Tuberkulosis Anak

01Pathophysiology

Childhood TB follows a distinct pathogenic course compared to adult TB, and understanding this is the key to unlocking nearly every exam question on the topic.

The initial event is exposure. A child inhales aerosolized M. tuberculosis from a nearby infectious source, typically an adult or older adolescent with active pulmonary TB. After inhalation, the bacilli reach the alveoli and are phagocytosed by alveolar macrophages. In approximately 65% of exposed children, the innate (nonspecific) immune response successfully eliminates the bacilli entirely (Juknis TB Anak 2023, Chapter 2C). These children have no signs of infection: TST and IGRA are negative, chest X-ray is normal, and cultures are sterile.

If innate defenses fail, infection is established. The macrophages carrying M. tuberculosis undergo inflammation at the alveolar level, forming the primary (Ghon) focus. Bacilli then migrate through lymphatics, causing lymphangitis, and settle in the regional hilar lymph nodes, causing lymphadenitis. Together, the Ghon focus, lymphangitis, and lymphadenitis constitute the primary complex (Ranke complex). This is the hallmark radiological finding in childhood TB and explains why hilar or paratracheal lymphadenopathy is the single most common chest X-ray abnormality in pediatric TB.

During this stage, occult hematogenous spread occurs: bacilli escape from the lungs into the bloodstream and seed distant organs that have high oxygen tension, such as the lung apices (Simon focus), the basal meninges, and vertebral bodies. These microcolonies form small dormant granulomas, called remote foci. Cell-mediated immunity (T-cell response) develops, turning the TST or IGRA positive, but the child remains asymptomatic.

The progression from infection to active disease depends on the immune balance. In immunocompetent older children, the granulomas contain the bacilli in a dormant state; this is termed TB infection (latent TB). The lifetime risk of reactivation for these individuals is 5-10% (Juknis TB Anak 2023, Chapter 4B). However, in infants, children under 5, and immunocompromised children (HIV, malnutrition), the period of infection may be extremely brief before progressing to active, often severe, TB because cell-mediated immunity is immature or impaired. This is why the exam always pairs young age or HIV with a high-risk scenario.

When immune containment fails, active (clinical) TB develops. The bacilli replicate inside granulomas, which break down and allow the organisms to spread. Spread can be per continuitatum (slow, local extension) or hematogenous (rapid, disseminated). Disseminated hematogenous spread produces miliary TB in the lungs and TB meningitis when bacilli lodge in the basal meninges, causing inflammation, adhesions, and obstruction of CSF flow. This pathogenesis explains why every child diagnosed with miliary TB must be evaluated with a lumbar puncture for possible TB meningitis, even in the absence of neurological symptoms, especially in children under 2 years old (Juknis TB Anak 2023, Chapter 7D).

A critically testable concept is paucibacillary disease: children, particularly those under 5, harbor far fewer bacilli than adults. This means sputum smears and even molecular tests are frequently negative in pediatric TB. This is the biological basis behind the reliance on clinical diagnosis (scoring system) rather than bacteriological confirmation in many children.

02Classification and Clinical Manifestation

03Diagnostic Workup

Serological tests (IgG TB, PAP TB, ICT TB, MycoDOT) are explicitly NOT recommended by WHO and are prohibited by Indonesian Ministry of Health directive (February 2013).

The approach to diagnosing pulmonary TB in a child follows a structured algorithm outlined in the Juknis TB Anak 2023, Chapter 5.

Step 1: Identify the symptomatic child. The entry point into the diagnostic algorithm is a child or adolescent (<15 years) presenting with one or more of: cough >2 weeks, fever >2 weeks, weight loss or failure to thrive, or malaise. Once symptoms are recognized, the clinician must first assess for danger signs (seizures, altered consciousness, respiratory distress). If danger signs are present and the child has a history of close TB contact, initiate anti-TB drugs immediately while awaiting workup results.

