Invasive Serogroup Research Articles

Invasive Meningococcal Disease in MSM

Historically, the most common source of meningococcal infection in adults has been exposure to an asymptomatic person with nasopharyngeal carriage of the organism. Now, researchers at the New York City Department of Health and Mental Hygiene (DOHMH) and the CDC report 18 cases of invasive serogroup C Neisseria meningitidis disease (SCMD) diagnosed …

Parents' experiences of support during and after their child's diagnosis of Meningococcal Disease

To understand parents'/carers' experiences of support received following their child's diagnosis of invasive meningococcal serogroup B disease (MenB). Structured interviews with parents/carers of 244 survivors of MenB disease in childhood, drawn from a population-based case-control study. Responses indicated that optimal support should encompass the whole treatment pathway, beginning with fast and accurate recognition of MenB by clinicians, followed by the provision of information about the symptoms and possible sequelae of MenB, better communication about the treatment process and disease progression and greater follow-up care. Parents' experience of support following their child's diagnosis of MenB could be significantly enhanced through better education and enhanced knowledge in health care professionals, improved access to information about short- and long-term sequelae and easier access to follow-up support and advice. Much of the data generated pertained to situations and processes common to most serious illnesses occurring in children and therefore it is likely that these findings pose wider questions about support and communication in paediatrics.

The Disease Burden of Invasive Meningococcal Serogroup B Disease in Canada

Invasive meningococcal disease remains a rare but deadly infection in Canada. New serogroup B vaccines may offer the potential for prevention and control. This report examines the disease burden caused by serogroup B invasive meningococcal infections. From 2002 to 2011, active, population-based metropolitan area surveillance for adult and pediatric hospital admissions for adult and pediatric hospital admissions for laboratory-confirmed infection with Neisseria meningitidis, was conducted by the 12 centers of the Canadian Immunization Monitoring Program, Active. A total of 769 invasive meningococcal cases occurred from 2002 to 2011; 54% (n = 413) in children with a peak incidence of 6.16 (95% confidence interval: 3.18-10.76) per 100,000 in children aged <1 year in 2009. Serogroup B accounted for the largest proportion of cases and had the highest incidence of all serogroups across all ages, with a peak incidence of 0.31 (0.23-0.40) per 100,000 in 2007. Serogroup B case fatality rate was 4.3% in children, and 21% of pediatric survivors had sequelae. B:17:P1.19 ST-269 was the most frequently detected antigenic type. Serogroup B invasive meningococcal infections caused substantial morbidity and mortality and are the leading cause of invasive meningococcal disease in Canada. The proportion of cases potentially preventable with the new serogroup B vaccines should be evaluated to determine whether universal immunization programs are warranted.

Genetic and antigenic characterization of invasive endemic serogroup B Neisseria meningitidis from Ontario, Canada, in 2001–2010

This study examined the antigenic and genetic diversity of serogroup B Neisseria meningitidis (MenB) recovered from invasive meningococcal disease (IMD) cases in Ontario, Canada, over the period 2001-2010 during which no MenB outbreaks had occurred. MenB was found to be responsible for 39 % of all IMD cases, with the remaining cases caused mainly by serogroups Y (28 %), C (23.5 %) and W135 (8 %). One hundred and ninety-three individual MenB case isolates were collected and characterized. Of the 88 sequence types (STs) identified, 75 were grouped into 14 known clonal complexes (CCs), whilst 13 STs were not assigned to any known CC. Fifty-seven different PorA genotypes and 88 STs defined the diversity of invasive MenB in Ontario, which supported the endemic nature of MenB disease in Ontario. Despite the presence of the hypervirulent ST-41/44 and ST-32 CCs, no single ST was predominant and responsible for a large number of IMD cases. Although the Québec outbreak clone of ST-269 was also found in Ontario, the 20 case isolates were genetically diverse: they grouped into seven STs and did not have a predominant PorA genotype. eburst analysis identified a new CC responsible for 14.5 % of the MenB case isolates. The six most common PorA variable region 2 (VR2) genotypes (VR2-9, -4, -14, -16, -13-1 and -16-3) were found in 67 % of invasive MenB isolates.

