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Background: In recent years, new progress has been made regarding the diagnosis, treatment and prevention of acute otitis media (AOM). The Italian Pediatric Society therefore decided to issue an update to the previous guidelines published in 2010., Methods: Literature searches were conducted on MEDLINE by Pubmed, including studies in children, in English or Italian, published between January 1, 2010, and December 31, 2018. The quality of the included studies was assessed using the grading of recommendations, assessment, development and evaluations (GRADE) methodology. In particular, the quality of the systematic reviews was evaluated using the AMSTAR 2 appraisal tool. The guidelines were formulated using the GRADE methodology by a multidisciplinary panel of experts., Results: The diagnosis of AOM is based on acute clinical symptoms and otoscopic evidence; alternatively, the presence of otorrhea associated with spontaneous tympanic membrane perforation allows the AOM diagnosis. The diagnosis of AOM must be certain and the use of a pneumatic otoscope is of fundamental importance. As an alternative to the pneumatic otoscope, pediatricians can use a static otoscope and a tympanometer. To objectively establish the severity of the episode for the formulation of a correct treatment program, an AOM severity scoring system taking into account clinical signs and otoscopic findings was developed., Conclusions: The diagnosis of AOM is clinical and requires the introduction of specific medical training programs. The use of pneumatic otoscopes must be promoted, as they are not sufficiently commonly used in routine practice in Italy.

Background: The incidence of drug-resistant forms of tuberculosis (DR-TB) and the number of children treated with second-line drugs (SLDs) are increasing. However, limited amount of information is available regarding the use of SLDs in this population., Methods: To describe the treatment of pediatric TB with SLDs and factors associated with use of SLDs in children with and without documented DR-TB, records of pediatric TB patients referred to a center in Italy from 2007 to 2018 were reviewed retrospectively., Results: Of 204 children diagnosed with active TB during the study period, 42 were treated with SLDs because of confirmed or probable drug resistance (42.8%), adverse reactions to first-line drugs (7.1%), central nervous system involvement (11.9%) or unconfirmed possible drug resistance (38.1%). There were no deaths or adverse reactions to SLDs reported. Treatment was successful in 85.2% children treated with first-line drugs and 92.9% children treated with SLDs. After adjusting for calendar period, the only factor associated with DR-TB was <2 years old [odds ratio (OR): 5.24 for <2 years vs. 5-18 years; P = 0.008]. Factors associated with treatment with SLDs were TB at 2 or more sites (OR: 11.30; P < 0.001), extrapulmonary TB (OR: 8.48; P < 0.001) or adverse reactions to first-line drugs (OR: 7.48; P = 0.002). No differences were noted in age or region of origin., Conclusions: A substantial proportion of TB children were treated with SLDs. The main reason for using SLDs was failure of a first-line drug regimen, suggesting possible DR-TB and underestimation of DR-TB in children. The use of SLD regimens was associated with a high success rate and good tolerability profile.

This study is the largest report on Mycobacterium tuberculosis transmission rate (TR) from children with pulmonary tuberculosis to school pupils. Higher TR (around 21.6%) was observed in contacts of smear-positive children. TR from pediatric smear-negative index cases was around 0. If our data are confirmed, school contacts of a smear-negative index case could be screened only by clinical evaluation and tuberculin skin test, avoiding the routine use of chest radiographs in children less than 5 years of age as well.

Background: The spread of carbapenem-resistant Enterobacteriaceae (CRE) is a health problem of major concern. CRE-related infections have significant morbidity and mortality, but data on CRE infection in pediatric population are limited. The aim of this study was to analyze epidemiologic and clinical characteristics, risk factors, therapeutic options and outcome of CRE infections in children in Italy., Methods: We performed a retrospective, multicenter, observational study of children with confirmed CRE infection or colonization admitted between January 1, 2011, and March 1, 2014, to 7 Italian pediatric centers., Results: Sixty-nine patients presenting 74 CRE infections and/or colonization were included. The most frequently isolated strain was Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Children with CRE infections had longer length of stay in hospital (P < 0.001), duration of disease (P = 0.001) and antimicrobial treatment (P < 0.001) than colonized children. Oncologic/immunosuppressive conditions are one of the factors significantly associated with a fatal outcome among children with CRE infections., Conclusions: Our study confirms that CRE infections affect mostly children with oncologic diseases and immunosuppression. Controlled studies in large cohorts are needed to evaluate the best therapeutic options and to assess further risk factors influencing outcomes and the survival of pediatric patients with infections caused by CRE.

