Pediatric Tuberculosis in Italian Children: Epidemiological and Clinical Data from the Italian Register of Pediatric Tuberculosis

Galli, Luisa; Lancella, Laura; Tersigni, Chiara; Venturini, Elisabetta; Chiappini, Elena; Bergamini, Barbara Maria; Codifava, Margherita; Venturelli, Cristina; Tosetti, Giulia; Marabotto, Caterina; Cursi, Laura; Boccuzzi, Elena; Garazzino, Silvia; Tovo, Pier Angelo; Pinon, Michele; Serre, Daniele Le; Castiglioni, Laura; Vecchio, Andrea Lo; Guarino, Alfredo; Bruzzese, Eugenia; Losurdo, Giuseppe; Castagnola, Elio; Bossi, Grazia; Marseglia, Gian Luigi; Esposito, Susanna; Bosis, Samantha; Grandolfo, Rita; Fiorito, Valentina; Valentini, Piero; Buonsenso, Danilo; Domenici, R; Montesanti, M; Salvini, Filippo; Riva, Enrica; Dodi, Icilio; Maschio, Francesca; Abbagnato, L; Fiumana, Elisa; Fornabaio, Chiara; Ballista, Patrizia; Portelli, V.; Bottone, Gabriella; Palladino, Nicola; Valenzise, Mariella; Vecchi, Barbara; Gangi, Maria Di; Lupi, Carla; Villani, Alberto; Martino, Maurizio de

doi:10.3390/ijms17060960

Cited by 34 publications

(37 citation statements)

References 31 publications

(42 reference statements)

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“…Recent data on pediatric TB indicate that immigration is an important risk factor for TB in countries where the incidence of TB is low 15–17. Our study is the first report on pediatric TB in Northern Sardinia, where the native children represented the large majority (9:1 ratio).…”

Section: Discussionmentioning

confidence: 61%

Pediatric Tuberculosis in the North Sardinia

Clemente¹,

Dore²,

Abis³

et al. 2017

Mediterr J Hematol Infect Dis

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Background and ObjectivesMigration flux is an increasing phenomenon in Italy, and it raises several public health issues and concerns in pediatric infectious diseases. This study investigated the clinical characteristics and outcomes of a pediatric population at high-risk for tuberculosis (TB) and the potential role of immigration as a risk factor.DesignWe performed an observational retrospective study of children referred to the only Pediatric Infectious Diseases Unit for Northern Sardinia over a 6-year-period (2009–2014). Main variables assessed included TB skin test (TST), confirmed by quantiFERON Gold in Tube test, thorax X-ray (TX), microbiological culture, direct microscopy for acid-fast bacilli and molecular assays.ResultsOf the 246 children (mean age = 5.8 ± 3.9 years) identified, 222 (90.2%) were native to Sardinia and 24 (9.8%) were immigrants. The majority of children (n=205; 83%) were TB-exposed but not infected based on a negative TST and TX. Among the TST positive group (n= 39; 16%), 19 (49%) had latent TB (TX negative), while 20 (51%) had active TB (TX positive). The percent of TST positive children was significantly higher in the immigrant than the native group (42.5% versus 14%, p<0.001). Clinical presentations included pulmonary involvement with hilar lymphadenopathy (72%), pleurisy (13,5%), lateral-cervical lymphadenopathy (9%), pneumonia with calcifications (4.5%) and disseminated TB (4.5%). One child had multidrug-resistant tuberculosis.ConclusionsPediatric TB represents a relevant and potentially worsening public health problem in Northern Sardinia. A strict surveillance system and appropriate treatment can prevent the most severe forms and reduce TB transmission.

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Section: Discussionmentioning

confidence: 61%

Pediatric Tuberculosis in the North Sardinia

Clemente¹,

Dore²,

Abis³

et al. 2017

Mediterr J Hematol Infect Dis

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“…Three were based in the Republic of Korea; a low tuberculosis burden and low MDR‐TB burden country (Jo 2014; Jeong 2015; Kwak 2015), according to WHO definitions of tuberculosis, tuberculosis/HIV and MDR‐TB burden (WHO 2015b). Four were conducted in low tuberculosis burden and low MDR‐TB burden European countries; Netherlands (Van Altena 2015), Italy (Galli 2016), Norway (Jensenius 2016) and France (Guglielmetti 2017). Two studies recruited from Europe, but also from high MDR‐TB burden former Soviet Union states (Migliori 2009; Tiberi 2016).…”

Section: Resultsmentioning

confidence: 99%

“…Two studies included children only (Seddon 2014; Galli 2016). Jensenius 2016 recruited participants of all ages.…”

Section: Resultsmentioning

confidence: 99%

“…Guglielmetti 2017 aimed to follow‐up until 24 months after ATT completion, Ferlazzo 2018 until six months from commencement, and Olayanju 2018 reported monthly follow‐up for the duration of hospital stay. Follow‐up duration and frequency were unclear for the remaining studies (Migliori 2009; Udwadia 2010; Jo 2014; Seddon 2014; Kwak 2015; Van Altena 2015; Galli 2016; Jensenius 2016; Tiberi 2016). …”

Section: Resultsmentioning

confidence: 99%

“…Disaggregated data were available from 12 studies (639 participants), on total number of ‘any' or ‘serious' adverse events or linezolid discontinuation, amongst participants receiving linezolid (Migliori 2009; Jo 2014; Seddon 2014; Zhang 2014; Kwak 2015; Van Altena 2015; Galli 2016; Jensenius 2016; Tiberi 2016; Guglielmetti 2017; Ferlazzo 2018; Olayanju 2018). Six studies (487 participants), provided data for total number of ‘any' or ‘serious' adverse events amongst participants who did not receive linezolid (Seddon 2014; Kwak 2015; Galli 2016; Guglielmetti 2017; Ferlazzo 2018; Olayanju 2018).…”