Safety and Immunogenicity of a Meningococcal B Bivalent rLP2086 Vaccine in Healthy Toddlers Aged 18–36 Months

A bivalent, recombinant, factor H-binding protein (rLP2086) vaccine was developed to protect against invasive Neisseria meningitidis serogroup B (MnB) in children and adolescents. Healthy toddlers (N = 99) were enrolled to 3 ascending dose-level cohorts (20, 60 or 200 μg). Within each cohort (n = 33), subjects were randomized to receive an initial formulation of the bivalent rLP2086 vaccine at 0, 1 and 6 months or hepatitis A vaccine/placebo control (2:1 ratio). Reactogenicity was assessed by parental reporting of local and systemic reactions using electronic diaries and reports of unsolicited adverse events. Immunogenicity was assessed by serum bactericidal activity assay using human complement and rLP2086-specific IgG binding. The vaccine was considered to be well tolerated. Tenderness was the most frequently reported local reaction. Upper respiratory tract infection was the most commonly reported adverse event and occurred more frequently in the control group. Three cases (200 μg dose) of severe erythema that did not interfere with limb movement were reported. Four toddlers developed fever >40.0°C, 3 in the 200 μg group and 1 in the 60 μg group. Postdose 3, seroconversion (serum bactericidal activity assay using human complement ≥4-fold rise from baseline) was observed in 61.1-88.9% of participants against MnB strains expressing LP2086 variants homologous or nearly homologous to vaccine antigens and 11.1-44.4% against MnB strains expressing heterologous LP2086 variants. Seroconversion was observed in 77.8-100% of participants against additional, exploratory MnB strains expressing vaccine-homologous or heterologous LP2086 variants. This study shows that the bivalent rLP2086 vaccine is well tolerated and immunogenic in toddlers.

Meningococcal disease: changes in epidemiology and prevention.

The human bacterial pathogen Neisseria meningitidis remains a serious worldwide health threat, but progress is being made toward the control of meningococcal infections. This review summarizes current knowledge of the global epidemiology and the pathophysiology of meningococcal disease, as well as recent advances in prevention by new vaccines. Meningococcal disease patterns and incidence can vary dramatically, both geographically and over time in populations, influenced by differences in invasive meningococcal capsular serogroups and specific genotypes designated as ST clonal complexes. Serogroup A (ST-5, ST-7), B (ST-41/44, ST-32, ST-18, ST-269, ST-8, ST-35), C (ST-11), Y (ST-23, ST-167), W-135 (ST-11) and X (ST-181) meningococci currently cause almost all invasive disease. Serogroups B, C, and Y are responsible for the majority of cases in Europe, the Americas, and Oceania; serogroup A has been associated with the highest incidence (up to 1000 per 100,000 cases) and large outbreaks of meningococcal disease in sub-Saharan Africa and previously Asia; and serogroups W-135 and X have emerged to cause major disease outbreaks in sub-Saharan Africa. Significant declines in meningococcal disease have occurred in the last decade in many developed countries. In part, the decline is related to the introduction of new meningococcal vaccines. Serogroup C polysaccharide-protein conjugate vaccines were introduced over a decade ago, first in the UK in a mass vaccination campaign, and are now widely used; multivalent meningococcal conjugate vaccines containing serogroups A, C, W-135, and/or Y were first used for adolescents in the US in 2005 and have now expanded indications for infants and young children, and a new serogroup A conjugate vaccine has recently been introduced in sub-Saharan Africa. The effectiveness of these conjugate vaccines has been enhanced by the prevention of person-to-person transmission and herd immunity. In addition, progress has been made in serogroup B-specific vaccines based on conserved proteins and outer membrane vesicles. However, continued global surveillance is essential in understanding and predicting the dynamic changes in the epidemiology and biological basis of meningococcal disease and to influence the recommendations for current and future vaccines or other prevention strategies.

