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.

HPyV6, HPyV7 and TSPyV DNA sequences detection in skin disease patients and healthy subjects.

BACKGROUND: The discovery, from 2007, of eight new human polyomaviruses (HPyVs) has revived interest in the Polyomaviridae family and their association with human diseases and cancer. In particular, HPyV6 and HPyV7 were discovered in skin swabs of healthy donors and TSPyV was discovered in a heart transplant recipient affected by virus-associated Trichodysplasia Spinulosa (TS), a rare skin disease, exclusively found in immunocompromised patients. OBJECTIVE: The presence of HPyV6, HPyV7 and TSPyV DNA in skin biopsies from patients affected by different skin diseases (cancers and inflammatory disorders) has been evaluated to confirm their skin tropism and the possible pathological association. METHODS: DNA extracted was amplified with HPyV6, HPyV7 and TSPyV specific PCR real time on Taqman platform with standard profile. RESULTS: HPyV7 and TSPyV sequences were not found in any skin specimen analysed. HPyV6, on the other hand, was detected in 30% of samples from healthy subjects vs. 14.3% of skin cancer patients and 2.9% of inflammatory disorders. HPyV6 sequences have been detected in primary cutaneous T-cell lymphoma (CTCL) patients (in 18.6% out of Mycosis Fungoides (MF) patients and in 16.7% out of CTCL not MF/SS(Sèzary syndrome) but have not been detected in primary cutaneous B-cell lymphoma (CBCL) patients. CONCLUSION: Our preliminary data suggest that these three novel human polyomaviruses seem not to play a significant role neither in the pathogenesis of cutaneous malignancies nor in that of inflammatory disorders but, according to literature, can inhabit the skin. On the basis of our data regarding the HPyV6 DNA presence with decreasing percentages in healthy subjects, skin cancer and inflammatory disorders patients, it could be an intriguing matter to study if the activated innate immune response in inflammatory disorders can suppress the virus. Further investigations are needed to better understand their relationship with the human host and its innate immune system.

The spread of drug-resistant tuberculosis in children: an Italian case series.

Drug-resistant paediatric tuberculosis (TB) is an overlooked global problem. In Italy, the epidemiology of TB has recently changed and data regarding drug-resistant forms in the paediatric setting is scanty. The aim of this case series was to report the cases of drug-resistant TB, diagnosed between June 2006 and July 2010 in four Italian tertiary centres for paediatric infectious diseases, in children and adolescents living in Italy. Twenty-two children were enrolled, of these 17 were resistant to one or more drugs and five had multidrug-resistant TB. All but one child were either foreign born or had at least one foreign parent. Twenty-one patients completed their treatment without clinical or radiological signs of activity at the end of treatment, and one patient was lost to follow up. The outcomes were good, with few adverse effects using second-line anti-TB drugs. Although this series is limited, it might already reflect the worrisome increase of drug-resistant TB, even in childhood.

A case of acute disseminated encephalomyelitis following influenza virus A-H1N1 infection.

We describe a case of acute disseminated encephalomyelitis (ADEM) occurring in a three-year old girl with influenza A (H1N1)v infection and manifesting with seizures and ataxia. The brain MRI revealed bilateral hyperintense signal changes in basal ganglia and brain stem. The patient was treated with intravenous methylprednisolone bolus followed by tapering steroids and progressively recovered without neurologic sequelae at the latest follow-up. ADEM may represent a rare postinfectious complication following novel pandemic influenza A H1N1v which should be taken into account in the differential diagnosis of associated neurologic manifestations for the specific therapeutic approach and adequate follow-up.

An adolescent with persistent cervical lymphadenopathy and retropharyngeal abscess: case report.

