ABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteria/isolation & purification , Brain Abscess/epidemiology , Adolescent , Anti-Bacterial Agents/pharmacology , Bacteria/classification , Bacteria/drug effects , Brain Abscess/drug therapy , Brain Abscess/microbiology , Child , Child, Preschool , Female , Humans , Incidence , Infant , Infant, Newborn , Italy/epidemiology , Male , Prevalence , Retrospective Studies , Risk Factors , Treatment OutcomeABSTRACT
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.
Subject(s)
DNA, Viral/genetics , Polyomavirus/genetics , Skin Diseases/virology , Case-Control Studies , Humans , Skin Diseases/geneticsABSTRACT
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.
Subject(s)
Emigration and Immigration/statistics & numerical data , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Pulmonary/epidemiology , Adolescent , Antitubercular Agents/therapeutic use , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Italy/epidemiology , Male , Retrospective Studies , Tertiary Care Centers , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Tuberculosis/transmission , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/transmission , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/transmissionABSTRACT
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.
Subject(s)
Infant Nutritional Physiological Phenomena/immunology , Lactoglobulins/immunology , Milk Hypersensitivity/prevention & control , Milk , Animals , Birth Weight , Body Height , Cattle , Child , Child, Preschool , Double-Blind Method , Equidae , Female , Humans , Immunoblotting , Immunoglobulin E/blood , Infant , Lactoglobulins/blood , Male , Milk Hypersensitivity/immunology , Milk, Human , Placebos , Prospective Studies , Skin TestsABSTRACT
Transplantation of HLA mismatched hematopoietic stem cells in patients with severe combined immunodeficiency (SCID) can result in a selective engraftment of T cells of donor origin with complete immunologic reconstitution and in vivo tolerance. The latter may occur in the absence of clonal deletion of donor T lymphocytes able to recognize the host HLA antigens. The activity of these host-reactive T cells is suppressed in vivo, since no graft-vs. -host disease is observed in these human chimeras. Here it is shown that the CD4+ host-reactive T cell clones isolated from a SCID patient transplanted with fetal liver stem cells produce unusually high quantities of interleukin 10 (IL-10) and very low amounts of IL-2 after antigen-specific stimulation in vitro. The specific proliferative responses of the host-reactive T cell clones were considerably enhanced in the presence of neutralizing concentrations of an anti-IL-10 monoclonal antibody, suggesting that high levels of endogenous IL-10 suppress the activity of these cells. These in vitro data correlate with observations made in vivo. Semi-quantitative polymerase chain reaction analysis carried out on freshly isolated peripheral blood mononuclear cells (PBMC) of the patient indicated that the levels of IL-10 messenger RNA (mRNA) expression were strongly enhanced, whereas IL-2 mRNA expression was much lower than that in PBMC of healthy donors. In vivo IL-10 mRNA expression was not only high in the T cells, but also in the non-T cell fraction, indicating that host cells also contributed to the high levels of IL-10 in vivo. Patient-derived monocytes were found to be major IL-10 producers. Although no circulating IL-10 could be detected, freshly isolated monocytes of the patient showed a reduced expression of class II HLA antigens. However, their capacity to stimulate T cells of normal donors in primary mixed lymphocyte cultures was within the normal range. Interestingly, similar high in vivo IL-10 mRNA expressions in the T and non-T cell compartment were also observed in three SCID patients transplanted with fetal liver stem cells and in four SCID patients transplanted with T cell-depleted haploidentical bone marrow stem cells. Taken together, these data indicate that high endogenous IL-10 production is a general phenomenon in SCID patients in whom allogenic stem cell transplantation results in immunologic reconstitution and induction of tolerance. Both donor T cells and host accessory cells contribute to these high levels of IL-10, which would suppress the activity of host-reactive T cell in vivo.
Subject(s)
HLA Antigens/immunology , Hematopoietic Stem Cell Transplantation , Immune Tolerance , Interleukin-10/biosynthesis , Severe Combined Immunodeficiency/immunology , Base Sequence , CD4-Positive T-Lymphocytes/immunology , Cell Division , Clone Cells , DNA , HLA-DR Antigens/immunology , Hematopoietic Stem Cells/immunology , Humans , Interleukin-2/biosynthesis , Liver/cytology , Male , Molecular Sequence Data , Monocytes/immunology , Polymerase Chain Reaction , Severe Combined Immunodeficiency/therapyABSTRACT
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 Subject(s)
Catheterization, Central Venous/adverse effects
, Hematologic Diseases/therapy
, Infections/epidemiology
, Neoplasms/therapy
, Upper Extremity Deep Vein Thrombosis/epidemiology
, Catheterization, Central Venous/instrumentation
, Child
, Equipment Design
, Female
, Hematologic Diseases/complications
, Hospitals, Pediatric
, Humans
, Incidence
, Infections/microbiology
, Male
, Neoplasms/complications
, Prospective Studies
, Risk Factors
, Sepsis/epidemiology
ABSTRACT
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.
