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Biomedical subjects

A Milne

Publications and source records attributed to A Milne.

At least 19 recordsLinked to original sources

Hepatitis B vaccination in children: five year booster study.

AIM: to demonstrate that appropriate doses of hepatitis B vaccines would be protective for at least five years in children. This would be shown by administering booster doses and measuring the response. METHODS: 2 micrograms intramuscular (IM) doses of Merck Sharp and Dohme (MSD) recombinant DNA vaccine (rDNAV) were given to 318 children who had received age appropriate doses of MSD plasma derived vaccine (PDV) five years earlier. Sera were tested for hepatitis B virus (HBV) seromarkers pre- and postbooster. RESULTS: all children who had responsed to primary immunisation demonstrated an anamnestic response. The geometric mean titre (GMT) of antibody to hepatitis B surface antigen (antiHBs) rose from 89 to 4777 IU/L. AntiHBs was detected in 94% of vaccinees just prior to the five year booster, and 96.5% a mean of 10 days later. CONCLUSION: when initial vaccine seroconversion is satisfactory, protection of responders persists for at least five years, assuming that the response to vaccine boosters mimics the response to wild virus. Therefore, for population control of hepatitis B in children in endemic areas, booster doses are not required for at least five years.

Antibodies, Viral

Hemispheric interactions: the bilateral advantage and task difficulty.

Twenty-five normal subjects made "same-different" responses to dot patterns presented in the LVF, RVF or bilaterally. Task difficulty was manipulated in each condition by varying the number of dots in the two patterns presented from two to four to six. The pairs of patterns always had the same number of dots on a given trial. Response latency and accuracy worsened as the number of dots increased for all three presentation conditions and for both "same" and "different" judgements. Overall, responding was faster and the number of errors lower on Bilateral presentations. For response latencies to identical patterns of dots, the size of the bilateral advantage increased relative to RVF responding as task difficulty increased but did not change significantly relative to LVF responding. When the two patterns were not identical the size of the advantage did not change as task difficulty increased. "Same" judgements were faster but less accurate than "different" judgements. A model of hemispheric interactions is proposed to account for the findings.

Adult

Serum immunoreactive erythropoietin in patients with idiopathic aplastic and Fanconi's anaemias.

In patients with idiopathic aplastic anaemia (n = 34) and Fanconi's anaemia (n = 8), sampled once or on several occasions, serum erythropoietin (Epo) increased with increasing severity of anaemia with apparently similar rates of increase in each group. However, after adjustment for Hb, log Epo values for the Fanconi's anaemics tended to be greater than those for the idiopathic aplastic anaemics (P < 0.01). Erythropoietin concentrations in serum samples from patients with Fanconi's and idiopathic aplastic anaemias tended to be greater than in samples from patients with anaemias from protein energy malnutrition, myelodysplasia and iron deficiency. The results suggest that there is no deficiency of erythropoietin in Fanconi's and idiopathic aplastic anaemias and that if exogenous erythropoietin is of any benefit it would need to be administered in doses large enough to induce a significant increase in log Epo. Results of the study illustrate the need to take account of the assumptions which underlie interpretation of the statistical analysis. Use of erythropoietin values in place of log Epo gives misleading conclusions demonstrable as invalid as the conditions for normality of distribution of the data and homogeneity of variances were not satisfied.

Adolescent

Seroepidemiology of hepatitis B infection in children in Vanuatu. Implications for vaccination strategy.

Four hundred and eighty-two unvaccinated children from three different age groups (12-18 months, 30-42 months, 54-115 months) in a hepatitis B virus (HBV) endemic area were tested for markers of HBV infection. HBV seromarkers were detected in 52.3% of children and 26.9% were hepatitis B surface antigen (HBsAg) positive. Evidence of infection was related to age, with HBV seromarker rates highest (67.5%) in school children aged 56-115 months. The HBsAg positive rate was highest (30.1%) in children 30-42 months of age. However, even children in the youngest age group (12-18 months) had high seromarker (26.8%) and HBsAg positive (17.0%) rates. A high proportion of HBsAg positive children (83.8%) were also hepatitis Be antigen (HBeAg) positive. Mothers of children in the youngest age group (12-18 months) were also tested, and 24.5% were HBsAg positive. Factors associated with higher rates of infection in children included maternal HBeAg positivity (for children in the youngest age group), increasing age, and residence on the islands of Emao or Nguna. Higher rates of HBsAg positivity were associated with these factors and with being male. Crossinfection between children is probably the most important source of infection, based on the evidence of the high rate of HBeAg positivity in children and the rising infection rate with age. A possible vehicle of spread is through skin infections and skin sores which are highly prevalent in children in Vanuatu. Since this study indicates that both perinatal and early child-to-child transmission are occurring, the most practical strategy to prevent the majority of infections is to vaccinate all children, commencing at birth and completing the course early in the first year of life.

