Off-label use of combined antiretroviral therapy, analysis of data collected by the Italian Register for HIV-1 infection in paediatrics in a large cohort of children.

BACKGROUND: Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children < 2 years of age and 60% in those aged 2-12 years, due to the lack of adequate paediatric clinical studies on pharmacokinetics, pharmacodynamics and drug safety in children. METHODS: An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. RESULTS: 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13-5.19; p = 0.024). Moreover, children < 2 years of age were at increased risk for receiving off-label HAART with respect to older children (OR: 3.24; 95% CI 1063-7.3; p = 0.001). Even if our safety data regarding off-label regimens where poor, no adverse event was reported. CONCLUSION: The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.

A randomized, placebo-controlled, double-blinded, single-centre, phase IV trial to assess the efficacy and safety of OM-85 in children suffering from recurrent respiratory tract infections.

BACKGROUND: Over many years, OM-85, a lysate of 21 common bacterial respiratory pathogens, has been demonstrated to prevent respiratory recurrences in children. However, further studies are needed to explore the true importance of OM-85 in the prevention of respiratory tract infections (RTIs) in children. This study was planned to further contribute to the evaluation of the role played by OM-85 in prevention of recurrent RTIs in children. METHODS: This study was a randomized (3:3:1), placebo-controlled, double-blind, single-centre, phase IV trial carried out in Italy to assess the efficacy of OM-85 (Broncho-Vaxom®; Vifor Pharma; Meyrin 2/Geneva, Switzerland) in reducing the number of new RTI episodes in 288 children aged 1 to 6 years with a history of recurrent RTIs and to compare the efficacy of the standard 3-month regimen with that of administration of OM-85 for 6 months during a 6-month study period. RESULTS: The number of RTIs and of children who experienced at least one RTI were significantly lower among patients receiving OM-85 for 3 months than among those given placebo (33% vs 65.1%, p < 0.0001). Differences were statistically significant for upper RTIs (i.e., common cold/viral pharyngitis and acute otitis media; p < 0.0001 and p = 0.006, respectively). Days of absence from day-care for children and working days lost by parents were significantly lower in the group with children treated with OM-85 for 3 months than in the placebo group (p = 0.007 and p = 0.004, respectively). No difference was seen between children who received OM-85 for 3 and those who received OM-85 for 6 months. The prevalence of atopy as well as the history of recurrent wheezing and age of the study child did not influence the results. Benefit was maximally evident among children with a history of frequent recurrences. OM-85 was well tolerated and safe, even in children who received an influenza vaccination. CONCLUSIONS: The use of OM-85 for 3 months in 3 series of 10 consecutive days each time reduces the risk of recurrent RTIs in children, with a favourable safety profile. The greater effect observed in children prone to several respiratory episodes than in non-prone children seems to indicate that this lysate should be administered especially to children with a proven high susceptibility to RTIs.

Streptococcus pneumoniae colonisation in children and adolescents with asthma: impact of the heptavalent pneumococcal conjugate vaccine and evaluation of potential effect of thirteen-valent pneumococcal conjugate vaccine.

BACKGROUND: The main aim of this study was to evaluate Streptococcus pneumoniae carriage in a group of school-aged children and adolescents with asthma because these results might indicate the theoretical risk of invasive pneumococcal disease (IPD) of such patients and the potential protective efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13). METHODS: Oropharyngeal samples were obtained from 423 children with documented asthma (300 males, 70.9%), and tested for the autolysin-A-encoding (lytA) and the wzg (cpsA) gene of S. pneumoniae by means of real-time polymerase chain reaction. RESULTS: S. pneumoniae was identified in the swabs of 192 subjects (45.4%): 48.4% of whom were aged <10 years, 46.9% aged 10-14 years, and 4.7% aged ≥15 years (p < 0.001). Carriage was significantly less frequent among the children who had received recent antibiotic therapy (odds ratio [OR 0.41]; 95% confidence interval [95% CI] 0.22-0.76). Multivariate analyses showed no association between carriage and vaccination status, with ORs of 1.05 (95% CI 0.70-1.58) for carriers of any pneumococcal serotype, 1.08 (95% CI 0.72-1.62) for carriers of any of the serotypes included in 7-valent pneumococcal conjugate vaccine (PCV7), and 0.76 (95% CI 0.45-1.28) for carriers of any of the six additional serotypes of PCV13. Serotypes 19 F, 4 and 9 V were the most frequently identified serotypes in vaccinated subjects. CONCLUSIONS: These results showed that carriage of S. pneumoniae is relatively common in all school-aged children and adolescents with asthma, regardless of the severity of disease and the administration of PCV7 in the first years of life. This highlights the problem of the duration of the protection against colonisation provided by pneumococcal conjugate vaccine, and the importance of re-colonization by the same pneumococcal serotypes included in the previously used vaccine.

