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Treatment of thromboembolic complications of fulminant meningococcal septic shock.

A patient report of fulminant meningococcal septic shock is described. The presentation, hospital course, and reconstructive efforts are outlined, and a brief review of meningococcal infection is included. Emphasis is placed on the algorithm used to determine treatment. A 19-year-old Hispanic male presented with all the hallmarks of Waterhouse-Friderichsen syndrome (WFS)-sudden onset, high fever, dyspnea with intermittent cyanosis, shock, disseminated intravascular coagulopathy, and the development of purpura. The pathognomonic feature of WFS-hemorrhage into the adrenal glands-if present, was not extensive, as he did not require steroid supplementation. Though cerebrospinal fluid latex agglutination was negative, his serum was positive for group C Neisseria and admission blood cultures grew Neisseria meningitidis. Thromboembolic complications were systemic with the highest morbidity peripherally in the lower extremities. Care for these injuries involved every rung of the reconstructive ladder-from local wound care and skin grafts to local flaps and microvascular transplantation.

Adult↗

The normal occurrence of two molecular forms of the eight complement component (C8) and their concentrations in a family with C8 deficiency.

A haemolytically inactive alpha-mobile complement C8 component was identified by crossed immunoelectrophoresis in a 27-year-old male with recurrent meningococcal infections and absence of complement mediated serum haemolytic activity. The patient's serum/plasma contained no demonstrable normal C8. C8 inhibitor activity was not demonstrable in his serum and the alternative activation pathway appeared to be intact. Serum from the proband's parents and both siblings had normal total haemolytic complement activity and they were without symptoms. However, both the normal and the haemolytically inactive C8 protein were demonstrable in their sera. Their normal C8 concentrations were less than one-half of the normal C8 mean value and distinctly below the lowest value found in ten healthy persons. The concentration of the inactive C8 component in the proband's serum was roughly 1 . 5 times higher than that of the other family members, whereas its concentration in sera of the family members was between 1 . 8 and 2 . 5 times the highest concentration found in ten healthy donors, all of whom also had an alpha-mobile C8 in measurable quantities.

Adult↗

Neisseria meningitidis in a primary school.

A prospective study of the nasopharyngeal carriage of sulphonamide resistant Neisseria meningitidis, group B, type 15 P1.16, was undertaken after a cluster of four cases of meningococcal infections had occurred, two of which were fatal, during a three year period among children attending an inner London primary school. Throughout the year of the study the overall carriage and acquisition rates of meningococci were less than 6% and 1%, respectively, and were no different from those of control children of similar age and ethnic origin from another school. The outbreak strain was isolated from three children in the study school, however, but from none in the control school. A comparison of bactericidal activity in serum against the outbreak strain in children from selected classes in each school showed that there was no lack of bactericidal activity to this strain in the study school. The low prevalence of strain specific bactericidal activity in sera taken from classroom contacts of carriers, combined with the low carriage and acquisition rats, suggested a pattern of prolonged colonisation with infrequent transmission of the organism from child to child, and was consistent with the pattern of cases seen in the school.

Carrier State↗

Efficacy of meningococcal vaccine and barriers to vaccination.

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.

Adolescent↗

Immunogenicity of 2 serogroup B outer-membrane protein meningococcal vaccines: a randomized controlled trial in Chile.

CONTEXT: Meningococcal disease occurs worldwide, and serogroup B disease accounts for a large proportion of cases. Although persons younger than 4 years are at greatest risk for serogroup B meningococcal disease, vaccine efficacy has not been demonstrated in this age group. OBJECTIVE: To evaluate serum bactericidal activity (SBA) against homologous vaccine type strains and a heterologous Chilean epidemic strain of Neisseria meningitidis as a potential correlate for vaccine efficacy. DESIGN: Double-blind, randomized controlled trial conducted between March 14 and July 20, 1994. All blood samples were taken by December 1994. SETTING: Santiago, Chile, where a clonal serogroup B meningococcal disease epidemic began in 1993. PARTICIPANTS: Infants younger than 1 year (n = 187), children aged 2 to 4 years (n = 183), and adults aged 17 to 30 years (n = 173). INTERVENTION: Participants received 3 doses of outer-membrane protein (OMP) meningococcal vaccine developed in either Cuba or Norway or a control vaccine, with each dose given 2 months apart. Blood samples were obtained at baseline, prior to dose 3, and at 4 to 6 weeks after dose 3. MAIN OUTCOME MEASURE: Immune response, defined as a 4-fold or greater rise in SBA titer 4 to 6 weeks after dose 3 compared with prevaccination titer. RESULTS: Children and adult recipients of either meningococcal vaccine were more likely than controls to develop an immune response to the heterologous epidemic strain. After 3 doses of vaccine, 31% to 35% of children responded to the vaccine vs 5% to placebo; 37% to 60% of adults responded to vaccine vs 4% to placebo (P<.05 vs control for all). Infants, however, did not respond. In contrast, against homologous vaccine type strains, the response rate was 67% or higher among children and adults and 90% or higher among infants (P<.001 vs control for all). Subsequent SBA against 7 isogenic homologous target strains identified class 1 OMP as the immunodominant antigen. CONCLUSIONS: These data suggest that neither serogroup B OMP meningococcal vaccine would confer protection during a heterologous epidemic. However, epidemic strain-specific vaccines homologous for class 1 OMP are promising candidates for the control of epidemic serogroup B meningococcal disease.

