Epidemiology of invasive Hemophilus influenzae B infections in Bedouins and Jews; conjugate Hib vaccines

From 1989 to 1996, 139 cases of invasive Hemophilus influenzae B (Hib) infections were identified in children in the Negev, 110 of which occurred before introduction of the conjugate vaccine (1989-92). At that time there were 60.5 cases of Hib per 100,000 in the Negev among children under 5 years of age. During 1995-1996, when Hib conjugate vaccine was part of the regular immunization program, Hib decreased to 6.5 cases per 100,000 in that age group. The effectiveness of PRP-OMP vaccine was 96.5% among Jews and 89% among Bedouins, and the efficacy of the immunization program was 99.99%. This degree of success exceeded all expectations based on the literature. During the whole study period, Hib infections were more frequent among Bedouins than Jews. There was no significant difference in the occurrence of Hib among Jews in the Negev before and after the vaccine was introduced. Hib among Bedouins in the Negev was significantly more frequent than in the Israeli population as a whole before the vaccine was introduced. That gap narrowed after the vaccine was introduced because of the decrease in morbidity among the 2 groups.     

Comparative study of the genomic organization of DNA repeats within the 5''-flanking region of the natural resistance-associated macrophage protein gene (NRAMP1) between humans and great apes

CONTEXT: Use of the quadrivalent meningococcal vaccine for control of outbreaks has increased in recent years, but the efficacy of meningococcal vaccine during mass vaccination campaigns in US civilian populations has not been assessed. OBJECTIVES: To evaluate the efficacy of the quadrivalent meningococcal vaccine against serogroup C meningococcal disease in a community outbreak setting and to evaluate potentially modifiable barriers to vaccination in an area with persistent meningococcal disease following immunization. DESIGN: Matched case-control study of vaccine efficacy using cases of serogroup C meningococcal disease in persons eligible for vaccination during mass vaccination campaigns. Control patients were matched by neighborhood and age. The control group was used to identify possible barriers to vaccination. SETTING: Gregg County, Texas, population 106076, from 1993 to 1995. PARTICIPANTS: A total of 17 case patients with serogroup C meningococcal disease eligible for vaccine and 84 control patients. MAIN OUTCOME MEASURES: Vaccine efficacy and risk factors associated with nonvaccination. RESULTS: Vaccine efficacy among 2- to 29-year-olds was 85% (95% confidence interval, 27%-97%) and did not change in bivariate analyses with other risk factors that were significant in univariate analysis. Among control patients, older age was strongly associated with nonvaccination; vaccination rates for 2- to 4-year-olds, 5- to 18-year-olds, and 19- to 29-year-olds were 67%, 48%, and 20%, respectively (chi2 for linear trend, P=.01). CONCLUSIONS: The meningococcal polysaccharide vaccine was effective against serogroup C meningococcal disease in this community outbreak. Although specific barriers to vaccination were not identified, older age was a risk factor for nonvaccination in the target population of 2- to 29-year-olds. In future outbreaks, emphasis should be placed on achieving high vaccination coverage, with special efforts to vaccinate young adults.     

Contrast sensitivity in patients with silicone intraocular lenses

Meningococcal clone ET-15/37, which appeared as a new one in the Czech Republic in 1993, caused an emergency epidemiological and clinical situation in invasive meningococcal disease, characterized by a high fatality rate (20%) compared to the "normal" fatality rate due to "non ET-15/37" strains. Morbidity rate increased since the first year of the new clone occurrence and reached the peak in 1995. This clone has spread all over the country and investigation of the epidemiological markers of Neisseria meningitidis allowed to quickly recognize the emergency situation and subsequently to provide a targeted vaccination with A + C polysaccharide meningococcal vaccine which prevented the spread of the disease caused by Neisseria meningitidis C. The most frequent phenotype of ET-15/37 clone was C:2a:P1.2(P1.5) and its percentage achieved 80% of group C Neisseria meningitidis strains tested. This antigenic shift of Neisseria meningitidis was associated with the age shift in invasive meningococcal disease morbidity: teenagers started to be the most affected age group and later age group of 1-4 olds followed with high morbidity rates. In 1995 B variant of ET-15/37 clone, B:2a:P1.2(P1.5), appeared, causing a high fatality rate, too. Some data are indicative of a possible decrease in the invasive meningococcal disease incidence in the Czech Republic; nevertheless, the active surveillance and detailed investigation of meningococci have to be continued. After four years following the vaccination and chemoprophylaxis strategy recommended in the Guidelines, set up by the National Reference Laboratory for Meningococcal Infections in 1993, it is possible to conclude, that there have been practically no secondary cases of invasive meningococcal disease in the Czech Republic.     

