Chapter 136. Meningococcal Infections (Part 8) ppt

Chapter 136. Meningococcal Infections (Part 8) Patients with fulminant meningococcemia often experience diffuse leakage of fluid into extravascular spaces, shock, and multiple-organ dysfunction (Chaps. 264 and 265). Myocardial depression may be prominent. Supportive therapy, although never studied in randomized, placebo-controlled trials, is recommended. Standard measures include vigorous fluid resuscitation (often requiring several liters over the first 24 h), elective ventilation, and pressors. Some authorities recommend early hemodialysis or hemofiltration. Fresh-frozen plasma is often given to patients who are bleeding extensively or who have severely deranged clotting parameters. Many European experts have administered antithrombin III to such patients. Patients with fulminant meningococcemia in whom shock persists despite vigorous fluid resuscitation should receive supplemental glucocorticoid treatment (hydrocortisone, 1 mg/kg every 6 h) pending tests of adrenal reserve. Although it has not been formally tested in patients with fulminant meningococcemia, activated protein C (drotrecogin alfa, Xigris) is approved for use in patients with severe sepsis and dysfunction of more than one organ (APACHE II score > 25). Because of the pathophysiology, patients with meningococcemia may represent a group most likely to benefit from administration of activated protein C. The recommended dose is 24 µg/kg per hour, given as a continuous IV infusion for 96 h. Drotrecogin alfa is contraindicated when the peripheral-blood platelet count is <50,000/µL, however, and when there is active bleeding or a high risk of bleeding. Clotting parameters should be monitored closely while the drug is being infused; its administration should be discontinued 4–6 h before the performance of an invasive procedure. Drotrecogin alfa should not be used in patients with meningitis pending further evidence that it does not induce intracranial bleeding when the meninges are inflamed. Prognosis When patients are first evaluated, the clinical features most strongly associated with a fatal outcome are shock, a purpuric or ecchymotic rash, a low or normal blood leukocyte count, an age of ≥60 years, and coma. The absence of meningitis, the presence of thrombocytopenia, low blood concentrations of antithrombin or proteins S and C, high blood levels of PAI-1, and a low erythrocyte sedimentation rate (or C-reactive protein level) have also been associated with increased mortality risk from meningococcal disease. It is possible that when meningitis symptoms are lacking, the patient may delay seeking medical therapy; this scenario could account for the increased mortality risk in asymptomatic meningitis. In contrast, the receipt of antibiotics before hospital admission has been associated with lower mortality rates in some studies. Prevention Meningococcal Polysaccharide Vaccines A single injection of quadrivalent meningococcal polysaccharide vaccine (serogroups A, C, W-135, and Y) immunizes ~80–95% of immunocompetent adults (Table 136-1). Children ≥3 months of age can be vaccinated to prevent serogroup A disease, but multiple doses are required; the vaccine is otherwise ineffective in children <2 years old. The duration of vaccine-induced immunity in adults is probably <5 years. There is currently no vaccine for serogroup B; its polysaccharide is a sialic acid homopolymer that is poorly immunogenic in humans. In addition to individuals with late-complement-component or properdin deficiency, persons with sickle cell anemia, asplenia, or splenectomy should receive the quadrivalent vaccine. Vaccination is also recommended for military recruits, pilgrims on the Hajj, and individuals traveling to sub-Saharan Africa during the dry months (June to December) or to other areas with epidemic meningococcal disease. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) recommends vaccination of incoming college freshmen who will live in dormitories. In general, the vaccine should be given only to persons >2 years of age. New meningococcal capsular oligosaccharide and polysaccharide conjugate vaccines (C; A and C; A, C, Y, and W-135) are being developed; some are currently undergoing clinical trials, and some are now in use in Europe and Canada. These vaccines are based on the approach used for the highly successful H. influenzae type b conjugate vaccines. Covalent linkage of the polysaccharide to a carrier protein converts the polysaccharide to a thymus-dependent antigen enhancing IgG anticapsular antibodies and memory B cells. Because levels of antibody in mucosal secretions are much higher after the administration of a conjugate vaccine than after vaccination with an unconjugated preparation, a major benefit of these vaccines may be the introduction of herd immunity. Memory response to meningococcal polysaccharide also appears to be an important effect of the conjugate vaccines. Meningococcal conjugate vaccines are not yet licensed in the United States. However, in the United Kingdom, serogroup C conjugate vaccines introduced in 2000 have had a marked impact on the incidence of serogroup C disease in the population vaccinated. If conjugate meningococcal vaccines prove to be capable of providing durable antibody or memory responses (particularly in infants and young children), their integration into the routine childhood immunization schedule would appear warranted. Vaccines for serogroup B meningococcal disease remain elusive; none of the group B vaccines studied in clinical trials has proven to be broadly effective, but these products have a role in the control of serogroup B epidemics. The identification of new meningococcal protective antigens and the development of better meningococcal vaccines are areas of continued research and hold promise for the prevention of diseases due to N. meningitidis. In one new approach, reverse vaccinology, the sequenced genome of N. meningitidis is used to identify previously unrecognized OMPs that are common to all meningococcal strains and serogroups and that may be universal vaccinogen candidates. Thus far, a few promising candidates have been identified and are ready to undergo clinical trials. Screening tests for complement-component deficiency should be conducted in patients who have a family history of meningococcal or disseminated gonococcal disease, especially in areas without epidemic or endemic meningococcal disease; in patients who have a recurrence; in patients whose first case occurs at ≥15 years of age; in patients with cases caused by serogroups other than A, B, or C; and in family members of patients found to have a complement deficiency. . Chapter 136. Meningococcal Infections (Part 8) Patients with fulminant meningococcemia often experience diffuse leakage. associated with lower mortality rates in some studies. Prevention Meningococcal Polysaccharide Vaccines A single injection of quadrivalent meningococcal polysaccharide vaccine (serogroups A, C, W-135,. introduction of herd immunity. Memory response to meningococcal polysaccharide also appears to be an important effect of the conjugate vaccines. Meningococcal conjugate vaccines are not yet licensed