Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice

Before vaccination, Alaska Natives experienced very high rates of invasive Haemophilus influenzae type b (Hib) disease and carriage. Vaccination with Hib conjugate vaccine PRP-OMP (polyribosylribitol phosphate Neisseria meningitidis outer membrane protein) began in 1991 and resulted in a sharp decline in cases. In 1996, after switching to a different Hib conjugate vaccine, DTP-HbOC (which combines diphtheria-tetanus-whole cell pertussis vaccines with HbOC [Hib oligosaccharide CRM197]), cases of invasive Hib disease increased, suggesting ongoing Hib transmission despite widespread vaccination. To determine the prevalence of and risk factors for carriage, a cross-sectional study of oropharyngeal Hib carriage was conducted among Alaska Native children aged 1-5 years in remote southwestern Alaska. Of 496 children with swabs taken, 46 (9.3%) were colonized with Hib. Carriage rates varied by village from 2.2% to 13.2% and by age from 6.1% in 1-year-olds to 14.7% in 5-year-olds. Crowding was associated with Hib carriage. Widespread vaccination with PRP-OMP Hib conjugate vaccine did not eliminate carriage in this population of Alaska Natives, and ongoing carriage contributed to disease resurgence.     

Spectrum of 2,836 cases of invasive bacterial or fungal infections in children: results of prospective nationwide five-year surveillance in Finland. Finnish Pediatric Invasive Infection Study Group

In a prospective nationwide laboratory-based surveillance study of all invasive bacterial and fungal infections among children < 16 years of age, 2,836 clinical cases were registered during the 5-year period 1985-1989. Of these cases, 136 were polymicrobial. During the study period, nationwide administration of Haemophilus influenzae type b conjugate vaccine reduced the incidence rates of invasive infection caused by this organism. The most common clinical diagnosis (48% of cases) was bacteremia without an identified focus of infection. The age-specific annual incidence rates of all invasive infections in children < or = 15 years of age, in children < or = 4 years of age, in children < or = 1 year of age, and in children < or = 28 days of age were 55.8, 141.4, 272.7, and 2,749.0 cases/100,000 person-years, respectively. Thirty percent of the children in the study had an underlying condition predisposing to infection. The case-fatality rate was 4.1% for all cases of invasive infection.     

Pitfalls of hyperfractionation: theoretical considerations of effect of repair time on late radiation damage]

We conducted a 3-year Taiwan-wide hospital-based survey of invasive Haemophilus influenzae infections in children less than 15 years of age. From January 1992 to December 1994, 105 cases (57 boys, 48 girls) were reported. Seventy-three patients (69.5%) had meningitis and 32 patients had other diseases (12 pneumonia, 10 sepsis, 7 cellulitis, 3 arthritis). Fourteen patients (13%) died, all of whom had meningitis or sepsis. Among the 63 patients who survived meningitis, 17 (27%) had neurologic sequelae and eight (47%) had hearing impairment. The number of cases of H. influenzae meningitis (30%) and other H. influenzae diseases (29%) peaked in children between 6 and 12 months of age. Patients with invasive infections (82%) and meningitis (73%) were younger than 24 months of age. Only 12 patients (11%) were older than 5 years of age and four had underlying diseases. The annual incidence of invasive H. influenzae infections in children less than 5 years old was 1.9 per 100,000 per year. During the same period a survey of purulent meningitis in children younger than 15 years of age was also conducted in 20 hospitals. A total of 198 patients, in whom the causative organisms were identified, were included; 94 patients were 2 months of age or under and the most frequent pathogen was group B streptococci (35 cases, 37%). Among the 104 patients who were older than 2 months of age, H. influenzae was the leading cause (38 cases, 37%). In conclusion, invasive H. influenzae type b (Hib) diseases exist in Taiwan but have an incidence lower than in Western countries. Hib meningitis is still the most common cause of purulent meningitis in children in Taiwan and is an important cause of mortality and morbidity. Continuous active surveillance of invasive H. influenzae infections is suggested to determine the best time to introduce an Hib conjugate vaccine in Taiwan.     