A measles epidemic controlled by immunisation

AIM: In 1997, an immunisation campaign, using measles-mumps-rubella vaccine, was planned for children aged 2-10 years to prevent a measles epidemic predicted by mathematical modelling. The epidemic started before the campaign and is described here. METHOD: Measles hospitalisation, notification and laboratory data were combined. RESULTS: The epidemic started in April 1997 and was largely over by January 1998. No deaths were identified and only one hospitalisation was coded as measles encephalitis, compared to seven deaths and ten cases of measles encephalitis in the 1991 epidemic. For the 12 months from 1 March 1997 there were 2,169 (60 per 100,000) measles cases identified, 314 (9 per 100,000) of whom were hospitalised. Two-thirds of hospitalised cases were notified. The age-standardised measles incidence rates were 33, 34, and 174 per 100,000 for Europeans, Maori and Pacific people, respectively. The respective age-standardised hospitalisation rates were 4, 9 and 32 per 100,000. Measles incidence was highest for under one-year-olds (904 per 100,000) and low for 11-16 year-olds (27 per 100,000)--the cohort previously offered a second vaccine dose. Most cases were aged 10 years and under, and this group were the main drivers of virus transmission. CONCLUSIONS: The immunisation campaign prevented 90-95% of predicted cases. The campaign was appropriately targeted at children aged 10 years and under.     

Age-related immunogenicity of meningococcal polysaccharide vaccine in aboriginal children and adolescents living in a Northern Manitoba reserve community

OBJECTIVE: To determine the total and functional serogroup C antibody response to a quadrivalent meningococcal polysaccharide vaccine in a group of aboriginal infants, children and adolescents. A secondary objective was to determine their prevalence of meningococcal carriage. DESIGN: Open prospective, before and after intervention study. SUBJECTS: Aboriginal children ages 0.5 to 19.9 years, living in a single Northern community and eligible for a public health immunization campaign conducted in all Manitoba native reserve communities to control a meningococcal serogroup C, electrophoretic type (ET) 15 outbreak. No outbreak cases had occurred in the community at the time of the study. METHODS: Total serogroup C capsular polysaccharide antibody (CPA) and functional bactericidal antibody (BA) responses were measured by enzyme-linked immunosorbent assay and bactericidal assay, respectively. RESULTS: Neisseria meningitidis was recovered from the oropharynx of 13 (5.2%) of 249 aboriginal children including 4 (1.6%) serogroup C isolates, all with the designation C:2a:P1.2,5 ET15. Paired sera from 152 children were available for assay. For CPA the geometric mean concentrations and proportions with > or =2 microg/ml before and after immunization were 0.69, 18% and 12.3, 96%, respectively. A significant increase in serum CPA was achieved by children of all ages, with the greatest response occurring after age 11 years. Among infants < lyear old 89% achieved concentrations of > or =2 microg/ml. For BA the pre- and post-vaccine geometric mean titers were 1.02 and 45.9. The response was significantly associated with age. BA titers > or =1:8 were present, before and after immunization, respectively, in 0 and 0% of infants <1 year old, 0 and 20% of 1- to 1.4-year-olds, 0 and 50% of 1.5- to 1.9-year-olds and 1 and 100% of > or =2-year-olds. CONCLUSION: The age-related total and functional group C meningococcal antibody response after quadrivalent polysaccharide vaccine among aboriginals is similar to that reported for Caucasian children. After age 2 all children made excellent CPA and BA responses. In the younger age groups the BA response was blunted but 82 to 95% achieved CPA titers of > or =2 microg/ml.     

