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[Acute infectious emergencies in adults in medical practice].

Infectious diseases belong to the most frequent reasons to seek emergency care. Life-threatening infectious emergencies, which require rapid diagnosis and hospitalisation, are, however, rare. Leading signs and symptoms are high fever combined with rapidly deteriorating general conditions, hypotonia, tachycardia, tachypnea, dyspnea, confusion, headache, or petechia or information about asplenia, immunosuppression or recent travel to the tropics. Life threatening situations, such as suspicion of invasive meningococcal infection or bacterial infection in an asplenic patient, septic-toxic shock, and acute bacterial meningitis with delayed hospitalisation require rapid start of empiric antibiotic therapy in the outpatient practice. In addition, acute infectious emergencies comprise situation for which post exposure prophylaxis is indicated.

Acute Disease↗

Protection against meningococcal serogroup ACYW disease in complement-deficient individuals vaccinated with the tetravalent meningococcal capsular polysaccharide vaccine.

Individuals with properdin, C3 or late complement component deficiency (LCCD) frequently develop meningococcal disease. Vaccination of these persons has been recommended, although reports on efficacy are scarce and not conclusive. We immunized 53 complement-deficient persons, of whom 19 had properdin deficiency, seven a C3 deficiency syndrome and 27 had LCCD with the tetravalent (ACYW) meningococcal capsular polysaccharide vaccine. Serological studies were performed in 43 of them. As controls 25 non-complement-deficient relatives of the complement-deficient vaccinees and 21 healthy non-related controls were vaccinated. Post-vaccination, complement-deficient individuals and controls developed a significant immunoglobulin-specific antibody response to capsular polysaccharides group A, C, Y, W135, but a great individual variation was noticed. Also, the proportion of vaccinees of the various vaccinated groups with a significant increase in bactericidal titre (assayed with heterologous complement) was similar. Opsonization of meningococci A and W135 with sera of the 20 LCCD individuals yielded in 11 (55%) and eight (40%) sera a significant increase of phagocytic activity after vaccination, respectively. Despite vaccination, four complement-deficient patients experienced six episodes of meningococcal disease in the 6 years post-vaccination. Four episodes were due to serogroup B, not included in the vaccine. Despite good response to serogroup Y upon vaccination, disease due to serogroup Y occurred in two C8beta-deficient patients, 3.5 and 5 years post-vaccination. These results support the recommendation to vaccinate complement-deficient individuals and to revaccinate them every 3 years.

Adolescent↗

Meningococcal vaccination for adolescents? An economic evaluation in Victoria.

OBJECTIVE: To undertake an economic evaluation of the options for vaccination of adolescents using meningococcal polysaccharide vaccine based on Victorian data. METHODOLOGY: Cost-effectiveness and cost-benefit analyses of three options for vaccination were undertaken for hypothetical populations aged 15-19 years. Baseline analyses assumed a single year of programme implementation and vaccine protection of 5 years. Sensitivity analyses of key variables were performed. Outcomes included the number of people vaccinated, cases averted, life years saved and disability adjusted life years (DALY) averted. Lost earnings avoided were included as a measure of vaccination benefit in cost-benefit analyses. RESULTS: Vaccination of people in Years 10-12 (secondary school) and first year university within a defined population with a high rate of disease was the most cost-effective option. Excluding direct cost savings and compared with no vaccination, this resulted in a discounted cost per DALY avoided of $17646 and benefits exceeding costs in discounted terms. The 'break-even' incidence rate for this option in the cost-benefit analysis was 11.9/100000. CONCLUSIONS: Economic evidence favours the use of vaccination within well-defined populations with a high rate of disease.

Adolescent↗

Meningococcal disease and vaccination in North America.

In North America, meningococcal disease occurs at a rate of I case per 100000 population per year, producing 2725 cases notified in the US in 1998 and 155 laboratory confirmed cases in Canada in the same year. A majority of these cases occur in the winter season and in early childhood, with a case fatality rate of approximately 10%. There has been an increase in the proportion of cases due to serogroup Y meningococci over the past decade: in 1995-98 in the US, 33% of cases were due to serogroup B, 28% were due to serogroup C and 34% were due to serogroup Y; in Canada in 1995-96, 47% of cases were due to serogroup B, 40% were due to serogroup C and 10% were due to serogroup Y. Outbreaks due to serogroup C were more common in the 1990s in the US and a number of outbreaks have occurred in Canada due to organisms from the hypervirulent ET-37 complex. College freshmen in the US in dormitories were found to be at an increased risk of disease. In addition, over the past 10 years, an outbreak of serogroup B disease occurred in the Pacific North-west of the US, with a fourfold increased rate of disease in that region. The explanations for these changes in epidemiology are unknown, but probably reflect the appearance of hypervirulent clones of meningococci and/or changing levels of population immunity. Meningococcal serogroup C polysaccharide-protein conjugate vaccines have been introduced recently in the UK, seem efficacious and offer the potential to reduce the burden of disease in the US and Canada too. Because serogroups other than serogroup C are prevalent in North America, a combination polysaccharide-protein vaccine, including C, Y and possibly W135 serogroups, would be attractive for this population. Although not currently an issue in industrialized nations, inclusion of serogroup A conjugates in any future vaccine policy would be an important decision in driving global prevention of meningococcal disease. A meningococcal conjugate vaccine against serogroup C was licensed in Canada in April 2001.

