Tuberculosis in children: treatment

Tuberculosis treatment in children is almost always effective when the regimen is chosen correctly and medications are taken with good adherence. The main goals of therapy are to completely cure the disease, prevent relapse, stop transmission within the family, and reduce the risk of late complications, especially those affecting the nervous system and bones. [1]

Modern tactics begin with classifying the case according to three questions. 1) Is there a suspicion of rifampicin resistance or other forms of drug resistance? 2) How severe is the disease and whether it is limited to “non-severe” forms? 3) Where is the process localized, because tuberculous meningitis and osteoarticular tuberculosis require a different duration of treatment. [2]

In children, rapid bacteriological confirmation and drug susceptibility testing are often impossible because the disease is often paucibacillary. Therefore, treatment decisions are often based on clinical, imaging, and epidemiological findings. However, whenever possible, microbiological samples should be obtained and rifampin resistance should be excluded, especially in cases of exposure to a patient with drug-resistant tuberculosis. [3]

A separate principle for pediatric practice is that drug doses are calculated based on body weight and adjusted as the child grows. To reduce errors, weight-based dosing ranges and pediatric dispersible fixed-dose combinations are used, and weight monitoring is part of the treatment. [4]

Treatment organization is also important. The World Health Organization emphasizes a family-centered approach, family education, adherence support, and the use of supervised medication management options, including health worker-supported options or digital solutions where appropriate. [5]

Table 1. What determines the treatment regimen for tuberculosis in a child

The Decisive Factor	Question	Why does this change treatment?
Drug sensitivity	Is there a risk of rifampicin resistance or is resistance confirmed?	The range of drugs, duration, and toxicity monitoring are changing.
Heaviness	Not a difficult process or a difficult one	In a mild case, a 4-month course is possible.
Localization	Lungs, lymph nodes, pleura, bones, meninges	The duration and need for adjuvant therapy changes
Age and weight	Infant, preschooler, teenager	Doses and formulations depend on weight and age.
Associated conditions	Human immunodeficiency virus, malnutrition, liver disease	Affect the choice of circuit and frequency of monitoring

[6]

Drug-sensitive pulmonary tuberculosis in children: when 4 months and when 6 months

For drug-susceptible tuberculosis in children, combination therapy with several first-line drugs remains the standard treatment. This is necessary to quickly suppress the proliferation of Mycobacterium tuberculosis and prevent the development of drug resistance during treatment. [7]

An important update in recent years concerns the duration of therapy. For children and adolescents aged 3 months to 16 years with mild drug-susceptible tuberculosis, a 4-month course of treatment is recommended. This is based on data from the Shorter Treatment for Minimal Tuberculosis in Children clinical trial, which demonstrated comparable efficacy of the shorter course in appropriately selected patients. [8]

Criteria for a "non-severe" course of the disease must be strictly adhered to. The guidelines define these as peripheral lymphadenitis, intrathoracic lymph nodes without airway obstruction, uncomplicated tuberculous pleurisy, and paucibacillary, non-cavitary lung lesions limited to one lobe or without miliary pattern. If the criteria are not met, a standard, longer-term regimen is used. [9]

The standard regimen for children who do not meet the criteria for mild disease progression remains 6 months. It includes a 2-month intensive phase with 4 drugs, followed by a 4-month continuation phase with 2 drugs, provided there is no evidence of drug resistance. [10]

Ethambutol's use in the intensive phase in children has been debated for some time due to concerns about ocular toxicity. Recent safety reviews, taken into account by the World Health Organization, indicate that the risk of ocular toxicity in children is considered extremely low when recommended doses are followed, particularly when ethambutol is used for a limited period during the intensive phase. [11]

Table 2. Criteria for mild tuberculosis in children for a 4-month course

Option	Included in the definition of a mild course	Clarification
Peripheral lymph nodes	Yes	Without affecting other localizations
Intrathoracic lymph nodes	Yes	Only if there is no airway obstruction
Pleural effusion	Yes	Only uncomplicated
Pulmonary damage	Yes	Paucibacillary, without cavities, limited to 1 lobe or without miliary pattern
disseminated process	No	Requires longer treatment
Meningitis	No	Requires a separate scheme and duration

[12]

Table 3. Basic treatment regimens for drug-susceptible tuberculosis in children

Clinical situation	Duration	Composition by phases
Not severe tuberculosis	4 months	2 months: isoniazid + rifampicin + pyrazinamide + ethambutol, then 2 months: isoniazid + rifampicin
Other forms without meningitis and bone and joint damage	6 months	2 months: isoniazid + rifampicin + pyrazinamide + ethambutol, then 4 months: isoniazid + rifampicin

