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[Epidemiologic markers of Neisseria (author's transl)].

The world-wide increase of gonococcal infections and meningococcal infections should incite to face up all necessary means of checking which can be actually envisaged against these diseases. The major phenomenon regarding gonococcal infections is the appearance, since 1976, of plasmidic resistance by a beta-lactamase secretion. Two different types of strains have been described: one originating from West-Africa, the other one from South-East Asia (that latter presenting a conjugating plasmid to totalizing 24,5 M-daltons involving coding plasmid for beta-lactamase). Among approximately thirty strains isolated in France, these ones appear to be equally shared out between these two types, following the results of our actual studies. Catlin's auxotype, which has been used in France and in some African countries (study in progress) tends to confirm the previous studies: auxotypes variations according to clinical forms an geographical distribution of strains. The other markers described in the literature are debated. As to meningococcus serogoups that we have carried out, they show a distribution well known in France, i.e. group B is largely predominating, groups A and C coming afterwards. It should be noted the appearance of some cases caused by groups Y and W135. The first results obtained thanks to serotyping, according to Frasch's technique appear to show a majority of type 2 or 2-associated in cases of diseases as other authors have proved.

Anti-Bacterial Agents↗

Atypical infections caused by pathogenic Neisseria species N. meningitidis and N. gonorrhoeae.

SUMMARYAtypical pathogenic Neisseria infections, including disseminated gonococcal infection, primary meningococcal conjunctivitis, and urogenital meningococcal infection, are clinically important yet under-recognized syndromes that challenge traditional species-disease paradigms. The increasing use of whole-genome sequencing has revealed adaptive convergence within the Neisseria genus, providing new insights into the evolution, pathophysiology, and tissue tropism of these infections. This review aims to outline current epidemiological, clinical, and genomic evidence to define transmission, risk factors, and molecular determinants underpinning disease. Improved understanding of these conditions is essential to optimize diagnosis, treatment, and public health guidance.

Neisseria gonorrhoeae↗

Australia's notifiable diseases status, 2000. Annual report of the National Notifiable Diseases Surveillance System.

In 2000, there were 89,740 notifications of communicable diseases in Australia collected by the National Notifiable Diseases Surveillance System (NNDSS). The number of notifications in 2000 was an increase of 5.9 per cent over those reported in 1999 (84,743) and the largest reporting year since the NNDSS commenced in 1991. Notifications in 2000 consisted of 28,341 bloodborne infections (32% of total), 24,319 sexually transmitted infections (27%), 21,303 gastrointestinal infections (24%), 6,617 vaccine preventable infections (7%), 6,069 vectorborne infections (7%), 2,121 other bacterial infections (legionellosis, meningococcal infection, leprosy and tuberculosis) (2%), 969 zoonotic infections (1%) and only one case of a quarantinable infection. Steep declines in some childhood vaccine preventable diseases such as Haemophilus influenzae type b, measles, mumps and rubella, continued in 2000. In contrast, notifications of pertussis and legionellosis increased sharply in the year. Notifications of bloodborne viral diseases (particularly hepatitis B and hepatitis C) and some sexually transmitted infections such as chlamydia, continue to increase in Australia. This report also summarises data on communicable diseases from other surveillance systems including the Laboratory Virology and Serology Surveillance Scheme (LabVISE) and sentinel general practitioner schemes. In addition this report comments on other important developments in communicable disease control in Australia in 2000.

Australia↗

Functional genomics of Neisseria meningitidis pathogenesis.

The pathogenic bacterium Neisseria meningitidis is an important cause of septicemia and meningitis, especially in childhood. The establishment and maintenance of bacteremic infection is a pre-requisite for all the pathological sequelae of meningococcal infection. To further understand the genetic basis of this essential step in pathogenesis, we analyzed a library of 2,850 insertional mutants of N. meningitidis for their capacity to cause systemic infection in an infant rat model. The library was constructed by in vitro modification of Neisseria genomic DNA with the purified components of Tn10 transposition. We identified 73 genes in the N. meningitidis genome that are essential for bacteremic disease. Eight insertions were in genes encoding known pathogenicity factors. Involvement of the remaining 65 genes in meningocoocal pathogenesis has not been demonstrated previously, and the identification of these genes provides insights into the pathogenic mechanisms that underlie meningococcal infection. Our results provide a genome-wide analysis of the attributes of N. meningitidis required for disseminated infection, and may lead to new interventions to prevent and treat meningococcal infection.