Outcomes of invasive meningococcal serogroup B disease in children and adolescents (MOSAIC): a case-control study

Serogroup B meningococcal disease is the commonest cause of meningitis and septicaemia in high-income countries. Assessment of new serogroup B meningococcal vaccines is hampered by a scarcity of data on the burden of disease in survivors. We aimed to estimate the disease burden in children having survived serogroup B meningococcal disease. In this case-control study, we recruited children from the UK National Meningococcal Registry between May, 2008, and September, 2010. Eligible children were survivors who had had serogroup B meningococcal disease confirmed by culture or PCR and were aged 1 month to 13 years at disease. Age-matched and sex-matched controls were recruited through the family doctor of the children who had the meningococcal disease. Physical, psychological, neurocognitive, and educational outcomes were assessed through a standardised interview with validated instruments. We did matched analyses using generalised estimating equations (GEE). Researchers were masked to the children's serogroup B meningococcal status. Of the 537 children who had serogroup B meningococcal disease and were available for recruitment, 245 were assessed. 328 controls were also recruited; 221 controls were matched with a case and 107 were additional unmatched controls. The mean age was 6·5 (SD 2·8) years in children with serogroup B meningococcal disease and 6·9 (2·9) in controls. In the full sample, children who had serogroup B meningococcal disease were more likely than controls to have bilateral sensorineural hearing loss of 40 dB or more (unmatched 11 [5%] of 232 children with meningococcal disease vs three [<1%] of 318 controls; matched odds ratio [OR] 4·8, 95% CI 1·3 to 17·4, p=0·02), lower full-scale IQ (matched mean 99·5 for children with meningococcal disease and 107·2 for controls; matched coefficient -7·6, 95% CI -9·9 to -5·4, p<0·0001), and psychological disorders (61 [26%] of 235 children with meningococcal disease vs 33 (10%) of 322 controls; matched full sample OR 2·6, 1·6 to 4·2, p<0·0001). Disabling amputations were noted in three (1%) of 239 children who had serogroup B meningococcal disease compared with none of the 322 controls. Children with meningococcal disease were also more likely to have deficits in executive function and multiple aspects of memory. Deficits were identified in 87 (36%) of 244 children with serogroup B meningococcal disease and 49 (15%) of 328 controls (matched OR 2·7, 1·8 to 4·1, p<0·0001). Major disabling deficits were identified in 21 (9%) of 244 children with meningococcal disease compared with six (2%) of 328 controls (matched OR 5·0, 2·0 to 12·6, p=0·001). No significant differences were noted in attentional function or post-traumatic stress disorder between children with serogroup B meningococcal disease and controls. Most children survive serogroup B meningococcal disease without major sequelae. However, about a tenth have major disabling deficits and more than a third have one or more deficits in physical, cognitive, and psychological functioning, with the additional burden of memory deficits and executive function problems. These findings should help to guide assessments of new vaccines and suggest that all survivors of serogroup B meningococcal disease should be screened for psychological disorders and cognitive deficits in addition to hearing loss. Meningitis Trust and Big Lottery Fund, UK.

A combined approach to assess the potential coverage of a multicomponent protein-based vaccine.

Meningococcal disease caused by Neisseria meningitidis serogroup B is a public health concern even in developed countries. Despite glycoconjugate vaccines against the other invasive serogroups (A, C, W135, Y) are already available and successfully introduced in many countries, no vaccine is currently in use for prevention of serogroup B meningitis. A protein based, multicomponent vaccine (4CMenB) has been developed and proposed for prevention of invasive serogroup B meningococcal disease (MenB). This novel vaccine has been tested in clinical trials and shown to be well tolerated and immunogenic, inducing bactericidal antibodies in infants, adolescents and adults. The high level of genetic and antigenic variability observed in MenB clinical isolates, requires a suitable method to assess the ability of the 4CMenB vaccine to cover genetically diverse menigococcal strains and to estimate the potential public health impact. To this purpose the Meningococcal Antigen Typing System (MATS) has been developed and recently described. This method provides a quick and reproducible tool to estimate the level of expression and immunoreactivity of each of the vaccine antigens, in any meningococcal isolate, and it is related to the likelihood that the isolate will be killed by sera from immunized subjects. A multi-laboratory study involving several European countries, demonstrates that the 4CMenB has the potential to protect against a significant proportion of menB strains circulating in Europe.

