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IntroductionChildhood pulmonary tuberculosis (TB) remains a diagnostic challenge. This study aimed to evaluate the performance of Xpert Ultra for the diagnosis of pulmonary TB in children in a low TB prevalence setting.MethodsProspective, multicentre, diagnostic accuracy study. Children with clinical or radiological suspicion of pulmonary TB were recruited at 11 paediatric units in Spain. Up to three gastric or sputum specimens were taken on 3 consecutive days, and analysed by Xpert MTB/RIF, Xpert Ultra and culture in parallel.Results86 children were included (median age 4.9 years, IQR 2.0–10.0; 51.2% male). The final diagnosis was pulmonary TB in 75 patients (87.2%); 33 (44.0%) were microbiologically confirmed. A total of 219 specimens, comprising gastric aspirates (n=194; 88.6%) and sputum specimens (n=25; 11.4%), were analysed. Using culture as reference standard and comparing individual specimens, the sensitivity was 37.8% (14/37) for Xpert MTB/RIF and 81.1% (30/37) for Xpert Ultra (p<0.001); specificity was 98.4% (179/182) and 93.4% (170/182), respectively (p=0.02). In the per-patient analysis, considering positive results on any specimen, the sensitivity was 42.9% (9/21) for Xpert MTB/RIF and 81.0% for Xpert Ultra (17/21, p=0.01); specificity was 96.9% (63/65) and 87.7% (57/65, p=0.07), respectively.ConclusionsIn children with pulmonary TB in a low burden setting, Xpert Ultra has significantly higher sensitivity than the previous generation of Xpert assay and only marginally lower specificity. Therefore, in children undergoing evaluation for suspected pulmonary TB, Xpert Ultra should be used in preference to Xpert MTB/RIF whenever possible.

There are not enough nationwide studies on perinatal HIV transmission in connection with a combination of antiretroviral treatments in Spain. Our objectives were to study sociodemographic changes and trends in the rates of HIV diagnoses and perinatal transmission in Spain from 1997 to 2015. A retrospective study using data from Spanish Paediatric HIV Network (CoRISpe) and Spanish Minimum Basic Data Set (MDBS) was performed. HIV- diagnosed children between 1997 and 2015 were selected. Sociodemographic, clinical and immunovirological data of HIV-infected children and their mothers were studied in four calendar periods (P1: 1997-2000; P2: 2001-2005; P3: 2006-2010; P4: 2011-2015). Rates of perinatal HIV diagnoses and transmission from 1997 to 2015 were calculated. A total of 532 HIV-infected children were included in this study. Of these children, 406 were Spanish (76.3%) and 126 immigrants (23.7%). A decrease in the number of HIV diagnoses, 203 (38.2%) children in the first (P1), 149 (28%) in the second (P2), 130 (24.4%) in the third (P3) and 50 (9.4%) in the fourth (P4) calendar periods was studied. The same decrease in the Spanish HIV-infected children (P1, 174 (46.6%), P2, 115 (30.8%), P3, 65 (17.4%) and P4, 19 (5.1%)) was monitored. However, an increase in the number of HIV diagnoses by sexual contact (P1: 0%; P2: 1.3%; P3: 4.6%; P4: 16%) was observed. The rates of new perinatal HIV diagnoses and perinatal transmission in Spanish children decreased from 0.167 to 0.005 per 100,000 inhabitants and 11.4% to 0.4% between 1997 and 2015, respectively. A decline of perinatal HIV diagnoses and transmission was observed. However, an increase of teen-agers HIV diagnoses with sexual infection was studied. Public awareness campaigns directed to teen-agers are advisable to prevent HIV infection by sexual contact.

Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution. Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit. 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5-6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 <1 with lower CD4 nadir and baseline CD4; older age at diagnosis and at cART initiation; and a previous exposure to mono-dual therapy. Multivariate analysis also revealed relationship between CD4/CD8 <1 and lower CD4 nadir (OR: 1.002, CI 95% 1.000-1.004) as well as previous exposure to mono-dual therapy (OR: 0.16, CI 95% 0.003-0.720). CD4/CD8 >1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1).