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Abstract Background Malaria caused by Plasmodium falciparum is one of the leading causes of human morbidity and mortality from infectious diseases, predominantly in tropical and sub-tropical countries. As genetic variations in the toll-like receptors (TLRs)-signalling pathway have been associated with either susceptibility or resistance to several infectious and inflammatory diseases, the supposition is that single nucleotide polymorphisms (SNPs) of TLR2, TLR4, TLR9, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and FCGR2A could modulate malaria susceptibility and severity. Methods This study was planned to make a further contribution to solving the problem of the real role of the most common polymorphisms of TLR4, TLR9, TIRAP and FCGR2A genes in modulating the risk of malaria and disease severity in children from Burundi, Central Africa. All the paediatric patients aged six months to 10 years admitted to the hospital of Kiremba, Burundi, between February 2011 and September 2011, for fever and suspicion of acute malaria were screened for malaria parasitaemia by light microscopy of thick and thin blood smears. In children with malaria and in uninfected controls enrolled during the study period in the same hospital, blood samples were obtained on filter paper and TLR4 Asp299Gly rs4986790, TLR9 G1174A rs352139, T-1486 C rs187084 TLR9 T-1237 C rs5743836, TIRAP Ser180Leu rs8177374 and the FCGR2A His131Arg rs1801274 polymorphisms were studied using an ABI PRISM 7900 HT Fast Real-time instrument. Results A total of 602 patients and 337 controls were enrolled. Among the malaria cases, 553 (91.9 %) were considered as suffering from uncomplicated and 49 (8.1 %) from severe malaria. TLR9 T1237C rs5743836CC was associated with an increased risk of developing malaria (p = 0.03), although it was found with the same frequency in uncomplicated and severe malaria cases. No other differences were found in all alleles studied and in genotype frequencies between malaria cases and uninfected controls as well as between uncomplicated and severe malaria cases. Conclusions TLR9 T1237C seems to condition susceptibility to malaria in Burundian children but not its severity, whereas none of the assessed SNPs of TLR4, TIRAP and FCGR2A seem to influence susceptibility to malaria and disease severity in this population.

In 177 children living in an area with high 13-valent pneumococcal conjugate vaccine 13 coverage, who had acute otitis media complicated with spontaneous tympanic membrane perforation, Streptococcus pneumoniae was identified in the middle ear fluid of 48 (27.1%) subjects, with 37 (77.1%) cases caused by nonpneumococcal conjugate vaccine 13 serotypes.

Hyaluronic acid (HA) treatment has been successfully performed in patients with recurrent upper airway infections or rhinitis. The aim of this study was to assess the efficacy and safety of the topical nasal administration of an HA-based compound by investigating its effects in children with recurrent or chronic middle ear inflammations and chronic adenoiditis. A prospective, single-blind, 1:1 randomised controlled study was performed to compare otoscopy, tympanometry and pure-tone audiometry in children which received the daily topical administration of normal 0.9% sodium chloride saline solution (control group) or 9 mg of sodium hyaluronate in 3 mL of a 0.9% sodium saline solution. The final analysis was based on 116 children (49.1% boys; mean age, 62.9 ± 17.9 months): 58 in the control group and 58 in the study group. At the end of follow-up, the prevalence of patients with impaired otoscopy was significantly lower in the study group (P value = 0.024) compared to baseline but not in the control group. In comparison with baseline, the prevalence of patients with impaired tympanometry at the end of the follow-up period was significantly lower in the study group (P value = 0.047) but not in the control group. The reduction in the prevalence of patients with conductive hearing loss (CHL) (P value = 0.008) and those with moderate CHL (P value = 0.048) was significant in the study group, but not in the control group. The mean auditory threshold had also significantly improved by the end of treatment in the study group (P value = 0.004) but not in the control group. Our findings confirm the safety of intermittent treatment with a topical nasal sodium hyaluronate solution and are the first to document its beneficial effect on clinical and audiological outcomes in children with recurrent or chronic middle ear inflammations associated with chronic adenoiditis., (© The Author(s) 2016.)

