PEDIATRIC TUBERCULOSIS : Clinical Manifestation and Diagnosis

 

History

 

  • Staging: Although the natural history of tuberculosis (TB) in children follows a continuum, the American Thoracic Society (ATS) definition of stages is useful:
    • Stage 1: Exposure has occurred, implying that the child has had recent contact with an adult who has contagious tuberculosis. The child has no physical signs or symptoms and has a negative tuberculin skin test (TST) result. The chest radiography does not reveal any changes at this stage. Not all patients who are exposed become infected, the TST result may not be positive for 3 months. Unfortunately, children younger than 5 years may develop disseminated tuberculosis in the form of miliary disease or tubercular meningitis before the TST result becomes positive. Thus, a very high index of suspicion is required when a young patient has a history of contact.
    • Stage 2: This stage is heralded by a positive TST result. No signs and symptoms occur, although an incidental chest radiography may reveal the primary complex.
    • Stage 3: Tuberculous disease occurs and is characterized by the appearance of signs and symptoms depending on the location of the disease. Radiographic abnormalities may also be seen.
    • Stage 4: This stage is defined as tuberculosis with no current disease. This implies that the patient has a history of previous episodes of tuberculosis or abnormal, stable radiographic findings with a significant reaction to the TST and negative bacteriologic studies. No clinical findings suggesting current disease are present.
    • Stage 5: Tuberculosis is suspected, and the diagnosis is pending.
  • Asymptomatic infection: Patients with asymptomatic infection have a positive TST result but do not have any clinical or radiographic manifestations. Children with asymptomatic infection may be identified on a routine well-child physical examination, or they may be identified subsequent to tuberculosis diagnosis in household or other contacts (eg, children who recently have immigrated, adopted children).
  • Disease evaluation: Any patient with pneumonia, pleural effusion, or a cavitary or mass lesion in the lung that does not improve with standard antibacterial therapy should be evaluated for tuberculosis. Also, patients with fever of unknown origin, failure to thrive, significant weight loss, or unexplained lymphadenopathy should be evaluated for tuberculosis.
    • Pulmonary tuberculosis may manifest itself in several forms, including endobronchial tuberculosis with focal lymphadenopathy, progressive pulmonary disease, pleural involvement, and reactivated pulmonary disease. Symptoms of primary pulmonary disease in the pediatric population are often meager. Fever, night sweats, anorexia, nonproductive cough, failure to thrive, and difficulty gaining weight may occur.
      • Endobronchial tuberculosis with enlargement of lymph nodes: This is the most common variety of pulmonary tuberculosis. Symptoms are the result of impingement on various structures by the enlarged lymph nodes. Persistent cough may be indicative of bronchial obstruction, whereas difficulty swallowing may result from esophageal compression. Vocal cord paralysis may be suggested by hoarseness or difficulty breathing.
      • Tubercular pleural effusion: Pleural effusions due to tuberculosis usually occur in older children and are rarely associated with miliary disease. Typical history reveals an acute onset of fever, chest pain that increases in intensity on deep inspiration, and shortness of breath. Fever usually persists for 14-21 days.
      • Progressive primary tuberculosis: Progression of the pulmonary parenchymal component leads to enlargement of the caseous area and may lead to pneumonia, atelectasis, and air trapping. This is more likely to occur in young children than in adolescents. The child usually appears ill with symptoms of fever, cough, malaise, and weight loss.
      • Reactivation tuberculosis: This condition usually has a subacute presentation with weight loss, fever, cough, and, rarely, hemoptysis. Reactivation tuberculosis typically occurs in older children and adolescents. The condition is more common in patients who acquire tuberculosis when aged 7 years and older.
    • Extrapulmonary tuberculosis includes peripheral lymphadenopathy, tubercular meningitis, miliary tuberculosis, skeletal tuberculosis, and other organ involvement.
      • Lymphadenopathy: Patients with lymphadenopathy (ie, scrofula) may have a history of enlarged nodes. Fever, weight loss, fatigue, and malaise are usually absent or minimal. Lymph node involvement typically occurs 6-9 months following initial infection by the tubercle bacilli. More superficial lymph nodes commonly are involved. Frequent sites of involvement include the anterior cervical, submandibular, and supraclavicular nodes. Tuberculosis of the skeletal system may lead to involvement of the inguinal, epitrochlear, or axillary lymph nodes.
      • Tubercular meningitis: One of the most severe complications of tuberculosis is tubercular meningitis. Tubercular meningitis develops in 5-10% of children younger than 2 years; thereafter, the frequency drops to less than 1%. A very high index of suspicion is required to make a timely diagnosis because of the insidious onset of the disease. A subacute presentation usually occurs within 3-6 months after the initial infection. Nonspecific symptoms such as anorexia, weight loss, and fever may be present. After 1-2 weeks, patients may experience vomiting and seizures or alteration in the sensorium. Deterioration of mental status, coma, and death may occur despite prompt diagnosis and early intervention.
      • Miliary tuberculosis: This is a complication of primary tuberculosis in young children. It may manifest subacutely with low-grade fever, malaise, weight loss, and fatigue. A rapid onset of fever and associated symptoms may also be observed. History of cough and respiratory distress may be obtained.
      • Bone or joint tuberculosis: This may present acutely or subacutely. Vertebral tuberculosis may go unrecognized for months to years because of its indolent nature.
      • Additional sites: Other unusual sites for tuberculosis include the middle ear, GI tract, skin, kidneys, and ocular structures.
    • Congenital tuberculosis is rare. Symptoms typically develop during the second or third week of life and include poor feeding, poor weight gain, cough, lethargy, and irritability. Other symptoms include fever, ear discharge, and skin lesions. To make a diagnosis of congenital tuberculosis, the infant should have proven tuberculosis lesions and at least one of the following:
      • Skin lesions during the first week of life, including papular lesions or petechiae
      • Documentation of tuberculosis infection of the placenta or the maternal genital tract
      • Presence of a primary complex in the liver
      • Exclusion of the possibility of postnatal transmission