Decline in meningococcal antibody levels in African children 5 years after vaccination and the lack of an effect of booster immunization

Antibodies to group A meningococcal polysaccharide were measured by hemagglutination (HA) and by ELISA in sera obtained from Gambian children before vaccination and 3 weeks, 2 years, and 5 years after vaccination with a group A + group C meningococcal capsular polysaccharide vaccine. Children were 1-4 years old at the time of vaccination. Most showed a good initial response to vaccination, including those aged 1-2 years. However, antibody titers declined progressively during follow-up, and 5 years after vaccination, antibody titers measured by both HA and ELISA had returned to prevaccination levels. This decline was not influenced significantly by a booster dose of vaccine given 2 years after initial immunization. Administration of malaria chemoprophylaxis reduced the rate at which antibody levels fell after initial immunization. Sustained protection of children against group A meningococcal disease will require the development of vaccines that are immunogenic in infants and that can induce T cell memory.     

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.     

The relationship between fatty liver and hyperinsulinemia in obese Japanese children

During 1994, 603 cases of bacterial meningitis were reported in Italy. Seventy-five percent of cases with determined etiology was due to three agents: Neisseria meningitidis (33.4%), Streptococcus pneumoniae (23.4%) and Haemophilus influenzae (18.6%). The majority of cases due to N. meningitidis and H. influenzae occurred in subjects below five years of age (35.7% and 84.8%, respectively) while S. pneumoniae accounted for 52.8% of meningitis cases in subjects older than 44 year of age. The estimated incidence of N. meningitidis on the national population in 1994 was 0.27 per 100,000. Serogroup B accounted for 62.5% of the serotyped isolates, group C for 23.1%, group A for 7.2%, group W135 for 3.6%, group Y for 1.8%. All tested meningococcal strains were susceptible to penicillin as well as to rifampin. Incidence of meningococcal meningitis in 1994 has been low suggesting that its relative importance compared to other bacteria causing meningitis is likely to change in the future. Therefore, extended surveillance on bacterial meningitis by other etiological agents has to be maintained and implemented in order to undertake the appropriate control measures and evaluate their effect.     

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.     

Effect of levodopa therapy on visual evoked potentials and visual acuity in amblyopia

Between 10 and 11 years after children were vaccinated with Vi capsular polysaccharide of Salmonella typhi or meningococcal A + C control vaccine in a double blind randomized trial, we traced 83 subjects, aged 16-20 years. A blood sample was taken for determination of Vi antibody titres in both groups by radioimmunoassay. TO and TH titres were also done to assess if the participants had had recent exposure to typhoid fever. Fifty-eight percent of subjects in both groups had protective levels of Vi antibody against Salmonella typhi (a titre greater than 1 microgram ml-1). There was no significant difference in the levels of Vi antibodies in the cases versus the controls (p = 0.5). Two of the children who had received meningococcal A + C vaccine had recently had typhoid fever. Our data show that adolescents in typhoid endemic areas have high levels of Vi antibodies regardless of previous vaccination status, suggesting that Vi antibodies are acquired in adolescence by a large percentage of the population in this area. Moreover, Vi vaccination has led to ongoing antibody production in greater than 50% of Vi vaccinated children in an endemic area for a period of 10 years. Ongoing antigenic exposure may have contributed to these antibody levels.     

Molecular epidemiology of sporadic (endemic) serogroup C meningococcal disease

Understanding the basis of sporadic (endemic) meningococcal disease may be critical to prevention of meningococcal epidemic outbreaks and to understanding fluctuations in incidence. Active, prospective, population-based surveillance and molecular epidemiologic techniques were used to study sporadic serogroup C meningococcal disease in a population of 2.34 million persons (Atlanta area). During 1988-1994, in which no outbreaks or case clusters were reported, 71 patients developed sporadic serogroup C meningococcal disease (annual incidence, 0.51/100,000). Eighty-three percent of patients were >2 years old. By multilocus enzyme electrophoresis, pulsed-field gel electrophoresis, and serotyping, 84% (52/62) of the isolates available for study were identical or closely related members of the electrophoretic type 37 (ET 37) complex responsible for multiple serogroup C outbreaks in the United States in the 1990s. Sporadic disease caused by 9 clonal strains occurred over periods up to 4 years and accounted for 45% (28/62) of cases. Sporadic serogroup C meningococcal disease was most often due to a limited number of related strains that appear to slowly circulate in the population.     

