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Osteonecrosis following meningococcemia and disseminated intravascular coagulation in an adult: case report and review.

Meningococcemia and disseminated intravascular coagulation (DIC) have a known association, and they have been identified as a rare cause of osteonecrosis in children. To our knowledge, we report only the second case of an adult with DIC and Neisseria meningitidis infection whose condition was subsequently diagnosed as osteonecrosis. We also review the world medical literature that pertains to osteonecrosis as a sequelae of meningococcal infection associated with DIC.

Adult↗

PCR and the notification of meningococcal disease.

The polymerase chain reaction (PCR) can be used to investigate suspected meningococcal infection, with rapid results. We became aware that Birmingham Health Authority was not being informed about certain patients on whom meningococcal PCR had been performed. To establish whether notification was overlooked in some patients with suspected meningococcal disease, or whether PCR was performed on patients in whom it was thought meningococcal disease was unlikely, we compared numbers of patients notified to us over six months who had PCR with numbers of patients not notified who had PCR. Between 1st August 1999 and 31st January 2000, 54 PCR requests were made on seventy-seven notified patients; 51 PCR requests were made on non-notified patients and none were positive. Median age and length of stay were shorter in the non-notified patients. We conclude: (i) PCR may be being used inappropriately on younger patients who have shorter admissions and are unlikely to have meningococcal disease; (ii) in a number of patients initially admitted and notified with meningococcal disease the diagnosis is subsequently reconsidered. A 'denotification' procedure for such patients could make information on meningococcal disease more reliable.

Adolescent↗

Early management of meningococcal disease--do attitudes of GPs influence practice?

BACKGROUND: Survival from early meningococcal disease might be improved if general practitioners followed guidelines by immediately administering parenteral antibiotics (before hospital referral). METHODS: Structured telephone interviews with 20 GPs who had previously treated meningococcal cases. RESULTS: General practitioners knew guideline recommendations for early management of meningococcal disease: early parenteral antibiotics would be given by about half the GPs entertaining a diagnosis of meningococcal infection. Barriers to immediate treatment were: diagnostic uncertainty, regarding the case as nonurgent, and practising close to a hospital. DISCUSSION: Diagnosing meningococcal disease is difficult in general practice. Early antibiotic administration for suspected cases is appropriate even in close proximity to referral hospitals.

Anti-Bacterial Agents↗

A normal platelet count at admission in acute meningococcal disease does not exclude a fulminant course.

OBJECTIVE: To determine the value of the platelet count at admission for the assessment of the severity of disease in acute meningococcal infections. DESIGN: Retrospective and prospective, descriptive patient study. SETTING: University Hospital Intensive Care Unit (ICU). PATIENTS: All patients (n = 92) with acute meningococcal disease from 1985 to 1997, who arrived at the ICU within 12 h after hospital admission and had more than one platelet count during the first 12 h. MEASUREMENTS AND RESULTS: After admission, platelets dropped in 95% of the patients. At admission, 2/41 (5%) of the non-hypotensive patients and 13/51 (25%) of the hypotensive patients had platelets fewer than 100 x 10(9)/l. During the following 12 h, these percentages increased to 15% and 71%, respectively. Fatalities had, at admission, a median platelet count of 111 x 10(9)/l (range, 19-302 x 10(9)/l), whereas the nadir, occurring at median 7.0 h (range, 1.3-12 h), was 31 x 10(9)/l (range, 12-67 x 10(9)/l). Plasma TNF, measured shortly after admission, correlated better with the platelet nadir (r = -0.65, p < 0.0001) than with the platelet count at admission. Similarly, serum lactate correlated better with the platelet nadir. CONCLUSIONS: As platelets drop after admission, the use of the platelet count at admission for the assessment of the prognosis in acute meningococcal disease may be misleading. Frequently repeated platelet counts are a better tool for evaluating the severity of disease.

Child, Preschool↗

Antibiotic resistance in Neisseria meningitidis.

