Impact of Deprivation on the Incidence and Severity of Tuberculosis in Children: A Retrospective Study from 2007 to 2020 in a Tertiary Care Center in Paris, France.

OBJECTIVE: To assess the association between deprivation and the incidence and clinical severity of tuberculosis (TB) in children. STUDY DESIGN: Children ≤18 years old who were admitted for TB between 2007 and 2020 at a tertiary hospital were included in this retrospective study. Deprivation was assessed using the French Deprivation Index. TB severity was assessed using the Wiseman classification. Multivariate analyses were carried out. RESULTS: In total, 222 patients were included. The median age was 10.8 years (IQR 4.5-14.4). TB was considered severe in 126 patients (56.8%), with 50% of the patients included in the 2 most deprived groups. The most-deprived children had a TB incidence that was 58 times greater than that of the least-deprived children (95% CI 28.49-119.40). There was no significant association between deprivation and severity in the multivariable analysis after adjusting for age and circumstances of diagnosis. Deprivation was associated with an increased length of stay in the most-deprived groups (OR 3.79, 95% CI 1.55-10.23). There was a trend toward a greater proportion of symptomatic children in the most-deprived group. CONCLUSIONS: TB incidence and hospital length of stay increased with deprivation levels but not with the severity of TB.

Tuberculosis in Children Hospitalized in a Low-burden Country: Description and Risk Factors of Severe Disease.

BACKGROUND: In high-income countries, few pediatric studies have described the clinical expression of tuberculosis (TB) according to age, and their results are discordant. Patients <2 years of age are usually considered to be at higher risk for severe disease than older children. Our aim was to better describe pediatric TB disease severity in a low-incidence country. METHODS: All children (<18 years of age) admitted with TB disease to the Robert Debré University Hospital, Paris, between 1992 and 2015 were included. Patients were classified by the severity of TB disease based on the original classification of Wiseman et al. Risk factors associated with severity were analyzed. RESULTS: We included 304 patients with a median age of 9.9 years (interquartile range 3.3-13.3) and a male to female ratio of 1.04. Overall, 280/304 (92%) were classified: 168/304 (55%) were classified as showing severe TB and 112/304 (37%) as showing non-severe TB. Central nervous system disease was more frequent among patients <2 years of age than patients 2-17 years of age (5/54; 9% vs. 5/229; 2% P = 0.024). An age of ≥10 years (P = 0.001) and being born abroad (P = 0.011) were both associated with disease severity in univariate analysis. In multivariate analysis, diagnosis through symptom-based screening was independently associated with severity (odds ratio 7.1, 95% confidence interval: 3.9-12.9, P < 0.0001). CONCLUSIONS: This description of the clinical spectrum of pediatric TB in a low-burden setting demonstrates that adolescents are the group most at risk of experiencing severe TB.

Nontuberculous lymphadenitis in children: What management strategy?

OBJECTIVES: Nontuberculous mycobacterial (NTM) lymphadenitis is a rare disease of children under 5 years. Its treatment is not standardized, even a "wait-and-see" approach is shown to be effective in the literature. Here, we discuss the diagnostic and therapeutic strategies employed in our departments. METHODS: Records of pediatric patients treated for NTM cervical lymphadenitis from 2010 to 2015 in our tertiary center were retrospectively reviewed. Patients underwent cervical echotomography and/or CT scan. Every patient but one had microbiological explorations (NTM polymerase chain reaction [PCR] and culture) on fine needle aspiration of pus and/or adenitis biopsy. Differential diagnoses (tuberculosis, cat scratch disease) were excluded with serologies, chest X-Ray, and PCR on adenitis samples. Patients were classified as "proven diagnosis" (NTM detected), "highly probable" (suggestive clinical and anatomopathological aspect) or "possible" infection (suggestive adenitis alone). Treatments, follow-up and adverse events were reviewed. RESULTS: Thirty-one patients were treated for NTM, median age 2.40 years (Interquartile Range IQR = [1.85-3.16]). Twenty-nine patients (96.77%) had an isolated cervico-facial localization. Median follow-up was 8.00 months (IQR = [4.20-13.43]). We found 17 "proven diagnosis" (58.62%), 5 "highly probable" (17.24%) and 7 "possible" infections (24.14%). "Proven" infections were due to: Mycobacterium avium (n = 12, 66.67%) and M. intracellulare (n = 5, 27.78%). All 29 patients received antibiotics, which were effective for 10 (34.48%, group 1); 10 underwent surgical excision for a poor outcome with antibiotics (34.48%, group 2); spontaneous or surgical drainage occurred in 9 on antibiotics (31.03%, group 3). The median times to resolution for group 1, 2 and 3 were respectively 6.33 months, 6.22 months and 9.53 months. Antibiotics treatment was mostly clarithromycin (n = 27, 93.10%) and/or rifampicin (n = 19, 65.52%); 18 patients (62.07%) received both. Median antibiotics duration was 6.23 months (IQR = [5.17-7.46]), with good compliance (79.31%). The observed adverse effects were 3 (13.04%) isolated transient transaminase elevations, 1 case (4.35%) of minor creatinine elevation, and 1 case (4.35%) of transient diarrhea. Surgical drainage caused 1 transient marginal mandibular nerve palsy, resolutive after 1 month. CONCLUSION: Antibiotics in NTM adenitis lead to resolution in 7 months, with good tolerance and compliance. The efficacy of "wait-and-see" attitude in the literature make excision surgery a second line treatment.

Estrogens protect against high-fat diet-induced insulin resistance and glucose intolerance in mice.

Although corroborating data indicate that estrogens influence glucose metabolism through the activation of the estrogen receptor alpha (ERalpha), it has not been established whether this pathway could represent an effective therapeutic target to fight against metabolic disturbances induced by a high-fat diet (HFD). To this end, we first evaluated the influence of chronic 17beta-estradiol (E2) administration in wild-type ovariectomized mice submitted to either a normal chow diet or a HFD. Whereas only a modest effect was observed in normal chow diet-fed mice, E2 administration exerted a protective effect against HFD-induced glucose intolerance, and this beneficial action was abolished in ERalpha-deficient mice. Furthermore, E2 treatment reduced HFD-induced insulin resistance by 50% during hyperinsulinemic euglycemic clamp studies and improved insulin signaling (Akt phosphorylation) in insulin-stimulated skeletal muscles. Unexpectedly, we found that E2 treatment enhanced cytokine (IL-6, TNF-alpha) and plasminogen activator inhibitor-1 mRNA expression induced by HFD in the liver and visceral adipose tissue. Interestingly, although the proinflammatory effect of E2 was abolished in visceral adipose tissue from chimeric mice grafted with bone marrow cells from ERalpha-deficient mice, the beneficial effect of the hormone on glucose tolerance was not altered, suggesting that the metabolic and inflammatory effects of estrogens can be dissociated. Eventually comparison of sham-operated with ovariectomized HFD-fed mice demonstrated that endogenous estrogens levels are sufficient to exert a full protective effect against insulin resistance and glucose intolerance. In conclusion, the regulation of the ERalpha pathway could represent an effective strategy to reduce the impact of high-fat diet-induced type 2 diabetes.