Population Snapshot of Invasive Serogroup B Meningococci in South Africa from 2005 to 2008

In South Africa, serogroup B meningococcal disease is sporadic. The aim of this study was to characterize serogroup B strains causing invasive meningococcal disease (IMD) in South Africa from 2005 to 2008. Isolates, collected through a national, laboratory-based surveillance program for IMD, were characterized by multilocus sequence typing (MLST). Two thousand two hundred thirty-four cases were reported, of which 1,447 had viable isolates. Intermediate resistance to penicillin was observed in 2.8% (41/1,447) of all strains. Serogroup B was the second most common serogroup (17%, 251/1,447) and increased from 14% (58/414) in 2005 to 25% (72/290) in 2008 (P < 0.001); however, incidence remained stable during the study period (average incidence, 0.13/100,000 population) (P = 0.54). Serogroup B was predominantly characterized by three clonal complexes, namely, ST-41/44/lineage 3, ST-32/ET-5, and the new complex ST-4240/6688, which accounted for 27% (65/242), 23% (55/242), and 16% (38/242) of isolates, respectively. ST-4240/6688 was more prevalent among young children (<5 years) than other clonal complexes (27/37 [73%] versus 108/196 [55%]; P = 0.04). In the most densely populated province of South Africa, Gauteng, the prevalence of ST-32/ET-5 increased from 8% (2/24) in 2005 to 38% (9/24) in 2008 (P = 0.04). Capsular switching was observed in 8/242 (3%) strains. The newly assigned clonal complex ST-4240/6688 was more common in young children.

Safety, immunogenicity, and tolerability of meningococcal serogroup B bivalent recombinant lipoprotein 2086 vaccine in healthy adolescents: a randomised, single-blind, placebo-controlled, phase 2 trial

Neisseria meningitidis serogroup B is a major cause of invasive meningococcal disease, but a broadly protective vaccine is not currently licensed. A bivalent recombinant factor H-binding protein vaccine (recombinant lipoprotein 2086) has been developed to provide broad coverage against diverse invasive meningococcus serogroup B strains. Our aim was to test the immune response of this vaccine. This randomised, placebo-controlled trial enrolled healthy adolescents from 25 sites in Australia, Poland, and Spain. Exclusion criteria were previous invasive meningococcal disease or serogroup B vaccination, previous adverse reaction or known hypersensitivity to the vaccine, any significant comorbidities, and immunosuppressive therapy or receipt of blood products in the past 6 months. Participants were randomly assigned with a computerised block randomisation scheme to receive ascending doses of vaccine (60, 120, or 200 μg) or placebo at 0, 2, and 6 months. Principal investigators, participants and their guardians, and laboratory personnel were masked to the allocation; dispensing staff were not. Immunogenicity was measured by serum bactericidal assays using human complement (hSBA) against eight diverse meningococcus serogroup B strains. The co-primary endpoints were seroconversion for the two indicator strains (PMB1745 and PMB17) analysed by the Clopper-Pearson method. Local and systemic reactions and adverse events were recorded. The study is registered at ClinicalTrials.gov, number NCT00808028. 539 participants were enrolled and 511 received all three study vaccinations--116 in the placebo group, 21 in the 60 μg group, 191 in the 120 μg group, and 183 in the 200 μg group. The proportion of participants responding with an hSBA titre equal to or greater than the lower limit of quantitation of the hSBA assays (reciprcocal titres of 7 to 18, depending on test strain) was similar for the two largest doses and ranged from 75·6 to 100·0% for the 120 μg dose and 67·9 to 99·0% for the 200 μg dose. Seroconversion for the PMB1745 reference strain was 17 of 19 (89·5%) participants for the 60 μg dose, 103 of 111 (92·8%) participants for the 120 μg dose, 94 of 100 (94·0%) participants for the 200 μg dose, and four of 73 (5·5%) participants for placebo. For the PMB17 reference strain seroconversion was 17 of 21 (81·0%) participants for the 60 μg dose, 97 of 112 (86·6%) participants for the 120 μg dose, 89 of 105 (84·8%) participants for the 200 μg dose, and one of 79 (1·3%) participants for placebo. The hSBA response was robust as shown by the high proportion of responders at hSBA titres up to 16. Mild-to-moderate injection site pain was the most common local reaction (50 occurrences with the 60 μg dose, 437 with the 120 μg dose, 464 with the 200 μg dose, and 54 with placebo). Systemic events, including fatigue and headache, were generally mild to moderate. Overall, adverse events were reported by 18 participants (81·8%) in the 60 μg group, 77 (38·9%) in the 120 μg group, 92 (47·2%) in the 200 μg group, and 54 (44·6%) in the placebo group. Fevers were rare and generally mild (one in the 60 μg group, 24 in the 120 μg group, 35 in the 200 μg group, and five in the placebo group; range, 0-6·3% after each dose). Incidence and severity of fever did not increase with subsequent vaccine dose within groups. One related serious adverse event that resolved without sequelae occurred after the third dose (200 μg). The bivalent recombinant lipoprotein 2086 vaccine is immunogenic and induces robust hSBA activity against diverse invasive meningococcus serogroup B disease strains and the vaccine is well tolerated. Recombinant lipoprotein 2086 vaccine is a promising candidate for broad protection against invasive meningococcus serogroup B disease. Wyeth, Pfizer.