[13]

Extrapulmonary tuberculosis: how the timeline changes and when glucocorticosteroids are needed

Extrapulmonary tuberculosis is common in children, and treatment is determined by the location. For most extrapulmonary forms, except for tuberculous meningitis and osteoarticular tuberculosis, the World Health Organization recommends the same 6-month course as for pulmonary tuberculosis, subject to drug susceptibility. [14]

There is an important exception to this reduction. For children with peripheral lymph node tuberculosis without other foci, a 4-month regimen may be used if the disease meets the criteria for a mild course. This allows for a reduced drug load while maintaining efficacy in appropriately selected patients. [15]

Osteoarticular tuberculosis in children requires longer treatment because drug penetration into the lesion and tissue repair rates vary. Guidelines for osteoarticular tuberculosis often recommend a treatment duration of approximately 12 months, with a prolonged continuation phase. [16]

Tuberculous meningitis is the most critical form in pediatrics. A 12-month regimen has long been the standard, and it remains an option. The World Health Organization also accepts an alternative 6-month intensive regimen, which includes isoniazid, rifampin, pyrazinamide, and ethionamide for 6 months, with higher doses of isoniazid and rifampin compared to the long-term regimen. [17]

Adjuvant glucocorticosteroids for tuberculous meningitis are recommended for all children and adolescents. Guidelines recommend the use of dexamethasone or prednisolone with a gradual dose reduction over 6-8 weeks, as this is associated with improved survival and reduced complications. [18]

Table 4. Duration of treatment by localization for drug-sensitive tuberculosis in children

Localization	Typical duration	Comment
It's not a difficult process.	4 months	Only if the criteria for a mild course of the disease are met
Most extrapulmonary forms	6 months	In addition to meningitis and bone and joint tuberculosis
Osteoarticular tuberculosis	12 months	Longer continuation phase
Tuberculous meningitis	9-12 months	The standard long-term scheme remains an option
Tuberculous meningitis, intensive variant	6 months	Alternative regimen with ethionamide, as indicated

[19]

Drug-resistant tuberculosis in children

Suspicion of drug resistance should arise when a child comes into contact with a patient confirmed to be rifampicin-resistant or multidrug-resistant, or when adequate therapy is ineffective. In such situations, the treatment regimen is abruptly altered, and the child should be managed in conjunction with a specialized service, as drug selection requires an assessment of susceptibility and safety. [20]

The current trend in the treatment of rifampicin-resistant and multidrug-resistant tuberculosis in children is a transition to oral regimens without injectable aminoglycosides whenever possible. The World Health Organization indicates that a standardized, shorter, all-oral regimen with bedaquiline can be used in children of all ages with programmatic management if eligibility criteria are met. [21]

Bedaquiline is considered a key drug in modern regimens and can be included in both standardized short-term regimens and individualized longer-term regimens. For children, the standard duration of bedaquiline use is typically 6 months, with extension considered only in specific situations with limited treatment options. [22]

In children, safety and monitoring issues are important: bedaquiline and a number of other drugs can affect the electrical activity of the heart, so monitoring is required, including electrocardiography according to protocol. For certain age groups and clinical situations, other drugs, including delamanid, may be used, in accordance with World Health Organization recommendations and available pediatric formulations. [23]

For severe and complex forms of drug-resistant tuberculosis, a "strong core" regimen is used, where preference is given to drugs with the highest efficacy and acceptable tolerability, and monitoring of side effects is planned in advance. This is especially important in children due to the duration of therapy and the impact on growth, nutrition, and learning. [24]

Table 5. First-line drugs in children and dosage guidelines

Preparation	Target daily dose	Comment
Isoniazid	10 mg/kg body weight, range 7-15 mg/kg	Doses are higher than for adults due to the metabolic peculiarities in children.
Rifampicin	15 mg/kg body weight, range 10-20 mg/kg	Doses are adjusted according to weight during treatment.
Pyrazinamide	35 mg/kg body weight, range 30-40 mg/kg	Usually used in the intensive phase
Ethambutol	20 mg/kg body weight, range 15-25 mg/kg	The risk of ocular toxicity in children is low when given at the correct dose.

[25]

Table 6. Drug-resistant tuberculosis in children: practical guidelines for treatment regimens

Situation	General principle of treatment	Example of key drugs
Rifampicin-resistant or multidrug-resistant, suitable for a short regimen	All-oral standardized shorter regimen if criteria are met	Bedaquiline as a base plus other drugs according to the protocol
Does not fit the standardized regimen or has complications	Individualized longer-term scheme	Bedaquiline as part of an individualized regimen, duration usually 6 months
Intolerance or contraindications to certain medications	Redesigning the circuit taking toxicity into account	The selection is carried out by a specialist with a monitoring plan.