Subject(s)
HIV Infections/complications , Neoplasms/complications , Acquired Immunodeficiency Syndrome/complications , Adolescent , Child , Child, Preschool , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/transmission , Humans , Incidence , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical , Italy/epidemiology , Lymphoma, AIDS-Related/drug therapy , Lymphoma, AIDS-Related/epidemiology , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/epidemiology , Male , Neoplasms/drug therapy , Neoplasms/epidemiology , Pregnancy , Prospective Studies , Registries , Treatment OutcomeABSTRACT
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.
Subject(s)
Hepatitis C/transmission , Infectious Disease Transmission, Vertical , Breast Feeding , Child, Preschool , Delivery, Obstetric/methods , Female , Fetal Diseases/virology , Genotype , HIV Infections/complications , Hepacivirus/genetics , Hepatitis C/genetics , Humans , Infant , Infant, Low Birth Weight , Infant, Newborn , Male , Polymerase Chain Reaction/methods , Pregnancy , Pregnancy Complications, Infectious/virology , Prospective Studies , RNA, Viral/analysis , Risk Factors , Sex FactorsABSTRACT
OBJECTIVE: To investigate the T-cell receptor (TCR) repertoire usage in infants born to mothers infected with HIV-1 in order to discern possible perturbations in TCR usage as a consequence of HIV-1 infection. DESIGN: Blood samples from five HIV-1-infected and six non-infected children born to HIV-1-seropositive mothers were collected at two to three timepoints during the first and second year of life and the TCR variable gene usage was determined. METHODS: Triple staining flow cytometry analysis using a panel of monoclonal antibodies (MAb) to TCR V alpha and V beta gene products and antibodies to CD4 and CD8 was performed. RESULTS: Frequent large expansions of CD8+ lymphocyte subpopulations bearing distinct V alpha and V beta gene products was seen in HIV-1-infected children (four out of five) but was rarely detected in uninfected children. CONCLUSION: The study demonstrated the frequent occurrence of persistent and clonal expansions of CD8+ T cells bearing distinct V alpha/V beta gene products in some HIV-1 vertically infected infants similar to those observed during primary infection in adults.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , HIV Infections/immunology , HIV-1 , Immunoglobulin Variable Region/immunology , Receptors, Antigen, T-Cell/immunology , CD8-Positive T-Lymphocytes/virology , HIV Infections/transmission , Humans , Immunoglobulin Variable Region/genetics , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical , Receptors, Antigen, T-Cell/genetics , Sequence AnalysisABSTRACT
OBJECTIVES: To estimate the risk of HIV-1 transmission through breast-milk in children born to infected mothers, and to determine the relationship between duration of breast-feeding and risk. DESIGN AND METHODS: The study population included 168 breast-fed and 793 bottle-fed children born to seropositive mothers. All subjects were enrolled and followed-up in the Italian Register for HIV Infection in Children; HIV sero-status was defined in all children. Multivariate analysis was performed using a logistic regression model. Independent variables included biological factors (duration of breast-feeding, gestational age, clinical condition of mother at delivery, mode of delivery, birth-weight and sex). Year of birth and age when HIV infection was diagnosed were also considered in the analysis attempting to control for possible selection biases. RESULTS: Breast-feeding increased the risk of HIV-1 transmission. The estimated adjusted odds ratio for 1 day of breast- versus bottle-feeding was 1.19 (95% confidence interval, 1.10-1.28). The infection odds ratio of breast- versus bottle-feeding increased with the natural logarithm of the duration of practice. CONCLUSIONS: These results are the first to provide an appraisal of the additional risk of HIV-1 transmission associated with a seropositive mother breast-feeding her child. Biological significance of this route of transmission was supported by demonstration of a relationship between duration of breast-feeding and risk of HIV-1 transmission.