Serogroup Y meningococcal disease in Chicago, 1991-1997

CONTEXT: In 1994, surveillance by the Chicago Department of Public Health detected a growing trend in the proportion of invasive meningococcal infections caused by serogroup Y. OBJECTIVE: To examine the emergence of serogroup Y meningococcal disease and compare its clinical characteristics with those of other meningococcal serogroups. DESIGN: Population-based retrospective review of surveillance records; medical record review and cohort analysis of serogroup Y vs non-serogroup Y case patients. SETTING: Chicago, III. PARTICIPANTS: City residents with Neisseria meningitidis isolated from a normally sterile site from January 1, 1991, through December 31, 1997; cohort analysis included those identified through March 31, 1996. MAIN OUTCOME MEASURES: Serogroup-specific incidence, demographics, and clinical outcomes. RESULTS: We identified 214 case patients; 53 (25%) had serogroup Y. The attack rate of serogroup Y meningococcal disease increased from 0.04 cases per 100000 in 1991 to a peak of 0.82 cases per 100000 in 1995 and subsequently decreased to 0.26 cases per 100000 and 0.34 cases per 100000 in 1996 and 1997, respectively. Compared with patients infected by other serogroups, patients with serogroup Y were older (median age, 16 years vs 1 year; P = .001) and more likely to have a chronic underlying illness (prevalence ratio, 2.3; 95% confidence interval, 1.2-4.4). Outcome did not differ significantly between the 2 groups. Multilocus enzyme electrophoresis typing of isolates from 19 case patients identified 5 different types. We found no clustering among the enzyme types by age, race/ethnicity, community area, or time. CONCLUSIONS: Serogroup Y emerged as the most frequent cause of meningococcal disease in Chicago in 1995 and accounted for a substantial proportion of cases in 1996 and 1997. Current data suggest that the magnitude of serogroup Y meningococcal disease is sufficient for vaccine developers to incorporate serogroup Y into new vaccines.     

Induction of immunologic refractoriness in adults by meningococcal C polysaccharide vaccination

Thirty-four adults were vaccinated with 1/50 of the usual dose of meningococcal polysaccharide vaccine (1 microg of A, C, Y, and W135 polysaccharides, given intramuscularly). This dose was selected as a probe to assess B cell memory. The probe elicited meningococcal C bactericidal antibody responses in all 18 adults who had been vaccinated 4 years earlier with an investigational meningococcal A and C oligosaccharide-protein conjugate vaccine and in the majority of the 11 subjects vaccinated for the first time. In contrast, the responses of the 5 adults given a full dose of licensed polysaccharide vaccine 4 years earlier were <1/10 of those of the other 2 groups. Thus, adults previously given a full dose of meningococcal polysaccharide vaccine show evidence of immunologic refractoriness to group C polysaccharide, whereas refractoriness is not observed after conjugate vaccination. These findings have implications for the use of meningococcal polysaccharide vaccine when the risk of disease is low.     

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.     

Changes in clinical and epidemiologic characteristics in Western Bohemia of invasive meningococcal disease associated with the occurrence of an invasive clone of Neisseria meningitidis

The authors analyzed the incidence of meningococcal diseases in the West Bohemian region in 1982-1996. The draw attention to changes of clinical and epidemiological characteristics of the disease which appeared in 1994 in conjunction with a new invasive clonus of Neisseria meningitidis C:2a:P1.2, P1.5, ET-15/37. While in 1982-1993 invasive meningococcal diseases had in 75% the course of meningitis with a relatively low fatality (4%), during the subsequent period a marked change occurred. Since 1994 the disease took in the West Bohemian region in 58% the course of sepsis with a fatality of 16%. 25% cases of meningococcal meningitis were diagnosed combined sepsis and meningitis in 17%. The disease lost its seasonal character and the authors confirmed the highest incidence of the disease in the age group from 15-19 years and 0-4 years. Neisseria meningitidis group C was detected in 1994-1996 in 73% and the invasive clone C:2a:P1.2, P1.5, ET-15/37 in 62%.     