Tuberculosis keeps on representing a serious threat worldwide and one of the major challenge of our century. Different strategies have been developed in order to eradicate the disease, and particular attention is paid to children, who are at great risk for developing severe manifestations and poor outcome. Age at exposure, nutritional conditions and immune status can lead to great variability of disease expressions, with subsequent difficulties in making an appropriate and rapid diagnosis. Moreover, children coming from tuberculosis-endemic areas should be carefully evaluated for M. tuberculosis infection. Here we present a infrequent manifestation of extrapulmonary tuberculosis in a 13-years-old girl coming from Latin America: a superficial persistent cervical lymphadenopathy was associated with a totally asymptomatic retropharyngeal abscess. Diagnostic approach was discussed. Treatment consisted with a combination of surgical drainage of the abscess and a prolonged combined 6-month chemotherapy. The cervical lymphadenopathy disappeared and no relapses were found during the subsequent follow up.

Tolerability of donkey's milk in 92 highly-problematic cow's milk allergic children.

OBJECTIVE: Not exclusively breastfed children with cow's milk allergy (CMA) require a formula or other alternative food, but past and present guidelines differ concerning the best choice. Our aim was to investigate the clinical tolerability, palatability and nutritional adequacy of donkey's milk (DM) in children with proven CMA. It was important to identify a CM replacement for these children, highly problematic from the feeding standpoint, in spite of their age. STUDY DESIGN: A prospective study was conducted on 92 children with CMA, diagnosed through a CM elimination diet, followed by double-blind, placebo-controlled food challenge (DBPCFC) unless contraindicated. Maternal milk was unavailable and current CM substitutes could not be used. Moreover, 89 percent were affected by multiple FA, and subjected to very restricted diets. Within 3 months after the last CM challenge, DBPCFC for DM was performed. CM or DM skin prick test and sIgE determination preceded the CM or DM challenge, respectively. Native electrophoresis and immunoblotting were used to identify CM and DM cross-reactive proteins. Z-scores of weight and length/stature for age were calculated at DM food challenge (T0) and during DM assumption. RESULTS: 83 children (90.2 percent) liked and tolerated DM, at challenge and during follow-up, with increased Z-score for weight and length/stature and improved nutritional parameters. Bovine beta-lactoglobulin was identified as the cross-reacting protein among the DM allergic patients. CONCLUSIONS: DM was found to be a valid alternative foodstuff, in terms of clinical tolerability, palatability and nutritional adequacy, in subjects with CMA who were highly problematic from the feeding standpoint.

Final height in patients perinatally infected with the human immunodeficiency virus.

INTRODUCTION: Data concerning final height are completely lacking in human immunodeficiency virus (HIV)-infected children. DESIGN: Retrospective evaluation of auxological data up to final height in a cohort of patients with perinatal HIV infection. PATIENTS AND METHODS: In 95 Caucasian patients (57 females and 38 males, median age 17.5 years) the following data were evaluated as standard deviation (SD) score: prepubertal height (PrH), height velocity (HV), final height (FH), target height (TH), FH minus PrH, predicted adult height (PAH), FH minus PAH, and FH minus TH. RESULTS: Patients showed a significantly reduced PrH and FH compared to their TH (p < 0.001), even if no difference was evidenced between PrH and FH. Age at puberty onset displayed a negative significant correlation with PrH (p = 0.002) and CD4+ cell percentage (p < 0.01). Finally, HV displayed a significant correlation with viremia (p = 0.001), but not with CD4+ cell percentage. CONCLUSIONS: HIV perinatally infected patients show a FH significantly reduced and not in accordance with TH. Our data seem to suggest that the losses in stature accumulated throughout the total period of childhood and adolescence may contribute to their reduced FH.

Prospective incidence study of bloodstream infection in infants and children with central venous catheters after cardiac surgery in Italy.

This prospective observational study was designed to assess the incidence of, risk factors for, and outcome of catheter-related bloodstream infection in children undergoing cardiac surgery. A staff specifically trained to handle the central venous catheters with proper aseptic techniques and an appropriate patient to medical staff ratio remain the most effective measures to prevent this infection.

A prospective 7-year survey on central venous catheter-related complications at a single pediatric hospital.

