Jean-Michel Alonso

Serogroup W135 meningococcal disease in Hajj pilgrims

An outbreak of W135 meningococcal disease occurred in the spring of 2000 among pilgrims returning from Saudi Arabia and their contacts. Clinical isolates from England and France were examined and compared with reference strains from other countries. Characterisation of isolates by a range of typing methods showed them to be of clonal origin (ET-37) and closely related to other meningococci with an established propensity to cause disease clusters. A reappraisal of vaccination strategies for travellers is required.

Down-regulation of pili and capsule of Neisseria meningitidis upon contact with epithelial cells is mediated by CrgA regulatory protein

The initial attachment of Neisseria meningitidis to the target cell surface appears to be largely pilus depend‐ent in capsulated bacteria. Intimate adhesion subsequently occurs to permit colonization. We recently reported that insertional inactivation of the crgA gene, which encodes a transcriptional regulator belonging to the LysR family, decreased meningococcal adhesion to epithelial cells and abolished intimate adhesion. In this report, we analyse expression of the pilE and sia genes, which are involved in the biosynthesis of pili and capsule respectively, during bacteria–host cell interactions. Western blotting, transcriptional fusion and reverse transcriptase polymerase chain reaction (RT‐PCR) analysis showed that the expression of these genes was downregulated during intimate adhesion. DNA‐binding assays, footprinting and RT‐PCR analysis indicated that this downregulation was directly mediated by the CrgA protein. The pilE and sia promoters were found to have a CrgA binding motif in common. These results strongly suggest that N. meningitidis displays an adaptive response upon cell contact. CrgA may play a central regulatory role in meningococcal adhesion, particularly in switching from initial to intimate adhesion by downregulating the bacterial surface structures that hinder this adhesion.

Neisseria meningitidis Serogroups W135 and A Were Equally Prevalent among Meningitis Cases Occurring at the End of the 2001 Epidemics in Burkina Faso and Niger

ABSTRACT Meningococcal infections occur as epidemics in the African meningitis belt. Neisseria meningitidis serogroup A is predominantly involved in these epidemics. We report here new data on the involvement of both serogroups A and W135 in meningitis cases in Burkina Faso and Niger at the end of the 2001 epidemic.

The Role of Particular Strains of Neisseria meningitidis in Meningococcal Arthritis, Pericarditis, and Pneumonia

The clinical presentations of meningococcal diseases other than meningitis or meningococcemia may lead to erroneous diagnosis. Although several reports have described unusual meningococcal diseases, the Neisseria meningitidis strains involved in these forms have been poorly characterized. In this study, meningococcal arthritis and pericarditis were confirmed by isolation of N. meningitidis and/or detection of meningococcal DNA in synovial or pericardial fluid, respectively, and meningococcal pneumonia was detected by isolation of N. meningitidis from blood. From 1999 through 2002, meningococcal disease was bacteriologically confirmed in 26 cases of arthritis, 6 cases of pericarditis, and 33 cases of pneumonia by the National Reference Center for the Meningococci in Paris. We found a statistically significant association between strains of serogroup W135, mostly of the clonal complex ET-37, and arthritis. Pneumonia was most frequently diagnosed in patients aged >70 years, and 54.5% of the strains belonged to serogroup W135, although these strains had heterogeneous phenotypes. Bacteremia is a key step in the pathophysiology of meningococcal disease and precedes any form of invasive infection.

Interlaboratory Comparison of PCR-Based Identification and Genogrouping of Neisseria meningitidis

ABSTRACT Twenty clinical samples (18 cerebrospinal fluid samples and 2 articular fluid samples) were sent to 11 meningococcus reference centers located in 11 different countries. Ten of these laboratories are participating in the EU-MenNet program (a European Union-funded program) and are members of the European Monitoring Group on Meningococci. The remaining laboratory was located in Burkina Faso. Neisseria meningitidis was sought by detecting several meningococcus-specific genes (crgA, ctrA, 16S rRNA, and porA). The PCR-based nonculture method for the detection of N. meningitidis gave similar results between participants with a mean sensitivity and specificity of 89.7 and 92.7%, respectively. Most of the laboratories also performed genogrouping assays (siaD and mynB/sacC). The performance of genogrouping was more variable between laboratories, with a mean sensitivity of 72.7%. Genogroup B gave the best correlation between participants, as all laboratories routinely perform this PCR. The results for genogroups A and W135 were less similar between the eight participating laboratories that performed these PCRs.

Neisseria meningitidis Strains Isolated from Invasive Infections in France (1999–2002): Phenotypes and Antibiotic Susceptibility Patterns

Infections due to Neisseria meningitidis are a major public health concern. In France, during 1999-2002, a total of 2167 clinical isolates of N. meningitidis from invasive infections were studied at the National Reference Center for Meningococci (Paris). Serogroup B strains were the most common (58%), followed by serogroup C strains (29%) and serogroup W135 strains (8%). Various phenotypes were observed, reflecting heterogeneity in the meningococcal population. Strains were susceptible to antibiotics currently used for treatment and chemoprophylaxis of meningococcal infections. However, the prevalence of meningococci with reduced susceptibility to penicillin is increasing. Such strains were heterogeneous and accounted for approximately 30% of isolates during this period, warranting continued surveillance of this phenomenon.

