Maria Elisabetta Rossi

Ten-year follow-up study of neonatal hepatitis B immunization : are booster injections indicated?

One hundred and fourteen children, born to HBsAg-positive mothers received in the first year of life passive active prophylaxis for hepatitis B virus (HBV). They have been followed up to 10 years. A booster dose given in a cohort at the 5th year does not seem to increase protection against HBV. No difference in immunological memory was present at the 10th year between the group of children who had received the booster dose at 5 years of age and the group who did not.

Mother-to-infant transmission of hepatitis C virus.

Anti‐hepatitis C virus (HCV) antibodies and HCV‐RNA were measured in the sera of 22 anti‐HCV positive, HIV‐1 negative mothers and their infants. ELISA and RIBA II were used for anti‐HCV determination. HCV‐RNA was measured by a nested polymerase chain reaction. HCV‐RNA was found in 12 of 22 mothers. All 22 children were followed for 12 months. All were anti‐HCV positive by the fourth month; 18 became anti‐HCV negative between the 8th and 12th month. HCV‐RNA was detected in 5 of 22 infants in the fourth month. They remained HCV‐RNA positive. All children born to HCV‐RNA negative mothers were HCV‐RNA negative while 5 of 12 babies born to HCV‐RNA positive mothers were infected. All five infected babies were born to mothers infected through transfusions or drug use. ALT levels in mothers seemed to have no effect on mother‐to‐infant transmission. Hence evidence for perinatal transmission of HCV from HCV‐RNA positive mothers was demonstrated in the present study.

Different Meaning of CD38 Molecule Expression on CD4+ and CD8+ Cells of Children Perinatally Infected with Human Immunodeficiency Virus Type 1 Infection Surviving Longer than Five Years

We investigated the relationship between CD4+CD38+ CD4+HLA-DR+, CD8+CD38+, and CD8+HLA-DR+ cell proportions (HLA-DR = major histocompatibility complex class II) (determined by two-color immunofluorescence) and the clinical condition, IL-2 and IL-6 production, viral RNA copy numbers, and the eventual immunologic-virologic course in 25 children perinatally infected with HIV-1 surviving longer than 5 y [median age, 92 (range, 63-136) mo]. Twelve healthy age-matched children were studied as control subjects. HIV-1+ children had lower percentages and absolute numbers of CD4+CD38+, whereas the percentages of CD4+HLA-DR+ and the percentages and absolute numbers of CD8+CD38+ and CD8+HLA-DR+ cells were higher than that of control subjects. The absolute numbers of CD4+ and the percentages of CD4+CD38+, CD8+CD38+, and CD8+HLA-DR+ cells directly correlated, whereas the percentages of CD4+CD38+ and CD4+HLA-DR+ cells, the percentages of CD4+CD38+ and CD8+CD38+ cells, the CD8+ cell absolute numbers, and the percentages of CD8+CD38+ cells did not. Severe manifestations and immunologic deterioration occurred in children with low CD4+CD38+ cell percentages, whereas virologic worsening was associated with low CD8+CD38+ and CD8+HLA-DR+ cell percentages. IL-2 production directly correlated with percentages and absolute numbers of CD4+CD38+ and CD8+CD38+ cells. RNA copy numbers inversely correlated with CD4+CD38+, CD4+HLA-DR+, CD8+CD38+, and CD8+HLA-DR+ cell percentages. This suggests that CD38 molecule expression on both CD4+ and CD8+ cell subsets is a favorable marker in HIV-1+ children. Perhaps CD8+CD38+ subsets are activated cells, whereas CD4+CD38+ subsets are immature cells, possibly the hosts attempt at CD4+ cell renewal.

Hepatitis C virus antibodies in a long-term follow-up of beta-thalassaemic children with acute and chronic non-A non-B hepatitis

The presence of antibodies toward hepatitis C virus (HCV) was examined in 78 polytransfused betathalassaemic children. The anti-HCV status was correlated with acute and chronic non-A non-B (NANB) hepatitis that developed during a follow up of about 13 years. Anti-HCV was present in 83.3% of children with acute NANB hepatitis and in 82.9% of those with chronic NANB hepatitis. The percentage of chronic evolution was 56.7% for acute anti-HCV positive NANB hepatitis and 50.0% for anti-HCV negative NANB hepatitis. The long-term persistence of anti-HCV antibodies did not correlate with chronic evolution of liver infection in thalassaemic patients. Histological features of chronic hepatitis showed little or no difference between HCV associated or non-associated liver disease. The multifactorial liver injury in beta-thalassaemic children explains the high prevalence of cirrhosis (about 30%) observed in these patients with NANB hepatitis. On the other hand, independent of liver disease, some patients never seroconverted during the follow up in spite of the high number of transfusions suggesting the existence of “non-responders”.

Should hepatitis B surface antigen positive mothers breast feed

Breast fed infants may be at greater risk of mother to infant hepatitis B virus infection compared with formula fed infants. We studied 85 infants born to 84 hepatitis B surface antigen positive mothers (only two of whom were hepatitis B e positive), and who had received immunisation against hepatitis B virus. Our results indicate that breast feeding does not increase the risk of developing hepatitis B virus infection in infants born to these mothers if immunisation is carried out.

