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.     

Meningitis caused by a serogroup W135 clone of the ET-37 complex of Neisseria meningitidis in West Africa

Summary Meningococci belonging to serogroup W135 caused several cases of meningococcal meningitis in The Gambia in 1995 and were isolated during a serogroup A epidemic in Mali in 1994. The eight isolates tested belonged to the same clone of the ET-37 complex and differed in several bands from the pulsed-field gel electrophoresis restriction pattern of serogroup C meningococci of the ET-37 complex isolated in Mali. Three of 6 patients infected in The Gambia died, indicating that this W135 clone is virulent. Vaccines that protect only against infections with meningococci belonging to serogroups A and C are usually used to control outbreaks in Africa, although vaccines containing the W135 polysaccharide are available. The findings of this study indicate that outbreaks of meningococcal meningitis in Africa can be associated with serogroup W135 infections and that serogrouping is essential before vaccination campaigns are started.     

Emergence of W135 meningococcal meningitis in Ghana

Neisseria meningitidis serogroup W135, well known for a long time as a cause of isolated cases of meningococcal meningitis, has recently increasingly been associated with disease outbreaks of considerable magnitude. Burkina Faso was hit by W135 epidemics in the dry seasons of 2002-2004, but only four W135 meningitis cases were recorded between February 2003 and March 2004 in adjoining Ghana. This reconfirms previous findings that bottlenecks exist in the spreading of new epidemic N. meningitidis clones within the meningitis belt of sub-Saharan Africa. Of the four Ghanaian W135 meningitis patients one died and three survived, of whom one had profound neurosensory hearing loss and speech impairment. All four disease isolates were sensitive to penicillin G, chloramphenicol, ciprofloxacin and cefotaxime and had the multi-locus sequence type (ST) 11, which is the major ST of the ET-37 clonal complex. Pulsed-field gel electrophoresis (PFGE) profiles of the Ghanaian disease isolates and recent epidemic isolates from Burkina Faso were largely identical. We conducted meningococcal colonization surveys in the home communities of three of the patients and in the Kassena Nankana District located at the border to Burkina Faso. W135 carriage rates ranged between 0% and 17.5%. When three consecutive surveys were conducted in the patient community with the highest carrier rate, persistence of W135 colonization over a period of 1 year was observed. Differences in PFGE profiles of carrier isolates taken at different times in the same patient community were indicative of rapid microevolution of the W135 bacteria, emphasizing the need for innovative fine typing methods to reveal the relationship between W135 isolates.     

Emergence of endemic serogroup W135 meningococcal disease associated with a high mortality rate in South Africa.

BACKGROUND: In the African meningitis belt, Neisseria meningitidis serogroup W135 has emerged as a cause of epidemic disease. The establishment of W135 as the predominant cause of endemic disease has not been described. METHODS: We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000-2005. The system was enhanced in 2003 to include clinical data collection of cases from sentinel sites. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS: A total of 2135 cases of invasive meningococcal disease were reported, of which 1113 (52%) occurred in Gauteng Province, South Africa. In this province, rates of disease increased from 0.8 cases per 100,000 persons in 2000 to 4.0 cases per 100,000 persons in 2005; the percentage due to serogroup W135 increased from 7% (4 of 54 cases) to 75% (221 of 295 cases). The median age of patients infected with serogroup W135 was 5 years (interquartile range, 2-23 years), compared with 21 years (range, 8-26 years) for those infected with serogroup A (P<.001). The incidence of W135 disease increased in all age groups. Rates were highest among infants (age, <1 year), increasing from 5.1 cases per 100,000 persons in 2003 to 21.5 cases per 100,000 persons in 2005. Overall case-fatality rates doubled, from 11% in 2003 to 22% in 2005. Serogroup W135 was more likely to cause meningococcemia than was serogroup A (82 [28%] of 297 cases vs. 11 [8%] of 141 cases; odds ratio, 8.9, 95% confidence interval, 2.2-36.3). A total of 285 (95%) of 301 serogroup W135 isolates were identified as 1 clone by pulsed-field gel electrophoresis; 7 representative strains belonged to the ST-11/ET-37 complex. CONCLUSIONS: Serogroup W135 has become endemic in Gauteng, South Africa, causing disease of greater severity than did the previous predominant serogroup A strain.     

