Latent tuberculosis in childhood: tolerability of two different therapeutic approaches

Tersigni, Chiara; Venturini, Elisabetta; Cordola, Chiara; Piccini, Paola; Bianchi, Leila; Montagnani, Carlotta; Sollai, Sara; Chiappini, Elena; Martino, Maurizio de; Galli, Luisa

doi:10.1080/14787210.2018.1441025

Cited by 6 publications

(3 citation statements)

References 16 publications

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“…Other adverse events were mostly observed in isolated cases. The association between anti-TB drugs and hepatotoxicity is known and has been analysed in numerous studies [37,38], but the fact that few children experienced it is consistent with Tersigni et al, who observed a lower incidence rate of hypertransaminasemia in the paediatric population [39] compared to the incidence rate in the general population [38]. Although the majority of studies associate second-line drugs with adverse events [40,41], only one second-line drug was suspended due to acute kidney injury, suggesting that second-line drugs were well tolerated by the children in the study.…”

Section: Discussionmentioning

confidence: 52%

Extrapulmonary and Drug-Resistant Childhood Tuberculosis: Unveiling the Disease to Adopt the Optimal Treatment Strategy

Pace,

Corvaglia,

Lisi

et al. 2023

Pathogens

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Paediatric tuberculosis (TB) is a substantial threat among infectious diseases, particularly considering the high risk of extrapulmonary tuberculosis (EPTB), severe forms of the disease, and the spreading of drug-resistant strains. Describing the characteristics of children with EPTB and those with drug-resistant tuberculosis (DR-TB) and analysing the role of second-line drugs could facilitate the management of these cases. This retrospective study was conducted on 271 children diagnosed with active TB disease (44 EPTB cases, 9 DR-TB cases), originating from diverse geographic areas, who were referred to the infectious disease unit at Meyer Children’s Hospital, Florence, Italy, from 2006 to 2022. In most patients, the management of therapies was complicated by the impossibility to obtain drug susceptibility testing (DST) results, which improved over the years: 17/154 (11.04%) children had DST results between 2006 and 2013, and 50/117 (42.73%, p < 0.001) between 2014 and 2022. Second-line drugs were not exclusively administered to DR-TB cases, but also to EPTB cases (20/44, 45.45%). Drugs were generally well tolerated; adverse events occurred in 13 children (13/271, 4.80%) and were generally mild and reversable. Therapies were successful in 267 children (98.52%) considered cured, while 4 (1.48%) presented sequelae. Both univariate and multivariate logistic regression analyses were conducted to investigate factors associated with EPTB, DR-TB, and second-line drugs administration. Originating from Asia emerged as a risk factor associated with both EPTB and DR-TB (p = 0.013 and p = 0.045, respectively). The introduction of GeneXpert tests has significantly improved TB diagnosis and the obtaining of DST results. The administration of second-line therapies should be limited primarily to DR-TB cases, but it is possible that these drugs may also be beneficial in selected EPTB cases.

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Section: Discussionmentioning

confidence: 52%

Extrapulmonary and Drug-Resistant Childhood Tuberculosis: Unveiling the Disease to Adopt the Optimal Treatment Strategy

Pace,

Corvaglia,

Lisi

et al. 2023

Pathogens

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“…Prophylactic and preventive treatment is usually welltolerated [15] and has been shown to be very effective [8,9]. However, evidence from high-incidence settings shows multifactorial barriers to successful implementation including factors concerning screening and adherence, healthcare provider acceptability, and fear of isoniazid resistance [16].…”

Section: Introductionmentioning

confidence: 99%

Pilot study to identify missed opportunities for prevention of childhood tuberculosis

