Safety and immunogenicity of a pediatric formulation of inactivated hepatitis A vaccine in Argentinean children.

BACKGROUND: Children are a reservoir of hepatitis A virus and must be considered as primary targets of any immunization strategy. The safety and immunogenicity were evaluated for a new formulation of an inactivated hepatitis A vaccine, Avaxim 80 units, containing one-half the antigen dose of the adult formulation. METHODS: The safety of two doses of this vaccine given 6 months apart was evaluated in an open study in 537 Argentinean children 12 months to 15 years old. Immunogenicity was evaluated at Weeks 0, 2, 24 and 27 in a subgroup of 120 subjects. RESULTS: Two weeks after the first vaccine dose, >99% of initially seronegative children had seroconverted (titers > or =20 mIU/ml), with a geometric mean titer of 98.5 mIU/ml. Before booster at 24 weeks all subjects had seroconverted. A strong anamnestic response was observed after the second dose at which time the geometric mean titer had increased >35-fold, and antibody titers were consistent with long term protection. Immediate adverse reactions were observed in 3 of 537 (0.6%) subjects after the first dose. Local reactions were mild and transient and did not increase with subsequent doses. Among the systemic events reported during the 7-day follow-up period, 37 cases of fever after the first dose and 22 cases after the second dose were reported. Only 3 cases of fever were clearly related to vaccination (< or =38.2 degrees C) after the first injection, all of which subsided in less than 1 day. CONCLUSIONS: This study demonstrated the safety and immunogenicity of a pediatric formulation of hepatitis A vaccine in children ages 12 months to 15 years in healthy children ages 12 to 47 months.

Incomplete hemolytic-uremic syndrome in Argentinean children with bloody diarrhea.

Argentina has an exceptionally high frequency of hemolytic-uremic syndrome (HUS). We sought to define prospectively the role of verocytotoxins (Shiga-like toxins [SLTs]) in 254 Argentinean children with grossly bloody diarrhea during spring and summer. Free fecal SLTs (I/II) and/or DNA probe-positive isolates were found in 99 (39%) of the children. During the follow-up period, HUS developed in 6 patients (4 with evidence of recent SLT infection based on stool studies); another 14 patients had some, but not all, of the abnormalities seen in typical HUS. The development of HUS or incomplete HUS in these children was significantly associated with recent SLT-Escherichia coli infection (p = 0.024). The high incidence of SLT-associated bloody diarrhea in Argentina explains, at least partially, the unusually high frequency of HUS. Our data indicate that incomplete forms of HUS may be common in patients with SLT-associated bloody diarrhea.

Tumor necrosis factor concentrations in hemolytic uremic syndrome patients and children with bloody diarrhea in Argentina.

Hemolytic uremic syndrome (HUS) is thought to be a vascular endothelial injury disease. The mechanism of injury is unknown although verocytotoxins (Shiga-like toxins (SLTs)) are known to be associated with it. Recent evidence suggests that in vitro treatment of some endothelial cells with tumor necrosis factor alpha (TNF-alpha) dramatically increases their susceptibility to SLTs. We studied 25 children with HUS, 63 children with SLT-positive bloody diarrhea, 62 children with bloody diarrhea not associated with SLTs and 39 children admitted for elective surgery, included as an age- and season-matched control group. The TNF-alpha concentrations were found to be significantly elevated in children with HUS (range, 1 to 95 pg/ml; geometric mean, 32.2 pg/ml) compared with the healthy controls (range, 0 to 53 pg/ml; mean, 12.5 pg/ml; P < 0.001). Because it is hypothesized that TNF-alpha elevation might precede development of HUS, we also studied children with blood diarrhea. The TNF-alpha serum concentrations were significantly higher during the first 10 days after onset of bloody diarrhea than after the first 10 days (P < 0.02). Such elevation could be associated with vascular endothelial glycolipid receptor up-regulation and increased susceptibility to the effects of SLTs.