Animals↗

Hereditary properdin deficiency in three families of Tunisian Jews.

Hereditary properdin deficiency is a rare genetic disorder of the complement system. Three propositi and six additional family members with properdin deficiency have been found following analysis of the hemolytic activity of the classical (CH50) and the alternative (AP50) complement pathways in the sera of 101 survivors of meningococcal infections and 59 survivors of severe pneumococcal and Haemophilus influenza infections. All the properdin-deficient individuals had undetectable levels of properdin by radial immunodiffusion and by Western blotting. They belonged to three non-related families of Tunisian Jews who came from different parts of Tunisia. Two patients had a meningococcal infection at 15 and 16 years of age, respectively, and one had Haemophilus influenza meningitis at 1.5 years of age. In contrast to the fulminant and fatal course of meningococcal infection which was previously described in some properdin-deficient patients, our patients had a relatively mild disease. Properdin deficiency may not be as rare as previously thought. Analysis of AP50, in addition to CH50, in sera of patients who had meningococcal infection, will probably disclose many more cases of hereditary properdin deficiency. In addition, our findings indicate that, as in other complement abnormalities, hereditary properdin deficiency may also be associated with the ethnic origin of the patient.

Adolescent↗

Incidence and prognosis of meningitis due to Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis in Sweden.

The incidence, concomitant conditions and case fatality rate of Haemophilus influenzae (Hi) and pneumococcal meningitis and of invasive meningococcal infections were studied retrospectively in Sweden (population 8.4 million) for the years 1987-89, the period before vaccination against Hi type b started. A total of 1,019 cases with culture-verified infection were found. The incidence rates per 100,000 per year were 1.8 for Hi meningitis, 1.2 for pneumococcal meningitis and 1.0 for invasive meningococcal infections. The age-specific incidence was highest in the 3-23 months age group for the 3 bacterial species. Pneumococcal meningitis was common in individuals > or = 60 years and meningococcal infections in the age-group 10-24 years. A serious concomitant condition was known in 57% of all patients with pneumococcal meningitis while this was uncommon for the other organisms. The case fatality rate was 2% for Hi meningitis, 24% for pneumococcal meningitis and 10% for meningococcal infections. All 81 pneumococcal isolates which had been serotyped belonged to serotypes in the 23-valent pneumococcal vaccine. Of the meningococcal isolates, 65% belonged to serogroup B. In conclusion, the high incidence of Hib meningitis justifies general Hib vaccination. Development of a vaccine against N. meningitidis group B should have high priority. Furthermore, improved pneumococcal vaccines are needed for patients with predisposing conditions. The currently available pneumococcal polysaccharide vaccine seems to be underused.

Adolescent↗

Prospective controlled study of the diagnostic value of skin biopsy in patients with presumed meningococcal disease.

Microbiological tests for diagnosis of acute meningococcal disease are important for the clinical management of patients with this often-fatal illness, but cultures are frequently negative after antibiotics have been administered. Retrospective studies suggest that examination of skin biopsies may aid a rapid diagnosis and that cultures of skin biopsies are often positive even after antimicrobial treatment has commenced. This prospective controlled study aimed to assess the diagnostic value of skin biopsy compared with investigations of blood and cerebrospinal fluid (CSF) in patients with skin lesions and presumed meningococcal disease. A total of 43 patients, 31 with suspected acute meningococcal infection and 12 controls, were included. All skin biopsies were investigated by Gram stain and routine microbiological culture. In 25 patients, meningococcal infection was diagnosed microbiologically. The clinical diagnosis was meningococcal meningitis in 8 patients, meningococcal sepsis in 11 patients, and a combination of both in 6 patients. The sensitivity of cultures of blood, CSF, and skin biopsies was 56%, 50%, and 36%, respectively. When culture and Gram stain were combined, positive results were obtained in 56%, 64%, and 56%, respectively. There was no correlation between the diagnostic yield of skin biopsies and previous antibiotic treatment. In 14 patients, the diagnosis was based exclusively on one positive sample: CSF in 7 (28%) patients, blood in 4 (16%) patients, and skin biopsy in 3 (12%) patients. The sensitivity of skin biopsies was highest in patients with the least extensive skin lesions. Specificity was 100%. Microbiological investigation of skin biopsies increased the diagnostic yield and could be considered a component of the routine diagnostic work-up in patients with suspected meningococcal infection, even after the initiation of antimicrobial treatment.