Impact of genetic polymorphisms on paediatric atopic dermatitis.

In order to investigate whether polymorphisms of genes encoding some factors of innate and adaptive immunity play a role in the development of, or protection against atopic dermatitis (AD) and condition its severity, we genotyped 33 candidate genes and 47 single nucleotide polymorphisms (SNPs) using Custom TaqMan Array Microfluidic Cards and an ABI 7900HT analyser (Applied Biosystems, Foster City, CA, USA). The study involved 104 children with AD (29 with mild-to-moderate and 75 with severe disease; 42 girls; mean age ± SD, 5.8 ± 3.3 years) and 119 healthy controls (49 girls; mean age, 4.8 ± 3.0 years). IL10-rs1800872T, TG and MBL2-rs500737AG were all significantly more frequent among the children with AD (P = 0.015, P = 0.004 and P = 0.030), whereas IL10-rs1800896C and TC were more frequent in those without AD (P = 0.028 and P = 0.032). The VEGFA-rs2146326A and CTLA4-rs3087243AG SNPs were significantly more frequent in the children with mild/moderate AD than in those with severe AD (P = 0.048 andP = 0.036). IL10-rs1800872T and TG were significantly more frequent in the children with AD and other allergic diseases than in the controls (P = 0.014 and P = 0.007), whereas IL10-rs1800896TC and C were more frequent in the controls than in the children with AD and other allergic diseases (P = 0.0055 and P = 0.0034). These findings show that some of the polymorphisms involved in the immune response are also involved in some aspects of the development and course of AD and, although not conclusive, support the immunological hypothesis of the origin of the inflammatory lesions.

Evaluation of pituitary function after infectious meningitis in childhood.

BACKGROUND: A number of studies of adults have shown that pituitary deficiencies can develop in a considerable proportion of subjects during the acute phase of meningitis or years after the infection has disappeared. The results of the very few studies of the impact of pediatric meningitis on hypothalamic-pituitary function are conflicting. METHODS: In order to determine the incidence of pituitary dysfunction in children with central nervous system infection, we evaluated pituitary function and anthropometric parameters in 19 children with meningitis of different etiologies (15 males; mean age ± standard deviation [SD] at pituitary evaluation, 5.9 ± 4.0 years; mean time from the acute event ± SD, 18 ± 10 months). RESULTS: All of the subjects had a normal stature and growth velocity for their age and gender, and none of them was obese. On the basis of Tanner's reference charts, 17 subjects (13 boys and all four girls) were pre-pubertal; two boys were in Tanner stage 2. None of the subjects had central hypothyroidism. All of the patients had normal serum of insulin growth factor (IGF)-I and prolactin. Their sex steroid and gonadotropin levels were concordant with their age and pubertal status. Early morning urine osmolality and serum electrolyte levels showed no signs of diabetes insipidus. All of the patients had normal plasma adrenocorticotropic hormone (ACTH) levels. Peak cortisol responses to the standard dose Synacthen test (SDST) were normal in all cases. CONCLUSIONS: The results showed that hypopituitarism following infectious meningitis appears to be infrequent in childhood and children's pituitary glands seem to be less vulnerable to damage than those of adults.

Genetic polymorphisms and risk of recurrent wheezing in pediatric age.

