Brain abscesses in children: an Italian multicentre study.

Brain abscess is uncommon in paediatric population, but of clinical importance because of significant long-term morbidity and mortality. In this multicentre study, promoted by the Italian Society for Paediatric Infectious Diseases, we retrospectively collected patients aged 0-18 years, with a diagnosis of 'brain abscess'. Seventy-nine children were included; the median age was 8·75 years. As predisposing factor, 44 children had preceding infections. The Gram-positive cocci were mostly isolated (27 cases). Sixty (76%) children underwent a surgical intervention. Intravenous antibiotic therapy was administered in all patients, then switched to oral treatment. Clinical sequelae were recorded in 31 (39·2%) children. Twenty-one of them had a single sequela, of which, the most represented, was epilepsy in nine of them. This study focus the attention on the need to have standardized national guidelines or adequate recommendations on type and duration of antibiotic treatment.

Prolonged in-hospital exposure to an infant with active pulmonary tuberculosis.

Active pulmonary tuberculosis was diagnosed in a 4-month-old infant 16 days after hospitalization; 186 exposed individuals were traced and one conversion detected. Although the risk of tuberculosis transmission in paediatric hospitals is low, paediatricians in low-incidence countries should maintain a high level of alert for timely identification of cases.

Italian consensus statement on paediatric HIV infection.

The objective of this document is to identify and reinforce current recommendations concerning the management of HIV infection in infants and children in the context of good resource availability. All recommendations were graded according to the strength and quality of the evidence and were voted on by the 57 participants attending the first Italian Consensus on Paediatric HIV, held in Siracusa in 2008. Paediatricians and HIV/AIDS care specialists were requested to agree on different statements summarizing key issues in the management of paediatric HIV. The comprehensive approach on preventing mother-to-child transmission (PMTCT) has clearly reduced the number of children acquiring the infection in Italy. Although further reduction of MTCT should be attempted, efforts to personalize intervention to specific cases are now required in order to optimise the treatment and care of HIV-infected children. The prompt initiation of treatment and careful selection of first-line regimen, taking into consideration potency and tolerance, remain central. In addition, opportunistic infection prevention, adherence to treatment, and long-term psychosocial consequences are becoming increasingly relevant in the era of effective antiretroviral combination therapies (ART). The increasing proportion of infected children achieving adulthood highlights the need for multidisciplinary strategies to facilitate transition to adult care and maintain strategies specific to perinatally acquired HIV infection.

BioEnterics intragastric balloon for treatment of morbid obesity in Prader-Willi syndrome: specific risks and benefits.

BACKGROUND: Obesity in Prader-Willi Syndrome (PWS) is progressive, severe, and resistant to dietary, pharmacological, and behavioral treatment. A body weight reduction is mandatory to reduce the risk of cardio-respiratory and metabolic complications. The aim of the study was to assess risks and benefits of BioEnterics Intragastric Balloon (BIB) for treatment of morbid obesity in PWS patients. METHODS: Twenty-one BIB were positioned in 12 PWS patients (4 M, 8 F), aged from 8.1 to 30.1 years, and removed after 8 +/- 1.4 months (range: 5-10 months). Auxological, clinical, and nutritional evaluations were performed every 2 months. Variations in body composition were analysed by dual energy X-ray absorbiometry (DXA). RESULTS: One patient (28.5 years, BMI: 59.3 kg/m(2)) died 22 days after BIB positioning because of gastric perforation. In another case (26.2 years, BMI: 57.6 kg/m(2)), BIB was surgically removed after 25 days because of symptoms suggesting gastric perforation (not confirmed). The remaining ten patients showed a significant decrease of BMI (p = 0.005) and of fat tissue as measured by DXA (p = 0.012). No significant modifications in bone mineral density (BMD) occurred, but a slight loss in lean body mass (p = 0.036) was documented. In five patients, BIB treatment was repeated more than once. CONCLUSION: This study shows that when noninvasive pharmacological therapies fail, BIB may be effective to control body weight in PWS patients with morbid obesity, particularly when treatment is started in early childhood. However, careful clinical follow-up and close collaboration with parents are crucial to avoid severe complications, which can be caused by persisting unrestrained food intake.

Lamivudine/abacavir maintains virological superiority over zidovudine/lamivudine and zidovudine/abacavir beyond 5 years in children.

