Tuberculosis (TB) is the most important infectious disease worldwide and one of the 10 leading causes of death, although its incidence and associated mortality are experiencing a marked decline. In 2015, there were 104 million new cases, 480,000 of them of multidrug-resistant TB (MDR-TB), and 1.4 million deaths caused by this disease. Through its End TB strategy, the WHO intends to decrease the incidence of TB by 80% and its mortality by 90% by year 2030.

Paediatric TB has been a hidden global epidemic for decades due to the difficulty of estimating its true impact. In highly endemic countries, the main barriers are poverty and the limited accessibility of health care. International policies have neglected this population due to the lower incidence of TB in children compared to adults and the low infectivity of TB. Even the Stop TB strategy, based on the quantification and treatment of individuals with active disease, excluded children because they rarely have positive sputum-smear results. Since 2012, there has been an increasing awareness of the need to include children in these programmes.2 The latest reports of the WHO1 provide more accurate data on the impact of childhood TB, with an actual incidence that exceeds published data by 25%, an estimated one million diseased children worldwide, and 169,000 dying from TB in 2015.

In Europe, the overall prevalence of childhood TB has been decreasing each year, but TB continues to be a public health priority, with more than 40,000 cases reported in the past decade and an overall prevalence of MDR-TB of 16% in newly diagnosed cases and 48% in previously treated cases. Eastern European countries are the most important contributors to these figures and pose a serious threat to the overall control of the disease.3 It is estimated that in 2014 there were 219,000 children infected with MDR strains in Europe, of who 2120 developed the disease.4

Spain is the country in Western Europe with the highest number of paediatric cases, although the incidence is progressively decreasing. In 2014, 303 cases were reported in children, corresponding to an incidence of 4.3 cases per 100,000 inhabitants.3 The epidemiology of TB, marked by HIV infection in the last two decades of the 20th century, has shifted, with immigrant status5 and immune disorders being the most important risk factors at present.6 The difficulties of its detection in children and the lack of drug formulations suitable for paediatric use pose the greatest challenges in the control of childhood TB. Deaths due to childhood TB are rare in Spain, but extrapulmonary forms of disease cause significant complications and sequelae.7 Last of all, we do not know the burden of drug-resistant TB in children in Spain. A prevalence of more than 4% has been estimated, exceeding the prevalence reported in adults, and with a predominance of cases in large cities.8

Exposure to TB is defined as meeting all of the following criteria9,10:

• a.

  Recent close contact (>4h a day in the same closed-off space), in the past 3 months, with an individual with confirmed/suspected active TB disease (pulmonary, laryngeal, tracheal or endobronchial).

• b.

  Negative tuberculin skin test (TST) (<5mm). Negative results in the interferon-gamma release assay (IGRA) when performed.

• c.

  Absence of clinical signs and symptoms compatible with TB.

• d.

  In immunosuppressed patients or young children, normal findings in chest radiographs (frontal and lateral views), when performed.

In this situation, given the risk of developing TB disease during the window period if there is an undiagnosed primary infection, the Sociedad Española de Infectología Pediátrica (Spanish Society of Paediatric Infectious Disease [SEIP]) has recommended initiation of primary prophylaxis with isoniazid (H) in all children aged less than 18 years since 2006.9 In 2010, the American Academy of Pediatrics (AAP) and the American Thoracic Society (ATS) proposed that prophylactic treatment be given only to children aged less than 4 years.11 Since 2014, the WHO recommends prophylaxis in children aged less than 5 years,12 while the AAP maintains the age limit of 4 years.13 In 2016, the British Thoracic Society (BTS) further reduced the age range to less than 2 years.14 These recommendations are based on studies that show that initiation of prophylaxis does not offer any advantages over the close monitoring of patients while awaiting the results of a second TST or IGRA, save in very young or immunosuppressed children, who are at higher risk of TB infection or disease following exposure.

Having reviewed the evidence, and in line with current updates, the SEIP puts forward new recommendations on post-exposure prophylaxis:

• –

  Initiate prophylaxis with H (Table 1):

  • ∘

    All children aged less than 5 years.

