Antibodies are essential in host defense against Neisseria meningitidis. Therefore, interactions among IgG and Fc receptors (Fc gamma R) on phagocytes may be crucial. Genetic polymorphic forms of Fc gamma RIIa (CD32) express different functional activities. In a retrospective study, Fc gamma R polymorphisms were determined in 25 children who survived fulminant meningococcal septic shock: 11 had Fc gamma RIIa-R/R131, the poor IgG2-binding allotype, which is a significantly more frequent rate than found in a healthy white population (44% vs. 23%; P = .028; odds ratio = 2.67; 95% confidence interval, 1.09-6.53). The relevance of this finding was further supported by the fact that neutrophils with the Fc gamma RIIa-R/R131 allotype phagocytized N. meningitidis opsonized with polyclonal IgG2 antibodies less effectively than did IIa-H/H131 neutrophils. Our findings suggest an important role for anti-N. meningitidis IgG2 and the Fc gamma RIIa polymorphism in host defense against systemic meningococcal infections.

The frequency of complement deficiency in 176 of 7,732 patients with meningococcal disease in the Netherlands from 1959 through 1992 was assessed. Complement deficiency was found in six patients (3%): 3 (7%) of the patients with Neisseria meningitidis serogroup C disease, 1 (2%) of the patients with N. meningitidis serogroup A disease, and 2 (33%) of the patients with infections due to uncommon serogroups and nongroupable strains of N. meningitidis. Of 91 additional patients with meningococcal infections due to uncommon serogroups, 33% also had complement deficiency. Thirty-four of the 36 complement-deficient patients with meningococcal disease who were from 33 families were 5 years of age or older. Twenty-six additional complement-deficient relatives were found. Screening individuals with meningococcal disease due to uncommon serogroups who were 5 years of age or older identified 30 of the 33 complement-deficient families. Only 27% of the complement-deficient relatives had had meningococcal disease. This risk was lower for relatives with properdin deficiency (18%) than for those deficient in the late component of complement (38%). Therefore, pedigree studies are warranted for identifying those complement-deficient persons who require vaccination for meningococcal disease.

Borrelia burgdorferi-related isolates were tested for their sensitivity to normal human serum (NHS) and their ability to activate complement. By dark-field microscopy, electron microscopy, and subsurface plating, it was shown that exposure of a Borrelia garinii isolate to 10% or more NHS resulted in immobilization, blebbing, and killing of the spirochetes. These effects were mediated by complement, since they were not seen after heat treatment of NHS, in the presence of EDTA, or in an agammaglobulinemic serum. All seven B. garinii type 5 or 6 and all four VS116/M19 strains were serum sensitive, whereas all eight Borrelia afzelii, five of eight B. garinii type 4, and three of seven B. burgdorferi sensu stricto isolates were serum resistant. The other isolates were partially serum sensitive. Four serum-sensitive B. garinii isolates had been isolated from human cerebrospinal fluid. Most likely, activation of both the alternative pathway and the classical pathway of complement was involved, since bactericidal activity was diminished in properdin-deficient sera as well as in a C1q-depleted serum and in a C4-deficient serum. Bactericidal activity could be restored when a serum lacking C1q or C4 was mixed with a properdin-deficient serum. Isolates with various genetic backgrounds were equally able to activate C3 as measured by enzyme-linked immunosorbent assay. In the presence of Mg-EGTA, C3 was activated by all isolates after exposure to >10% NHS. This study shows that B. burgdorferi-related spirochetes can be either serum sensitive or serum resistant in vitro and that this characteristic is associated with their genetic background. Lyme borreliosis (LB) is a multisystem disorder caused by the tick-borne spirochetes Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii. Erythema migrans (EM), a skin lesion surrounding the site of the initial tick bite, is often the presenting symptom of LB (54). Subsequently, spirochetes can disseminate to other skin sites, resulting in multiple EM lesions and finally acrodermatitis chronica atrophicans (ACA), or to various organs, such as the heart, the joints, the eyes, or the central nervous system (54). Dissemination of Borrelia from the skin to distant sites is generally considered to occur hematogenously. After needle or tick-borne inoculation of mice with B. burgdorferi, all inoculated mice had positive blood cultures up to 6 weeks postinoculation (p.i.), while after 1 year only 1 of 10 mice was positive (6). Spirochetes have been cultured in low frequency from blood from rabbits 2 weeks p.i. (26) and from rhesus monkeys 1 to 6 weeks p.i. (41), although in another study blood cultures from such animals were negative (37). Culture of spirochetes from human blood has been successful in a few cases (7, 34, 58) but is usually negative (35). These findings suggest that spirochetes are present in the circulation in the early stage of infection but that they disappear in later stages of the disease. Whether the humoral immune system plays a role in the prevention o...