Adolescent↗

A 10-year serogroup B meningococcal disease epidemic in New Zealand: descriptive epidemiology, 1991-2000.

OBJECTIVE: New Zealand has experienced an epidemic of meningococcal disease since 1991. This paper describes the characteristics of this epidemic during its first 10 years (1991-2000), current control measures, and potential future interventions. METHODOLOGY: Meningococcal disease surveillance in New Zealand uses combined notification and laboratory data. Population census data from 1991 and 1996 were used to calculate disease rates. RESULTS: The annual incidence of meningococcal disease increased from 53 cases (1.6 per 100 000 population) in the pre-epidemic year of 1990 to a peak of 613 (16.9 per 100000) in 1997, followed by consistently raised rates. Over the 1996-2000 period, there was an average of 502 cases per year (13.9 per 100 000). The epidemic has resulted in 3547 cases since 1991 approximately 3000 in excess of the number expected based on pre-epidemic disease incidence. Of the total cases, 158 (4.5%) were fatal. A disproportionately large number of cases have been in Maori and Pacific Islands children in the northern part of the North Island of New Zealand. Since 1991, the epidemic has increasingly been dominated by serogroup B meningococci with subtype P1.7b,4, which by 2000 accounted for 84.6% of all cases for whom this testing was carried out. The majority of these organisms were characterised as B:4:P1.7b,4. CONCLUSION: Meningococcal disease rates are likely to remain elevated in New Zealand for at least several more years. A vaccine which could induce immunity to the P1.7b,4 PorA subtype may have a role in controlling this epidemic. Efforts are underway to obtain and trial such a vaccine. Measures are also underway to reduce overcrowded living conditions which are contributing to the epidemic. Early recognition and antibiotic treatment of cases improves outcomes and should continue to be promoted. Integrated notification and laboratory-based surveillance of meningococcal disease provides relatively complete surveillance of this disease in New Zealand and has supported the development of public health interventions.

Adolescent↗

Introduction of a conjugate meningococcal type C vaccine programme in the UK.

OBJECTIVE: The purpose of the UK initiative was to accelerate the development and introduction of new conjugate meningococcal C vaccine into the routine immunisation programme, and to implement a catch-up campaign based on the disease epidemiology. METHODOLOGY: Collaboration between Government supported institutions and the vaccine industry lead to a collaborative programme of research designed to answer policy specific questions and to accelerate the availability of new vaccines. RESULTS: Three new conjugate meningococcal C vaccines were developed and licensed for use in the UK after satisfactory data on safety and immunogenicity had been generated. A nationwide campaign was designed to offer vaccine to all infants at the same time as their three doses of primary immunisations, two doses were offered to children over 4 months and under 1 year old; all those over 1 and under 18 years old were offered a single dose of vaccine. The programme was on course for completion within approximately twelve months, with around 15 million immunisations being offered. The programme was implemented simultaneously through school and primary care services. CONCLUSIONS: A safe and effective new vaccine, against group C meningococcal disease, has been introduced into the UK immunisation programme after just a 5 year development to implementation process. Early indications point to high coverage and impacts on disease are already apparent in the groups that have been immunised. These vaccines may play an equally important role in other countries where there is a significant burden from Group C meningococcal disease.

Humans↗

Acute infectious purpura fulminans: pathogenesis and medical management.

Purpura fulminans (PF) is a potentially disabling and life-threatening disorder characterized by acute onset of progressive cutaneous hemorrhage and necrosis, and disseminated intravascular necrosis. Acute infectious PF occurs most commonly in the setting of meningococcemia due to elaboration of endotoxin. Presence of purpura, particularly when generalized, is an important predictor of a poor outcome following meningococcal infection. Histopathologic hallmarks of acute infectious PF are dermal vascular thrombosis and secondary hemorrhagic necrosis, findings which are identical to those of the Shwartzman reaction. Acute infectious PF and the Shwartzman reaction have a common pathogenesis, involving a disturbance in the balance of anticoagulant and procoagulant activities of endothelial cells. This disturbance, which is triggered by endotoxin, appears to be mediated by cytokines, particularly interleukin-12, interferon-gamma, tumor necrosis factor-alpha, and interleukin-1, leading to the consumption of proteins C and S and antithrombin III. State-of-the-art therapeutic interventions based on recent advances in our understanding of the pathogenesis of acute infectious PF are discussed.