Physical

  • Primary tuberculosis is characterized by the absence of any signs on clinical evaluation. These patients are identified by a positive TST result. Tuberculin hypersensitivity may be associated with erythema nodosum and phlyctenular conjunctivitis.
  • Signs of disease depend on the site involved (pulmonary or extrapulmonary).
  • Pulmonary disease may manifest itself in several forms, including endobronchial tuberculosis with focal lymphadenopathy, progressive pulmonary disease, pleural involvement, and reactivated pulmonary disease.
    • Endobronchial disease: Enlargement of lymph nodes may result in signs suggestive of bronchial obstruction or hemidiaphragmatic paralysis. Vocal cord paralysis may occur as a result of local nerve compression. Dysphagia due to esophageal compression also may be observed.
    • Progressive primary pulmonary tuberculosis: This condition presents with classic signs of pneumonia, including tachypnea, nasal flaring, grunting, dullness to percussion, egophony, decreased breath sounds, and crackles.
    • Pleural effusion: Signs include tachypnea, respiratory distress, dullness to percussion, decreased breath sounds, and, occasionally, features of mediastinal shift.
    • Reactivation tuberculosis: Physical examination results may be normal or may reveal posttussive crackles.
  • Manifestations of extrapulmonary tuberculosis include peripheral lymphadenopathy, tubercular meningitis, miliary tuberculosis, skeletal tuberculosis, and other organ involvement.
    • Lymphadenopathy: This usually involves the anterior or posterior cervical and supraclavicular nodes. Less-commonly involved lymph nodes include: submandibular, submental, axillary, and inguinal lymph nodes. Typically, infected lymph nodes are firm and nontender with nonerythematous overlying skin. The nodes are initially nonfluctuant. Suppuration and spontaneous drainage of the lymph nodes may occur with caseation and the development of necrosis.
    • Tubercular meningitis: Three stages of tubercular meningitis have been identified.
      • Stage 1: No focal or generalized neurologic signs are present. Possibly, only nonspecific behavioral abnormalities are found.
      • Stage 2: This stage is characterized by the presence of nuchal rigidity, altered deep tendon reflexes, lethargy, and/or cranial nerve palsies. Tubercular meningitis most often affects the sixth cranial nerve, resulting in lateral rectus palsy. This is due to the pressure of the thick basilar inflammatory exudates on the cranial nerves or to hydrocephalus. The third, fourth, and seventh cranial nerves may also be affected. Funduscopic changes may include papilledema and the presence of choroid tubercles, which should be carefully sought.
      • Stage 3: This final stage comprises major neurologic defects, including coma, seizures, and abnormal movements (eg, choreoathetosis, paresis, paralysis of one or more extremities). In the terminal phase, decerebrate or decorticate posturing, opisthotonus, and/or death may occur. Patients with tuberculomas or tubercular brain abscesses may present with focal neurologic signs. Spinal cord disease may result in the acute development of spinal block or a transverse myelitis–like syndrome. A slowly ascending paralysis may develop over several months to years.
    • Miliary tuberculosis: Physical examination includes lymphadenopathy, hepatosplenomegaly, and systemic signs including fever. Respiratory signs may evolve to include tachypnea, cyanosis, and respiratory distress. Other signs, which are subtle and should be carefully sought in the physical examination, include papular, necrotic, or purpuric lesions on the skin or choroidal tubercles in the retina.
    • Bone tuberculosis: Common sites involved include the large weightbearing bones or joints, including the vertebrae (50%), hip (15%), and knee (15%). Destruction of the bones with deformity is a late sign of tuberculosis. Manifestations may include angulation of the spine (gibbus deformity) and/or Pott disease (severe kyphosis with destruction of the vertebral bodies). Cervical spine involvement may result in atlantoaxial subluxation, which may lead to paraplegia or quadriplegia.
  • Signs of congenital tuberculosis include failure to thrive, icterus, hepatosplenomegaly, tachypnea, and lymphadenopathy.