Section: Resultsmentioning

confidence: 99%

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Linezolid for drug-resistant pulmonary tuberculosis

Singh

Cocker

Ryan

et al. 2019

Cochrane Database of Systematic Reviews

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BackgroundLinezolid was recently re‐classified as a Group A drug by the World Health Organization (WHO) for treatment of multi‐drug resistant tuberculosis (MDR‐TB) and extensively drug‐resistant tuberculosis (XDR‐TB), suggesting that it should be included in the regimen for all patients unless contraindicated. Linezolid use carries a considerable risk of toxicity, with the optimal dose and duration remaining unclear. Current guidelines are mainly based on evidence from observational non‐comparative studies.ObjectivesTo assess the efficacy of linezolid when used as part of a second‐line regimen for treating people with MDR and XDR pulmonary tuberculosis, and to assess the prevalence and severity of adverse events associated with linezolid use in this patient group.Search methodsWe searched the following databases: the Cochrane Infectious Diseases Specialized Register; CENTRAL; MEDLINE; Embase; and LILACS up to 13 July 2018. We also checked article reference lists and contacted researchers in the field.Selection criteriaWe included studies in which some participants received linezolid, and others did not. We included randomized controlled trials (RCTs) of linezolid for MDR and XDR pulmonary tuberculosis to evaluate efficacy outcomes. We added non‐randomized cohort studies to evaluate adverse events.Primary outcomes were all‐cause and tuberculosis‐associated death, treatment failure, and cure. Secondary outcomes were treatment interrupted, treatment completed, and time to sputum culture conversion. We recorded frequency of all and serious adverse events, adverse events leading to drug discontinuation or dose reduction, and adverse events attributed to linezolid, particularly neuropathy, anaemia, and thrombocytopenia.Data collection and analysisTwo review authors (BS and DC) independently assessed the search results for eligibility and extracted data from included studies. All review authors assessed risk of bias using the Cochrane ‘Risk of bias' tool for RCTs and the ROBINS‐I tool for non‐randomized studies. We contacted study authors for clarification and additional data when necessary.We were unable to perform a meta‐analysis as one of the RCTs adopted a study design where participants in the study group received linezolid immediately and participants in the control group received linezolid after two months, and therefore there were no comparable data from this trial. We deemed meta‐analysis of non‐randomized study data inappropriate.Main resultsWe identified three RCTs for inclusion. One of these studies had serious problems with allocation of the study drug and placebo, so we could not analyse data for intervention effect from it. The remaining two RCTs recruited 104 participants. One randomized 65 participants to receive linezolid or not, in addition to a background regimen; the other randomized 39 participants to addition of linezolid to a background regimen immediately, or after a delay of two months. We included 14 non‐randomized cohort studies (two prospective, 12 retrospective), with a total of 1678 partici...

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Screening tests for active pulmonary tuberculosis in children

Vonasek

Ness

Takwoingi

et al. 2021

Cochrane Database of Systematic Reviews

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Background Globally, children under 15 years represent approximately 12% of new tuberculosis cases, but 16% of the estimated 1.4 million deaths. This higher share of mortality highlights the urgent need to develop strategies to improve case detection in this age group and identify children without tuberculosis disease who should be considered for tuberculosis preventive treatment. One such strategy is systematic screening for tuberculosis in high‐risk groups. Objectives To estimate the sensitivity and specificity of the presence of one or more tuberculosis symptoms, or symptom combinations; chest radiography (CXR); Xpert MTB/RIF; Xpert Ultra; and combinations of these as screening tests for detecting active pulmonary childhood tuberculosis in the following groups. – Tuberculosis contacts, including household contacts, school contacts, and other close contacts of a person with infectious tuberculosis. – Children living with HIV. – Children with pneumonia. – Other risk groups (e.g. children with a history of previous tuberculosis, malnourished children). – Children in the general population in high tuberculosis burden settings. Search methods We searched six databases, including the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, on 14 February 2020 without language restrictions and contacted researchers in the field. Selection criteria Cross‐sectional and cohort studies where at least 75% of children were aged under 15 years. Studies were eligible if conducted for screening rather than diagnosing tuberculosis. Reference standards were microbiological (MRS) and composite reference standard (CRS), which may incorporate symptoms and CXR. Data collection and analysis Two review authors independently extracted data and assessed study quality using QUADAS‐2. We consolidated symptom screens across included studies into groups that used similar combinations of symptoms as follows: one or more of cough, fever, or poor weight gain and one or more of cough, fever, or decreased playfulness. For combination of symptoms, a positive screen was the presence of one or more than one symptom. We used a bivariate model to estimate pooled sensitivity and specificity with 95% confidence intervals (CIs) and performed analyses separately by reference standard. We assessed certainty of evidence using GRADE. Main results Nineteen studies assessed the following screens: one symptom (15 studies, 10,097 participants); combinations of symptoms (12 studies, 29,889 participants); CXR (10 studies, 7146 participants); and Xpert MTB/RIF (2 studies, 787 participants). Several studies assessed more than one screening test. No studies assessed Xpert Ultra. For 16 studies (84%), risk of bias for the reference standard domain was unclear owing to concern about incorporation bias...

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Pediatric Tuberculosis in Italian Children: Epidemiological and Clinical Data from the Italian Register of Pediatric Tuberculosis

Cited by 34 publications

References 31 publications

Pediatric Tuberculosis in the North Sardinia

Pediatric Tuberculosis in the North Sardinia

Linezolid for drug-resistant pulmonary tuberculosis

Screening tests for active pulmonary tuberculosis in children

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