A combination of two molecular typing methods for characterization of Pnemococci isolates from Saudi

Streptococcus pneumonia is a major worldwide causative agent of morbidity and mortality among young children, adults and old patients. The ability of pneumococci to cause disease is directly related to its capsule which is a major virulence factor of pneumococcal pneumonia. The aim of the present study was to characterize epidemiologically important Pneumococcus by using two molecular typing. A total of 266 pneumococci isolates from cerebral spinal fluid, nosopharengile aspirate, pleural fluid from children, adults and old patients were donated by Al-Karj hospital, Riyadh Saudi Arabia were analyzed by polymerase chain reaction (PCR) and light cycler with specific primers. Our study indicated the presence of frequent strains (6A and 19A). These new strains are not included in (11-Valent conjugate vaccine) component which is being used as a vaccine in Saudi Arabia. Since the capsular components of these new serotypes do not include this vaccine, we propose the addition of these invasive serotype capsular components to the current (11-Valent conjugate Vaccine) which is being used in Saudi Arabia. Key words: Pneumococci, capsular typing, invasive serogroups, multiplex PCR.

Invasive serogroup B Neisseria meningitidis in Quebec, Canada, 2003 to 2010: persistence of the ST-269 clone since it first emerged in 2003.

In the era after the introduction of the meningococcal serogroup C conjugate vaccine, from 1 January 2003 to 31 December 2010, serogroup B meningococci were the major cause of invasive meningococcal disease in the province of Québec, Canada, being responsible for 72% of all meningococcal disease cases. Of the 334 invasive serogroup B Neisseria meningitidis strains analyzed, 53.9% belonged to the ST-269 clonal complex (CC). Since it first emerged in 2003, the percentage of invasive serogroup B isolates that belonged to the ST-269 CC had increased from 35% in 2003 to 76% in 2010. Among the 180 meningococci in the ST-269 CC, 91.7% belonged to a single ST (ST-269). The most common PorA genotypes identified in the ST-269 CC were (i) VR1 19-1, VR2 15-11, VR3 36 (84%) and (ii) VR1 18-7, VR2 9, VR3 35-1 (9%). Cases of invasive disease due to the ST-269 CC were commonly found in those aged 11 to 19 years (30.5%) and 20 to 40 years (25.5%). Meningococci of the ST-269 CC were uncommon in other Canadian provinces. In contrast to the ST-269 CC, invasive serogroup B meningococci that belonged to the ST-41/44 CC were much more diverse genetically. However, one ST (ST-571), which is uncommon in the United States, accounted for 35% of all cases due to this CC. The current finding suggests that the ST-269 clone may indeed represent an emerging hypervirulent clone of meningococci.

Genetic and antigenic analysis of invasive serogroup C Neisseria meningitidis in Canada: A decrease in the electrophoretic type (ET)-15 clonal type and an increase in the proportion of isolates belonging to the ET-37 (but not ET-15) clonal type during the period from 2002 to 2009.

