Tuberculosis in children

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mashal Awais, M.D.[2]; Alejandro Lemor, M.D. [3]

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Overview

Tuberculosis in children aged 15 years or younger is considered a public health issue of special significance because it is a marker for recent transmission of TB. The likelihood of developing life-threatening forms of tuberculosis, such as miliary TB or TB meningitis is more in infants and young children. Screening in children is essential, because the signs and symptoms are usually vague or non-specific. History of close contact with tuberculosis patients plays an major role in the diagnosis of TB in children. The treatment is similar to adults, with adjustment of the doses 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

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: Chest X-ray TST Sputum or gastric aspirates microscopy evaluation and culture

Screening Children with HIV

Algorithm adapted from Guidance for National Tuberculosis Programmes on the Management of Tuberculosis in Children
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? Weight loss or poor weight gain Cough Fever History of close contact with a TB case

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? Active hepatitis Peripheral neuropathy

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, the WHO does not recommend this system for the evaluation of children with suspected TB.

Diagnostic Approach in Children with Suspected Tuberculosis
History and Symptoms	Evaluate for close contact with a case of TB. Symptoms include cough, fever, poor appetite, weight loss, lethargy, fatigue. Growth chart should be evaluated to determine an altered growth development.
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

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 and WHO Childhood TB: Training Toolkit

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

• 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. 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. and Guidance for national tuberculosis programmes on the management of tuberculosis in children 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. and WHO Guidance for national tuberculosis programmes on the management of tuberculosis in children