BACKGROUND: Wheezing during early life is a very common disorder, but the reasons underlying the different wheezing phenotypes are still unclear. The aims of this study were to analyse the potential correlations between the risk of developing recurrent wheezing and the presence of specific polymorphisms of some genes regulating immune system function, and to study the relative importance of the associations of different viruses and genetic polymorphisms in causing recurrent episodes. METHODS: The study involved 119 otherwise healthy infants admitted to hospital for a first episode of wheezing (74 of whom subsequently experienced recurrent episodes) and 119 age- and sex-matched subjects without any history of respiratory problem randomly selected from those attending our outpatient clinic during the study period. All of the study subjects were followed up for two years, and 47 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped on whole blood using an ABI PRISM 7900 HT Fast Real-time instrument. RESULTS: IL8-rs4073AT, VEGFA-rs833058CT, MBL2-rs1800450CT and IKBKB-rs3747811AT were associated with a significantly increased risk of developing wheezing (p = 0.02, p = 0.03, p = 0.05 and p = 0.0018), whereas CTLA4-rs3087243AG and NFKBIB-rs3136641TT were associated with a significantly reduced risk (p = 0.05 and p = 0.04). IL8-rs4073AT, VEGFA-rs2146323AA and NFKBIA-rs2233419AG were associated with a significantly increased risk of developing recurrent wheezing (p = 0.04, p = 0.04 and p = 0.03), whereas TLR3-rs3775291TC was associated with a significantly reduced risk (p = 0.03). Interestingly, the study of gene-environment interactions showed that rhinovirus was significantly associated with recurrent wheezing in the presence of IL4Ra-rs1801275GG and G (odds ratio [OR] 6.03, 95% confidence interval [CI]: 1.21-30.10, p = 0.03) and MAP3K1-rs702689AA (OR 4.09, 95% CI: 1.14-14.61, p = 0.03). CONCLUSIONS: This study shows a clear relationship between the risk of wheezing and polymorphisms of some genes involved in the immune response. Although further studies are needed to confirm the results, these findings may be useful for the early identification of children at the highest risk of developing recurrent episodes and possibly subsequent asthma.

Preventing HIV mother-to-child transmission in a vertically infected pregnant woman with multiclass drug resistance, role of bis-in-die dolutegravir and neonatal AZT prophylaxis: A case report.

A suppressive antiretroviral therapy (ART) is necessary to prevent mother-to-child transmission (MTCT) of HIV during pregnancy. During this period, it is recommended to continue an ongoing safe and suppressive regimen, but history of multiclass drug-resistance (MDR) might need tailored, uncommon approaches posing tolerability and toxicity issues. This is the case of a 33 years of age, vertically infected woman with MDR HIV infection suppressed on a darunavir/cobicistat + atazanavir regimen switched during pregnancy to lamivudine + darunavir/ritonavir + dolutegravir 50 mg bis-in-die, maintaining complete viral suppression and delivering via caesarian section and without zidovudine (AZT) intrapartum prophylaxis a healthy HIV-negative newborn who received AZT post-exposure prophylaxis and showed regular growth patterns up to 2 years. Our case shows how archived MDR might complicate the preservation of HIV RNA suppression and highlights the importance of a tailored, multidisciplinary approach for pregnant women with MDR HIV and their newborns.

Clinical profile of recurrent community-acquired pneumonia in children.

