Epidemic Serogroup Research Articles

Immunogenicity and efficacy of serogroup A and D bacterins against Pasteurella multocida in mice.

Pasteurella multocida is a widespread respiratory pathogen in pigs, causing swine pneumonia and atrophic rhinitis, and the capsular serogroups A and D are the main epidemic serogroups in infected animals. This study investigated the protective effects of serogroup A and D bacterins against current circulating P. multocida strains, to better understand the immunity generated by bacterins. 13 serogroup A (seven A: L3 and six A: L6 strains) and 13 serogroup D (all D: L6 strains) P. multocida strains were isolated, and used as inactivated whole cell antigen to prepare P. multocida bacterins. Mice were immunized with these bacterins at 21-day interval and intraperitoneally challenged with the homologous and heterologous P. multocida strains, respectively. The antibody titer levels and immunization protective efficacy of vaccines were evaluated. All of the bacterins tested induced high titer levels of immunoglobulin G antibodies against the parental bacterial antigen in mice. Vaccination with the six A: L6 bacterins provided no protection against the parent strain, but some strains did provide heterologous protection against A: L3 strains. Vaccination with the seven A: L3 bacterins provided 50%-100% protection against the parent strain, but none gave heterologous protection against the A:L6 strains. Immunization with the thirteen D: L6 bacterins offered 60%-100% protection against the parent strain, and almost all D: L6 strains gave cross-protection. This study found that the cross-protectivity of serogroup A strains was poor, while serogroup D strains was effective, which provided some insights for P. multocida vaccine development.

Immune Protective Efficacy of China's Traditional Inactivated and Attenuated Vaccines against the Prevalent Strains of Pasteurella multocida in Mice.

Capsular type A and D strains of Pasteurella multocida are the main epidemic serogroups in pigs in China. In this study, we preliminarily evaluated the immune protective efficacy of the two traditional vaccines, an inactivated C44-1 aluminum-hydroxide-gel-adjuvanted (Alh–C44-1) vaccine and a live EO630 vaccine, against currently circulating strains of P. multocida in a mouse model. Mice immunized twice with conventional vaccines generated higher antibody titers, and significantly higher levels of IgG were observed in the mice inoculated with the inactivated Alh–C44-1 vaccine on day 35 (p < 0.05) than those with the live EO630 vaccine. The mice immune protection test showed that the vaccination groups had a 57% or 71% protection effect against the serogroup B strain, but had no protective effect against epidemic strains. In conclusion, our study found that the widely used traditional P. multocida vaccines in China provide good protection against homologous strains, but could not provide cross-protection against heterologous strains in a mouse model.

IgA1 Protease as a Vaccine Basis for Prevention of Bacterial Meningitis

The review covers the study of the protective properties of IgA1 protease and the possibility of creating a vaccine preparation for the prevention of bacterial meningitis of various origins on its basis. Bacterial meningitis belongs to the group of socially dangerous diseases and is characterized by a severe course, numerous complications and high mortality. The approaches used at present in world practice to create antimicrobial vaccines are based on a narrow targeting against a specific pathogen. The development of a monocomponent vaccine against a wide range of bacterial pathogens with a common virulence factor is still relevant. IgA1 protease, a protein that is one of the main virulence factors of a number of gram-negative and gram-positive bacteria, can serve as such an antigen. Bacterial IgA1 protease is uniquely specific for immunoglobulins A1 (IgA1), cleaving peptide bonds in the hinge regions of the IgA1 in humans and other higher primates. Bacteria, getting on the mucous membrane, destroy IgA1, which acts as the first barrier to protect the body from infections. Neutralization of IgA1 protease at this stage can become an obstacle to the development of infection, hindering the adhesion of a number of pathogens that produce this protein. The data available in the literature on the mechanism of antibacterial protection are scattered and ambiguous. The review considers the literature data and the results of our own experiments on the protective activity of IgA1 protease. We have shown that the recombinant meningococcal IgA1 protease and some of its fragments protect mice from infection with a live virulent culture not only of meningococci of the main epidemic serogroups (A, B, C, and W135), but also of some of the most common virulent pneumococcal serotypes. The data obtained indicate the possibility of creating a monocomponent vaccine against these and, possibly, other bacterial infections. Currently, significant progress has been made in studying the structure and functions of secreted proteins in the bacteria Neisseria meningitidis and Haemophilus influenzae. In this review we describe protein translocation systems of N. meningitidis, which are related to the secretion of proteins in these bacteria, and also present modern data on the functions of these proteins. Analysis of experimental data on the structure of IgA1 protease of N. meningitidis and the formation of immunity during vaccination is of key importance in the development of prophylactic preparations.