 

The tuberculin skin test is used to determine whether a person has Latent TB infection. The Mantoux tuberculin skin test is the preferred type of skin test because it is the most accurate and is the only type of test that should be used.

Whether a reaction to the Mantoux tuberculin skin test is classified as positive depends on the size of the reaction, the person’s risk factors for TB, and for people who may be exposed to TB on the job, the risk of exposure to TB.

Several factors can affect how the skin test reaction is interpreted. Close contacts of someone with infectious TB disease who have a negative reaction to the tuberculin skin test should be retested 10 weeks after the last time they were in contact with the person who has TB.

A new serological test QuantiFERON-TB Gold ® has recently been approved by the FDA and is used in place of the skin test as it is usually more specific.

There are four steps in diagnosing TB disease: medical history, tuberculin skin test, chest x-ray, and bacteriologic examination.

A medical history includes asking the patient whether they have been exposed to a person with TB, symptoms of TB disease, if they have had Latent TB infection or TB disease before, or risk factors for developing TB disease. The symptoms of pulmonary TB disease may include:

  • Coughing
  • Pain in the chest when breathing or coughing
  • Coughing up sputum or blood

The general symptoms of TB disease (pulmonary or extrapulmonary) may include:

  • Weight loss
  • Fatigue
  • Malaise
  • Fever
  • Night sweats.

The symptoms of extrapulmonary TB disease depend on the part of the body that is affected by the disease.

 