BACKGROUND: The aim of this case-control study was to analyse the clinical characteristics of children with recurrent community-acquired pneumonia (rCAP) affecting different lung areas (DLAs) and compare them with those of children who have never experienced CAP in order to contribute to identifying the best approach to such patients. METHODS: The study involved 146 children with ≥2 episodes of radiographically confirmed CAP in DLA in a single year (or ≥3 episodes in any time frame) with radiographic clearing of densities between occurrences, and 145 age- and gender-matched controls enrolled in Milan, Italy, between January 2009 and December 2012. The demographic and clinical characteristics of the cases and controls were compared, and a comparison was also made between the cases with rCAP (i.e. ≤3 episodes) and those with highly recurrent CAP (hrCAP: i.e. >3 episodes). RESULTS: Gestational age at birth (p = 0.003), birth weight (p = 0.006), respiratory distress at birth (p < 0.001), and age when starting day care attendance (p < 0.001) were significantly different between the cases and controls, and recurrent infectious wheezing (p < 0.001), chronic rhinosinusitis with post-nasal drip (p < 0.001), recurrent upper respiratory tract infections (p < 0.001), atopy/allergy (p < 0.001) and asthma (p < 0.001) were significantly more frequent. Significant risk factors for hrCAP were gastroesophageal reflux disease (GERD; p = 0.04), a history of atopy and/or allergy (p = 0.005), and a diagnosis of asthma (p = 0.0001) or middle lobe syndrome (p = 0.001). Multivariate logistic regression analysis, adjusted for age and gender, showed that all of the risk factors other than GERD and wheezing were associated with hrCAP. CONCLUSIONS: The diagnostic approach to children with rCAP in DLAs is relatively easy in the developed world, where the severe chronic underlying diseases favouring rCAP are usually identified early, and patients with chronic underlying disease are diagnosed before the occurrence of rCAP in DLAs. When rCAP in DLAs does occur, an evaluation of the patients' history and clinical findings make it possible to limit diagnostic investigations.

SARS-CoV-2 infection in children: A 24 months experience with focus on risk factors in a pediatric tertiary care hospital in Milan, Italy.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is characterized by a wide variety of expressions ranging from asymptomatic to, rarely, critical illness. The basis of this variability is not yet fully understood. The aim of this study was to identify clinical and genetic risk factors predisposing to disease susceptibility and progression in children. Methods: We enrolled 181 consecutive children aged less than 18 years hospitalized with or for SARS-CoV-2 infection during a period of 24 months. Demographic, clinical, laboratory, and microbiological data were collected. The development of coronavirus disease 2019 (COVID-19)-related complications and their specific therapies were assessed. In a subset of 79 children, a genetic analysis was carried out to evaluate the role of common COVID-19 genetic risk factors (chromosome 3 cluster; ABO-blood group system; FUT2, IFNAR2, OAS1/2/3, and DPP9 loci). Results: The mean age of hospitalized children was 5.7 years, 30.9% of them being under 1 year of age. The majority of children (63%) were hospitalized for reasons different than COVID-19 and incidentally tested positive for SARS-CoV-2, while 37% were admitted for SARS-CoV-2 infection. Chronic underlying diseases were reported in 29.8% of children. The majority of children were asymptomatic or mildly symptomatic; only 12.7% developed a moderate to critical disease. A concomitant pathogen, mainly respiratory viruses, was isolated in 53.3%. Complications were reported in 7% of children admitted for other reasons and in 28.3% of those hospitalized for COVID-19. The respiratory system was most frequently involved, and the C-reactive protein was the laboratory test most related to the development of critical clinical complications. The main risk factors for complication development were prematurity [relative risk (RR) 3.8, 95% confidence interval (CI) 2.4-6.1], comorbidities (RR 4.5, 95% CI 3.3-5.6), and the presence of coinfections (RR 2.5, 95% CI 1.1-5.75). The OAS1/2/3 risk variant was the main genetic risk factor for pneumonia development [Odds ratio (OR) 3.28, 95% CI 1-10.7; p value 0.049]. Conclusion: Our study confirmed that COVID-19 is generally less severe in children, although complications can develop, especially in those with comorbidities (chronic diseases or prematurity) and coinfections. Variation at the OAS1/2/3 genes cluster is the main genetic risk factor predisposing to COVID-19 pneumonia in children.

Early acute cerebellar ataxia after meningococcal B vaccine: a case report of a 7-month-old infant and a review of the literature.