Serogroup C meningococcal disease has been endemic in Canada since the early 1990s, with periods of hyperendemic disease documented in the past two decades. The present study characterized invasive serogroup C meningococci in Canada during the period from 2002 to 2009. Serogroup C meningococci were serotyped using monoclonal antibodies. Their clonal types were identified by either multilocus enzyme electrophoresis or multilocus sequence typing. The number of invasive serogroup C Neisseria meningitidis isolates received at the National Microbiology Laboratory (Winnipeg, Manitoba) for characterization has dropped from a high of 173 isolates in 2001 to just 17 in 2009, possibly related to the introduction of the serogroup C meningococcal conjugate vaccine. Before 2006, 80% to 95% of all invasive serogroup C meningococci belonged to the electrophoreic type (ET)-15 clonal type, and the ET-37 (but not ET-15) type only accounted for up to 5% of all isolates. However, beginning in 2006, the percentage of the ET-15 clonal type decreased while the ET-37 (but not ET-15) type increased from 27% in 2006 to 52% in 2009. The percentage of invasive serogroup C isolates not belonging to either ET-15 or ET-37 also increased. Most ET-15 isolates expressed the antigenic formula of C:2a:P1.7,1 or C:2a:P1.5. In contrast, the ET-37 (but not ET-15) isolates mostly expressed the antigens of C:2a:P1.5,2 or C:2a:P1.2. A shift in the antigenic and clonal type of invasive serogroup C meningococi was noted. This finding suggests vigilance in the surveillance of meningoccocal disease is warranted.

Prevalence and genetic diversity of pneumococcal serogroup 6 in Australia

The prevalence of the newly discovered pneumococcal serotype 6C has increased in some countries since the introduction of seven-valent conjugate pneumococcal vaccine (PCV7). The distribution of invasive serogroup 6 serotypes, in Australia, including 6C and 6D, has not been reported previously. During the period 1999 to 2008, 6097 isolates were referred to the New South Wales Pneumococcal Reference Laboratory for serotyping. Of these, 847 were identified by Quellung reaction as belonging to serogroup 6 and 702 were available for further study. Serotypes were determined by serotype-specific PCR as follows: 6A, 197 (28.1%); 6B, 452 (64.4%); 6C, 52 (7.4%) and one 6D. The average numbers of invasive serogroup 6 isolates, per annum, fell from 62.2 before (2000– 2005) to 49.7 after (2006–2008) the introduction of PCV7. The proportions of invasive 6B fell (from 72.4% to 47.3%, p 0.03), those of 6C rose (from 3.3% to 17%, p 0.02) significantly and those of 6A remained fairly constant (24.3% vs 27%, p 0.69) between the two periods. All 6C and 6D and selected 6A and 6B isolates were further characterized by multilocus sequence typing and sequence analysis of cps genes cpsA-cpsB (wzg-wzh) and wchA-wciNbeta-wciO, wciP. Results showed considerable diversity within serotype 6C, apparently as a result of both mutation and recombination. Sequence typing indicates that, in Australia, 6C has been largely derived from 6A. The genetic diversity and rapid increase in incidence of serotype 6C causing invasive pneumococcal disease has potential implications for vaccine efficacy.

Genetic characterisation of the emerging invasive Neisseria meningitidis serogroup Y in Sweden, 2000 to 2010

Neisseria meningitidis serogroups B and C have been responsible for the majority of invasive meningococcal disease in Europe. Recently, an increase of N. meningitidis disease due to serogroup Y has been noted in Sweden (in 2010, the proportion was 39%, with an incidence of 0.23 per 100,000 population), as well as in other northern European countries. We aimed to investigate the clonal pattern of the emerging serogroup Y in Sweden during 2000 to 2010. The serogroup Y isolates identified during this time (n=85) were characterised by multilocus sequence typing and sequencing of the fetA, fHbp, penA, porA and porB genes. The most frequent clone (comprising 28 isolates) with identical allele combinations of the investigated genes, was partly responsible for the observed increased number of N. meningitidis serogroup Y isolates. It was sulfadiazine resistant, with genosubtype P1.5-2,10-1,36-2, sequence type 23, clonal complex 23, porB allele 3-36, fetA allele F4-1, fHbp allele 25 and penA allele 22. The first case with disease due to this clone was identified in 2002: there was a further case in 2004, six during 2006 to 2007, eight during 2008 to 2009, with a peak of 12 cases in 2010. An unusual increase of invasive disease in young adults (aged 20–29 years) caused by this clone was shown, but no increase in mortality rate was observed.