The aims of this study were to assess the incidence and risk factors of major central venous catheter (CVC)-related complications in a large cohort of children affected by oncological, hematological, or immunological diseases in a 7-year prospective observational study at a single center. Nine hundred fifteen CVCs were inserted in 748 children for a total period of 307,846 CVC-days. Overall, 298 complications were documented with a complication rate of 0.97/1,000 CVC-days: 105 mechanical complications (dislocations 0.30/1,000 CVC-days, ruptures 0.04/1,000 CVC-days), 174 infections (bloodstream infections 0.46/1,000 CVC-days, tunnel infections 0.10/1,000 CVC-days), and 19 thrombosis (0.06/1,000 CVC-days). Significant risk factors were: diagnosis of acute lymphoblastic leukemia (ALL) and age

Prolonged follow up of seven patients affected by hepatosplenic granulomata due to cat-scratch disease.

This study is a retrospective analysis of seven patients with hypoechogenic lesions in the liver and/or spleen due to Bartonella henselae, who were followed from 1998 through to 2005 by the Department of Pediatrics, Turin University. In addition to showing constitutional symptoms, four children had skin lesions suggestive of injuries inflicted by cats, and one child had a history of exposure to cats. The origin of the infection remained undefined in the other two patients. Humoral tests enabled a precise diagnosis in all children. Treatment with macrolides or combinations of two active antibiotics for at least 2-3 weeks led to the definitive clearance of infection, although residual intraparenchymal lesions persisted in five patients for several months or years. Conclusion B. henselae serology allows an easy diagnosis of multiple hepatosplenic granulomata, a clinical picture that appears to be under-recognized. Macrolides or a combination of two active antibiotics for 2-3 weeks leads to a rapid clinical response and a definitive clearance of infection.

[Human papillomavirus vaccination. Consensus Conference in pediatric age]. / La vaccinazione verso il papillomavirus umano. Consensus Conference dell'area pediatrica.

Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection worldwide. Spontaneous clearance of HPV infection occurs in most cases, but chronic infection with high risk genotypes is associated with the development of cervical cancer. In particular, HPV 16 and 18 are responsible for 70% of cancers of the cervix and, in variable proportions, for cancers of the vagina, vulva, anus, penis and oropharinx. Low risk HPV genotypes, such as HPV 6 and 11, cause genital warts. Two prophylactic vaccines using virus like particles (VLPs) of L1 capside protein of HPV 16 and 18 have been developed. Of these, one also containing VLPs of HPV 6 and 11, has been approved by FDA, EMEA and AIFA for use in 9-26 year-old females. Large scale studies have shown that these vaccines are safe, well tolerated, elicits high levels of neutralizing antibodies, prevent chronic HPV infections due to genotypes present in the vaccine, and associated cervical lesions (and genital wars for the quadrivalent vaccine). To be effective the vaccines should be given prior to sexual debut. In Italy, the vaccination will be offered to 12 year-old girls. This article is the result of a targeted Consensus Conference by a panel of experts, which reviews the cornerstones of HPV infection, its association with cervical cancer, the advances in prophylactic vaccines, and the primary role of the paediatrician for the optimal adoption of this new preventive strategy.

When does mother to child transmission of hepatitis C virus occur?

OBJECTIVE: To investigate when hepatitis C virus (HCV) infection from mother to child occurs, and evaluate possible associated factors. DESIGN: Prospective cohort study. PATIENTS: Fifty four HCV infected children tested within three days of birth and their mothers. MAIN OUTCOME MEASURES: HCV RNA polymerase chain reaction (PCR) results. RESULTS: Seventeen of the children (31%, 95% confidence interval 19% to 46%) were positive in the first 3 days of life and could be assumed to have acquired infection in utero. Testing PCR positive was not associated with sex (53% v 49% boys; p=0.77) or mode of delivery (29% elective caesarean section in both groups; p=0.98). Children with evidence of intrauterine infection were significantly more likely to be of lower birth weight and infected with genotype 1 (58% v 12%, p=0.01). Although a higher proportion of infants born to HCV/HIV co-infected women were PCR positive in the first 3 days of life, this difference did not reach statistical significance; excluding infants born to co-infected women did not affect the results. Thirty seven of the children (68%) were negative in the first 3 days of life, 27 of whom were positive when tested again at 3 months, and nine were first PCR positive after 3 months (one child had no further tests). CONCLUSIONS: These results suggest that at least one third and up to a half of infected children acquired infection in utero. Although postpartum transmission cannot be excluded, these data suggest that it is rare. The role of HCV genotypes in the timing and mechanism of infection should be explored further.