Laboratory Studies

  • Making the diagnosis of tuberculosis (TB) in children is extremely challenging because of the difficulty in isolating M tuberculosis. Definitive diagnosis of tuberculosis depends on isolation of the organism from secretions or biopsy specimens.
  • Despite innovations in rapid diagnosis, many of the classic diagnostic tools remain useful and continue to be used in the evaluation of patients with tuberculosis.
  • Detection and isolation of the mycobacterium are accomplished as follows:
    • The initial step is to obtain appropriate specimens for bacteriologic examination. Examination of sputum, gastric lavage, bronchoalveolar lavage, lung tissue, lymph node tissue, bone marrow, blood, liver, cerebrospinal fluid (CSF), urine, and stool may be useful, depending on the location of the disease.
    • Gastric aspirates are used in lieu of sputum in very young children (<6 y) who usually do not have a cough deep enough to produce sputum for analysis.
      • Using the correct technique for obtaining the gastric lavage is important because of the scarcity of the organisms in children compared to adults. An early morning sample should be obtained before the child has had a chance to eat or ambulate because these activities dilute the bronchial secretions accumulated during the night.
      • Initially, the stomach contents should be aspirated, and then a small amount of sterile water injected through the orogastric tube. This aspirate should also be added to the specimen.
      • Because gastric acidity is poorly tolerated by the tubercle bacilli, neutralization of the specimen should be performed immediately with 10% sodium carbonate or 40% anhydrous sodium phosphate. Even with careful attention to detail and meticulous technique, the tubercle bacilli can be detected in only 70% of infants and in 30-40% of children with disease.
    • Sputum specimens may be used in older children. Nasopharyngeal secretions and saliva are not acceptable. In older children, bronchial secretions may be obtained by the stimulation of cough by an aerosol solution of propylene glycol in 10% sodium chloride.
    • Bronchoalveolar lavage may also be used to provide bronchial secretions for detection of tubercle bacilli.
    • Decontamination of other microorganisms in the specimens obtained may be performed by the addition of sodium hydroxide, usually in combination with N -acetyl-L -cysteine. Other body fluids (eg, CSF, pleural fluid, peritoneal fluid) can also be centrifuged; the sediment can be stained and evaluated for presence of acid-fast bacilli (AFB). CSF smear results are positive in fewer than 10% of patients in some series. Enhancement of the yield may be possible by staining any clot that may have formed in standing CSF specimens, as well as using the sediment of a centrifuged specimen. Increased yield may also be obtained from cisternal or ventricular fluid.
    • Obtain overnight urine specimens in the early morning. Send immediately for analysis because the tubercle bacilli poorly tolerate the acidic pH of urine.
  • Staining of the specimen is as follows:
    • Because M tuberculosis is an AFB, staining of AFB provides preliminary confirmation of the diagnosis.
    • Staining can also give a quantitative assessment of the number of bacilli being excreted (eg, 1+, 2+, 3+). This can be of clinical and epidemiologic importance in estimating the infectiousness of the patient and in determining the discontinuation of respiratory isolation. However, for reliably producing a positive result, smears require approximately 10,000 organisms/mL. Therefore, in early stages of the disease or in children in whom the bacilli in the respiratory secretions are sparse, the results may be negative. A single organism on a slide is highly suggestive and warrants further investigation.
    • A significant drawback of AFB smears is that they cannot be used to differentiate M tuberculosis from other acid-fast organisms such as other mycobacterial organisms or Nocardia species.
    • Conventional methods include the Ziehl-Neelsen staining method. The Kinyoun stain is modified to make heating unnecessary. Fluorochrome stains, such as auramine and rhodamine, are variations of the traditional stains. The major advantage of these is that slides can be screened faster because the acid-fast material stands out against the dark, nonfluorescent background. However, fluorochrome-positive smears must be confirmed by Ziehl-Neelsen staining.
  • Conventional growth techniques are as follows:
    • Culture of mycobacterium is the definitive method to detect bacilli. It is also more sensitive than examination of the smear. Approximately 10 AFB/mm of a digested concentrated specimen are sufficient to detect the organisms by culture.
    • Another advantage of culture is that it allows specific species identification and testing for recognition of drug susceptibility patterns. However, because M tuberculosis is a slow-growing organism, a period of 6-8 weeks is required for colonies to appear on conventional culture media.
    • Conventional solid media include the Löwenstein-Jensen medium, which is an egg-based medium, and the Middlebrook 7H10 and the 7H11 media, which are agar-based media. Liquid media (eg, Dubos oleic-albumin media) are also available, and they require incubation in 5-10% carbon dioxide for 3-8 weeks. These media usually have antibacterial antibiotics, which are slightly inhibitory for tubercle bacilli.
  • Modern approaches in diagnosis are as follows:
    • Because mycobacteria require 6-8 weeks for isolation from conventional media, automated radiometric culture methods (eg, BACTEC) are increasingly used for the rapid growth of mycobacteria. The methodology uses a liquid Middlebrook 7H12 medium that contains radiometric palmitic acid labeled with radioactive carbon 14 (14 C). Several antimicrobial agents are added to this medium to prevent the growth of nonmycobacterial contaminants. Production of14 CO2 by the metabolizing organisms provides a growth index for the mycobacteria. Growth is generally detected within 9-16 days.
    • Another rapid method for isolation of mycobacteria is SEPTICHEK. This nonradiometric approach has a biphasic broth-based system that decreases the mean recovery time versus conventional methods.