BACKGROUND: Acute cerebellar ataxia (ACA) and acute cerebellitis represent disorders characterized by a para-infectious, post-infectious, or post-vaccination cerebellar inflammation. They are relatively common neurologic disorders among children, and may follow infections, or, more rarely, vaccinations. Few cases are instead described among infants. Although the immunization with meningococcal group B (MenB) vaccine has been associated with some neurological side effects, suspected ACA has been reported only once in the literature. CASE PRESENTATION: we describe a 7-month-old female that presented ACA within 24 h from the MenB second dose vaccination. Extensive laboratory studies and magnetic resonance imaging excluded other causes. We then conducted an extended review of other vaccine related cases reported in the literature, focusing on the clinical characteristics of ACA and finding that ataxia and cerebellitis of para- or post-infectious cause are very rarely described in the first year of life. We collected 20 articles published in the last 30 years, including an amount of 1663 patients (1-24 years) with ACA. CONCLUSIONS: a very small number of suspected post-vaccinal ataxias has been described in recent years, compared to other causes, and vaccination remains an unquestionable medical need. Further research is needed to clarify the complex pathogenesis of this disorder and its eventual link with vaccinations.

Impact of rhinoviruses on pediatric community-acquired pneumonia.

This study of 592 children seen in our Emergency Department with radiographically confirmed community-acquired pneumonia (CAP) was designed to evaluate the role of rhinoviruses (RVs) in the disease. The respiratory secretions of each child were assayed using RVP Fast in order to detect 17 respiratory viruses, and the RV-positive samples were characterised by means of real-time polymerase chain reaction and sequencing. RVs were identified in 172 cases (29.0%): 48/132 children aged<1 year (36.3%), 80/293 aged 1-3 years (27.3%), and 44/167 aged≥4 years (26.3%). Sequencing demonstrated that 82 RVs (49.1%) were group A, 17 (10.1%) group B, and 52 (31.1%) group C; 21 (12.2%) were untyped. RVs were found as single agents in 99 cases, and together with two or more other viruses in 73 (40.7%). There were only marginal differences between the different RV groups and between single RV infection and RV co-infections. RV CAP is frequent not only in younger but also in older children, and RV-A is the most common strain associated with it. The clinical relevance of RV CAP seems to be mild to moderate without any major differences between the A and B strains and the recently identified RV C.

Epidemiology and antimicrobial susceptibility of Staphylococcus aureus in children in a tertiary care pediatric hospital in Milan, Italy, 2017-2021.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent worldwide and can cause severe diseases. MRSA is associated with other antibiotic resistance. COVID-19 pandemic increased antimicrobial resistance in adult patients. Only a few data report the antimicrobial susceptibility of S. aureus in the Italian pediatric population, before and during the COVID-19 pandemic. METHODS: We included all the S. aureus positive samples with an available antibiogram isolated from pediatric patients (< 18 years old) in a tertiary care hospital in Milan, Italy, from January 2017 to December 2021. We collected data on demographics, antimicrobial susceptibility, and clinical history. We compared methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA strains. We calculated the frequency of isolation by year. The incidence of isolates during 2020 was compared with the average year isolation frequency using the univariate Poisson test. We compared the proportion of MRSA isolates during 2020 to the average proportion of other years with the Chi-squared test. RESULTS: Our dataset included a total of 255 S. aureus isolated from 226 patients, 120 (53%) males, and 106 (47%) females, with a median age of 3.4 years (IQR 0.8 - 10.5). The mean isolation frequency per year was 51. We observed a significant decrease of isolations during 2020 (p = 0.02), but after adjusting for the total number of hospitalization per year there was no evidence that the incidence changed. Seventy-six (30%) S. aureus were MRSA. Twenty (26%) MRSA vs 23 (13%) MSSA (p = 0.02) were hospital-acquired. MRSA strains showed higher resistance to cotrimoxazole, clindamycin, macrolides, levofloxacin, gentamicin, and tetracyclin than MSSA strains. None of MRSA were resistant to linezolid and vancomycin, one was resistant to daptomycin. The proportion of MRSA did not change during the COVID-19 pandemic. The overall clindamycin resistance was high (17%). Recent antibiotic therapy was related to MRSA infection. CONCLUSION: The proportion of MRSA did not change during the COVID-19 pandemic and remained high. Clindamycin should not be used as an empirical MRSA treatment due to its high resistance.

