Tuberculosis Disease in Children

21/07/15
Tuberculosis disease in children
O fficial re print from UpToDate

www.uptodate .com 2015 UpToDate

Authors
Lisa V Adams, MD
Jeffrey R Starke, MD
Section Editors
C Fordham von Reyn, MD
Morven S Edwards, MD
Deputy Editor
Elinor L Baron, MD, DTMH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2015. | This topic last updated: Jun 16, 2015.
INTRODUCTION Formal policies and control efforts addressing tuberculosis (TB) in children have been
limited, in part due to lack of a standardized case definition and difficulties associated with establishing a
definitive diagnosis [1]. However, since diagnostic and treatment tools for TB in children have begun to improve
significantly, TB in children has received increasing attention by researchers, clinicians, and policy makers.
Issues related to TB disease in children will be reviewed here. Issues related to diagnosis and treatment of
latent TB infection (LTBI) in children are discussed in detail separately. (See "Latent tuberculosis infection in
children".)
EPIDEMIOLOGY
Global epidemiology Estimating the global burden of tuberculosis (TB) disease in children is challenging
due to the lack of a standard case definition, the difficulty in establishing a definitive diagnosis, the frequency of
extrapulmonary disease in young children, and the relatively low public health priority given to TB in children
relative to adults [2].
The World Health Organization's (WHO's) global TB data include age breakdowns only for smear-positive TB
cases; among children, such cases represent only a small subset of the burden of disease due to TB (about 8
percent) [3]. The WHO estimates that, of the 8.7 million incident cases of TB in 2011, approximately 500,000
occurred among children under age 15 [4]. Additionally, it is estimated that there were 64,000 pediatric deaths
due to TB (among HIV-negative children) [4]. Approximately 75 percent of these cases occurred in the 22
highest TB-burden countries (table 1) [5]. In many developing countries, children compose more than one-half of
the population, suggesting that the reported cases of childhood TB are likely underestimated.
Children under age five represent an important demographic group for understanding TB epidemiology, since TB
frequently progresses rapidly from latent infection to disease, and severe disease manifestations, such as
miliary TB and meningitis, are more common in this age group. Therefore, these children serve as sentinel
cases, indicating recent and/or ongoing transmission in the community.
Most children are infected by household contacts with TB disease, particularly parents or other caretakers.
Even in circumstances when adult index cases are sputum smear-negative, transmission to children has been
documented in 30 to 40 percent of households [6].
It has been estimated that, of nearly one million children who developed tuberculosis disease in 2010, 32,000
had multidrug-resistant TB [7]. Additional effort is needed to improve detection of drug-resistant TB among
children.
United States epidemiology Risk factors for pediatric TB in the United States include being foreign-born,
having a parent who is foreign-born, or having lived outside the United States for more than two months [8,9]. In
the United States, TB among children is relatively rare. In 2010, there were 818 cases of TB in children and
adolescents under 18 years of age reported by the United States Centers for Disease Control and Prevention
(CDC); this number represented 7 percent of the total 11,181 cases reported that year [8,10]. However, TB in
children and adolescents is prone to both under- and over-reporting due to the difficulties related to diagnosis.
Nonetheless, in the United States, TB in children and adolescents appears to be declining. Between 2007 and
2010, TB annual case notifications in those under age 18 years decreased from 997 (in 2007) to 818 cases (in
2010) [8].
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Between 2008 and 2010, most children and adolescents with TB were born in the United States (69 percent). In
contrast, most adults with TB in the United States are born in areas where the disease is endemic (table 2).
Roughly half of all nonUnited Statesborn patients under age 18 diagnosed with TB in this time period were
adolescents between the ages of 13 and 17 [8]. Among the child and adolescent TB patients who were born in
the United States, 66 percent had at least one nonUnited Statesborn parent [8]. One-quarter (25 percent) of
pediatric TB patients diagnosed in the United States had no known international connection through family or
residence history [8]. A small proportion of nonUnited Statesborn pediatric TB patients (4 percent) had
parents who were both born in the United States; these cases may arise from international adoptions, but this
could not be confirmed with available data [8].
Between 2008 and 2010, among the 2628 children and adolescents with TB with known race/ethnicity, 45
percent were Hispanic, 27 percent were black, 20 percent were Asian, 7 percent were white, and 1 percent
American Indian or Native Alaskan [8]. HIV status was only known for approximately half of the pediatric
patients reported; of these, only 1 percent was HIV-infected [8]. The isolates from 19 percent of the 918 children
and adolescents with positive cultures and drug susceptibility testing had detectable resistance to one or more
drugs, and 2 percent were multidrug-resistant TB [8].
CLINICAL MANIFESTATIONS
Pulmonary tuberculosis Pulmonary disease and associated intrathoracic adenopathy are the most frequent
presentations of tuberculosis (TB) in children [11,12]. Common symptoms of pulmonary TB in children include
[5]:
Chronic, unremitting cough that is not improving and has been present for more than three weeks
Fever of more than 38C for at least two weeks, other common causes having been excluded
Weight loss or failure to thrive (based on child's growth chart)
However, these symptoms are fairly nonspecific. In one study comparing symptoms of children with cultureproven TB with children with other lung diseases, there was no difference between the two groups with respect
to weight loss, chronic cough, and duration of symptoms [13]. The only factors differentiating the groups were
history of contact with an infectious TB case and a positive tuberculin skin test (TST).
Physical exam findings may suggest the presence of a lower respiratory infection, but there are no specific
clinical signs or findings to confirm that pulmonary TB is the cause. Children ages 5 to 10 may present with
clinically silent (but radiographically apparent) disease, particularly in the setting of contact investigation [11]. In
contrast, infants are more likely to present with signs and symptoms of lung disease. Common radiographic
findings are discussed below. (See 'Chest radiography' below.)
Extrapulmonary tuberculosis The clinical presentation of extrapulmonary TB depends on the site of
disease. The most common forms of extrapulmonary disease in children are TB of the superficial lymph nodes
and of the central nervous system (CNS) [14]. Neonates have the highest risk of progression to TB disease with
miliary and meningeal involvement [14]. Some forms of TB and their common physical signs are as follows [15]:
Tuberculous meningitis meningitis not responding to antibiotic treatment, with a subacute onset,
communicating hydrocephalus, stroke, and/or elevated intracranial pressure (see "Central nervous system
tuberculosis")
Pleural TB pleural effusion (see "Tuberculous pleural effusions in HIV-negative patients")
Pericardial TB pericardial effusion (see "Tuberculous pericarditis")
Abdominal TB distended abdomen with ascites, abdominal pain, jaundice, or unexplained chronic
diarrhea (see "Tuberculous enteritis" and "Tuberculous peritonitis")
TB adenitis painless, fixed, enlarged lymph nodes, especially in the cervical region, with or without
fistula formation (see "Tuberculous lymphadenitis")
TB of the joint nontender joint effusion (see "Skeletal tuberculosis")
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Vertebral TB back pain, gibbus deformity, especially of recent onset (rarely seen) (see "Skeletal
tuberculosis")
Skin warty lesion(s), papulonecrotic lesions, lupus vulgaris; erythema nodosum may be a sign of
tuberculin hypersensitivity
Renal sterile pyuria, hematuria (see "Renal disease in tuberculosis")
Eye iritis, optic neuritis, phlyctenular conjunctivitis (see "Tuberculosis and the eye")
In the context of exposure to TB, presence of these signs should prompt further investigation of extrapulmonary
TB.
Perinatal infection Perinatal TB can be a life-threatening infection; the mortality in the setting of congenital
and neonatal TB is about 50 percent [16-18]:
Congenital TB is rare and most often is associated with tuberculous endometritis or disseminated TB in
the mother. It can be acquired hematogenously via the placenta and umbilical vein or by fetal aspiration (or
ingestion) of infected amniotic fluid [16,18].
Clinical manifestations of congenital TB include respiratory distress, fever, hepatomegaly, splenomegaly,
poor feeding, lethargy, irritability, and low birth weight [17]. Clinical evaluation of the infant in the setting of
suspected congenital TB should include TST, HIV testing, chest radiograph, lumbar puncture, cultures
(blood and respiratory specimens), and evaluation of the placenta with histologic examination (including
acid-fast bacilli [AFB] staining culture). The TST in newborns is usually negative, but an interferon-gamma
release assay (IGRA) test may be positive in some cases.
Neonatal TB develops following exposure of an infant to his or her mother's aerosolized respiratory
secretions. This is more common than congenital TB, and diagnosis of neonatal TB can lead to
identification of previously unrecognized diagnosis of TB in the mother [19].
In the setting of congenital or neonatal TB, the mother should be evaluated as outlined in detail separately. (See
"Diagnosis of pulmonary tuberculosis in HIV-negative patients".)
Adolescent infection Adolescents with TB can present with features common in children or adults. In one
review including 145 cases of adolescent TB, the following features were noted [20]:
Most adolescents presented with clinical symptoms.
Rates of extrathoracic TB were high, including six immunocompetent adolescents with TB meningitis.
Most cases were AFB sputum smear-negative.
Only half of patients with intrathoracic TB had positive cultures.
Antituberculous medications were generally well tolerated.
DIAGNOSIS Tuberculosis (TB) in children is often diagnosed clinically. Because pulmonary TB in children
typically presents with paucibacillary, noncavitary pulmonary disease, bacteriologic confirmation is achievable in
only about 30 to 40 percent of cases. Obtaining sputum samples from young children is challenging because
they lack sufficient tussive force to produce adequate sputum samples by expectoration alone [21]. For these
reasons, gastric aspiration is the principal means of obtaining material for culture from young children; induced
sputum may also be collected if feasible.
For diagnosis of extrapulmonary TB, specimens for culture should be collected from any site where infection is
suspected. The most common extrapulmonary specimens include whole blood, bone marrow, tissue specimens
(such as lymph node or bone), cerebrospinal fluid, urine, and pleural fluid. Diagnostic yield is variable. In pleural
TB, adenosine deaminase (ADA) levels over 40 units/L in the pleural fluid are observed in the majority of patients
[11]. (See "Tuberculous pleural effusions in HIV-negative patients".)
A diagnosis of TB (pulmonary or extrapulmonary) in a child is often based on the presence of the classic triad:
(1) recent close contact with an infectious case, (2) a positive tuberculin skin test (TST) or interferon-gamma
release assay (IGRA), and (3) suggestive findings on chest radiograph or physical examination [15].
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The approach outlined by the World Health Organization (WHO) for evaluation of a child suspected of having TB
includes [5]:
Careful history (including history of TB contact and symptoms consistent with TB)
Clinical examination (including growth assessment)
TST and/or IGRA (both tests, if available, to increase sensitivity)
Bacteriological confirmation whenever possible
Investigations relevant for suspected pulmonary and extrapulmonary TB
HIV testing (eg, in high HIV prevalence areas)
All data, including thorough history, physical exam, and diagnostic testing, must be considered carefully. A
history of recent close contact with an infectious (sputum smear positive) case of TB is a critical factor in
making the diagnosis of TB in children, especially for those under the age of five years. However, the ill adult
may have not yet been diagnosed, so asking about ill contacts and facilitating evaluation for ill adults can also
expedite diagnosis for children.
In many cases of TB in children, laboratory confirmation is never established (particularly among children under
five years of age). In such cases, a presumptive diagnosis may be made based on clinical and radiographic
response to empiric treatment. Treatment is often guided by the culture and drug susceptibility results from the
index case (eg, the adults TB contact).
Screening tests
Tuberculin skin test A positive TST may be present in both contained latent TB infection (LTBI) and in
active TB disease. Thus, although a positive TST may help support a diagnosis of active disease, this finding
alone is not diagnostic of active disease; it must be considered together with other diagnostic criteria. The TST
is helpful for diagnosis of TB in children only in circumstances when it is positive. Criteria for positive TST are
outlined in the Table (table 3) [15]. A positive TST may be falsely positive due to prior vaccination with Bacille
Calmette-Gurin (BCG), infection with nontuberculous mycobacteria, and improper administration or
interpretation (table 4).
A negative TST does NOT rule out TB disease, since false-negative results can occur in a variety of
circumstances (eg, incorrect administration or interpretation of the TST, age less than six months,
immunosuppression by HIV, other disease or medication, certain viral illnesses or recent live-virus
immunization, overwhelming TB infection) [15,22]. (See "Diagnosis of latent tuberculosis infection (tuberculosis
screening) in HIV-negative adults", section on 'False-negative tests'.)
Because the TST cannot distinguish between TB disease, latent Mycobacterium tuberculosis infection, and
infection due to nontuberculous mycobacteria, the result must be interpreted in the context of the clinical
features and history of TB exposure [23]. Overall, up to 40 percent of immunocompetent children with cultureconfirmed TB disease may have a negative TST [24,25]. TST positivity rates vary by form of disease; in
pulmonary and extrapulmonary TB, the TST is typically positive (90 and 80 percent respectively), while in miliary
TB and TB meningitis, the TST is usually positive in only 50 percent of cases [26-28].
Interferon gamma release assays IGRAs are in vitro blood tests of cell-mediated immune response.
These assays have greater specificity than TST for diagnosis of LTBI and are most useful for evaluation of LTBI
in BCG-vaccinated individuals [29]. As with the TST, IGRAs cannot distinguish LTBI from active disease. IGRAs
may prove a useful tool to improve the diagnosis of TB, although evidence for use of IGRAs in children is limited
[30-34]. Use of both TST and IGRA may increase sensitivity for evaluation of children with suspected TB.
Additional issues related to use of IGRAs are discussed further separately. (See "Interferon-gamma release
assays for diagnosis of latent tuberculosis infection".)
Imaging
Chest radiography Frontal and lateral chest radiography can be a very useful tool for diagnosis of TB in
children (image 1A-K) [35,36]. The most common chest radiograph finding in a child with TB disease is a
primary complex, which consists of opacification with hilar or subcarinal lymphadenopathy, in the absence of
notable parenchymal involvement [5]. When adenopathy advances, consolidation or a segmental lesion may
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occur, leading to collapse in the setting of infiltrate and atelectasis.

