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PubMed2005

Vascular endothelial growth factor is increased during the first 48 hours of human septic shock and correlates with vascular permeability.

Meningococcal septic shock is an important cause of morbidity and mortality in children and young adults worldwide and is the prototypical gram-negative septic shock. One of the key factors in the development of shock is increased microvascular permeability. Vascular endothelial growth factor (VEGF) is a central factor in angiogenesis and is an important mediator of vascular permeability. Thirteen patients with meningococcal infection (eight presenting with shock) were investigated in the early phase of invasive meningococcal disease. Cytokines, complement activation, and VEGF plasma concentrations were measured during the first 48 h on the pediatric intensive care unit. Increased cytokine concentrations and activation of the complement system were observed. VEGF plasma concentrations were increased (median 193 pg/mL, range 71-1082) and were highest in the presence of shock (208 pg/mL, 169-1082) compared with patients presenting without shock (92 pg/mL range 71-299). VEGF concentration at admission correlated with the severity of disease (pediatric risk of mortality score, R=0.90 [Spearman], P=0.0001) and the amount of fluids administered within the first 24 h (R=0.90, P<0.0001). In all patients, a decrease in VEGF was associated with a decrease in fluid intake during t=24 to 48 h. The results suggest that apart from correlation with IL-1 beta, -10, -12, and complement activation, microvascular permeability in sepsis is also closely linked to the plasma concentration of VEGF. The role of VEGF in sepsis-associated increased microvascular permeability needs further exploration and may represent a new therapeutic target.

Capillary Permeability↗

PubMedDate not supplied

Potential and limitations of polysaccharide vaccines in infancy.

Of infections caused by encapsulated bacteria, those due to Haemophilus influenzae b (Hib) are among the most restricted to infancy and require very early immunisation. Hib capsular polysaccharide (CPS) has the most typical T-cell independent profile. The absence of efficacy of this vaccine in infants triggered development of conjugate vaccines which are so effective that there is now no room for plain polysaccharide Hib vaccines. Pneumococcal infections pose similar problems to Hib, but are more complex. The immunogenicity of the different pneumococcal serotypes varies considerably in infancy. Although the current CPS vaccine provides limited protection in infancy, the burden of pneumococcal infection is so high that its use could be reconsidered should conjugate vaccines be available later than expected. Meningococcal infections are less a specific problem for infants. Again, serogroup immunogenicity varies widely. Group B meningococcal CPS is not immunogenic even in adults, Group C behaves as Hib CPS, whereas Group A is immunogenic as early as 6 months of age. Group A CPS may prove of interest for an infant vaccine, especially in epidemic situations. Typhoid fever is uncommon in infancy; Vi CPS is poorly immunogenic in infancy and is, therefore, of limited interest for use as an infant vaccine.

Bacterial Capsules↗

PubMed1989

Acute urethritis due to Neisseria meningitidis group A acquired by orogenital contact: case report.

A case of heterosexual transmission of Neisseria meningitidis group A by fellatio, which resulted in acute purulent urethritis in the male partner, is presented. The emotional impact of a mistaken diagnosis of gonococcal infection and the need to treat asymptomatic throat carriage in sexual contacts makes early recognition of meningococcal infection important in this unusual circumstance.

Acute Disease↗

PubMed2003

Primary meningococcal arthritis and endogenous endophthalmitis: a case report.

INTRODUCTION: Arthritis and endophthalmitis are both recognised complications of meningococcal infection. They may occur in the presence or absence of meningitis or meningococcaemia. Primary meningococcal arthritis (PMA) and endophthalmitis are important diagnoses to recognise as delayed treatment would result in permanent joint and eye damage. We report the first patient with both PMA and meningococcal endophthalmitis and present a review of the literature. CLINICAL PICTURE: An afebrile, non-toxic, 54-year-old female presented with arthritis and a painful red left eye following an episode of diarrhoea. An initial diagnosis of reactive arthritis with uveitis was made. However, subsequent microbiological investigations isolated Neisseria meningitides thus confirming the final diagnosis. TREATMENT: Antibiotics were instituted. OUTCOME: There was complete resolution of the arthritis but her left eye vision had deteriorated to just perception of light. CONCLUSION: The presentations of PMA and meningococcal endophthalmitis are often confusing. This should be considered in the differential diagnosis of reactive arthritis and acute dermatitis-arthritis syndrome.