Meningococcal Disease in Pediatric Age: A Focus on Epidemiology and Prevention.

Meningococcal disease is caused by Neisseria meningitidis; 13 serogroups have been identified and differentiated from each other through their capsular polysaccharide. Serotypes A, B, C, W, X, and Y are responsible for nearly all infections worldwide. The most common clinical manifestations are meningitis and invasive meningococcal disease, both characterized by high mortality and long-term sequelae. The infection rate is higher in children younger than 1 year and in adolescents, who are frequently asymptomatic carriers. Vaccination is the most effective method of preventing infection and transmission. Currently, both monovalent meningococcal vaccines (against A, B, and C serotypes) and quadrivalent meningococcal vaccines (against serogroups ACYW) are available and recommended according to local epidemiology. The purpose of this article is to describe the meningococcal vaccines and to identify instruments that are useful for reducing transmission and implementing the vaccination coverage. This aim could be reached by switching from the monovalent to the quadrivalent vaccine in the first year of life, increasing vaccine promotion against ACYW serotypes among adolescents, and extending the free offer of the anti-meningococcal B vaccine to teens, co-administering it with others proposed in the same age group. Greater awareness of the severity of the disease and increased health education through web and social networks could represent the best strategies for promoting adhesion and active participation in the vaccination campaign. Finally, the development of a licensed universal meningococcal vaccine should be another important objective.

Gut-dependent inflammation and alterations of the intestinal microbiota in individuals with perinatal HIV exposure and different HIV serostatus.

OBJECTIVE: HIV-exposed infected (HEI) and uninfected (HEU) children represent the two possible outcomes of maternal HIV infection. Modifications of the intestinal microbiome have been linked to clinical vulnerability in both settings, yet whether HEI and HEU differ in terms of gut impairment and peripheral inflammation/activation is unknown. DESIGN: We performed a cross-sectional, pilot study on fecal and plasma microbiome as well as plasma markers of gut damage, microbial translocation, inflammation and immune activation in HIV-infected and uninfected children born from an HIV-infected mother. METHODS: Fecal and plasma microbiome were determined by means of 16S rDNA amplification with subsequent qPCR quantification. Plasma markers were quantified via ELISA. RESULTS: Forty-seven HEI and 33 HEU children were consecutively enrolled. The two groups displayed differences in fecal beta-diversity and relative abundance, yet similar microbiome profiles in plasma as well as comparable gut damage and microbial translocation. In contrast, monocyte activation (sCD14) and systemic inflammation (IL-6) were significantly higher in HEI than HEU. CONCLUSION: In the setting of perinatal HIV infection, enduring immune activation and inflammation do not appear to be linked to alterations within the gut. Given that markers of activation and inflammation are independent predictors of HIV disease progression, future studies are needed to understand the underlying mechanisms of such processes and elaborate adjuvant therapies to reduce the clinical risk in individuals with perinatal HIV infection.

Corrigendum: Disappearance of seasonal respiratory viruses in children under two years old during COVID-19 pandemic: A monocentric retrospective study in Milan, Italy.

[This corrects the article DOI: 10.3389/fped.2021.721005.].

Intrapartum use of zidovudine in a large cohort of pregnant women living with HIV in Italy.