Perspective: a five-country analysis of the impact of four different Haemophilus influenzae type b conjugates and vaccination strategies in Scandinavia

Prior to vaccinations against invasive Haemophilus influenzae type b (Hib) diseases in Scandinavia, first initiated in Finland in 1986, the incidence of cases in those five countries was 49/100,000/year in 0- to 4-year-olds and 3.5/100,000 overall. During the following decade, Hib conjugates administered to young children had approximately 95% effectiveness, regardless of which conjugate was used, whether two or three primary doses were administered, and at what age in early infancy the first vaccination was given. The herd immunity effect has extended protection to older age groups. A similar effectiveness of different conjugates in five countries despite considerable diversity in approach suggests that the same impact would occur in other regions with comparable epidemiology. The Scandinavian experience supports the view that three primary vaccine doses are not imperative, thus suggesting that reducing doses of costly Hib vaccines would be one way to facilitate their usage in regions with limited resources.     

Epidemiology of Haemophilus influenzae type b, Neisseria meningitidis, and Streptococcus pneumoniae in children in the Valencia Community, Spain. Acute diseases study group

OBJECTIVE: To asses the incidence of Haemophilus influenzae type b (Hib), Neisseria meningitidis and Streptococcus pneumoniae meningitis in children of de Valencian Community (VC), Spain, and to describe the microbiologic characteristics. MATERIAL AND METHODS: Prospective surveillance system with paediatrician and microbiologist participation of all public hospitals of the VC. Cases are children less than 15 with clinical meningitis and with isolation of Hib, N. meningitidis or S. pneumoniae from CSF of blood. RESULTS: From 1st December 1995 to 30th November 1996, 51 cases were declared, 33.3% were Hib, 49.0% N. meningitidis and 17.7% S. pneumoniae. The annual incidence of meningitis was 7.6 cases/100,000 < 15 years, 20.5/100,000 < 5 years and 56.2/100,000 < 1 year. 84.3% of the cases occurred in children younger than 5. S. pneumoniae had the highest mortality. CONCLUSIONS: Hib is a frequent cause of meningitis in spite of that one third of children are vaccinated. 43% of the N. meningitidis isolated in meningitis are serogroup C. S. pneumoniae meningitis are more frequent in children less than one, and has a high mortality rate.     

The decline of Haemophilus influenzae type b disease in Australia

Between July 1993 and June 1996, there were 412 cases of invasive Haemophilus influenzae type b (Hib) disease reported to the Hib Case Surveillance Scheme, 71% in children under the age of five years. Meningitis was the most frequent illness reported, followed by epiglottitis, septicaemia and pneumonia. There were 18 deaths. Thirty-four cases were classified as vaccine failures. The number of vaccine failures increased over time and the total number of cases of Hib disease fell, consistent with an increase in Hib vaccine coverage. Based on an estimated vaccine coverage of 50% in April 1995, the vaccine efficacy for all vaccines in the period was estimated to be 89%. Invasive Hib is a serious illness of childhood which is being significantly reduced by the use of Hib vaccines, and has the potential to be eliminated from this country. Vaccination providers should aim to immunise all children against Hib disease on time and according to the National Health and Medical Research Council Standard Vaccination Schedule.     

Anterior-inferior capsular length insufficiency in the painful shoulder

BACKGROUND: Haemophilus influenzae type b (Hib) conjugate vaccines have demonstrated an impressive impact in diminishing Hib disease in industrialized countries. However, their high cost prompts nonindustrialized countries to corroborate their effectiveness under local conditions before considering their programmatic implementation. Such a postlicensure evaluation of vaccine effectiveness was undertaken in Chile. METHODS: After its licensure in Chile polyribosylribitol phosphate-tetanus toxoid protein conjugate vaccine (PRP-T), combined with diphtheria-tetanus-pertussis vaccine, was introduced into the Expanded Program on Immunization schedules in 36 health centers throughout metropolitan Santiago for 12 months, whereas 35 similar health centers administered only diphtheria-tetanus toxoid-pertussis vaccine. Bacteriologic surveillance data for invasive Hib cases collected over the ensuing 30 months were analyzed. RESULTS: In an intent-to-vaccinate (effectiveness) analysis, PRP-T provided 90.2% protection (95% confidence interval, 74.5 to 100%) against invasive Hib disease (40 vs. 4 cases, P < 0.001). Vaccine effectiveness was 91.3% against meningitis (22 vs. 2 cases) and 80% against pneumonia and empyema (10 vs. 2 cases, P = 0.039). Vaccine efficacy among infants who received all three doses of PRP-T was 91.7% (95% confidence interval, 64.8 to 100%). CONCLUSIONS: Programmatic use of Hib conjugate vaccine administered in combination with diphtheria-tetanus-pertussis vaccine constitutes a highly effective and practical intervention in Chile, a newly industrializing country.     