Neisseria meningitidis serogroup W-135 isolated from healthy carriers and patients in Sudan after the Hajj in 2000

The first epidemic in the world of meningococcal disease due to serogroup W-135 was reported during the Hajj in 2000, with subsequent spread. The aims of the present study were to investigate whether the Hajj 2000 Neisseria meningitidis serogroup W-135 had also been carried to Sudan in the eastern part of the African meningitis belt, by examining healthy Sudanese pilgrims (Hajj 2000) and members of their families, and whether the strain was causing meningitis. The phenotypic character of W-135 meningococci from Sudanese carriers (n = 5) and patients (n = 2) 1 y later was similar to W-135 strains associated with Hajj 2000. The present study, using the combination of the 2 molecular techniques; sequencing of the porA gene for variable regions (VR1, VR2 and VR3) and pulsed-field gel electrophoresis of the entire genome (using SpeI and NheI), shows that the Hajj 2000 serogroup W-135 clone (P1.5,2,36-2 of the ET-37 complex) most probably was introduced into Sudan, by pilgrims returning from the Hajj 2000. This strain has not been diagnosed before in Sudan. Close epidemiological surveillance is required to identify a possible new emerging meningitis epidemic.     

Neisseria meningitidis serogroup W-135 carriage among US travelers to the 2001 Hajj

In 2000, a large international outbreak of meningococcal disease caused by Neisseria meningitidis serogroup W-135 was identified among pilgrims returning from the Hajj in Saudi Arabia. To assess ongoing risk, we evaluated N. meningitidis carriage among US travelers to the 2001 Hajj. Of 25 N. meningitidis isolates obtained, 15 (60%) were nongroupable and 8 (32%) were serogroup W-135 when tested by standard slide-agglutination techniques. Two additional nongroupable isolates were characterized as serogroup W-135 when tested by polymerase chain reaction. Nine of 10 serogroup W-135 isolates were indistinguishable from the Hajj-2000 clone. None of the departing, but 9 (1.3%) of the returning, pilgrims carried serogroup W-135 (P=.01); all carriers reported previous vaccination. Carriage of N. meningitidis serogroup W-135 increased significantly in pilgrims returning from the Hajj. Although the risk of disease to pilgrims appears to be low, the risk of spread to others of this pathogenic strain remains a concern.     

W135 meningococcal disease in England and Wales associated with Hajj 2000 and 2001

An outbreak of W135 meningococcal disease was seen in 2000 and 2001 among pilgrims returning from Saudi Arabia and their contacts. The Public Health Laboratory Service set up enhanced surveillance to monitor spread and virulence of the outbreak strain, and to collect data on case characteristics. The number of cases reported from England and Wales in 2001 was similar to the number reported during 2000, despite a change in the recommendation for pilgrims to receive quadrivalent vaccine (against serogroup A, C, W135, and Y) instead of the A/C vaccine recommended in 2000. Both the recommendation and vaccine were not available until January, 2001, and coverage among pilgrims to the Hajj 2001 was low. The case--fatality ratio was high, and sustained transmission of the virulent outbreak strain was seen. Current control policies, both in primary and secondary prevention, might need better implementation.     

Meningococcal W135 carriage; enhanced surveillance amongst east London Muslim pilgrims and their household contacts before and after attending the 2002 Hajj

BACKGROUND: For two successive years, 2000 and 2001, there was a world-wide outbreak of W135 meningococcal disease amongst pilgrims who attended the Hajj and in their contacts after returning home. METHODS: Beginning January 2002, we offered meningococcal quadrivalent polysaccharide vaccine (against serogroups A, C, Y and W135) to pilgrims and collected a throat swab for meningococcal W135 carriage before and after their pilgrimage. RESULTS: The overall Neisseria meningitidis carriage pre-Hajj was 8.3% and 6.3% post-Hajj. We found W135 carriage rates of 0.8% before and 0.6% after Hajj, respectively. 21% (36/174) of the pilgrims were treated with antibiotics for respiratory illness. CONCLUSION: The carriage of meningococcus W135 among UK pilgrims who visited the Hajj in 2002 was low. This contrasts with another study suggesting pilgrims frequently acquired N. meningitidis W135 carriage during 2001 Hajj. The use of the quadrivalent vaccine may account for this difference.     