BACKGROUND: Intravenous administration of zidovudine (ZDV) during labour is a key step for vertical HIV transmission (VT) prevention, but there is no evidence of benefit when maternal HIV-RNA at delivery is <50 copies/mL. The aim of this study is evaluating the appropriateness of intrapartum ZDV use in Italy. METHODS: Observational study including mother-infant pairs with perinatal HIV exposure during 2002-2019, enrolled in the Italian Register for HIV Infection in Children. Univariable and multivariable logistic regression were used to evaluate factors associated with VT. RESULTS: A total of 3,861 infants, born from 3,791 pregnancies were included. The frequency of ZDV use was 79.9%, 92.1%, 93.7% and 92.8% when HIV-RNA was not available, ≥400 copies, between 50 and 399 copies, and <50 copies/mL. Thirty-three out of 3861 (0.85%) infants were subsequently diagnosed with HIV, 25/3861 (0.6%) of them born to mothers receiving intrapartum ZDV, and 31 (93.9%) to mothers with HIV-RNA ≥50 copies/mL or not available. In women with HIV-RNA < 50 copies/mL, ART discontinuation during pregnancy was the strongest risk factor for VT (odds ratio, OR, 23.1, 95%CI 2.4-219.3), while a higher gestational age (OR 0.6, 95%CI 0.4-0.8) and PEP administration to the newborn (aOR 0.004, 95%CI <0.0001-0.4) were protective factors. Intrapartum ZDV administration did not influence the final outcome in this group. CONCLUSIONS: In ART era, more transmission events may occur in utero, limiting value of intrapartum ZDV, particularly for women with suppressed HIV-RNA load. More attention to the HIV-RNA testing of mothers before delivery may avoid unnecessary ZDV use.

Antibody response of healthy children to pandemic A/H1N1/2009 influenza virus.

BACKGROUND: Little is known about the proportion of pediatric pandemic A/H1N1/2009 influenza cases who showed seroconversion, the magnitude of this seroconversion, or the factors that can affect the antibody level evoked by the pandemic A/H1N1/2009 influenza. Aims of this study were to analyse antibody responses and the factors associated with high antibody titres in a cohort of children with naturally acquired A/H1N1/2009 influenza infection confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Demographic, clinical and virologic data were collected from 69 otherwise healthy children with pandemic A/H1N1/2009 influenza (27 females, mean age ± SD: 5.01 ± 4.55 years). Their antibody levels against pandemic A/H1N1/2009 and seasonal A/H1N1 influenza viruses were evaluated by measuring hemagglutination-inhibiting antibodies using standard assays. Sixty-four patients (92.8%) with pandemic A/H1N1/2009 influenza had A/H1N1/2009 antibody levels of ≥ 40, whereas only 28/69 (40.6%) were seroprotected against seasonal A/H1N1 influenza virus. Those who were seroprotected against seasonal A/H1N1 virus were significantly older, significantly more often hospitalised, had a diagnosis of pneumonia significantly more frequently, and were significantly more often treated with oseltamivir than those who were not seroprotected (p < 0.05). The children with the most severe disease (assessed on the basis of a need for hospitalisation and a diagnosis of pneumonia) had the highest antibody response against pandemic A/H1N1/2009 influenza virus. CONCLUSIONS: Otherwise healthy children seem to show seroprotective antibody titres after natural infection with pandemic A/H1N1/2009 influenza virus. The strength of the immune response seems to be related to the severity of the disease, but not to previous seasonal A/H1N1 influenza immunity.

An open-label, randomized clinical trial assessing immunogenicity, safety and tolerability of pandemic influenza A/H1N1 MF59-adjuvanted vaccine administered sequentially or simultaneously with seasonal virosomal-adjuvanted influenza vaccine to paediatric kidney transplant recipients.

BACKGROUND: The aim of this study was to investigate the immunogenicity, safety and tolerability of the 2009 A/H1N1 MF59-adjuvanted influenza vaccine, administered sequentially or simultaneously with the seasonal 2009-10 virosomal-adjuvanted influenza vaccine, to paediatric kidney transplant recipients. METHODS: Thirty-two children and adolescents with transplanted kidneys and 32 age- and gender-matched healthy controls were randomized 1:1 to receive the pandemic vaccine upon enrolment and the seasonal vaccine 1 month later (16 transplant recipients and 16 healthy controls), or to receive the two vaccines simultaneously upon enrolment (16 transplant recipients and 16 healthy controls). RESULTS: When the pandemic vaccine was administered sequentially to the seasonal vaccine, it was significantly less immunogenic in the patients than in the controls (P < 0.05); when it was administered together with the seasonal vaccine, the immune response of both patients (P < 0.05) and controls (P < 0.05) was significantly greater than when it was administered sequentially. Seroconversion rates and the geometric mean titres of all of the seasonal antigens were significantly lower in the patients, regardless of the type of vaccine administration (P < 0.05). Simultaneous administration was associated with a better immune response against A/H1N1 and A/H3N2 antigens in both patients and controls, and did not increase the mild local and systemic reactions. No impact on renal function was observed. CONCLUSIONS: Paediatric kidney transplant recipients have a lower immune response to the pandemic influenza A/H1N1 MF59-adjuvanted and seasonal virosomal-adjuvanted influenza vaccines than healthy controls. The simultaneous administration of the two vaccines seems to increase immune response to both pandemic and seasonal A/H1N1 and A/H3N2 antigens, and has the same safety profile as that of the pandemic vaccine administered sequentially to the seasonal vaccine.

