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Safety follow-up in a cohort of Biken acellular DPT vaccine recipients in Japan.

In October 1984 in Sweden, a phase II trial of Biken acellular Pertussis vaccine was started and in 1986, a phase III trial of the same vaccine was begun. During the phase III trial, there were three cases of deaths out of 1,385 of study children at two, four and ten weeks after the second dose of the vaccine, due to severe invasive bacterial infections such as H. influenzae, Pneumococcus, or Meningococcus infection. A number of arguments arose about the results of the Phase III trial. No one can either prove or disprove the association between invasive bacterial infection and administration of acellular pertussis vaccine. The purpose of this paper is to discuss the side effects of Biken acellular DPT vaccine. The pediatricians inquired about the physical status of the children who received Biken acellular DPT vaccine. During the observation period, three out of 940 infants suffered from infectious diseases. One suffered from measles, the other from varicella and the last from mumps. Our retrospective study did not reveal any severe invasive bacterial infection cases cases such as the ones experienced in Sweden.

Bacterial Infections↗

Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock.

BACKGROUND: Myocardial failure has a central role in the complex pathophysiology of septic shock and contributes to organ failure and death. During the sepsis-induced inflammatory process, specific factors are released that depress myocardial contractile function. We aimed to identify these mediators of myocardial depression in meningococcal septic shock. METHODS: We combined gene-expression profiling with protein and cellular methods to identify a serum factor causing cardiac dysfunction in meningococcal septic shock. We identified genes that were significantly upregulated in blood after exposure to meningococci. We then selected for further analysis those genes whose protein products had properties of a myocardial depressant factor--specifically a 12-25 kDa heat-stable protein that is released into serum shortly after onset of meningococcal infection. FINDINGS: We identified 174 significantly upregulated genes in meningococcus-infected blood: six encoded proteins that were of the predicted size and had characteristics of a myocardial depressant factor. Of these, interleukin 6 caused significant myocardial depression in vitro. Removal of interleukin 6 from serum samples of patients with meningococcaemia and from supernatants of inflammatory cells stimulated by meningococci in vitro abolished the negative inotropic activity. Furthermore, concentrations in serum of interleukin 6 strongly predicted degree of myocardial dysfunction and severity of disease in children with meningococcal septic shock. INTERPRETATION: Interleukin 6 is a mediator of myocardial depression in meningococcal disease. This cytokine and its downstream mediators could be a target for future treatment strategies.

Adult↗

[Group specific antibodies in generalized forms of meningococcal infection].

Seroconversion was revealed in the indirect hemagglutination test with a stable erythrocytic diagnostic agent containing meningococcus antigen of serogroup A in 93.4% of patients with generalized forms of meningococcus infection. A study of the sera obtained at various periods of the disease from 168 patients showed that the antibodies increased sharply during the first days, reaching the maximum (1:2560--1:10240) on the 5th--10th day of the disease; then the titres decreased somewhat becoming stabilizaed at the same level up to recovery. In 75--92% of the persons of control group (patients with meningites of nonmeningococcal etiology, healthy persons and those suffering from gonorrhea) the antibody titre was not over 1:20--1:40; no dynamic increase in its level was noted. The diagnostic value of the reaction for differentiation of meningococcus etiology from other meningites is emphasized.

Adolescent↗

Study of brain and vascular plexus gangliosides in meningoencephalitis of various etiology.

The content of brain and vascular plexus gangliosides and their composition have been studied in 15 cases of meningoencephalitis of various etiology and degree of disease. The most pronounced decrease of ganglioside concentration was found in brain of children, who died from herpes virus infection. Decrease of ganglioside content was revealed in brain grey matter of patients with influenza virus or meningococcus infection, but not in cases of mycoplasma infection. These data provide evidence of nerve cell destruction due to meningoencephalitis of various etiology. The biochemical data obtained are in good agreement with the results of the brain of children infection by herpes virus (increase of GD1b content in grey matter). Ganglioside content in vascular plexes of patients with meningoencephalitis was found to be, on the contrary, much higher (ca 4 times) than in the controls. The higher the lesion of choroid plexes in meningoencephalitis is, the higher the ganglioside content in them is.

Brain↗

[Erythrocyte metabolism in meningococcal infection and purulent meningitis].