In a study of 326 traced contacts under five years of age, 9 percent of children diagnosed with intrathoracic TB
were asymptomatic and had radiographic findings only of the primary complex [37]. A miliary pattern of
opacification is highly suspicious for TB, as is opacification that does not improve or resolve following a course
of antibiotics [5].
Adolescents with TB generally present with typical adult disease findings of upper lobe infiltrates, pleural
effusions, and cavitations on chest radiograph [5]. (See "Diagnosis of pulmonary tuberculosis in HIV-negative
patients".)
Computed tomography scan Computed tomography (CT) scan of the chest may be used to further
delineate the anatomy for cases in which radiographic findings are equivocal. Endobronchial involvement,
bronchiectasis, and cavitations may be more readily visualized on CT scans than chest radiographs [38].
However, there is no role for routine use of CT scans in the evaluation of an asymptomatic child since treatment
regimens are based on chest radiography findings [11].
In the setting of tuberculous meningitis, CT scan of the head is useful. Hydrocephalus and basilar meningeal
enhancement are observed in 80 and 90 percent of cases, respectively; chest radiography may be normal [11].
Laboratory studies The likelihood of achieving bacteriological confirmation depends on the extent of disease
and the type of specimen. The initial approach for diagnosis of TB in children consists of sputum examination:
expectorated (for adolescents), swallowed and collected as gastric contents (young children), or induced.
Gastric aspiration is the primary method of obtaining material for acid-fast bacilli (AFB) smear and culture from
young children.
Sputum specimens should be sent for examination by smear microscopy and mycobacterial culture. Nucleic
acid amplification (NAA) testing can be used for rapid diagnosis of an organism belonging to the M. tuberculosis
complex (24 to 48 hours) in patients for whom the suspicion for TB is moderate to high [39]. (See "Diagnosis of
pulmonary tuberculosis in HIV-negative patients", section on 'Diagnostic microbiology'.)
Acid-fast bacilli smear and culture
Sputum Obtaining expectorated sputum from children for detection of AFB is difficult and its
examination of low yield (15 percent or less for microscopic examination and 30 percent or less for culture)
[40,41]. However, most adolescents can produce expectorated sputum spontaneously.
Sputum induction has higher yield than expectorated sputum in children, and the use of sputum induction for
obtaining TB diagnostic specimens in children is increasing. Sputum induction is performed via administration of
aerosolized heated saline combined with salbuterol (or similar drug to minimize wheezing), followed by
suctioning to capture the expectorated sputum. In a study of 250 children (median age 13 months), sputum
induction was found to be a safe and effective procedure in children as young as one month of age [40]. In two
studies, outpatient sputum induction yielded culture results comparable to or better than inpatient gastric
aspiration [24,40]. Minimal adverse effects associated with the procedure included coughing, epistaxis,
vomiting, and wheezing. Children with underlying reactive airways disease should receive pretreatment with a
bronchodilator to prevent bronchospasm during or following the procedure [40].
Gastric aspirate Early morning gastric contents collected from a fasting child contain sputum
swallowed during the night. Gastric aspiration specimens may be obtained in the inpatient or outpatient setting
[42,43]. Ideally, three early morning samples collected on different days before the child eats or ambulates
optimize specimen yield [44].
Gastric aspiration remains the most common method for obtaining respiratory samples from children (in
facilities where this procedure may be performed). In general, cultures of gastric aspirate specimens are positive
for TB in only 30 to 40 percent of cases [45]. Smears are even less reliable with positive results in fewer than 10
percent of cases [45]; in addition, false-positive smear results caused by the presence of nontuberculous
mycobacteria can occur [25]. Similar yields have been reported with nasopharyngeal aspiration, a less invasive
technique that can be performed in the outpatient setting [46].
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Other specimens Other body fluid and/or tissue samples may be necessary in some circumstances,
depending on suspicion for extrapulmonary TB. The approach to these diagnostic tools is outlined separately.
(See "Diagnosis of pulmonary tuberculosis in HIV-negative patients", section on 'Pleural effusion' and "Diagnosis
of pulmonary tuberculosis in HIV-negative patients", section on 'Tissue biopsy'.)
Diagnosis of TB should prompt HIV testing. (See "Screening and diagnostic testing for HIV infection".)
Rapid testing The GeneXpert MTB/RIF assay is an automated nucleic acid amplification test that can
simultaneously identify M. tuberculosis and detect rifampin resistance. This test performs substantially better
than smear microscopy [47,48]. In a randomized trial including 452 children in South Africa with suspected
pulmonary TB, 6 percent had a positive sputum smear, 16 percent had a positive sputum culture, and 13
percent had a positive sputum GeneXpert MTB/RIF result [47]. The initial GeneXpert MTB/RIF test detected 100
percent of culture-positive cases that were smear positive but only 33 percent of those that were smear
negative; a second GeneXpert MTB/RIF test improved the detection of smear-negative cases to 61 percent.
Overall, with induced sputum specimens, the sensitivity and specificity were 59 and 99 percent, respectively, for
one GeneXpert MTB/RIF test and 76 and 99 percent for two GeneXpert MTB/RIF tests. Test performance was
unaffected by patient HIV status. Results for GeneXpert MTB/RIF were available within a median of one day
(versus 12 days for culture). Detection of rifampin resistance was less promising: 1 of 3 rifampin-resistant
isolates was not detected, and 4 of 74 rifampin-sensitive isolates had an "indeterminate" result.
While the GeneXpert MTB/RIF test appears to be highly specific, its sensitivity for sputum smear negative TB in
children remains low. Since culture was used as the gold standard in the study described above, the sensitivity
of GeneXpert MTB/RIF is expected to be even lower in sputum culture-negative, clinically confirmed cases.
Therefore, it cannot replace current methods used to suspect and diagnose TB in infants and children. Most
children in the study presented with symptomatic pulmonary TB and extensive disease. The GeneXpert
MTB/RIF test is meant to be a rapid diagnostic test that may take the place of sputum microscopy but not
mycobacterial culture. A negative GeneXpert MTB/RIF test should be interpreted in the context of the childs
clinical and radiolographic findings. Sputum culture remains a more sensitive test and is required to detect the
full drug susceptibility profile of the infecting organism. Further study of the assay is needed in areas with high
and low prevalence of TB. (See "Diagnosis of pulmonary tuberculosis in HIV-negative patients", section on 'Xpert
MTB/RIF assay'.)
Use of the GeneXpert MTB/RIF test on gastric lavage and nasopharyngeal specimens may be beneficial in
settings where induced sputum and mycobacterial culture are not feasible. In one study in Zambia, sensitivity
and specificity were found to be similar for sputum and gastric lavage aspirates (sensitivity 90 and 69 percent
respectively; specificity 99 percent for both) [49]. Among over 900 children in South Africa, the sensitivity of
GeneXpert MTB/RIF was similar for induced sputum and nasopharyngeal aspirate specimens (71 and 65
percent, respectively); specificity was >98 percent [50].
Molecular line probe assays are rapid tests that can be used to detect the presence of M. tuberculosis as well
as genetic mutations that confer rifampin resistance alone or in combination with isoniazid resistance. These
assays have high sensitivity (90 to 97 percent) and specificity (99 percent) compared with drug susceptibility
testing [51]. (See "Natural history, microbiology, and pathogenesis of tuberculosis", section on 'Drug
susceptibility tests'.)
Drug resistance New technologies including GeneXpert MTB/RIF and line probe assays can facilitate
diagnosis of drug-resistant TB among children, since these assays do not require culture. Culture and drug
susceptibility testing (DST) are recommended whenever possible [52]. For most children, the diagnosis of drugresistant TB is established based on clinical criteria including signs and symptoms, radiographic findings,
history of contact with a presumed or confirmed source case with drug-resistant TB, and failure to respond to
first-line TB drugs [53].
To avoid unnecessary exposure to toxic second-line agents, extensive effort should be made to obtain multiple
high-quality specimens from the most accessible site(s) of disease [53]. All isolates with resistance to rifampin
should undergo complete second-line drug susceptibility testing and genotyping [53].
Issues related to diagnosis of drug resistance are discussed further separately. (See "Diagnosis, treatment, and
prevention of drug-resistant tuberculosis".)
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Investigational diagnostic methods Because of the difficulty in achieving microbiologic confirmation of