Acute Disease↗

Epidemiological pattern of meningococcal disease in Valencia, Spain. Impact of a mass immunization campaign with meningococcal C polysaccharide vaccine.

The objective of this study was to define the epidemiological pattern of meningococcal disease in the autonomous region of Valencia, Spain, and the impact of a mass immunization campaign against serogroup C meningococcus. Data were obtained from a prospective surveillance program for invasive bacterial diseases in children < 15 y of age that began in the Valencia region on 1 December, 1995. During the period 1996-98, 213 cases of meningococcal disease were detected, representing an annual incidence of 11.3/100,000 children < 15 y. Serogroup C accounted for 31% and 38.5% of cases in 1996 and 1997, respectively (annual incidences of 2.9 and 5.4 cases/100,000 children < 15 y). An immunization campaign with the meningococcal C polysaccharide vaccine, which included all persons between 18 months and 19 y of age, began in late 1997 (vaccination coverage of 86%). In 1998, the annual incidence of meningococcal C disease fell to 1.4 cases per 100,000 children < 15 y of age. These results mirror the increase in the reported incidence of serogroup C meningococcal disease in Spain in the 1990s, a trend that was reversed after the introduction of the mass vaccination campaign. Meningococcal polysaccharide vaccine seems to be an effective public health tool for the management of this serious communicable disease.

Adolescent↗

The effect of subcapsular meningococcal B + C vaccine on the prognosis of patients with meningococcal disease.

The effectiveness of the meningococcal Cuban vaccine (VaMengoc B + C) was examined in terms of the prognosis of patients who develop disease. All cases in the vaccinee age category admitted to the Meningococcal Disease Reference Centre, Rio de Janeiro between August 1990 and December 1993 were enrolled. Vaccine effectiveness (VE) was estimated from the relationship 1-OR, where the OR (odds ratio) was the exponential of the logistic regression coefficient for the association between death from meningococcal disease and previous vaccination. The case fatality rate for vaccinees was 6.1% and that for non-vaccinees was 10.6% (relative risk 0.58; 95% confidence interval [CI] 0.33-1.01). An overall protective effect of the vaccine against a fatal outcome was identified (VE 53%; 95% CI 12-75%) controlling for sex, age at time of immunization, elapsed time since vaccination and time between onset of disease and hospital admission. This study suggests that, for some people, even if the vaccine does not protect against the development of disease it may have a beneficial effect in terms of preventing a fatal outcome. This protective effect needs to be further investigated in a prospective cohort study specifically designed to evaluate the new generation of meningococcal vaccines.

Brazil↗

Neisseria meningitidis W-135 carriage during the Hajj season 2003.

During the 2003 Hajj pilgrimage to Mecca, 344 pilgrims of 29 different nationalities were screened by means of a throat swab to detect Neisseria meningitidis carriage. N. meningitidis was isolated from 11 subjects; 2 were serogroup W-135, 1 serogroup B, and 8 were non-groupable. The results indicate a very low colonization rate for N. meningitidis among the tested cohort, with a predominance of non-groupable strains. These results, combined with a review of the published data, warrant a re-evaluation of current recommendations by the Saudi Ministry of Health for the use of ciprofloxacin for Saudi pilgrims departing at the end of the Hajj season. However, vaccination with the meningococcal quadrivalent vaccine, for all pilgrims, should continue to be recommended. The possibility of new strains arising as a cause of future meningococcal outbreaks should be considered, and annual surveillance may give an early warning.

Adolescent↗

Reactogenicity and safety of meningococcal A and C vaccine in Saudi children.

During an outbreak caused by group A Neisseria meningitidis in March 1992, groups A and C meningococcal polysaccharide vaccine was administered to 1,168 children aged from 2 to 18 years. Parents were surveyed to ascertain reactions of children to the vaccine and development of invasive group A meningococcal disease after immunization. The most common reactions were mild local pain (21.9%), erythema (12.2%), and swelling at the injection site (7.2%). Only 1.7% of the children experienced fever and 3.7% displayed irritability. The vaccine was well tolerated and all adverse reactions disappeared within 24-48 hours of immunization. No cases of meningitis or sepsis caused by group A meningococci were seen in the 1st 12 months of observation among the vaccinated children.

Adolescent↗