Infectious Diseases in Internationally Adopted Children and Intercountry Discrepancies Among Screening Protocols, A Narrative Review.

Internationally adopted children (IAC) require thorough health assessments at time of arrival in the host country. As these children are at higher risk for infectious diseases, such as gastrointestinal parasites, tuberculosis, hepatitis, syphilis, and human immunodeficiency virus, early diagnosis of infectious diseases is fundamental for the optimal management of the child and, also, to reduce the risk of transmission to the adopting community. Comparative analysis of the screening protocols adopted in Europe, the United States, and Canada revealed different approaches to the adopted children. A homogeneous and internationally shared standard of care in the management of IAC should be provided.

Auxo-endocrinological features in a cohort of internationally adopted children in Italy.

BACKGROUND: Internationally adopted children (IAC) can present growth impairment at arrival, which usually recovers over time. Moreover, a major prevalence of precocious puberty has been reported in this group. METHODS: All IAC referred to a tertiary level hospital in Italy from January 2016 to June 2017, underwent a standardized screening protocol and were prospectively enrolled in the study. The analyses of possible risk factors for growth impairment and precocious puberty were performed. RESULTS: Overall, 422 children were included (males 59.5%), with median age of 6.5 years (IQR 9.4-3.9), 29.9% adopted from Europe, 26.8% from Asia, 23.9% from Africa and 19.4% from Latin America. Children were in Italy from a median of 75 days (IQR 137.0-38.7). Stunting was observed in 12.9% of children, wasting in 4.3%, underweight in 12.9%. Precocious puberty was diagnosed in 2.2% of children. 17.1% IAC had diagnosis of special needs. Fetal alcohol spectrum disorders represented the 41.7% of children with special needs and 48.1% of Russian children. Independent predictive factors for stunting were age < 5 years, a diagnosis of special need and having been living in Italy for < 60 days since the arrival. CONCLUSION: Stunting among IAC is a frequent finding especially in children < 5 years and in those with special needs, independently from their geographical origin.

Chest Imaging of a rare case of cat-scratch disease in a 2-years-old baby.

Cat-scratch disease (CSD) is usually a self-limiting infection that in the majority of cases occurs as lymphadenitis in children who have been scratched or bitten by a cat. Rarely, Bartonella henselae is cause of fever of unknown origin (FUO), with dissemination to various organs, mimicking an inflammatory rather than a lymphoproliferative disease. This manuscript will present a case of thoracic manifestations of CSD in an immunocompetent 2-years baby without history of cat contact, with fever of unknown origin, investigated by chest CT and MRI.

Utility of tuberculin skin test and IGRA for tuberculosis screening in internationally adopted children: Retrospective analysis from a single center in Florence, Italy.

BACKGROUND: Most of internationally adopted children (IAC) come from countries in which tuberculosis (TB) is endemic. Interpretation of discordant Tuberculin Skin Test (TST) and Quantiferon-Gold In Tube (QFT) results is under debate. METHODS: Children consecutively referred to our IAC Center between 2009-2017 were prospectively evaluated and screened with protocol recommended by the America Academy of Pediatrics, including TST and QFT. TB infection prevalence was evaluated and possible risk factors associated with discordant TST/QFT results were investigated. RESULTS: 1775 IAC were enrolled (median age: 5.8; IQR:3.3-8.2; 1065 [60.0%] males). Most of the children came from a European country (715; 40.3%) and, among them, 428 (59.9%) from Russia. Active pulmonary TB was diagnosed in 7 (0.4%) children while LTBI was diagnosed in 255 (14.4%) children. Concordant TST-/QFT-result was observed in 1520 (85.6%) children, concordant TST+/QFT + result in 63 children (3.5%), while 169 children (9.5%) displayed TST+/QFT-result and the remaining 23 children (1.3%) TST-/QFT+. Factor significantly associated with discordant TST+/QFT-result was BCG vaccination (aOR:2.62; 95%CI. 1.12-6.12; P = 0.026) and age <5 years (aOR: 5.59; 95%CI:2.27-12.18; P < 0001). . No significant association was evidenced with, continent of origin, eosinophilia or gender. CONCLUSIONS: Our data suggest that QFT might be used as unique screening assay in IAC, but further studies are needed at this regard.

Internationally adopted children: not only infectious diseases!

