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Biomedical subjects

Elena Chiappini

Publications and source records attributed to Elena Chiappini.

18 recordsLinked to original sources

Cancer rates after year 2000 significantly decrease in children with perinatal HIV infection: a study by the Italian Register for HIV Infection in Children.

PURPOSE: To evaluate the impact of highly active antiretroviral therapy (HAART) on cancer incidence in HIV-infected children throughout a 20-year period. PATIENTS AND METHODS: An observational population study was conducted on 1,190 perinatally HIV-infected children enrolled onto the Italian Register for HIV Infection in Children from 1985 to 2004 and never lost to follow-up (total observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods and compared using Poisson regression adjusted for age. The proportion of HAART-treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in 2004. In the same time frame, the proportion of children receiving HAART for at least 2 years increased from 3.1% to 77.0%. RESULTS: Overall, 35 cancers occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to 6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to 1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no significant difference comparing the periods from 1985 to 1995 and 1996 to 1999 (P = .081). By contrast, cancer rates were significantly lower in the period from 2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by separately analyzing data from children observed from birth (P = .418 for 1985 to 1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004). CONCLUSION: Dramatically reduced cancer rates were observed only in the late HAART period in parallel to the increasing proportion of children receiving HAART therapy.

Antiretroviral Therapy, Highly Active↗

Virologic, immunologic, and clinical benefits from early combined antiretroviral therapy in infants with perinatal HIV-1 infection.

OBJECTIVE: To investigate the impact of early versus deferred combined antiretroviral treatment (ART) in asymptomatic or moderately symptomatic [Centers for Disease Control and Prevention (CDC) category N, A or B] infants with perinatal HIV-1 infection. METHODS: A multi-centre nationwide case-control study was conducted. Data from 30 infants treated with combined ART with three or more drugs before 6 months of age were compared with data from 103 infants starting ART with three or more drugs after 6 months of age. The median follow-up time was 4.1 years (range, 1.0-6.5 years). RESULTS: No difference was evident in the first available viral load and CD4 T-lymphocyte percentage between the two groups of children. Early-treated infants showed significantly lower viral loads than infants receiving deferred treatment at all the follow-up periods. A higher proportion of early-treated infants than infants receiving deferred treatment (73.3% versus 30.1%; P < 0.0001) reached an undetectable viral load. Higher CD4 T-lymphocyte percentages were found in early-treated infants at 13-24 (P < 0.0001), 25-36 (P < 0.0001), and 37-48 (P = 0.003) months of age. No early-treated infant versus 20 of 103 (19.4%) infants receiving deferred ART (P = 0.02) showed a CD4 T-lymphocyte percentage of less than 15% at one time point during follow-up. No CDC category A, B or C clinical event occurred in early-treated infants over the follow-up period while 44 of 103 (42.7%) infants receiving deferred treatment presented a decline in the CDC category. Kaplan-Meier analyses revealed significant differences in CDC category A (P = 0.0002), B (P = 0.0003), and C (P = 0.0018) event-free survivals. CONCLUSION: The data suggest virologic, immunologic, and clinical benefits from early administration of ART.

Age Factors↗

Lower mother-to-child HIV-1 transmission in boys is independent of type of delivery and antiretroviral prophylaxis: the Italian Register for HIV Infection in Children.

The relationship between infant's gender and rate of HIV-1 mother-to-child transmission (MTCT) was evaluated in a prospective cohort of 4151 children (2166 boys and 1985 girls) born to HIV-1-infected mothers enrolled in the Italian Register for HIV Infection in Children. Logistic regression models were performed to estimate crude odds ratios (ORs) and adjusted odds ratios (AORs) and 95% CIs for factors potentially influencing MTCT separately for the period 1985-1995 and the period 1996-2001. To evaluate rates of MTCT by gender in specific subgroups, separate logistic regression models by mode of delivery and antiretroviral prophylaxis were performed. Among children born in 1985-1995, 15.5% boys (95% CI: 13.6-17.7) and 17.9% girls (95% CI: 15.7-20.3) were infected (P = 0.1181). After 1995, a lower proportion of boys (3.1% [95% CI: 2.0-4.4]; AOR: 0.43 [95% CI: 0.26-0.71], P = 0.0008) than girls (AOR: 6.3%, 95% CI: 4.8-8.1) was infected. Lower AORs for boys persisted independently of elective cesarean delivery (AOR: 0.31, 95% CI: 0.14-0.71); other than elective cesarean (AOR: 0.38, 95% CI: 0.19-0.78) and antiretroviral prophylaxis (zidovudine monotherapy (AOR: 0.11, 95% CI: 0.03-0.38); none (AOR: 0.43, 95% CI: 0.21-0.90). No difference was observed when combined therapy in the mother was administered (AOR: 1.14, 95% CI: 0.30-4.32), but results were likely to be biased by the very low rate of infected children in this group. A lower proportion of HIV-1-infected boys in children born after 1995 was found. Factor(s) intrinsic to gender (rather than type of delivery or maternal antiretroviral prophylaxis) may be involved, because the risk of infection in boys was lower independent of interventions. A possible explanation is that, among infected fetuses, more girls survive up to the end of pregnancy and may take advantage of the benefits of preventive strategies.