Invasive infection with Haemophilus influenzae type b in spite of complete vaccination

Five patients, 4 boys and 1 girl aged 13-41 months, developed invasive Haemophilus influenzae type b (Hib) disease (2 epiglottitis, 3 meningitis) despite full (or at least 3 times) vaccination. At admission as well during convalescence, 3 out of 5 had IgG anti Hib antibody levels < or = 5 U/ml. Serum immunoglobulin levels, including IgG subclasses, as well as complement were normal in all cases. In 2 of the 3, booster vaccinations with Hib conjugate vaccine elicited adequate antibody titres. Since the incorporation of the conjugated Hib polysaccharide tetanus toxoid vaccine (HibTT) in the National Vaccination Programme in the Netherlands, the number of invasive infections caused by Hib has dropped significantly. Causes of Hib conjugate vaccine failures are mostly unknown. In about one-third of the cases serum immunoglobulin levels are deficient, most often IgG2 or IgM. Susceptibility to Hib infection is in part also genetically determined. In the follow-up of Hib vaccine failures, anti Hib antibody titres should be determined. Booster vaccinations may be necessary.     

Potential and limitations of polysaccharide vaccines in infancy

Of infections caused by encapsulated bacteria, those due to Haemophilus influenzae b (Hib) are among the most restricted to infancy and require very early immunisation. Hib capsular polysaccharide (CPS) has the most typical T-cell independent profile. The absence of efficacy of this vaccine in infants triggered development of conjugate vaccines which are so effective that there is now no room for plain polysaccharide Hib vaccines. Pneumococcal infections pose similar problems to Hib, but are more complex. The immunogenicity of the different pneumococcal serotypes varies considerably in infancy. Although the current CPS vaccine provides limited protection in infancy, the burden of pneumococcal infection is so high that its use could be reconsidered should conjugate vaccines be available later than expected. Meningococcal infections are less a specific problem for infants. Again, serogroup immunogenicity varies widely. Group B meningococcal CPS is not immunogenic even in adults, Group C behaves as Hib CPS, whereas Group A is immunogenic as early as 6 months of age. Group A CPS may prove of interest for an infant vaccine, especially in epidemic situations. Typhoid fever is uncommon in infancy; Vi CPS is poorly immunogenic in infancy and is, therefore, of limited interest for use as an infant vaccine.     

Echocardiographic diagnosis of thrombus originating from the ductus arteriosus

OBJECTIVES: This study examined the impact of French routine programs urging the combined measles-mumps-rubella immunization of 15-month-old children. METHODS: We applied a cohort analysis to surveillance data collected by general practitioners to estimate the cumulative incidence rate per 1000 unvaccinated children and the proportion of susceptible children, by age and for each birth cohort between 1985 and 1995. RESULTS: More than 70% of unvaccinated children born in 1985 and 1986 had measles by the age of 10. This incidence rate dramatically decreased after implementation of the routine measles-mumps-rubella immunization program in 1989, but the proportion of 5-year-olds susceptible to measles has not decreased appreciably. In 1996, more than 15% of the children born between 1990 and 1995 were susceptible. CONCLUSIONS: The measles vaccine coverage achieved by the French routine immunization program remains insufficient as regards reducing the number of susceptible children.     

Recent developments in bacterial conjugate vaccines

Study of the epidemiology of childhood infection reveals that the brunt of disease for a number of invasive bacterial infections is borne by children under the age of 4 years. Haemophilus influenzae type b (Hib), Neisseria meningitidis and Streptococcus pneumoniae, the three most important causes of childhood meningitis, illustrate this phenomenon, which is caused by the inability of infants and young children to mount antibodies to the carbohydrates that form a capsule surrounding these organisms. Carbohydrates are traditionally viewed as T-independent antigens with a number of unique and important immunological properties that are not encountered when inducing an immune response to proteins. These properties include no overt requirement for the presence of T cells to induce an immune response, dominance of IgM, failure to induce memory following immunisation, an absence of affinity maturation following immunisation, and poor immunogenicity in infants, the elderly and the immunocompromised. These properties of carbohydrates have precluded the use of pure carbohydrate vaccines in those patients most at risk. Conjugate vaccine technology, where a carbohydrate antigen is coupled chemically to a protein carrier, has overcome the limitations of carbohydrates as vaccine antigens by rendering the carbohydrate moiety of such vaccines immunogenic, even in the very young. The dramatic success of the Hib conjugate vaccines, the first conjugates licensed clinically for human use, in reducing the incidence of invasive Hib disease has demonstrated the potential value of such conjugate vaccines. Similar technology is, therefore, being applied to a number of other vaccines in development, including N. meningitidis (groups A and C) and S. pneumoniae vaccines. The large number of pneumococcal carbohydrate serotypes that require inclusion in a vaccine makes this conjugate formulation far more complicated than that for Hib, and it is likely that the dramatic success of the Hib conjugate vaccines will be more difficult to repeat for the pneumococcus.     

