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 mebooksfree.com  mebooksfree.com           mebooksfree.com              of meningococcal meningitis can be made if gram-negative   131    mebooksfree.com
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                                                                                        CHAPTER 16  Gram-Negative Cocci
                        meningococci, especially those in group A, are most likely
                                                                         cocci are seen in a smear of spinal fluid (see Figure 16–4).
                        to cause epidemics of meningitis. Group B meningococci
                                                                         The organism grows best on chocolate agar incubated at
                        cause many  cases  of  meningitis  in  developed  countries
                                                                         37°C in a 5% CO  atmosphere. A presumptive diagnosis of
                        because it is not present in the capsular polysaccharide vac-
                                                                                      2
                                                                         Neisseria can be made if oxidase-positive colonies of gram-
                        cine (see “Prevention,” later). Overall, N. meningitidis ranks
                        second to S. pneumoniae as a cause of meningitis but is the
                                                                         ferentiation between N. meningitidis and N. gonorrhoeae is
                        most common cause in persons between the ages of 2 and
                        18 years.
                                                                         made on the basis of sugar fermentation: meningococci
                          Meningococci have four important virulence factors:  negative diplococci are found (see Figure 16–5). The dif-
                                                                         ferment maltose, whereas gonococci do not (both organ-
                                                                         isms ferment glucose). Immunofluorescence can also be
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                          (1) A polysaccharide capsule that enables the organism
                                                                         used to identify these species. Tests for serum antibodies
                        to resist phagocytosis by polymorphonuclear leukocytes
                                                                         are not useful for clinical diagnosis. However, a procedure
                        (PMNs). The capsule is the immunogen in several com-
                        monly used vaccines against meningococci.
                                                                         meningitis  is  the  latex  agglutination  test,  which  detects
                          (2) Endotoxin, which causes fever, shock, and other
                                                                         capsular polysaccharide in the spinal fluid.
                        pathophysiologic changes (in purified form, endotoxin can
                        reproduce many of the clinical manifestations of
                                                                         Treatment
                        meningococcemia).
                          (3) An  immunoglobulin A  (IgA) protease that helps
                                                                         Penicillin G is the treatment of choice for meningococcal
                        the bacteria attach to the membranes of the upper respira-
                                                                         axone can also be used. Strains resistant to penicillin have
                        tory tract by cleaving secretory IgA.
                          (4) Factor H binding protein (FHBP) on meningo-
                                                                         rarely emerged, but sulfonamide resistance is common. In
                        cocci binds Factor H, an inhibitor of complement factor   infections. A third-generation cephalosporin such as ceftri-
                                                                         2007–2008, strains of  N. meningitidis resistant to cipro-
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                                                                         floxacin emerged.
                        C3b. The presence of Factor H on the surface of meningo-
                        cocci reduces the opsonizing activity of C3b and reduces
                        the amount of membrane attack complex produced (see
                                                                         Prevention
                        complement action in Chapter 63). FHBP is the immuno-
                        gen in the vaccine against group B meningococci.
                                                                         prevent meningococcal disease. Either rifampin or cipro-
                                                                         floxacin can be used for prophylaxis in people who have
                          Resistance to disease correlates with the presence of
                        antibody to the capsular polysaccharide. Most carriers
                                                                         had close contact with the index case. These drugs are
                        develop protective antibody titers within 2 weeks of coloni-
                                                                         preferred because they are efficiently secreted into the
                                                                         saliva, in contrast to penicillin G.
                        zation. Because immunity is group-specific, it is possible to
                                                                           The vaccines against groups A, C, Y, and W-135 menin-
                        have protective antibodies to one group of organisms yet be
                        susceptible to infection by organisms of the other groups.
                        Complement is an important feature of the host defenses,
                                                                         gen. The vaccine against group B meningococci contains
                        because people with complement deficiencies, particularly   gococci contain the polysaccharide capsule as the immuno-
                                                                         Factor H binding protein as the immunogen.
 mebooksfree.com  mebooksfree.com           mebooksfree.com              nogen. There are two forms of the conjugate vaccine: Men-         mebooksfree.com
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                                                                           There are three forms of the polysaccharide vaccine for
                        in the  late-acting complement components (C6–C9),
                        have an increased incidence of meningococcal bacteremia.
                                                                         use in the United States, all of which contain the capsular
                                                                         polysaccharide of groups A, C, Y, and W-135 as the immu-
                        Clinical Findings
                                                                         actra contains the four polysaccharides conjugated to
                        The two most important manifestations of disease are
                                                                         diphtheria toxoid as the carrier protein, whereas Menveo
                        meningococcemia (see Figure 16–1) and meningitis. The
                                                                         contains the four polysaccharides conjugated to a nontoxic
                        most severe form of meningococcemia is the life-threatening
                                                                         mutant of diphtheria toxin as the carrier protein. Meno-
                        Waterhouse–Friderichsen syndrome, which is character-
                                                                         mune,  the  unconjugated  vaccine,  contains  only  the  four
                        ized  by  high  fever,  shock,  widespread  purpura,  dissemi-
                        nated intravascular coagulation, thrombocytopenia, and
                                                                         conjugate vaccines induce higher titers of antibodies in chil-
                        adrenal insufficiency. Bacteremia can result in the seeding
                                                                         dren than does the unconjugated vaccine. The vaccines
                        of many organs, especially the meninges. The symptoms of   polysaccharides (not conjugated to a carrier protein). The
                                                                         induce similar antibody titers in adults. Note that none of the
                        meningococcal  meningitis  are  those  of  typical  bacterial
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                                                                         vaccines contain the group B polysaccharide because it is not
                        meningitis, namely, fever, headache, stiff neck, and an
                                                                         immunogenic in humans. A fourth vaccine created for use in
                        increased level of PMNs in spinal fluid.
                                                                         gate vaccine that contains only the group A polysaccharide.
                        Laboratory Diagnosis
                                                                           In general, the conjugate vaccines are preferred over the
                        The principal laboratory procedures are smear and culture
                                                                         unconjugated version. The unconjugated vaccine is effec-
                                                                         tive in preventing epidemics of meningitis and in reducing
                        of blood and spinal fluid samples. A presumptive diagnosis
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