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.

Oral lactoferrin in HIV-1 vertically infected children: an observational follow-up of plasma viral load and immune parameters.

Lactoferrin (LF) is a mammalian iron-binding glycoprotein with antiviral effects. This preliminary study evaluated 6 months' LF (3 g/day, orally) treatment in 22 human immunodeficiency virus type 1 (HIV-1) vertically infected children. Plasma viral load and CD4+ cell counts were assessed every 3 months; before, during and after LF administration. No significant changes were observed during the pre-treatment period. By 6 months, mean (+/- SD) plasma viral load (log10) declined from 4.54 (+/- 0.65) to 4.28 (+/- 0.60); median percentage CD4+ cell count increased from 21.5% to 24.5%. Two months after treatment discontinuation, mean plasma viral load did not differ significantly from baseline or month 6 levels, but the percentage CD4+ cell count remained significantly higher than the baseline value. LF plus antiretroviral (ARV) therapy was more effective at increasing CD4+ cell count than LF alone. None of the patients showed any new HIV-1-related symptoms at follow-up. LF might be a useful addition to ARV therapy, but further large-scale studies are required.

Longitudinal long-term follow-up study of children with vertically acquired hepatitis C virus infection.

Seventeen children with vertically acquired hepatitis C virus (HCV) infection were followed from birth for a mean of 104 months. Alanine aminotransferase (ALT) levels were increased significantly at 3 and 6 months of age but were stable thereafter. HCV polymerase chain reaction was positive at 3 months in 16 patients and at 12 months in one patient. Viral load remained stable during follow-up at a mean value of 5.4 +/- 0.4 log10. Mild chronic hepatitis was the most common histopathological feature on liver biopsy, occurring in six of the seven children biopsied at a mean age of 4.0 +/- 2.4 years. Genotype did not seem to be related to the type of liver involvement. The results of this study suggest that vertically acquired HCV infection has a benign course in children, despite the presence of viraemia and persistent alterations in ALT levels.

[Autoimmune neutropenia: which therapy?]. / Neutropenia autoimmune: quale terapia?

We observed a case of primary autoimmune neutropenia in a 10-months-old girl affected by a 4 x 6 cm latero-cervical abscess caused by a Staphylococcus aureus infection. The severity of this finding prompted us to start a G-CSF treatment (5 ug/Kg, 3 times-a-week). Granulocyte Colony Stimulating Factor immediately increased neutrophil count and led to a complete resolution of neutropenia in a 8-months period of time.

Follow-up of vertically HIV-1-infected long-surviving children.

This study describes the clinical, immunologic, and virological characteristics of 30 vertically human immunodeficiency virus type 1 (HIV-1)-infected children older than 8 years of age (long-survivors) before the introduction of protease inhibitors therapy. All of them were followed from birth. At the age of 8 years, 7 children presented no HIV-1-associated signs or only mild ones and only 5 had severe clinical manifestations (acquired immune deficiency virus [AIDS]). The remaining 18 children presented moderate signs with some immunodeficiency. The follow-up from 8 years of age (3.5 years on the average) showed that 6 children remained asymptomatic and were therefore defined as long-survivors nonprogressors (average, 13 years) and only 4 children developed AIDS. Progressive encephalopathy was the most striking clinical manifestation at follow-up and occurred in 6 children (always after immunodeficiency) with a polymorphic picture combining eye movement alterations, pyramidal signs and symptoms and mental deterioration. The majority of our long-survivors carried a virus with nonsyncytia-inducing phenotype, thus confirming its association with long survival. A switch to syncytia-inducing phenotype was observed only in 2 cases during the follow-up, but their clinical status did not change at follow-up.

Chronic ulcerative herpes simplex virus infection in HIV-infected children.

The frequency and severity of chronic herpes simplex virus (HSV-1) ulcerative infections were recorded in six HIV-infected children with severe immunodeficiency (mean CD4 + T lymphocytes/cmm = 39.4: range 8-66). The first episode of HSV infection consisted of vesicular-crusty lesions affecting the centro-facial cutis area. In five cases, relapses occurred 4 months later in the form of chronic ulcerative lesions that were always accompanied by a significant loss of tissue. Furthermore, three of the six children also showed perianal ulcerative lesions. Cytodiagnostic analysis revealed the typical cells in balloon degeneration; all of the children had HSV-1-positive vesicular fluid sample cultures. In our experience, chronic ulcerative HSV infection is relatively frequent in HIV-infected children (6.6%), and has unusual clinical manifestations with a good initial response to acyclovir treatment. Relapses are common and become increasingly worse and less responsive to treatment.

Occurrence of anti-thyroid autoantibodies in children vertically infected with HIV-1.