    • Mycobacterial growth indicator tubes (MGITs), which presently are used as a research tool, have round-bottom tubes with oxygen-sensitive sensors at the bottom. MGITs indicate microbial growth and provide a quantitative index of M tuberculosis growth.
  • Identification of species is as follows:
    • M tuberculosis can be reliably differentiated from other species on the basis of culture characteristics, growth parameters, and other empiric tests. M tuberculosis produces heat-sensitive catalase, reduces nitrates, produces niacin, and grows slowly. Serpentine cording is demonstrated on smears prepared from the BACTEC system.
    • Addition of p -nitro-acetyl-amino-hydroxy-propiophenone (NAP) inhibits the growth of M tuberculosis complex (including M bovis and M africanum) but does not inhibit growth of other mycobacteria. This provides the basis for the NAP differentiation test.
    • Chromatographic analysis of mycobacterial cell wall lipids can provide further speciation. The most useful approaches include gas-liquid chromatography and high-performance liquid chromatography (HPLC). The unique mycolic acid pattern associated with the species can be detected by the chromatographic separation of the ester. A significant drawback of these methods is the requirement of bacterial colonies grown in conventional solid media, a process that takes at least 3 weeks. However, the recent combination of HPLC with fluorescence detection has made the method more sensitive, thus BACTEC broth culture can be used instead of conventional solid media. This may make the method comparable to the NAP and AccuProbe tests. The expense of the initial equipment limits the availability of HPLC.
  • Nucleic acid probes are used as follows:
    • Because biochemical methods are time-consuming and laborious, nucleic acid hybridization using molecular probes has become widely accepted. Commercially available probes, including the AccuProbe technology, help advance identification of the M tuberculosis complex. Sensitivity and specificity approach 100% when at least 100,000 organisms are present.
    • The basic principle is the use of a chemiluminescent, ester-labeled, single-strand DNA probe. A luminometer is used to assess the chemiluminescence.
    • Positive test results should be reported as M tuberculosis complex because the probe does not reliably differentiate between M tuberculosis and other members of the complex (eg, M bovis). Final identification to species level is required because pyrazinamide should not be included in the treatment regimen if the isolate is M bovis.
    • Niacin production, nitrate reduction, pyrazinamidase, and susceptibility to thiophene-2-carboxylic acid hydrazide can help differentiate between M bovis and M tuberculosis.
  • Polymerase chain reaction (PCR) and other amplification tests are used as follows:
    • Nucleic acid amplification allows the direct identification of M tuberculosis in clinical specimens, unlike the nucleic acid probes, which require substantial time for bacterial accumulation in broth culture.
    • The US Food and Drug Administration (FDA) has approved 2 tests, the amplified M tuberculosis direct test and the AMPLICOR M tuberculosis test. The AMPLICLOR test targets the DNA. The most commonly used target sequence for the detection of M tuberculosis has been the insertion sequence IS6110. The amplified M tuberculosis direct test is an isothermal transcription-mediated amplification that targets RNA.
    • Although amplification techniques are promising tools for the rapid diagnosis of tuberculosis, several caveats remain. Contamination of samples by products of previous amplification and the presence of inhibitors in the sample may lead to false-positive or false-negative results.
    • Although the sensitivity and specificity of the nucleic acid techniques in smear-positive cases exceed 95%, the sensitivity of smear-negative cases varies from 40-70%. Thus, discordance between the acid-fast smear result and the nucleic acid amplification techniques requires careful clinical appraisal and judgment.
  • T-SPOT Tb and QuantiFERON-TB Gold, interferon-gamma release assays (IGRAs), are 2 blood tests recently available to aid in the diagnosis of tuberculosis.9
    • The QuantiFERON-TB Gold has recently been approved by the FDA as an in vitro diagnostic test and the CDC has published a guideline for its use. The test is an enzyme-linked immunoassay (ELISA) that basically detects the presence of interferon gamma release protein (IFN-g) from the blood of sensitized patients when incubated with the early secretory antigenic target-6 (ESAT6) and culture filtrate protein 10 (CFP10) peptides. The test is as sensitive as, and more specific than, the tuberculin skin test (TST) and has been recommended as a screening tool in all situations in which the tuberculin skin test has been used (ie, for diagnosing disease as well as infection).
    • Other advantages include the fact that no return visits are needed to read the skin tests and no boosting occurs due to the tests.
    • Initial studies are underway to determine if these tests can be used to monitor response to therapy.
  • M tuberculosis drug susceptibility is determined as follows:
    • Because of the emergence of multidrug-resistant (MDR) organisms, determination of the drug susceptibility panel of an isolate is important so that appropriate treatment can be ensured.
    • Numerous chromosomal mutations are associated with drug resistance. Genotypic methods now being evaluated to identify these mutations include DNA sequencing, solid phase hybridization, and PCR–single-strand combination polymorphism analysis.
    • Mutations of the catalase peroxidase gene katG, the inhA gene involved in fatty acid biosynthesis, the ahpc gene, and the oxyR gene have been identified as major determinants for isoniazid (INH) resistance.
    • Resistance to rifampin is determined by mutations in the rpoB gene encoding the beta subunit of the RNA polymerase.
    • Phenotypic susceptibility assays, which remain experimental, use mycobacteriophages to type the mycobacteria grown in the presence of antituberculous agents.
  • Serology is as follows:
    • M tuberculosis increases the levels of antibody titers in the serum.
    • No available serodiagnostic test for tuberculosis has adequate sensitivity and specificity for routine use in diagnosing tuberculosis in children.