Successful unrelated cord blood transplantation in two children with severe combined immunodeficiency syndrome.

We describe the successful unrelated cord blood transplantation in two patients affected by a Zap-70 deficiency and an Omenn-like syndrome, respectively. The patients were hospitalised for recurrent infections at the age of 13 and 2 months, respectively. An unrelated cord blood unit was found for each. The conditioning regimen was cyclophosphamide, busulfan and antithymocyte globulin. The total number of infused cells was 15.1 x 10(7)/kg and 17 x 10(7)/kg, respectively. Neutrophil engraftment was achieved on days +15 and +23, and platelet count >50 x 10(9)/l was achieved on days +21 and +52, respectively. One patient presented acute Graft-versus-host disease (GVHD) grade I and the other grade III. Chimerism was mixed and full donor. Normal lymphoproliferative response to mitogens and alloantigens was detectable at 6 months for both. No chronic GVHD was observed in either. The patients are alive and well at 53 and 15 months after transplantation. In conclusion, umbilical cord blood represents a valid alternative source of haemopoietic stem cells.

Legionella pneumophila pneumonia in a newborn after water birth: a new mode of transmission.

We report a case of Legionella pneumophila pneumonia in a 7-day old neonate. Because the hospital water, and particularly the pool water for water birthing, was contaminated by L. pneumophila serogroup 1, the newborn was infected following prolonged delivery in contaminated water, perhaps by aspiration. This is the first case of nosocomial Legionella pneumonia in neonate after water birth.

Puberty in perinatal HIV-1 infection: a multicentre longitudinal study of 212 children.

OBJECTIVE: To define age at entry into Tanner stages in children with perinatal HIV-1 infection. DESIGN: Multicentre longitudinal study including 212 perinatally HIV-1-infected children (107 girls and 105 boys) followed-up during puberty (from 8 and 9 years onwards in girls and boys, respectively). Healthy children (843 girls and 821 boys) provided reference percentiles. P2 or B2 stages in girls and P2 or G2 stages in boys defined onset of puberty. METHODS: The cumulative probability [95% confidence limit (CI)] of entry into each stage at different ages was estimated by the Kaplan-Meier product-limit method; differences were evaluated by log rank test. Relationships were tested using the Spearman's rank correlation coefficient. RESULTS: Ages of girls [years (95%CI)] at P2 [12.9 (12.6-13.2)], P3 [13.4 (13.0-13.8)], P4 [14.6 (14.0-15.2)], B2 [12.7 (12.2-13.2)], B3 [13.3 (12.8-14.0)] and B4 [14.6 (14.0-15.2)] stages were > 97th percentile (> or = 21 month delay) of controls. Ages of boys [years (95%CI)] at P2 [12.6 (12.1-13.1)], P3 [13.9 (13.4-14.4)], P4 [14.9 (14.2-15.6)], G2 [12.1 (11.5-12.7)], G3 [13.6 (13.1-14.1)] and G4 [14.9 (14.1-15.7)] stages were at the 75-97th percentiles (< or = 15 month delay). Age at onset of puberty was not related to clinical and immunological condition, antiretroviral treatment, weigh for height and age at onset of severe disease or immune suppression. CONCLUSION: Perinatal HIV-1 infection interferes with sexual maturation. The mechanisms by which this occurs should be elucidated and intervention strategies designed. Intervention could save much psychological distress, since associated linear growth failure can exacerbate adolescents' feelings of being different and unwell.