Meningococcal disease epidemiology and control in New Zealand

Epidemiology, surveillance and research New Zealand has a high quality surveillance system for meningococcal disease that successfully integrates notification and laboratory data. Since 1991, New Zealand has had elevated incidence rates of meningococcal disease rising to 6.2 per 100,000 population in 1994. This represents a rate that is four times that recorded in 1989/90. Serogroup B infection predominates and international experience suggests that these elevated rates may continue for 5 to 15 years. Rates of meningococcal disease in Maori and Pacific Islands populations were three times higher than in Europeans at 10.0 and 12.3 per 100,000 respectively in 1994. The rates were particularly high for infants with the rate in Maori infants under 1 year reaching 120 per 100,000. The case fatality rate at 5.3% for 1994 would appear to be relatively low by international standards. Case control studies could be used to investigate potentially modifiable primary risk factors for disease. Intensive case review studies to investigate the role of such factors as preadmission antibiotics in reducing severe outcomes may be of benefit. The Ministry of Health or research funding organisations should consider the potential value of such studies in more detail.     

Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial

CONTEXT: Meningococcal polysaccharide vaccines are not used routinely in infants and toddlers, the groups at highest risk of invasive disease, because of poor immunologic responses to the Neisseria meningitidis serogroup C polysaccharide in these age groups. Meningococcal C conjugate vaccines offer the prospect of circumventing this problem. OBJECTIVE: To assess the immunogenicity and the induction of immunologic memory in toddlers by meningococcal C conjugate vaccine. DESIGN: A multicenter, randomized, observer-blinded controlled trial. SETTING: Urban and suburban family medicine or pediatric practices. PARTICIPANTS: Two hundred eleven healthy toddlers aged 15 to 23 months. INTERVENTION: Two injections at 2 months apart of meningococcal C conjugate (group 1, n = 69), plain meningococcal polysaccharide (group 2, n = 72), or hepatitis B virus vaccine (group 3, n = 70). All toddlers received a follow-up dose of plain meningococcal polysaccharide vaccine 12 months later. MAIN OUTCOME MEASURES: IgG meningococcal C anticapsular antibody concentrations determined by enzyme-linked immunosorbent assay and complement-mediated bactericidal antibody. RESULTS: In group 1, the magnitude of the IgG response to meningococcal C conjugate vaccine was more than 4-fold higher after dose 1 and more than 10-fold higher after dose 2 compared with meningococcal polysaccharide vaccine (group 2) (P<.001). Higher titers persisted in the meningococcal C conjugate group for at least 12 months (P<.001). Group 1, primed with meningococcal C conjugate, had 25-fold higher IgG responses to the meningococcal polysaccharide 1-year booster dose than the controls who had received hepatitis B virus vaccine initially and were given meningococcal polysaccharide vaccine 1 year later for the first time (P<.001). In contrast, group 2, primed with meningococcal polysaccharide, had a 2-fold lower response to the 1-year booster meningococcal polysaccharide dose than the hepatitis B virus control group (P = .006). Serum bactericidal responses paralleled the enzyme-linked immunosorbent assay responses. CONCLUSIONS: Immunization of toddlers with meningococcal C conjugate vaccine induces high titers of anticapsular and bactericidal antibody. Furthermore, this vaccine induces immunologic memory to meningococcal C polysaccharide. In contrast, meningococcal polysaccharide vaccine is less immunogenic than the conjugate vaccine and also induces a hyporesponsive state that persists for at least 12 months.     