Information on prevalence of special needs in internationally adopted children (IAC) is incomplete. We reviewed data from 422 IAC screened at a single Centre in Italy in 2015-16. Prevalence of special needs reached 17.1% (n = 72). Among these children, the most frequent conditions were fetal alcohol spectrum disorders (FASD; n = 30; 7.1%), cleft lip palate (n = 8; 1.9%) and other congenital malformations (n = 20; 4.7%). Worrisomely, 25 out of 52 (48.1%) Russian children presented with FASD.

Latent tuberculosis in childhood: tolerability of two different therapeutic approaches.

BACKGROUND: Isoniazid monotherapy for six or nine months and the combination of isoniazid and rifampicin for three or four months are the most used regimens for treating latent tuberculosis. The main aim of this retrospective study is to evaluate the safety of latent tuberculosis treatment by analysing side effects in both regimens. RESEARCH DESIGN AND METHODS: Children with latent tuberculosis and treated with isoniazid or isoniazid and rifampicin were included. Periodic evaluations with clinical assessment and blood exams were carried out to detect any adverse reaction, including elevated serum transaminases. RESULTS: 441 children were included, 14.5% treated with isoniazid and 85.5% with isoniazid and rifampicin. Five patients under combined treatment developed hepatotoxicity within the first month. None of the patients under isoniazid monotherapy presented hepatotoxicity. A slight increase of transaminases level was found in both groups (18.7% in isoniazid and 10.3% in isoniazid/rifampicin groups, respectively) without causing discontinuation of treatment, with values normalization at the subsequent checks. CONCLUSIONS: Both regimens resulted safe. Hepatotoxicity occurred rarely and within the first month. For this reason, it may be appropriate to perform liver function tests after about one month from the beginning of therapy to avoid diagnostic delays.

Sleep habits and pattern in 1-14 years old children and relationship with video devices use and evening and night child activities.

BACKGROUND: Sleep in childhood and adolescence is crucial for mental and physical health; however several researches reported an increasing trend towards a sleep deprivation in this age. Due to the lack of recent epidemiological studies in Italy, the aim of our study was to depict sleep habits and patterns in Italian children aged 1-14 years and to evaluate their relationships with video devices use (TV, tablet, smartphone, PC) and evening/night child activities. METHODS: A structured interview was conducted during 2015 by 72 Family Pediatricians in 2030 healthy children aged 1-14 years by a cross-sectional survey named "Ci piace sognare". Total sleep duration was calculated, 2015 National Sleep Foundation Recommendations were used as reference. Optimal sleepers were defined children sleeping in own bed all night without awakenings. Multivariable median regression was performed to identify predictors of sleep duration and multivariable logistic regression for predictors of optimal sleep. RESULTS: Total sleep duration and numbers of awakenings decreased with age. Only 66.9% of children had sleep duration in agreement with Recommendations (50% in 10-14 years group). Before sleeping 63.5% of children used video devices (39.6% at 1-3 years), 39.1% read, 27.5% drank and 19.5% ate. Bottle users at bedtime were 30.8% at 1-3 years, 16.6% at 3-5 years and 4.9% at 5-7 years. Overall, 23.4% of children changed sleeping place during the night, 22.4% referred sleeping problems in the first year of life. Video devices use was negative predictor of sleep duration (-0.25 h [95%CI:-0.35,-0.14], p < 0.001). Optimal sleep was inversely related with bedroom TV (OR 0.63 [0.50,0.79], p < 0.001), with sleeping disorders in the first year (OR 0.62 [0.48,0.80], p < 0.001)), with bottle use (OR 0.64 [0.44,0.94], p < 0.05) and posivively related with high mother's education level (OR 1.44 [1.11,1.88], p < 0.01). CONCLUSIONS: About one third of 1 to 14 year Italian children sleep less than recommended, one half in teenage. Modifiable risk factors for sleep abnormalities such as video devices use, bedroom TV and bottle use should be target of preventive strategies for a correct sleep. Pediatricians should give priority to the identification of sleep disorders early in life.

Malaria in Children Adopted from the Democratic Republic of the Congo.

Data are lacking regarding asymptomatic and symptomatic malaria prevalence in internationally adopted children. Among 20 children from Democratic Republic of the Congo evaluated in Florence, Italy, in April 2016, malaria prevalence was 80%; 50% of infected children had symptomatic malaria. Adopted children from areas of high malaria endemicity should be screened for malaria.