The assessment of fractures is a key issue in forensic anthropology; however, very few studies deal with the features of fractures due to explosion in comparison with other traumatic injuries. This study focuses on fractures resulting from blast trauma and two types of blunt force trauma (manual compression and running over), applied to corpses of pigs; 163 osteons were examined within forty fractures by the transmission light microscopy. Blast lesions showed a higher percentage of fracture lines through the Haversian canal, whereas in other types of trauma, the fractures went across the inner lamellae. Significant differences between samples hit by blast energy and those runover or manually compressed were observed (p<0.05). The frequency of pattern A is significantly higher in exploded bones than in runover and compressed. Microscopic analysis of the fracture line may provide information about the type of trauma, especially for what concerns blast trauma., (© 2015 American Academy of Forensic Sciences.)

Objective: To evaluate whether physicians follow current guidelines for managing acute otitis media (AOM) and whether educational programs are needed to improve knowledge of AOM treatment among paediatricians (PEDs) and otolaryngologists (ENTs) Methods: A total of 1270 PEDs and 852 ENTs were randomly selected and interviewed with an anonymous questionnaire about how they managed AOM., Results: Inappropriate AOM approaches were identified among 60.2% of PEDs and 88.5% of ENTs (p < 0.001). Amoxicillin and amoxicillin with clavulanic acid were appropriately chosen as first-line drugs by the majority of PEDs and ENTs, although significantly more ENTs reported otherwise (15.8% PEDs vs 25.5% ENTs; p < 0.001). ENTs were significantly more likely than PEDs to report prescribing decongestants, mucolytics, anti-inflammatory drugs, and steroids (p < 0.001)., Conclusion: These results show that AOM prescriptions for antibiotics and adjunctive treatments are often inappropriate and highlight the need for educational strategies aimed at PEDs and ENTs to improve their compliance with evidence-based guidelines for AOM treatment.

Objective: Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder in which hearing loss (HL) has been reported. However, no data are available concerning the association between audiological findings, clinical severity score and genotype., Methods: The study involved 44 pediatric patients aged 1-18 years with a confirmed diagnosis of CdLS, all of whom underwent a full otolaryngological and audiological examination. The presence of NIPBL and SMC1 mutations was also evaluated., Results: According to the severity of clinical phenotypes, 12 (27.3%) children were mild, 15 (34.1%) were moderate and 17 (38.6%) were severe. Thirty-eight children (86%) had OME. Eight children had normal hearing, including one (12.5%) with a severe phenotype. Bilateral sensorineural hearing loss (SNHL) was diagnosed in 10 children (22.7%): the degree of HL was severe in 8 (80%), all with a severe phenotype. Conductive hearing loss (CHL) was present in 26 patients (59.1%), of whom 8 (30.8%) had a severe phenotype. A severe phenotype was more prevalent among the patients with moderate to severe HL (10/16, 62.5%) than among those with slight/mild HL or normal hearing (7/28, 25.0% p=0.013). NIPBL mutations were detected in 22 patients (50%): 13 (59.1%) with truncating mutations, four (18.2%) with missense mutations, and five (22.7%) with splicing mutations. The frequency of NIPBL truncating mutations was similar in the children with SNHL and those with CHL, whereas this kind of mutation was not found in children with normal hearing., Conclusion: Together with SNHL, CHL is an important cause of HL in children with CdLS, and can be associated with a severe phenotype. Moreover, CHL can be associated with NIPBL mutations, particularly truncating mutations. These results highlight the importance of the early identification of audiological problems in children with CdLS and their precise genetic characterization., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: It has been shown that nasal saline irrigation (NSI) alone can be effective in children with infectious and/or allergic respiratory problems, but no study has assessed the awareness or clinical use of NSI among practising pediatricians. The main aim of this study was to evaluate the use of NSI in pre-school children by primary care pediatricians working in northern Italy., Methods: Nine hundred randomly selected National Health Service primary care pediatricians with an e-mail address were sent an e-mail asking whether they were willing to respond to a questionnaire regarding the use of NSI. The 870 who answered positively were sent an anonymous questionnaire by post and e-mail that had 17 multiple-choice items., Results: Completed questionnaires were received from 860 of the 870 primary care pediatricians (98.8%). NSI was used by almost all the respondents (99.3%), although with significant differences in frequency. It was considered both a prophylactic and a therapeutic measure by most of the respondents (60.3%), who prescribed it every day for healthy children and more frequently when they were ill. Most of the primary care pediatricians (87%) indicated an isotonic solution as the preferred solution, and the most frequently recommended administration devices were a nasal spray (67.7%) and bulb syringe (20.6%). Most of the pediatricians (75.6%) convinced parents to use NSI by explaining it could have various beneficial effects, and two-thirds (527/854; 61.7%) thought that most of the parents agreed about the importance of NSI. Analysis of possible associations between NSI prescribing behaviour and the demographic data revealed an associations with age and gender, with pediatricians aged <50 years prescribing NSI more frequently than their older counterparts (p < 0.01), and females prescribing NSI more frequently than males (p < 0.01)., Conclusions: In Northern Italy, most primary care pediatricians prescribe NSI for both the prophylaxis and therapy of upper respiratory tract problems in pre-school children. However, many aspects of the procedure are not clarified, and this reduces parental compliance. Given the medical and economic advantages of NSI, this situation should be changed as soon as possible.

