Chapter 9: Pediatric tuberculosis

Figures & data

Table 1. Childhood TB cases in Canada, 2019 by population group.

		AGE (years)
Population group	<1	1-4	5-14	Total <15	% of all childhood cases
Inuit	4	9	22	35	31
First Nations	2	14	13	29	25
Metis	0	4	1	5	4
Total Indigenous	6	27	36	69	61
Canadian-born non-Indigenous	0	9	8	17	15
Total Canadian-born	7	37	45	89	78
Foreign-born	0	3	15	18	16
Unknown origin	1	2	4	7	6
Total cases	14	42	64	114	100

Table 2. Average age-specific risk for disease development after untreated primary infection.

Age at primary infection	Manifestations of disease	Risk of disease (%)
<12 months	No disease	50
	Pulmonary disease	30-40
	TB meningitis or miliary disease	10-20
12-23 months	No disease	70-80
	Pulmonary disease	10-20
	TB meningitis or miliary disease	2-5
2-4 years	No disease	95
	Pulmonary disease	5
	TB meningitis or miliary disease	0.5
5-10 years	No disease	98
	Pulmonary disease	2
	TB meningitis or miliary disease	<0.5
>10 years	No disease	80-90
	Pulmonary disease	10-20
	TB meningitis or miliary disease	<0.5

Source: Adapted from Marais et al.⁹

Table 3. Childhood TB by site of disease for the combined years 2018 and 2019.

Age group (yrs)	Pulmonary/Intrathoracic (n)^a	Extrathoracic (n)	Extrathoracic site
			Peripheral lymph node (n)	CNS (n)	Bone and joint (n)
<1	14	1	0	0	1
1-4	81	3	3	0	0
5-14	91	21	8	4	3
All <15	186	25	11	4	4

Abbreviations: TB, tuberculosis; n, number.

^aIncludes pleural TB and intrathoracic lymphadenopathy.

Source: Public Health Agency of Canada.

Table 4. Drugs used for treatment of TB in children.

	Daily dose (range)		Thrice-weekly dose^a(range)
	By weight (mg/kg)	Max (mg)	By weight (mg/kg)	Max (mg)	Available dosage forms	Principal side effects
Isoniazid	10 (10-15)^b	300	20-30	900	10 mg/mL suspension^c 100 mg tablet 300 mg tablet	Mild liver transaminase elevation Hepatitis Gastritis Peripheral neuropathy Hypersensitivity
Rifampin	Pulmonary: 15 (10-20) Meningitis/ Disseminated: 20-30	600, however if >60kg 10 mg/kg can be used up to 900 mg with close monitoring	10-20	600, however if >60kg 10 mg/kg can be used up to 900 mg with close monitoring	150 mg capsule 300 mg capsule Non-commercial suspension 25 mg/mL^d	Orange discoloration of secretions Vomiting Hepatitis Flu-like illness
Pyrazinamide	35 (30-40)	2000	70 (60-80)	see footnotes^e	500 mg scored tablet Non-commercial suspension 100 mg/mL	Hepatotoxicity Hyperuricemia Arthralgia
Ethambutol	20 (15-25)	see foonotes^f	40 (30-50)	see foonotes^g	100 mg tablet 400 mg tablet Non-commercial suspension 50 mg/mL	Optic neuritis with decreased visual acuity and decreased red-green color discrimination Gastrointestinal disturbance
Pyridoxine(Used to prevent isoniazid neuropathy: has no anti-TB activity)	1 mg/kg	25			25 mg. tablet 50 mg tablet	Few

Table adapted from Red Book.

Abbreviations: TB, tuberculosis; INH, isoniazid; ATS, American Thoracic Society.

a Intermittent doses should be prescribed only when directly observed therapy is available. In general, daily therapy is definitely preferred over intermittent regimens.

b Hepatotoxicity is greater when INH doses are more than 10-15mg/kg daily.

c Only isoniazid is available as a commercial suspension in Canada.

d Rifampin, pyrazinamide (PZA) and ethambutol (EMB) may be compounded into suspensions using these published references (English)⁶⁵ and (French).⁶⁶

e For PZA: 3000 mg according to ATS, 2000 mg according to Red Book.

f EMB: 1600 mg according to ATS, 2500 mg according to Red Book.

g For EMB: 2400 mg according to ATS, 2500 mg according to Red Book.

Table 5. IGRA in young children.