clinically suspected TB in children, interest has grown in alternate methods of laboratory diagnosis. One
candidate method is microarray analysis of blood samples to identify a pattern of RNA expression that is
associated with active TB infection. One study identified an RNA expression risk score that distinguished with
high sensitivity and specificity culture-confirmed TB from latent TB and diseases other than TB among children
in sub-Saharan Africa. However, the risk score did not perform as well among children with clinically diagnosed,
culture-negative TB [54]. Moreover, in order to be a practical tool in resource-limited settings, where its use
would be most relevant, the technology would require substantial modification to reduce cost and complexity.
TREATMENT
Susceptible disease Guidelines endorsed by the United States Centers for Disease Control (CDC) and the
World Health Organization (WHO) for the treatment of tuberculosis (TB) in children emphasize the use of shortcourse multidrug regimens under directly observed therapy [15]. In general, the pediatric treatment regimens
outlined by the WHO are comparable to the adult regimens (table 5) [25,55]. Because TB in young children can
rapidly disseminate with serious sequelae, prompt initiation of therapy is critical. Appropriate dosing is outlined
in the Table (table 6). (See "Treatment of pulmonary tuberculosis in HIV-negative patients".)
Pyridoxine supplementation is not routinely recommended for children receiving isoniazid (INH) but should be
considered for exclusively breastfed infants, malnourished children or those with diets poor in pyridoxine, and
HIV-infected children [25,56].
In many cases of TB in children, laboratory confirmation is never established (particularly among children under
five years of age). In such cases, a presumptive diagnosis may be made based on clinical and radiographic
response to empiric treatment. If the cultures are negative, the isolates of contacts (if known/available) should
guide decisions about treatment with respect to susceptibility.
Drug susceptibility testing (DST) should be performed on initial isolates from each site of disease. Susceptibility
testing should be repeated if the patient remains culture-positive after three months of therapy or positive
cultures are detected after negative cultures have been documented.
In HIV-positive children not on antiretroviral therapy (ART), ART should be initiated within eight weeks of starting
antituberculous therapy or within two to four weeks if the CD4 count is <50 cells/mm3. Children with TB
meningitis may be the only exception. Emerging evidence suggests that there is no survival benefit to starting
ART before two months of antituberculous therapy and, in fact, delaying ART until that time may reduce adverse
events [57]. Selection of an optimal ART regimen should be made in consultation with a pediatric HIV specialist.
Unexplained deterioration among immunocompetent children receiving appropriate therapy for pulmonary and/or
extrapulmonary TB has been described [58,59]. In one study of 110 children, clinical or radiographic
deterioration was observed in 14 percent of cases after initiating therapy (range 10 to 181 days; mean 80 days)
[58]. The most common complication was enlarging intrathoracic lymphadenopathy, often causing airway
compromise. Deterioration was more likely among children with weight-for-age 25th percentile and multiple
sites of disease. All children achieved clinical or radiographic cure; corticosteroids were administered in 60
percent of cases. In another study of 115 immunocompetent children, 12 developed paradoxical worsening
within 15 to 75 days (median 39 days) of starting TB therapy; children with paradoxical reactions tended to be
younger (median age at diagnosis of 26 months versus 66 months) and had never received BCG vaccination
[59]. The most common manifestation was worsening of preexisting pulmonary lesions, observed in 75 percent,
while 25 percent had new disease present in new anatomic locations.
Drug-resistant TB Expert consultation is important for management of drug-resistant TB. Ensuring treatment
adherence and support through a multidisciplinary care team are critical components of care.
Selection of drugs for treatment of drug-resistant TB in children should be guided by the DST results of the
childs isolate; in the absence of such data, treatment should be guided by the DST results of the presumed
source case.
Ideally, the regimen for treatment of drug-resistant TB should include at least four drugs to which the isolate is
known to be, or presumed to be, susceptible [53]. The number of drugs and duration of therapy should be
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determined by the extent of disease, site of disease (and correlating drug penetration), and treatment response
[53]. Children with cavitary or extensive disease with resistance to only rifampin and isoniazid can achieve a
favorable outcome when treated for 18 months from the time the first negative culture is obtained [53].
Whenever possible, first-line TB drugs should be used since they have the most favorable efficacy and toxicity
profiles. In general, treatment of multidrug-resistant TB should include a fluoroquinolone and an injectable agent
(although there is no role for use of more than one fluoroquinolone or injectable agent) (table 7). Subsequently, if
needed, ethionamide, cycloserine, and aminosalicylic acid may be added to complete the regimen such that it
consists of at least four active drugs. Alternative agents should be added only when the preceding drugs are not
sufficient. Treatment of children with second-line agents is complicated by the absence of pediatric formulations
for most of these drugs, which can lead to under- or over-dosing.
Individualized treatment in children has been associated with generally good outcomes. In a retrospective study
of 149 children under 15 years of age (median age 36 months) with documented or suspected drug-resistant TB
in South Africa, treatment regimens included at least four active drugs, included an injectable agent in 66
percent of patients, and were given for a median of 13 months [60]. Cure or probable cure was achieved in 92
percent. Similar outcomes were reported in a series of 38 children in Peru who received 18 to 24 months of a
supervised individualized treatment regimen (five to seven drugs) based on susceptibility results of their M.
tuberculosis isolate or the source case's isolate (usually a household contact) [61].
Drug toxicity is common; in one meta-analysis of children treated for multidrug-resistant TB, it was reported in
39 percent of cases [62]. Similarly, in the series from Peru, adverse effects occurred in 42 percent of cases,
although no events required suspension of therapy for >5 days [61]. Children on treatment for drug-resistant TB
should be monitored at least monthly for adherence, response to treatment (eg, sputum analysis for those with
pulmonary TB), and potential adverse events.
PREVENTION Measures for prevention of tuberculosis (TB) include infection control interventions and prompt
identification and treatment of latent TB infection (LTBI). Suspicion of TB disease in a child should be reported to
the health department so that an investigation can be started right away. (See "Tuberculosis transmission and
control", section on 'Contact investigation' and "Latent tuberculosis infection in children".)
The optimal treatment for prevention of TB among children with exposure to multidrug-resistant (MDR) TB cases
is uncertain. Some experts recommend using a fluoroquinolone antibiotic for treatment of MDR LTBI that is
presumed fluoroquinolone susceptible; some would give a second drug to which the organism is likely
susceptible. Further study is needed [63].
In countries where TB is endemic, routine childhood Bacille Calmette-Gurin (BCG) immunization is also an
important preventive measure. (See "BCG vaccination".)
SUMMARY AND RECOMMENDATIONS
Estimating the global burden of tuberculosis (TB) disease in children is challenging due to the lack of a
standard case definition, the difficulty in establishing a definitive diagnosis, the frequency of
extrapulmonary disease in young children, and the relatively low public health priority given to TB in
children relative to adults. As a result, there is likely significant underreporting of childhood TB from highprevalence countries. (See 'Epidemiology' above.)
Children under the age of five years represent an important demographic group for understanding TB
epidemiology; in this group, TB frequently progresses rapidly from latent infection to TB disease.
Therefore, these children serve as sentinel cases, indicating recent and/or ongoing transmission in the
community. (See 'Epidemiology' above.)
Common symptoms of pulmonary TB in children include cough (chronic, without improvement for more