Objectives: To compare the prevalence of acute otitis media (AOM) and otitis media with effusion (OME) in children hospitalized for acute lower respiratory infections (LRTIs) in Burundi and Italy., Methods: The study, which was conducted from 1 February to 30 April 2011 at the hospital of Kiremba (Burundi, Africa) and at Paediatric Clinic 1 of the University of Milan (Italy), enrolled patients aged <5 years who were hospitalised because of LRTIs. Upon admission, the children underwent an otological examination (pneumatic otoscopy and tympanometry), and middle ear diseases were compared between the two groups., Results: A total of 108 children enrolled in Burundi (44 males; median age 17 months) were compared to 108 patients enrolled in Italy (53 males; median age 19 months). About one-third of the children in Burundi (33, 30.6%) had normal middle ears. AOM was never diagnosed, whereas OME was detected in 74 children (68.5%: bilateral in 51, 68.9%, and unilateral in 23, 31.1%). The prevalence of OME decreased with increasing age: it was 86.5% in children aged <12 months, 73.7% in those aged 12-24 months, and 43.8% in those aged >24 months (p < 0.001). There was no difference in the proportion of children with OME in Burundi (68.5%) and Italy (63.9%; p = 0.47). OME was significantly more frequent in the children with pneumonia admitted in Burundi than in the children with pneumonia admitted in Italy (p = 0.004)., Conclusions: In children hospitalized for lower respiratory tract infection, OME is almost as frequently seen in developing countries like Burundi, Africa, as in developed countries like Italy. Follow-up monitoring of these children might be required to assess if OME is just a transient phenomenon., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: The aim of this study was to evaluate whether a deficit in vitamin D (VD) is associated with an increased risk of recurrent acute otitis media (AOM) and whether VD supplementation is effective in reducing the number of AOM episodes in otitis-prone children., Methods: A total of 116 children with a history of recurrent AOM (≥3 episodes in preceding 6 months or ≥4 episodes in preceding 12 months) were prospectively and blindly randomized to receive oral VD 1000 IU/d or placebo for 4 months. Episodes of AOM were monitored for 6 months., Results: Fifty-eight children received placebo and 58 with similar characteristics were treated with VD. The number of children experiencing ≥1 AOM episode during the study period was significantly lower in the treatment group (26 versus 38; P = 0.03). There was a marked difference in the number of children who developed uncomplicated AOM (P < 0.001), but no difference in the number of children with ≥1 episode of spontaneous otorrhea. The likelihood of AOM was significantly reduced in the patients whose serum VD concentrations were ≥30 ng/mL., Conclusions: VD hypovitaminosis is common in children with recurrent AOM and associated with an increase in the occurrence of AOM when serum 25(OH)D levels are <30 ng/mL. The administration of VD in a dosage of 1000 IU/d restores serum values of ≥30 ng/mL in most cases and is associated with a significant reduction in the risk of uncomplicated AOM.