Anti-HIV Agents↗

Viraemia is a common finding in immunocompetent children with rotavirus infection.

Rotavirus infection is usually localized to the intestine but involvement of extra-intestinal sites, including the respiratory tract, liver, kidney, lymph nodes, and central nervous system, has been reported. The extra-intestinal spread of the virus may occur through blood since viraemia has been documented occasionally in animals and humans. Nevertheless, the questions of how common viraemia is in immunocompetent children and whether it is associated with extra-intestinal manifestations remain unsolved. Serum samples from 54 immunocompetent children hospitalized for acute diarrhea were evaluated prospectively for the presence of rotavirus RNA by nested reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate this issue. Rotavirus antigens were detected in the stools of 14 children. A bacterial aetiology was documented in 14 cases, and in the remaining cases the aetiology remained unknown. Rotavirus RNA was detected in the blood of 9/14 (64.3%) rotavirus infected children but in no child with diarrhea of other origin. Positive RT-PCR was associated with high fever and/or evidence of extra-intestinal involvement. All positive samples were collected within 3 days of illness onset, suggesting that viraemia was detectable for only a few days. Children in whom rotavirus was detected only in stool samples had high fever but no other extra-intestinal feature. These data suggest that viraemia is common in children infected with rotavirus, which may be associated with extra-intestinal involvement.

Antigens, Viral↗

Henoch Schonlein purpura in childhood: epidemiological and clinical analysis of 150 cases over a 5-year period and review of literature.

OBJECTIVE: To examine epidemiological, clinical, and outcome in Italian children affected with Henoch Schönlein purpura (HSP). METHODS: Retrospective study of children discharged with a diagnosis of HSP from the Meyer Children's Hospital, between 1998 and 2002. Epidemiological, clinical, laboratory data, treatment, and outcome were collected by reviewing medical charts. One year after data collection, the children's parents were interviewed by telephone about the outcome. RESULTS: 150 children entered the study: M:F=1.8:1; mean age 6.1+/-2.7 years. At onset, purpura was present in all cases, arthritis/arthralgias in 74%, abdominal involvement in 51%, scrotal edema in 13%, renal involvement in 54%, severe nephropathy in 7%, acute renal insufficiency in 2%, and intussusception in 0.6%. Purpura was the presenting symptom in 74%, arthritis in 15%, and abdominal pain in 12%. The most frequent laboratory abnormalities were high-erythrocyte sedimentation rate (ESR) (57%), hyper-IgA (37%), and proteinuria (42%). All patients recovered within 2 months. Recurrences, verified in 35%, were correlated with high ESR values and corticosteroid (CS) treatment, independently from other variables. After a mean 2.5-years follow-up, 2 patients had hematuria with normal renal function. CONCLUSION: Epidemiological and clinical findings in our cohort are similar to those in the literature, even though the mean disease duration was shorter than previously reported. Relapses occurred significantly more frequently in children treated with CS. This finding supports the recommendation to limit the use of steroids to a carefully selected group of HSP children. The prognosis was excellent; although severe nephropathy was found in a small percentage of the children, at follow-up all had normal renal function. Thus, our study confirms the benignity of HSP in Italian children, especially regarding renal outcome.

Adolescent↗

Persistently high IgA serum levels are a marker of immunological or virological failure of combined antiretroviral therapy in children with perinatal HIV-1 infection.