  • ∘

    Children of any age undergoing treatment that leads to immunosuppression (prolonged corticosteroid therapy, TNF-alpha antagonists, immunosuppressive agents, etc.) or with comorbidities involving the immune system (HIV infection, chronic kidney failure, solid or blood tumours, primary immunodeficiencies, etc.).12–14

  Table 1.

  Recommended doses of the first-line antituberculous drugs used most frequently in the paediatric age group.12

  	Daily dosage, mg/kg/day (dose range)	Maximum daily dose (mg)
  Isoniazid	10 (7–15)a,b	300
  Rifampicin	15 (10–20)a	600
  Pyrazinamide	35 (30–40)	2000
  Ethambutol	20 (15–25)c	2500
  Streptomycin	15–20	1000

  a

  The high-end doses of isoniazid and rifampicin are used in cases of tuberculous meningitis.

  b

  Add pyridoxine at 15–50mg/day (maximum 50mg/day) in children who are exclusively breastfed or follow a vegetarian diet, with changes in nutrition or with HIV, and in pregnant adolescents.

  c

  It is recommended that ethambutol be used at more potent doses (20–25mg/kg/day) during the initiation phase, decreasing the dose to 15–20mg/kg/day during the continuation phase.

  Intermittent therapy with higher doses given 3 days a week can be considered in especial cases, always as directly observed therapy.
• –

  When 8–10 weeks13–15 have elapsed since the last exposure to a source of infection, another TST will be performed, whether treatment with H was initiated or not. Subsequent management will depend on its results:

  • ∘

    If the induration in the new TST is <5mm (or in case of a negative IGRA, when applicable) and there are no clinical manifestations: discontinue prophylaxis if it has been initiated. Exceptions: immunosuppressed children or infants aged less than 3 months with a high-risk contact (close contact with a noncompliant source case, a retreatment case, etc.) in who completion of a course of treatment for latent tuberculosis infection (LTBI) is recommended even in the absence of a positive TST.

  • ∘

    If the induration in the new TST ≥5mm (or the IGRA positive, if applicable): follow recommendations for LTBI.

It is important to temporarily prevent further contact between the exposed child and the TB disease source, with the child isolated in a separate room in the home until confirmation that the source is not contagious13; which is estimated to occur starting from at least 2 weeks of adequate treatment.

In newborns of mothers with active TB disease, prophylaxis with H should be initiated after ruling out TB infection and disease. If the induration in the repeated TST is 0mm at 10–12 weeks and the decision is made to discontinue prophylactic treatment, the possibility of administering the BCG vaccine should be assessed, as the window period may not have concluded.16 Breastfeeding is not recommended against, except in cases of tuberculous mastitis.16 Maternal milk extraction and administration with a bottle are recommended to avoid mother–baby contact under the following circumstances16:

• –

  The mother has been treated for fewer than 2 weeks.

• –

  The mother continues to be contagious despite treatment.

• –

  The causative TB strain is not susceptible to first-line antibiotics.

Latent tuberculosis infection (LTBI) in children and adolescents is defined as infection through contact with an individual with active disease that does not progress to TB disease and remains as an asymptomatic latent infection.

In clinical practice, LTBI is diagnosed in asymptomatic patients with normal chest radiographs (frontal and lateral) and with:

• –

  A positive TST.

• –

  Known contact with an individual with active TB (source).

• –

  No known contact with an active TB source, but positive TST and/or IGRA results, especially in children aged less than 5 years or who are immunosuppressed.17

In the absence of known contacts and risk factors, if there is a history of vaccination with BCG combined with a positive TST and a negative IGRA, the TST reaction will be interpreted as an effect of the BCG vaccine. Such cases are not considered LTBIs.

Children with MDR-TB will be managed in appropriate units with experience in this disease. Even if they are not contagious, children will remain hospitalised in a negative pressure room until 3 consecutive sputum samples, taken at least 1 week apart, are negative. Visitors and health care staff will wear FFP3 masks until it is confirmed that the patient not contagious. Efforts will be made to mitigate the psychosocial impact of a prolonged hospital stay, offering social and psychological support.

Table 7 presents the schedule for the follow-up, monitoring and early detection of adverse events in these cases.

The authors have no conflicts of interest to declare.