The red blood cell metabolic parameters ATP, ADP, sigma AN, ATP/ADP, ATP/ATP, energy charge, PAD, 2,3-DPH, Pn were studied in 106 patients with generalized meningococcus infection (GMI) and meningitis of other etiology over their natural history. There was a typical adaptative red blood cell response that featured glycolytic stimulation on hypoxia that ran with impaired red blood cell energy metabolism (RBCEM), negative energy balance. It was the most pronounced at the peak of disease. RBCEM changes occurred in the presence of antioxidative disorders of red blood cells as lowered PAD levels. When early complications, such as shock, brain edema, death developed, there was a high incidence of signs of erythrocytic biochemical disadaptation. The RBCEM changes were associated with the magnitude of cytolysis, i.e. serum AST and AST/ALT levels. The significance of the metabolic changes found in the red blood cells in the pathogenesis and clinical picture of GMI and purulent meningitis is discussed in the paper.

Adenine Nucleotides↗

Antibody response to infection in multiple myeloma. Implications for vaccination.

We report the humoral immune response of a patient with multiple myeloma to rapidly successive episodes of meningococcal and pneumococcal meningitis. Specific antibody responses included a high bactericidal titer (1:640) against the infecting meningococcus and a sharp increase (from 198 to 8,097 ng/ml antibody nitrogen) in antibody to the type-specific capsular polysaccharide of the infecting pneumococcus. These data, showing the production of protective antibodies against the two pathogens, suggest that some patients with multiple myeloma might also respond to appropriately administered bacterial vaccines. This fact should be ascertained because vaccination could potentially reduce the high rate of bacterial infections associated with this disease.

Antibodies, Bacterial↗

[Model of meningococcal sepsis in mice].

The authors studied a possibility of obtaining experimental meningococcus sepsis model on mice. The use of cyclophosphane, iron compounds, yolk medium produced no significant organism. When 4--5% mucine was injected intraperitoneally together with meningococcus culture mice died with sepsis phenomena. Differences were revealed in the sensitivity of linear and mongrel mice to meningococcus infection--AKR mice proved to be more sensitive. At the same time it was found that mongrel mice weighing from 10 to 12 g could be used to induce meningococcus sepsis.

Animals↗

[Serologic pattern of meningococci in a focus of infection].

The authors present the results of typing of meningococci (isolated from the patients and carriers) by the sera of serological groups A, B, C, D, X, Y, and Z made at the Leningrad Institute of Vaccine and Sera. The causative agents of serological group A were most frequently isolated from the patients with the generalized forms of meningococcus infection. The percentage of detection of meningococci of serological group A was the greatest in the patients and much less in the carriers in and outside the foci of this infection. Many dissociated cultures were revealed among the strains isolated from the carriers. Sera of the Leningrad Institute of Vaccine and Sera have permitted typing of meningococci cultures belonging to various serological groups in accordance with the international classification.

Humans↗

[Fulminant meningococcemia presenting as a gastroenteritis-like syndrome].

Neisseria meningitidis infection (meningococcemia) is very common throughout the world. It usually presents as meningitis or sometimes pharyngitis. A gastroenteritis-like syndrome, with diarrhea, vomiting and abdominal pain, may occur in children but is very rare in adults. Search of the medical literature revealed only 3 such cases, all in young adults. We report an 80-year-old woman who presented with fever, diarrhea and abdominal pain. Meningococcus infection was later suspected, and proved by culture. Although treatment was intensive and included ceftriaxone (Rocephin) and garamycin, she did not respond and died 40 hours after admission. We draw attention to the possibility that what is usually a common symptom can be the first presentation of a serious, often fatal condition.

Abdominal Pain↗

Analysis of damage to human ciliated nasopharyngeal epithelium by Neisseria meningitidis.

We used an in vitro model of human nasopharyngeal tissue in organ culture to evaluate the effects of Neisseria meningitidis on human cilia and ciliary function. Encapsulated, viable meningococci damaged ciliated epithelium of nasopharyngeal organ cultures, whereas Neisseria subflava, a commensal species, did not. Meningococcus-induced ciliary damage was due to loss of ciliated cells to which meningococci were not attached. Damage was seen with piliated and nonpiliated meningococci and did not appear to require the presence of other specific meningococcal surface proteins. Meningococcal viability was a requirement for both ciliary damage and interactions of meningococci with microvilli of nonciliated epithelial cells. That is, filter-sterilized supernatants from meningococcus-infected organ cultures, heat-killed meningococci at high inoculum, and purified meningococcal or gonococcal lipopolysaccharide at concentrations of 100 micrograms/ml did not damage ciliary activity of nasopharyngeal organ cultures. In contrast, meningococcal lipopolysaccharide at 10 micrograms/ml markedly damaged ciliary activity of human fallopian tube organ cultures, suggesting a selective toxicity of lipopolysaccharide for specific human ciliated cells. Damage to nasopharyngeal ciliated epithelium by N. meningitidis may be an important first step in meningococcal colonization of the human nasopharynx, but meningococcal lipopolysaccharide does not appear to be directly responsible for this toxicity.