than three weeks), fever (more than 38C for more than two weeks), and weight loss or failure to thrive.
Physical exam findings may suggest the presence of a lower respiratory infection but there are no specific
findings to confirm that pulmonary TB is the cause. (See 'Pulmonary tuberculosis' above.)
The clinical presentation of extrapulmonary TB depends on the site of disease. The most common forms of
extrapulmonary disease in children are TB of the superficial lymph nodes and of the central nervous
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system (CNS). Infants have the highest risk of progression to TB disease with dissemination (miliary TB)
and meningeal involvement. (See 'Extrapulmonary tuberculosis' above.)
Forms of perinatal TB include congenital and neonatal disease. Congenital TB is very rare and most often
is associated with maternal tuberculous endometritis or miliary TB. Neonatal TB is more common and
develops following exposure of an infant to his or her mother's aerosolized respiratory secretions. (See
'Perinatal infection' above.)
TB in children is often diagnosed clinically; in many cases, laboratory confirmation is never established
(particularly among children under five years of age). Diagnosis is often based on the presence of the
classic triad: (1) recent close contact with an infectious case, (2) a positive tuberculin skin test (TST) or
interferon-gamma release assay (IGRA), and (3) suggestive findings on chest radiograph or physical
examination. (See 'Diagnosis' above.)
In children, the TST or IGRA may be used as a tool for diagnosis of TB disease or latent TB (LTBI)
(although in adults the TST or IGRA may be used only for diagnosis of LTBI, not TB disease). The TST or
IGRA is helpful for diagnosis of TB in children only in circumstances when it is positive (table 3). (See
'Tuberculin skin test' above.)
The most common chest radiograph finding in a child with TB disease is a primary complex, which
consists of opacification with hilar or subcarinal lymphadenopathy, in the absence of notable parenchymal
involvement. (See 'Imaging' above.)
Gastric aspiration is the primary method of obtaining material for acid-fast bacilli (AFB) smear and culture
from young children, since these patients lack sufficient tussive force to produce adequate sputum
samples by expectoration alone. Alternative approaches include sputum induction or expectoration (for
older children). For diagnosis of extrapulmonary TB, specimens for culture should be collected from any
site where infection is suspected. Diagnosis of TB should also prompt HIV testing. (See 'Laboratory
studies' above.)
The pediatric treatment regimens for TB are outlined in the Tables (table 5 and table 6). Because TB in
young children can rapidly disseminate with serious sequelae, prompt initiation of therapy is critical.
Use of UpToDate is subject to the Subscription and License Agreement.
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22. Drobac PC, Shin SS, Huamani P, et al. Risk factors for in-hospital mortality among children with
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Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy
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35. Gie RP, Beyers N, Schaaf HS, Goussard P. The challenge of diagnosing tuberculosis in children: a
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perspective from a high incidence area. Paediatr Respir Rev 2004; 5 Suppl A:S147.
36. Gwee A, Pantazidou A, Ritz N, et al. To x-ray or not to x-ray? Screening asymptomatic children for
pulmonary TB: a retrospective audit. Arch Dis Child 2013; 98:401.
37. Marais BJ, Gie RP, Hesseling AC, et al. Radiographic signs and symptoms in children treated for
tuberculosis: possible implications for symptom-based screening in resource-limited settings. Pediatr
Infect Dis J 2006; 25:237.
38. Lighter J, Rigaud M. Diagnosing childhood tuberculosis: traditional and innovative modalities. Curr Probl
Pediatr Adolesc Health Care 2009; 39:61.
39. Centers for Disease Control and Prevention (CDC). Updated guidelines for the use of nucleic acid
amplification tests in the diagnosis of tuberculosis. MMWR Morb Mortal Wkly Rep 2009; 58:7.
40. Zar HJ, Hanslo D, Apolles P, et al. Induced sputum versus gastric lavage for microbiological confirmation
of pulmonary tuberculosis in infants and young children: a prospective study. Lancet 2005; 365:130.
41. Marais BJ, Gie RP, Schaaf HS, et al. Childhood pulmonary tuberculosis: old wisdom and new challenges.
Am J Respir Crit Care Med 2006; 173:1078.
42. Lobato MN, Loeffler AM, Furst K, et al. Detection of Mycobacterium tuberculosis in gastric aspirates
collected from children: hospitalization is not necessary. Pediatrics 1998; 102:E40.
43. Mukherjee A, Singh S, Lodha R, et al. Ambulatory gastric lavages provide better yields of Mycobacterium
tuberculosis than induced sputum in children with intrathoracic tuberculosis. Pediatr Infect Dis J 2013;
32:1313.
44. Cruz A, Revell P, Starke J. Gastric Aspirate Yield For Children With Suspected Pulmonary Tuberculosis.
J Ped Infect Dis 2013; 2:171.
45. Starke JR. Pediatric tuberculosis: time for a new approach. Tuberculosis (Edinb) 2003; 83:208.
46. Owens S, Abdel-Rahman IE, Balyejusa S, et al. Nasopharyngeal aspiration for diagnosis of pulmonary
tuberculosis. Arch Dis Child 2007; 92:693.
47. Nicol MP, Workman L, Isaacs W, et al. Accuracy of the Xpert MTB/RIF test for the diagnosis of
pulmonary tuberculosis in children admitted to hospital in Cape Town, South Africa: a descriptive study.
Lancet Infect Dis 2011; 11:819.
48. Smith MS, Williams DE, Worley SD. Potential uses of combined halogen disinfectants in poultry
processing. Poult Sci 1990; 69:1590.
49. Bates M, O'Grady J, Maeurer M, et al. Assessment of the Xpert MTB/RIF assay for diagnosis of
tuberculosis with gastric lavage aspirates in children in sub-Saharan Africa: a prospective descriptive
study. Lancet Infect Dis 2013; 13:36.
50. Zar HJ, Workman L, Isaacs W, et al. Rapid molecular diagnosis of pulmonary tuberculosis in children
using nasopharyngeal specimens. Clin Infect Dis 2012; 55:1088.
51. Perez-Velez CM. Pediatric tuberculosis: new guidelines and recommendations. Curr Opin Pediatr 2012;
24:319.
52. World Health Organization. Guidance for national tuberculosis programmes on the management of
tuberculosis in children, Second edition. Geneva, Switzerland 2014. WHO/HTM/TB/2014.03
53. Seddon JA, Furin JJ, Gale M, et al. Caring for children with drug-resistant tuberculosis: practice-based
recommendations. Am J Respir Crit Care Med 2012; 186:953.
54. Anderson ST, Kaforou M, Brent AJ, et al. Diagnosis of childhood tuberculosis and host RNA expression in
Africa. N Engl J Med 2014; 370:1712.
55. Donald PR, Maher D, Maritz JS, Qazi S. Ethambutol dosage for the treatment of children: literature review
and recommendations. Int J Tuberc Lung Dis 2006; 10:1318.
56. Cruz AT, Starke JR. Treatment of tuberculosis in children. Expert Rev Anti Infect Ther 2008; 6:939.
57. Trk ME, Yen NT, Chau TT, et al. Timing of initiation of antiretroviral therapy in human immunodeficiency
virus (HIV)--associated tuberculous meningitis. Clin Infect Dis 2011; 52:1374.
58. Thampi N, Stephens D, Rea E, Kitai I. Unexplained deterioration during antituberculous therapy in children
and adolescents: clinical presentation and risk factors. Pediatr Infect Dis J 2012; 31:129.
59. Olive C, Mouchet F, Toppet V, et al. Paradoxical reaction during tuberculosis treatment in
immunocompetent children: clinical spectrum and risk factors. Pediatr Infect Dis J 2013; 32:446.
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60. Seddon JA, Hesseling AC, Godfrey-Faussett P, Schaaf HS. High treatment success in children treated
for multidrug-resistant tuberculosis: an observational cohort study. Thorax 2014; 69:458.
61. Drobac PC, Mukherjee JS, Joseph JK, et al. Community-based therapy for children with multidrugresistant tuberculosis. Pediatrics 2006; 117:2022.
62. Ettehad D, Schaaf HS, Seddon JA, et al. Treatment outcomes for children with multidrug-resistant
tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12:449.
63. Seddon JA, Hesseling AC, Finlayson H, et al. Preventive therapy for child contacts of multidrug-resistant
tuberculosis: a prospective cohort study. Clin Infect Dis 2013; 57:1676.
Topic 8007 Version 34.0
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GRAPHICS
The 22 highest tuberculosis-burden countries
Afghanistan
Bangladesh
Brazil
Cambodia
China
Democratic Republic of the Congo
Ethiopia
India
Indonesia
Kenya
Mozambique
Myanmar
Nigeria
Pakistan
Philippines
Russian Federation
South Africa
Tanzania
Thailand
Uganda
Vietnam
Zimbabwe
Data from: World Health Organization. Global Tuberculosis Report 2014. Available at:
http://www.who.int/tb/country/en/index.html (Accessed on July 9, 2015).
Graphic 68082 Version 6.0
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Countries with high rates of tuberculosis (TB)