EMLA cream provides rapid pain relief for the curettage of molluscum contagiosum in children with atopic dermatitis without causing serious application-site reactions

BACKGROUND: Determination of the etiology of pneumonia in young children is difficult because blood culture, the usual method of diagnosis, is positive in only a small proportion of cases. For this reason vaccine trials that include bacterial pneumonia as an endpoint must be large. OBJECTIVES: To determine whether a diagnostic test based on a polymerase chain reaction could be used as an alternative to conventional blood culture for diagnosis of invasive Haemophilus influenzae type b (Hib) infections in young children investigated during the course of a large vaccine trial. METHODS: DNA was extracted from blood culture supernatants and probed for the presence of Hib DNA with a PCR assay with primers derived from the cap gene locus of Hib. Results of the PCR assay were compared with those obtained by conventional culture techniques. RESULTS: Blood cultures were obtained from 1544 children with suspected pneumonia, meningitis or septicemia and from 31 healthy control children who were contacts of cases. Blood culture supernatants were tested for Hib DNA in the PCR test. The sensitivity and specificity of a positive PCR test in blood culture supernatant as against culture of Hib from any normally sterile site were 100 and 99%, respectively. Eleven children had positive Hib PCR tests on blood culture supernatants but were negative by culture. In one of these cases Hib was isolated from a lung aspirate and in two other patients H. influenzae strains other than Hib were obtained from the cerebrospinal fluid. Eight of these 11 children were in the control group. When the results of the PCR assay were used to determine vaccine efficacy, a value of 86% was obtained compared with a figure of 95% obtained when conventional culture techniques were used. CONCLUSIONS: An Hib PCR assay on blood culture supernatants proved to be sensitive and specific for the diagnosis of Hib disease in children. The distribution of PCR-positive, culture-negative cases between Hib-vaccinated and control groups paralleled that of culture-positive cases, suggesting that most of these children had been infected with Hib. A trial of a highly efficacious vaccine provides a novel way for evaluating new diagnostic tests for which there is no standard diagnostic test of 100% reliability.     

Alterations in myelin formation in fetal brains of twins

AIM: To study the epidemiology of invasive pneumococcal infections in infants and young children in Santiago, Chile, as a representative pediatric population in a newly industrializing country where pneumococcal conjugate vaccines may be used in the future. METHODS: A 5-year retrospective laboratory-based review (1989 to 1993) was followed by a 3-year prospective laboratory and hospital surveillance study in two of the six health administrative areas of Santiago to detect all hospitalized cases of invasive pneumococcal disease (defined as Streptococcus pneumoniae isolated from blood, cerebrospinal fluid or another normally sterile site) among infants and children (0 to 23 months of age in the retrospective and 0 to 59 months of age in the prospective study). RESULTS: During the 5-year retrospective survey the incidence of invasive pneumococcal disease was 90.6 cases per 10(5) infants 0 to 11 months old and 18.5 cases per 10(5) toddlers 12 to 23 months old. Similar rates (60.2 per 10(5) infants and 18.1 per 10(5) toddlers) were recorded during the 3 years of prospective surveillance. Among the 110 cases in children 0 to 59 months of age detected during the 3-year prospective surveillance, 2 clinical forms, pneumonia and meningitis, accounted for 87.2% of all cases; 13 of the 49 pneumonia patients (26%) had empyema as a complication. Notably 40 of the 110 cases (36.4%) occurred before 6 months of age (63.4% of the 63 infant cases). Serotypes 1, 14, 5 and 6B were the most prevalent. Overall 76 and 69%, respectively, of S. pneumoniae isolates were antigenic types that would be covered by the 11- or 9-valent conjugate vaccines under development. CONCLUSIONS: Invasive pneumococcal infections in Santiago, Chile, exhibit an epidemiologic pattern intermediate between that of developing and industrialized countries. The high burden of disease in early infancy dictates that an accelerated immunization schedule (beginning in the perinatal period) or maternal immunization with pneumococcal vaccines should be explored.     