Adolescent↗

Effectiveness of a mass immunization campaign against serogroup C meningococcal disease in Quebec.

CONTEXT: An outbreak of meningococcal disease in Quebec province prompted a mass immunization program. The impact of this campaign on the epidemiology of meningococcal disease has not been studied. OBJECTIVES: To study the impact of a mass immunization campaign using polysaccharide vaccine on the epidemiology of meningococcal disease (MCD) and to assess serogroup C vaccine effectiveness (VE). DESIGN, SETTING, AND SUBJECTS: Analysis of MCD cases reported in Quebec from 1990 to 1998, before and after the mass immunization campaign was conducted during the winter of 1992-1993, when 84% of residents aged 6 months to 20 years (the target population, approximately 1.9 million individuals) were vaccinated. MAIN OUTCOME MEASURES: Incidence of MCD in 1990-1998; incidence of culture-proven serogroup C MCD between April 1, 1993, and March 31, 1998, compared among vaccinated and unvaccinated persons in the target population. RESULTS: The incidence of serogroup C disease decreased after the mass immunization campaign, from 1.4 per 100 000 in 1990-1992 to 0.3 per 100 000 in 1993-1998, and the overall incidence of other serogroups remained stable at 0.7 per 100 000, with a small increase in the proportion of cases caused by serogroup Y (P =.009). Protection from serogroup C MCD was indicated in the first 2 years after vaccine administration (VE, 65%; 95% confidence interval [CI], 20%-84%), but not in the next 3 years (VE, 0%; 95% CI, -5% to 65%). Vaccine effectiveness was strongly related to age at vaccination: 83% (95% CI, 39%-96%) for ages 15 through 20 years, 75% (95% CI, - 17% to 93%) for ages 10 through 14 years, and 41% (95% CI, -106% to 79%) for ages 2 through 9 years. There was no evidence of protection in children younger than 2 years; all 8 MCD cases in this age group occurred in vaccinees. CONCLUSIONS: Serogroup C polysaccharide vaccine is effective for controlling outbreaks in teenaged individuals but should not be used in children younger than 2 years. The mass campaign did not induce significant serogroup switching.

Adolescent↗

Effectiveness of a mass immunization campaign using serogroup C meningococcal conjugate vaccine.

CONTEXT: Meningococcal polysaccharide vaccines are of limited effectiveness. New protein-polysaccharide conjugate vaccines have yet to be evaluated in field conditions. OBJECTIVE: To assess the effectiveness of a serogroup C conjugate meningococcal vaccine in an outbreak setting. DESIGN, SETTING, AND PARTICIPANTS: Population-based observational study of cases of invasive serogroup C meningococcal disease from 1996 through 2002 in Quebec identified from the provincial registry of notifiable diseases and from the provincial reference laboratory. In 2001, a mass immunization campaign with a conjugate vaccine was conducted to control an emerging epidemic. The number of vaccinated individuals was extracted from meningococcal immunization registries. MAIN OUTCOME MEASURES: Incidence of invasive meningococcal disease before and 1 year after the campaign in vaccinated and unvaccinated individuals. RESULTS: Vaccination coverage of those 2 months to 20 years was 82.1%. After the campaign, the number of cases of serogroup C disease decreased from 58 in 2001 to 27 in 2002, and the incidence from 7.8 per million to 3.6 per million. Vaccine effectiveness was found to be 96.8% (95% confidence interval, 75.0%-99.9%). There was no observed increase in the incidence of the other serogroups. CONCLUSION: The new conjugate vaccine was effective in controlling an emerging epidemic of serogroup C meningococcal disease, as well as providing short-term protection across a wide age range.

Adolescent↗

Appearance of new strains associated with group B meningococcal disease and their use for rapid vaccine development.

There has been a decrease in the prevalence of disease in the United States due to meningococcal serotypes 2a and 2b containing class 2 proteins with a concomitant increase in nonserotypable strains containing class 3 major outer membrane proteins. A new disease associated strain was identified using monoclonal antibodies as B:4:P1.15. Serotype 4 strains have been heretofore isolated almost only from carriers. This B:4:P1.15 strain predominated among group B disease isolates in Cuba from the late 1970s to the present and among Miami, Florida isolates recovered in 1981 and 1982. To determine whether protein vaccines for new strains or serotypes could be prepared using our present methods, a combined vaccine was prepared from a group B strain (B:8:P1.15) recovered during a recent outbreak in Virginia, and a serotype 2b strain, plus group C polysaccharide. The vaccine was prepared with aluminum hydroxide, or with trehalose dimycolate plus monophosphoryl lipid A, or without adjuvant. Four weeks after immunization antibody levels were much higher in mice that received vaccine containing adjuvant.