Non-expensive and low-complexity surrogate markers for monitoring the response to combined antiretroviral therapy (combined-ART) are needed in poor-resource settings where routine assessment of CD4+ T-lymphocyte count and viral load can not be afforded. We longitudinally evaluated Ig serum levels in 234 HIV-1 infected children receiving combined-ART with > or = 3 drugs. Since Ig levels physiologically vary with age, differences at different age periods were evaluated as differences in z-scores calculated using the mean and standard deviation of the normal population for each age period. Data from 17 (7.3%) children with immunological failure and from 54 (23.1%) children with virological failure of combined-ART were compared with data from not-failed children. At baseline children with immunological failure showed higher IgM z-scores (P = 0.042) than children without. After 3-12 months of therapy immunologically failed children displayed higher viral loads (P < 0.0001) and IgA (P = 0.043) z-scores than not-failed children. Similarly, at the same follow-up time, children with virological failure showed lower CD4(+) T-lymphocyte percentages (P = 0.005) and higher IgA z-scores (P < 0.0001) than not-failed children. No difference in IgG or IgM z-scores was evidenced between failed and not-failed children after 3-12 months of therapy. In conclusion, IgA serum level is a cheap and low-complexity marker of immunological or virological failure of combined-ART which might be adopted in poor-resource settings.

Adolescent↗

Interleukin-7 and immunologic failure despite treatment with highly active antiretroviral therapy in children perinatally infected with HIV-1.

Baseline interleukin-7 (IL-7) level has been proposed as a predictor of immunologic response to antiviral therapy, and the use of exogenous IL-7 has been suggested in the treatment of HIV-infected patients. Therefore, we investigated the relationships between IL-7 serum levels and immunologic outcome of highly active antiretroviral therapy (HAART) in 24 children perinatally infected with HIV-1. IL-7 serum levels were evaluated by enzyme-linked immunosorbent assay before switching antiretroviral treatment from double therapy to HAART and then again after 12 weeks of HAART. Differences were analyzed between children with immunologic failure and those without. At baseline, IL-7 levels were significantly higher in HIV-1-infected children than in 24 healthy age-matched uninfected children (16.6 +/- 8.7 vs. 9.5 +/- 2.4 pg/mL, respectively; P < 0.001). IL-7 levels inversely correlated with CD4 T-lymphocyte percentage both at baseline (r = -0.71, P < 0.001) and after 12 weeks of HAART (r = -0.49, P = 0.01). We observed no correlation between IL-7 levels and viral load (r = 0.29, P = 0.17 at baseline; r = 0.30, P = 0.15 after 12 weeks). Baseline IL-7 levels were similar in HIV-1-infected children with or without subsequent immunologic failure (15.1 +/- 8.8 vs. 17.5 +/- 8.7 pg/mL, respectively; P = 0.75). After 12 weeks of HAART, IL-7 levels were 21.6 +/- 13.5 pg/mL in children with immunologic failure (P = 0.08 when compared with baseline levels) and 8.2 +/- 3.8 pg/mL in children without immunologic failure (P = 0.002 when compared with baseline levels). IL-7 levels were significantly higher (P = 0.003) in children with immunologic failure than in those without. Findings indicate that baseline IL-7 serum levels do not predict immunologic outcome of HAART and that immunologic failure occurs even in the presence of high IL-7 serum levels, thus suggesting no benefit from therapy with exogenous IL-7.

Adolescent↗

Immunological recovery despite virological failure is independent of human immunodeficiency virus-type 1 resistant mutants in children receiving highly active antiretroviral therapy.

Relationships between human immunodeficiency virus-type-1 (HIV-1) drug-resistant mutants and immunological recovery were investigated after 12-week antiretroviral therapy in 43 children infected perinatally with virological failure. Twenty-two children received highly active antiretroviral therapy (HAART) and 21 received double therapy with reverse transcriptase inhibitors. At baseline, no difference in reverse transcriptase or protease inhibitors resistant mutants was present among the groups. After 12 weeks, the two groups were similar regarding proportion of children with reverse transcriptase resistant mutants. Sixteen (73%) HAART-treated children, but no child receiving double therapy had HIV-1 with primary resistance mutations to protease inhibitors. Secondary protease mutations were found in all HAART-treated and in 17/21 (81%) children receiving double therapy. The mutation numbers in reverse transcriptase or protease genes were significantly higher after HAART than after double therapy. Nevertheless, 12 (55%) of HAART-treated children (but no child receiving double therapy) showed immunological recovery. The frequency and number of mutations were similar in HAART-treated children with or without immunological recovery both at baseline and after 12 weeks. The findings suggest, immunological recovery notwithstanding, virological failure is independent of drug-resistant mutations and consequent possible changes in viral fitness.

Adolescent↗

Reduced frequency of wheezing respiratory illness in infants with perinatal human immunodeficiency virus-type 1 infection: a model for immunologic and inflammatory mechanisms of airway obstruction?

