Long-term follow-up of hepatitis A vaccination in children

We conducted this follow-up study to evaluate the long-term immunogenicity of an inactivated hepatitis A vaccine in children. Ninety-six children who had seroconversion to antibody to HAV (anti-HAV) after receiving a three-dose schedule of inactivated hepatitis A vaccine were enrolled into this study. Sixty months after the initial vaccination, all vaccinees who received annual follow-up still had protective levels of anti-HAV. The geometric mean titer (GMT) of anti-HAV, peaking at month 7 (4133 mIU/mL), kept declining throughout the follow-up period. The GMTs in months 12, 24, 36, 48 and 60 were 1722, 896, 896, 645 and 403 mIU/mL, respectively. Nine of the vaccinees were hepatitis B virus carriers. Their anti-HAV titers tended to be lower than those of the remaining vaccinees at all time-points, but the difference was not significant (p > 0.05). Natural booster was noted in one vaccinee during the follow-up period. In conclusion, inactivated hepatitis A vaccine is safe and immunogenic in children, the duration of protection against HAV infection is longer than five years.     

Immunogenicity of an inactivated hepatitis A vaccine in healthy children: two years' follow-up

To investigate the long-term immunogenicity of an inactivated hepatitis A vaccine in children, 100 healthy children, aged between 1 and 7 years old and all lacking the antibody to hepatitis A (HA) virus, were enrolled in this trial. They received 3 doses of strain HM 175 HA vaccine with 360 enzyme-linked immunosorbent assay (ELISA) units at 0, 1 and 6 months, respectively. Blood sampling for antibody and aminotransferases was performed 7 days before, then 1, 6, 7, 12, and 24 months after the first dose. The titers of antibody to HA virus were tested by radioimmunoassay and ELISA methods. All subjects became ELISA seropositive at Month 6 after two doses of vaccine. Except for one boy, 99 remained seropositive at Month 24, with a geometric mean titer of 1,148 mIU/ml. Antibody titers for females were significantly higher than those for males throughout the follow-up period. It was concluded that the inactivated HA vaccine used in the present trial was immunogenic and safe in children below seven years old. The vaccine-induced antibody persisted for at least two years in 99% of the vaccinees.     

Safety and immunogenicity of a recombinant hepatitis B vaccine administered to infants at 2, 4 and 6 months of age. The Kaiser-UCLA Vaccine Study Group

A recombinant hepatitis B vaccine was administered to over 5000 infants in a prospective, randomized and blinded study. Infants were given either recombinant hepatitis B vaccine (Engerix-B, SmithKline Beecham Pharmaceuticals, 10 micrograms dose-1) or a Haemophilus influenzae type b (Hib) conjugate vaccine at 2, 4 and 6 months of age simultaneously with diphtheria-tetanus-pertussis and oral polio vaccines. Adverse reactions were ascertained by parental reports and interviews, and review of medical records. Blood specimens collected from 269 infants given hepatitis B vaccine were assayed for antibody to hepatitis B surface antigen (anti-HBs) by enzyme immunoassay. Infants given hepatitis B vaccine experienced low rates of adverse reactions that were similar or lower than the rates in infants given Hib conjugate vaccine. The geometric mean anti-HBs concentrations were 9.6 mIU ml-1 after one dose, 333 mIU ml-1 after two doses and 1812 mIU ml-1 after three doses (99% had levels > or = 10 mIU ml-1). Antibody responses to diphtheria and tetanus toxoids were unaffected by simultaneous administration of hepatitis B or Hib conjugate vaccine. Engerix-B vaccine was safe and immunogenic when given with other routine childhood immunizations at 2, 4 and 6 months of age, and should provide long-term protection against hepatitis B virus infection.     