Penicillin has long been recognized as the antibiotic of choice for treatment of meningococcal infections, but clinicians have recently become concerned about the susceptibility of meningococci to penicillin and other antibiotics used in the management of meningococcal disease. Strains relatively resistant to penicillin (minimum inhibitory concentrations ranging from 0.1 mg/L to 1.28 mg/L) have been reported from a large number of countries, although the frequency with which such isolates are found varies widely. The mechanism of relative resistance to penicillin involves, at least in part, the production of altered forms of one of the penicillin-binding proteins. Although treatment with penicillin is still effective against these relatively resistant strains, there is evidence that low-dose treatment regimens can fail. beta-Lactamase production in meningococci is extremely rare but has been reported, and this finding is of great concern. Resistance to sulfonamides and rifampin is of particular concern in regard to the management of contacts of patients with meningococcal disease.

Drug Resistance, Microbial↗

The acute arthritis-dermatitis syndrome. The changing importance of Neisseria gonorrhoeae and Neisseria meningitidis.

Sexually active young adults with an acute arthralgia or arthritis, with or without associated skin lesions, often have disseminated gonococcal infection (DGI). In recent years, an increasing proportion of patients seen with such complaints at the University of Washington Hospitals, Seattle, have had systemic meningococcal infection rather than DGI. Among 151 patients with acute arthritis studied prospectively from 1970 to 1972, blood or synovial fluid cultures yielded Neisseria gonorrhoeae in 30 patients and Neisseria meningitidis in two. Among 62 patients meeting the same criteria who were studied prospectively from 1980 to 1983, blood or synovial fluid cultures yielded gonococci in nine and meningococci in five. Separate analysis of blood culture results from two University of Washington Hospitals also revealed a decline in the number of cases of gonococcemia from 1970 through 1984 and a shift in the relative numbers of patients with bacteremia due to N gonorrhoeae and N meningitidis. The observed decline in gonococcemia coincides with a decline in the proportion of gonorrhea in Seattle caused by gonococcal strains that have been associated with DGI.

Acute Disease↗

Isolation of Neisseria meningitidis strains with increase of penicillin minimal inhibitory concentrations.

We report the isolation and characterization of ten strains showing an increase in the minimal inhibitory concentrations to penicillin (MICs greater than 0.1 microgram/ml), and describe the epidemiological, clinical and microbiological features. The susceptibility of 3432 meningococcal strains isolated from patients in the recent epidemic wave (1978-86) in Spain, to several antimicrobial agents used in the treatment and chemoprophylaxis of meningococcal infection has been tested. Most were resistant to sulphadiazine but sensitive to other antibiotics. The possible existence of a new pattern of behaviour of meningococcal to penicillin is discussed.

Aged↗

[Changes in indicators of nonspecific humoral immunity in carriers of N. meningitidis].

The aim of the work was to assess the immunity response of the macroorganism to "sound" meningococcal carriership in relation to its length. Furthermore the author wanted to assess the state of immunity changes during the inter-epidemic period. Although the differences in the immunity response in different groups are not significant, they exist and correlate with data reported in the literature. The most important finding is that during the period of the maximum drop of IgG and IgM antibodies there is an increase of the IgA class of immunoglobulins and the C3 component of complement. This correlates with the maximum number of carriers in the investigated group. Despite existing described changes of non-specific humoral immunity, the author considers specific, in particular collective immunity which determines the epidemic process of meningococcal infections, decisive for the development of meningococcal carriership.

Carrier State↗

Improved methods of detection of meningococcal DNA from oropharyngeal swabs from cases and contacts of meningococcal disease.