Anti-Bacterial Agents↗

PubMed1986

Bacterial meningitis. Rational selection and use of antibacterial drugs.

Bacterial meningitis is a continuing challenge. This applies especially to infections in the neonate and the elderly, and to those which are hospital acquired. Factors which maintain the high morbidity and significant mortality from this disease include microbial virulence, a limited host response to infection within the cerebrospinal fluid (CSF), where phagocyte function is often impaired and complement and opsonic antibody activity are deficient, as well as delays in diagnosis and treatment. Added to these adverse factors is the pharmacokinetic hurdle of the 'blood-brain barrier', which limits drug concentrations achievable within the CSF. Inflammatory changes certainly improve the penetration of many agents, especially the penicillins and cephalosporins, but it must be remembered that with resolution of inflammation, achievable concentrations decline. Hence, the necessity for continuing parenteral administration of antibiotics throughout the treatment period. Although penicillin G (benzylpenicillin) remains the drug of choice for both pneumococcal and meningococcal infections, increasing resistance to ampicillin among Haemophilus influenzae has lead to greater reliance on alternative agents. Chloramphenicol is widely used, yet is potentially toxic, so that therapy with cefuroxime and the newer cephalosporins has been increasingly advocated. The advent of these potent, broad spectrum cephalosporins has induced a reappraisal of the treatment of Gram-negative bacillary meningitis, where ampicillin resistance and poor CSF penetration by the aminoglycosides have contributed to an unsatisfactory impact on outcome. Agents such as cefotaxime and ceftazidime have proved effective, although greater controlled experience is required. Finally, the contagious nature of meningococcal and H. influenzae infections justifies offering chemoprophylaxis to selected contacts, with rifampicin (or minocycline for contacts of patients with meningococcal infections).

Aminoglycosides↗

PubMed1997

[Rapid epidemiological characterization of Neisseria meningitidis using polymerization chain reaction from biological samplings].

OBJECTIVES: Due to the spread of the meningococcal infections, a good epidemiological surveillance is needed. Prophylactic measures should be undertaken because of the high transmissibility of these bacteria. One problem which hinders the epidemiological characterization is that the responsible strain should be isolated. The aim of this work is to develop a rapid and non culture typing method of Neisseria meningitidis. METHODS: Six cerebrospinal fluids were obtained from 5 different patients with meningococcal meningitis. A specific locus, pil A, for N. meningitidis was amplified by polymerization chain reaction (PCR). The polymorphism of this locus was then analyzed by digesting the PCR products with one of three different restriction enzymes. RESULTS: The polymorphism of this locus allowed us to establish the clonal relationships between the meningococcal strains involved in the infection. Three CSF corresponded to epidemiological strains. CONCLUSION: This typing method allows a rapid and less expensive epidemiological characterization of meningococcal infections. Moreover, it is a non culture typing method.

Child, Preschool↗

PubMed1997

Prognostic factors in meningococcal disease. Development of a bedside predictive model and scoring system. Barcelona Meningococcal Disease Surveillance Group.

CONTEXT: Meningococcal disease is associated with significant morbidity and mortality. Development of a prognostic model based on clinical findings may be useful for identification and management of patients with meningococcal infection. OBJECTIVES: To construct and validate a bedside model and scoring system for prognosis in meningococcal disease. DESIGN: Prospective, population-based study. SETTING: Twenty-four hospitals in the metropolitan area of Barcelona, Spain. PATIENTS: A total of 907 patients with microbiologically proven meningococcal disease. Patients diagnosed with meningococcal disease from 1987 through 1990 were used to develop the prognostic model, and those diagnosed in 1991 and 1992 were used to validate it. OUTCOME MEASURES: Clinical independent prognostic factors for mortality in meningococcal disease. The association between outcome and independent prognostic factors was determined by logistic regression analysis. A scoring system was constructed and tested using receiver operating characteristic curves. RESULTS: Among 624 patients in the derivation set, 287 (46%) were male, the mean age was 12.4 years, and 34 patients (5.4%) died. Among 283 patients in the validation set, 124 (43.8%) were male, the mean age was 12.7 years, and 17 patients (6.0%) died. In multivariate analysis, independent predictors of death were hemorrhagic diathesis (odds ratio [OR], 101; 95% confidence interval [CI], 30-333), focal neurologic signs (OR, 25; 95% CI, 7-83), and age 60 years or older (OR, 10; 95% CI, 3-34), whereas receipt of adequate antibiotic therapy prior to admission was associated with reduced likelihood of death (OR, 0.09; 95% CI, 0.02-0.4). Hemorrhagic diathesis was scored with 2 points, presence of focal neurologic signs with 1 point, age of 60 years or older with 1 point, and preadmission antibiotic therapy was scored as -1. The clinical scores of -1, 0, 1, 2, and 3 or more points were associated with a probability of death of 0%, 2.3%, 27.3%, 73.3%, and 100%, respectively. CONCLUSIONS: Hemorrhagic diathesis, focal neurologic signs, and age of 60 years or older were independent predictors of death in meningococcal disease, whereas receipt of adequate antibiotic therapy was associated with a more favorable prognosis. The scoring system presented is simple, is based on findings readily available at the bedside, and may be useful to help guide aggressive therapy.

