Emergence of serogroup C meningococcal disease associated with a high mortality rate in Hefei, China

ABSTRACT: BACKGROUND: Neisseria meningitidis serogroup C has emerged as a cause of epidemic disease in Hefei. The establishment of serogroup C as the predominant cause of endemic disease has not been described. METHODS: We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000--2010. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS: A total of 845 cases of invasive meningococcal disease were reported. The incidence increased from 1.25 cases per 100,000 population in 2000 to 3.14 cases per 100,000 in 2003 (p < 0.001), and peaked at 8.43 cases per 100,000 in 2005. The increase was mainly the result of an increase in the incidence of serogroup C disease. Serogroup C disease increased from 2/23 (9%) meningococcal cases and 0.11 cases per 100,000 in 2000 to 33/58 (57%) cases and 1.76 cases per 100,000 in 2003 (p < 0.01). Patients infected with serogroup C had serious complications more frequently than those infected with other serogroups. Specifically, 161/493 (32.7%) cases infected with serogroup C had at least one complication. The case-fatality rate of serogroup C meningitis was 11.4%, significantly higher than for serogroup A meningitis (5.3%, p = 0.021). Among patients with meningococcal disease, factors associated with death in univariate analysis were age of 15--24 years, infection with serogroup C, and meningococcemia. CONCLUSIONS: The incidence of meningococcal disease has substantially increased and serogroup C has become endemic in Hefei. The serogroup C strain has caused more severe disease than the previously predominant serogroup A strain.     

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.     

The changing epidemiology of meningococcal disease in the United States, 1992-1996

New meningococcal vaccines are undergoing clinical trials, and changes in the epidemiologic features of meningococcal disease will affect their use. Active laboratory-based, population-based US surveillance for meningococcal disease during 1992-1996 was used to project that 2400 cases of meningococcal disease occurred annually. Incidence was highest in infants; however, 32% of cases occurred in persons >/=30 years of age. Serogroup C caused 35% of cases; serogroup B, 32%; and serogroup Y, 26%. Increasing age (relative risk [RR], 1.01 per year), having an isolate obtained from blood (RR, 4.5), and serogroup C (RR, 1.6) were associated with increased case fatality. Among serogroup B isolates, the most commonly expressed serosubtype was P1.15; 68% of isolates expressed 1 of the 6 most common serosubtypes. Compared with cases occurring in previous years, recent cases are more likely to be caused by serogroup Y and to occur among older age groups. Ongoing surveillance is necessary to determine the stability of serogroup and serosubtype distribution.     

Epidemiological pattern of meningococcal disease in Valencia, Spain. Impact of a mass immunization campaign with meningococcal C polysaccharide vaccine

The objective of this study was to define the epidemiological pattern of meningococcal disease in the autonomous region of Valencia, Spain, and the impact of a mass immunization campaign against serogroup C meningococcus. Data were obtained from a prospective surveillance program for invasive bacterial diseases in children < 15 y of age that began in the Valencia region on 1 December, 1995. During the period 1996-98, 213 cases of meningococcal disease were detected, representing an annual incidence of 11.3/100,000 children < 15 y. Serogroup C accounted for 31% and 38.5% of cases in 1996 and 1997, respectively (annual incidences of 2.9 and 5.4 cases/100,000 children < 15 y). An immunization campaign with the meningococcal C polysaccharide vaccine, which included all persons between 18 months and 19 y of age, began in late 1997 (vaccination coverage of 86%). In 1998, the annual incidence of meningococcal C disease fell to 1.4 cases per 100,000 children < 15 y of age. These results mirror the increase in the reported incidence of serogroup C meningococcal disease in Spain in the 1990s, a trend that was reversed after the introduction of the mass vaccination campaign. Meningococcal polysaccharide vaccine seems to be an effective public health tool for the management of this serious communicable disease.     