Abdominal acute pain as initial symptom of invasive meningococcus serogroup A illness

The abdominal acute pain as an initial symptom of meningococcemia is an infrequent entity rarely described in the literature. We present a 10 month-old infant with fever and acute abdominal pain, who was admitted in Emergency Care. Later, Neisseria meningitidis serogroup A was isolated from blood cultures.

Serotype-Specific Typing Antisera for Pneumococcal Serogroup 6 Serotypes 6A, 6B, and 6C

Streptococcus pneumoniae strains can express one of at least 92 capsular serotypes. To our knowledge, our laboratory is one of two that maintain antisera for resolution of the first 90 discovered pneumococcal serotypes (4; unpublished data). Recently, the evaluation of serogroup 6 isolates using monoclonal antibodies led to the discovery of the 91st serotype, 6C (7), which has become the prevalent invasive serogroup 6 serotype within the United States (2, 9). The pneumococcal 7-valent conjugate vaccine (PCV7) does not protect against it, and it is not included within the newly licensed 13-valent conjugate vaccine. In addition, serotype 6C carriage may also be common within PCV7-vaccinated populations (3). Prior to the discovery of serotype 6C, serotypes 6A and 6B were the 2 known serogroup 6 serotypes. CDC antisera for quellung-based resolution of serotypes 6A and 6B are designated as Danish factors 6b and 6c (DF-6b and DF-6c), respectively. Our original DF-6b antiserum was positive for both 6A and 6C serotypes, preventing their resolution (Table ​(Table11). TABLE 1. DF-6b, DF-6c, and DF-6d quellung results We produced DF-6d antiserum specific to serotype 6C and DF-6b antiserum specific to 6A as follows. New Zealand White female rabbits were inoculated with S. pneumoniae serotypes 6C or 6A formalin-fixed whole cells. The inocula consisted of serotype 6C or 6A cell suspensions (108 to 109 cells per ml in phosphate-buffered saline), which were administered intravenously via the marginal ear vein (Table ​(Table2).2). Blood was drawn after week 4 of dosing, and serum was evaluated for antibody titer to serotype 6C or 6A and cross-reactivity to serotypes 6A, 6B, and 6C by the quellung reaction. Cross-reactivity was removed from DF-6d by absorbing the serum with formalin-fixed cells of serotypes 6A and 6B. DF-6b antiserum was absorbed with formalin-fixed cells of serotypes 6B and 6C. The resulting DF-6d antiserum was specific for serotype 6C only, and DF-6b was specific to 6A only (Table ​(Table11). TABLE 2. Dosing schedule for preparation of antisera The specificity of DF-6b, DF-6c, and DF-6d antisera was evaluated with stock strains and 159 clinical isolates, each representing one of the serotypes 6A, 6B, or 6C. For all strains, Neufeld quellung results were compared to PCR testing specific for the serotype 6C wicN6C locus (2, 7, 8) with no inconsistencies observed. We have replaced our previous methods with these procedures for producing specific factor sera against serotypes 6A and 6C. We have now learned that Statens Serum Institute (SSI) has also recently produced factor 6d against serotype 6C (5). Our DF-6b, unlike the SSI factor 6b, is now serotype 6A specific and does not cross-react against serotype 6C. Serotype 6C-specific antiserum will be useful for laboratories which utilize quellung testing. Recently a fourth serogroup 6 serotype, serotype 6D, has been discovered in nature (1, 6) that is recognizable by a positive quellung test for serotype 6B combined with a positive PCR test for wciN6C. Despite extensive screening, we have not yet encountered this serotype (2). We do not yet know if our DF-6d antiserum would cross-react with serotype 6D. Consequently we screen all quellung test 6B strains by PCR for the presence of wciN6C (2, 8).