Subject(s)
Breast Feeding , HIV Infections/transmission , HIV-1 , Milk, Human/microbiology , Female , Follow-Up Studies , HIV Infections/epidemiology , Humans , Infant , Infant, Newborn , Italy/epidemiology , Male , Risk Factors , Time FactorsABSTRACT
OBJECTIVE: To investigate the timing of onset of each clinical sign in infants and children with HIV-1 perinatal infection. DESIGN AND METHODS: A total of 200 HIV-1-infected children followed-up from birth were studied. Failure and conditional probabilities were estimated by the Kaplan-Meier product-limit method. Cox proportional hazard analysis was used to evaluate independently associated factors. Results of 934 seroreverters were used to calculate reference values of CD4+ cell counts and predictivity of early signs. RESULTS: Median age at the onset of any sign was 5.2 months (range, 0.03-56 months). The probability of remaining asymptomatic was 19% [95% confidence interval (CI), 14-25.1] at 12 months and 6.1% (95% CI, 2.6-11.7) at 5 years. Lymphadenopathy (69.5%), splenomegaly (62.4%) and hepatomegaly (58.4%) were the most common signs in the first year of life. Peculiar to the first year of life (compared with subsequent ages) was the onset of primary HIV-1 hepatitis and diarrhoea (rate ratios, 23.3 and 15.2, respectively). When CD4+ cell counts in the asymptomatic stage (age, 2 months; range, 0.03-5.9 months) were below rather than above the fifth percentile in seroreverters, onset of signs was earlier [3 range, 0.03-19) versus 5 (range, 0.03-56) months]. Children manifesting signs before the 5.2-month breakpoint had a lower survival rate [74% (range, 65.9-82%) at 12 months and 45% (range, 32.9-57%) at 5 years] than children manifesting signs later [98% (range, 92.2-100%) at 12 months and 74% (range, 60.3-87.7%) at 5 years]. Children whose birthweight was < or = 2400 g had an earlier onset (24 months; range, 1-57 months) of severe conditions than children with higher birthweight (71 months; range, 1-71 months). Development of lymphadenopathy or hepatosplenomegaly within 3 months of life were reliable indicators of infection. CONCLUSIONS: This study describes the sequence of onset of signs in perinatal HIV-1 infection. Infection is shown to progress faster than in adults and in a different manner. Low birthweight, early decreased CD4+ cell counts, and early onset of signs are predictive of rapid progression.
Subject(s)
Acquired Immunodeficiency Syndrome/diagnosis , HIV-1/physiology , AIDS-Related Complex/diagnosis , Acquired Immunodeficiency Syndrome/immunology , Acquired Immunodeficiency Syndrome/mortality , Age of Onset , Birth Weight , CD4 Lymphocyte Count , Child, Preschool , Cohort Studies , Diarrhea, Infantile/diagnosis , Disease Progression , Female , Hepatitis, Viral, Human/diagnosis , Hepatomegaly , Humans , Infant , Infant, Newborn , Male , Probability , Splenomegaly , Survival RateABSTRACT
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.
Subject(s)
HIV Infections/physiopathology , HIV-1 , Puberty/physiology , Adolescent , Age Distribution , Anti-HIV Agents/therapeutic use , Child , Female , Fetal Diseases/virology , HIV Infections/drug therapy , HIV Infections/immunology , HIV Infections/virology , Humans , Infant, Newborn , Longitudinal Studies , MaleABSTRACT
One thousand eight hundred eighty-seven children born to human immunodeficiency virus type 1 (HIV-1) seropositive mothers, including 1045 infants prospectively followed up from birth, were studied. Intravenous drug use was the most frequent maternal risk factor, although the percentage of women infected by sexual contact increased from 5.8% in 1985 to 28.5% in 1990. Of the 551 first children followed up from birth and older than 15 months of age, 101 (18.3%) acquired infection and seroconverted to HIV-1. Another 31 (5.6%) asymptomatic seronegative children showed the presence of viral markers, for an apparent mother-to-offspring transmission rate of 23.9%. Overlapping results were seen in 22 second-born children followed up from birth. Of 59 sibships with definite infection status, when the first child was infected, 14 (40%) of 35 second children were infected, whereas when the first child was not infected, only 2 of 24 (8.3%) second children were infected. Discordance in HIV-1 transmission was found in 1 of 18 pairs of twins. Univariate and multivariate analyses of possible risk factors for HIV-1 transmission performed on the entire population of children and in the cohort of those followed up from birth were basically in agreement in indicating that the development of symptoms in the mother before delivery and breast-feeding (indeed adopted in only 22 infants in whom HIV-1 infection was identified at birth) were significantly and independently associated with a higher transmission rate. In addition, girls were more frequently infected than boys.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
HIV Infections/congenital , HIV Infections/transmission , HIV-1 , Maternal-Fetal Exchange , Breast Feeding , Child , Child, Preschool , Diseases in Twins/epidemiology , Female , Follow-Up Studies , HIV Infections/epidemiology , HIV Infections/mortality , HIV Seropositivity , Humans , Incidence , Infant , Infant, Newborn , Italy/epidemiology , Male , Multivariate Analysis , Parity , Pregnancy , Prospective Studies , Risk Factors , Sex Factors , Sexual Partners , Substance Abuse, IntravenousABSTRACT
Erythrocyte adenosine deaminase (ADA) activity was assessed in 33 children born to human immuno-deficiency virus (HIV)-positive mothers. The enzyme values were significantly increased in infected, symptom-free children compared with a control group of HIV-negative subjects (mean +/- SD: 0.34 +/- 0.01 unit/ml red blood cells (RBC) vs. 0.25 +/- 0.04 unit/ml RBC, P less than 0.01) and a further significant increase was found in symptomatic children (0.45 +/- 0.02 unit/ml RBC, P less than 0.01 vs. infected, symptom-free children). ADA values were slightly enhanced also in the group of infants in whom the state of HIV infection was indeterminate (0.29 +/- 0.03 unit/ml RBC, P not significant vs. controls). These data indicate that increased erythrocyte ADA activity may be a useful though indirect marker of HIV infection in children at risk and be of possible prognostic relevance. Since increased values were present also in children without overt infections or hematologic disorders, and ADA activity of erythrocytes obtained from healthy donors did not increase after 1 hour incubation with patients' serum, HIV could induce large amounts of cellular enzyme infecting directly erythroid precursor cells.