Epidemiology of serogroup B invasive meningococcal disease in Ontario, Canada, 2000 to 2010

ABSTRACT: BACKGROUND: Invasive meningococcal disease (IMD) caused by serogroup B is the last major serogroup in Canada to become vaccine-preventable. The anticipated availability of vaccines targeting this serogroup prompted an assessment of the epidemiology of serogroup B disease in Ontario, Canada. METHODS: We retrieved information on confirmed IMD cases reported to Ontario's reportable disease database between January 1, 2000 and December 31, 2010 and probabilistically-linked these cases to Public Health Ontario Laboratory records. Rates were calculated with denominator data obtained from Statistics Canada. We calculated a crude number needed to vaccinate (NNV) using the inverse of the infant (<1 year) age-specific incidence multiplied by expected vaccine efficacies between 70 % and 80 %, and assuming only direct protection (no herd effects). RESULTS: A total of 259 serogroup B IMD cases were identified in Ontario over the 11-year period. Serogroup B was the most common cause of IMD. Incidence ranged from 0.11 to 0.27/100,000/year, and fluctuated over time. Cases ranged in age from 13 days to 101 years; 21.4 % occurred in infants, of which 72.7 % were <6 months. Infants had the highest incidence (3.70/100,000). Case-fatality ratio was 10.7 % overall. If we assume that all infant cases would be preventable by vaccination, we would need to vaccinate between 33,784 and 38,610 infants to prevent one case of disease. CONCLUSIONS: Although rare, the proportion of IMD caused by serogroup B has increased and currently causes most IMD in Ontario, with infants having the highest risk of disease. Although serogroup B meningococcal vaccines are highly anticipated, our findings suggest that decisions regarding publicly funding serogroup B meningococcal vaccines will be difficult and may not be based on disease burden alone.     

Epidemiology of meningococcal disease in Denmark 1980-1988.

Based on epidemiological data of notified cases of meningococcal disease (MD) in Denmark during the period 1980-88 the recommendations for prophylaxis are evaluated. In 1986 the incidence of MD increased about 60% to 5.5 per 100,000 population. The clinical diagnosis of MD was verified by culture of Neisseria meningitidis in 79% of notified cases. About 40% of all patients were less than 4 years of age. The mortality in 1988 was found to be 10%. Serogroup B disease accounted for about 80% of the cases. Two co-primary and 28 secondary cases were registered. Two major outbreaks of serogroup C disease occurred in 1984 and 1986, respectively. In small clusters of 2-3 cases within socially well-defined groups the recommendations for prophylaxis are sufficient. But for the new pattern of clusters spread over months to years in certain geographical areas or open social groups, especially among teenagers, the existing recommendations are insufficient. The occurrence of localized clusters of serogroup B disease emphasises the need for a vaccine against serogroup B disease.     

Carriage of serogroup W-135, ET-37 meningococci in The Gambia: implications for immunisation policy?

We found high levels of symptomless carriage of a hyperinvasive Neisseria meningitidis strain (electrophoretic type 37 [ET-37], serogroup W-135) during a vaccine trial in Gambian children in 1996. Serogroup C, ET-37 complex meningococci cause 30-40% of meningococcal disease in countries such as the UK, and have a point prevalence of 0.5-1.0%. The recent Haj-associated spread of serogroup W-135, ET-37 complex meningococci, which has been accompanied by numerous secondary cases, might be explained by the apparently raised carriage rates reported here.     

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.     

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.     

江西省2005-2015年脑膜炎奈瑟菌血清分型和分子分型分析

目的 对江西省2005-2015年分离的脑膜炎奈瑟菌(Neisseriameningitidis,Nm)进行血清分型和分子分型研究,揭示菌群特征和变迁情况。方法 对2005-2015年分离的200株脑膜炎奈瑟菌采用血清凝集的方法鉴定血清群,对引起流脑流行的血清群进行脉冲场凝胶电泳(Pulsed Field Gel Electrophoresis,PFGE)和多位点序列分型(Multilocus Sequence Typing,MLST),使用BioNumerics 软件构建最小生成树。分析不同来源、不同年份分离株的血清型和分子型别以及变迁情况。结果 200株脑膜炎奈瑟菌中,有168株可鉴定为已知血清群,包括C群(101株)、B群(50株)、A群(12株)、W135群(2株)、Y群(2株)和X群(1株),另外32株为不可分群菌株。临床病人、密切接触者和健康人群分离株中分别有100%、86.0%和28.9%的菌株为C群。针对健康人群分离株,2005年、2007年、2008年、2012年分离的菌株中,C群分别占1.9%、58.8%、81.5%和0%。95株C群菌株分为14个PFGE型,其中NMNh.JX0001和NMNh.JX0002为优势带型,分别包含46和30株菌。NMNh.JX0001型菌株在2005-2006年、2007-2008年、2013-2014年3个时间段在C群菌株中所占比例分别为97.2%、28.6%、10.0%;而NMNh.JX0002型菌株在2005-2006年、2007-2008年、2013-2014年3个时间段在C群菌株中所占比例分别为2.8%、57.1%、90.0%。挑选优势带型以及相似带型的33株菌株进行MLST分型,均为ST-4821型。结论 江西省2005-2015年的流脑病例均为C群菌株引起。在健康人群中存在C群脑膜炎奈瑟菌。虽然近10年流行的C群菌株MLST序列型未发生改变,但是PFGE型别发生了变迁,提示菌株基因组存在微进化。PFGE型别的变迁有可能导致流行模式发生改变,所以有必要开展持续监测,密切关注新型菌株在人群中的传播扩散以及引起的流脑病例。     