Haemophilus influenzae type b osteoarthritis. A report of 7 cases and a review of the literature

OBJECTIVE: The epidemiological and clinical characteristics, treatment and evolution of osteoarthritis by Haemophilus influenzae type b (HIB) are reviewed since there has been little published on this subject in our country. PATIENTS AND METHODS: The clinical histories of the 7 children with osteoarthritis due to Hib infection are reviewed. The diagnostic criteria included classical signs and symptoms of septic arthritis, radiological alterations compatible with joint infection and isolation of microorganisms in joint effusion and/or in the blood. RESULTS: During a 24-year period (1973-1996), 248 cases of invasive infection by Hib were documented. Seven cases (2.82%) had osteoarticular infections. The ages were between 5 and 7 years and there were more males than females (71.4% vs. 28.6%). Four children/58%) had previous upper respiratory infections (URI). The microorganism was isolated in the joint effusion in 5 children and in the blood sample of the other 2. C-reactive protein was high and radiology showed alterations in 100% of the cases. Surgical treatment with articular drainage was necessary in 5 children/71.4%). In 6 cases (85.7%) initial medical treatment was i.v. beta-lactam antibiotics for 2-3 weeks followed by oral antibiotic treatment for a minimum of 6 weeks. Three children (42.8%) had sequelae. CONCLUSIONS: Early diagnosis of bacterial osteoarthritis by Hib is difficult. Final therapeutical success depends on an early clinical diagnosis and aggressive multidisciplinary treatment. Drainage of the hip joint is mandatory for successful outcome. Currently, arthritis by Hib can be avoided and its sequelae prevented by vaccination.     

Haemophilus influenzae type b-specific antibody in infants after maternal immunization

OBJECTIVE: To study the kinetics of Haemophilus influenzae type b (Hib)-specific antibody in infants born to mothers immunized with an Hib polysaccharide or one of two Hib conjugate vaccines. STUDY DESIGN: Serum antibody to the polyribosylribitol (PRP) moiety of Hib was measured by radioimmunoassay and enzyme-linked immunosorbent assay at birth and at 2 and 6 months of age in infants born to women immunized with Hib polysaccharide or conjugate vaccine (PRP-D and HbOC). A subset of infants > or = 6 months of age was immunized with Hib conjugate vaccine after licensure of this vaccine for infants. A comparison group of 18 infants born to unimmunized women received the same Hib conjugate vaccine on a similar schedule. RESULTS: Total PRP antibody concentrations were 1.50, 14.4 and 20.4 microg/ml in 2-month-old infants born to mothers immunized with polysaccharide, PRP-D and HbOC vaccines, respectively, and 2.54, 1.35 and 2.46 microg/ml in 6-month-old infants. Infants born to mothers immunized with polysaccharide vaccine had significantly less PRP antibody at 2 months of age but similar antibody concentrations at 6 months of age. Persistence or increases in total PRP antibody during 6 months were noted in 21 of 47 (44.6%) study infants. A subset of study and comparison infants was immunized with a mean of 2.6 doses of Hib vaccines between 6 months and 2 years of age, and all infants had total PRP antibody concentrations > or = 0.15 microg/ml. CONCLUSION: Conjugate Hib vaccines administered during the last trimester of pregnancy resulted in significantly higher PRP antibody titers in infants at birth and 2 months of age than did polysaccharide vaccine. A subset of infants born to immunized mothers was subsequently immunized with Hib conjugate vaccine and had antibody concentrations similar to those in infants born to nonimmunized women.     

Preclinical studies on a recombinant group B meningococcal porin as a carrier for a novel Haemophilus influenzae type b conjugate vaccine

In anticipation of future combination vaccines, a recombinant class 3 porin (rPorB) of group B meningococci was evaluated as an alternative carrier protein for a Haemophilus influenzae type b (Hib) polyribosylribotol phosphate (PRP) conjugate vaccine. The use of rPorB may avoid undesirable immunologic interactions among vaccine components, including epitopic suppression from conventional carriers (e.g. tetanus toxoid [TT]), as well as provide desirable immunomodulatory effects. Rats were found to be more reliable and consistent than mice or guinea pigs for studying antibody responses to the Hib conjugates. Different Hib conjugates, Hib-TT and Hib-rPorB, consisting of PRP conjugated by reductive amination to TT or rPorB, were compared in rats. Commercially available, licensed vaccines, HbOC (HibTITER) and PRP-T (OmniHib), were used as reference controls. Maximum geometric mean ELISA IgG titers were obtained in rats after only two doses, showing booster effects for all. However, Hib-rPorB immunization consistently resulted in responses that were 1-2 orders of magnitude greater than those for the other conjugates, including the licensed control vaccines. A maximum 4600-fold rise was observed for Hib-rPorB after two doses, and, unlike the other conjugates, a 100% response rate was always achieved without adjuvant. These results warrant further investigation of Hib-rPorB in combination with DTaP.     

