Tuberculosis in children

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Template:Masahl Awais; Alejandro Lemor, M.D. [2]

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Overview

Tuberculosis in children aged 15 years or younger is a public health problem of special significance because it is a marker for recent transmission of TB. Infants and young children are more likely to develop life-threatening forms of tuberculosis, such as miliary TB or TB meningitis. Screening in children is very important, as the clinical manifestations are usually poor or non-specific. History of close contact with tuberculosis patients has an important role in the diagnosis of TB in children. The treatment is similar to adults, with adjusted dosing according to the child's weight.

Screening for Tuberculosis

Symptom-based Screening Approach

Algorithm adapted from Guidance for National Tuberculosis Programmes on the Management of Tuberculosis in Children[1]

 
 
 
 
 
 
 
 
 
Child in close contact with a confirmed TB case
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
< 5 yrs old
 
 
 
 
 
 
 
 
 
> 5 yrs old
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Asymptomatic
 
 
 
Symptomatic
 
 
 
Symptomatic
 
 
 
Asymptomatic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer INH 10 mg/kg/d x 6 months
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No preventive treatment is recommended.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If the child develops symptoms
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If the child develops symptoms
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm the diagnosis of TB with:
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Screening Children with HIV

Algorithm adapted from Guidance for National Tuberculosis Programmes on the Management of Tuberculosis in Children[1]
IPT: Isoniazid preventive therapy (INH 10 mg/kg/d x 6 months)

 
 
 
 
 
 
 
 
 
Child with HIV and older than 1 year
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient has any of the following symptoms?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assess for the diagnosis of TB (TST, chest X-ray, sputum studies) and rule out other diseases
 
 
 
 
 
 
 
 
 
Does the patient has any of the following contraindications for IPT?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TB confirmed
 
 
 
TB ruled out, other diagnosis confirmed
 
 
 
Yes
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer 2HRZE/4HR regimen
 
 
 
Give appropriate treatment for the disease and consider IPT
 
 
 
Do not administer IPT
 
 
 
Administer IPT
 
 
 
 
 

Diagnosis

  • Children must have a complete evaluation for tuberculosis, which includes a meticulous medical history, a complete physical examination, tuberculin skin test (TST), chest X-ray, sputum or gastric aspirate studies (microscopy and culture), and HIV testing.
  • Bacteriological testing might be difficult among children, but it should be performed whenever possible.
  • Adolescents usually have the adult clinical presentation, but may also present with symptoms and findings seen in smaller children.
  • Even though a scoring system has been developed in some countries[2][3][4][5][6], the WHO does not recommend this system for the evaluation of children with suspected TB.[1]
Diagnostic Approach in Children with Suspected Tuberculosis
History and Symptoms
Physical Examination
  • The physical examination might be unremarkable in children.
  • Extrapulmonary tuberculosis presents with abnormal physical findings.
Tuberculin Skin Test
  • Important for evaluating children with no history of close contact and to screen for TB infection.
  • In immunocompetent children, > 10 mm is considered positive.
  • In immunosuppressed children, > 5mm is considered positive.
Chest X-ray
  • Common findings include consolidation associated with an enlarged lymph node in the hilum.
Bacteriological Tests
  • Sputum or gastric aspirates should be assessed for the presence of M. tuberculosis.
  • Microscopy and culture should be done in every case possible to confirm the diagnosis.
HIV Test
  • In children with suspected TB, HIV testing should be offered.
Adapted from Guidance for National Tuberculosis Programmes on the Management of Tuberculosis in Children[1]