Bacterial Outer Membrane Proteins↗

Molecular epidemiology and emergence of worldwide epidemic clones of Neisseria meningitidis in Taiwan.

BACKGROUND: Meningococcal disease is infrequently found in Taiwan, a country with 23 million people. Between 1996 and 2002, 17 to 81 clinical cases of the disease were reported annually. Reported cases dramatically increased in 2001-2002. Our record shows that only serogroup B and W135 meningococci have been isolated from patients with meningococcal disease until 2000. However, serogroup A, C and Y meningococci were detected for the first time in 2001 and continued to cause disease through 2002. Most of serogroup Y meningococcus infections localized in Central Taiwan in 2001, indicating that a small-scale outbreak of meningococcal disease had occurred. The occurrence of a meningococcal disease outbreak and the emergence of new meningococcal strains are of public health concern. METHODS: Neisseria meningitidis isolates from patients with meningococcal disease from 1996 to 2002 were collected and characterized by serogrouping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The genetic relatedness and clonal relationship between the isolates were analyzed by using the PFGE patterns and the allelic profiles of the sequence types (STs). RESULTS: Serogroups A, B, C, W135, Y, and non-serogroupable Neisseria meningitidis were, respectively, responsible for 2%, 50%, 2%, 35%, 9%, and 2% of 158 culture-confirmed cases of meningococcal disease in 1996-2002. Among 100 N. meningitidis isolates available for PFGE and MLST analyses, 51 different PFGE patterns and 30 STs were identified with discriminatory indices of 0.95 and 0.87, respectively. Of the 30 STs, 21 were newly identified and of which 19 were found in serogroup B isolates. A total of 40 PFGE patterns were identified in 52 serogroup B isolates with the patterns distributed over several distinct clusters. In contrast, the isolates within each of the serogroups A, C, W135, and Y shared high levels of PFGE pattern similarity. Analysis of the allelic profile of the 30 STs suggested the serogroup B isolates be assigned into 5 clonally related groups/ clonal complexes and 7 unique clones. The ST-41/44 complex/Lineage 3, and the ST-3439 and ST-3200 groups represented 79% of the serogroup B meningococci. In contrast, isolates within serogroups A, serogroup W135 (and C), and serogroup Y, respectively, simply belonged to ST-7, ST-11, and ST-23 clones. CONCLUSION: Our data suggested that serogroup B isolates were derived from several distinct lineages, most of which could either be indigenous or were introduced into Taiwan a long time ago. The serogroup A, W135 (and C), and Y isolates, respectively, belonged to the ST-7, ST-11, and ST-23, and the represented clones that are currently the major circulating clones in the world and are introduced into Taiwan more recently. The emergence of serogroup A, C and Y strains contributed partly to the increase in cases of meningococcal disease in 2001-2002.

Communicable Diseases, Emerging↗

[CBO-guideline 'Bacterial meningitis'].

Neisseria meningitidis and Streptococcus pneumoniae are the most frequent causes of bacterial meningitis. The incidence of Haemophilus meningitis in the Netherlands is low due to successful Haemophilus influenzae type b vaccination. This implies that there is no need to take account into this microorganism in using initial empiric antimicrobial therapy for bacterial meningitis. Vomiting (especially children), headache, fever, and a stiff neck characterize acute bacterial meningitis. However, even without these signs a patient may still have acute bacterial meningitis. The characteristics in neonates are less specific. An emergency lumbar puncture should be performed in all patients with meningeal irritation or other signs of bacterial meningitis. Examination of the CSF is not indicated for convulsive children (between the ages of 6 months and 6 years) who do not exhibit other clinical signs. In patients who respond adequately to the treatment, it is not necessary to examine the CSF again. Papilloedema or focal neurological symptoms contraindicate a lumbar puncture in patients with bacterial meningitis, until CT results justify that it can be performed safely. Antibiotic treatment should not be delayed until after the CT. General practitioners should treat their patients with suspected meningococcus infection by admitting them to the hospital without first injecting antibiotics. In the Netherlands, patients with suspected pneumococcus meningitis may still be treated with benzylpenicillin. Patients with bacterial meningitis have no fluid restrictions; only in case of the syndrome of inadequate secretion of antidiuretic hormone is fluid reduction indicated. The physician is responsible for prescribing prophylaxis to family members. The Regional Health Services organize chemoprophylaxis for classmates. The latter is only indicated if at least 2 related cases occur in one month.