Afghanistan
Dominican Republic
Lithuania
Rwanda
Algeria
Ecuador
Madagascar
Sao Tome and

Principe
Angola
Equatorial Guinea
Malawi
Senegal
Azerbaijan
Eritrea
Malaysia
Sierra Leone
Bangladesh
Ethiopia
Mali
Solomon Islands
Belarus
Fiji
Marshall Islands
Somalia
Benin
Gabon
Mauritania
South Africa
Bhutan
Gambia
Micronesia
(Federated States
of)
South Sudan
Bolivia (Plurinational
State of)
Georgia
Mongolia
Sri Lanka
Botswana
Ghana
Morocco
Sudan
Brunei Darussalam
Greenland
Mozambique
Swaziland
Burkina Faso
Guatemala
Myanmar
Tajikistan
Burundi
Guinea
Namibia
Thailand
Cote d'Ivoire
Guinea-Bissau
Nepal
Timor-Leste
Cabo Verde
Guyana
Nicaragua
Togo
Cambodia
Haiti
Niger
Turkmenistan
Cameroon
Honduras
Nigeria
Tuvalu
Central African
India
Northern Mariana
Uganda
Republic
Islands
Chad
Indonesia
Pakistan
Ukraine
China
Kazakhstan
Papua New Guinea
United Republic of
Tanzania
China, Hong Kong