[26]

Management during treatment: monitoring of effectiveness, side effects, adherence

Monitoring a child's effectiveness is based primarily on clinical dynamics: a decrease in temperature, improved appetite, weight gain, decreased cough, and improved well-being. Even in the absence of bacteriological confirmation, the child should be monitored according to a predetermined schedule, and a lack of improvement requires a review of the diagnosis, an assessment of adherence, and the exclusion of drug resistance. [27]

Safety monitoring is essential. The World Health Organization recommends regular follow-up visits and assessment of side effects throughout therapy, with the specific examinations depending on the regimen and risk factors. For drug-resistant tuberculosis, more intensive monitoring is required, including assessment of the side effects of specific drugs. [28]

Hepatotoxicity remains a significant risk, particularly with pyrazinamide and the combination of several drugs. Clinical literature emphasizes that laboratory monitoring of liver function is performed as indicated and is more often needed in children with risk factors, and that if symptoms of liver injury appear, immediate evaluation and therapy adjustment are required. [29]

For ethambutol, current data indicate a very low risk of ocular toxicity in children when doses are maintained. Practically, this means that, whenever possible, it is useful to conduct a baseline vision assessment in children who are able to cooperate, and then guide treatment based on symptoms and duration of use, especially if there is renal disease or a longer course is needed. [30]

If a child is infected with the human immunodeficiency virus (HIV), treatment for tuberculosis requires coordination with antiretroviral therapy due to drug interactions. For tuberculous meningitis in children with HIV, the World Health Organization recommends delaying the initiation of antiretroviral therapy for at least 4 weeks after the start of anti-TB treatment and initiating it within 4-8 weeks to reduce the risk of complications. [31]

Table 7. Side effects: what to watch for at home and during visits

Problem	How can it manifest itself?	What to do
Possible liver damage	Nausea, vomiting, pain in the right hypochondrium, dark urine, jaundice	Urgent physician assessment, laboratory monitoring
Allergic reactions	Rash, itching, swelling	Assessment of severity and decision to change the drug
Visual disturbances with ethambutol	Complaints of blurred vision and color vision impairment in older children	Immediate assessment and decision to discontinue the drug
Neurological symptoms in meningitis	Increased headache, drowsiness, convulsions	Emergency care, therapy adjustment
Commitment issues	Missed doses, refusal of medications	Simplification of the regime, family support, supervised intake

[32]

Treatment of tuberculosis infection without disease: preventive therapy after exclusion of the active process

In children, tuberculosis infection without disease often proceeds asymptomatically, but the risk of progression to active disease is higher during childhood, especially in young children and those with immunodeficiency. Therefore, after exposure to a tuberculosis patient and ruling out active disease, preventive treatment is recommended, which significantly reduces the risk of developing the disease. [33]

The World Health Organization recommends several preventive treatment options for children and adolescents. These include 6 or 9 months of daily isoniazid for all ages, 3 months of daily isoniazid plus rifampin for all ages, and 3 months of weekly isoniazid plus rifapentine for children 2 years and older. The choice depends on age, dosage form availability, and expected adherence. [34]

Preventive treatment regimens require regular follow-up visits with a healthcare professional. The World Health Organization recommends examinations at least monthly for 3-month regimens and at least every 2 months for 6-month regimens, with assessment of symptoms of possible toxicity and signs of disease. [35]

Prevention of pyridoxine deficiency during isoniazid therapy is important in children with HIV. Clinical guidelines for pediatrics recommend supplementing with pyridoxine at a dose of 1–2 mg/kg body weight per day, with a maximum of 50 mg per day, for children with HIV receiving isoniazid. [36]

Preventive treatment does not replace observation. If persistent cough, fever, night sweats, weight loss, or failure to gain weight develop during prophylaxis, the child requires re-evaluation for active tuberculosis and a review of management. [37]

Table 8. Preventive treatment of tuberculosis in children after exclusion of active disease

Mode	Who is it suitable for?	Key feature
6 months of isoniazid daily	All ages	Long-term regimen, requires sustained commitment
9 months of isoniazid daily	All ages	Used where accepted as standard
3 months of isoniazid plus rifampin daily	All ages	Shorter course, often easier to complete
3 months of isoniazid plus rifapentine once a week	Age from 2 years	High completion rate, but dependent on rifapentine availability

[38]

The material is for reference only and does not replace an in-person consultation with a doctor, since treatment regimens and doses should be selected individually based on body weight, localization of the process, results of drug sensitivity testing and concomitant conditions. [39]