In the UK the increasing use of pre-admission parenteral antibiotic therapy in meningococcal disease has lessened the value of routine cultures as a tool to confirm diagnosis, and laboratory confirmation of invasive meningococcal infection is achieved increasingly by non-culture, nucleic acid amplification methods. The purpose of this study was to evaluate a DNA extraction and meningococcal-specific DNA amplification methodology for detection of meningococci from oropharyngeal swabs. One hundred and six swabs from suspected or confirmed cases of meningococcal disease, and 94 swabs from contacts of meningococcal disease cases were examined. Of laboratory-confirmed cases, 38/65 (58.5%) yielded a positive oropharyngeal swab PCR result and 5/24 (20.8%) swabs from suspected but laboratory-unconfirmed cases were PCR positive. No significant differences in PCR positivity rates were found between the types of swab transport systems utilized, but transport time to the testing laboratory was found to affect PCR positivity (P < 0.05). Application of meningococcus-specific PCR to oropharyngeal swabs, in addition to routine culture of swabs, can provide valuable epidemiological information as well as case confirmation for contact management. PCR amplification of meningococcal PCR from oropharyngeal swabs will also increase the ascertainment in swabbing surveys carried out as part of meningococcal disease outbreak investigation and management.

DNA, Bacterial↗

Gene expression pattern in human brain endothelial cells in response to Neisseria meningitidis.

To extend our knowledge of target proteins in endothelial cells infected with the meningitis-causing pathogen Neisseria meningitidis, we characterized the interaction between the bacterial and human brain microvascular endothelial cell (HBMEC) monolayers. By use of human cDNA microarrays, transcriptional analysis revealed distinct responses to 4 and 8 h of infection. We also addressed the question of whether the major virulence factor of meningococci, i.e., the capsule, influences the host cell response. Of the 1,493 (at 4 h postinfection) and 1,246 (at 8 h postinfection) genes with altered expression upon bacterial contact, about 49.4% and 45%, respectively, depended on capsule expression. In particular, we identified an increase of expression for genes encoding proteins involved in bacterial adhesion and invasion. High levels of apoptosis-related gene (bad, bak, asp, and immediate-early response gene 1) expression could also be detected in infected cells. Further analyses confirmed that HBMECs displayed several hallmarks of apoptosis in response to N. meningitidis infection, namely, phosphatidylserine translocation and activation of caspase 3 and AMP-activated protein kinase alpha. Moreover, several differentially regulated genes not previously known to respond to meningococcal infection were identified. Of these, genes encoding cell adhesion proteins (CD44, CD98, and CD99), genes involved in downstream signaling of integrins (integrin-linked kinase, mitogen-activated protein kinase kinase 1, and mitogen-activated protein kinase kinase kinase 10) as well as negative regulators of these pathways (dual-specificity phosphatases 1, 5, and 14 and G protein pathway suppressor 2), and genes involved in cytoskeleton reorganization (those encoding Arp2/3, p34-arc, actinin alpha 1, vasodilatator-stimulated protein, and Wiskott-Aldrich syndrome protein) were the most prominent. This global transcriptional analysis creates a new platform for further molecular and cellular analysis of the interaction between N. meningitidis and target cells.

AMP-Activated Protein Kinases↗

Meningococcal disease in siblings caused by rifampicin sensitive and rifampicin resistant strains.

Two brothers presented with meningococcal infection in a five day period, the first with a rifampicin sensitive strain and the second, who had received rifampicin chemoprophylaxis, with a resistant strain. Secondary cases of meningococcal disease can occur despite chemoprophylaxis, and may be rifampicin resistant. Close contacts should be informed of the early symptoms of meningococcal disease and of the need to seek medical advice urgently if they occur.

Antibiotic Prophylaxis↗

Clinical and hematologic features do not reliably identify children with unsuspected meningococcal disease.