Analysis of current epidemiological and clinical characteristics for laboratory confirmed epidemic cerebrospinal meningitis cases in Shandong Province, 2007-2016

Objective: To analyze epidemiological and clinical characteristics of laboratory confirmed epidemic cerebrospinal meningitis cases. Methods: Epidemiological and clinical informations and cerebrospinal fluid (CSF) and blood specimens of AMES (acute meningitis/encephalitis syndrome) cases were collected in the six sentinel hospitals from 2007 to 2016. neisseria meningitides (Nm) species and serogroup identification were detected by the methods of real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and bacterial culture, and epidemiological and clinical characteristics of laboratory confirmed epidemic cerebrospinal meningitis cases were analyzed. Results: 6 809 AMES cases were reported from 2007 to 2016. Total 4 422 cases were detected, and 90 cases were Nm positive. Through the methods of Real-time PCR, bacterial blood culture and CSF culture, the numbers of Nm positive cases were 90, 2 and 1 respectively. Twenty-two Nm cases were identified from 2007 to 2011 (4 cases were ungrouped), which with the highest incidence in serogroup C cases (17/18), and one cases was ungroupable Nm. Nm laboratory confirmed cases (68 cases) were increased dramatically and mainly occurred in serogroup B cases (43/67, 64.2%) from 2012 to 2016, with serogroup C cases highly decreased (5/67, 7.5%) and ungroupable Nm cases increased (13/67, 19.4%) meanwhile. Serogroup W135 and X cases were first detected at 2012 and 2014, and serogroup A remaining a low level which only detected one case at 2013. The morbidity of epidemic cerebrospinal meningitis was occured in the whole year, and mainly in winter and spring. The ratio of Nm laboratory confirmed cases to AMES cases during November to May (3.5%, 67/1 920) was higher than that during June to October (0.9%, 23/2 502) (χ(2)=34.45, P<0.001). Most Nm cases were children, students and farmers, and account for 30.0% (27/90), 31.1% (28/90), 18.9% (17/90), respectively. The majority of Nm cases were under 20 years old (60/90, 66.67%), and serogroup C cases (17/22, 77.3%) mainly occurred in over 12 years old population, while serogroup B (24/43, 55.8%) and ungroupable (6/14) cases mainly occurred in under 12 years old population. The main clinical symptoms of epidemic cerebrospinal meningitis cases were fever (78/90, 86.7%), headache (59/90, 65.6%) and vomiting (51/90, 56.7%). Misdiagnosis rate of admitting diagnosis was up to 87.8% (79/90) for the reason of atypical features in specific symptoms and blood or CSF positive index. The well-healed ratio in correct diagnosed group (7/11) was higher than that in misdiagnosed group (2.5%, 2/79) (χ(2)=40.61, P<0.001). Conclusion: The clinical symptoms of epidemic cerebrospinal meningitis cases were atypical, and the diagnosed sensitivity and accuracy would be improved by enhanced molecular biology detection. The predominant epidemic serogroup of Nm switched from serogroup C to B, and the key work was surveaylance of serogroup transition.

Analysis of epidemic characteristics for meningococcal meningitis in China during 2015-2017

Objective: To analyze the characteristics of epidemiology and neisseria meningitidis (Nm) serogroups distribution for meningococcal meningitis (MM) cases in China from 2015 to 2017. Methods: The data of MM cases were collected from National Notifiable Diseases Registry System (NNDRS) and case-based MM surveillance system (MMSS) from 2015 to 2017; Demographic data are from the National Bureau of statistics. Inclusion criteria: the date of onset was January 1, 2015 to December 31, 2017, the status of infectious disease report card was "final examination card", the cases are classified as "laboratory confirmed cases" and "clinical diagnostic cases", and the card data information of disease name was "Meningococcal meningitis". According to the Diagnostic Criteria for Meningococcal meningitis (WS295-2008), laboratory confirm was made for reported cases or clinically diagnosed cases of meningococcal meningitis. Results: From 2015 to 2017, a total of 325 MM cases were reported in China, with an average annual incidence of 0.007 9 per 100 000 population. And 148 cases were laboratory confirmed. There were 3, 15, 12, 5, 2 and 18 provinces which were reported serogroup A, B, C, W, Y, Others and NG MM Cases, respectively. Except for Tibet and Hainan, other provinces have reported group A cases; The provinces reporting group B, C, W and Y cases increased by 9, 11, 13 and 2 provinces in 2007, respectively compared with 2005. Serogroup B was the primary reason causing the cases of <1 year old and 1-6 years old children; and in this age group, 51.43% (18 cases) and 68.18% (15 cases) of group B were accounted for in laboratory confirmed, respectively; Serogroup C, others and NG was the major reason in the cases of 7-12 and >12 years old students and adults: 33.33% (5 cases) and 26.32% (20 cases) of group C were accounted for in laboratory confirmed respectively, then 26.67% (4 cases) and 34.21% (26 cases) of group others and NG were accounted for respectively; 2 cases of serogroup Y were all >12 years old. Conclusion: The epidemic serogroup of Nm caused MM cases showed a diversifying trend. To develop and provide new vaccines for serogroup B and other bacteria groups should be one of the important tasks for MM control and prevention in the future.