Impaired Superoxide Anion, Platelet-Activating Factor, and Leukotriene B4 Synthesis by Neutrophils in Cirrhosis

BACKGROUND Several alterations of polymorphonuclear leukocyte (PMN) function were found in alcoholic cirrhotics that may contribute to augmented susceptibility to infections. We evaluated function and synthesis of lipid mediators in PMN obtained from nonalcoholic cirrhotics. METHODS We evaluated the phagocytic and chemotactic response together with superoxide anion (O2-), leukotriene B4, (LTB4) and platelet-activating factor (PAF) production in response to different stimuli in PMN from nonalcoholic cirrhotics as compared with controls. RESULTS PMN from cirrhotics showed, after stimulation with opsonized zymosan (STZ) and phorbol-12-myristate-13-acetate, a reduced capacity to produce O2- when compared with controls. [3H]acetate incorporation into PAF was significantly higher in PMN obtained from controls in respect to cirrhotics. Gas chromatography/mass spectrometry analysis confirmed a reduced PAF synthesis by PMN obtained from cirrhotics. LTB4 production from PMN, after stimulation with calcium ionophore (A23187) and STZ, was significantly reduced in cirrhotics. [3H]arachidonic acid release from prelabeled PMN, measured upon stimulation with A23187 and STZ, was higher in controls than in cirrhotics. CONCLUSIONS An altered synthesis of LTB4 and PAF is associated with an impaired O2- production by PMN in nonalcoholic cirrhosis. Reduced synthesis of lipid mediators may be related to an altered phospholipase A, activity.

Amoxicillin allergy in children: five-day drug provocation test in the diagnosis of nonimmediate reactions.

BACKGROUND The drug provocation test (DPT) is the gold standard to rule out drug hypersensitivity. There are standardized DPT protocols to diagnose immediate reactions to drugs, but not for nonimmediate reactions. OBJECTIVE The aim of this study was to show the sensitivity and specificity of an allergy work-up that included a 5-day DPT in children with histories of nonimmediate reactions to amoxicillin through focusing on a pediatric population with histories of immediate and nonimmediate reactions to amoxicillin. METHODS Two hundred consecutive patients with histories of amoxicillin reactions referred to the Allergy Unit of Anna Meyer Childrens Hospital for suspected drug allergy from 2008 to 2011 underwent in vivo tests with the culprit drug according to European Academy of Allergy and Clinical Immunology guidelines. Moreover, most of those children, regardless of the skin tests results, were challenged with amoxicillin for a total of 5 days. RESULTS In 4 years, 200 patients were evaluated for a history of drug hypersensitivity to amoxicillin. The majority of patients (76%) had a history of mild nonimmediate reactions. All 200 patients underwent skin tests, and 9 of 200 tested positive. A total of 177 DPTs were performed with amoxicillin for 5 days in each child. Diagnosis of amoxicillin allergy was confirmed by a DPT in 17 patients (9.6%); 14/17 had history of nonimmediate reactions; 4/14 (26.6%) reacted on day 5. CONCLUSION According to our results, a long-term DPT protocol increases the sensitivity of the allergy work-up, and it should be recommended for patients with a history of amoxicillin nonimmediate reaction.

Acellular pertussis vaccine in children with perinatal human immunodeficiency virus-type 1 infection

The immunogenicity of an acellular pertussis vaccine containing genetically detoxified pertussis toxin, filamentous haemoagglutinin and pertactin was studied in 12 children [median age: 45 (6-107) months] with perinatal human immunodeficiency virus-type 1 (HIV-1) infection. Antibody response to all antigens was observed in six cases and another children 3 reacted to two or one antigen(s), but titres were lower than those from healthy controls. Antibody titre fold-rise correlated with preimmunization CD4-positive cell counts. Significant titres were still detectable 4 months after the third dose. The acellular vaccine is immunogenic in a portion of children with perinatal HIV-1 infection but early vaccination might be more effective, taking advantage of still adequate CD4-positive cell numbers.

Hepatitis G Virus Infection in Human Immunodeficiency Virus Type 1-Infected Mothers and Their Children

Hepatitis G virus (HGV) RNA and anti-E2 glycoprotein antibody (E2Ab) seroprevalence was studied in 58 human immunodeficiency virus type 1 (HIV-1)-infected mothers (34 injecting drug users [IDUs] and 24 with risky sexual behavior [RSB]) and their children (median age, 5 days; range, 1-27). Twelve women (20.6%) were RNA- and 20 (34.4%) E2Ab-positive. Seroprevalence was similar in the IDU and RSB groups and high in RSB partners of IDU men. Five (41.6%) children of RNA-positive mothers were HGV-infected, at a median age of 5 days (range, 1-27), independent of maternal CD4 T lymphocyte numbers, mode of delivery, and HIV-1 transmission; no other child at risk became RNA-positive subsequently. No HGV-infected child (follow-up, 16 months; range, 12-52) showed increased liver enzyme levels; 3 children cleared RNA and E2Ab-seroconverted after 10-48 months. Thus, in HIV-1-infected women, HGV infection is common and also sexually transmitted, and clearance may be impaired. Mother-to-child transmission is frequent and occurs antenatally; children remain long infected without evident disease.

Five-year follow-up of vaccination against hepatitis B virus in newborns vaccinated with a reduced number of doses

The protective efficacy and long-term immunogenicity of a schedule with a reduced number of vaccinations in infants born to mothers positive for hepatitis B surface antigen (HBsAg) has been investigated: 494 infants immunized with a plasma derived hepatitis B vaccine (Hevac B Pasteur) at day 20 after birth and 2 months later were studied. Anti-HBs seroconversion rate was 96% after the second dose, a value similar to that obtained in older children. At 5 years of life anti-HBs at protective levels was still 95.8%. In conclusion, we suggest that this effective and economical reduced vaccination schedule, which before this study was applied to older children, can be used in newborns from HBsAg positive mothers with good protective efficacy shifting the beginning of active immunization from birth to day 20.