Phenotypic and molecular characterization of invasive serogroup W135 Neisseria meningitidis strains from 1990 to 2005 in Brazil

Neisseria meningitidis serogroup W135 has been associated with global outbreaks since the 2000 Hajj. Considering that N. meningitidis serogroup W135 is the third most prevalent serogroup isolated in Brazil in the last 10 years, and the possibility that the Hajj-related N. meningitidis serogroup W135 clone has been causing disease in Brazil, the present study characterized invasive N. meningitidis serogroup W135 isolates recovered in Brazil from 1990 to 2005. The isolates were characterized by serotyping, PorA and PorB VR typing, FetA and 16S rRNA typing, multilocus sequence typing (MLST) and pulsed field gel electrophoresis (PFGE). Based on MLST, 73% of the isolates were clustered in one major clone of ST-11 complex/ET37 complex. Strains of this clone had the same STs, serotypes and PorA VR types as found in Hajj-related N. meningitidis serogroup W135 clone. One of these strains had the Hajj-2000 outbreak strain genotype, including 16S rRNA gene sequence 31 and 84% relatedness by PFGE. Taken together, these data suggest that the Hajj-related N. meningitidis serogroup W135 clone is present in Brazil but has not yet caused a substantial number of infections. Given the emergence of N. meningitidis serogroup W135 globally and the unpredictability of meningococcal disease epidemiology, continued surveillance for this invasive N. meningitidis serogroup W135 clone is needed for control and prevention strategies.

A new meningococcal conjugate vaccine: What should physicians know and do?

A quadrivalent meningococcal conjugate vaccine for serogroups A, C, Y and W135 (MCV4 [Menactra, sanofi pasteur, Canada]) was introduced in Canada in 2007 for persons two years of age or older. MCV4 adds three serogroups to the meningococcal serogroup C conjugate vaccine, which has been used for several years. The rates of invasive meningococcal serogroup C infection have decreased over the past decade, attributable to the meningococcal C conjugate vaccine. However, the incidence of infection caused by serogroups A, B, Y and W135 have not changed substantially. MCV4 induces the production of protective antibodies to serogroups A, C, Y and W135 in adults and children older than two years of age. Serious adverse events from MCV4 are low. In view of the effectiveness of the meningococcal C conjugate vaccine for young infants and the historic high number of meningococcal serogroup C infections in Canada, physicians should encourage and promote publicly funded immunization programs for infants starting at two months of age. MCV4 should also be given to children aged two years who are at increased risk for meningococcal infection. MCV4 may also be considered for HIV-positive children two years of age or older. All adolescents should be offered a booster dose with MCV4 or a meningococcal C conjugate vaccine at approximately 12 years of age. Both vaccines are generally safe and well tolerated.

Un nouveau vaccin conjugué contre le méningocoque: Que devraient faire et savoir les médecins?

A quadrivalent meningococcal conjugate vaccine for serogroups A, C, Y and W135 (MCV4 [Menactra, sanofi pasteur, Canada]) was introduced in Canada in 2007 for persons two years of age or older. MCV4 adds three serogroups to the meningococcal serogroup C conjugate vaccine, which has been used for several years. The rates of invasive meningococcal serogroup C infection have decreased over the past decade, attributable to the meningococcal C conjugate vaccine. However, the incidence of infection caused by serogroups A, B, Y and W135 have not changed substantially. MCV4 induces the production of protective antibodies to serogroups A, C, Y and W135 in adults and children older than two years of age. Serious adverse events from MCV4 are low. In view of the effectiveness of the meningococcal C conjugate vaccine for young infants and the historic high number of meningococcal serogroup C infections in Canada, physicians should encourage and promote publicly funded immunization programs for infants starting at two months of age. MCV4 should also be given to children aged two years who are at increased risk for meningococcal infection. MCV4 may also be considered for HIV-positive children two years of age or older. All adolescents should be offered a booster dose with MCV4 or a meningococcal C conjugate vaccine at approximately 12 years of age. Both vaccines are generally safe and well tolerated.