Subject(s)
Adenosine Deaminase/analysis , Erythrocytes/enzymology , HIV Infections/congenital , Nucleoside Deaminases/analysis , Analysis of Variance , Child, Preschool , HIV Infections/enzymology , Humans , Infant , PrognosisABSTRACT
BACKGROUND: To compare the Centers for Disease Control and Prevention (CDC) paediatric classification system with the long-term course of perinatal human immunodeficiency virus type 1 (HIV-1) infection. METHODS: Prospective study on 366 perinatally infected children followed-up from birth and checked at least every 2 months. Survival, smoothed hazard, adjusted hazard ratio of death, and transition probabilities in clinical and immunological categories were outcome measures. RESULTS: Survival was 49% (95% CI : 40-58%) at 8 years. The risk of death was high before the age of 2, relatively low between ages 2 and 7, and contained thereafter. Children did not advance through the categories sequentially. Survival at 8 years was 61.7% (95% CI : 49.8-73.6%) in those children who had passed through clinical category A; the hazard ratio of death was 2.5 (95% CI : 1.7-3.8) for 175 (47.9%) children who skipped this category. Transition probability in clinical category B was 39.9% (95% CI : 32.3-45.6%) after one year, but 59.1% (95% CI : 51.4-66.8%) after 5 years. Before 2 years of age, the probability of entry into category C (40%; 95% CI : 35-45%) was higher than that of entry into immunological category 3 (28%; 95% CI : 22-34%). Conclusions The classification system stands comparison with the clinical reality, but the CD4-positive cell thresholds in infancy should be adjusted and category B indicator diseases better distributed to improve their predictive value.
Subject(s)
HIV Infections/classification , HIV Infections/mortality , Infectious Disease Transmission, Vertical , CD4 Lymphocyte Count , Child , Child, Preschool , Disease Progression , Female , HIV Infections/transmission , HIV-1 , Humans , Infant , Infant, Newborn , Male , Predictive Value of Tests , Prognosis , Prospective Studies , Severity of Illness Index , Survival AnalysisABSTRACT
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.
Subject(s)
Fetal Blood , Severe Combined Immunodeficiency/therapy , Stem Cell Transplantation/methods , Antilymphocyte Serum/therapeutic use , Busulfan/therapeutic use , Cyclosporine/therapeutic use , Gastroenteritis/complications , Gastroenteritis/microbiology , Graft vs Host Disease/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Infant , Infant, Newborn , Salmonella Infections/complications , Severe Combined Immunodeficiency/etiology , Severe Combined Immunodeficiency/immunology , T-Lymphocytes/immunology , Transplantation Chimera , Transplantation Conditioning/methods , Transplantation, Homologous , Treatment OutcomeABSTRACT
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.