OBJECTIVE: To determine the frequency of unsuspected meningococcal disease (UMD) in young febrile children with meningococcal infections and evaluate whether clinical and laboratory parameters commonly used in the evaluation of fever can help identify children with UMD. METHODS: We reviewed the records of children with meningococcal disease from 1985 to 1996 at four referral centers. Children who were evaluated as outpatients and then discharged to home, from whom Neisseria meningitidis was isolated from blood or cerebrospinal fluid cultures obtained during these outpatient visits, were considered to have UMD. We compared clinical and laboratory parameters between these children and 6414 febrile outpatients 3 to 36 months old with negative blood cultures enrolled in a separate study of occult bacteremia. RESULTS: We identified 381 children with meningococcal disease, of whom 45 (12%) had UMD. Of the 45 with UMD, 37 (82%) were 3 to 36 months old. Compared with the 6414 culture-negative patients, these 37 patients with UMD were significantly younger (8.9 +/- 5.4 vs 14.2 +/- 8.1 months) and had significantly higher band counts (14.3 +/- 11.1 vs 7.3 +/- 7.5%). There were no significant differences, however, in temperature, white blood cell counts, and absolute neutrophil counts. Multivariate analysis identified young age and the band count as independent predictors of UMD. CONCLUSIONS: Children ultimately diagnosed with meningococcal disease have commonly been evaluated as outpatients and discharged to home before diagnosis. Of the hematologic parameters frequently used in the evaluation of fever, only the band count differs significantly between young febrile children with UMD and those with negative cultures. Because UMD is uncommon in young febrile pediatric outpatients, however, the predictive value of the band count is low. Thus, the complete blood count is not routinely helpful for the diagnosis of UMD.

Analysis of Variance↗

Latex agglutination for bacterial antigens and meningococcus PCR: two useful tools in legal sudden deaths.

Bacterial infections are considered to be a major cause of sudden deaths. The recognition of infections caused by Neisseria meningitidis is an essential duty of medicolegal offices due to the risk of secondary cases. Since other microorganisms, such as Haemophilus influenzae and Streptococcus pneumoniae, are also involved in infectious sudden deaths, the identification of the pathogen responsible for death is essential in order to establish a positive diagnosis while also preventing secondary meningococcal cases. However, because of the unreliability of culture methods used for autopsy specimens and the fragile nature of the microorganisms, other techniques were used. In this study, the detection of specific antigens of N. meningitidis (serogroups A, B, C, Y and W135), H. influenzae type b, S. pneumoniae and Group B Streptococcus was undertaken in 40 samples from sudden death cases in legal procedures with a latex agglutination test. In addition, a meningococcus polymerase chain reaction (PCR) assay (ctrA, crgA and siaD genes) was also used as a corroboration method for positive N. meningitidis agglutinations. Eleven cases of sudden death were confirmed to be due to meningococcus while one case was confirmed to have been caused by H. influenzae type b fulminant epiglottitis. Rapid laboratory diagnosis of meningococcal infection allowed contacts management and notification to the health authorities. From the point of view of the authors, forensic diagnosis of unascertained deaths should include latex agglutination and meningococcus PCR when a fulminant infection by N. meningitidis or H. influenzae is suspected as well as in deaths where the cause is unclear.

Adolescent↗

Acute abdomen as an atypical presentation of meningococcal septicaemia.

The clinical manifestations and course of meningococcal disease have been well described, but atypical presentations may, if unrecognized, lead to a delay in treatment. We describe here an unusual case of this disease in a 21-y-old woman who presented with an acute rigid abdomen, clinical and laboratory features of sepsis, shock and early DIC with no indication of meningococcal infection. She developed a rapidly spreading purpuric rash, conjunctival haemorrhages, hypotension and tachycardia and a low urine output. Laboratory investigations showed a low platelet count, low haemoglobin and normal WBC. A presumptive diagnosis of meningococcal septicaemia was made and recovery followed treatment with cefotaxime, fluids and inotropes. A fully sensitive Neisseria meningitis Group C, type 2a, subtype NT was isolated from blood cultures, but not from CSF obtained after antibiotic treatment.

Abdomen, Acute↗

Plasminogen activator inhibitor type 1 gene polymorphism and sepsis.

Plasminogen activator inhibitor type 1 (PAI-1) is a 50-kilodalton glycoprotein of the serine protease inhibitor family. The primary role of PAI-1 in vivo is the inhibition of both tissue- and urokinase-type plasminogen activators. In addition to this function, PAI-1 acts as an acute-phase protein during acute inflammation. PAI-1 is a pivotal player in the pathogenesis of sepsis, a complex clinical syndrome that results from a systemic inflammatory response. In patients with sepsis, the levels of PAI-1 are positively related to poor outcome, increased severity of disease, and increased levels of various cytokines, acute-phase proteins, and coagulation parameters. The 4G/5G insertion/deletion promoter polymorphism, which leads to differences in PAI-1 production, has been demonstrated to affect the risk of developing severe complications and dying from sepsis during meningococcal infection and multiple trauma.