Adolescent↗

PubMed1985

[Current problems in the pathological anatomy of acute neuroinfections in children].

The analysis of the autopsy material of children dying from acute neuroinfections in a specialized department of the Research Institute of Children's Infections from 1954 to 1984 is presented. The increase of the importance of hypertoxic forms of meningococcal infection, purulent meningoencephalitis (particularly those of pneumococcal etiology) as well as acute viral encephalitis (particularly herpetic ones) is noted at present. The results of the materials studied by the author from 182 children dying of those infections at the period from 1971 to 1984, the problems of their patho- and tanatogenesis are discussed. Special attention is drawn to the necessity of considering the type of an etiological agent, its properties, the features of tissue response and those of the immunological resistance in the brain for the diagnosis and epicritic assessment of acute neuroinfections.

Acute Disease↗

PubMed1999

Endothelial cell adhesion molecules in meningococcal disease.

BACKGROUND: Endothelial damage is important in meningococcal disease. Cell adhesion molecules, including P selectin, E selectin, and intercellular cell adhesion molecule 1 (ICAM-1), are expressed by activated endothelium and then subsequently shed. METHODS: ICAM-1, P selectin, and E selectin were measured on admission to hospital in children with meningococcal infections. RESULTS: Concentrations of shed cell adhesion molecules are reported for 78 children. Eleven did not have meningococcal disease. Of the 67 with meningococcal disease, 40 had mild disease (Glasgow meningococcal septicaemia prognostic score (GMSPS) < 8) and 27 had severe disease (GMSPS > or = 8). E selectin and ICAM-1 values were higher in those with meningococcal disease. The E selectin values in those with severe disease were higher than in those with mild disease. P selectin concentrations were not altered in meningococcal disease, but those who died had lower concentrations. CONCLUSIONS: Endothelial activation in meningococcal disease is reflected by shed ICAM-1 and E selectin concentrations.

Adolescent↗

PubMed1978

Protection against group B meningococcal disease. II. Infection and resulting immunity in a guinea pig model.

A guinea pig subcutaneous chamber model was used to evaluate the specificity of the immune response resulting from Neisseria meningitidis infection. Small numbers of meningococci easily infected the chambers. The infections persisted for 6-8 days with relatively high levels of organisms (10(5)-10(6)/milliliter) in the chambers, and were then rapidly eliminated and no organisms could be cultured beyond day 14. Clearance of infection correlated with appearance of circulating antibody. Antibody against both the protein serotype antigen and the capsular polysaccharide were induced as a result of meningococcal infection. The group-specific polysaccharide response peaked 2-3 wk after the animals were inoculated, while the type-specific protein response peaked at 5-6 wk. The animals were quite resistant to reinfection with either the homologous serogroup or serotype.

Animals↗

PubMed1998

[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↗

PubMed1997

Development of the epidemiological situation in invasive meningococcal disease in the Czech Republic caused by emerging Neisseria meningitidis clone ET-15/37.