Molecular characteristics of Neisseria meningitidis strains isolated in Burkina Faso in 2001

In the course of an epidemic of meningitis in Burkina Faso in 2001, 27 cerebrospinal fluid samples from patients in 7 districts were forwarded to Norway for isolation and characterization of the causative agents. Neisseria meningitidis was isolated from 13 (48%) samples. The isolates were analysed using serological and genetic methods. Of the 13 strains, 4 were serogroup A, serotype 21:P1.9, sequence type (ST)-5 and belonged to clonal subgroup III, while the remaining 9 strains were serogroup W135, serotype 2a:P1.5,2, ST-11 and belonged to the electrophoretic type-37 complex. PCR analyses revealed meningococcal DNA in 13/14 culture-negative samples. Sequence analysis of the PCR products demonstrated that at least 3 different meningococcal strains were responsible for these 13 cases. Our results show that the W135 strain associated with the 2000 hajj (Muslim pilgrimage) outbreak was a significant cause of disease in Burkina Faso in 2001. Further studies are warranted to determine whether W135 is about to replace serogroup A in sub-Saharan Africa.     

W135 in Africa: origins, problems and perspectives

Serogroup A meningococci have been the major cause of epidemic meningococcal disease in Africa throughout the last 100 years. The reasons for this unusual pattern of behaviour have remained unclear and there remain significant debates and logistic difficulties around the appropriate use of plain A/C polysaccharide vaccination to control African meningococcal disease. Since the Hajj pilgrimage of 2000 serogroup W135 organisms (of the ST-11 clonal complex) have emerged as a further significant cause of epidemic meningococcal disease in Africa. Whilst advances in molecular biological and genetic techniques have yielded increasing insights into meningococcal epidemiology there remain many unanswered questions about the reason for the emergence of a serogroup W135 clone capable of epidemic behaviour and in particular its relation to past use of group A/C polysaccharide. The high cost and short supply of quadrivalent (A,C,Y, W135) vaccine to protect against W135 disease has added to what was already the significant burden of controlling serogroup A meningococcal disease. The ability of virulent meningococcal clones to acquire new capsule types raises further concerns about the future nature of meningococcal disease in Africa and the strategies of vaccination use and development necessary to contain it.     

Genotype-specific carriage of Neisseria meningitidis in Georgia counties with hyper- and hyposporadic rates of meningococcal disease

Carriage of Neisseria meningitidis in a Georgia county with hypersporadic incidence of meningococcal disease ("hypersporadic county") and in a county with no cases of meningococcal disease was determined by a cross-sectional pharyngeal culture study of high school students. Among 2730 students from whom culture samples were obtained, meningococcal carriage was 7.7% (140/1818) in the hypersporadic county and 6.1% (56/912) in the comparison county. Carriage rates by serogroup and genetic type (i.e., electrophoretic type [ET]) did not differ significantly between counties, but apartment or mobile home residency was a risk factor for carriage in the hypersporadic county. Although most cases of meningococcal disease in the hypersporadic county were caused by members of the serogroup C ET-37 clonal group, no ET-37 meningococcal isolates were recovered from carriers in this county. However, 38% of all meningococcal isolates recovered from carriers in both counties were members of the serogroup Y ET-508 clonal group, an emerging cause of meningococcal disease in Georgia and throughout the United States during 1996-2001. Shifts in carriage and transmission of meningococcal strains with different pathogenic potential are important determinants of meningococcal disease incidence.     

Usefulness of pulsed-field gel electrophoresis in tracking two outbreaks of invasive meningococcal disease serogroup C in British Columbia

Two major outbreaks of invasive meningococcal disease serogroup C (IMD-C) were identified in British Columbia between 2000 and 2004. Pulsed-field gel electrophoresis (PFGE) and porA gene sequencing of all retained IMD-C isolates were used to assess correlations between genotypes and epidemiological patterns. PFGE patterns of IMD-C genotypes correlated with epidemiological patterns between 2000 and 2004 in British Columbia, and demonstrated that PFGE can identify outbreak-related cases. Both IMD-C outbreaks correlated with a respective PFGE pattern. PFGE analysis demonstrated that the 2004 British Columbia outbreak strain in men who have sex with men was closely related to the 2001 Abbotsford outbreak strain. PorA sequencing data indicated low diversity of class 1 outer membrane proteins in British Columbia, and did not correlate with epidemiological trends. There was a trend for outbreak-associated PFGE types to demonstrate higher case fatality rates.     