High immunogenicity and good tolerability of a new hepatitis A vaccine candidate

Immunogenicity and tolerability of a new formalin-inactivated, alum-adjuvanted whole virus vaccine against hepatitis A (VAQTA, MSD, West Point, USA) were evaluated by immunizing 52 healthy, anti-HAV negative volunteers with a 1 ml dose. A booster dose was given 6 months later. In these young adult vaccinees [27 males and 25 females, 19-34 (mean 26) years of age] VAQTA proved to be well tolerated and highly immunogenic. Two weeks after administration of one vaccine dose, all but one of the recipients (98%) had anti-HAV concentrations above the presumed minimum protective level of 10 IU l-1 with a geometric mean concentration (GMC) of 165 IU l-1. After 4 weeks, a 100% seroconversion rate could be demonstrated with a fourfold increase of the GMC to 728 IU l-1. Six months after vaccination, all but one of the 50 volunteers coming back for booster (98%) showed anti-HAV levels within the protective range. The antibody concentrations had decreased in the majority of vaccinees to a GMC of 362 IU l-1. The booster dose given at that time was shown to be very effective, leading to a pronounced rise of anti-HAV levels in all recipients with a 17-fold increase of the GMC to 6040 IU l-1. Six months after the booster, all vaccinees were still seropositive with a GMC of 3444 IU l-1. Higher antibody levels were found in females, the difference being significant 4 weeks and 6 months after vaccination and 4 weeks after booster. No serious local or systemic adverse reactions were observed.     

Occlusion of the femoral artery induced fos-like immunoreactive neurons in the lateral habenular nucleus projecting to the midbrain periaqueductal gray in the rat

BACKGROUND: Inactivated hepatitis A vaccines are licensed with a vaccination schedule based on two injections of vaccine given at least 6 months apart. METHODS: Two vaccination schedules for the inactivated hepatitis A vaccine, AvaximTM (Pasteur Mérieux Connaught, Lyon, France), were compared in a monocentric, randomized, open trial. Two doses of the vaccine were given at intervals of either 6 months (0-6 month group) or 12 months (0-12 month group) to 96 adult volunteers. Anti-hepatitis A virus (HAV) antibody titers were determined in a blind fashion using the modified RIA (mRIA) HAVABtrade mark assay. After excluding subjects with positive preimmunization anti-HAV titers and those with protocol deviations, both groups were still comparable by sex ratio and mean age. RESULTS: Four weeks (28 6 4 days) after the first dose, the seroconversion (SC) rate of initially HAV-seronegative subjects (antibody titer < 20 mIU/mL) was 100% in the 0-6 month group and 96. 9% in the 0-12 month group, with corresponding geometric mean titer (GMT) values (95% CI) of 369 mIU/mL (274-497 mIU/mL) and 445 mIU/mL (292-679 mIU/mL), respectively. After 6 months, SC was obtained in all subjects, and the corresponding GMT values were 349 mIU/mL and 359 mIU/mL in the 0-6 month group and the 0-12 month group, respectively. Four weeks after the booster dose given at 6 months, a 14.5-fold rise in GMT was observed. In the 0-12 month group, anti-HAV GMT values decreased by only 20% from 6 months to 12 months with a pre-booster GMT value of 286 mIU/mL at the 12-month evaluation. Four weeks after the booster given at 12 months, a 22. 5-fold rise in GMT was observed. Statistical analysis showed that the two vaccination schedules were comparable in their ability to boost antibody titers. Unsolicited reactions to vaccination were not different to those reported during earlier trials. Less than 12% of the vaccinees reported reactions after the first dose (11/93), or after the booster dose (11/92). CONCLUSIONS: This trial demonstrated antibody persistence is excellent for at least 12 months after one dose of this vaccine, and that a booster may be given at any time between 6 and 12 months after primary immunization.     

Low seroconversion with hepatitis B vaccination in peritoneal dialysis patients

OBJECTIVE: To compare seroconversion using hepatitis B vaccine between hemodialysis (HD) and peritoneal dialysis (PD) patients. DESIGN: Data on PD patients vaccinated were collected retrospectively for the period 1992 to 1995. The data on HD patients were collected prospectively from 1991 to 1994. SETTING: A university outpatient dialysis center. PARTICIPANTS: All adult patients who received all four doses of hepatitis B vaccine while on dialysis were included (47 PD and 50 HD patients). INTERVENTION: Recombinant hepatitis B vaccine (Engerix), 40 micrograms IM was administered at 0, 1, 2, and 6 months. MAIN OUTCOME MEASURE: Seroconversion was measured after completion of the vaccination series. RESULTS: 74% of the HD patients seroconverted compared to 53% of PD patients (p = 0.03). Older, heavier patients compared to all the other patients had a lower seroconversion rate in both the HD patients (55% vs. 78 %) and PD patients (38% vs. 59%) (p = 0.03). CONCLUSION: The seroconversion rate to recombinant hepatitis B vaccine is lower in patients on PD than on HD for unclear reasons. Further studies are required to determine the etiology of this difference.     