Infectious diseases prevalence, vaccination coverage, and diagnostic challenges in a population of internationally adopted children referred to a Tertiary Care Children's Hospital from 2009 to 2015.

Infectious diseases are common in internationally adopted children (IAC).With the objective to evaluate infectious diseases prevalence in a large cohort of IAC and to explore possible risk factors for tuberculosis (TB) and parasitic infections, clinical and laboratory data at first screening visit of all IAC (<18 years) consecutively referred to our Center in 2009 to 2015 were collected and analyzed.In total, 1612 children (median age: 5.40 years; interquartile range: 3.00-7.90) were enrolled, 123/1612 (7.60%) having medical conditions included in the special needs definition. The most frequent cutaneous infections were Molluscum contagiosum (42/1612; 2.60%) and Tinea capitis (37/1612; 2.30%). Viral hepatitis prevalence was <1% (hepatitis B virus [HBV]: 13 children, 0.80%; hepatitis C virus: 1 child, 0.10%; hepatitis A virus: 6 children, 0.40%). A parasitic infection was diagnosed in 372/1612 (23.10%) children. No risk factors for parasitosis were evidenced. Active TB was diagnosed in 4/1355 (0.3%) children, latent TB in 222/1355 (16.40%). Only 3.7% (51/1355) children had concordant positive tuberculin skin test (TST) and QuantiFERON-TB-Gold In-Tube (QFT-G-IT) results. Risk factors for TST+/QFT-G-IT- results were previous Bacille de Calmette-Guérin vaccination (adjusted odds ratio [aOR]: 2.18; 96% confidence interval [CI]: 1.26-3.79; P = 0.006), and age ≥5 years (aOR: 1.49; 95% CI: 1.06-2.11; P = 0.02). The proportion of children with nonprotective titers for vaccine-preventable diseases (VPD) ranged from 15.70% (208/1323) for tetanus to 35.10% (469/1337) for HBV.Infectious diseases were commonly observed in our cohort. The high rate of discordant TST/QFT-G results brings up questions regarding the optimal management of these children, and suggests that, at least in children older than 5 years, only QFT-G-IT results may be reliable. The low proportion of children protected for VPD, confirms importance of a timely screening.

Use of specific immunoglobulins and vaccines for the management of accidental needlestick injury in the child: a practical review in the anti-vaccination movement era.

INTRODUCTION: Accidental needle injury is a common but still discussed problem. OBJECTIVE: We discuss possible options to optimize the management of injured children in light of the available literature findings. RESULTS: The risk of viral infection is low. However, blood investigations are mandatory, as well as appropriate counselling. Anti-HBV immunoglobulins are recommended in all unvaccinated subjects exposed to a HBsAg-positive source; however, there is no agreement regarding their administration in unvaccinated children. Use of anti-tetanus immunoglobulins in unvaccinated child with minor and clean wound is well defined; however, wound type classification in the event of needlestick injury may be difficult and subjective. There is no agreement on the routine use of antiretroviral prophylaxis. CONCLUSION: From a practical point of view, several unsolved issues have emerged regarding the management of the children with needlestick injury, which appear particularly relevant in the anti-vaccination movement era. International guidelines should be encouraged at this regard.

Performance of a non-contact infrared thermometer in healthy newborns.