Step 2: Risk-stratify. Children under 2 years old, children with HIV, and children with severe malnutrition are considered high-risk and should proceed directly to sputum collection for molecular rapid testing. Children who are not in the high-risk category should first have alternative diagnoses considered and treated (antibiotics for possible bacterial infection, asthma therapy if wheezing). If symptoms persist despite appropriate alternative therapy, the child is then reclassified as a suspected TB case and proceeds to bacteriological workup.

Step 3: Obtain specimens for molecular rapid testing. Sputum is the primary specimen. In young children who cannot expectorate, alternatives include induced sputum, gastric aspirate (gastric lavage), nasopharyngeal aspirate, or stool. The first-line bacteriological test is Xpert MTB/RIF or Xpert Ultra.

Step 4: Interpret results and apply the scoring system.

If the molecular test is positive, the diagnosis is bacteriologically confirmed TB regardless of the scoring system result, and treatment is initiated.

If the molecular test is negative or unavailable, and the facility has access to chest X-ray and TST/IGRA, apply the IDAI scoring system. A score >=6 indicates clinical TB, and treatment should begin. A score <6 combined with a positive TST/IGRA and close TB contact history and a suggestive chest X-ray also warrants treatment as clinical TB.

If the molecular test is negative, no chest X-ray or TST is available, and the child has no TB contact, observe for 2 weeks to 2 months with antibiotics/symptomatic therapy and nutritional rehabilitation. If symptoms persist, refer for further workup or consider treating as clinical TB.

If the child has TB contact but bacteriological tests are negative and imaging is unavailable, the physician must weigh the clinical picture. In high-risk children (under 2, HIV, severe malnutrition), the threshold to treat as clinical TB should be low because the consequences of untreated TB in this group are devastating.

A trial of anti-TB therapy to confirm diagnosis is explicitly NOT recommended (Juknis TB Anak 2023, Chapter 5).

For adolescents aged 15 and older, the adult diagnostic algorithm is used.

04Management and Treatment

Drug-Sensitive TB (DS-TB)

Regimen Selection

Acute management

Before starting therapy, assess for danger signs (Table 6.4 of the Juknis TB Anak 2023): seizures, altered consciousness, respiratory distress, central cyanosis, or oxygen saturation <90%. Children with these findings must be stabilized first. If a child with danger signs has known TB contact, OAT should be started immediately without waiting for confirmatory results.

Regimen initiation

All OAT is given daily (not intermittent) during both intensive and continuation phases. This is a departure from some older adult regimens. The drugs are administered using Fixed-Dose Combinations (FDC) whenever possible (Juknis TB Anak 2023, Table 6.5). For children <=30 kg, the pediatric FDC is used: intensive phase tablet = R 75 mg / H 50 mg / Z 150 mg; continuation phase tablet = R 75 mg / H 50 mg, dosed by weight band. Children >30 kg use the adult FDC.

Ethambutol is added (making 4-drug RHZE) in the following situations:

• Bacteriologically confirmed pulmonary TB

• Severe or extensive pulmonary disease

• Extrapulmonary TB (except non-severe lymphadenitis)

• HIV co-infection

• Adolescents >=15 years (all forms)

Corticosteroids are indicated for TB meningitis, pericardial TB, and endobronchial TB with airway compression. Prednisone 2-4 mg/kg/day (max 60 mg/day) for 4 weeks, then taper over 6-8 weeks. Dexamethasone 0.3-0.6 mg/kg/day is an alternative.

Pyridoxine (Vitamin B6) supplementation at 0.5-1 mg/kg/day is given to children with HIV on ART, severe malnutrition, or diabetes mellitus, as INH increases the risk of symptomatic pyridoxine deficiency in these groups.

Monitoring

Clinic visits every 2 weeks during the intensive phase, then monthly during the continuation phase. At each visit: assess symptom improvement, weigh the child and adjust drug doses for weight gain, evaluate medication adherence, and check for adverse effects. For bacteriologically confirmed cases, repeat sputum for AFB smear at 2 months and at end of treatment. For miliary TB, repeat chest X-ray after 1 month of treatment.