Author/ Year	Total population	Design	Tests	Duration of follow- up	Population description	Outcomes
Ho 2021^99	2,088 children; 936 < 5 years of age	Prospective observational cohort	TST, QFT, T-SPOT in all	Cross sectional (Follow-up data for children is in Ahmed 2020, below)	US, at risk for TB	TST, QFT, T-SPOT + ve: All US-born: 11%, 12%, 8% Non-US born: 43%, 26%, 22% <5 years old US-born: 10%, 14%, 8% Non-US born 26%, 3.5%, 1.5%
Ahmed 2020^100	3,593 children <15 years of age	Prospective cohort	TST, QFT, T-SPOT	2 years then cross referenced with TB registry	Born outside of US, 25% less than 5 years	4 developed TB disease Concordance 80%, less in children younger than 2 years 533 children TST positive and IGRA negative; none who were treated, none develop disease, including 54 under 2 years of age Specificity TST 73%, QFT-GIT 90%, T-SPOT 92.9%
Wendorf 2020^101	3,371 children <5 years of age	Comparison of database with TB registry	TST 24%, IGRA 56%	10,797 person-years, follow-up median 3 years in negative cases	California Refugee Health electronic information system; born in high-incidence countries	No cases of TB 1.4% IGRA positive 13% TST positive
Kay 2018^97	778 patients <18 years with laboratory confirmed	Registry	TST, IGRA vs TB disease (50% laboratory confirmed)		California TB registry for children	IGRA vs TST (sensitivity) Less than 2 yrs: 80% vs 87% 2-4 yrs: 91% vs 91% 5-18 yrs: 96% vs 83%
Lombardi 2019^102	226 children with TB disease	Retrospective multicenter study in Italy	QFT-IT vs TB disease (44% lab confirmed)	9 years	Majority foreign-born	TB disease: <2 yrs − 93% 2-5 yrs − 96% 5-16 yrs 96% positive
						Lab confirmed: 94, 100, 04%
						Overall sensitivity: 98% in children vs 81% in adults

Abbreviations: TST, tuberculin skin test; QFT, quantiferon; T-SPOT, type of interferon-gamma release assay; IGRA, interferon-gamma release assay; QFT-GIT, Quantiferon Gold In-Tube type of IGRA; TB, tuberculosis.

Table

Patients should not eat for 6 hours prior to the procedure, or be exposed to food, in order to prevent the stomach from emptying. Ideally this is done just after the child wakes from sleep before the stomach has emptied. If the child cannot be admitted as an inpatient, then they should arrive at clinic first thing in the morning prior to eating or drinking.
The child should be supine for the procedure, and may also need to be swaddled, depending on age.
Measure the expected distance of nasogastric (NG) insertion from nose to stomach.
Do not use bacteriostatic lubricant to moisten the NG tube.
Insert NG tube and aspirate the stomach contents first and discard.
If <10 cc of mucous is aspirated, then instill no more than 20-30 cc of sterile water (not normal saline) into the NG tube. Withdraw the aspirate quickly and place contents into a buffered specimen container or regular specimen container. (Note: Review local lab guidelines as to specimen collection containers available.)
If a buffered container is not available, ensure the lab is open to immediately receive and neutralize specimen.

With thanks to Ann Loeffler, Oregon Health Sciences University. See also⁶³ where a video and many other resources are available.

Table

Equipment Hypertonic saline: 3% Sodium Chloride, prefilled syringe Nebulizer with appropriately sized mouthpiece and facemask Personal protective equipment (PPE): gloves, gown, N95 respirator and eye protection Sputum sample cup, patient label and biohazard bag Ventolin: either metered dose inhaler with age appropriate aerochamber or liquid nebule with aerosol mask set-up (including oxygen) Suction setup, including appropriate size catheter and suction tip 100% oxygen setup and resuscitation equipment within close proximity

Protocol Appropriately trained personnel will review patient record to ensure no medical contraindications exist. Medical contraindications: severe asthma, severe chronic lung disease, severe hemoptysis, hemodynamic instability, new acute respiratory illness or fasting <2 hours Note: for details around appropriate rooms to perform this procedure in refer to Chapter 14: Prevention and Control of Tuberculosis Transmission in Healthcare Settings Identify patient and explain procedure to patient and family. Perform hand hygiene. Don PPE. Perform pre-induction assessment: vital signs, history of asthma and intercurrent illness Administer bronchodilator. Assemble nebulizer with hypertonic saline and attach appropriately sized mouthpiece and facemask. Initiate treatment with patient in sitting position. Inform either the caregiver or patient (when appropriate) that coughing can occur and instruct them to attempt to breathe normally. Instruct the patient to cough into the sputum container and/or suction contents from nasopharynx. Label specimen container and place into biohazard bag. Dispose of equipment and remove PPE (only remove N95 respirator after exiting from room). Perform hand hygiene. Document procedure in patient record.

Sample video of sputum induction procedure: FIND The Global Alliance for Diagnostics.¹⁶⁴

* Adapted from “Sputum Induction Procedure” developed by the Respiratory Therapy Services at the Children’s Hospital of Eastern Ontario, version date: May 2017.

Table

Use tablets crushed into semisoft vehicles, such as sugar-free pudding, to avoid stomach upset from the liquid preparation. Emphasize which medications are to be taken with meals (ethambutol and pyrazinamide) and which are to be taken on an empty stomach (isoniazid and rifampin).
Warn the family that the first couple of weeks of therapy will be challenging.
See patients monthly and supply only 1 month of medication at a time. Provide some extra doses to allow for spillage, or for when patients cannot make it to the follow-up appointment on time.
Provide written education regarding reasons for therapy, benefits of therapy, symptoms of TB and potential side effects/toxicity.
Develop a small, dedicated and enthusiastic team of staff providers, nurses and interpreters.
Develop systems to encourage adherence. We encourage caregivers to consider the best time in their child’s routine for them to take their TB medications. Establishing reward systems for children is also helpful.
Have convenient clinic hours and short waiting times.
Develop a system of immediately following up on patients who have missed appointments.
Praise the family and child for good adherence and clinic attendance.

