Atypical presentation of Neisseria meningitidis serogroup W disease is associated with the introduction of the 2013 strain.

Since 2015, the incidence of invasive meningococcal disease (IMD) caused by serogroup W (MenW) has increased in Sweden, due to the introduction of the 2013 strain belonging to clonal complex 11. The aim of this study was to describe the clinical presentation of MenW infections, in particular the 2013 strain, including genetic associations. Medical records of confirmed MenW IMD cases in Sweden during the years 1995-2019 (n = 113) were retrospectively reviewed and the clinical data analysed according to strain. Of all MenW patients, bacteraemia without the focus of infection was seen in 44%, bacteraemic pneumonia in 26%, meningitis in 13% and epiglottitis in 8%, gastrointestinal symptoms in 48% and 4% presented with petechiae. Phylogenetic analysis was used for possible links between genetic relationship and clinical picture. The 2013 strain infections, particularly in one cluster, were associated with more severe disease compared with other MenW infections. The patients with 2013 strain infections (n = 68) were older (52 years vs. 25 years for other strains), presented more often with diarrhoea as an atypical presentation (P = 0.045) and were more frequently admitted for intensive care (P = 0.032). There is a risk that the atypical clinical presentation of MenW infections, with predominantly gastrointestinal or respiratory symptoms rather than neck stiffness or petechiae, may lead to delay in life-saving treatment.

An international invasive meningococcal disease outbreak due to a novel and rapidly expanding serogroup W strain, Scotland and Sweden, July to August 2015.

The 23rd World Scout Jamboree in 2015 took place in Japan and included over 33,000 scouts from 162 countries. Within nine days of the meeting ending, six cases of laboratory-confirmed invasive serogroup W meningococcal disease occurred among scouts and their close contacts in Scotland and Sweden. The isolates responsible were identical to one-another by routine typing and, where known (4 isolates), belonged to the ST-11 clonal complex (cc11) which is associated with large outbreaks and high case fatality rates. Recent studies have demonstrated the need for high-resolution genomic typing schemes to assign serogroup W cc11 isolates to several distinct strains circulating globally over the past two decades. Here we used such schemes to confirm that the Jamboree-associated cases constituted a genuine outbreak and that this was due to a novel and rapidly expanding strain descended from the strain that has recently expanded in South America and the United Kingdom. We also identify the genetic differences that define the novel strain including four point mutations and three putative recombination events involving the horizontal exchange of 17, six and two genes, respectively. Noteworthy outcomes of these changes were antigenic shifts and the disruption of a transcriptional regulator.

Global epidemiology of capsular group W meningococcal disease (1970-2015): Multifocal emergence and persistence of hypervirulent sequence type (ST)-11 clonal complex.

Following an outbreak in Mecca Saudi Arabia in 2000, meningococcal strains expressing capsular group W (W) emerged as a major cause of invasive meningococcal disease (IMD) worldwide. The Saudi Arabian outbreak strain (Hajj clone) belonging to the ST-11 clonal complex (cc11) is similar to W cc11 causing occasional sporadic disease before 2000. Since 2000, W cc11 has caused large meningococcal disease epidemics in the African meningitis belt and endemic disease in South America, Europe and China. Traditional molecular epidemiologic typing suggested that a majority of current W cc11 burden represented global spread of the Hajj clone. However, recent whole genome sequencing (WGS) analyses revealed significant genetic heterogeneity among global W cc11 strains. While continued spread of the Hajj clone occurs in the Middle East, the meningitis belt and South Africa have co-circulation of the Hajj clone and other unrelated W cc11 strains. Notably, South America, the UK, and France share a genetically distinct W cc11 strain. Other W lineages persist in low numbers in Europe, North America and the meningitis belt. In summary, WGS is helping to unravel the complex genomic epidemiology of group W meningococcal strains. Wider application of WGS and strengthening of global IMD surveillance is necessary to monitor the continued evolution of group W lineages.

Meningococcemia due to the 2000 Hajj-associated outbreak strain (Serogroup W-135 ST-11) with immunoreactive complications.

We present the first reported case of systemic infection with Neisseria meningitidis serogroup W-135 sequence type (ST)-11 in Japan. A 44-year-old woman presented with high fever, sore throat, and fatigue and was diagnosed with N. meningitidis bacteremia. The causative strain was identified as serogroup W-135 ST-11 by polymerase chain reaction and multilocus sequence typing. Approximately 1 month after treatment, she developed high fever, dyspnea, chest pain, and shoulder pain due to pericarditis, polyarthritis, and tenosynovitis, which are all relatively common immunoreactive complications of W-135 ST-11 meningococcal infections. This causative strain was the same as that responsible for an outbreak of meningitis among Hajj pilgrims in 2000. The strain is now found worldwide because it can attain a high carriage rate and has a long duration of carriage. We suspect that our patient's infection was acquired from an imported chronic carrier.

Serogroup W135 meningococcal disease, The Gambia, 2012.