Adolescent↗

Correlating epidemiologic trends with the genotypes causing meningococcal disease, Maryland.

Epidemic meningococcal infection is generally caused by single clones; whether nonepidemic increases in infection are clonal is unknown. We studied the molecular epidemiology of meningococcal infection during a period that the incidence increased in two age groups. Serogroup C and Y meningococcal isolates were analyzed by pulsed-field gel electrophoresis and multilocus sequence typing. From 1992 to 1999, 96.4% (27/28) of serogroup C isolates from persons 15-24 years of age were in clonal group 1, compared with 65.6% (21/32) of isolates from persons < or =14 years, and 64.3% (9/14) of isolates from adults > or =25 years (p < or = 0.01). The proportion of clonal group 2 serogroup Y strains increased from 7.7% (1/13) in 1992 to 1993 to 52.0% (13/25) in 1998 to 1999 (p < 0.01). The nonepidemic age-specific increases in serogroup C meningococcal infection in Maryland were clonal in nature and the changes in serogroup Y incidence were associated with a shift in the genotypes of strains causing invasive disease.

Adolescent↗

[Uric acid as a prognostic marker in critically ill patients].

BACKGROUND: Elevated uric acid concentrations reflect adenosine triphosphate degradation and suggest poor prognosis since they indicate a cellular bioenergetic crisis. OBJECTIVE: To study uric acid concentrations as a prognostic marker of disease severity in critically ill children. PATIENTS AND METHODS: Seventy-eight patients admitted to our pediatric intensive care unit with different diseases were prospectively studied. Thirty-five patients with meningococcal infection were retrospectively studied. Data on uric acid concentrations, diagnosis, length of stay, age, weight, the therapeutic intervention scoring system (TISS) and the pediatric risk of mortality score (PRISM) were collected. In patients with meningococcal infection severity was evaluated by studying evolution (death and the presence of sequelae or otherwise). RESULTS: Uric acid concentrations on admission were significantly correlated with TISS on the first day (r 0.260; p 0.023) and with PRISM during the first 24 hours (r 0.277; p 0.015). In patients without craniocerebral trauma, correlations between uric acid concentrations and PRISM during the first 24 hours (r 0.524; p < 0.001) and correlations between uric acid concentrations with TISS on day 1 (r 0.483; p < 0.001) and day 2 (r 0.373; p 0.014) improved. In patients with craniocerebral trauma no significant correlations were found between uric acid and any of the other variables. In patients with meningococcal infection, uric acid concentrations on admission were closely related to evolution (uric acid concentrations were 13.20 8.2 mg/dl in patients who died, 8.01 1.77 mg/dl in those with sequelae and 4.72 1.84 mg/dl in in those without sequelae; p < 0.003). CONCLUSIONS: Serum uric acid concentrations can be considered as a marker of severity in critically ill patients without craniocerebral trauma and especially in patients with meningococcal infection.

Child, Preschool↗

[The range of individual sensitivity to adhesion by Neisseria meningitidis serogroup B in young men].

5,340 young adult males, including 5,149 healthy persons, 141 N. meningitidis carriers, 25 patients with generalized meningococcal infection and 6 patients with nasopharyngitis of meningococcal etiology, were examined. The study revealed that red blood cells of 17.4% of healthy persons were highly sensitive to N.meningitidis adhesion (adhesion indices equal to 0.25 and less), red blood cells of 20.4% of persons had low sensitivity to N.meningitidis adhesion (adhesion indices equal to 2 and greater). All other persons with high sensitivity of their red blood cells proved to be patients with meningococcal infection or carriers of N.meningitidis of the same group.