Subject(s)
Cardiac Surgical Procedures , Cross Infection/epidemiology , Adolescent , Adult , Catheterization, Central Venous/adverse effects , Child , Child, Preschool , Extracorporeal Circulation/adverse effects , Female , Humans , Infant , Infant, Newborn , Italy/epidemiology , Length of Stay , Male , Postoperative Complications , Pseudomonas Infections/epidemiology , Risk FactorsABSTRACT
Airway resistance was measured by the interrupter technique in 54 children [aged 63.8 months (range: 9.1-131.6 months)], with perinatal human immunodeficiency virus-type 1 (HIV-1) infection and in a control group of 315 gender, height, and race-matched healthy children. In addition, 14 HIV-infected children, aged 75-131 months, had spirometry performed. Resistance was significantly higher in infected children than in controls (0.84 +/- 0.3 vs 0.64 +/- 0.08 kPa x l(-1) x s; t = 9.991; P < 0.0001). Resistance decreased with age in controls (r = -0.95; P < 0.001), but not in infected children (r= -0.22; P = 0.105). Resistance did not correlate with mothers' intravenous drug addiction, perinatal data, T-cell subset numbers, treatment, clinical course, or presence of respiratory complications. Resistance was higher (t = 3.103; P < 0.003) in p24 antigen-positive than in negative children. Thirty-nine children underwent a second evaluation 12.3 months (range 11.1-14 months) after the first. Resistance was higher (t = 3.960; P < 0.0001) at the second evaluation compared to the first. Eight of 14 children had abnormal spirometric measurements. We conclude that perinatal HIV-1 infection is associated with increased airway resistance and often abnormal spirometry. The degree of abnormalities in resistance depends on the duration of the infection rather than on HIV-1-related respiratory complications.
Subject(s)
Acquired Immunodeficiency Syndrome/congenital , Acquired Immunodeficiency Syndrome/physiopathology , Airway Resistance , HIV-1 , Acquired Immunodeficiency Syndrome/immunology , Acquired Immunodeficiency Syndrome/transmission , Child , Child, Preschool , Female , Humans , Infant , Infectious Disease Transmission, Vertical , Male , Respiratory Function Tests , Spirometry , Statistics, NonparametricABSTRACT
BACKGROUND: This study has been conducted on a series of HIV-1 infected children, with the aim of illustrating the features of encephalopathy onset, its evolution and its influence on life expectancy. The most useful exams for diagnosis are also outlined. METHODS: The perspective study lasted from January 1989 to June 1997. Forty six symptomatic patients, out of 142 seropositive children, were followed up in the Department of Paediatric and Adolescence Sciences of the University of Turin. The patients, now between 1 yr 2 mth and 13 yr 9 mth old, were born from HIV-1 seropositive mothers; seroreverters have been excluded. Scheduled neuropsychiatric consultations were used, consisting of a neurologic exam and an interview with parents, cognitive evaluations, EEGs, Evoked Potentials and CT scans. The results have been evaluated with log-rank test for the analysis of the survival curves. RESULTS: We found a significantly higher mortality rate in encephalopathic versus non encephalopathic patients; encephalopathic patients, in whom neurologic signs began in the first year of life, have a worse prognosis than the other patients, in whom encephalopathy appeared later. We did not find a statistical correlation between clinical course and immunological deficit. The clinical features of encephalopathy are mainly characterized by pyramidal signs and cognitive deterioration. Clinical sign evolution is linked to the age of encephalopathy onset: plateau pattern encephalopathy, characterized by an early onset, severe motor signs and cognitive delay from the very beginning, shows a greater severity and a shorter survival than progressive encephalopathy, characterized by a slowly progressive evolution of pyramidal signs, to which a cognitive deterioration may be added. CONCLUSIONS: Neuropsychological exams can be helpful in the diagnosis and follow-up of encephalopathy.
Subject(s)
AIDS Dementia Complex/physiopathology , AIDS Dementia Complex/mortality , Child , Child, Preschool , Disease Progression , Female , Humans , Infant , Infant, Newborn , Male , Prognosis , Prospective StudiesABSTRACT
Evoked potentials (EP) help guide the diagnosis of central nervous system involvement in demyelinating pathologies regarding both children and adults, and in human immunodeficiency virus-1 (HIV-1) correlated pathologies only in regard to adult patients. EP have been shown to be useful in highlighting early signs of the disease. We therefore studied EP in HIV-1 infected children with the aim of verifying the association of results with disease progression, clinical signs and electroencephalogram, and individualizing the most reliable test. Thirty-six patients (20 male and 16 female subjects, age range: 10 months to 12 years) belonging to a group of 45 symptomatic subjects seen at the Pediatric Department were included into the study from November 1991 to December 1994. Ten presented with neurological signs as of disease onset, eight others developed encephalopathy during the follow-up. One hundred seventeen EP, i.e., 27 pattern visual, 64 flash visual and 26 brain stem auditory EP, were recorded. Univariate statistical analysis using the Wilcoxon-Mann-Whitney U test and Student's t test was done. As a whole, we found 22.5% of abnormal EP in subjects without neurological signs and 28.3% in subjects with neurological signs. Results that were obtained suggested a close relationship between both the pattern of visual and brain stem auditory EP exams and disease progression.