Meningococcal clone ET-15/37, which appeared as a new one in the Czech Republic in 1993, caused an emergency epidemiological and clinical situation in invasive meningococcal disease, characterized by a high fatality rate (20%) compared to the "normal" fatality rate due to "non ET-15/37" strains. Morbidity rate increased since the first year of the new clone occurrence and reached the peak in 1995. This clone has spread all over the country and investigation of the epidemiological markers of Neisseria meningitidis allowed to quickly recognize the emergency situation and subsequently to provide a targeted vaccination with A + C polysaccharide meningococcal vaccine which prevented the spread of the disease caused by Neisseria meningitidis C. The most frequent phenotype of ET-15/37 clone was C:2a:P1.2(P1.5) and its percentage achieved 80% of group C Neisseria meningitidis strains tested. This antigenic shift of Neisseria meningitidis was associated with the age shift in invasive meningococcal disease morbidity: teenagers started to be the most affected age group and later age group of 1-4 olds followed with high morbidity rates. In 1995 B variant of ET-15/37 clone, B:2a:P1.2(P1.5), appeared, causing a high fatality rate, too. Some data are indicative of a possible decrease in the invasive meningococcal disease incidence in the Czech Republic; nevertheless, the active surveillance and detailed investigation of meningococci have to be continued. After four years following the vaccination and chemoprophylaxis strategy recommended in the Guidelines, set up by the National Reference Laboratory for Meningococcal Infections in 1993, it is possible to conclude, that there have been practically no secondary cases of invasive meningococcal disease in the Czech Republic.

Adolescent↗

PubMed2004

[Surveillance of notifiable infectious diseases in Bavaria - results in 2002].

In 2002 nearly 36 000 cases of notifiable infectious diseases were reported in Bavaria representing a 10 % increase compared to 2001 (33 000 cases). As in 2001, around 75 % of reported cases were gastrointestinal infections. Every third infection was due to salmonella. As compared to last year, the incidence of Norwalk-like virus infections increased fivefold. These infections occurred mostly as outbreaks in nursing homes, hospitals or other institutions, affecting as many as 200 persons. Other frequently reported infections in Bavaria are tuberculosis and hepatitis. The relatively high incidence of measles is mainly due to an outbreak in Coburg. The decline in the incidence of tuberculosis observed over the last years has ceased. Around 70 % of reported hepatitis cases were due to hepatitis C. It should be noted that these cases were a mixture of new infections and ongoing infections diagnosed for the first time. Of great epidemiological importance are diseases caused by meningitis pathogens. The incidence of meningococcal infections was practically unchanged as compared to last year. Around half of them were caused by serotype B, which is currently not preventable by vaccination. Meningitis caused by Haemophilus influenzae B is continually declining due to the high vaccination rate and is very rarely reported. Several cases of FSME were described. According to investigations carried out by health departments these infections were acquired in countries not yet classified as FSME risk areas. Hence, the endemics maps of FSME have to be revised. Two years of reporting according to IfSG (infectious disease control law) yielded very encouraging results, i. e. rapid accessibility of data, flexibility, complete and standardised reporting with high quality of data. We thank all the reporting physicians and laboratories and the staff of the Bavarian health departments for their continuous support.

Adolescent↗

PubMed1998

Creating a national service for the diagnosis of meningococcal disease by polymerase chain reaction.

The widening gap observed between numbers of culture confirmed and notified cases of meningococcal infection has driven the development of non-culture based polymerase chain reactions (PCRs) to enhance the detection of meningococcal disease. The development of a national PCR-based service increased the number of laboratory confirmed cases of meningococcal disease by 35% in the first year. Advancing technology in the laboratory is reducing in-lab processing time.

England↗

PubMed2005

Porin A-specific antibody avidity in patients who are convalescing from meningococcal B disease.