Autoimmune phenomena, especially occurrence of non organ-specific autoantibodies, are common in congenitally acquired HIV infection, mostly in the symptomatic stages of the disease. Anti-thyroid autoantibodies detected in adult patients represent the only type of organ-specific autoantibodies reported in HIV infection. As far as we know, occurrence of these autoantibodies has not been observed in HIV infected children. In this study thyroid biochemical pattern and possible occurrence of anti-thyroid autoantibodies were investigated in 40 vertically HIV infected, 18 seroreverted and 22 healthy children. 34% of HIV infected symptomatic children showed anti-thyroglobulin antibodies. Asymptomatic patients, seroreverted and healthy controls did not show any anti-thyroid antibodies at the time of the study. High Tg levels were observed in 38% of the 40 HIV infected patients and high TSH concentrations were found in 27.5% of the HIV children. High TSH values were more frequently observed in the infected children with moderate or severe immunocompromised status. Thyroxine binding globulin levels were high in 68% of the HIV children and in 22% of the seroreverted. The finding of anti-thyroid autoantibodies in congenital HIV infected children confirms the thyroid's involvement in HIV infection and provides more information about the wide spectrum of autoimmune phenomena observed in the infection.

Probiotics, prebiotics and child health: where are we going?

Changes in gastrointestinal (GI) bacteria caused by diet, antibiotics or other factors could alter enteric and systemic immune functions; changing the gut microflora composition by diet supplementation with specific live microbiota (probiotics) may be beneficial. The 'natural' target of ingested probiotics is the intestine, its microflora and associated immune system. Most published data concern use of probiotics to prevent and treat GI infections. Evidence for possible beneficial effects on mucosal barrier dysfunctions, including food allergy, inflammatory bowel disease, and respiratory and urinary tract infections, is emerging. The role of prebiotics (non-digestible oligosaccharides that reduce the growth or virulence of pathogens and induce systemic effects) is being investigated. Preliminary studies indicate that prebiotics may be useful dietary adjuncts for managing GI infections. Prebiotic and probiotic use in infants is attempting to modify a complex microbial ecosystem. Better understanding of the long-term effects of these interventions on infant gut microflora is an important goal.

[Familial transient red cell aplasia from parvovirus B-19 infection]. / Esordio familiare di crisi aplastica transitoria da Parvovirus B-19.

In our Paediatric Clinic we observed a case of transient aplastic crisis caused by Parvovirus B19 in a child and his mother, both affected by spherocytic haemolytic anemia. Anti-Parvovirus IgM antibody titre and viral search by PCR were positive. Anemia was treated with transfusion of concentrated red blood cells. In case of a family onset of hyperacute anemia it is necessary to consider a bone marrow aplastic crisis of the red series, induced by Parvovirus B19, especially if there is notice of an ongoing outbreak of erythema infectiosum.

[Nosocomial infections at a pediatric age]. / Infezioni nosocomiali in età pediatrica.

The overall incidence of nosocomial infections in children ranges from 2.3% to 12.6%. Even if there are great variations among data in literature, most authors agree that nosocomial infections are less frequent in children than in adults. Differences between these two populations concern anatomical sites of infection and microrganisms: in children, most frequent are gastrointestinal infections (10-35%), respiratory infections (5-30%) and bacteremia (10-23%); Gram positive bacteria account for 31-50% of infections, Gram negative for 23-35% and viruses for 22-27%. All these percentages change enormously depending on the type of department and child age. Because of increasing rates of resistance to antimicrobial agents, it is important to identify the main infectious agents and their sensibility, considering carefully when to give antibiotic therapy and what drug should be chosen.

Proposal of a step-wise follow-up for hepatitis C seropositive mothers and their infants.

Mother-to-child transmission of hepatitis C virus can take place in utero, during labour or after birth. Rate of vertical transmission varies widely between surveys but is around 5-6%. Maternal risk factors which may condition perinatal transmission risk are HIV/HCV coinfection, drug use, viral load, viral genotype, type of delivery and breastfeeding. On the basis of recent data, we propose a step-wise follow-up for HCV seropositive mothers and their infants. This proposal might represent an important occasion to unify behaviors in different Obstetrics-Gynecology and Neonatology Units.

Infants vertically infected with hepatitis C: a long term longitudinal follow-up.

HCV vertically acquired infection is asymptomatic and characterized by a high chronic infection rate; only 9% of HCV infected children shows spontaneous remission. As far as a mild course of the disease has been observed during childhood, we hypothesize that any eventual treatment intervention could be postpone until adolescent age.

Time-course of antibody and cell-mediated immune responses to Porcine Reproductive and Respiratory Syndrome virus under field conditions.