Immunogenic and Protective Properties of Neisseria meningitidis IgA1 Protease and of Its Truncated Fragments

Four recombinant proteins, MA28–P1004LEH6, ME135–H328LEH6, MW329–H622LEH6 and MH835–P1004LEH6, were prepared based on the genomic sequence of IgA1 protease from Neisseria meningitidis serogroup B strain H44/76. The immunogenic and protective properties of these proteins were studied in a mouse model. The predicted T- and B-epitopes located in the N-terminal part of amino acid sequence of this enzyme are very important for the formation of effective protection against meningococci of the three main epidemic serogroups A, B, and C. The small-sized recombinant protein having the sequence ME135–H328LEH6 (molecular weight 23367 Da) appears to be as protective against meningococci of the tested serogroups as the high molecular MA28–P1004LEH6 (molecular weight 109019 Da), the latter being a large-sized analog of full-length IgA1 protease. These proteins can be promising candidates for a polyvalent meningococcal vaccine.

Descriptive Characterization of Epidemic Meningococcal Serogroup W in the Upper West Region of Ghana

Descriptive Characterization of Epidemic Meningococcal Serogroup W in the Upper West Region of Ghana

Safety and immunogenicity of meningococcal ACWY CRM197-conjugate vaccine in children, adolescents and adults in Russia

Neisseria meningitidis is the leading cause of bacterial invasive infections in people aged <15 years in the Russian Federation. The aim of this phase III, multicenter, open-label study was to assess the immunogenicity and safety of the quadrivalent meningococcal CRM197-conjugate vaccine MenACWY when administered to healthy Russian subjects aged 2 years and above. A total of 197 subjects were immunized with a single dose of the vaccine, and serogroup-specific serum bactericidal activity was measured pre and 1-month post-vaccination with human complement (hSBA) serum titers. Regardless of baseline serostatus, 1 month after a single dose of MenACWY-CRM197 85% (95%CI, 79–90%) of subjects showed serologic response against serogroup A, 74% (67–80%) against serogroup C, 60% (53–67%) against serogroup W, and 83% (77–88%) against serogroup Y. The percentage of subjects with hSBA titers ≥ 1:8 1 month after vaccination was 89% (83–93%) against serogroup A, 84% (78–89%) against serogroup C, 97% (93–99%) against serogroup W, and 88% (82–92%) against serogroup Y. Comparable results were obtained across all subjects: children (2 to 10 years), adolescents (11 to 17 years), and adults (≥18 years). The MenACWY-CRM197 vaccine showed an acceptable safety profile and was well tolerated across all age groups, with no serious adverse events or deaths reported during the study. In conclusion, a single dose of meningococcal MenACWY-CRM197 vaccine is immunogenic and has an acceptable safety profile, provides a broad protection against the most frequent epidemic serogroups, and is a suitable alternative to currently available unconjugated monovalent or bivalent polysaccharide vaccines in Russia.

Variability of genes encoding surface proteins used as vaccine antigens in meningococcal endemic and epidemic strain panels from Norway