SAR
Kenya
Peru
Uzbekistan
China, Macao SAR
Kiribati
Philippines
Vanuatu
Congo
Kyrgyzstan
Republic of Korea
Vietnam
Democratic People's
Republic of Korea
Lao People's
Democratic Republic
Republic of Moldova
Zambia
Democratic Republic
of the Congo
Lesotho
Romania
Zimbabwe
Djibouti
Liberia
Russian Federation
Reproduced with permission from: World Health Organization, Global Tuberculosis Control: Estimated
burden of TB in 2013. http://www.who.int/tb/country/data/download/en/ Copyright 2013 World
Health Organization.
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Definitions of positive tuberculin skin test (TST) results in infants,

children, and adolescents*
Induration 5 mm or greater
Children in close contact with known or suspected contagious people with tuberculosis
disease
Children suspected to have tuberculosis disease:
Findings on chest radiograph consistent with active or previous tuberculosis disease
Clinical evidence of tuberculosis disease
Children receiving immunosuppressive therapy or with immunosuppressive conditions,
including human immunodeficiency (HIV) infection
Children at increased risk of disseminated tuberculosis disease:
Children younger than four years of age
Children with other medical conditions, including Hodgkin disease, lymphoma, diabetes
mellitus, chronic renal failure, or malnutrition
Children with likelihood of increased exposure to tuberculosis disease:
Children born in high-prevalence regions of the world
Children who travel to high-prevalence regions of the world
Children frequently exposed to adults who are HIV infected, homeless, users of illicit
drugs, residents of nursing homes, incarcerated, or institutionalized
Children age four years or older without any risk factors
* These definitions apply regardless of previous bacille Calmette-Gurin immunization; erythema
alone at TST site does not indicate a positive test result. Tests should be read at 48 to 72 hours
after placement.
Evidence by physical examination or laboratory assessment that would include tuberculosis in
the working differential diagnosis (eg, meningitis).
Including immunosuppressive doses of corticosteroids or tumor necrosis factor-alpha
antagonists.
From: American Academy of Pediatrics. Tuberculosis. In: Red Book: 2012 Report of the Committee
on Infectious Diseases, 29th ed, Pickering LK (Ed), American Academy of Pediatrics, Elk Grove
Village, IL 2012. Used with the permission of the American Academy of Pediatrics. Copyright
2012. The contents of this table remain unchanged in the Red Book: 2015 Report of the Committee
on Infectious Diseases, 30th ed.
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Potential causes of false-negative tuberculin tests

Technical (potentially correctable)
Tuberculin material:
Improper storage (exposure to light or heat)
C ontamination, improper dilution, or chemical denaturation
Administration:
Injection of too little tuberculin, or too deeply (should be intradermal)
Administration more than 20 minutes after drawing up into the syringe
Reading:
Inexperienced or biased reader
Error in recording
Biologic (not correctable)

Infections:
Active tuberculosis (especially if advanced)
Other bacterial infection (typhoid fever, brucellosis, typhus, leprosy, pertussis)
HIV infection (especially if C D4 count <200)
Other viral infection (measles, mumps, varicella)
Fungal infection (South American blastomycosis)
Recent live virus vaccination (measles, mumps, polio)

Immunosuppressive drugs (corticosteroids, tumor necrosis factor inhibitors, and others)
Metabolic disease: chronic renal failure, severe malnutrition, stress (surgery, burns)
Diseases of lymphoid organs (lymphoma, chronic lymphocytic leukemia, sarcoidosis)
Age: infants <6 months, older adults
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Classic Ghon complex in a child infected with

Mycobacterium tuberculosis
This radiograph shows a classic Ghon complex in a child infected with

