Emilia Massironi

Perinatal transmission and manifestation of hepatitis C virus infection in a high risk population.

We studied the perinatal transmission of hepatitis C virus (HCV) in 70 high risk mother/infant pairs. Seventy-six percent of the mothers (53 of 70) were coinfected with human immunodeficiency virus (HIV) and 79% (55 of 70) had a history of drug addiction. During the follow-up HCV RNA was detected in 14 of 70 (20%) infants: 12% (2 of 17) in infants born to HIV-negative mothers; and 23% (12 of 53) in infants to HIV-positive mothers. The rate of vertical transmission was significantly higher in vaginally delivered infants than in those delivered by cesarean section (32% vs. 6%; P < 0.05). All 56 uninfected infants lost passively acquired anti-HCV by age 9 \pm 4 months and only 2 of 56 infants (4%) had evidence of HIV infection. Four of 14 HCV RNA-positive infants (29%) had evidence of HTV coinfection. We observed 3 clinical patterns of HCV infection: a transient viremia in 2 infants; an acute pattern in 2 infants; and a chronic pattern in 10 infants. All 4 HIV-coinfected infants had chronic HCV infection. All infants with a chronic pattern, had increased alanine aminotransferase values for more than 6 months and 5 had a liver biopsy that showed signs of chronic persistent hepatitis. HCV perinatal transmission was more frequent in infants born to HIV-coinfected mothers than in infants born to HIV-noninfected women, particularly when delivered vaginally.

HIV-1 transmission through breast-milk: appraisal of risk according to duration of feeding.

ObjectivesTo 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 methodsThe 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 serostatus 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. ResultsBreast-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. ConclusionsThese 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.

Impaired response to hepatitis B vaccine in HIV infected children

Eighteen human immunodeficiency virus (HIV) vertically infected children (HIV group) and 33 seroreverted children (SR group), who had completed hepatitis B vaccination (Engerix B, 20 micrograms dose) were studied. Four out of 18 (22%) HIV children failed to develop protective antibody levels (anti-HBs titres less than 10 mIU ml-1) compared with 1 out of 33 (3%) SR children (p less than 0.05). Magnitude of response among HIV children was significantly lower than among SR children. In HIV children the probability that anti-HBs titres persist above the protective levels was significantly lower than in the SR group at any time during the 24 month follow-up. These results show that HIV children have a suboptimal response to hepatitis B immunization and the protection is less durable. Further studies are needed to determine the optimal protocol for hepatitis B immunization in HIV children.

Differential Development of Type 1 and Type 2 Cytokines and β-Chemokines in the Ontogeny of Healthy Newborns

Interleukin (IL)-2, interferon gamma (IFN-γ; type 1 cytokines), IL-4, and IL-10 (type 2 cytokines), and β-chemokines (MIP-1α and RANTES) production by cord blood lymphocytes (CBL) and peripheral blood lymphocytes (PBL) of newborns was analyzed in a cross-sectional study to examine the maturation of these components of the immune response. Immunophenotyping was performed on the same specimens. Results showed that the CD4/CD8 ratio remains stable, the percentage of natural killer cells decreases, and the number and percentage of B cells increase after birth. Analysis of cytokine production suggested that the production of all cytokines increases gradually and steadily after birth, and that IFN-γ and IL-10 production is reduced at birth whereas IL-2 and IL-4 production is not. Finally, mitogen-stimulated β-chemokine production was present at birth and increased slightly but significantly with age. These data indicate that a differential functional maturation of immune response after birth favoring a more precocious development of IL-2 (a type 1 cytokine) is present and should help to analyze the ontogeny of the immune system.

Occurrence of infections in children infected with human immunodeficiency virus

To evaluate the occurrence of infections in asymptomatic and symptomatic human immunodeficiency virus (HIV)-infected children we performed a prospective comparative cohort study. Twenty-seven HIV-infected children were individually matched with paired immunocompetent controls and followed up for a total of 543 months (mean per child, 19.4 +/- 11 months). Collected data were evaluated considering HIV-infected children both as a whole and as P1 and P2 patients according to the Centers for Disease Control classification. Twenty-seven HIV-infected children had 185 infectious episodes vs. 27 matched controls who experienced 118 infections. P1 children had a number of infections similar to those of normal controls (99 vs. 86) whereas P2 children had a significantly higher number of infections than did controls (86 vs. 32). Pneumonia and oral candidiasis occurred significantly more frequently in symptomatic HIV-infected children than in normal controls. Severe infections occurred almost exclusively in HIV-infected symptomatic children.