Background: Highly active antiretroviral therapy (HAART) has transformed human immunodeficiency virus infection (HIV) into a chronic condition. The effects of long-term HAART on the immune system activity of early infected children are not fully understood. Hence, the aim of this review is to investigate immune system recovery and residual alteration in HIV-infected children receiving HAART in high-income countries., Methods: A systematic review was performed by searches of PubMed and references of the relevant articles. Studies published between January 1, 2000 and April 1, 2014 and conducted in high-income countries reporting data on immunological features in HIV-infected children receiving HAART were included in this review., Results: Fifty-three articles were included in this review. Present knowledge on B-cell and T-cell function, immunoglobulin production, response to vaccine and innate immune system activity in HIV-infected children receiving HAART is discussed., Conclusion: Starting therapy as soon as diagnosis is ascertained and monitoring vaccine response in children under HAART are the most important tools to safeguard immunological function in HIV-infected children.

The introduction of combination antiretroviral therapy (ART) in HIV-infected children led to a dramatic reduction in HIV-related morbidity and mortality. The decision about which ART regimen to use on children and when to start the treatment needs to focus on assuring normal growth and neuropsychological development. According to the available treatment guidelines, all infants under 1 year of age with HIV should be started on an ART at diagnosis. It is difficult to balance between the benefits of providing treatment to asymptomatic children >1 year and the concerns about long-term resistance and antiretroviral drug side effects if the treatment is started too early. Current guidelines agree that the need for antiretroviral treatment among asymptomatic children >12 months depends on age-specific CD4+ T-cell count thresholds and viral loads. Recent studies showed that the introduction of combination ART during the first year of life preserves a good function of B-cell and T-cell compartments. Starting treatment earlier might have fundamental roles both in preserving the not yet depleted immune function and in preventing the progressive HIV encephalopathy. The comparison of the international guidelines available for starting HIV treatment in children in developed countries highlights a gray area. New randomized controlled studies are needed to clarify the appropriate approach in asymptomatic children between 2 and 5 years of age.

Worldwide, the benefits of combined antiretroviral (ARV) therapy in morbidity and mortality due to perinatally acquired human immunodeficiency virus infection are beyond question and outweigh the toxicity these drugs have been associated with in HIV-infected children and adolescents to date. In puberty, abnormal body fat distribution is stigmatizating and leads to low adherence to ARV treatment. The other metabolic comorbidities (mitochondrial toxicity, dyslipidemias, insulin resistance and low bone mineral density) and renal toxicity, albeit nonsymptomatic in most children, are increasingly being reported and potentially put this population at risk for early cardiovascular or cerebrovascular atherosclerotic disease, diabetes, pathologic fractures or premature renal failure in the third and fourth decades of life. Evidence from available studies is limited because of methodological limitations and also because of several HIV-unrelated factors influencing, to some degree, the development of these conditions. Current recommendations for the prevention, diagnosis, monitoring and treatment of metabolic and renal adverse effects in HIV-children and adolescents are based on adult studies, observational pediatric studies and experts' consensus. Healthy lifestyle habits (regarding diet, exercise and refraining from toxic substances) and wise use of ARV options are the only preventive tools for the majority of patients. Should abnormal findings arise, switches in one or more ARV drugs have proved useful. Specific therapies are also available for some of these comorbidities, although the experience in the pediatric age is still very scarce. We aim to summarize the epidemiological, clinical and therapeutic aspects of metabolic and renal adverse effects in vertically HIV-infected children and adolescents.

Background: During the last decades remarkable scientific advances have been made toward the prevention of HIV mother-to-child transmission, in particular in developed nations. The aim of this review was to analyze the latest findings and available international recommendations on the prevention of HIV mother-to-child transmission in high-income countries., Methods: We performed a literature search of the Cochrane Library, MEDLINE by PubMed and EMBASE from database inception through June 2014, using the following terms: HIV, mother-to-child transmission and mother-to-child-transmission prevention. All types of articles in the English language were included. US and available European guidelines were searched and included in the analysis., Results: One hundred fifty articles were selected for inclusion in this review., Conclusions: Global epidemiology of HIV infection is rapidly evolving, in particular in high-resource countries. The interpretation of clinical and epidemiological studies is crucial for the development of evidence-based recommendations to guide the management of HIV mother-to-child transmission. Although significant progress has been made, heterogeneity between countries in specific interventions still exists, which may address future research.

In the industrialized world, extraordinary successes have been attained in reducing mother-to-child HIV transmission and improving the survival of children with HIV infection; however, significant challenges remain.

The natural history of the pediatric HIV epidemic has changed since the introduction of strategies for the prevention of mother-to-child transmission and the implementation of highly active antiretroviral therapy. The demographic characteristics of the pediatric HIV-infected population and the incidence and pattern of HIV-related morbidity, as well as mortality rates, have been remarkably modified. This report gives an overview on the main changes that occurred in Western countries.