Mycobacterium tuberculosis about six months previously, based on
results of a contact investigation. There is a calcifed parenchymal
lesion and calcification of the regional hilar lymph node. Although a
Ghon complex contains live organisms, the number is small (as seen in
infection rather than disease), so management with isoniazid alone as
for latent infection is sufficient.
Courtesy of Jeffrey R Starke, MD.
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Expansile pneumonia caused by tuberculosis
This two-year-old toddler, infected by his mother, has an expansile

pneumonia caused by tuberculosis and, perhaps, a secondary
infection. The child presented with high fever, cough, and weight loss.
The clinical symptoms improved with conventional antibiotics, but
cultures of the gastric aspirates grew Mycobacterium tuberculosis. A
subsequent computed tomography (CT) scan of the chest revealed
extensive right-sided hilar adenopathy with obstruction of the main
bronchus to the right upper lobe.
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Extensive miliary pulmonary lesions in disseminated

TB
Extensive miliary pulmonary lesions in a young child with disseminated

tuberculosis (TB). The child presented in a shock-like state with
extreme respiratory distress, weight loss, and fever. After appropriate
treatment, the child had a full recovery and a normal chest
radiograph.
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Extensive pulmonary tuberculosis in a preadolescent child
Extensive pulmonary tuberculosis in a pre-adolescent child. There is

advanced disease in the left lung, with disease in the right lung
occurring, perhaps, via lymphatic spread.
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Progressive primary tuberculosis in a toddler
Progressive primary tuberculosis in a toddler. There is extensive hilar

adenopathy with subsequent collapse-consolidation in the left lung,
and a miliary-like presentation in the right lung.
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Cavitary tuberculosis in an adolescent male
Cavitary tuberculosis in an adolescent male. There is infiltrate and a

cavity along the horizontal fissure on the right. Note the absence of
hilar adenopathy, which is typical of so-called reactivation or adulttype tuberculosis in adolescents.
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Enlarged right-sided hilar lymph nodes with local

infiltrate and atelectasis
Enlarged right-sided hilar lymph nodes with local infiltrate and

atelectasis caused by tuberculosis. This child was asymptomatic, this
lesion having been discovered during a contact investigation
conducted after this child's uncle was suspected of having pulmonary
tuberculosis.
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Left upper lobe infiltrate and possible cavity in

pulmonary TB
Left upper lobe infiltrate and possible cavity in an adolescent with

sputum smear-positive pulmonary tuberculosis. This patient had a one
month history of cough, eight pound weight loss, and night sweats.
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Partially calcified primary tuberculous complex in a

three-year-old
This is a partially calcified primary tuberculous complex in a threeyear-old girl. There is right-sided hilar adenopathy with some
atelectasis along the horizontal fissure.
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Culture-positive tuberculous pleural effusion in a 9year-old patient
This is a culture-positive tuberculous pleural effusion in a nine-yearold girl. The source case was a school janitor. The child complained
only of a mild cough and was discovered through a contact
investigation of the school case.
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Extensive primary tuberculosis in a toddler
This is extensive primary tuberculosis in a toddler. There is right-sided

hilar adenopathy, narrowing of the right mainstem bronchus, and
collapse-consolidation of the right lower lobe.
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Treatment of tuberculosis in children

Regimen
Diagnostic category
New cases
(daily or three times weekly)*

Intensive phase
Continuation phase
New smear-positive pulmonary TB
INH
INH
New smear-negative pulmonary TB with

extensive parenchymal involvement
RIF
RIF
PZA
(4 months)
Severe forms of extrapulmonary TB (not

including meningitis or osteoarticular
disease)
EMB
(2 months)
Severe concomitant HIV disease

TB meningitis (see text)
INH
INH
RIF
RIF
PZA
(7 to 10 months) [1]
SM or AM or Eto
(2 months)
Osteoarticular TB
INH
INH
RIF
RIF
PZA
(7 to 10 months) [1]
EMB
(2 months)
New smear-negative pulmonary TB
INH
INH
(other than above categories)
RIF
RIF
Less severe forms of extrapulmonary TB
PZA
(4 months)
(2 months)
Previously treated cases
Smear-positive pulmonary TB
Relapse
Treatment after interruption
Treatment failure
INH
INH
RIF
RIF
PZA
EMB
EMB
(5 months)
SM
(2 months)
Followed by
INH
RIF
PZA
EMB
(1 month)
Chronic and MDR-TB
Individualized regimens
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TB: tuberculosis; INH: isoniazid; RIF: rifampin (rifampicin); PZA: pyrazinamide; EMB: ethambutol;
SM: streptomycin; AM: amikacin; Eto: ethionomide; HIV: human immunodeficiency virus; MDR-TB:
multidrug resistant TB.
* Direct observation of drug administration is recommended. Intermittent therapy (two or three
times weekly) is not recommended for children with HIV infection.
For treatment of meningitis, EMB is replaced by SM or Am or Eto. The decision about which
drug to use may be guided by drug susceptibility data of the index case if available, or countrylevel rates of specific drug resistance.
EMB may be omitted during the initial phase of treatment for patients in the following
categories:
Patients with non-cavitary, smear-negative pulmonary TB and known to be HIV-negative
Patients known to be infected with fully drug-susceptible bacilli
Reference:
1. Rapid Advice: Treatment of tuberculosis in children. World Health Organization, Geneva, 2010.
(WHO/HTM/TB/2010.13).
Reproduced with permission from: World Health Organization, Childhood TB Subgroup. Guidance for
national tuberculosis programmes on the management of tuberculosis in children, Geneva. Available
at http://whqlibdoc.who.int/hq/2006/WHO_HTM_TB_2006.371_eng.pdf. Copyright 2006 World
Health Organization.
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Drug dosing for the treatment of tuberculosis in children

Twice a
Drugs
Dosage
forms
Daily
dosage,
mg/kg
week
dosage,
Maximum
Adverse
dose
reactions
mg/kg
per
dose
Ethambutol
Tablets:
20
50
2.5 g
Optic neuritis
(usually
reversible),
decreased redgreen color
discrimination,
gastrointestinal
tract disturbances,
hypersensitivity
10 to 15
20 to 30
Daily, 300
mg
Mild hepatic
enzyme elevation,
hepatitis,
peripheral
neuritis,
hypersensitivity
100 mg
400 mg
Isoniazid*
Scored
tablets:
100 mg
Twice a
week, 900
mg
300 mg
Syrup:
10 mg/mL
Pyrazinamide*
Scored
tablets:
30 to 40
50
2g
Hepatotoxic
effects,
hyperuricemia,
arthralgia,
gastrointestinal
tract upset
10 to 20
10 to 20
600 mg
Orange
discoloration of
secretions or
urine, staining of
contact lenses,
vomiting,
hepatitis,
influenza-like
reaction,
thrombocytopenia,
pruritus; oral
500 mg
Rifampin*
Capsules:
150 mg
300 mg
Syrup
formulated
capsules
contraceptives
may be ineffective
* Rifamate is a capsule containing 150 mg of isoniazid and 300 mg of rifampin. Two capsules
provide the usual adult (>50 kg) daily doses of each drug. Rifater, in the United States, is a
capsule containing 50 mg of isoniazid, 120 mg of rifampin, and 300 mg of pyrazinamide.
Isoniazid and rifampin also are available for parenteral administration.
When isoniazid in a dosage exceeding 10 mg/kg per day is used in combination with rifampin,
the incidence of hepatotoxic effects may be increased.
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From: American Academy of Pediatrics. Tuberculosis. In: Red Book: 2012 Report of the Committee
on Infectious Diseases, 29th ed, Pickering LK, Baker CJ, Kimberlin DW, Long SS (Eds), American
Academy of Pediatrics, Elk Grove Village, IL 2012. Used with the permission of the American
Academy of Pediatrics. Copyright 2012. The contents of this table remain unchanged in the Red
Book: 2015 Report of the Committee on Infectious Diseases, 30th ed.
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Dosing of second line antituberculosis drugs in children
Drug
Daily
pediatric
dosage
Levofloxacin*
Age 5 years:
7.5 to 10 mg/kg
orally
Maximum
daily dose
750 mg*
Age <5 years:

15 to 20 mg/kg
orally in two
divided doses*
Moxifloxacin*
7.5 to 10 mg/kg
orally*
400 mg*
Ofloxacin*
15 to 20 mg/kg
orally in two
divided doses*
800 mg*
Capreomycin
15 to 30 mg/kg
1g
IM or IV
Main
adverse
Pregnancy
affects
GI toxicity,
sleep
disturbance,
arthritis, CNSheadache,
peripheral
neuropathy, QT
prolongation
(moxifloxacin >
levofloxacin)
Potential choice
when there are
no suitable
alternatives
Auditory and
Avoid
vestibular
toxicity,
nephrotoxicity,
electrolyte
disturbances
Kanamycin
15 to 30 mg/kg
IM or IV
1g
Ototoxicity,
nephrotoxicity
Avoid
Amikacin
15 to 22.5
1g
Ototoxicity,
Avoid
mg/kg IM or IV
nephrotoxicity
Streptomycin
15 to 30 mg/kg
IM or IV
1g
Vestibular and
ototoxicity,
neurotoxicity,
nephrotoxicity
Avoid
Ethionamide
15 to 20 mg/kg
orally in two
divided doses
1g
GI and hepatic
toxicity,
neurotoxicity,
Potential choice
when there are
no suitable
hypothyroidism,
optic neuritis,
metallic taste.
alternatives
Pyridoxine 50 to
100 mg orally
per day may be
useful in
preventing or
reducing
neurotoxicity.
Cycloserine
10 to 20 mg/kg
orally in two
divided doses
1g
Psychiatric
symptoms,
headaches,
seizures.
Potential choice
when there are
no suitable
alternatives
32/34
21/07/15
Pyridoxine 50
mg (oral once
per day) for
every 250 mg of
cycloserine may
be useful in
preventing or
reducing
neurotoxicity.
Paraaminosalicylic
acid
150 mg/kg
orally in two or
three divided
doses
12 g
GI toxicity,
malabsorption,
hypersensitivity,
hepatitis,
hypothyroidism
Potential choice
when there are
no suitable
alternatives
TB: tuburculosis; IM: intramuscular; IV: intravenous; GI: gastrointestinal; CNS: central nervous
system; max: maximum.
* According to the American Academy of Pediatrics, although fluoroquinolones are generally
contraindicated in children <18 years old, their use may be justified in certain circumstances,
such as multidrug-resistant tuberculosis. The optimal dose is not known.
Generally given five to seven times per week (15 mg/kg, or a maximum of 1 g per dose) for an
initial two to four months, and then (if needed) two to three times per week (20 to 30 mg/kg, or
a maximum of 1.5 g per dose). Dosage should be decreased if renal function is diminished.
For patients who are overweight or obese, dose is based on ideal body weight or dosing
weight (see UpToDate calculator). When available, serum drug monitoring is advised to
establish optimal dosing.
When available, serum drug monitoring is advised to establish optimal dosing. Recommended
peak (two to four hours post-dose) level is not higher than 30 microg/mL.
Data from:
1. Seddon J, et al. Caring for children with drug-resistant tuberculosis: practice-based
recommendations. Am J Respir Crit Care Med 2012; 186:953.
2. Guidelines for the programmatic management of drug-resistant tuberculosis. Geneva, World
Health Organization, 2008.
Adapted with special permission from: Treatment Guidelines from The Medical Letter, April 2012;
Vol. 10 (116):29. www.medicalletter.org.
33/34
21/07/15
Disclosures
Disclosures: Lisa V Adam s, MD Grant/Research/Clinical Trial Support: Oxford Immunotec [Tuberculosis (Diagnostic test for TB
infection)]. Jeffrey R Starke, MD Other Financial Interest: Otsuka Pharmaceuticals [DSMB (delamanid (anti-tuberculosis drug for MDR
TB))]. C Fordham von Reyn, MD Nothing to disclose. Morven S Edw ards, MD Consultant/Advisory Boards: Novartis Vaccines
[Group B streptococcus]. Elinor L Baron, MD, DTMH Nothing to disclose.
Contributor disclosures are review ed for conflicts of interest by the editorial group. When found, these are addressed by vetting
through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately
referenced content is required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy
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Tuberculosis disease in children

Tuberculosis disease in children

Tuberculosis disease in children

Tuberculosis disease in children

Tuberculosis disease in children

occur, leading to collapse in the setting of infiltrate and atelectasis.

Tuberculosis disease in children

Tuberculosis disease in children

Investigational diagnostic methods Because of the difficulty in achieving microbiologic confirmation of

Tuberculosis disease in children

Tuberculosis disease in children

Tuberculosis disease in children

Tuberculosis disease in children

Tuberculosis disease in children

Tuberculosis disease in children

Tuberculosis disease in children

Countries with high rates of tuberculosis (TB)

Sao Tome and

Papua New Guinea

China, Hong Kong

China, Macao SAR

Tuberculosis disease in children

Definitions of positive tuberculin skin test (TST) results in infants,

Tuberculosis disease in children

Potential causes of false-negative tuberculin tests

Biologic (not correctable)

Recent live virus vaccination (measles, mumps, polio)

Tuberculosis disease in children

Classic Ghon complex in a child infected with

This radiograph shows a classic Ghon complex in a child infected with

Tuberculosis disease in children

Expansile pneumonia caused by tuberculosis

This two-year-old toddler, infected by his mother, has an expansile

Tuberculosis disease in children

Extensive miliary pulmonary lesions in disseminated

Extensive miliary pulmonary lesions in a young child with disseminated

Tuberculosis disease in children

Extensive pulmonary tuberculosis in a preadolescent child

Extensive pulmonary tuberculosis in a pre-adolescent child. There is

Tuberculosis disease in children

Progressive primary tuberculosis in a toddler

Progressive primary tuberculosis in a toddler. There is extensive hilar

Tuberculosis disease in children

Cavitary tuberculosis in an adolescent male

Cavitary tuberculosis in an adolescent male. There is infiltrate and a

Tuberculosis disease in children

Enlarged right-sided hilar lymph nodes with local

Enlarged right-sided hilar lymph nodes with local infiltrate and

Tuberculosis disease in children

Left upper lobe infiltrate and possible cavity in

Left upper lobe infiltrate and possible cavity in an adolescent with

Tuberculosis disease in children

Partially calcified primary tuberculous complex in a

Tuberculosis disease in children

Culture-positive tuberculous pleural effusion in a 9year-old patient

Tuberculosis disease in children

Extensive primary tuberculosis in a toddler

This is extensive primary tuberculosis in a toddler. There is right-sided

Tuberculosis disease in children

Treatment of tuberculosis in children

(daily or three times weekly)*