Safety and immunogenicity of a novel mammalian cell-derived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in neonates

BACKGROUND: Most of the licensed hepatitis B vaccines produced by recombinant DNA contain the S protein component of the hepatitis B virus surface antigen particle but lack two important components, Pre-S1 and Pre-S2. These components have recently been shown to play an important immunogenic role by enhancing the hepatitis B surface antibody (anti-HBs) titers, stimulating response and circumventing genetic nonresponsiveness. OBJECTIVE: To assess safety, tolerability and immunogenicity in neonates of a novel recombinant HBV vaccine (Bio-Hep-B) containing the S, Pre-S1 and Pre-S2 components compared with a licensed recombinant vaccine (Engerix-B) containing the S component only. METHODS: Healthy neonates were randomized to receive either Bio-Hep-B (2.5 micrograms/dose) or Engerix-B (10 micrograms/dose) at ages < 24 h, 1 month and 6 months. Blood was obtained at ages 0, 1, 7 and 12 months. Tolerability was assessed by diary cards filled by the parents for 5 successive days after immunization. Immunogenicity was assessed by determination of anti-HBs antibody. RESULTS: Of 205 neonates 153 were in the Bio-Hep-B group and 52 were in the Engerix-B group. Both vaccines were well-tolerated and all infants became seroprotected (anti-HBs > 10 mIU/ml). After the first dose a significantly higher proportion of neonates seroconverted in the Bio-Hep-B group than in the Engerix-B group (83% vs. 34%; P < 0.001); this difference in seroresponse was even more pronounced for those achieving seroprotective concentrations (> 10.0 mIU/ml) after the first dose: 54% vs. 7%, respectively (P < 0.001). Geometric mean concentrations were significantly higher at all points in the Bio-Hep-B group. CONCLUSION: Both vaccines were well-tolerated and immunogenic. Bio-Hep-B, despite its low dose, was significantly more immunogenic and elicited more rapid antibody response. This finding has implication for future vaccine programs in regions where maternal screening for hepatitis B virus surface antigen and administration of hepatitis B immunoglobulin are not routinely practiced at birth for infants of hepatitis B virus carrier mothers.     

Impaired response to hepatitis B vaccine in children receiving anticancer chemotherapy

Serologic responses to hepatitis B vaccine were investigated in 197 pediatric cancer patients. The patients, ages 1 to 21 years, comprised 66 with solid tumors, 101 with hematologic malignancies and 30 with various benign conditions. Of them 51 were receiving cytotoxic chemotherapy and 114 had not received chemotherapy for 0.2 to 11 years. Three doses of plasma-derived hepatitis B vaccine (20 micrograms) were given at 0, 1 and 6 months; and antibody concentrations to hepatitis B surface antigen were determined at 3, 6 and 8 months. The geometric mean antibody concentration after 3 vaccine doses was 1076 mIU/ml in cancer patients receiving chemotherapy and 18,833 mIU/ml in cancer patients not receiving chemotherapy. The protective titer of antibody (> or = 10 mIU/ml) was reached after 3 doses of vaccine by 67% of patients receiving chemotherapy and by 97% of those not receiving chemotherapy. The patients being treated for solid tumors had weaker responses than those being treated for hematologic malignancies: after 3 vaccine doses no response was observed in 6 of 11 patients with solid tumors compared with 3 of 25 of patients with hematologic malignancies. Children receiving anticancer chemotherapy have essentially weaker responses to hepatitis B vaccine than children not receiving chemotherapy or those with benign conditions. This reflects the profound immunosuppression during chemotherapy. The effect of more intensive immunization schedules should be investigated.     