Surface-expressed protein antigens such as factor H-binding protein (fHbp), Neisserial adhesin A (NadA), Neisserial heparin-binding antigen (NHBA) and Porin protein A (PorA); all express sequence variability that can affect their function as protective immunogens when used in meningococcal serogroup B vaccines like the recently-approved 4CMenB (Bexsero®). We assessed the sequence variation of genes coding for these proteins and two additional proteins (“fusion partners” to fHbp and NHBA) in pathogenic isolates from a recent low incidence period (endemic situation; 2005–2006) in Norway. Findings among strains from this panel were contrasted to what was found among isolates from a historic outbreak (epidemic situation; 1985–1990). Multilocus sequence typing revealed 14 clonal complexes (cc) among the 66 endemic strains, while cc32 vastly predominated in the 38-strain epidemic panel. Serogroup B isolates accounted for 50/66 among endemic strains and 28/38 among epidemic strains. Potential strain-coverage (“sequence match”) for the 4CMenB vaccine was identified among the majority (>70%) of the endemic serogroup B isolates and all of the epidemic serogroup B isolates evaluated. Further information about the degree of expression, surface availability and the true cross-reactivity for the vaccine antigens will be needed to fully characterize the clinical strain-coverage of 4CMenB in various geographic and epidemiological situations.

Molecular typing ofLeptospiraspp. strains isolated from field mice confirms a link to human leptospirosis

In recent years, human leptospirosis has been reported in Jinping and Liping counties, Guizhou province, but the leptospires have never been isolated. To track the source of infection and understand the aetiological characteristics, we performed surveillance for field mice carriage of leptospirosis in 2011. Four strains of leptospire were isolated from Apodemus agrarius. PCR confirmed the four isolates as pathogenic. Multiple-locus variable-number tandem repeat analysis (MLVA) showed that the four strains were closely related to serovar Lai strain 56601 belonging to serogroup Icterohaemorrhagiae, which is consistent with the antibody detection results from local patients. Furthermore, the diversity of leptospiral isolates from different hosts and regions was demonstrated with MLVA. Our results suggest that A. agrarius may be the main carrier of Leptospira in Jinping and Liping counties, and the serogroup Icterohaemorrhagiae serovar may be the epidemic serogroup of Leptospira. This will contribute to the control and prevention of leptospirosis in these localities.

Study of the stability of proteoliposomes as vehicles for vaccines against Neisseria meningitidis based on recombinant porin complexes

Although effective against epidemic serogroup B Neisseria meningitidis strains, vaccines based on outer membrane vesicles continue to present important limitations, and great efforts are currently being focused in the development of a variety of new vaccine candidates and in the reformulation of currently existing ones. In this work, three N. meningitidis proteins, the PorA and PorB porins and the RmpM protein, were cloned, purified and incorporated into liposomes to build defined systems. The ability of proteoliposomes to allow the refolding porin complexes, and their stability during storage at 4°C and after lyophilization in presence of two cryoprotection agents, glucose and trehalose, were evaluated. This approach allowed to mimic the porin complexes present in natural OMVs, reducing the content of hypervariable protein PorA. During storage at 4°C, our systems showed some changes in the morphology and aggregation after three months, while after lyophilization the systems maintained their properties during the whole nine months of storage checked, with glucose allowing the best preservation of the antigenic properties of the proteins in the proteoliposomes.

Conjugate vaccine introduction in the African meningitis belt: meeting surveillance objectives

The epidemiology of bacterial meningitis will change with introduction of meningococcal and pneumococcal conjugate vaccines in the African meningitis belt. The principal objectives of surveillance are to evaluate the impact of vaccination, to detect and investigate epidemics and provide material for research. The capacity of existing surveillance activities in the meningitis belt to meet these objectives varies due to infrastructural and financial constraints. Impact assessment of conjugate vaccine against meningococcal serogroup A will be limited to comparing incidence trends from a few surveillance sites with data obtained before vaccine introduction and to comparing trends in the incidence of suspected cases or localised epidemics in most other settings. The timeliness of detection of epidemics and identification of epidemic meningococcal serogroups could be improved in most countries by analysing suspected case data in health centre level resolution and by investigating outbreaks with mobile teams. For research and impact assessment of pneumococcal conjugate vaccines, several surveillance sites covering at least 0.5 million inhabitants should be maintained which undertake exhaustive case finding and systematic laboratory confirmation of meningitis and pneumonia. Molecular diagnostics will facilitate surveillance in remote areas, but the available techniques should be evaluated for diagnostic performance in the field and long-term sustainability.