Drug-Induced Hepatotoxicity (ADIH). The hepatotoxic drugs are R, H, and Z. ADIH criteria: ALT/AST elevated >=5x upper limit of normal without symptoms, OR >=3x with symptoms, OR total bilirubin >1.5 mg/dL. Management: stop all hepatotoxic OAT (RHZ). When ALT falls below 2x normal, reintroduce in order: Rifampicin first (less hepatotoxic than INH), check liver function in 3-7 days, then add INH. Pyrazinamide is not reintroduced. Alternative regimens include 9 months RHE or 6-9 months RZE.

Treatment in special populations

• HIV co-infection: Always use 4-drug RHZE regardless of severity. Start ART within 2 weeks of OAT initiation, except for TB meningitis where ART is delayed 4-8 weeks. Give pyridoxine to all. Be aware of immune reconstitution inflammatory syndrome (IRIS), which can cause paradoxical clinical worsening within the first 1-3 months of ART.

• Neonates born to mothers with TB: If symptomatic and life-threatening, start OAT (2RHZE/4RH) immediately. If asymptomatic, give TPT (INH 6 months or RH 3 months) and defer BCG vaccination until TPT is completed.

• Diabetes mellitus: Same regimen, but treatment may extend to 9 months if glycemic control is poor. Rifampicin reduces the efficacy of sulfonylurea oral hypoglycemics.

Drug-Resistant TB (DR-TB)

The short regimen for non-severe DR-TB in children <15 years is 6 months of Bedaquiline-Levofloxacin-Linezolid-Clofazimine-Cycloserine (6 Bdq-Lfx-Lzd-Cfz-Cs). The long regimen for severe DR-TB is 9-12 months; for DR-TB meningitis, miliary, or osteoarticular: 12-18 months (Juknis TB Anak 2023, Table 6.10). Kanamycin and capreomycin are no longer recommended.

05TB Preventive Therapy (TPT)

TPT aims to prevent progression from TB infection to active TB disease. Approximately 5-10% of individuals with TB infection will develop active TB during their lifetime, with the highest risk occurring within the first 2 years after initial infection. In HIV-positive children, progression can occur within 12 months. TPT kills dormant M. tuberculosis bacilli within granulomas, keeping the bacterial load minimal and maintaining dormancy (Juknis TB Anak 2023, Chapter 4B).

Priority Target Populations for TPT

Prerequisites Before Starting TPT

The child must NOT have active TB. Before initiating TPT, screen for symptoms (cough, fever, weight loss, night sweats). If screening is positive, proceed to diagnostic workup (Chapter 5 algorithm). Only start TPT after active TB has been excluded.

No contraindications to TPT must be present. Contraindications include:

• Acute or chronic hepatitis

• Peripheral neuropathy (if using Isoniazid)

• Regular or heavy alcohol consumption (relevant in adolescents)

Evidence of TB infection should be sought (though not always required before starting, depending on the population):

• TST (Mantoux): Intradermal injection of PPD RT 23 2 TU on the volar forearm. Read at 48-72 hours. Positive = induration >=10 mm (>=5 mm if immunocompromised).

• IGRA: In vitro blood test measuring interferon-gamma release in response to M. tuberculosis antigens (CFP-10, ESAT-6, TB 7.7). Single visit, not affected by prior BCG vaccination, but expensive and not routinely available in the Indonesian national program.

Neither TST nor IGRA can distinguish between infection and active disease, and neither can predict progression to active TB. They are therefore not used as screening tools but rather as evidence of infection to support TPT decisions in certain age groups.

Decision Algorithms by Population

HIV-Positive Children and Adolescents

Household Contacts of DS-TB and DR-TB Cases

Other High-Risk Groups

TPT Regimens

Regimens marked with asterisk (*) depend on logistic availability and national program policy.

Practical Administration

• All TPT drugs are taken once daily, preferably at the same time each day, on an empty stomach (1 hour before or 2 hours after meals).

• Doses must be adjusted monthly based on weight gain.

• If clinical TB symptoms develop during TPT, stop TPT, perform diagnostic workup, and start OAT if TB is confirmed.