Tuberculin skin test, QuantiFERON-TB Gold In-Tube and T-SPOT.TB were performed in 338 children at risk for tuberculosis (TB), including 70 active TB cases. In children <5 years of age, QuantiFERON-TB Gold In-Tube sensitivity was 73.3% [95% confidence interval (CI): 57.5-89.1]; and T-SPOT.TB sensitivity was 59.3% (95% CI: 40.1-77.8); both were inferior to tuberculin skin test sensitivity (90.0%; 95% CI: 79.3-100). In children ≥ 5 years QuantiFERON-TB Gold In-Tube sensitivity was 92.5% (95% CI: 84.4-100); T-SPOT.TB sensitivity was 73.0% (95% CI: 58.6-87.3) ; and tuberculin skin test sensitivity was 97.5% (95% CI: 92.6-100).Test specificities were similar in all age groups.

Background: The diagnosis of latent or active tuberculosis in children is often challenging. Recently, interferon-γ release assays have been licensed, but their diagnostic accuracy in young children remains questionable as frequent false-negative or indeterminate results have been reported., Methods: We performed a multicenter, retrospective study in children 0-24 months of age who were tested at least once with QuantiFERON-TB Gold-in-tube (QTF-IT) ± tuberculin skin test (TST), to analyze its use and performance in clinical practice., Results: Eight-hundred and twenty-three children (449 males, median age 13.5 months) were enrolled. QTF-IT sensitivity and specificity for active tuberculosis were 92.4% and 98.6%, respectively. Indeterminate tests (4.2 %) were not related to age (P = 0.838) or gender (P = 0.223); 32 children (91.4 %) with an indeterminate QTF-IT ultimately resulted uninfected. In the 616 subjects with valid paired results of QTF-IT and TST, sensitivity and specificity were comparable (91.1% vs. 85.1% and 98.1% vs. 97.9%, respectively). Diagnostic concordance between tests was higher in Bacillus Calmétte-Guerin nonvaccinated children (κ = 0.802). A high rate of discordant tests was observed in latent infections., Conclusions: QTF-IT showed good sensitivity and specificity, and a low rate of indeterminate results in the first 2 years of life, supporting its use at this age. However, considering costs and the similar performance between QTF-IT and TST, it is reasonable to suggest the latter as first-line testing in young children. The complementary use of TST and interferon-γ release assays may be considered in selected cases to improve the accuracy of testing.

Data from 484 children (median age: 6 years; 46.5% immigrants) hospitalized for tuberculosis in 31 Tuscan hospitals in 1997-2011 were analyzed. Incidence increased from 7.3 (95% confidence interval: 4.9-9.4) to 12.5 (95% confidence interval: 9.6-15.4) per 100,000 (P=0.009). Increases were particularly profound in children<5 years of age, reaching 13.3 (95% confidence interval: 7.8-18.9; P<0.0001 for 2011 vs.1997) per 100,000. Pediatric tuberculosis is a major issue in Tuscany.

We performed a prospective study to investigate T-SPOT.TB and QuantiFERON-TB Gold In-Tube (QFT-G-IT) dynamics during antitubercular treatment in active tuberculosis (TB) or latent TB. Eighteen children with latent TB and 26 with TB were enrolled. At 6 months of follow-up reversion rate was 5.88% (95% CI:0-13.79) for QFT-G-IT; 9.09% (95% CI:0.59-17.58) for T-SPOT.TB (P=0.921) in TB cases. Significant decline in quantitative response was observed exclusively in TB cases. Our results suggest that serial IGRA have limited use in children receiving antitubercular treatment.

Background: Interferon-gamma release assays (IGRAs) have been recently developed for the diagnosis of tuberculosis (TB) infection. The aim of the present study was to evaluate the performance of an enzyme-linked immunosorbent assay (ELISA)-based IGRA for detecting TB in children., Methods: A prospective study in 336 children at risk for TB infection was carried out. All children were tested with tuberculin skin test (TST) and a commercial ELISA-based IGRA [QuantiFERON-TB Gold In-Tube (Cellestis)]., Results: TST were positive in 58 of 336 (17.3%) and IGRA in 60 of 336 (17.9%) children. Two (0.6%) IGRA results were indeterminate. The overall agreement between the 2 tests was intermediate (86.2%, kappa= 0.533). IGRA was positive in 15 of 16 (93.8%) children with active pulmonary TB. The discordant pattern IGRA-/TST+ was significantly associated with Bacille Calmette-Guérin (BCG) vaccination. Among IGRA+ children (excluding cases of TB disease), TST- were significantly younger than TST+ children., Conclusions: The good agreement between positive IGRA and active TB disease suggests a good sensitivity of IGRA. Discrepancies between IGRA and TST can be a result of higher specificity of IGRA that is not influenced by previous BCG vaccination. IGRA may be more sensitive in children younger than 48 months.

The pharmacokinetics of valganciclovir were studied in 8 infants ranging in age from 4 to 90 days (mean 20 days). We suggest that doses of 15 mg/kg given twice daily may be suitable for neonates and young infants.