Vaccine development against Neisseria meningitidis

SummaryMeningococcal disease is communicable by close contact or droplet aerosols. Striking features are high case fatality rates and peak incidences of invasive disease in infants, toddlers and adolescents. Vaccine development is hampered by bacterial immune evasion strategies including molecular mimicry. As for Haemophilus influenzae and Streptococcus pneumoniae, no vaccine has therefore been developed that targets all serogroups of Neisseria meningitidis. Polysaccharide vaccines available both in protein conjugated and non‐conjugated form, have been introduced against capsular serogroups A, C, W‐135 and Y, but are ineffective against serogroup B meningococci, which cause a significant burden of disease in many parts of the world. Detoxified outer membrane vesicles are used since decades to elicit protection against epidemic serogroup B disease. Genome mining and biochemical approaches have provided astounding progress recently in the identification of immunogenic, yet reasonably conserved outer membrane proteins. As subcapsular proteins nevertheless are unlikely to immunize against all serogroup B variants, thorough investigation by surrogate assays and molecular epidemiology approaches are needed prior to introduction and post‐licensure of protein vaccines. Research currently addresses the analysis of life vaccines, meningococcus B polysaccharide modifications and mimotopes, as well as the use of N. lactamicaouter membrane vesicles.

Development of O-antigen gene cluster-specific PCRs for rapid typing six epidemic serogroups of Leptospira in China

BackgroundLeptospira is the causative agent of leptospirosis. The O-antigen is the distal part of the lipopolysaccharide, which is a key component of outer membrane of Gram-negative bacteria and confers serological specificity. The epidemiology and clinical characteristics of leptospirosis are relative to the serology based taxonomic unit. Identification of Leptospira strains by serotyping is laborious and has several drawbacks.ResultsIn this study, the O-antigen gene clusters of four epidemic Leptospira serogroups (serogroup Canicola, Autumnalis, Grippotyphosa and Hebdomadis) in China were sequenced and all genes were predicted in silico. Adding published sequences of two serogroups, Icterohaemorrhagiae (strain Lai and Fiocruz L1-130) and Sejroe (strain JB197 and L550), we identified six O-antigen-specific genes for six epidemic serogroups in China. PCR assays using these genes were developed and tested on 75 reference strains and 40 clinical isolates.ConclusionThe results show that the PCR-based assays can be reliable and alternative means for rapid typing of these six serogroups of Leptospira.

The Vibrio Cholerae Type VI Secretion System: Evaluating its Role in the Human Disease Cholera

Vibrio cholerae, the marine bacterium responsible for the diarrheal disease cholera, utilizes a multitude of virulence factors to cause disease. The importance of two of these factors, the toxin co-regulated pilus (TCP) and cholera toxin (CT), has been well documented for pandemic O1 and epidemic O139 serogroups. In contrast, endemic non-O1 and non-O139 serogroups can cause localized outbreaks of cholera-like illness, often in the absence of TCP and CT. One virulence mechanism used by these strains is the type VI secretion system (T6SS) to export toxins across the cell envelope and confer toxicity toward eukaryotic and prokaryotic organisms. The V. cholerae strain V52 (an O37 serogroup strain) possesses a constitutively active T6SS and was responsible for an outbreak of gastroenteritis in Sudan in 1968. To evaluate a potential role of the T6SS in the disease cholera, we compared the T6SS clusters of V. cholerae strains with sequenced genomes. We found that the majority of V. cholerae strains, including one pandemic strain, contain intact T6SS gene clusters; thus, we propose that the T6SS is a conserved mechanism that allows pandemic and endemic V. cholerae to persist both in the host and in the environment.

Characterization of potentially virulent non-O1/non-O139 Vibrio cholerae strains isolated from human patients

Traditional methods of typing Vibrio cholerae define virulent strains according to their recognition by sera directed against the known epidemic serogroups O1 and O139, overlooking potentially virulent non-O1/non-O139 strains. Here, we have undertaken the characterization of eight clinical isolates of non-O1/non-O139 V. cholerae, collected during cholera outbreaks in Brazil. Seven of these were typed as O26 and one, 17155, was defined as non-typable. A PCR-based approach has previously detected in these strains several virulence genes derived from the CTXφ prophage and generally associated with pathogenic strains. Here, the presence of the O1-specific wbeN gene was investigated through PCR and found to be restricted to strain 17155, as well as one of the O26 strains, 4756, although neither strain was recognized by O1-specific antisera. The same two isolates were the only strains able to express the cholera toxin in culture, assayed by western blotting. They also possessed four repeats of the heptanucleotide TTTTGAT upstream of the ctxAB genes encoding the cholera toxin. The remaining strains possessed only two intact repeats, whereas pathogenic O1 possessed four to six repeats. To define their evolutionary relationships, selected 16S–23S intergenic rRNA spacer regions were sequenced from the various strains and the resulting sequences used to build phylogenetic trees. Strains 4756 and 17155 always clustered with control O1 strains, whereas the remaining O26 strains clustered separately. These results confirm that, despite their serological phenotype, these two strains are genotypically related to O1 strains and potentially able to produce epidemic cholera.