Access to a three-dimensional measure of vertebral axial rotation

BACKGROUND: A combined diphtheria-tetanus-whole cell pertussis-hepatitis B (DTPwHB) vaccine might facilitate the achievement of universal vaccination of infants against hepatitis B. METHODS: A double blind, randomized, two-armed, single center study was undertaken to evaluate the immunogenicity and reactogenicity of combined tetravalent DTPwHB vaccine, with two dosages of hepatitis B component (10 microg and 5 microg). The combined vaccine was tested in the context of a simplified vaccination schedule at 1.5, 3.5 and 6 months of age, to 120 healthy infants born to hepatitis B surface antigen-negative mothers after priming with one dose of hepatitis B vaccine (10 microg) at birth. Antibodies to each antigenic component were measured from blood samples collected immediately after birth, pre- and postvaccination blood samples. RESULTS: The reactogenicity profiles were similar in the two groups. No serious adverse events were reported. One month after completion of the four-dose vaccination schedule, all subjects except one in Group 1 (10 microg) had protective titers of anti-HBs (10 mIU/ml). At this time the geometric mean titer in Group 1 (10 microg) was higher than that observed in Group 2 (5 microg), 696 vs. 488 mIU/ml (P = 0.19). One month after three doses all subjects in both groups had protective antidiphtheria titers and antitetanus titers. The vaccine response rate to the Bordetella pertussis component of the vaccine was 88.0% in Group 1 and 96.2% in Group 2 (P = 0.86). CONCLUSION: Both combined tetravalent vaccines are safe and immunogenic when administered to infants born to a hepatitis B surface antigen-negative mother, with a 10-microg dose of priming hepatitis B vaccine at birth. This combined tetravalent DTPwHB vaccine may play an important role to promote integration of HB vaccine into the Expanded Program of Immunization in hepatitis B-endemic areas.     

Hepatitis A vaccination

The safety and immunogenicity of an inactivated hepatitis A virus vaccine were assessed in 101 healthy adults. Seronegative persons with normal serum aminotransferase levels were grouped according to age: Group 1 (n = 24) and group 3 (n = 22) were between 18 and 40 years of age, and group 2 (n = 25) and group 4 (n = 30) were older than 40 years. Groups 1 and 2 received vaccine on a 0-, 1-, and 2-month schedule (schedule A), and groups 3 and 4 received the vaccine on a 0-, 1-, and 12-month schedule (schedule B). Of the 101 vaccinated subjects, 98 (97%) seroconverted with antibody titers to hepatitis A virus of > or = 20 IU per liter after the first dose, and all subjects seroconverted after the second dose. The geometric mean titers a month after the third vaccine dose were significantly greater (P < .03) on both schedules for younger subjects (schedule A, 1,743 IU per liter, and schedule B, 7,882 IU per liter) than for older subjects (schedule A, 826 IU per liter, and schedule B, 4,279 IU per liter). Also, the differences in geometric mean titers a month after the third dose were significantly greater (P < .001) for subjects in both age groups on schedule B (group 3, 7,882 IU per liter, and group 4, 4,279 IU per liter) than for those on schedule A (group 1, 1,743 IU per liter, and group 2, 826 IU per liter). The hepatitis A virus was well tolerated, with mild discomfort at the injection site being the main side effect. This vaccine is both safe and highly immunogenic.     

Safety and immunogenicity of hepatitis A vaccine in patients with chronic liver disease

Acute hepatitis A superimposed on chronic liver disease (CLD) has been associated with severe or fulminant hepatitis. An open, multicenter study was performed to compare the safety and immunogenicity of an inactivated hepatitis A vaccine in patients with CLD with that in healthy subjects. A secondary objective was to compare the safety of the hepatitis A vaccine with that of a commercial hepatitis B vaccine in subjects with chronic hepatitis C. A total of 475 subjects over the age of 18 years were enrolled into 1 of 5 groups according to history, serological data, and previous diagnosis. Patients in groups 1 (healthy adults), 2 (chronic hepatitis B), 3 (chronic hepatitis C), and 5 (other CLD not caused by viral hepatitis) were vaccinated with two doses of inactivated hepatitis A vaccine, 6 months apart. Patients in group 4 (chronic hepatitis C) received 3 doses of a recombinant hepatitis B vaccine, according to a 0-, 1-, and 6-month schedule. Local injection-site symptoms were the most common reactions reported following vaccination in all groups (35.5% of all doses), with the hepatitis B vaccine eliciting fewer injection-site symptoms than the hepatitis A vaccine (19.8% compared with 37.5%). Although a higher percentage of healthy subjects (93%) seroconverted after a single dose of the hepatitis A vaccine than did subjects with chronic hepatitis C (73.7%) or CLD of nonviral etiologies (83.1%), more than 94% of all vaccinees were seropositive for anti-HAV after the complete vaccination course. At each time point, a lower geometric mean concentration of anti-HAV was observed for each group of CLD patients compared with the healthy control subjects. In conclusion, hepatitis A vaccine was well tolerated and induced a satisfactory immune response in patients with chronic hepatitis B, chronic hepatitis C, and miscellaneous CLD.     