The Rise and Fall of Epidemic Neisseria meningitidis Serogroup W135 Meningitis in Burkina Faso, 2002–2005

BACKGROUND During the period 2001-2002, Burkina Faso reported its first meningitis epidemic due to Neisseria meningitidis (Nm) serogroup W135, prompting concerns that this serogroup would persist as a cause of epidemic disease. METHODS During the period 2002-2005, hospital- and population-based surveillances were conducted in 3 districts in Burkina Faso. Etiology was determined by culture, polymerase chain reaction (PCR), and latex agglutination. Reference laboratories determined phenotype and genotype. RESULTS Of 2004 subjects who received a lumbar puncture, 265 were identified as having Nm, including 93 who had Nm serogroup A (NmA) and 146 who had Nm serogroup W135 (NmW135). Over the study period, the proportion of cases due to NmW135 decreased by >75%, primarily because of decreased occurrence among young children and in a single district. During peak epidemic months, the annualized incidence of NmW135 decreased from 146 cases to <1 case per 100,000 population. All but 2 NmW135 isolates were phenotype W135:2a:P1.5,2 (sequence type [ST]-11 clonal complex). All NmA isolates were phenotype A:4:P1-9 (ST-2859 of the ST-5 clonal complex). We identified 1 isolate from serogroup Y (ST-11 clonal complex), 1 isolate from serogroup X that was similar to strains previously associated with epidemic disease, and 1 isolate from serogroup W135 of the newly described ST-4375 complex. CONCLUSIONS For unknown reasons, serogroup W135 achieved epidemic status, primarily among young children, and then largely disappeared over a short time period. The continued circulation of multiple strains with epidemic potential emphasizes the need for ongoing surveillance and the potential benefit of vaccines that are protective across serogroups.

Continuing Diversification of Neisseria meningitidis W135 as a Primary Cause of Meningococcal Disease after Emergence of the Serogroup in 2000

ABSTRACT The occurrence of a clonal outbreak of serogroup W135 (of the electrophoretic type 37 [ET-37] clonal complex) meningococcal disease among Hajj pilgrims in 2000 has led to enhanced surveillance of the evolution of this particular serogroup, formerly considered rare, in invasive infections. Since the first case of meningococcal disease due to a serogroup W135 strain was detected in France in 1994, all isolates were characterized phenotypically. We further used phenotypic and genotypic approaches to type the 101 serogroup W135 strains isolated from patients with invasive meningococcal diseases in France in 2001 and 2002. Overall, 55% of these isolates had Hajj strain-related phenotypes (60 and 52% in 2001 and 2002, respectively), although only 45% belonged to the ET-37 clonal complex. Moreover, pulsed-field gel electrophoresis of the ET-37 clonal complex isolates showed that only 32% of the serogroup W135 isolates were indistinguishable from the 2000 Hajj-related strain. Our results suggest the continuous emergence of new genetic lineages of serogroup W135 independently of the 2000 global outbreak.

The duality of virulence and transmissibility in Neisseria meningitidis

Neisseria meningitidis is a commensal bacterium of the human nasopharynx that occasionally provokes invasive disease. Carriage strains of N. meningitidis are heterogeneous, more frequent in nature and are transmitted among carriers. Disease is not a part of this transmission cycle and is caused by virulent strains. N. meningitidis is highly variable and variants that are modified in their virulence and/or transmissibility are continually generated. These events probably occur frequently, thus explaining not only the heterogeneous nature of meningococcal populations in carriers but probably also the evolutionary success of this human-restricted bacterium.

Transgenic Mice Expressing Human Transferrin as a Model for Meningococcal Infection

ABSTRACT The pathogenesis of meningococcal disease is poorly understood due to the lack of a relevant animal model. Moreover, the use of animal models is not optimal as most meningococcal virulence determinants recognize receptors that are specifically expressed in human tissues. One major element of the host specificity is the system of meningococcal iron uptake by transferrin-binding proteins that bind specifically human transferrin but not murine transferrin. We developed a new mouse model for experimental meningococcal infection using transgenic mice expressing human transferrin. Intraperitoneal challenge of transgenic mice induced bacteremia for at least 48 h with an early stage of multiplication, whereas the initial inoculum was rapidly cleared from blood in wild-type mice. Inflammation in the subarachnoidal space with a high influx of polymorphonuclear cells was observed only in transgenic mice. Meningococcal mutants that were unable to use transferrin as a source of iron were rapidly cleared from both wild-type and transgenic mice. Thus, transgenic mice expressing human transferrin may represent an important advance as a new mouse model for in vivo studies of meningococcal virulence and immunogenicity factors.