Adhesins, Bacterial↗

[Evaluation of the role of specific antimeningococcal antibodies in the spread of meningococcal carrier states in collectives].

The results of serological, bacteriological and epidemiological studies carried out in populations with different epidemic pattern of meningococcal infection are presented. A-group specific antibody was found to have the leading role in the intensity of the spread of meningococcal infection in the populations. The presence of antibody to this antigen in 16.7% of serum samples inhibited dissemination of meningococci in the populations. Simultaneously with an increase in the herd immunity level to 34.8% the attenuation of the active meningococcal dissemination cycle was observed. Meningococci isolated in the populations with different epidemic patterns of meningococcal infection were shown to have different ecological properties.

Antibodies, Bacterial↗

[Role of viral-bacterial associations in meningitis in children].

A total of 50 section cases of meningitis in children were investigated. All patients revealed acute viral respiratory infections with generalization, including lesions of the central nervous system (CNS). In 14 children moreover meningococcal infection was diagnosed. In 30 children lesions of the CNS were due to mixed bacterial microflora. In 6 children along with acute viral respiratory infections (AVRI) mycoplasmosis was also revealed. Etiology of the process was determined on the basis of characteristic structural changes in the CNS and other organs, findings of virological and bacteriological investigations. In the majority of children the intravascular blood coagulation was observed. Waterhouse-Friderichsen's syndrome was revealed mainly in meningococcal infection. In order to ascertain the data obtained case records of 120 children, who had undergone treatment in connection with meningococcal infection, were analysed. It turned out that all 42 children, who had developed this disease independently, recovered. Combination of the disease with AVRI led to fatal outcomes in 12 cases out of 72.

Acute Disease↗

[Etiological diagnosis of suppurative bacterial meningitis today].

As the result of laboratory examination of 2165 patients with virulent bacterial meningitides, including cases of meningococcal infection, the etiological diagnosis was confirmed in 1407 patients (65.0%), the number of cases confirmed by the laboratory examination being significantly greater among adults than among children: 67.5 +/- 1.37% and 63.1 +/- 1.53%, respectively, (t = 2.1). Meningococcal infection was confirmed in 1111 (70.6%) out of 1572 patients under examination. Of the patients with purulent meningitides, pneumococcal etiology was determined in 27.4%, type b of Haemophilus influenzae in 13.5%, other infective agents in 10.0%. The comparison of the results obtained in the examination, carried out by different methods, of 946 children and 770 adults with meningococcal infection revealed a considerable difference in the number of positive results yielded by the bacteriological method and countercurrent immunoelectrophoresis (CIE). Among adults meningococci were isolated twice as frequently (41.1 +/- 2.5% - 19.4 +/- 1.6%), and the results yielded by CIE were predominantly positive (55.1 +/- 2.5% and 40.1 +/- 2.5%). CIE and the immunoenzyme assay were shown to have advantages in the diagnosis of the disease. Under the conditions of intensive antibiotic therapy the methods based on the detection of specific antigens in body fluids can greatly assist in diagnosis.

Adolescent↗

[The diagnostic value of a meningococcal-B erythrocyte diagnostic agent based on the group-specific polysaccharide].

In this work the diagnostic value of group B meningococcal erythrocyte diagnosticum was determined. 585 blood serum samples taken from adult donors were studied: 220 samples from practically healthy persons and 365 samples from 144 patients with meningococcal infection and purulent bacterial meningitis of nonmeningococcal etiology. Group B meningococcal erythrocyte diagnosticum was found to possess serological activity and to reveal the growth of specific antibodies in the sera of patients with meningococcal infection, serologically confirmed by the isolation of group B meningococcal culture, in 100% of cases on weeks 2-3 of the disease. Diagnostic characteristics--specificity and sensitivity--for group B erythrocyte diagnosticum were, respectively, 90.2% and 63.5%. The study revealed that antibodies to several group-specific meningococcal polysaccharides in blood sera can be simultaneously determined in the passive hemagglutination test with a set of erythrocyte diagnostica, which should be taken into consideration in the clinical interpretation of serological results.