Long-Term Resistance to HIV Infection in Vertical HIV Infection: Cytokine Production, HIV Isolation, and HIV Phenotype Define Long-Term Resistant Hosts

We analyzed immunologic (CD4 and CD8 slopes; interferon-gamma, interleukin-2, interleukin-10, and chemokines production; concentration of IgE; beta 2-microglobulin) and virologic (p24; HIV isolability and phenotype; plasma viremia) parameters in HIV vertically infected children > or = 8 years of age without disease progression or mild symptoms and an absolute CD4+ count > or = 500/microliter with CD4+ percentage > or = 25%. The results were compared to those of two control groups: (1) slow progressors, children > or = 8 years of age with moderate symptomatology and/or moderate CD4 depletion, and (2) progressors, children > or = 8 years of age with severe clinical disease and/or severe CD4 depletion. Pediatric long-term resistant hosts were characterized by higher production of interleukin-2 and interferon-gamma and lower production of interleukin-10, normal concentration of IgE, HIV isolates with a non-syncytium-inducing phenotype, and lower plasma viremia. This condition was not associated with the concentration of beta 2-microglobulin, p24, and chemokines, or with HIV isolability. The IL-10/IL-2 ratio best correlated with both CD4 counts and disease progression. Thus, vertically infected children showing resistance to disease progression are immunologically and virologically distinct from those in whom progressive HIV infection is observed.

T-cell subsets and serum immunoglobulin levels in infants born to HIV-seropositive mothers: A longitudinal evaluation

T-lymphocyte subsets and serum immunoglobulins were assayed in 27 neonates and 12 infants younger than 6 months, all born to HIV-seropositive mothers. No differences in T-lymphocyte subsets between the 27 seropositive and 34 seronegative infants were found at birth. Twelve seroreverted and 14 infected children were followed. CD4+ cell counts were significantly lower in the latter at 3 and 24 months of age. Serum immunoglobulin levels and CD8+ percentages became higher in the infected group, starting from the sixth month, while CD4+ percentages and CD4+/CD8+ ratios became lower, starting from the twelfth month.

C-reactive protein in acute otitis media.

This study was designed to explore whether C-reactive protein (CRP) in serum is helpful in assessing the etiologic diagnosis of acute otitis media (AOM) in children. CRP was measured serially by a radial immunodiffusion method in sera from 67 children with AOM and in 67 matched controls, affected by noninfectious neurologic disorders. In the study group 43 (64%) children had a confirmed bacterial AOM and 24 (36%) showed no bacterial growth from middle ear fluid. The upper limit of CRP in controls was 15 mg/liter. Concentrations of CRP in patients with bacterial AOM ranged from <6 to 150 mg/liter; in 71% of the cases the value was > 15 mg/liter. In the patients with sterile middle ear fluid CRP ranged from <6 to 110 mg/liter; in 67% of the cases the level was >15 mg/liter. CRP >15 mg/liter showed sensitivity of 72%, specificity of 33%, predictive value of a positive test of 66% and predictive value of a negative test of 40%, in detecting bacterial AOM. Measurement of CRP should not be used in the decision regarding antimicrobial therapy for AOM in children.

Early diagnosis of HIV infection in infants.

Eighteen infants born to anti-HIV-positive mothers were tested bimonthly for immunoglobulin M (IgM) anti-HIV by Western blot and HIV p24 antigen (Ag) by enzyme-linked immunosorbent assay (ELISA) in order to determine the role of these markers in the early diagnosis of HIV infection. Twelve healthy infants were also studied as a control group. In 11 out of 18 children (61.1%) an IgM response was demonstrable, in 13 out of 18 (72.2%) IgM anti-HIV and/or p24 antigen (Ag) were detected. Two patterns of IgM response were identified: a precocious IgM positivity (group of five children positive at birth) and a later appearance of IgM, always within the third month (six cases). Early p24 antigenemia occurred in one infant. Three out of four children who developed antigenemia after birth were symptomatic within the sixth month. No clinical or immunological abnormalities were found among the three children who were persistently negative for both IgM anti-HIV and p24 Ag. Serial IgM anti-HIV and p24 Ag testing may be helpful in the early identification of HIV-infected patients.

Mother to child transmission of hepatitis C virus detected by nested polymerase chain reaction

Serum samples from eight pregnant women and their offspring were studied by nested polymerase chain reaction (PCR) for detection of hepatitis C virus (HCV) RNA to evaluate mother-to-child transmission of this virus. The mothers were all infected with human immunodeficiency virus (HIV); none showed symptoms of HCV infection. Anti-HCV antibodies were tested for by recombinant immunoblot assay. HCV viral sequences were found in five of the mothers and four of eight children, three of them at birth. Viremia was persistent in one infant who had chronic transaminase elevation and persistently remained anti-HCV-positive. The other three babies had intermittent viremia; all were asymptomatic and lost anti-HCV antibodies during follow-up. This loss of antibodies was also observed in PCR-negative infants. Thus, these results demonstrate transmission of HCV from mother to child by women coinfected with HCV and HIV. They indicate the usefulness of PCR for direct and early detection of HCV viremia in neonates.