et al. 2022

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Tuberculosis (TB) in exposed children can be prevented with timely contact tracing and preventive treatment. This study aimed to identify potential barriers and delays in the prevention of childhood TB in a low-incidence country by assessing the management of children subsequently diagnosed with TB. A pilot retrospective cohort study included children (< 15 years) treated for TB between 2009 and 2016 at a tertiary care hospital in Berlin, Germany. Clinical data on cases and source cases, information on time points of the diagnostic work up, and preventive measures were collected and analyzed. Forty-eight children (median age 3 years [range 0.25–14]) were included; 36 had been identified through contact tracing, the majority (26; 72.2%) being < 5 years. TB source cases were mostly family members, often with advanced disease. Thirty children (83.3%) did not receive prophylactic or preventive treatment, as TB was already prevalent when first presented. Three cases developed TB despite preventive or prophylactic treatment; in three cases (all < 5 years), recommendations had not been followed. Once TB was diagnosed in source cases, referral, assessment, TB diagnosis, and treatment were initiated in most children in a timely manner with a median duration of 18 days (interquartile range 6–60, range 0–252) between diagnosis of source case and child contact (information available for 35/36; 97.2%). In some cases, notable delays in follow-up occurred.Conclusion: Prompt diagnosis of adult source cases appears to be the most important challenge for childhood TB prevention. However, improvement is also needed in the management of exposed children. What is Known:• Following infection with Mycobacterium tuberculosis, young children have a high risk of progression to active and severe forms of tuberculosis (TB).• The risk of infection and disease progression can be minimized by prompt identification of TB-exposed individuals and initiation of prophylactic or preventive treatment. What is New:• We could show that there are avoidable time lags in diagnosis in a relevant proportion of children with known TB exposure.• Delayed diagnosis of adult source cases, losses in follow-up examinations, and delay in referral to a specialized TB clinic of TB-exposed children, especially among foreign-born children, appear to be the main issue in this German pediatric study cohort.

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“…Hepatotoxicity is a well-known adverse effect of INH and RMP. The administered dose, TB disease severity, and being an "INH slow-acetylator" have been identified as risk factors for INH-or RIF-associated hepatotoxicity [40,41]. However, a very low incidence of adverse events and an increased compliance with the shorter combination therapy compared to 9-months INH has been clearly demonstrated in children [42,43].…”

Section: Plos Onementioning

confidence: 99%

Management of childhood and adolescent latent tuberculous infection (LTBI) in Germany, Austria and Switzerland

et al. 2021

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Background Majority of active tuberculosis (TB) cases in children in low-incidence countries are due to rapid progression of infection (latent TB infection (LTBI)) to disease. We aimed to assess common practice for managing paediatric LTBI in Austria, Germany and Switzerland prior to the publication of the first joint national guideline for paediatric TB in 2017. Methods Online-based survey amongst pediatricians, practitioners and staff working in the public health sector between July and November 2017. Data analysis was conducted using IBM SPSS. Results A total of 191 individuals participated in the survey with 173 questionnaires included for final analysis. Twelve percent of respondents were from Austria, 60% from Germany and 28% from Switzerland. Proportion of children with LTBI and migrant background was estimated by the respondents to be >50% by 58%. Tuberculin skin test (TST) and interferon-γ-release-assay (IGRA), particularly Quantiferon-gold-test, were reported to be used in 86% and 88%, respectively. In children > 5 years with a positive TST or IGRA a chest x-ray was commonly reported to be performed (28%). Fifty-three percent reported to take a different diagnostic approach in children ≤ 5 years, mainly combining TST, IGRA and chest x-ray for initial testing (31%). Sixty-eight percent reported to prescribe isoniazid-monotherapy: for 9 (62%), or 6 months (6%), 31% reported to prescribe combination therapy of isoniazid and rifampicin. Dosing of isoniazid and rifampicin below current recommendations was reported by up to 22% of respondents. Blood-sampling before/during LTBI treatment was reported in >90% of respondents, performing a chest-X-ray at the end of treatment by 51%. Conclusion This survey showed reported heterogeneity in the management of paediatric LTBI. Thus, regular and easily accessible educational activities and national up-to-date guidelines are key to ensure awareness and quality of care for children and adolescents with LTBI in low-incidence countries.

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Latent tuberculosis in childhood: tolerability of two different therapeutic approaches

Abstract: Both regimens resulted safe. Hepatotoxicity occurred rarely and within the first month. For this reason, it may be appropriate to perform liver function tests after about one month from the beginning of therapy to avoid diagnostic delays.

Cited by 6 publications

References 16 publications

Extrapulmonary and Drug-Resistant Childhood Tuberculosis: Unveiling the Disease to Adopt the Optimal Treatment Strategy

Extrapulmonary and Drug-Resistant Childhood Tuberculosis: Unveiling the Disease to Adopt the Optimal Treatment Strategy

Pilot study to identify missed opportunities for prevention of childhood tuberculosis

Management of childhood and adolescent latent tuberculous infection (LTBI) in Germany, Austria and Switzerland

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