Prevention and control of hepatitis B virus infection in Singapore

Hepatitis B virus (HBV) accounted for 24% to 54% of the reported acute viral hepatitis cases in Singapore from 1982 to 1996. The prevalence of HBV infection, as indicated by the presence of markers of HBV, increased from 9.3% in children below 5 years of age to 54.6% in adults above 55 years. The overall hepatitis B surface antigen (HBsAg) prevalence was 5.7% for males and 3.4% for females, with the highest rate among the Chinese. About 39% of the HBsAg carriers were hepatitis B 'e' antigen positive. The main mode of transmission during the first year of life was perinatal, with 43% of the babies born to HBsAg-positive mothers developing the carrier state. Horizontal transmission within the infected household was significantly associated with sharing of personal and household articles. Based on the findings of seroprevalence surveys in various population groups and clinical trials on the safety, immunogenicity and efficacy of various doses and schedules with the plasma-based and yeast-derived hepatitis B vaccines in newborn babies, a national childhood hepatitis B vaccination programme was formulated and implemented in phases, starting with babies born to carrier mothers on 1 October 1985 and finally extending to all newborns on 1 September 1987. The hepatitis B prevention and control programme has been successful. During the period 1994 to 1996, more than 90% of children completed the full schedule of immunisation by below one year of age, and 85% had evidence of vaccination at school entry at age six. Follow-up of 2 cohorts of vaccinated children showed that perinatal transmission has been reduced by 80% to 100%. Horizontal transmission has also declined through other public health measures. The efficacy of the hepatitis B vaccine and the adequacy of reduced doses in the long-term protection of chronic carrier state have been shown in children and adults. The incidence of acute hepatitis B has declined from 10.4 per 100,000 in 1985 to 4.8 per 100,000 in 1996. There is a noticeable reduction in HBsAg prevalence in selected population (school children, national servicemen and antenatal women). The age-standardised incidence rate of primary liver cancer among males had also dropped from 27.8 per 100,000 per year during 1978 to 1982 to 19.0 per 100,000 per year during 1988 to 1992.     

Prospective study of bacterial meningitis in North East Thames region, 1991-3, during introduction of Haemophilus influenzae vaccine

OBJECTIVE: To describe the epidemiology of primary bacterial meningitis in the North East Thames region over a three year period before and during the introduction of the vaccine for Haemophilus influenzae type b. DESIGN: Analysis of information on cases of primary bacterial meningitis identified by microbiology laboratories in the region, with collection of case data by questionnaire. MAIN OUTCOME MEASURES: Annual incidence rates for types of meningitis according to age and ethnic group. RESULTS: The annual incidence rates for the three major causes of bacterial meningitis in the general population were 1.9/100,000 for Neisseria meningitidis, 1.6/100,000 for Haemophilus influenzae before vaccination, and 1.0/100,000 for Streptococcus pneumoniae. Higher rates of H influenzae meningitis were found in Asians compared with white people (3.6/100,000 v 1.5/100,000, P = 0.01). As a result of the vaccine programme introduced in October 1992 the number of cases of H influenzae meningitis in children under 5 years has fallen by 87%. CONCLUSIONS: Bacterial meningitis is a serious problem especially in preschool children. There are differences in the incidence of some causes of bacterial meningitis in different ethnic groups; with H influenzae type b being significantly more common among black and Asian people than among white people. The immunisation programme for H influenzae type b in the North East Thames region has been successful in reducing the incidence of this type of meningitis in Asian and white populations. The numbers were too small to evaluate in the black population.     

Association of class I HLA antigens with invasive meningococcal disease

BACKGROUND: The majority of meningococcal infections are characterized by nasopharyngeal carriership. In some patients invasive disease with a mild course develops, while some cases have a lethal outcome. The reasons of this wide variation range are not clear. The objective of the present work was to assess whether the development of invasive meningococcal disease or its prognosis are associated with HLA class I. METHODS AND RESULTS: The group of patients was formed by 40 patients (29 females, 11 males, mean age 16 years, range 8 months to 52 years). In 28 patients the disease was caused by N. meningitidis group C, in 9 cases group B, in three cases the serotype was not assessed. The etiology was confirmed by cultivation or latex agglutination. Twenty-three patients had a mild course of the disease, 8 a medium severe one, 9 patients a severe clinical course (score according to Stiehme, Damrosch and Rosenblat). The patients were compared with 227 non-related blood donors (114 women, 113 men, 18 to 50 years old). In patients and controls 24 lymphocytic HLA antigens class I were identified as to type. Typing was done using the standard microlymphocytotoxic test in the NIH modification. The results were processed by statistical methods using Fisher's exact test and the 2 x 2 test with Yates correction. In patients with a mild course HLA antigens B7 and B12 predominate (p = 0.03; p = 0.02), in medium severe cases antigen A11 (p = 0.03), in patients with the most severe course antigen A9 (p = 0.04). In invasive infections caused by N. meningitidis serotype B antigen B17 predominates (p = 0.05). CONCLUSIONS: The severity of meningococcal invasive infections is associated with HLA class I. Invasive disease caused by N. meningitidis serotype B are more likely to occur in carriers of HLA B17. No relationship was found between HLA class I and invasive disease caused by N. meningitidis regardless of serotype and with serotype C.