Association of respiratory tract infection symptoms and air humidity with meningococcal carriage in Burkina Faso

To evaluate risk factors for meningococcal carriage and carriage acquisition in the African meningitis belt, comparing epidemic serogroup A (NmA) to non-epidemic serogroups. During the non-epidemic meningitis season of 2003, pharyngeal swabs were taken at five monthly visits in a representative population sample (N = 488) of Bobo-Dioulasso, Burkina Faso (age 4-29 years) and analysed by culture. Standardized questionnaires were administered. In 2006, a similar study was performed in 624 individuals (age 1-39 years) during an NmA meningitis epidemic. We evaluated serogroup-specific risk factors for carriage, carriage acquisition and clearance using multivariate logistic and Poisson regression, and a Cox proportional hazard model. The prevalence of NmA carriage (current or recent pharyngitis or rhinitis) was 16% (31%) vs. 0% (9%) in the epidemic vs. the hyperendemic setting. During the epidemic situation, NmA carriage was significantly associated with recent sore throat (adjusted odds ratio (OR), 3.41) and current rhinitis (OR 2.65). During the non-epidemic meningitis season in 2003, air humidity (20-39% and >or=40%, compared to <20%) during the month before swabbing was significantly and positively associated with carriage acquisition of non-groupable meningococci (OR 2.18 and 1.55) and inversely with carriage clearance (hazard ratio 0.61 and 0.27, respectively). Respiratory tract infections may increase meningococcal carriage, and thus contribute to epidemic risk, in addition to seasonality in the meningitis belt. Humid climate may favour carriage of unencapsulated meningococci. These findings may help identifying interventions against epidemic and hyperendemic meningococcal meningitis due to non-vaccine serogroups.

Association of Vibrio cholerae O1 El Tor and O139 Bengal with the Copepods Acartia tonsa and Eurytemora affinis

The association of Vibrio cholerae with zooplankton has been suggested as an important factor in transmission of human epidemic cholera, and the ability to colonize zooplankton surfaces may play a role in the temporal variation and predominance of the two different serogroups (V. cholerae O1 El Tor and O139) in the aquatic environment. To date, interactions between specific serogroups and species of plankton remain poorly understood. Laboratory microcosm experiments were carried out to compare quantitatively the colonization of two copepod species, Acartia tonsa and Eurytemora affinis, by each of the epidemic serogroups. V. cholerae O1 consistently achieved higher abundances than V. cholerae O139 in colonizing adults of each copepod species as well as the multiple life stages of E. affinis. This difference in colonization may be significant in the general predominance of V. cholerae O1 in cholera epidemics in rural Bangladesh where water supplies are taken directly from the environment.

Laboratory‐Acquired Serogroup A Meningococcal Meningitis

Neisseria meningitidis causes fulminant meningitis and sepsis. Worldwide, N. meningitidis serogroup A is responsible for large epidemic outbreaks (e.g., subSaharan Africa) and serogroups B, C, Y and W-135 cause epidemic and endemic disease. Meningococci are usually transmitted from person to person through close contact with contaminated aerosols and secretions from the human nasopharynx. Laboratory-acquired infection has been reported infrequently but laboratory technicians are at increased risk. Most of the reported cases of laboratory-acquired infections occur in clinical microbiology laboratories and have been due to serogroups B and C. For reasons that are unclear, the reported mortality of laboratory-acquired N. meningitidis sepsis or meningitis is ~50% , which is higher than mortality from endemic infections. We present the first reported case of laboratoryacquired serogroup A N. meningitidis meningitis in a 21 yr-old research laboratory assistant.

Hypermutable bacteria isolated from humans – a critical analysis

Hypermutable bacteria of several species have been described among isolates recovered from humans over the last decade. Interpretation of the literature in this area is complicated by diversity in the determination and definition of hypermutability, and this review outlines the different methods used. Inactivation of the mismatch repair gene mutS is often implicated in the mutator phenotype; the reported effect of mutS inactivation on mutation frequency varies widely between species, from under 10-fold to nearly 1,000-fold, but also varies among different reports on the same species. Particularly high proportions of mutators have been reported among Pseudomonas aeruginosa and other species in the cystic fibrosis lung, epidemic serogroup A Neisseria meningitidis, and Helicobacter pylori. Aspects of the biology of these infections that could be relevant to hypermutability are discussed, and some future directions that may increase our understanding of mutators among bacteria isolated from humans are considered.