In 2012, an outbreak of Neisseria meningitidis serogroup W135 occurred in The Gambia. The attack rate was highest among young children. The associated risk factors were male sex, contact with meningitis patients, and difficult breathing. Enhanced surveillance facilitates early epidemic detection, and multiserogroup conjugate vaccine could reduce meningococcal epidemics in The Gambia.

[Emergence of W135 meningococcal serogroup in Chile during 2012]. / Emergencia de la cepa W135 causante de enfermedad meningocócica invasora en Chile 2012.

The epidemiologic behavior of the Invasive Meningococcal Disease (IMD) in Chile has changed. At the end of 2011, the W135 serogroup belonging to the hypervirulent clone ST-11 emerged. It affected diverse countries of the world, after the Mecca pilgrimage in 2000. In Chile, there have been 133 IMD cases during 2012. These figures represent an incidence of 0.7 per 100,000 inhabitants, which is 30% higher than expected. Eighty eight percent of cases were confirmed by the National Reference Laboratory at the Chilean Public Health Institute. The serogroup was determined in 103 strains and 58% belonged to the W135 serogroup, surpassing for the first time the B serogroup (37%). The Metropolitan Region concentrated 80% of these cases, and the remaining 20% affected other seven regions of the country. Forty seven percent of cases corresponded to children less than 5 years of age. The predominant clinical presentation of the W135 serogroup was a sepsis in 67% of cases. The fatality ratio of IDM during 2012 was 27%, the highest in the past 20 years. With this information, the Chilean Ministry of Health decreed a sanitary alert and implemented an integrated approach to control and prevent W-135 IDM, denominated "W-135 Action Plan".

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

OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

[Genotypic characteristics of Neisseria meningitidis serogroup W-135 strains isolated as the agent of fatal meningitis in a military hospital]. / Bir askeri hastanede fatal menenjit etkeni olarak izole edilen Neisseria meningitidis serogrup W-135 suslarinin genotipik özellikleri.

The aim of this study was to describe the genetic characterization of a total of 6 Neisseria meningitidis serogroup W-135 strains isolated from patients with meningitis and carriers in a military hospital in 2007-2008. Suspected colonies on modified Thayer-Martin medium plates were screened for oxidase reactivity and Gram stain. If gram-negative diplococci were present, a biochemical profile by the API NH system was used for species confirmation. Pulse field gel electrophoresis typing of Nhel-digested DNA was performed by a previously described method. Multi-locus sequence typing (MLST) was performed using the standard primers as listed on the Neisseria MLST website. Three distinct sequence types (STs) were identified: ST-11, ST-2754, ST-3751. One of the clinical isolates was identified as the same sequence type with Hajj isolate (ST-11) and the isolate with ST-2754 was the same as the first Turkish clinical strain isolated in 2003. These data demonstrated that along with ST-11 which is a known Hajj isolate, the ST-2754 strain causing meningococcal disease in Turkey beginning from the year 2003, should be carefully monitored.

[Molecular characters of epidemic cerebrospinal W135 Neisseria meningitidis strain firstly isolated in Guangdong province].

OBJECTIVE: To analyze the molecular characters of the W135 Neisseria meningitidis strain firstly isolated from patients in Guangdong province. METHODS: Biochemical profile by using the API NH system (bio-Merieux, France) was used for confirmation,and sero-grouping of the meningococcal isolates including one serogroup W135, one serogroup C and three serogroups of a Neisseria meningitidis isolated from patients in Guangdong province in recent two years were performed. The subtype was determined after amplifying porA and porB respectively from the genome DNA of Neisseria meningitidis. Multilocus sequence typing (MLST) was performed for determining the allele profiles and the sequence types (STs). The polygenetic tree was obtained by analyzing the allele profiles with program Splits tree online. The molecular characters of the serogroup W135 Neisseria meningitidis was analyzed by its evolution relationship and the variable regions in porA and porB which encoding the outer membranes proteins (OMPs). RESULTS: The subtype determined by porA variable regions of the serogroup W135 Neisseria meningitidis was P1.5,2, which was one of the most invasive types. The types of variable regions (VRs) I, IV, V, VII with porB were 1, 1, 1, 17, and there was no VI and VIII in porB. The allele profile of the W135 strain in this study was 2, 123, 4, 3, 8, 4, 6, and its sequence type was ST-2960, which belonged to ST-11/ET-37 clone complex. The subtypes of the serogroup C and serogroup A strains were P1.20, while their types of VR IV were all 7, and they all hadn't VR VII in porB. The strain serogroup C belonged to ST-4821 clone complex, and the 3 serogroup A strains belonged to ST-5 clone complex. CONCLUSION: The molecular character of the serogroup W135 Neisseria meningitidis should be the same with the strains isolated in foreign country, and be different from the epidemic types in the area. This serogroup W135 Neisseria meningitis isolated from patients in Guangdong for the first time was thought to be a new type appearing in the local area.