Diagnostic Approach for Extrapulmonary Tuberculosis

Location Common Clinical Presentation Diagnostic Workup
Peripheral Adenopathy Painless lymph node enlargement, commonly in one side of the neck. Fine needle aspiration or biopsy of the lymph node, culture of aspirate.
Miliary Tuberculosis Lethargy, fever, non-specific symptoms. Order a chest X-ray and a lumbar puncture in suspicion of meningeal involvement.
Tuberculous Meningitis Lethargy, neck stiffness, headache, irritability, bulging fontanelle. Lumbar puncture, head CT.
Pleural Effusion Decreased breath sounds, dullness to percussion, chest pain. Order a chest X-ray, perform an analysis of the pleural fluid.
Tuberculous Peritonitis Order an abdominal ultrasound, consider abdominal fluid aspiration for analysis. Abdominal tenderness, ascites.
Bone or Joint Infection Altered ROM, joint swelling, monoarticular pain. X-ray of the affected limb, joint fluid aspiration and analysis.
Tuberculous Pericarditis Distant heart sounds, tachycardia, signs of heart failure (edema, dyspnea). Echocardiography, consider pericardiocentesis for fluid analysis.
Adapted from Guidance for National Tuberculosis Programmes on the Management of Tuberculosis in Children[1] and WHO Childhood TB: Training Toolkit [7]

Treatment Adapted from Guidance for National Tuberculosis Programmes on the Management of Tuberculosis in Children[1] and WHO Childhood TB: Training Toolkit [7]

  • Empirical treatment should be started and the regimen should be modified according to the DST (Drug susceptibility testing) results.
  • Drug dosing should be calculated according to the child's weight, regardless the age.
  • Pediatricians should closely monitor adverse drug reactions and manage them appropriately.
  • For drug-resistant tuberculosis, hospitalization is often required for the administration of IV medications.
  • The treatment duration for drug-susceptible TB is 6 months.
  • The treatment duration for drug-resistant tuberculosis will depend on the culture results. The duration of therapy should be at least 18 months after the culture is negative.
  • Weight gain and resolution of symptoms are good markers for a good response to treatment.


▸ Click on the following categories to expand treatment regimens.

Tuberculosis in Children

  ▸  Drug Susceptible TB

  ▸  MDR-TB

  ▸  XDR-TB

Drug Susceptible TB Regimen
Initial phase
(Administer each drug daily for 8 weeks)
Isoniazid 10 mg/kg PO (Max: 300 mg/day)
PLUS
Rifampicin 15 mg/kg PO (Max: 600 mg/day)
PLUS
Pyrazinamide 35 mg/kg PO (Max: 2 g/day)
PLUS
Ethambutol 20 mg/kg PO (Max: 1.6 g/day)
Continuation phase
(Administer each drug daily for 18 weeks)
Isoniazid 10 mg/kg PO (Max: 300 mg/day)
PLUS
Rifampicin 15 mg/kg PO (Max: 600 mg/day )
Table adapted from WHO 2013 Treatment of Tuberculosis: Guidelines – 4th ed.[8]
MDR-TB Regimen
Standard Regimen
Group 1: First-line oral drugs

Pyrazinamide 20-30 mg/kg (Max: 600 mg)
OR
Ethambutol 15-20 mg/kg
OR
Rifabutin 5 mg/kg

PLUS
Group 2: Injectable drugs

Capreomycin 15-30 mg/kg (Max: 1000 mg)
OR
Kanamycin 15-30 mg/kg (Max: 1000 mg)
OR
Amikacin 15-22.5 mg/kg (Max: 1000 mg)
OR
Streptomycin 12-18 mg/kg

PLUS
Group 3: Fluoroquinolones

Levofloxacin 7.5-10 mg/kg
OR
Moxifloxacin 7.5-10 mg/kg
OR
Ofloxacin 15-20 mg/kg divided q12h (Max:800 mg)

PLUS
Group 4:Oral bacteriostatic second-line drugs

Ethionamide 15-20 mg/kg divided q12h (Max: 1000 mg)
OR
Protionamide 15-20 mg/kg divided q12h (Max: 1000 mg)
OR
Cycloserine 10-20 mg/kg (Max: 1000 mg)
OR
Terizidone 10-20 mg/kg (Max: 1000 mg)
OR
Para-aminosalicylic acid 150 mg/kg divided q8-12h(Max: 12 000 mg)