Table

Isoniazid, pyrazinamide and ethambutol pills may be crushed and reduced into powder format to facilitate administration. When possible, pyrazinamide and ethambutol should be given with meals, isoniazid on an empty stomach. Rifampin capsules may be opened and sprinkled on or mixed into food.
To mask the taste of medications, crushed pills or powder can be mixed in a small quantity (1-2 teaspoons) of food that will mask the taste; popular examples include fruit purees, chocolate pudding and nut butters.
Never mix the medications (liquid or powder form) with any of the child’s essential foods (eg, milk, cereal).
Never add the medications directly to an infant’s bottle.
Do not administer medications after a meal or feeding, to minimize risk of vomiting.
If vomiting occurs within 10 minutes of administration, the medication should be re-administered.

* Adapted by Denis Blais from: The Practical Guide to Applying DOT.¹⁶⁵

Table

Infants (0-1 year): Medications typically taken without difficulty prior to a feed. Always use small quantities and ensure amount has been fully swallowed before administering next amount. Monitor the baby for at least 30 minutes after administration because of risk of vomiting.
Toddlers (1-4 years): This is the most difficult age for administering TB drugs; multiple attempts may be needed to find the optimal format (i.e., suspension vs crushed powder) and food for mixing. It is important to identify nonessential foods that are palatable to the child, given the duration of treatment and tendency toward rapid aversion to certain foods. Support may be needed to guide caregivers administering these medications; this includes the approach (calm, firm), attitude (no negotiation, positive reinforcement) and how to properly hold a child who categorically refuses to take their medication to administer it.
School aged (5-12 years): Generally administered without difficulty. Choice of suspension vs pills depends on the child; ability to swallow pills varies by individual and may not be related to age.
Adolescents (12-18 years): Generally administered without difficulty in pill format. Adherence in this age group is a particular challenge; parents or caregivers need to be responsible for reinforcing adherence.

* Adapted by Denis Blais from: The Practical Guide to Applying DOT.¹⁶⁵

Marais BJ, Gie RP, Schaaf HS, et al. The clinical epidemiology of childhood pulmonary tuberculosis: A critical review of literature from the pre-chemotherapy era. International Journal of Tuberculosis and Lung Disease. 2004;8(3):278–285.

 PubMed Web of Science ®Google Scholar

SickKids. Compounding Pharmacy Service. Available at: https://www.sickkids.ca/en/care-services/for-health-care-providers/compounding-service/. Accessed August 8, 2021.

 Google Scholar

Centre Hospitalier Universitaire Sainte-Justine. Guide de Formulations Magistrales. Available at: https://www.chusj.org/fr/soins-services/P/Pharmacie/Outils/Formulations-magistrales. Accessed August 8, 2021.

 Google Scholar

Ho CS, Feng PI, Narita M, Stout JE, Chen M, Pascopella L, Garfein R, Reves R, Katz DJ; Tuberculosis Epidemiologic Studies Consortium. Comparison of three tests for latent tuberculosis infection in high-risk people in the USA: an observational cohort study. Lancet Infect Dis. 2022;22(1):85–96. doi:10.1016/S1473-3099(21)00145-6.

 PubMed Web of Science ®Google Scholar

Ahmed A, Feng PI, Gaensbauer JT, Reves RR, Khurana R, Salcedo K, Punnoose R, Katz DJ, for the TUBERCULOSIS EPIDEMIOLOGIC STUDIES CONSORTIUM. Interferon-γ Release Assays in Children <15 Years of Age. Pediatrics. 2022;145(1):e20191930. doi:10.1542/peds.2020-0467.

 Google Scholar

Kay AW, Islam SM, Wendorf K, et al. Interferon-γ Release Assay Performance for Tuberculosis in Childhood. Pediatrics. 2018;141(6):e20173918. doi:10.1542/peds.2017-3918.

 Web of Science ®Google Scholar

Lombardi G, Pellegrino MT, Denicolò A, Corsini I, Tadolini M, Bergamini BM, Meacci M, Garazzino S, Peracchi M, Lanari M, Re MC, Dal Monte P. QuantiFERON-TB Performs Better in Children, Including Infants, than in Adults with Active Tuberculosis: a Multicenter Study. J Clin Microbiol. 2019;57(10):e01048–19. doi:10.1128/JCM.01048-19.

 PubMed Web of Science ®Google Scholar

Curry International Tuberculosis Center. Resources: Medication Delivery Tips. Available at: https://www.currytbcenter.ucsf.edu/products/pediatric-tuberculosis-online-presentation/resources. Accessed August 8, 2021.

 Google Scholar

FIND The Global Alliance for Diagnostics. Sample collection: Inducing Sputum Training Video. 2019. Available at: https://www.youtube.com/watch?v=0LPkpY4KIkU.Accessed. Accessed September 7, 2021.

 Google Scholar

Montreal Public Health. The Practical Guide to Applying DOT. 2013.

 Google Scholar