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A Salmonella enterica serotype Typhi strain was cultured from blood and fecal samples from a 54-year-old man with fever and diarrhea. He had returned from travel to the Philippines a few days earlier. Phenotypic and genotypic analysis confirmed the production of the SHV-12 extended-spectrum beta-lactamase.

SUMMARYIndividuals with either a late (C5±9) complement component deficiency (LCCD) or properdin deficiency are at increased risk to develop meningococcal disease, often due to serogroups W135 and Y. Anti-meningococcal defence in both LCCD persons and properdin-deficient individuals without bactericidal antibodies depends mainly on phagocytosis. Three types of opsonin receptors are involved in phagocytosis by polymorphonuclear cells (PMN). These represent the polymorphic FcgRIIa (CD32) and FcgRIIIb (CD16b) receptors, and the C3 receptor CR3 (CD11b/CD18). When the distribution of FcgRIIa and Fcg RIIIb allotypes was assessed in 15 LCCD and in 15 properdin-deficient patients with/ without previous meningococcal disease, we found the combination of FcgRIIa-R/R131 with FcgRIIIb-NA2/NA2 allotypes to be associated with previous meningococcal disease (odds ratio 13´9, Fisher's test P 0´036). No such relation was observed in the properdin-deficient patients. The importance of FcgRIIa allotypes was also demonstrated using in vitro phagocytosis assays. PMN from Fcg RIIa-R/ R131 homozygous donors internalized IgG2 opsonized meningococci W135 significantly (P , 0´05) less than PMN from FcgRIIa-H/H131 donors. When properdin-deficient serum was tested, it was observed that reconstitution with properdin resulted in enhanced PMN phagocytosis of the W135 meningococci (P 0´001). This enhanced phagocytosis was parallelled by an increase in C3 deposition onto the opsonized meningococci W135 (r 0´6568, P 0´01). We conclude that the occurrence of meningococcal disease in LCCD patients is associated with certain FcgR allotypes. Properdin-deficient individuals are susceptible to meningococcal disease because of an insufficient C3 deposition on the surface of meningococci, resulting in insufficient phagocytosis.

SUMMARYMannan-binding protein (MBP), a calcium-dependent plasma lectin, may play a role in the innate defence against microorganisms. After binding lo carbohydrate structures at the bacterial surface, MBP activates the classical pathway of the complement system. To investigate the binding capacity of MBP to various bacteria associated with meningitis, an assay was developed to study the binding of MBP to bacteria grown in a semisynthctic lluid culture medium. Salmonella montevideo (containing a mannose-rich lipopolysaceharide (EPS)), used as a positive control strain, showed binding of radioiabclled MBP at a level of 80% compared with binding of MBP to zymosan. Binding of labelled MBP to Salm. monievideo was time-dependent, temperaturedependent and saturablc. The binding, was inhibited by unlabelled MBP., by mannose and by Nacetyl-ij-glucosamine. Among bacterial pathogens often found to cause meningitis, a wide range of MBP binding capacities could be determined. The encapsulated Neisseriu meningitidis (representatives from 11 serogroups other than group A were included: n ~ 22), N. mucosa {n = \), iUicmophilus mfiuenzae type b \n = 10) and Streptococcus agalactiae [n = 5) had a low MBP binding capacity of21-7% (95% confidence interval (Cl)3'3 4i)\%). Escheriehia coliK\ (« = 11).Strep, suis {n = 5), Strep, pneumoniae (n = 10) and N. meningitidis scrogroup A (n = 2) showed intermediate MBP binding capacity of 58-4% (95% Cl 40-0-76 8%). A third group consisting of non-encapsulated Listeria monocytogenes (rt = 11), non-encapsulated H. injluenzae (n = 2), nonencapsulated N. meningitidis (n = 2), N. cinera {n = \) and N. .subflava {n = \) strains had a high MBP binding capacity of 875% (95% C! 62'5 112 5%). The majority of encapsulated pathogens causing bacterial meningitis seem to have a rather low MBP binding capacity.