Objective: The use of a pacifier has been reported to be a causative factor of recurrent acute otitis media (RAOM) because the negative pressure which is generated during sucking may cause a negative intra-tympanic pressure and favour the reflux of nasopharyngeal secretions into the Eustachian tube. Push and pull (P&P) plastic bottle caps, recently marketed in Italy, might also induce negative nasopharyngeal pressure. This study was aimed to investigate if there is a difference in the prevalence of habitual use of P&P plastic bottle caps among children with a positive history of RAOM and healthy controls., Methods: A telephonic interview was performed in order to retrospectively evaluate the prevalence of habitual use of P&P plastic bottle cap among children with a history of RAOM and healthy controls, comparable to the former for environmental risk factors for RAOM., Results: Data were obtained from 57 Caucasian patients (males=36/57; 63.2%) with a median age of 59 (range=21-90) months, including 28 children with a history of RAOM and 29 healthy controls. Habitual use of P&P plastic bottle cap was significantly (p=0.047) more frequent in children with a history of RAOM (14/28; 50.0%) than in control group (7/29; 24.2%). Multivariate logistic regression analysis adjusted for age confirmed a significant association (p<0.01; Pseudo R(2)=0.2) between the use of P&P plastic bottle cap and a positive history of RAOM (adjusted OR=4.0; range=1.1-15.0)., Conclusions: Our preliminary data show a significantly increased prevalence of P&P plastic cap bottle habitual users among children with a history or RAOM and support the need for larger studies to confirm the role of using P&P bottles as risk factor of RAOM and to identify the age groups at higher risk., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Nasopharyngeal fiberendoscopy (NFE) is the gold standard diagnostic procedure in children with suspected adenoidal disease, but it is not always easily feasible in younger children, and there is no consensus on the optimal technical approach according to children's age or disease. This paper aims to report our experience with NFE performed during routine paediatric clinical examination, also with regards to tolerability and patients' satisfaction., Methods: NFE was performed in paediatric patients with suspected adenoidal obstruction by means of a 2.7 mm-diameter flexible endoscope with the child seated in a chair or on parent's knees under outpatients basis and without administering local decongestants, anaesthetic agents, or sedatives. Relationship between possible confounders and patients' satisfaction, NFE tolerability, or needing for restraining was evaluated., Results: NFE was successfully performed in all but one syndromic 2-year old patient. Analysis was conducted on 191 children (mean age = 5.58; standard error, SE = 2.52 years). Restraining was required more frequently (p < 0.001) in younger children; NFE tolerability was good, as documented by mean visual analogue scale (VAS) values of 2.06 (SE = 1.58), and a better NFE tolerance was reported more frequently (p < 0.001) in older children. No significant relationship was found between needing for restraining or VAS and gender. No major or minor adverse events occurred., Conclusions: Our results support the feasibility and tolerability of flexible NFE performed by a skilled ENT specialist for nasopharyngeal evaluation in children aged more than 2 years with suspected adenoidal disease., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

As vitamin D (VD) has a significant regulatory effect on innate and adaptive immunity, the aim of this prospective, randomized, single-blinded, placebo-controlled study was to measure the impact of VD administration on the immune response to trivalent influenza vaccination (TIV). A total of 116 children (61 males, 52.6%; mean age 3.0 ± 1.0 y) with a history of recurrent acute otitis media (AOM), who had not been previously vaccinated against influenza, were randomized to receive daily VD 1,000 IU or placebo by mouth for four months. All of them received two doses of TIV (Fluarix, GlaxoSmithKline Biologicals) one month apart, with the first dose administered when VD supplementation was started. There was no difference in seroconversion or seroprotection rates, or antibody titers, in relation to any of the three influenza vaccine antigens between the VD and placebo groups, independently of baseline and post-treatment VD levels. The safety profile was also similar in the two groups. These data indicate that the daily administration of VD 1,000 IU for four months from the time of the injection of the first dose of TIV does not significantly modify the antibody response evoked by influenza vaccine.

Background: It has recently been demonstrated that vitamin D (VD) deficiency during pregnancy and lactation can give rise to problems in mothers and their children., Aim: To discuss the implications of VD deficiency during pregnancy and the best VD supplementation to use in order to avoid risks for the mother and child., Methods: PubMed was used to select all of the clinical studies published in the last 15 years concerning VD deficiency in pregnant women and its impact on the fetuses, neonates and infants, as well as the use of VD supplementation during pregnancy., Results: Several studies have suggested that VD deficiency is associated with possible major outcomes in the preconception period, during pregnancy, perinatally and in childhood. A 25(OH)D concentration of >32 and <50-60 ng/mL seems to be associated with the lowest risk of disease, and the administration of 2,000 IU/day to pregnant and breastfeeding women seems to maintain adequate 25(OH)D levels. However, not all the experts agree with these conclusions because some of them do not think that VD deficiency can really cause extraskeletal manifestations and consider that the traditionally suggested 400-600 IU/day can be enough to permit an adequate bone development., Conclusions: Despite an increasing amount of data seems to suggest that pregnant women need a greater amount of VD than recommended in the past, further studies are needed to determine how much VD has to be given to assure a regular evolution of the pregnancy and an adequate development of the fetus and the young child.