Animals↗

[Combined-heterozygous deficiency of complement C7 in a patient with recurrent meningitis].

BACKGROUND: The association between complement deficiencies and the increased risk for meningococcal infections and bacterial meningitis is well described and most striking in patients with deficiencies of one of the late complement components, i.e., C5-C9. CASE REPORT: In the presented study the first case of a patient with combined-heterozygous deficiency of complement C7 is described. The defect led to a strongly reduced but still measurable production of C7. However, the low concentration of C7 was not protective against recurrent bacterial meningitis. CONCLUSION: The reported case illustrates once again the necessity of complement analysis in patients with meningitis. Not only patients with undetectable complement activity but also those with strongly reduced but still measurable complement function should be analyzed for a possible complement deficiency.

Adult↗

Vaccine strategies of meningococcal disease: results of a 10-year population-based study.

UNLABELLED: Invasive meningococcal disease (IMD) is an important cause of morbidity and mortality in children and adults. This study was conducted to determine a possible increase in IMD in recent years with special interest focused on serogroup C disease. From January 1st 1993 to December 31st 2002, IMD was studied in one million residents of Austria. We used active, population-based surveillance data from the Office of Public Health. A total of 126 patients with positive blood and/or cerebrospinal fluid culture or positive swabs for Neisseria meningitidis were studied. The median age of all patients was 9.5 years (range 1 month to 63 years). The average incidence of all IMD subgroups was 1.05 cases per 100,000 person years and was highest in children 0-4 years old (7.08 cases per 100,000 person years) followed by young adults aged 15 to 19 years (4.35 cases per 100,000 person years). Serogroup C IMD occurred in 1.30 cases/100,000 person years in patients aged 0 to 4 years and in 1.92 cases/100,000 person years in patients aged 15 to 19 years. Overall mortality was 11.1%. There was a significant increase (P =0.001) in IMD due to serogroup B disease within the last 10 years. In contrast, serogroup C disease did not increase during the last decade. CONCLUSION: Currently, we do not recommend mass vaccination against serogroup C disease in Austria, but young adults aged 15 to 19 years display a high incidence of meningococcal C disease. In this age group, vaccination against serogroup C disease should be considered.

Adolescent↗

Founder effect of the C9 R95X mutation in Orientals.

A nonsense mutation at codon 95 (R95X) in the C9 gene is responsible for most Japanese C9 deficiency (C9D) cases, with a carrier frequency of 6.7%. Upon analysis of microsatellite markers and newly identified dinucleotide repeat number polymorphisms in the 3' flanking region of the C9 gene, a founder effect was demonstrated for the R95X mutation of the C9 gene in Japanese. Screening for the R95X mutation in Korean and Chinese individuals showed that the R95X carrier frequencies in Koreans and Chinese were 2.0% and 1.0%, respectively. Although homozygotes for the R95X mutation were not found in Korea or China, the shared haplotype of the dinucleotide repeat number polymorphisms appeared to be associated with the R95X mutation in the heterozygotes in Korea and China. The founder effect found in East Asians (Japanese, Koreans and Chinese) but not in Caucasians, as well as the haplotype sharing in only a small chromosomal interval, suggested that the R95X mutation of C9 gene was ancient and had occurred after the divergence of East Asians and Caucasians, and before migration of the Yayoi people to Japan. Since the mortality of meningococcal infections in complement-deficient patients is lower than that in normal individuals, a founder effect and a selective advantage in isolation might be the main reasons for the high frequency of the R95X mutation in Japan.

Alleles↗

Epidemiology of meningococcal disease in Switzerland, 1999-2002.

In Switzerland, immunisation against serogroup C meningococcal disease is recommended for persons at increased risk but is not included in the national vaccination programme. The aim of this study was to present the nationwide surveillance data on invasive meningococcal disease collected from 1999 to 2002, emphasising the evolution in the absence of extended vaccination. The number of reported cases of meningococcal disease peaked at 178 cases in 2000 (incidence rate of 2.5/100,000 person-years), with 61% of all cases attributed to serogroup C meningococci (incidence rate, 1.5/100,000 person-years). Since 2001, a spontaneous decrease in the reported cases was observed, resulting in an overall incidence rate of 1.4/100,000 person-years in 2002 (serogroup C cases, 0.8/100,000 person-years). On the other hand, the case-fatality rate of serogroup C cases increased to 18% in 2002, leading to an increase in the overall case-fatality rate from 8% to 14% (P>0.05). The small sample size reduces the interpretability of this observation. However, when the introduction of a generalised vaccination against serogroup C meningococcal disease is discussed, the fluctuations in the number of vaccine-preventable deaths should receive greater attention.

Adolescent↗