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Literature review current through: Jun 2015. | This topic last updated: Jun 16, 2015.
INTRODUCTION — Forma l 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 — E stimating the global burden of tuberculosis (TB) disease in children is challenging
due to the lack of a standard case def inition, 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 near ly one million children who de veloped 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
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]:
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]:
DIAGNOSIS — Tuberculosis (TB) in children is often diagnosed clinically. Because pulmonary TB in childrentypically 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].
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")●
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] s taining 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].
●
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.●
The approach outlined by the World Health Organization (WHO) for evaluation of a child suspected of having TB
includes [5]:
All data, including thorough history, physical exam, and diagnostic test ing, 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 adult’s 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 posit ive 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-Guérin (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", sect ion 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 culture-
confirmed 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 miliaryTB 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
Careful history (including history of TB contact and symptoms consistent with TB)●
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 diseaseand 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 10percent 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].
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", sect ion 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 child’s
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", sect ion 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 susceptibilitytesting [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 drug-
resistant 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 multiplehigh-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
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 short-
course mult idrug 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, andHIV-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/mm . 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 multiplesites 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
child’s 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
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 notsufficient. 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-Guérin (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 high-
prevalence 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 38ºC 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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* 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.
Δ 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;
Disclosures: Lisa V Adams, 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 Edwards, MD Consultant/Advisory Boards: Novartis Vaccines[Group B streptococcus]. Elinor L Baron, MD, DTMH Nothing to disclose.
Contributor disclosures are review ed for conf licts of interest by the editorial group. When found, these are addressed by vetting
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referenced content is required of all authors and must conform to UpToDate standards of evidence.