• Children with severe malnutrition or HIV on ART should receive pyridoxine (Vitamin B6) 5-10 mg/day throughout TPT to prevent INH-induced neuropathy.

• TPT is continued even if the index case dies, moves away, or converts to smear-negative.

• If a child vomits within 30 minutes of taking the dose, the dose should be re-administered.

Monitoring During TPT

At every monthly visit, evaluate:

• Emergence of TB symptoms (especially weight loss). If present, proceed with full diagnostic workup.

• Adverse effects: nausea, vomiting, peripheral neuritis symptoms, hepatic dysfunction. If present, hold the drug.

• Adherence: review medication cards, discuss barriers with caregivers, and address non-adherence promptly.

TPT in the Neonatal Context

For asymptomatic newborns born to mothers with active TB:

1. Give TPT: INH for 6 months or RH for 3 months

2. Defer BCG vaccination until TPT is completed

3. Two weeks after completing TPT, perform TST:

   • If TST positive: no BCG needed (immunity established)

   • If TST negative or unavailable and no HIV: give BCG

   • If HIV-positive infant: BCG may be given only if on ART, clinically stable, and immunologically stable (CD4 >25% for <5 years)

4. If the mother has drug-resistant TB, the infant should not breastfeed directly but should receive expressed breast milk. TPT regimen is Levofloxacin for 6 months.

06Differential Diagnosis and Distractors

07Traps and High-Yield Pearls

The single most common way students lose points on childhood TB questions is by demanding bacteriological confirmation before starting treatment. In adult TB, the clinical expectation is positive sputum. In pediatric TB, the disease is paucibacillary; molecular tests and cultures are frequently negative. The exam will present a child with a TB contact history, failure to thrive, a suggestive chest X-ray showing hilar lymphadenopathy, and a positive TST, but with a negative Xpert result. The correct answer is to treat as clinical TB (scoring system >=6), not to "wait for culture results" or "repeat Xpert in 2 weeks."

A second classic trap is the negative TST in a severely ill child. Exam-takers who know that TST should be positive in TB infection may be led astray when the vignette provides a negative TST in a child with miliary TB or TB meningitis. This is anergy: the immune system is so overwhelmed or suppressed (by disseminated disease, HIV, or severe malnutrition) that it cannot mount a delayed-type hypersensitivity response. A negative TST does not rule out TB in these contexts.

Third, watch for the asymmetric, persistent wheezing distractor. The vignette will describe a child with "wheezing unresponsive to bronchodilators." The wrong answer is asthma or reactive airway disease. The correct answer is TB with endobronchial compression from enlarged mediastinal lymph nodes. The discriminating clue is that the wheezing is asymmetric (unilateral) and does not respond to standard bronchodilator therapy.

Fourth, remember that a trial of anti-TB treatment is NOT a valid diagnostic strategy in children (Juknis TB Anak 2023, Chapter 5). The exam may offer "start a trial of OAT and see if the child improves" as an answer option. This is explicitly discouraged in the guideline because it confounds the clinical picture and delays proper workup.

Fifth, for neonatal TB vignettes: when a mother has active TB and the newborn is asymptomatic, the correct action is to give Isoniazid preventive therapy for 6 months (or RH for 3 months), defer BCG until after TPT is completed, and perform TST two weeks after finishing TPT to determine whether BCG should then be given. Never vaccinate with BCG while the infant is receiving TPT.

Finally, keep the scoring system cutoff firmly in mind: a total score of >=6 in the IDAI scoring system supports a diagnosis of clinical TB and warrants treatment initiation. The parameters tested most often are: bacteriologically confirmed TB contact (3 points), positive TST (3 points), suggestive chest X-ray (1 point for "suggestive"), severe malnutrition (2 points), and persistent symptoms (1 point each for fever and cough >2 weeks). The exam will give you a combination of these and ask whether the total meets threshold.

The core competency being tested across all question formats is the ability to synthesize clinical, epidemiological, and radiological data to make a probabilistic diagnosis in a paucibacillary setting, rather than relying on a single confirmatory test.