Porin A (PorA), which determines the serosubtype of Neisseria meningitidis, is the main antigen of a candidate vaccine against serogroup B meningococci, which has been shown to induce high-avidity antibodies in children. We characterized the immune response of children after convalescing from meningococcal infection with a serosubtype P1.7-2,4 strain. Acute- and convalescent-phase sera of 21 children with meningococcal septic shock caused by strains with PorA subtype P1.7-2,4 were collected. The serum bactericidal antibody titers, IgG isotype distribution, and antibody avidity were measured. We determined whether the differences in avidity of anti-outer membrane vesicle antibodies were PorA specific. Serum bactericidal activity against H44/76 P1.7-2,4 was <4 in all convalescent sera. The IgG isotype distribution of the convalescent sera was dominated by IgG(1), followed by IgG(3), whereas no IgG(2) or IgG(4) was found. The geometric mean avidity index (GMAI) of convalescent sera measured against a strain with the identical subtype as the infective isolate was significantly higher than that against a strain with a heterologous PorA subtype or a PorA-negative mutant strain (57 versus 35 and 23%, respectively; p = 0.005 and p < 0.001). Geometric mean avidity titers were highest for P1.7-2,4, corresponding with the highest GMAI. The GMAI after invasive meningococcal disease was lower than after vaccination of healthy toddlers with a monovalent P1.7-2,4 outer membrane vesicle vaccine.

Antibody Affinity↗

PubMed1993

Meningococcal disease in patients with late complement component deficiency: studies in the U.S.S.R.

The purpose of this study was to examine the occurrence of late complement component deficiency (LCCD) states in the USSR. Thirty deficient individuals were detected: 27 with C8 beta and 3 with C7 deficiency. Among individuals with a first episode of meningococcal infection, about 1% had LCCD, whereas among patients with recurrent bacterial meningitis the prevalence of LCCD rose to approximately 50%. This corresponds to a prevalence for LCCD of approximately 12 per 100,000 in the general population. The individuals with LCCD identified in this study experienced about 77 episodes of meningococcal disease and acute bacterial meningitis. Mathematical analysis of the morbidity from meningococcal disease in individuals with LCCD demonstrated that the probability of disease did not change with the age of the patient and was not affected by prior episodes of infection. This finding suggest that in contrast to the situation in the general population, prior infection fails to protect the deficient individual from recurrent disease. In comparison to complement-sufficient persons, the course of disease in individuals with LCCD is less severe, as shown by a reduction in the number of episodes of endotoxic shock and mortality as well as their more rapid recovery. These findings suggest that exuberant complement activation and concomitant formation of membrane attack complexes during meningococcal infection in complement-sufficient patients plays an important role in the activation and injury of peripheral blood cells and endothelial cells during endotoxic shock.

Adolescent↗

PubMed2000

Neisseria meningitidis induces the expression of the TNF-alpha gene in endothelial cells.

Pilus-mediated adhesion plays a prominent role in the pathogenesis of Neisseria meningitidis by allowing the initial localized adhesion to epithelial and endothelial cells. Non-piliated bacteria are not adherent. Moreover, cytokine production during infection is a key feature of meningococcal pathogenesis. Tumour necrosis factor alpha (TNF-alpha) is known to be produced early during meningococcal infections and experimental endotoxemia. Monocytic cells are thought to be responsible for this systemic production of TNF-alpha which is involved in many aspects of meningococcal pathogenesis such as coagulopathy and activation of endothelial cells. In this report, both adherent and non-adherent N. meningitidis were shown to induce the expression of TNF-alpha gene in monocytic cells, however, only adherent N. meningitidis was able to induce the expression of TNF-alpha gene in endothelial cells. This latter induction required the presence of monocytes. These data suggest that endothelial cells may be activated selectively and efficiently by adherent N. meningitidis and can locally produce TNF-alpha upon bacterial adhesion.

Cells, Cultured↗

PubMed1996

Variation in the tumor necrosis factor-alpha gene promoter region may be associated with death from meningococcal disease.

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the pathophysiology of sepsis. Levels of TNF-alpha are directly correlated with severity in meningococcal disease (MD). A polymorphism in the promoter region of the TNF-alpha gene is associated with differences in the secretion of TNF-alpha. The TNF2 allele is associated with higher constitutive and inducible levels of TNF-alpha secretion than is the TNF1 allele. To investigate whether possession of the TNF2 allele is associated with severity in MD, the frequency of TNF1 and TNF2 alleles in 98 children with MD was compared. There were more deaths among children who had the TNF2 allele (P = .03; relative risk [RR], 2.5; 95% confidence interval [CI], 1.1-5.7) than in those who did not. There was also an increased risk of severe disease in children with the TNF2 allele (P = .02; RR, 1.6; 95% CI, 1.1-2.3). Possession of the TNF2 allele predisposes to a worse outcome in children with meningococcal infection.

Alleles↗