Adult↗

[Changes in the acid-base condition and gas composition of the blood in meningoencephalitis of meningococcal etiology].

A study of the acid-base state in meningococcous meningoencephalitis demonstrates that there are different metabolic changes: metabolic acidosis, metabolic alkolosis, respiratory alkalosis and metabolic and respiratory alkalosis. These studies also detected a significant correlation between the character of these changes and syndromes of brain lesions. Deep lesions are characterized by metabolic acidosis, basal-stem lesions by respiratory alkalosis, multiple lesions--by metabolic alkalosis. These data give ground to speak of the significance of brain pathology in the pathogenesis of general metabolic disturbances in meningococcus infections.

Acid-Base Imbalance↗

[Nasopharyngeal microorganisms--antagonists of meningococci].

A study was made of the species composition of symbiotic microbial flora of the nasopharynx in healthy persons and meningococcus carriers, inhibiting in vitro the growth of the test strains of miningococci. Saprophytic streptococci and particularly Str. salivarius served as the principal and the most active antagonists of meningococci in both groups of the persons examined. Comparison of the inhibitory activity of antagonists in the groups examined revealed no significant differences. However, there were seen differences in the quantitative composition of the isolated antagonists: saprophytic streptococci, particularly Str. salivarius were isolated in great amounts, and more frequently from healthy individuals, and nondifferentiated Gram positive cocci of conditionally distinguished group--from carriers. Taking into consideration the high inhibitory activity of Str. salivarius it is supposed that it can be used as an indicator of the state of insensitiveness of the human organism to the meningococcus infection.

Antibiosis↗

[Lymphocyte reaction in meningitis to the addition of anti-inflammatory preparations to the cell culture].

Microbial stimulation of lymphocytes of patients suffering from meningococcus infection increased primarily under the effect of antiphlogistic preparations in vitro; more rarely it was inhibited. In experiments with lymphocytes of the patients this increase was more than 5-fold, and with those of healthy donors -- not more than 2-fold. With a low initial lymphocyte reactivity the intersification of specific stimulation with the preparations was more pronounced than with the average and the high one. There were differences in the action of pyrasolone derivatives and hydrocortisone -- the latter inhibited this reaction more frequently than amidopyrinum and butadion.

Aminopyrine↗

[Parvovirus B19 infection--a meningococcus-like sepsis].

Two otherwise healthy adults with fever and haemorrhagic exanthema are described. In both, primary human parvovirus infection was diagnosed. The clinical picture of fever and haemorrhagic exanthema should always arouse suspicion of serious disease such as meningococcal infection. If the patient is unaffected, however, primary human parvovirus infection should be borne in mind.

Adult↗

Serum immunoglobulin levels in various forms of meningococcal infection and in meningococcus carriers.

The levels of serum IgG, IgA and IgM were examined in 191 adults including 103 patients with various forms of meningococcal infection, 32 meningitis convalescents and 56 carriers, in order to elucidate the causes of different susceptibility to the meningococcal infection. The IgD level was determined in 54 meningitis patients as well as in convalescents and carriers. The amount of immunoglobulins was determined by radial immunodiffusion. The level of IgG at the beginning of the disease in patients with the generalized forms of meningococcal infection (meningitis, meningitis combined with meningococcaemia, meningococcaemia) was found to be considerably lower than in healthy subjects. The levels of all immunoglobulins, particularly of IgA and IgM, increased in the course of the disease. The levels of IgG, IgA and IgM in meningitis convalescents a year after recovery were found to be the same as in the controls. The levels of IgG, IgA and IgM in patients with meningococcal nasopharyngitis were significantly lower than in healthy subjects. The carriers showed a decreasd level of IgA and a considerably increased level of IgG while the levels of IgM and IgD did not differ from the control.

Carrier State↗

[Antibody response to capsular polysaccharide antigen in an infection caused by meningococcus serogroup B in children].

The continuous synchronous cultivation of serogroup B meningococci and the use of the selected clones of producer strains has made it possible to obtain the serologically active preparation of the group-specific antigen from the culture in the exponential phase. The erythrocyte diagnosticum produced on the basis of this preparation has permitted the detection of group-specific antibodies in the sera of immunized rabbits and children with generalized infection caused by serogroup B meningococci. The intensity of immune response depends on the age of children. This new technique of the passive hemagglutination test is recommended for the confirmation of generalized infection caused by serogroup B meningococci.

Antibodies, Bacterial↗