Imaging Studies

  • Chest radiography
    • Chest radiography is a classic diagnostic tool when evaluating patients for pulmonary tuberculosis.
    • Initial studies include posteroanterior and lateral views. Apical-lordotic and oblique views may be helpful if further evaluation of the extent of lung involvement is indicated (eg, patients with apical lesions or extensive hilar adenopathy).
    • If pleural effusion is present, lateral decubitus views aid in the determination of the nature of effusion (ie, free moving, loculated).
  • CT scanning and MRI
    • CT scanning and MRI are not routinely indicated when chest radiography findings are unremarkable.
    • However, in patients with pulmonary tuberculosis, these imaging studies can help demonstrate hilar lymphadenopathy, endobronchial tuberculosis, pericardial invasion, and early cavitations or bronchiectasis.

Other Tests

  • The TST is a widely used diagnostic test for evaluation of patients who have symptoms of tuberculosis or in whom infection with M tuberculosis is suspected. Although the sensitivity and the specificity of the TST are less than 100%, no better diagnostic test is widely available.
  • The American Academy of Pediatrics (AAP) has issued the following guidelines for pediatric testing:10
    • Immediate skin testing is indicated for the following children:
      • Those who have been in contact with persons with active or suspected tuberculosis
      • Immigrants from countries in which tuberculosis is endemic (eg, Asia, Middle East, Africa, Latin America) or children with travel histories to these countries
      • Those who have radiographic or clinical findings suggestive of tuberculosis
    • An annual TST is indicated for the following children:
      • Children who are infected with HIV or those living in a household with persons infected with HIV
      • Incarcerated adolescents
    • Testing at 2-year to 3-year intervals is indicated if the child has been exposed to high-risk individuals including those who are homeless, institutionalized adults who are infected with HIV, users of illicit drugs, residents of nursing homes, and incarcerated adolescents or adults.
    • Testing when children are aged 4-6 years and 11-16 years is indicated for the following children:
      • Children without risk factors residing in high-prevalence areas
      • Children whose parents emigrated from regions of the world with a high prevalence of tuberculosis or who have continued potential exposure by travel to the endemic areas and/or household contact
    • Performing an initial TST before the initiation of immunosuppressive therapy is recommended in any patient.
  • Administration of TST is as follows:
    • The recommended TST is the Mantoux test. The dosage of 0.1 mL or 5 TU purified protein derivative (PPD) should be injected intradermally into the volar aspect of the forearm using a 27-gauge needle. A detergent called Tween 80 to prevent loss of efficacy on contact and adsorption by glass stabilizes the PPD. A wheal should be raised and should measure approximately 6-10 mm in diameter.
    • Skilled personnel always should read the test 48-72 hours after administration. Measure the amount of induration and not erythema. This should be measured transverse to the long axis of the forearm.
    • Multiple puncture tests (eg, tine test, Heaf test) lack sensitivity and specificity and hence are not recommended.
  • The CDC and the AAP have provided recommendations on the size of the induration created by the TST that is considered a positive result and indicative of disease. The TST is interpreted on the basis of rule of 5 mm, 10 mm, and 15 mm.
    • Induration of 5 mm or more is considered a positive TST result in the following children:
      • Children having close contact with known or suspected contagious cases of the disease, including those with household contacts with active tuberculosis whose treatment cannot be verified before exposure
      • Children with immunosuppressive conditions (eg, HIV) or children who are on immunosuppressive medications
      • Children who have an abnormal chest radiography finding consistent with active tuberculosis, previously active tuberculosis, or clinical evidence of the disease