Major discrepancies are observed between experimental trials of PRRS-virus (PRRSV) infection in isolation facilities and observations made in the field on farm. Owing to the above, a cohort study was carried out in a farrow-to-finish, PRRSV-infected pig farm to characterize the time-course of the virus-specific immune response in two groups of replacement gilts. Despite the occurrence of three and two distinct waves of infection in groups 1 and 2, respectively, the large majority of animals showed little if any PRRSV-specific response in an interferon-gamma release assay on whole blood, whereas non-specific responses were consistently observed. To rule out any possible bias of our test procedure, this was used along with an ELISPOT assay for interferon-gamma-secreting cells with the same reagents on a group of PRRS-virus infected pigs in isolation facilities. A very good agreement was shown between the two sets of results. Also, as opposed to the PRRS model, plenty of Pseudorabies virus-vaccinated pigs under field conditions scored positive in another experiment in the interferon-gamma release assay, ad hoc modified for the Pseudorabies virus. Our results indicate that under field conditions poor or no development rather than delayed development of the PRRS virus-specific interferon-gamma response could be the rule for a long time in non-adult pigs after PRRS virus infection. Housing and hygiene conditions, as well as heavy exposure to environmental microbial payloads in intensive pig farms could adversely affect the host's immune response to PRRS virus and partly account for the discrepancies between experimental and field studies.

[Evaluation of the immune status of children never treated wtih chemoantibiotics (children 3 to 6 years old)]. / Valutazione dello stato immunitario di bambini mai sottoposti a terapia chemioantibiotica (bambini dai 3 ai 6 anni).

Six children aged between three and six years, born from undamaged families and free from malformative, chronic, degenerative or metabolic diseases, never treated with chemoantibiotics, were checked for their immune status. They were compared with other six children with the same somatic characteristics, the same health status and the same economical-social condition as the first six ones; but frequently treated with chemoantibiotics (not less than three therapy periods during each year of their life). The comparative study was performed by checking various parameters (lymphocyte blastization; rosette "E"; T3, T4, T8 lymphocytes with T4/T8 ratio; B lymphocytes; NK cells, chemotaxis; phagocytosis; killing; serum immunoglobulins A, G, M; C3; C4) index of immune functions, in uniform conditions. Results were statistically elaborated by means of "t-Student between groups test", "on ordinal ranks test", "t-Student for paired data test" and "Pearson's correlation coefficient" calculation. Significative differences by means of "t-Student between groups test" were recorded for what C3 is concerned, higher in never treated children, for PWM stimulation Blastization, lower in never treated children, for unstimulated blastization, chemotaxis and plasma IgM lower in frequently treated children. By means of "t-Student for paired data test" the above mentioned differences were confirmed and significantly higher values of plasma Immunoglobulin G and B lymphocyte in never treated children were pointed out. The differences between the last children and the controls are much higher than those previously recorded between similar groups 6-12 years old.

[Primary response to tetanus toxoid stimulation in early infancy]. / Studio della risposta primaria dopo stimolazione con tossoide tetanico nel giovane lattante.

The authors attempt to evaluate the degree of immune response to the first dose of anti-tetanus vaccination in young infants and to study the correlation between maternal and infantile antitetanus antibody titers. The sample studied comprised 5 males and 5 females aged between 61 and 75 days old, without acute and/or chronic pathologies and uncircumsized. Three samples of peripheral venous blood were collected for each infant: 1 at time 0, and the other two during the 15 days after the administration of the first dose of tetanus toxoid. The results support the hypothesis that vaccinal stimulation has a greater effect on cellular rather than humoral immunity, causing an increase in the CD4/CD8 ratio and a decrease in CD16. The study confirms that women with high antitetanus antibody titers during pregnancy have children with protective antibody titers. This underlines the importance of vaccinating pregnant women who, for various reasons, have not been immunised so as to prevent infantile tetanus and to allow the possibility of delaying, if necessary, the administration of the first dose of toxoid in infants without the risk of short-term toxoinfection.

Geological and seismological evidence of strike-slip displacement along the E-W Adriatic-Central Apennine belt

New geological, geophysical and seismological data produced in the last decade allow an improved definition of the kinematics of the Tyrrhenian Sea-central Apennines-Adriatic Sea system. The integration of these different types of dataset outlines a complex E-W deformational belt running from the Adriatic Sea, at Gargano latitudes, to the Latium-Abruzzi Platform domain (central Apennines). Its possible prosecution in the Tyrrhenian Sea is discussed. This belt has its own seismotectonic characteristics, and divides the Apennines into two zones with different seismotectonic behaviour. All these data were integrated into a multidisciplinary model that results in the introduction of a strike-slip displacement sometimes in Pliocene to recent times along the central Apennines-Adriatic Sea E-W belt. This relative motion can take for the strike-slip block tectonics observed in the central Apennines as well as for the uplift of Gargano and Tremiti Islands areas, including their seismicity. The displacement is related to a differing behaviour of the chain, foreland systems across this bend and can be justified either by assuming a partially active sinking of the southern Adriatic lithosphere or a slower sinking processes in the northern Adriatic one