Identification of MDR-TB Beijing/W and other Mycobacterium tuberculosis genotypes in Nairobi, Kenya.

SETTING: Suspected tuberculosis (TB) patients in Nairobi, Kenya. OBJECTIVE: To identify the presence of multidrug-resistant (MDR) Beijing/W type and other genotypes of Mycobacterium tuberculosis. METHODS: Thirty-three isolates resistant to one or more drugs (resistance ratio method), including 15 MDR isolates and 40 susceptible isolates selected at random, were analysed by dot-blot hybridisation for mutations associated with resistance to isoniazid, rifampicin, streptomycin and ethambutol. All strains were genotypically classified using spoligotyping. RESULTS: Of the 33 drug-resistant isolates, 21 (64%) were from males and 12 (36%) were from females. Mutations associated with resistance to isoniazid (katG 315) and rifampicin (rpoB526, 531) were confirmed in 83.3% and 100% of the isolates, respectively, and in 87% of the MDR isolates. Mutations were detected in 25% and 71.5% of the isolates resistant to streptomycin (rpsL43) and ethambutol (embB306), respectively. No mutations were detected in drug-susceptible isolates. Spoligotyping grouped the isolates into 25 groups. Ten of these groups corresponded to previously identified strain groups, including seven families in the international database. One of these families (CAS1) comprised six (40%) of the 15 MDR isolates. Another family (Beijing) had six (8.3%) isolates, of which two (33.3%) were MDR (Beijing/W). CONCLUSION: This study is the first in Kenya and the second in sub-Saharan Africa to report the presence of MDR Beijing/W type and other possible drug-resistant outbreak strains. Application of the molecular techniques and markers will allow us to monitor the spread of existing drug-resistant strains and the appearance of new ones.     

Molecular epidemiologic techniques in analysis of epidemic and endemic Shigella dysenteriae type 1 strains.

During 1988 the number of Shigella dysenteriae type 1 infections reported in the United States increased fivefold. To determine if recent isolates from Mexico were related to those that caused epidemics of dysentery worldwide, Southern hybridization analysis was done with Shiga toxin and ribosomal RNA gene probes. Western hemisphere and Eastern Hemisphere strains differed by the size of a single EcoRI fragment carrying the Shiga toxin genes. Three ribosomal DNA (rDNA) patterns were observed, which correlated with the strain's continental origin for 81 of 83 isolates tested. Together the Shiga toxin and rDNA probe results indicated that recent Mexican isolates were chromosomally similar to earlier Central American isolates and distinct from Asian and African strains. This suggests there has been no significant exchange of organisms between continents in recent decades and that the 1988 outbreak in Mexico was caused by strains present in Central America since at least 1962.     

医院内鼠伤寒沙门菌病暴发流行菌株的研究

苏州市儿童医院1989年发生一起鼠伤寒沙门菌病暴发流行。流行菌株为多重耐药菌,耐药种类达11～13种。质粒检测结果表明流行菌株均含四个质粒,最大质粒为122.6或103.3kb,其余三个为93.5、13.9和4.1kb。103.3kb质粒编码庆大霉素、卡那霉素和妥布霉素的耐药性。122.6kb质粒除编码上述三种药物的耐药性外,还编码对氯霉素、四环素及复方新诺明的耐药性。根据药敏试验、质粒检测和限制性内切酶分析,证实此次暴发流行是由两株不同的鼠伤寒沙门菌引起的。     

Molecular and epidemiological study of the first outbreak of vanB type vancomycin-resistant Enterococcus faecalis in Japan