Spontaneous seroconversion in chronic hepatitis B: role of mutations in the precore/core gene

The mechanism underlying spontaneous clearance of hepatitis B e antigen (HBeAg) and the appearance of antibodies (anti-HBe seroconversion) in chronic hepatitis B is not known. Previous studies have demonstrated mutations within the precore/core gene before, during, and after seroconversion, suggesting that the emergence of mutations in the core gene may abrogate tolerance and that this event may act as a general principle for the initiation of the clearance of HBeAg. To investigate this hypothesis, we studied three patients with adult-acquired chronic hepatitis B virus (HBV) infection before spontaneous seroconversion by sequential sequencing and single-stranded conformation polymorphism (SSCP) analysis of the entire precore/core genome. In one patient, a new viral strain appeared six months before seroconversion, but no mutations or new viral strains could be detected in the other two patients. SSCP analysis confirmed the sequencing results and revealed no evidence for the emergence of new viral subpopulations before seroconversion. These results suggest that the appearance of nucleotide changes within the precore/core region of the dominant viral strain is not a prerequisite for the induction of seroconversion in patients with chronic hepatitis B virus infection acquired during adulthood.     

Failure of ganciclovir prophylaxis to prevent allograft reinfection following orthotopic liver transplantation for chronic hepatitis B infection

The effect of ganciclovir prophylaxis on reinfection of hepatic allografts by hepatitis B virus (HBV) was studied in 26 patients undergoing orthotopic liver transplantation (OLT) for decompensated cirrhosis due to HBV. Patients were randomized to receive either ganciclovir (6 mg/kg/day intravenously for a total of 100 days) or acyclovir (10 mg/kg every 8 hours intravenously until discharged and then 800 mg orally every 6 hours) for a total of 100 days after OLT as part of a study of prophylaxis against cytomegalovirus infection. All patients received hepatitis B immunoglobulin (HBIG), 10,000 units intravenously, during the anhepatic phase, daily for the first 7 days, after OLT, and then every 4 weeks for 6 months, Seven of 12 (58%) patients in the ganciclovir group developed recurrent HBV, compared with 6/14 (46%) of the acyclovir group (nonsignificant). No significant difference was observed in time to recurrent HBV in the ganciclovir group (mean 13.2 months) compared to the acyclovir group (mean 11 months). Our results suggest that ganciclovir administered prophylactically for 100 days after OLT does not prevent or delay graft reinfection by HBV.     

Suboptimal response following intradermal hepatitis B vaccine in infants

Two hundred and twenty-five infants were randomly assigned to receive 2 micrograms of plasma-derived hepatitis B vaccine (Heptavax) intradermally (ID-2), 10 micrograms intramuscularly (IM-10), or 2 micrograms intramuscularly (IM-2) in the deltoid region at birth, 2 and 4 months. At 6 months, ID-2 infants were less likely to have developed > or = 10 mIU ml-1 of antibody to hepatitis B surface antigen (anti-HBs) than IM-10 infants (91 versus 100%; p = 0.02) and had a lower geometric mean concentration of anti-HBs (312 mIU ml-1 versus 2248 mIU ml-1; p < 0.01). At 6 months IM-10 infants had significantly lower mean weights and lengths than infants receiving 2 micrograms doses of vaccine. Intramuscular administration of 2 micrograms and 10 micrograms doses of Heptavax in the deltoid of young infants was well tolerated and effective; however, intradermal administration of Heptavax provided no immunological benefit over intramuscular administration and resulted in significantly higher rates of induration and persistent hyperpigmentation. Intramuscular immunization at birth, 2 and 4 months is an acceptable, effective alternative schedule for immunizing infants.     