Serogroup W135 meningococcal meningitis, Northern Cameroon, 2007-2008.

We analyzed results of recent microbiologic surveillance of meningitis in northern Cameroon. During the 2007 and 2008 meningitis seasons, all 57 identified meningococcal isolates were serogroup W135. This situation might indicate that the area is experiencing a period between epidemic waves due to 2 different clones of serogroup A meningococci.

Annual report of the Australian Meningococcal Surveillance Programme, 2007.

In 2007 there were 242 laboratory-confirmed cases of invasive meningococcal disease analysed by the National Neisseria Network, a nationwide network of reference laboratories. The phenotypes (serogroup, serotype and serosubtype) and antibiotic susceptibility of 127 isolates of Neisseria meningitidis from invasive cases of meningococcal disease were determined and an additional 115 cases were confirmed by non-culture based methods. Nationally, 192 (85%) confirmed cases where a serogroup was determined were infected with serogroup B and 14 (6.2%) with serogroup C meningococci. The total number of confirmed cases was 29 fewer than the 271 cases identified in 2006. The only jurisdiction to record a substantial increase in laboratory confirmed cases was New South Wales and this was in sporadic cases of serogroup B infection. Typical primary and secondary disease peaks were observed in those aged 4 years or less and in adolescents and young adults respectively. Serogroup B cases predominated in all age groups and jurisdictions. The common phenotypes circulating in Australia were B:15:P1.7, B:4:P1.4 and C:2a:P1.5. No evidence of meningococcal capsular 'switching' was detected. About three-quarters of all isolates showed decreased susceptibility to the penicillin group of antibiotics (minimum inhibitory concentration [MIC] 0.06-0.5 mg/L). All isolates remained susceptible to rifampicin. A single serogroup B isolate had decreased susceptibility to ciprofloxacin (MIC 0.06 mg/L). This was the first local isolate of this type since the original report of this phenomenon in Australia in 2000.

High prevalence of Neisseria meningitidis hypervirulent lineages and emergence of W135:P1.5,2:ST-11 clone in Southern Brazil.

OBJECTIVES: The aim of this study was to characterize Neisseria meningitidis strains causing invasive disease in Rio Grande do Sul (RS), during 2003-2005, monitoring the occurrence of hypervirulent lineages, as well as to determine the diversity of PorA VR types for the corresponding isolates and clinical specimens. METHODS: Isolates and clinical specimens were characterized by MLST and PorA VR typing. RESULTS: This study demonstrated high prevalence of some hypervirulent lineages and emergence of new ones, including the emergence of lineages W135:P1.5,2:ST-11 complex, and C:P1.22,14-6:ST-103 complex. These lineages are probably responsible for the increasing incidence of serogroups C and W135, despite the overall decrease in serogroup B cases during the period. The most prevalent complex was serogroup B ST-32/ET-5 complex. The most prevalent PorA types found for serogroup B were P1.19,15, P1.7,16, and P1.18-1,3, representing a different distribution of PorA types compared to other states of Brazil. CONCLUSIONS: This study highlights the importance of monitoring each population, even within the same country. The different distribution of PorA VR types in RS has implications in vaccine design and efficacy. Detailed and accurate meningococcal characterization is an important element in studies of meningococcal epidemiology, population biology, and evolution and provides information for the design of control strategies.

Neisseria meningitidis serogroup W135 in Portugal: presence of the ST-11/ET-37 clonal complex.

Invasive serogroup W135 Neisseria meningitidis strains were isolated in Portugal between 1995 and 2002. Nine of 12 isolates showed "Hajj-2000"-associated phenotypes and belonged to the ST-11/ET-37 clonal complex. Pulsed-field gel electrophoresis clustered the ST-11/ET-37 isolates together with the "Hajj-2000" strain although the profiles were distinguishable.

Meningitis serogroup W135 outbreak, Burkina Faso, 2002.

In 2002, the largest epidemic of Neisseria meningitidis serogroup W135 occurred in Burkina Faso. The highest attack rate was in children <5 years of age. We describe cases from 1 district and evaluate the performance of the Pastorex test, which had good sensitivity (84%) and specificity (89%) compared with culture or PCR.

Genetic diversification of Neisseria meningitidis during waves of colonization and disease in the meningitis belt of sub-Saharan Africa.

Although Neisseria meningitidis is a highly variable organism, most invasive disease is caused by a minority of genotypes. Hypervirulent lineages have been identified and their pandemic spread has been traced. During a longitudinal meningococcal colonization study in a district of northern Ghana clonal waves of carriage and disease were observed. Genetic diversification of genoclouds was analysed by pulsed field gel electrophoretic (PFGE) analysis of isolates from healthy carriers and from meningitis patients. Even during the limited time of persistence in the district, microevolution of the dominating genoclouds took place. Population genomic analyses are required to understand the genetic basis for the emergence of new lineages with epidemic potential, which is of crucial importance for the development of long-term global vaccination strategies against meningococcal disease.