Proteasomes are a target of the anti-tumour drug vinblastine.

Proteasomes, the proteolytic machinery of the ubiquitin/ATP-dependent pathway, have a relevant role in many processes crucial for cell physiology and cell cycle progression. Proteasome inhibitors are used to block cell cycle progression and to induce apoptosis in certain cell lines. Here we examine whether proteasomal function is affected by the anti-tumour drug vinblastine, whose cytostatic action relies mainly on the disruption of mitotic spindle dynamics. The effects of vinblastine on the peptidase activities of human 20 S and 26 S proteasomes and on the proteolytic activity of 26 S proteasome were assessed in the presence of specific fluorogenic peptides and (125)I-lysozyme-ubiquitin conjugates respectively. The assays of ubiquitin-protein conjugates and of inhibitory kappa B alpha (I kappa B alpha), which are characteristic intracellular proteasome substrates, by Western blotting on lysates from HL60 cells incubated with or without vinblastine, illustrated the effects of vinblastine on proteasomes in vivo. We also evaluated the effects of vinblastine on the signal-induced degradation of I kappa B alpha. Vinblastine at 3--110 microM reversibly inhibited the chymotrypsin-like activity of the 20 S proteasome and the trypsin-like and peptidyl-glutamyl-peptide hydrolysing activities of both proteasomes, but only at 110 microM vinblastine was the chymotrypsin-like activity of the 26 S proteasome inhibited; furthermore, at 25--200 microM the drug inhibited the degradation of ubiquitinated lysozyme. In HL60 cells exposed for 6 h to 0.5--10 microM vinblastine, the drug-dose-related accumulation of polyubiquitinated proteins, as well as that of a high-molecular-mass form of I kappa B alpha, occurred. Moreover, vinblastine impaired the signal-induced degradation of I kappa B alpha. Cell viability throughout the test was approx. 95%. Proteasomes can be considered to be a new and additional vinblastine target.

Nosocomial infections in pediatric cardiac surgery, Italy.

OBJECTIVE: To evaluate the incidence of nosocomial infection (NI) in pediatric patients who received cardiothoracic surgery and to identify possible associated risk factors. DESIGN: Prospective observational study. SETTING: The cardiac surgery and cardiac intensive care units at the Regina Margherita Children's Hospital, Turin, Italy. PATIENTS: All patients who underwent surgery from July 20, 1998, to July 19, 1999, were enrolled, except patients with operative catheterization only. METHODS: Clinical data were collected daily from July 20, 1998, to July 19, 1999. NIs were diagnosed according to US Centers for Disease Control and Prevention criteria. RESULTS: 104 patients were included in the present study, 80 (76.9%) of whom underwent extracorporeal circulation. The NI ratio was 48.1% (50/104); the percentage of patients with NI was 30.8% (32/104): 23.1% developed one infection, 7.7% two or more. The rate of NI was 2.17 per 100 days of hospitalization (50/2,304). The most common pathogen was Pseudomonas aeruginosa. Important risk factors were length of preoperative admission >5 days, total length of admission >10 days, open chest during postoperative phase, and cyanotic heart disease. There was a significant association between sepsis and central venous catheterization for 3 days or more. Rate of sepsis was 19 per 1,000 catheter days (16/852). CONCLUSION: NIs represent a frequent complication for children who undergo heart surgery. Based on our data, we suggest decreasing the preoperative stay as much as possible. The higher NI incidence in patients with an open chest postoperatively suggests that an alternative antibiotic strategy should be considered for these patients.

Human immunodeficiency virus-related cancer in children: incidence and treatment outcome--report of the Italian Register.