Adult↗

Deficiency of the sixth component of complement and susceptibility to Neisseria meningitidis infections: studies in 10 families and five isolated cases.

Complement component C6 deficiency (C6D) was diagnosed in 15 patients who presented, independently, with recurrent meningococcal infection. This condition is thus not particularly rare in the Cape. Ten of the patients belonged to multiplex families, and family studies led to the diagnosis of another 12 C6D cases among the siblings. Segregation analysis showed that C6D occurred more frequently among the siblings of affected individuals than would be expected for co-dominant inheritance. The possible reasons for this are discussed. We also observed that the 12 non-proband C6D siblings included only four with a history suggestive of meningococcal infection, and thus C6D individuals apparently differ in susceptibility to Neisseria meningitidis infection. We confirmed previous observations that primary infection occurs later in C6D individuals than amongst susceptible complement-sufficient individuals. Among 123 patients presenting with primary meningitis, one case of C6D was diagnosed. The data show that C6D is an important factor associated with susceptibility to meningococcal infection in the Cape.

Adolescent↗

National enhanced surveillance of meningococcal disease in England, Wales and Northern Ireland, January 1999-June 2001.

Enhanced surveillance of meningococcal disease (ESMD) was implemented nationally across ten regions of England, Wales and Northern Ireland from 1 January 1999. It aims to deliver more sensitive surveillance than laboratory reporting by including clinically diagnosed but laboratory unconfirmed cases. Consultants in Communicable Disease Control (CsCDC) report all clinically diagnosed cases of meningococcal disease (MD) to the Regional Epidemiologist in the relevant regional unit of the Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC). These reports are reconciled with laboratory data from the PHLS Meningococcal Reference Unit and then forwarded to the national CDSC where further reconciliation with laboratory data takes place. In addition, CsCDC are asked to report any clusters of MD that occur. Between 1 January 1999 and 30 June 2001, 12,074 cases of MD were ascertained through ESMD. The majority (57%) were laboratory confirmed. The estimated incidence of MD fell between 1999 and 2001 from 9.2 to 8.0 per 100,000 population. Of laboratory confirmed cases, the number of cases of serogroups B and W135 increased and of serogroup C and of ungrouped meningococcal infection decreased. Variation between regions was considerable and deserves further investigation. Of 11,522 cases with a reported clinical diagnosis, 53.6% were diagnosed as septicaemia, 32.6% as meningitis, 12.5% as both septicaemia and meningitis, and 13% had other invasive MD. Between 1 January 1999 and 30 June 2001 698 deaths were reported, an overall case fatality rate (CFR) of 5.8%; 567 deaths were in confirmed cases and 131 probable (CFR 8.2% and 2.5%, respectively). CFR was higher in serogroup C (13.5%) than B (5.8%). No peak in serogroup C meningococcal infection occurred in the winter of 2000/1 and no clusters of serogroup C meningococcal infection were reported in the first half of 2001. ESMD provides information about the epidemiology of MD that is more complete than statutory notification and laboratory surveillance and is useful for evaluating the impact of the meningococcal serogroup C vaccination programme and of the other non-vaccine preventable serogroups.

Adolescent↗

[Assessment of severity of meningococcal sepsis in children].

Despite advances in critical care medicine, acute meningococcal infection remains complicated by high mortality. Different prognostic scoring systems have been developed but none of them is largely used. The objective of this study was to evaluate the performance at admission to the pediatric intensive care unit (PICU) of five severity scores in children with proven and unproven meningococcal infection. Our results seem to indicate that the Neisseria Sepsis Index (NESI) and the Rotterdam Score (RS) perform better than the other scores, being appropriate tools to assess severity of illness at admission to the PICU in children with proven or presumed meningococcal infection.

Adolescent↗