OBJECTIVE: To evaluate the performance of a non-contact infrared thermometer (NCIT) in comparison with digital axillary thermometer (DAT) and infrared tympanic thermometers (ITT) in a population of healthy at term and preterm newborns nursed in incubators. SETTING: 1 level III maternity hospital, and its intensive neonatal care unit. PARTICIPANTS: 119 healthy at term newborns and 70 preterm newborns nursed in incubators were consecutively enrolled. Exclusion criteria were unstable/critical conditions, polymalformative congenital syndromes and severe congenital syndromes. INTERVENTIONS: Body temperature readings were prospectively collected. Each participant underwent bilateral axillary temperature measurement with DAT, bilateral tympanic measurement with ITT and mid-forehead temperature measurements using NCIT. PRIMARY OUTCOME MEASURES: Degree of agreement between methods was evaluated by the Bland and Altman method. RESULTS: 714 measurements in 119 healthy at term newborns and 420 measurements in 70 preterm newborns nursed in incubators were performed. Clinical reproducibility of NCIT was 0.0455 °C for infants in incubators and 0.0861 °C for infants outside an incubator. Bias was 0.029 °C for infants in incubators and <0.0001 °C for infants outside an incubator. Zero outliers were recorded. The mean difference between methods was good both for newborns at term (0.12 °C for NCIT vs DAT and 0.02 °C for NCIT vs ITT) and preterm newborns in incubators (0.10 °C for NCIT vs DAT and 0.14 °C for NCIT vs ITT). Limits of agreement were 0.99 to -0.75 and 0.78 to -0.75 in at term newborns and were particularly satisfactory in preterm newborns in incubators (95% CI: 0.48 to -0.27 and 0.68 to -0.40). CONCLUSIONS: Our results with Bland and Altman analysis demonstrate that NCIT is a very promising tool, especially in preterm newborns nursed in incubators. TRIAL REGISTRATION: The study was approved by the Careggi University Hospital Ethics Committee (07/2011).

Comparison of the transcutaneous bilirubinometers BiliCare and Minolta JM-103 in late preterm and term neonates.

OBJECTIVES: To assess the agreement of transcutaneous bilirubin (TcB) measurement with the Bilicare™ System in comparison to TcB measured with JM-103™ and total serum bilirubin (TSB). METHODS: Caucasian infants with gestational age ≥35 weeks with non-hemolytic jaundice received TcB measurement with both Bilicare™ and JM-103™ devices. TSB was also obtained in infants at risk of phototherapy. RESULTS: We studied 458 infants measuring TcB with Bilicare™ and JM-103™, correlating the results and with TSB. The mean difference ± 2SD between Bilicare™ and JM-103™ TcB was 2.02 ± 4.46 mg/dL and decreased from 2.88 ± 3.17 to 1.20 ± 4.55, and to -0.95 ± 4.58 mg/dL at mild, moderate and high TcB values, respectively. CONCLUSIONS: Bilicare™ and JM-103™ TcB measurements are well correlated, but Bilicare™ over-estimates TcB for mild and moderate values and under-estimates it for high values compared to JM-103™. This could increase the prescription of TSB measurements for less serious cases and decrease them in the most worrisome.

Strategies for the prevention of mother to child transmission in Western countries: an update.

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.

Interferon-gamma release assay sensitivity in children younger than 5 years is insufficient to replace the use of tuberculin skin test 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.

Vaccine effectiveness against severe laboratory-confirmed influenza in children: results of two consecutive seasons in Italy.

OBJECTIVE: To evaluate the effectiveness of seasonal influenza vaccine in preventing Emergency Department (ED) visits and hospitalisations for influenza like illness (ILI) in children. METHODS: We conducted a test negative case-control study during the 2011-2012 and 2012-2013 influenza seasons. Eleven paediatric hospital/wards in seven Italian regions participated in the study. Consecutive children visiting the ED with an ILI, as diagnosed by the doctor according to the European Centre for Disease Control case definition, were eligible for the study. Data were collected from trained pharmacists/physicians by interviewing parents during the ED visit (or hospital admission) of their children. An influenza microbiological test (RT-PCR) was carried out in all children. RESULTS: Seven-hundred and four children, from 6 months to 16 years of age, were enrolled: 262 children tested positive for one of the influenza viruses (cases) and 442 tested negative (controls). Cases were older than controls (median age 46 vs. 29 months), though with a similar prevalence of chronic conditions. Only 25 children (4%) were vaccinated in the study period. The overall age-adjusted vaccine effectiveness (VE) was 38% (95% confidence interval -52% to 75%). A higher VE was estimated for hospitalised children (53%; 95% confidence interval -45% to 85%). DISCUSSION: This study supports the effectiveness of the seasonal influenza vaccine in preventing visits to the EDs and hospitalisations for ILI in children, although the estimates were not statistically significant and with wide confidence intervals. Future systematic reviews of available data will provide more robust evidence for recommending influenza vaccination in children.