Clinical Trials as Topic↗

Interlaboratory comparison of agar dilution and Etest methods for determining the MICs of antibiotics used in management of Neisseria meningitidis infections.

Previous studies have shown that there is considerable variation in the methods and media used to determine the susceptibility of Neisseria meningitidis to antimicrobial agents in different countries. In this study, national and regional reference laboratories used a standardized methodology to determine the MICs of antibiotics used in the management of meningococcal infection. Fourteen laboratories participated in the study, determining the susceptibility to penicillin G, rifampin, cefotaxime, ceftriaxone, ciprofloxacin, and ofloxacin of a collection of 17 meningococci, of which 11 strains were previously defined as having intermediate resistance to penicillin (Pen(I)) by sequencing and restriction fragment length polymorphism analysis of the penA gene. The MIC was determined by agar dilution and Etest with Mueller-Hinton agar (MH), MH supplemented with sheep blood (MH+B), and MH supplemented with heated (chocolated) blood. Several laboratories encountered problems obtaining confluent growth with unsupplemented MH. MH+B was considered to give the most congruent and reproducible results among the study laboratories. The modal MIC for MH+B for each antibiotic and method was calculated to define the MIC consensus, allowing assessment of each individual laboratory's data in relation to the others. The agreement in each antibiotic/method/medium combination was defined as the percentage of laboratories with a result within one dilution of the modal result. For the whole study, an agreement of 90.6% was observed between agar dilution and Etest methods. The agreement in each laboratory/antibiotic/method combination ranged from 98.2% to 69.7%, with six laboratories demonstrating agreement higher than 90% and 11 more than 80%. The ability of the laboratories to detect the Pen(I) isolates ranged from 18.2% to 100%. The apparent difficulty in interpreting susceptibility to rifampin, particularly with the Etest method, is very interesting.

Anti-Bacterial Agents↗

[Bronchopneumonia caused by Neisseria meningitidis--probable transmission by a family member who had been in Hong Kong].

A 22-year-old man came to our hospital complaining of bloody sputum. No abnormalities were seen on a chest X-ray film, but computed tomography of the chest showed infiltrates in the middle and lower lung fields. Neisseria meningitidis was isolated from cultured samples of naso pharyngeal secretions, from sputum, and from a sample obtained during bronchoscopy; bacterial bronchopneumonia was diagnosed. Family members were studied for meningococcal infection, and the bacterium was cultured from a nasopharyngeal smear from the patient's mother. The mother was asymptomatic. Both bacteria belonged to Group B serum group and their drug sensitivities were equal. The patient's family had been in Hong Kong, where this bacterium is endemic, for two years. They then returned to Japan and started to live together with the patient nine months before the onset of symptoms. The mother may have become infected in Hong Kong and may have passed the bacterium to her son after her return. Oral ampicillin was effective in both mother and son. Investigation of the patient's family was necessary to establish the probable route of infection and to decide on the treatment.

Adult↗

Transcriptome-based antigen identification for Neisseria meningitidis.

The identification of suitable antigens is crucial to successful vaccine development based on subunit approaches. While many methods exist for the identification of vaccine candidates which are surface-exposed or secreted, immunogenic and conserved, contain B and T cell epitopes, most of these have a major drawback: they do not yield any information on whether the antigen is indeed expressed by the pathogen during infection. However, DNA microarrays offer a novel tool for the investigation of the transcriptional activity of all genes of a pathogenic microorganism under in vivo conditions. Employing whole genome DNA microarrays, we have analyzed the transcriptome of Neisseria meningitidis serogroup B bacteria during different stages of infection, i.e. exposure to human serum and the interaction with human epithelial and endothelial cells. Combined with data derived from genome-based approaches (such as reverse vaccinology) and immunogenicity studies, this novel transcriptome-based antigen identification should reveal ideal vaccine candidates against serogroup B meningococcal infection.

Antigens, Bacterial↗