OBJECTIVE: To describe the long-term efficacy over 5 years of regimens including combinations of abacavir, lamivudine and/or zidovudine in previously untreated children in the PENTA 5 trial. DESIGN: PENTA 5 was a 48-week randomised controlled trial comparing three dual nucleoside reverse transcriptase inhibitor (NRTI) combinations as part of first triple antiretroviral therapy (ART). METHODS: 128 ART-naïve children were randomised to zidovudine\lamivudine (n = 36), zidovudine\abacavir (45) or lamivudine\abacavir (47). Asymptomatic children (n = 55) were also randomised to nelfinavir or placebo; all other children received open-label nelfinavir. Analyses are intent-to-treat and adjusted for minor baseline imbalances and receipt of nelfinavir/placebo. RESULTS: Median follow-up was 5.8 years. By 5 years, 17 (47%), 28 (64%) and 18 (39%) children had changed their randomised NRTIs in the zidovudine\lamivudine, zidovudine\abacavir and lamivudine\abacavir groups respectively, but 18%, 50% and 50% of these changes were either early single drug substitutions for toxicity or switches with viral suppression (HIV-1 RNA < 400 copies/ml; e.g. to simplify regimen delivery). At 5 years, 55%/32% zidovudine\lamivudine, 50%/25% zidovudine\abacavir and 79%/63% lamivudine\abacavir had HIV-1 RNA < 400/< 50 copies/ml respectively (p = 0.03/p = 0.003). Mean increase in height-for-age 0.42, 0.68, 1.05 (p = 0.02); weight-for-age 0.03, 0.13, 0.75 (p = 0.02). Reverse transcriptase resistance mutations emerging on therapy differed between the groups: zidovudine\lamivudine (M41L, D67N, K70R, M184V, L210W, T215Y); zidovudine\abacavir (M41L, D67N, K70R, L210W, T215F/Y, K219Q); lamivudine\abacavir (K65R, L74V, Y115F, M184V). CONCLUSIONS: Five year data demonstrate that lamivudine\abacavir is more effective in terms of HIV-1 RNA suppression and growth changes, with lower rates of switching with detectable HIV-1 RNA than zidovudine\lamivudine or zidovudine\abacavir, and should be preferred as first-line NRTI backbone.

Herpetic whitlow as a harbinger of pediatric HIV-1 infection.

Herpetic whitlow applies to a primary or recurrent herpes simplex infection of the fingers. It is a rare condition in immunocompetent patients, and usually has a rapid evolution and prompt response to treatment. We report a 10-year-old girl referred to our department of infectious diseases with recurrent and unresponsive ulcerated and necrotic lesions of the fingers of both hands as a first sign of human immunodeficiency virus infection. Numerous instances of extensive or recurrent herpes lesions of the mouth, lips, and perianal areas have been found in the literature, but we have not found any report of periungual infection as a first manifestation of human immunodeficiency virus infection. Pediatricians and dermatologists need to be aware of this association in order to make an early diagnosis and start treatment of these patients' disease.

Pharmacokinetics and pharmacodynamics of nelfinavir administered twice or thrice daily to human immunodeficiency virus type 1-infected children.

We studied the pharmacokinetics and pharmacodynamics of nelfinavir administered 2 or 3 times per day to human immunodeficiency virus type 1 (HIV-1)-infected children receiving highly active antiretroviral therapy containing nelfinavir. The geometric mean trough concentrations of nelfinavir for the thrice- and twice-daily regimens were 1.55 mg/L and 1.11 mg/L, respectively (P=not significant). Nelfinavir concentrations did not correlate with total daily dose, dose per kilogram of weight, age, weight, previous protease inhibitor (PI) experience, or CD4(+) cell percentage. In the 25 PI-naive children, the virus load reductions at 24 weeks of treatment with the twice- and thrice-daily regimens were comparable. A significantly higher percentage of children in the twice-daily group had a trough concentration of nelfinavir of less than the inhibitory concentration of 95% (P=.042). The decrease in the virus load at 24 weeks of treatment was not correlated with the trough concentration of nelfinavir. The variability of trough concentrations was extremely high, particularly among recipients of the twice-daily regimen, resulting in a higher number of patients with subinhibitory concentrations of nelfinavir in this group.

Serum leptin and CD4+ T lymphocytes in HIV+ children during highly active antiretroviral therapy.

OBJECTIVE: Because leptin, the adipocyte-derived hormone, affects thymocyte survival, proliferation of naïve T lymphocytes and the production of proinflammatory cytokines, we aimed to investigate the role of this molecule in immunoreconstitution during highly active antiretroviral therapy (HAART). DESIGN: Prospective longitudinal cohort study. A series of 20 HIV+ children were studied. The subjects were grouped by their increase in serum leptin levels after HAART. METHODS: All participants were weight-stable, free of endocrine disorders and opportunistic infections and equally distributed for sex (males, n=10; females, n=10). Body mass index (BMI), serum lipids, leptin, CD4+ T cells and HIV-1 RNA were measured before initiation of HAART and after a 2-year follow-up. RESULTS: Serum leptin concentration positively correlated with CD4+ lymphocyte number before treatment. HAART significantly reduced viraemia and increased serum levels of lipids in all patients, whereas a significant increase in CD4+ cells and serum leptin was observed in the majority of patients. Notably, in children where HAART was not effective in increasing CD4+ lymphocyte counts, serum leptin did not increase. CONCLUSION: To our knowledge, these findings reveal for the first time a novel link among CD4+ T lymphocytes, serum leptin and highly active anteretroviral theraphy.