PURPOSE: To outline the incidence, presenting features, treatment response, and outcome of human immunodeficiency virus (HIV)-associated malignancies in infancy and childhood, together with the estimated risk of HIV-associated cancer in children born to mothers infected with HIV. PATIENTS AND METHODS: The Italian Register for HIV Infection in Children collected data by specific registration and follow-up forms. By March 1999, 5,060 children were recruited, including 4,889 with perinatal exposure to HIV-1. Overall, 1,331 infected children were enrolled onto the Register and classified according to current Centers for Disease Control criteria; of them, 1,163 were vertically infected (24% of those with perinatal exposure). Of these 1,163, 569 (49%) were considered to have been prospectively followed-up since they had been registered at birth or within the first 3 months of age. RESULTS: Of the 1,331 children observed for a median time of 6.5 years, 35 developed 36 malignancies, four of which occurred in patients with blood-borne risk. For the 1,163 vertically infected children, the cumulative number of years of observation was 7,178 child-years and the cumulative incidence of HIV-associated tumors was 4.18 per 1,000 children/yr (95% confidence interval [CI], 2.92 to 5.98). When only the 569 vertically infected children prospectively followed up since birth were considered, the cumulative number of years of observation was 2,803 child-years. In this group, 10 tumors were observed, with a cumulative incidence of HIV-associated tumors of 3.57 per 1,000 children per year (95% CI, 1.92 to 6.63). CONCLUSION: The risk of cancer was significantly higher but not restricted to symptomatic and/or immune-compromised children. Cancer-directed treatment should be given promptly to these patients, who have a fair chance to survive their tumor in view of potential highly aggressive antiretroviral therapy-associated improvement in survival and quality of life.

Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Italian Register for HIV Infection in Children and the Italian National AIDS Registry.

CONTEXT: Since the introduction of combined antiretroviral therapy, mortality rates in adults with human immunodeficiency virus type 1 (HIV-1) infection have decreased. However, little information is available outside the setting of controlled trials on survival of perinatally HIV-infected children treated with antiretroviral therapy. OBJECTIVE: To assess effect of availability of antiretroviral therapy on decreasing mortality in perinatally HIV-infected children. DESIGN: Population-based, multicenter longitudinal study involving data collected by the Italian Register for HIV Infection in Children. SETTING: A network of 106 pediatric clinical centers. SUBJECTS: A total of 1142 children born between November 1980 and December 1997 with perinatally acquired HIV infection with a median follow-up of 5.9 years. MAIN OUTCOME MEASURE: Time to HIV-related death calculated for birth cohort and calendar period and grouped by distribution of predominant type of antiretroviral therapy administered over time. RESULTS: Survival was longer in the 1996-1997 birth cohort (crude relative hazard [RH] of death, 0.39; 95% confidence interval [CI], 0.15-0.96) and 1996-1998 calendar period (crude RH of death, 0.65; 95% CI, 0.45-0.95) than in birth cohort and calendar period 1980-1995, but not when adjusted for maternal antiretroviral treatment during pregnancy and clinical condition at time of delivery, gestational age, and birth weight (adjusted RH of death, 0.55; 95% CI, 0.20-1.50, for birth cohort; and adjusted RH of death, 0.71, 95% CI, 0.43-1.16, for calendar period). In a multivariate model with 1980-1995 as comparison, the 1996-1997 birth cohort had an RH of 0.57 (95% CI, 0.22-1.47; P=.27) but RH for calendar period 1996-1998 was 0.63 (95% CI, 0.47-0.85; P<. 01). When the effects of birth cohort, calendar period, and type of antiretroviral therapy were evaluated simultaneously in the same model, the RH of death was not significantly different from 1.0 for the 1996-1997 birth cohort (P=.19) and calendar period 1996-1998 (P=. 83) suggesting a causal relationship between decreased risk of death and use of combination therapy. The RH of death in children receiving monotherapy or double or triple combination therapy was 0. 77 (95% CI, 0.55-1.08), 0.70 (95% CI, 0.42-1.17), and 0.29 (95% CI, 0.13-0.67), respectively, vs no antiretroviral therapy. CONCLUSION: Survival of perinatally HIV-infected children improved in 1996-1998 as a result of the introduction of combined antiretroviral therapies. JAMA. 2000;284:190-197