Acute otitis media (AOM) is common in infants and children. Although approximately two-thirds of cases are due to bacteria, almost all of the episodes are preceded by upper respiratory viral infection. Several viruses, among which respiratory syncytial virus is the most common, are involved in the determination of AOM. However, a significant number of AOM cases are associated with influenza infection, and influenza viruses are among the most frequently found respiratory viruses in the middle ear fluid during an acute episode of AOM. Consequently, influenza vaccination may have a favorable impact on the incidence and course of AOM. Moreover, as Streptococcus pneumoniae is one of the leading AOM bacterial pathogens and it is well known that influenza virus infection predisposes to pneumococcal infection, there is a further reason to suggest the use of influenza vaccine to reduce the risk of AOM. On the other hand, the administration of pneumococcal conjugate vaccine is considered per se a possible means of reducing the incidence of the disease. However, although a number of studies have measured the impact of both vaccines on AOM, it is still not known whether (and to what extent) they are really effective, nor what impact the more recently licensed vaccines may have. The aim of this review is to examine the clinical impact of vaccinations on AOM.

Influenza is frequent among otherwise healthy day-care and school-aged children. Recent studies have demonstrated its significant effect on various outcome factors, including significantly more school and parental work absenteeism, and secondary illnesses among family members. Other studies have shown that the potential benefit of vaccinating children against influenza extends to other members of their families, thus supporting earlier economic modeling analyses of immunization programs. Although there are some differences in the clinical and socio-economic impact of seasonal and pandemic influenza, the benefits of vaccination are similar in both cases. The vaccination of otherwise healthy children may significantly reduce direct and indirect influenza-related costs, which supports the recommendation to make wider use of influenza vaccine in healthy children of any age in order to reduce the burden of infection on the community.

Every year for the last few decades, the health authorities of most countries throughout the world have issued specific recommendations for the prevention and treatment of pediatric influenza, including recommendations concerning the use of vaccines. However, different evaluations of the importance of the disease and the efficacy of influenza vaccination frequently lead to conflicting recommendations. This is clearly demonstrated not only by the differences in the subjects for whom the vaccine is recommended, but also by the inaccurate manner in which subjects at risk of influenza-related complications are defined. Only further studies that consider the burden of the disease and vaccine efficacy in adequate numbers of healthy children and high-risk children with different chronic underlying diseases can overcome all of the current limitations and significantly improve vaccination coverage in both categories.

This study evaluated the immunogenicity of a double dose of the seasonal virosomal-adjuvanted influenza vaccine (Inflexal V, Crucell, The Netherlands) in 65 previously unvaccinated children aged less than 3 years: 43 received double doses (two doses of 0.50 mL 4 weeks apart) and 22 standard doses (two doses of 0.25 mL 4 weeks apart). Both treatments evoked a response that satisfied the EMEA criteria for adequate immunogenicity for all three vaccine strains, but the double dose had a significantly greater effect on all of the studied parameters of humoral and cell-mediated immune response (p<0.05). This result was achieved without any increase in the incidence of local and systemic adverse events. This means that doubling the dose of the virosomal-adjuvanted influenza vaccine (i.e. administering the same dose as that usually given to older children) effectively and safely increases the immune response to inactivated influenza vaccine in unprimed children aged less than 3 years., ((c) 2010 Elsevier Ltd. All rights reserved.)

The development of children who have syndromes with mental retardation and/or language delay can be worsened by sensorineural or conductive hearing loss (HL). Given the existing scarcity of data, we investigated the prevalence of otitis media with effusion and/or HL in 50 children with Cornelia de Lange syndrome (CdLS) aged 1-18 years, and its impact on the children's performance. The children underwent otological and audiological examinations in order to ascertain the relative frequencies of otitis media with effusion and/or hearing impairment; their demographic and clinical data were obtained by questionnaires and from information in their medical charts. Otitis media with effusion was diagnosed in 94%, and its prevalence was similar in all age groups; HL was detected in 40 children (80%). Conductive HL due to middle ear effusion was the main cause of hearing impairment alone (60%) or in combination with sensorineural deficit (20%). HL had a negative impact on performance regardless of the type. A history of routine audiological and/or otological assessments was reported by a minority of parents. Our findings indicate that otitis media with effusion and/or HL is an important feature of children with CdLS and may negatively affect their performance. Careful follow-up throughout childhood is necessary to detect and treat any hearing loss in children with CdLS in order to minimize its impact on performance.