Prevalence of tuberculosis in migrant children in Switzerland and relevance of current screening guidelines.

AIMS: Since 2016, Swiss guidelines recommend screening of all migrant children <5 years of age for tuberculosis (TB) and to screen older children only if they have risk factors for TB. Our goals were to describe the epidemiology of latent tuberculosis (LTBI) in migrant children at the Lausanne University Hospital, to identify determinants of LTBI and tuberculosis disease (TBD), and to evaluate the risk of a false-positive tuberculin skin test (TST) when using a positivity limit of 5 mm. METHODS: Newly arrived migrant children 0–18 years of age were prospectively enrolled from 31 August 2015 to 31 August 2017. Every migrant child was assessed for the risk of TB exposure and TBD and was administered a TST. A TB-spot test was performed in children ≥5 years of age when the TST was positive. Children with clinical and/or radiological signs of TBD were further investigated. Children ≥5 years of age with a positive TB-spot test and children <5 years of age with a positive TST, without clinico-radiological signs of TBD received a diagnosis of LTBI. A false-positive TST result was diagnosed in children ≥5 years of age when the TB-spot test was negative. Potential determinants of TB (LTBI and TBD) and of false-positive TSTs were identified. Student’s t-test or the Kruskal-Wallis test were used for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. All variables with a p-value <0.05 were included in a multivariate logistic regression model. RESULTS: Two hundred and fifty-three patients were eligible for the study. The median age of the patients was 8.1 years (interquartile range [IQR] 4.5–12.8) and 104 (41%) were female. Twenty-four percent of the patients (62/253) came from a country with a moderate–high incidence of TBD (≥80 cases per 100,000 individuals). Twenty-eight patients (11%) had positive TSTs, and TB was confirmed in 17 (6.7%) of these patients (16 with LTBI and 1 with TBD). On multivariate analysis, moderate–high incidence of TBD in the country of origin (adjusted odds ratio [aOR] 18.8, 95% confidence interval [CI] 5.1–68.6; p <0.001), older age (aOR 1.1, 95% CI 1.0–1.3; p = 0.025), and contact with a TBD patient (aOR 8, 95% CI 1.8–36.2; p = 0.007) were associated with a diagnosis of TB. Among the 23 children over 5 years of age who had a positive TST with measurement available, a measure between 5–9 mm was more frequent in case of a false-positive TST (5/9, 56% vs 0/14, 0%, p = 0.002). BCG vaccination was the only predictor of a false-positive TST (p = 0.03). CONCLUSION: Screening migrant children ≥5 years of age for TB could confer a public health benefit even in the absence of other risk factors. The limit of TST positivity could be raised from ≥5 mm to ≥10 mm to decrease the rate of false-positive results. A national assessment of migrant children between the ages of 5 and 15 should be carried out to confirm our findings.

Insights into the variability of nasal potential difference, a biomarker of CFTR activity.

BACKGROUND: Nasal potential difference (NPD) is used to evaluate CFTR function in vivo. We aimed to evaluate the intrasubject and intersubject variability of NPD measurements. METHODS: We reviewed NPD tracings of 116 patients with CF enrolled in the placebo arm of a multicenter study. Patients carried at least one nonsense mutation and underwent repeated NPD tests every 16 weeks. NPD parameters included basal potential difference (basal PD), inhibition of sodium absorption by amiloride (Δ Amiloride), chloride (Cl-) transport in response to a Cl--free solution (Δ Low Cl-), isoproterenol (Δ Isoproterenol), the sum of Δ Low Cl- and Δ Isoproterenol (Δ Low Cl--Isoproterenol) and ATP (Δ ATP). RESULTS: Basal PD and Δ Amiloride displayed the highest variabilities, mainly stemming from intercenter and intrasubject effect. Δ Low Cl-, Δ Isoproterenol and Δ Low Cl--Isoproterenol demonstrated a large intrasubject variability but a smaller intersubject variability. The intrasubject measurement variability for Δ Low Cl--Isoproterenol, was within ± 7.2 mV with 95% probability. It was greater in patients reporting ongoing pulmonary exacerbations. CONCLUSIONS: The large intercenter variability of basal PD and Δ Amiloride highlights the operator-dependent aspect of these measurements. A difference greater than 7.2 mV in Δ Low Cl--Isoproterenol in a given patient on CFTR modulator can be attributed, with 95% probability, to a treatment effect rather than to the variability inherent in the measurement.