    • Induration of 10 mm or more is considered a positive TST result in the following children:
      • Children who are at a higher risk of dissemination of tuberculous disease, including those younger than 5 years or those who are immunosuppressed because of conditions such as lymphoma, Hodgkin disease, diabetes mellitus, and malnutrition
      • Children with increased exposure to the disease, including those who are exposed to adults in high-risk categories (eg, homeless, HIV infected, users of illicit drugs, residents of nursing homes, incarcerated or institutionalized persons); those who were born in or whose parents were born in high-prevalence areas of the world; and those with travel histories to high-prevalence areas of the world
    • Induration of 15 mm or more is considered a positive TST result in children aged 5 years or older without any risk factors for the disease.
  • False-positive reactions and false-negative results can have various causes.
    • False-positive reactions often are attributed to asymptomatic infection by environmental nontuberculous mycobacteria (due to cross-reactivity).
    • False-negative results may be due to vaccination with live-attenuated virus, anergy, immunosuppression, immune deficiency, or malnutrition. Other factors that may cause a false-negative result include improper administration (eg, subcutaneous injection, injection of too little antigen), improper storage, and contamination. PPD has been recognized to have an initial false-negative rate of 29%.
  • The following are important when administering the TST to prior recipients of bacille Calmette-Guérin (BCG) vaccine:
    • Immunization with BCG is not a contraindication to the TST. BCG vaccination is used in many parts of the world, especially in developing countries.
    • Differentiating tuberculin reactions caused by vaccination with BCG versus reactions caused by infection with M tuberculosis is difficult. History of contact with a person with contagious tuberculosis or emigration from a country with a high prevalence of tuberculosis suggests that the positive results are due to infection with M tuberculosis. However, multiple BCG vaccinations may increase the likelihood that the positive TST result is due to BCG vaccination. The positive reactivity caused by BCG vaccination generally wanes with the passage of time. With the administration of TST, this positive tuberculin reactivity may be boosted.
    • A prior BCG vaccination does not affect interpretation of a TST result for a person who is symptomatic or in whom tuberculosis is strongly suspected.

Patients with symptoms of TB disease may be given a tuberculin skin test or QuantiFERON TB Gold test ®. However, they should be evaluated for TB disease, regardless of their skin tests or QFT Gold results.

The chest x-ray is used to help rule out the possibility of pulmonary TB disease in a person who has a positive reaction to the tuberculin skin test and check for lung abnormalities in people who have symptoms of TB disease. The results cannot confirm or rule out that a person has TB disease.

The fourth step is a bacteriologic examination. A sputum specimen is obtained from patients suspected of having pulmonary TB disease; other specimens are obtained from patients suspected of having extrapulmonary TB disease. The specimen is examined under a microscope for the presence of acid-fast bacilli. When AFB are seen, they are counted. Patients with positive AFB smears are considered infectious. The specimen is then cultured, or grown, to determine whether it contains M. tuberculosis. A positive culture for M. tuberculosis confirms the diagnosis of TB disease.

After the specimen has been cultured, it may be tested for drug susceptibility. The results of drug susceptibility tests can help clinicians choose the appropriate drugs for use in treatment.

Supported  by
CLINICAL PEDIATRIC ONLINE 

Yudhasmara Foundation 

JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010

phone : 62(021) 70081995 – 5703646 

email : judarwanto@gmail.com,

http://clinicalpediatric.wordpress.com/

 

Clinical and Editor in Chief :

DR WIDODO JUDARWANTO 

 

Copyright © 2009, Clinical Pediatric Online Information Education Network. All rights reserved.

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