Controversies in preventive therapy for children contacts of multidrug-resistant tuberculosis.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is emerging as an increasing problem worldwide and no consensus has been reached about the management of children contacts of DR-TB cases. OBJECTIVE: To evaluate the role of post-exposure chemoprophylaxis in paediatric DR-TB contacts, focusing on literature findings and recommendations from existing international guidelines. METHODS: We conducted a literature search of the Cochrane Library, MEDLINE by PubMed and EMBASE from database inception through September 2012, using an appropriate search strategy. RESULTS: Eighteen articles were included: four retrospective and two prospective population studies, eight international guidelines and four narrative reviews. CONCLUSIONS: General agreement exists that preventive therapy could be beneficial in specific high-risk groups, including immunocompromised children and those aged < 5 years. However, no consensus exists on the use of preventive therapy in older or immunocompetent children and on which regimen should be preferred.

Increasing incidence of tuberculosis in Tuscan youth, 1997 to 2011.

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.

Drug use and upper gastrointestinal complications in children: a case-control study.

OBJECTIVE: To evaluate the risk of upper gastrointestinal complications (UGIC) associated with drug use in the paediatric population. METHODS: This study is part of a large Italian prospective multicentre study. The study population included children hospitalised for acute conditions through the emergency departments of eight clinical centres. Patients admitted for UGIC (defined as endoscopically confirmed gastroduodenal lesions or clinically defined haematemesis or melena) comprised the case series; children hospitalised for neurological disorders formed the control group. Information on drug and vaccine exposure was collected through parental interview during the children's hospitalisation. Logistic regression was used to estimate ORs for the occurrence of UGIC associated with drug use adjusted for age, clinical centre and concomitant use of any drug. RESULTS: 486 children hospitalised for UGIC and 1930 for neurological disorders were enrolled between November 1999 and November 2010. Drug use was higher in cases than in controls (73% vs 54%; p<0.001). UGICs were associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) (adjusted OR 2.9, 95% CI 2.1 to 4.0), oral steroids (adjusted OR 2.9, 95% CI 1.7 to 4.8) and antibiotics (adjusted OR 2.3, 95% CI 1.8 to 3.1). The duration of use of these drug categories was short (range 1-8 days). Paracetamol showed a lower risk (adjusted OR 2.0, 95% CI 1.5 to 2.6) compared to ibuprofen (adjusted OR 3.7, 95% CI 2.3 to 5.9), although with partially overlapping CIs. CONCLUSIONS: NSAIDs, oral steroids and antibiotics, even when administered for a short period, were associated with an increased risk of UGIC.

Potential role of M. tuberculosis specific IFN-γ and IL-2 ELISPOT assays in discriminating children with active or latent tuberculosis.

BACKGROUND: Although currently available IGRA have been reported to be promising markers for TB infection, they cannot distinguish active tuberculosis (TB) from latent infection (LTBI). OBJECTIVE: Children with LTBI, active TB disease or uninfected were prospectively evaluated by an in-house ELISPOT assay in order to investigate possible immunological markers for a differential diagnosis between LTBI and active TB. METHODS: Children at risk for TB infection prospectively enrolled in our infectious disease unit were evaluated by in-house IFN-γ and IL-2 based ELISPOT assays using a panel of Mycobacterium tuberculosis antigens. RESULTS: Twenty-nine children were classified as uninfected, 21 as LTBI and 25 as active TB cases (including 5 definite and 20 probable cases). Significantly higher IFN-γ ELISPOT responses were observed in infected vs. uninfected children for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p = 0.003), and AlaDH (p = 0.001), while differences were not significant considering Ag85B (p = 0.063), PstS1 (p = 0.512), and HspX (16 kDa) (p = 0.139). IL-2 ELISPOT assay responses were different for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p<0.0001), HspX (16 kDa) (p<0.0001), PstS1 (p<0.0001) and AlaDH (p = 0.001); but not for Ag85B (p = 0.063). Comparing results between children with LTBI and those with TB disease differences were significant for IFN-γ ELISPOT only for AlaDH antigen (p = 0.021) and for IL-2 ELISPOT assay for AlaDH (p<0.0001) and TB 10.3 antigen (p = 0.043). ROC analyses demonstrated sensitivity of 100% and specificity of 81% of AlaDH-IL-2 ELISPOT assay in discriminating between latent and active TB using a cut off of 12.5 SCF per million PBMCs. CONCLUSION: Our data suggest that IL-2 based ELISPOT with AlaDH antigen may be of help in discriminating children with active from those with latent TB.