Table adapted from WHO 2013 Treatment of tuberculosis: guidelines – 4th ed.[8] and Guidance for national tuberculosis programmes on the management of tuberculosis in children [1]
XDR-TB Regimen
Standard Regimen
Group 1: First-line oral drugs

Pyrazinamide 20-30 mg/kg (Max: 600 mg)
OR
Ethambutol 15 mg/kg
OR
Rifabutin 5 mg/kg

PLUS
Group 4:Oral bacteriostatic second-line drugs

Ethionamide 15-20 mg/kg (Max: 1000 mg)
OR
Protionamide 15-20 mg/kg (Max: 1000 mg)
OR
Cycloserine 10-20 mg/kg (Max: 1000 mg)
OR
Terizidone 10-20 mg/kg (Max: 1000 mg)
OR
Para-aminosalicylic acid 150 mg/kg/d divided q8-12h

PLUS
Group 5
Use at least 2 of the following:

Clofazimine 50 mg/d AND 300 mg once a month
OR
Amoxicillin/clavulanate
OR
Linezolid 300-600 mg
OR
Imipenem 500mg q6h
OR
Clarithromycin 500-1000 mg q12h
OR
Thioacetazone 2.5 mg/kg
OR
Isoniazid (high-dose) 16–20 mg/kg

Table adapted from WHO 2013 Treatment of tuberculosis: guidelines – 4th ed.[8] and WHO Guidance for national tuberculosis programmes on the management of tuberculosis in children [1]

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "WHO Guidance for national tuberculosis programmes on the management of tuberculosis in children, 2014" (PDF).
  2. Isabella Coimbra, Magda Maruza, Maria de Fatima Pessoa Militao Albuquerque, Joanna D.'Arc Lyra Batista, Maria Cynthia Braga, Libia Vilela Moura, Democrito Barros Miranda-Filho, Ulisses Ramos Montarroyos, Heloisa Ramos Lacerda, Laura Cunha Rodrigues & Ricardo Arraes de Alencar Ximenes (2014). "Validating a scoring system for the diagnosis of smear-negative pulmonary tuberculosis in HIV-infected adults". PloS one. 9 (4): e95828. doi:10.1371/journal.pone.0095828. PMID 24755628.
  3. Constantino Giovani Braga Cartaxo, Laura C. Rodrigues, Carolina Pinheiro Braga & Ricardo Arraes de Alencar Ximenes (2014). "Measuring the accuracy of a point system to diagnose tuberculosis in children with a negative smear or with no smear or culture". Journal of epidemiology and global health. 4 (1): 29–34. doi:10.1016/j.jegh.2013.10.002. PMID 24534333. Unknown parameter |month= ignored (help)
  4. Sandra Christo dos Santos, Ana Maria Campos Marques, Roselene Lopes de Oliveira & Rivaldo Venancio da Cunha (2013). "Scoring system for the diagnosis of tuberculosis in indigenous children and adolescents under 15 years of age in the state of Mato Grosso do Sul, Brazil". Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia. 39 (1): 84–91. PMID 23503490. Unknown parameter |month= ignored (help)
  5. Stephen M. Graham (2011). "The use of diagnostic systems for tuberculosis in children". Indian journal of pediatrics. 78 (3): 334–339. doi:10.1007/s12098-010-0307-7. PMID 21165720. Unknown parameter |month= ignored (help)
  6. Emily C. Pearce, Jason F. Woodward, Winstone M. Nyandiko, Rachel C. Vreeman & Samuel O. Ayaya (2012). "A systematic review of clinical diagnostic systems used in the diagnosis of tuberculosis in children". AIDS research and treatment. 2012: 401896. doi:10.1155/2012/401896. PMID 22848799.
  7. 7.0 7.1 "WHO Childhood TB: Training Toolkit".
  8. 8.0 8.1 8.2 "2013 WHO Treatment of Tuberculosis: Guidelines for National Programmes (4th Edition)".

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