Child

Detection of Helicobacter pylori infection of the gastric mucosa by measurement of gastric aspirate ammonium and urea concentrations.

Helicobacter pylori possesses unusually high urease activity that lowers the urea concentration and raises the ammonium concentration of the gastric juice in infected people. The value of measuring urea and ammonium concentrations in gastric juice obtained during upper gastrointestinal endoscopy as a means of diagnosing the presence and eradication of the infection was assessed. Twenty four subjects with the infection and 14 in whom it had been eradicated were examined. Their H pylori status was confirmed by antral biopsy and 14C urea breath test. The median (range) gastric juice urea concentration in infected subjects was 0.8 mmol/l (0.5-2.9 mmol/l), which was lower than that in the uninfected subjects (2.1 mmol/l (1.0-3.7 mmol/l)) (p less than 0.001). The median gastric juice ammonium concentration in infected subjects was 3.4 mmol/l (1.0-13.0 mmol/l), which was higher than that in the uninfected subjects (0.64 mmol/l (0.02-1.4 mmol/l)) (p less than 0.001). Though the two groups overlapped in respect of their urea and ammonium concentrations, they were completely different when the urea: ammonium ratios were calculated--the ratios ranged from 0.04-0.7 (median 0.26) and from 1.1-113 (median 3.4) in infected and uninfected subjects respectively (p less than 0.001). Treatment with H2 antagonists did not change the concentrations of urea and ammonium or their ratio in gastric juice. Measurement of the urea: ammonium ratio in aspirated gastric juice obtained during routine upper gastrointestinal endoscopy may provide a rapid method of detecting H pylori infection and of confirming its eradication.

Adolescent

Hepatitis B vaccine boosters: further studies in children.

Two groups of children were given reduced dose boosters with Merck Sharp and Dohme (MSD) recombinant DNa, yeast derived hepatitis B vaccine (YDV), 30 and 34 months respectively after primary immunisation with MSD plasma derived vaccine (PDV). In the first group of unselected children the geometric mean titre (GMT) rose from 387 to 8346 IU/L, with all children protected. The second group were selected as the poorest responders to their primary course of vaccine. The booster raised the GMT from 14.6 to 325 IU/L, with 95% having protective levels of anti-HBs (greater than 10 IU/L). This study confirms that the vaccine used by the New Zealand Department of Health for the hepatitis B immunisation programme in preschoolers, will provide protection for the great majority of children for at least three years.

Adolescent

Very low dose hepatitis B vaccination in the newborn: anamnestic response to booster at four years.

Seventy-eight children who had received three very low doses (1 or 2 microg) of Merck, Sharp and Dohme (MSD) plasma-derived vaccine (PDV) in early infancy were followed to approximately four years of age. Of the 70 who had responded to the initial course of vaccine with measurable anti-HBs, levels had fallen to below 10 mlU/ml in 38% of subjects given 1 microg doses and in 17% of those who had been given 2 microg doses. None of the children were positive for anti-HBc. Two weeks after 2 microg dose of MSD recombinant DNA (rDNA) vaccine all subjects had more than 10 mlU/ml of anti-HBs, with 90% exceeding 1,000 mlU/ml. A response to hepatitis B vaccine in infancy is followed by an effective immunological memory for several years, even if anti-HBs falls to low levels. The rDNA hepatitis B vaccine (MSD) in 2 microg doses is an effective booster following a primary course of plasma derived vaccine.

Child, Preschool

Mass vaccination against hepatitis B in preschool children: immunogenicity after three reduced doses.

The immunising effect of three reduced doses of Merck Sharp and Dohme (MSD) H-B Vax plasma derived vaccine delivered at monthly intervals was evaluated in 1225 four year old children. Eighteen children had evidence of previous or current infection with HBV. Of the remaining 1207 children, 1186 (98.3%) had antibody to hepatitis B surface antigen (anti-HBs) when tested by enzyme immunoassay (EIA). Levels of anti-HBs in 96 randomly selected sera were independently quantitated by radioimmunoassay (RIA) and all were positive for anti-HBs, with a geometric mean titre of 1013. There was no significant difference in seroconversion or anti-HBs levels between the groups of children nationwide. In 19 of the 39 centres, seroconversion was 100%. No centre had less than 92% seroconversion. This study confirms that three 2 microgram doses of MSD H-B Vax plasma derived vaccine given intramuscularly (IM) at monthly intervals are highly immunogenic in this paediatric population.

Child, Preschool

Liver disease and hepatitis B infection in a large New Zealand family.