Kinetics of the T-cell receptor CD4 and CD8 V beta repertoire in HIV-1 vertically infected infants early treated with HAART.

OBJECTIVES: To determine the kinetics and the relationship between the T-cell receptor V beta (TCRBV) complementary determining region 3 length, the CD4 T-cell count and HIV viral load changes in HIV-1 infected infants treated early with highly active antiretroviral therapy (HAART) during 1 year of follow-up. DESIGN: Two HIV-1 vertically infected infants, two HIV-1 vertically exposed uninfected and two healthy controls were analysed by spectratyping. Evaluation of viral load, CD4 naive and memory cell counts and a proliferation test were also carried out. METHODS: Twenty-six families and subfamilies of the TCR on CD4 and CD8 T cells were analyzed by spectratyping. Flow cytometric analysis on peripheral blood mononuclear cells for CD4CD45Ra, CD4CD45Ro, CD8CD38, proliferation tests and plasma viral load measurements were performed at baseline, 1, 6 and after 12 months of therapy. RESULTS: HAART induced a marked reduction of viral load in both HIV-1 infected infants and an increase to normal CD4 T-cell count in the symptomatic infant. At baseline the TCRBV family distribution in the majority of CD8 and a few of the CD4 T cells was highly perturbed, with several TCRBV families showing a monoclonal/oligoclonal distribution. During HAART a normalization of the TCR repertoire in both CD8 and CD4 subsets occurred. TCR repertoire normalization was associated with a good virological and immunological response. CONCLUSION: These results suggest that complete and early virus replication control as a result of early HAART leads to a marked reduction of T-cell oligoclonality and is an essential prerequisite to the development of a polyclonal immune response in HIV-1 infected infants.

Role of immunity in maternal-infant HIV-1 transmission.

Factors influencing human immunodeficiency virus type 1 (HIV-1) mother-to-child transmission include both immunological and virological parameters: higher viral loads have been associated with clinical stage of HIV-1-infected individuals as well as higher risk of mother-to-child transmission. Furthermore, we have shown that transmitting mothers more frequently harbour HIV-1 isolates with rapid/high syncytium-inducing (SI) biological phenotype than non-transmitting mothers do. Genetically homogeneous virus populations have been found in HIV-1-infected children at birth, in contrast to the heterogeneous virus populations often found in their infected mothers. This observation suggests that a few virus variants are transmitted or initially are replicating in the child. By comparing the HIV-1 gp120 V3 region of sequentially obtained samples from infected children with samples obtained from their mothers at delivery we found, however, that multiple variants of HIV-1 with different outgrowth kinetics can be transmitted. In addition, we have obtained results indicating an impaired ability of the immune response to adapt to the sequence evolution of HIV-1 in transmitting mothers, as assessed by measuring serum reactivities to peptides representing selected yet closely related V3 sequences. By analysing the presence of antibodies in maternal serum at delivery, which neutralize autologous isolates as well as other primary virus isolates, we have indications that a protective immunity in HIV-1 mother-to-child transmission might exist. Immunotherapy has been assessed in infected adult individuals by passive immunization with a variety of HIV-1-specific antibody products. Data from these studies indicated a differential response to therapy according to the stage of the disease. Active vaccine strategies, including envelope glycoproteins, pursued so far in seronegative adult subjects have shown limitations because broadly neutralizing antibodies, such as can be found in infected individuals, have not been evoked. Further investigations are therefore needed to give support for the potential use of either passive and/or active immunization for the prevention of HIV-1 mother-to-child transmission.

[Diffusion of HIV infection in children]. / Diffusione dell'infezione da HIV in età pediatrica.

Human immunodeficiency virus (HIV) infection has spread to almost every country so as to show the characteristics of a pandemic. According to WHO estimates, there are over 10 million infected subjects all over the world of whom two thirds are believed to be Africans. The infection is transmitted mainly heterosexually, and therefore spreads especially among young people, hence the growing number of seropositive infants, particularly in Africa. In certain European nations including France, Spain, and Italy, the percentage of infected babies is associated with maternal drug addiction whereas in Romania pediatric transmission is horizontal. According to WHO estimates, AIDS will become the main cause of death for children in many African and American Countries in the next few years. In addition, there will be a considerable number of orphans below the age of 10 whose number is expected to rise to 10 million in the course of the nineties.