Recommendations and reports: 2005;54:RR-15:49–55. Guidelines for the investigation of contacts of persons with infectious tuberculosis: recommendations from the national Tuberculosis Controllers Association and CDC.
Tuberculosis - CODES
Tuberculosis - icd9
011.9 Pulmonary tuberculosis, unspecified
Tuberculosis - FAQ
- Q: If the child has completed a course of INH and is re-exposed, what are the risks of infection?
- A: One course of preventive therapy is believed to confer immunity to subsequent exposure.
- Q: Should all children in close proximity to inner-city areas with a prevalence of TB be screened annually with purified protein derivative?
- A: The AAP and CDC encourage targeted screening based on risk factors indicated above. The Targeted screening questionnaire should be administered at every visit until age 2, then annually thereafter. See tools on http://www.cdc.gov/tb
- Q: Can we use the whole blood assay “quatiferon gold” to differentiate children who were born in other countries and had BCG instead of the TST (parents are requesting the test).
- A: The test is not licensed for pediatric use and hence cannot be interpreted. A large study in the navy recruits in 2006 demonstrated in foreign born individuals with a TST >20 and the “quantiferon Gold Test” was equivalent.
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Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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