A multivariate analysis using a logistic regression model evaluated odds ratio (OR) and 95% confidence limits (95% CL) of pediatrician-diagnosed wheezing respiratory illness in 75 infants with perinatal human immunodeficiency virus-type 1 (HIV-1) infection, 205 uninfected infants of HIV-1 infected mothers, and 1780 infants of HIV-1 uninfected mothers. Infants were prospectively followed-up for the first 2 years of life. Covariates were risk factors for wheezing respiratory illness (preterm delivery, low birth weight, maternal smoking, formula feeding, and neonatal respiratory disorders). Maternal use of illicit drugs in pregnancy, antiretroviral treatment in pregnancy, maternal HIV-1-related clinical condition at the time of delivery were also included in the models when infants of HIV-1 infected mothers were taken into account. Although the frequency of risk factors for wheezing respiratory illness was higher in infants of HIV-1 infected than in those of uninfected mothers, HIV-1 infection emerged as a protective factor [OR: 0.001 (95% CL: 0.0001-0.01); p < 0.001]. The frequency of risk factors was similarly high among infants of infected mothers, but OR was lower in HIV-1 infected than in uninfected infants of infected mothers (0.005; 95% CL: 0.0004-0.06; p < 0.001). Finally, OR was higher in uninfected infants of HIV-1 infected mothers (who evidenced a higher frequency of risk factors) than in infants of HIV-1 uninfected mothers (9.97; 95% CL: 4.87-20.40; p < 0.001). Understanding the reason why HIV-1 protects against wheezing respiratory illness could shed light on the immunologic and inflammatory mechanisms of airway obstruction.

Adult↗

Results of a 5-year prospective surveillance study of antibiotic resistance among Salmonella enterica isolates and ceftriaxone therapy among children hospitalized for acute diarrhea.

BACKGROUND: The spread of resistant Salmonella strains continues to increase worldwide. It is necessary to establish epidemiologic information to determine an appropriate empiric antibiotic regimen (when indicated) in infants and children with suspected Salmonella infections for whom the results of susceptibility tests are not yet available. OBJECTIVES: The aim of the present study was to investigate resistance rates and their modifications among Salmonella enterica strains isolated from Italian children hospitalized for acute diarrhea over 5 years. In addition, when antibiotic treatment was indicated, we assessed the in vivo success of parenteral ceftriaxone therapy. METHODS: This study included children admitted consecutively for acute diarrhea to the Division of Pediatrics and Infectious Diseases, Department of Pediatrics, University of Florence, Italy, from January 1, 1997, to December 31, 2001. S enterica strains were isolated from stool cultures, biochemically identified, and serotyped. These isolates were tested by disk-diffusion assay, using the Kirby-Bauer method, for susceptibilities to ampicillin, ceftriaxone, ciprofloxacin, chloramphenicol, neomycin, tetracycline, and trimethoprim/sulfamethoxazole. The limits used for definition of resistance were those established by the guidelines of the National Committee for Clinical Laboratory Standards. RESULTS: A total of 2003 children (1051 boys, 952 girls; median age, 10.3 years; age range, 1 month-16.8 years) with acute diarrhea were admitted to the study. S enterica strains were isolated using stool cultures from 218 (10.9%) children (108 boys, 110 girls; median age, 3.3 years; age range, 2 months-15.8 years). A total of 148 (67.9%) isolates were resistant to at least 1 antibiotic and 57 (26.1%) were multiresistant. The highest rates of resistance were those to tetracycline (132/218 [60.6%]), ampicillin (102/218 [46.8%]), and chloramphenicol (47/218 [21.6%]). The lowest rate of resistance was to ceftriaxone (4/218 [1.8%]). Overall, the rate of resistance to ciprofloxacin (19/218 [8.7%]) was significantly higher than that for ceftriaxone (P = 0.003). Salmonella typhimurium (119/218 [54.6%]) and Salmonella enteritidis (62/218 [28.4%]) were the most frequently identified serotypes. Ceftriaxone was effective in vivo in all 56 children who required antibiotic therapy. CONCLUSIONS: There was a high prevalence of resistant S enterica strains. Ceftriaxone was used effectively in the treatment of S enterica infection in the population studied.

Acute Disease↗

Varicella-zoster virus acquired at 4 months of age reactivates at 24 months and causes encephalitis.

Varicella-zoster virus (VZV) reactivation in the brain caused encephalitis in a 2-year-old immunocompetent child who had chickenpox 20 months before. Radiologic findings were consistent with large to medium-vessel-vasculitis. VZV-DNA was detected in cerebrospinal fluid. Early acquisition of VZV may predispose to major neurologic complications that can occur years after the primary infection.

Age Factors↗