Hepatitis B vaccination in preterm infants

AIM: To investigate the immunogenicity and safety of existing recommendations for hepatitis B vaccination in preterm infants. METHODS: Recombinant hepatitis B vaccine (H-B-VAX II, 5 micrograms per dose) was given to 85 preterm infants divided into two groups, using two different schedules. Forty four group A infants with birthweights of < 2000 g received three doses at 1, 2, and 7 months of age. Forty one group B infants with birthweights of > or = 2000 g received three doses at 0, 1, and 6 months of age. RESULTS: After vaccination, 42 infants from group A (95%) and 37 infants from group B (90%) developed protective levels of antibody. The final seropositive rate and the geometric mean concentration of hepatitis B surface antibody between the two groups were not significantly different. The immune response of preterm infants to hepatitis B vaccines was similar to that of term infants in a previous study. CONCLUSIONS: Preterm infants can be given hepatitis B vaccines using one of the above two different schedules, at a cutoff birthweight of 2000 g.     

Inhibition by wheat bran cereals of the development of aberrant crypt foci and colon tumours

BACKGROUND: Double inactivation by solvent/detergent treatment plus heating at 100 degrees C for 30 minutes after lyophilization has been adopted to improve viral safety of factor VIII and factor IX concentrates, particularly with respect to non-lipid-enveloped viruses. The aim of this study was to evaluate the safety of concentrates exposed to these virucidal methods. STUDY DESIGN AND METHODS: Twenty-six previously untreated hemophiliacs, 19 with factor VIII deficiency and 7 with factor IX deficiency, were investigated in a prospective multicenter study over a 12-month follow-up period by the use of serologic and virologic markers for lipid- and non-lipid-enveloped viruses (human immunodeficiency virus types 1 and 2; hepatitis A, B, and C viruses; B19 parvovirus antibodies; and B19 DNA). Overall, 270,000 U of factor VIII and 102,000 U of factor IX concentrate were administered during the study period. RESULTS: None of the 26 patients seroconverted for human immunodeficiency virus or hepatitis C virus. Hepatitis B virus markers remained negative in the 10 unvaccinated hemophiliacs. No hepatitis A virus seroconversion occurred among 17 susceptible patients. B19 seroconversion (IgM) and B19 viremia were observed within 2 weeks of the first concentrate infusion in 8 of 15 susceptible patients, 5 of 11 treated with factor VIII and 3 of 4 with factor IX concentrate. CONCLUSION: This prospective study indicates that very high temperatures applied to lyophilized concentrates appear to prevent the transmission of hepatitis A virus to hemophiliacs. However, B19 parvovirus still contaminates concentrates despite the use of this robust virucidal method.     

CpG DNA can induce strong Th1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice

Successful neonatal immunization of humans has proven difficult. We have evaluated CpG-containing oligonucleotides as an adjuvant for immunization of young mice (1-14 days old) against hepatitis B virus surface antigen. The protein-alum-CpG formulation, like the DNA vaccine, produced seroconversion of the majority of mice immunized at 3 or 7 days of age, compared with 0-10% with the protein-alum or protein-CpG formulations. All animals, from neonates to adults, immunized with the protein-alum vaccine exhibited strong T helper (Th)2-like responses [predominantly IgG1, weak or absent cytotoxic T lymphocytes (CTL)]. Th2-type responses also were induced in young mice with protein-CpG (in 1-, 3-, and 7-day-old mice) and protein-alum-CpG (in 1- and 3-day-old mice) but immunization carried out at older ages gave mixed Th1/Th2 (Th0) responses. DNA vaccines gave Th0-like responses when administered at 1 and 7 days of age and Th1-like (predominantly IgG2a and CTL) responses with 14-day-old or adult mice. Surprisingly, the protein-alum-CpG formulation was better than the DNA vaccine for percentage of seroconversion, speed of appearance, and peak titer of the antibody response, as well as prevalence and strength of CTL. These findings may have important implications for immunization of human infants.     