Where''s the cash?

This study was done to analyze the epidemiology of invasive Haemophilus influenzae disease in Bochum city area. Forty-eight children with invasive Haemophilus influenzae infections were treated at the University Children's Hospital in Bochum during the study period from January 1971 to June 1992. Clinical manifestations included meningitis (n = 34), epiglottitis (n = 8), pneumonia (n = 2), bacteremia (n = 2), cellulitis (n = 1) and osteomyelitis (n = 1). The overall yearly incidence rate for all invasive Haemophilus influenzae infections was 13 per 100,000 children younger than five years of age, with a marked increase in the last six years. Haemophilus influenzae meningitis showed no significant change during the study period with an overall yearly incidence of 9 per 100,000 children younger than five years. Twenty-eight cases (58%) of all invasive Haemophilus influenzae infections occurred in patients under two years of age and five cases (10%) were younger than six months. Invasive Haemophilus influenzae disease showed no seasonal prevalence. All isolates were susceptible to ampicillin. No deaths occurred, but severe bilateral deafness resulted in one patient with meningitis. Prospective epidemiologic studies are needed to estimate clinical efficacy of the Haemophilus influenzae type b immunization program in Germany.     

The immunogenicity of three Haemophilus influenzae type B conjugate vaccines after a primary vaccination series in Philippine infants

Serum antibody responses to three Haemophilus influenzae type b (Hib) capsular polysaccharide-protein conjugate vaccine (PRP-OMP, PRP-T, and HbOC) were evaluated in 174 Philippine infants after a primary vaccination series. Children were randomized to receive one of the Hib vaccines (Hib groups) or into a control group. Vaccination was carried out at six, 10 and 14 weeks of age based on the local Expanded Program of Immunization schedule. Sera were collected at six weeks of age for the Hib groups and one month after the third dose for all subjects. Anti-Hib concentrations were determined by the Farr-type radioimmunoassay. There were no significant differences (P = 0.3626) in the prevaccination anti-Hib geometric mean concentration (GMC) among the three Hib groups. Differences in the GMC after the primary series of three doses were significant (P < 0.0001); GMC was highest for PRP-T (6.62 micrograms/ml), followed by HbOC (1.9 micrograms/ml), then PRP-OMP (1.06 micrograms/ml), and lowest for the control group (0.11 microgram/ml). We conclude that all three Hib conjugate vaccines (PRP-T, HbOC, and PRP-OMP) were immunogenic after three primary doses among Philippine infants.     

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.     

An economic analysis of alternatives for childhood immunisation against Haemophilus influenzae type b disease

Cost-effectiveness and cost-utility analyses of immunisation strategies against invasive Haemophilus influenzae type b (Hib) disease in Australia were based on a hypothetical birth cohort of 250,000 non-Aboriginal Australian children. The model predicted that, without immunisation, 625 cases of invasive Hib disease would occur in under-five-year-olds, with direct costs of $10.2 million. Universal public sector vaccination beginning before six months of age (6MVAC) prevented 80 per cent of cases; vaccination at 12 months (12MVAC) 62 per cent and at 18 months (18MVAC) 46 per cent. At a vaccine cost of $15 per dose, 18MVAC gave the lowest cost per quality-adjusted life year (QALY) over a wide range of model assumptions, with 6MVAC the 'best' alternative. The best estimate ($ per QALY) for 6MVAC was $6930 (three doses), for 12MVAC $9136 (two doses) and for 18MVAC $1231 (one dose). The cost per QALY of single dose catch-up immunisation of older children was estimated at $8630 at two years, $27,000 at three years and $117,000 at four years if done at a scheduled visit; these values were increased if an additional medical visit was included. The threshold cost per vaccine dose at which an immunisation program became cost-saving was estimated for 6MVAC, 12MVAC and 18MVAC as $11, $10 and $14. Even under a worst-case scenario, an immunisation program at 6, 12 or 18 months became cost-saving if indirect costs of death were included. Comparison with previous analyses revealed the importance of the incidence and age distribution of disability and assumptions about vaccine administration costs in determining model outcomes.