In July, 1999, an outbreak of vancomycin-resistant Enterococcus faecalis (VREF) with the vanB genotype occurred for the first time in Japan at Hokushin General Hospital, Nakano City, Nagano Prefecture. Four VREF strains were isolated from the clinical specimens of four inpatients, and 16 VREF strains were isolated by the screening of asymptomatic carriers and by surveillance of the hospital environment. All of the isolates possessed vanB genes. In a pulsed-field gel electrophoresis analysis, 19 out of 20 VREF isolates exhibited the indistinguishable restriction endonuclease digestion patterns of the chromosomal DNA. Additional investigation by Southern hybridization using the vanB probe implied that the vanB gene of these 19 isolates was encoded on a 110-kb plasmid. These findings indicate that the outbreak was principally caused by a single clone. The restriction endonuclease digestion patterns of the remaining single isolate was different from those of the other isolates. The vanB gene was encoded on the chromosome.     

Clones of serogroup B Neisseria meningitidis causing systemic disease in The Netherlands, 1958-1986

Serogroup B isolates of Neisseria meningitidis recovered from 278 patients with systemic disease in the Netherlands between 1958 and 1986 were analyzed with respect to serotype and multilocus enzyme genotype. Of the isolates, 28% were serotype 2b and 53% were neither serotypeable nor serosubtypeable. There were 145 distinct multilocus genotypes (electrophoretic types, ETs), with up to 31 isolates belonging to the same ET. Temporal changes in the genotypic composition of meningococcal populations in the Netherlands were demonstrated by the recent occurrence of disease caused by three clone lineages, I, III, and VI, that were not found before 1975. The epidemic of 1966-1967 and the hyperendemic wave of 1972 were caused, in large part, by two closely related but distinct clones of serotype 2b isolates, ET-11 and ET-17, respectively. Deviations in male-to-female ratio and age distribution of patients were observed for disease caused by isolates of individual clone lineages.     

Epidemiological patterns of meningococcal meningitis in Niger in 2003 and 2004: under the threat of N. meningitidis serogroup W135

Since the Neisseria meningitidis serogroup W135 epidemic in Burkina Faso in 2002, the neighbouring countries dread undergoing outbreaks. Niger has strongly enhanced the microbiological surveillance, especially by adding the polymerase chain reaction (PCR) assay to the national framework of the surveillance system. During the 2003 epidemic season, 8113 clinically suspected cases of meningitis were notified and nine districts of the 42 crossed the epidemic threshold, while during the 2004 season, the number of cases was 3521 and four districts notified epidemics. In 2003 and 2004, serogroup A was identified in most N. meningitidis from cerebrospinal fluid (CSF) specimens (89.7% of 759 and 87.2% of 406, respectively). Although serogroup W135 represented only 8.3% of the meningococcal meningitis in 2003 and 7.9% in 2004, and was not involved in outbreaks, it was widespread in various areas of the country. In the regions that notified epidemics, the proportion of serogroup W135 was tiny while it exceeded 40% in several non-epidemic regions. Despite the wide distribution of W135 serogroup in Niger and the fears expressed in 2001, the threat of a large epidemic caused by N. meningitidis W135 seems to have been averted in Niger so far. There is no clear indication whether this serogroup will play a lasting role in the epidemiology of meningococcal meningitis or not. As early as in the 1990s, a significant but transient increase in the incidence of N. meningitidis serogroup X was observed. Close microbiological surveillance is crucial for monitoring the threat and for identifying at the earliest the serogroups involved in epidemics.     

Clinical features and outcome of sporadic serogroup W135 disease Taiwan

Background  

Few published reports have evaluated the clinical features and outcome of serogroup W135 meningococcal disease. In Taiwan, W135 is the second most prevalent meningococcal disease serogroup.     

Chronicle of an outbreak foretold: meningococcal meningitis W135 in Burkina Faso

Burkina Faso lies within the African meningitis belt. Until recently, serogroup A of Neisseria meningitidis was the most common cause of epidemic meningitis in Burkina Faso. However, during the epidemic that started in January 2002, W135 was the predominant serogroup of meningococcus. Vaccine against the W135 serogroup is expensive and in short supply. Strategies to react to a future African epidemic of W135 meningococcal meningitis with a sufficient and affordable supply of vaccine must be put into place now.