This study illustrates the relationship between the hepatitis B virus (HBV) carrier state and primary hepatocellular carcinoma in a large family of Maori (173 members) amongst whom four brothers have died of primary hepatocellular carcinoma. The brothers were from a generation of fourteen siblings, eleven of whom were tested for hepatitis B surface antigen (HBsAg) and all found to be positive. Amongst the offspring of this generation there were 13 HBsAg positives from 28 children (46%) born to female carriers but no HBsAg positives amongst the 28 offspring of male carriers. The study provides further evidence that the morbidity which often follows HBsAg carriage, may be associated with early (perinatal) infection. There was a marked decrease in HBV serologic markers in succeeding generations, from 100% in generation two, to 55% in generation three and 14% in generation four, unrelated to the use of hepatitis B vaccine.

Adult

Modes of hepatitis B virus transmission in New Zealand.

We review some of the current literature on modes of transmission of hepatitis B virus (HBV) and report a descriptive study of lifestyle practices of children in the eastern Bay of Plenty and east coast of New Zealand. We also report a small case-control study of possible HBV infection risk factors in a group of central North Island school children, with a hepatitis B surface antigen (HBsAg) seroprevalence of 1.5%, and an HBV immune seroprevalence of 16%. Toothbrush, bathtowel and bed sharing were found to be risk factors for HBV infection in this group. The primary mode of HBV transmission in New Zealand is currently unknown, although it appears that direct contact by parenteral means (through blood and sores) may be the most likely route of spread. Direct contact by non parenteral means, including sharing food contaminated with blood, may also be important. Environment-mediated spread may play a role, particularly as a means of spread between cuts and sores. Avenues for further research are also suggested.

Carrier State

Prevalence of hepatitis B in children in a high risk New Zealand community, and control using recombinant DNA vaccine.

Two hundred and sixty-six children aged 3-10 years were tested for hepatitis B virus (HBV) serologic markers. Thirty-eight were positive, including seven who were positive for hepatitis B surface antigen (HBsAg). Two hundred and fifteen healthy children were randomised to receive either 3 x 5 micrograms doses or 3 x 10 micrograms doses of Smith Kline Biologicals Engerix B recombinant DNA (rDNA) hepatitis B vaccine into the deltoid muscle at 0, 1 and 6 months. They were tested for seroconversion and levels of antibody to hepatitis B surface antigen (anti-HBs) one month after dose 3. Ninety-nine percent of children in each group seroconverted for anti-HBs. Geometric mean titres (GMT) or anti-HBs in IU/L were higher with 10 micrograms doses. Nevertheless, 3 x 5 micrograms is the appropriate regimen for protecting children in this age group, as long as cost of vaccine remains a major factor in immunisation programmes.

Child

Comparison of the immunogenicity of reduced doses of two recombinant DNA hepatitis B vaccines in New Zealand children.

A group of 201 hepatitis B virus (HBV) sero-negative children 1-12 years of age received either three 2 micrograms doses of Merck Sharp and Dohme (MSD) or Smith Kline and French (SKF) recombinant DNA (rDNA) hepatitis B vaccine I.M. at monthly intervals. Each recipient was tested 4-6 weeks later for antibody to hepatitis B surface antigen (anti-HBs) by enzyme immunoassay (EIA) and radioimmunoassay (RIA). Ninety-six 4-5-year-old children, given 2 micrograms doses of a plasma-derived vaccine (MSD, H-B-Vax) I.M. at 0, 1, 2 months, were tested at the same time with the same assays for comparison. Anti-HBs responses and geometric mean titres (GMT) were significantly higher with the MSDrDNA vaccine (96% and 338.9 IU/liter) than with the SKF/r DNA vaccine (82.3% and 69.4 IU/liter). We conclude that for the protection of young children, 2 micrograms doses of the MSD rDNA hepatitis B vaccine may be used under similar circumstances in which 2 micrograms of the MSD plasma-derived vaccine was used. Further studies are needed before the other rDNA hepatitis B vaccine may be used in lower than the 10 micrograms dose recommended in children.

Child

Hepatitis B virus: the importance of age at infection.

Recent studies have demonstrated the importance of age at infection with hepatitis B virus (HBV). Age affects whether the infection is self-limited or results in the chronic carrier state, the severity of the acute infection, and the incidence of various sequelae of the chronic carrier state. In particular, although the acute infection is more severe in adults, infections in infants and preschool children carry much greater risks of chronic carriage which increases the risk of primary hepatocellular carcinoma and cirrhosis later in life. This has two important implications for areas where HBV is endemic. First, more impact can be gained by vaccinating infants and preschool children than by vaccinating healthy adults. Second, if funds are limited, greater impact will be gained by immunising a larger number of children with low doses of vaccine so that they are protected during the early years of life when the risk of chronic carriage is highest, rather than using the standard dose in a smaller number of children even though protection may be longer lasting with standard doses. These two considerations provide the basis for an efficient strategy for control in communities or countries where HBV is endemic or hyperendemic.

Adolescent