Ogura and Powers: "Functional restitution of traumatic stenosis of the larynx and pharynx." (Laryngoscope 1964;74: 1081-1110)

The objective of this study was to evaluate the immune response and reactogenicity of a combined hepatitis B, diphtheria, tetanus and whole-cell Bordetella pertussis (DTPw-HBV) vaccine administered to healthy infants at 2, 4 and 6 months of age. A total of 179 infants (6-12 weeks of age) received three doses of DTPw-HBV vaccine. Blood samples for antibody determinations were taken before vaccination, 2 months after the second dose and 1 month after the third dose. Solicited and unsolicited symptoms were recorded by parents in a diary card. All vaccinees had protective levels of anti-HBs [geometric mean titre (GMT): 1526 mIU.ml-1], anti-diphtheria and anti-tetanus antibodies, 1 month after the third dose. Ninety-two percent of the subjects exhibited a response to the B. pertussis component. Most (99.4%) solicited reactions occurred within the first 48 h and the majority were mild or moderate. The safety, immunogenicity of this tetravalent vaccine was demonstrated when it was administered in infants following the 0, 2, 4-month dosing schedule.     

Safety and efficacy of interferon retreatment in children with chronic hepatitis B

More than 50% of children with chronic hepatitis B do not respond to treatment with alpha-interferon. Since these patients continue to display high viral replication and progressive liver disease, retreatment should be considered. To date it has not been well evaluated whether a second course of treatment could increase the response rate. In two alpha-interferon retreatment trials in adult patients the response rate, defined by seroconversion from HBeAg to anti-HBe, ranged between 11% and 44%. One beta-interferon retreatment study in children reported a seroconversion rate of 32%. Regrettably, none of the studies included a control group observing the 'spontaneous' seroconversion rate after a first interferon cycle. Thus, a nonrandomized alpha-interferon retreatment study in children including control patients was performed. Alpha-interferon for retreatment was administered 3 times a week for 16-24 weeks in 15 children (5-16 years) at least 6 months after ceasing the first cycle. Four children received 5 MU/m2 of a natural alpha-interferon and 11 children 9 MU/m2 recombinant alpha-interferon 2b. Follow up was 18-47 months after initial treatment. In parallel, a control group of 19 unretreated children with comparable clinical and demographic data was followed for 12-39 months. HBeAg seroconversion was observed in 5 (33%) of the retreated children and in 5 (26%) of the control patients during follow up. The difference is not significant. In the initially nonresponding children, those with high ALT levels before the first treatment showed late HBeAg seroconversion more frequently than those with low ALT levels (P=0.017) irrespective of retreatment. The ALT level before retreatment was not a predictor for response. CONCLUSIONS: A second cycle of alpha-interferon during the 3 years following the first treatment in nonresponding children with chronic hepatitis B can be safely performed but did not increase HBeAg/anti-HBe seroconversion compared with the spontaneous seroconversion rate of patients without retreatment.     

Infection with HIV and hepatitis C virus among injecting drug users in a prevention setting: retrospective cohort study

OBJECTIVES: To estimate the incidence of HIV and hepatitis C virus and risk factors for seroconversion among a cohort of injecting drug users. DESIGN: Retrospective cohort study. SETTING: Primary healthcare facility in central Sydney. SUBJECTS: Injecting drug users tested for HIV-1 antibody (n=1179) and antibodies to hepatitis C virus (n=1078) from February 1992 to October 1995. MAIN OUTCOME MEASURES: Incidence of HIV-1 and hepatitis C virus among seronegative subjects who injected drugs and underwent repeat testing. Demographic and behavioural risk factors for hepatitis seroconversion. RESULTS: Incidence of HIV-1 among 426 initially seronegative injecting drug users was 0.17/100 person years (two seroconversions) compared with an incidence of hepatitis C virus of 20.9/100 person years (31 seroconversions) among 152 injecting drug users initially negative for hepatitis C virus. Incidence of hepatitis C virus among injecting drug users aged less than 20 years was 75.6/100 person years. Independent risk factors for hepatitis C virus seroconversion were age less than 20 years and a history of imprisonment. CONCLUSIONS: In a setting where prevention measures have contributed to the maintenance of low prevalence and incidence of HIV-1, transmission of hepatitis C virus continues at extremely high levels, particularly among young injecting drug users.