Variation in colonization, ADP-ribosylating and vacuolating cytotoxin, and pulmonary disease severity among mycoplasma pneumoniae strains.

RATIONALE: Mycoplasma pneumoniae was recently discovered to produce an ADP-ribosylating and vacuolating cytotoxin, designated CARDS toxin, which is hypothesized to be a primary pathogenic mechanism responsible for M. pneumoniae-induced pulmonary inflammation. It is unknown if cytotoxin production varies with M. pneumoniae strain or if variation in cytotoxin production affects pulmonary disease severity. OBJECTIVES: To examine the production of CARDS toxin by various strains of M. pneumoniae and compare the disease manifestations elicited by these strains in an experimental model of M. pneumoniae respiratory infection. METHODS: BALB/c mice were inoculated once intranasally with SP4 broth (negative control) or three different M. pneumoniae strains: M129-B7, M129-B9, or S1. Mice were assessed at 1, 2, 4, 7, 10, and 14 days after inoculation. Outcome variables included comparisons among M. pneumoniae strains relative to bronchoalveolar lavage (BAL) M. pneumoniae quantitative culture, CARDS toxin-based PCR, and CARDS toxin protein determinations, as well as cytokine and chemokine concentrations. Graded lung histopathologic score (HPS) was also assessed. MEASUREMENTS AND MAIN RESULTS: CARDS toxin concentrations were significantly increased in mice inoculated with strain S1 compared with mice inoculated with M129-B7 or M129-B9 strains. Quantitative M. pneumoniae culture and polymerase chain reaction were also significantly greater in mice infected with S1 strain compared with the other two strains, as were lung HPS and concentrations of IFN-γ, IL-12, IL-1α, macrophage inflammatory protein-1α, and keratinocyte-derived chemokine. In addition, a significant positive correlation was found between CARDS toxin concentration and lung HPS. CONCLUSIONS: CARDS toxin concentrations in BAL are directly linked to the ability of specific M. pneumoniae strains to colonize, replicate, and persist, and elicit lung histopathology. This variation among strains may predict the range in severity of pulmonary disease observed among patients.

Pediatric Septic Arthritis of the Knee Due to a Multi-Sensitive Streptococcus pyogenes Strain Responsive to Clindamycin-A Case Report.

Septic arthritis is an inflammatory process usually generated by a bacterial infection. The knee is one of the most frequently involved joints. The etiology varies depending on age, and hematogenous spread remains the primary cause in children. Herein, we report a case of a previously healthy three-year-old female who was referred to our institution for acute swelling of her right knee. After a clinical and radiological diagnosis of septic arthritis, an empirical treatment with a combination of cefotaxime and clindamycin was initiated. The isolation of a multi-sensitive Streptococcus pyogenes strain from the joint's effusion prompted the discontinuation of clindamycin and the usage of cefotaxime alone. One week later, an ultrasound was executed due to worsening in the patient's clinical conditions, and an organized corpuscular intra-articular effusion with diffuse synovial thickening was revealed. Cefotaxime was therefore replaced with clindamycin, which improved the symptoms. Despite the antibiotic sensitivity test having revealed a microorganism with sensitivity to both cephalosporin and clindamycin, clinical resistance to cefotaxime was encountered and a shift in the antimicrobial treatment was necessary to ensure a full recovery. This case study confirms that an antibiotic regimen based solely on a susceptibility test may be ineffective for such cases.