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.     

Molecular epidemiology and emergence of worldwide epidemic clones of Neisseria meningitidis in Taiwan

Background  

Meningococcal disease is infrequently found in Taiwan, a country with 23 million people. Between 1996 and 2002, 17 to 81 clinical cases of the disease were reported annually. Reported cases dramatically increased in 2001–2002. Our record shows that only serogroup B and W135 meningococci have been isolated from patients with meningococcal disease until 2000. However, serogroup A, C and Y meningococci were detected for the first time in 2001 and continued to cause disease through 2002. Most of serogroup Y meningococcus infections localized in Central Taiwan in 2001, indicating that a small-scale outbreak of meningococcal disease had occurred. The occurrence of a meningococcal disease outbreak and the emergence of new meningococcal strains are of public health concern.     

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.     

Meningococcal disease: risk for international travellers and vaccine strategies

International travel and migration facilitate the rapid intercontinental spread of meningococcal disease. Serogroup A and, less so serogroup C, have been responsible for epidemics in the past (mainly in Africa). In recent years, W135 has emerged (first in Saudi Arabia, then in West Africa) as a serogroup that requires attention. Serogroups X and Y are infrequent, but associated with slowly rising trends. There are significant variations in the incidence of meningococcal disease and the distribution of serogroups responsible for meningococcal disease, both geographically and with time. Vaccine strategies need to address this variation, and broad coverage against all serogroups for which vaccines are currently available should be offered to travellers. Tetravalent polysaccharide meningococcal vaccines are limited by their poor immunogenicity in small infants and by the lack of long-term protection. In contrast, the novel tetravalent conjugate vaccine that is currently only available in North America is immunogenic in young infants, induces long-term protection and reduces nasopharyngeal carriage. The tetravalent conjugate meningococcal vaccine will be a leap forward in the control of meningococcal epidemics in affected countries. It will also boost the uptake of meningococcal vaccines in travellers because the duration of protection is longer and it eliminates the problem of immune hyporesponsiveness of serogroup C with repeated dosing. Current vaccine recommendations are to vaccinate all Hajj pilgrims, all travellers to areas with current outbreaks, travellers to the SubSaharan meningitis belt, and individuals with certain medical conditions.     

Incidence, serogroups and case-fatality rate of invasive meningococcal infections in a Swedish region 1975-1989.

In a retrospective study of invasive meningococcal infections in Greater Gothenburg, Sweden, 213 cases of culture-verified meningitis or septicaemia were identified during the 15-year period 1975-1989. The annual incidence was 2.0/100,000. Cases were seen in all age-groups with the highest rates in the 0-4 and 15-19 year-old groups, 9.5 and 6.2/100,000 respectively. 20% of the patients were less than 2 years. 91% of the patients had no known risk factors. In only 10 cases (5%) was contact with another case of meningococcal infection known. The main clinical manifestations were meningitis (57%), septicaemia with no sign of focal infection (25%) and septic shock (17%). The case-fatality rate for all the patients was 6.6% and did not change during the 15-year period. One-third of the patients who presented with septic shock died. The serogroup was known for strains from 192 patients. 51% of the strains belonged to serogroup B, 10% to group A and 23% to group C. In conclusion, the incidence of meningococcal infection was low but the relatively high case-fatality rate warrants a search for effective prophylaxis. About 30% of the cases were potentially preventable by the currently available tetravalent (A, C, Y and W135) polysaccharide vaccine, which is immunogenic in children greater than 2 years. Widespread use of antibiotic prophylaxis to close contacts of known cases would not lower the incidence markedly.     

Meningococcal disease in the Middle East and North Africa: an important public health consideration that requires further attention

This paper reviews the epidemiological data describing meningococcal disease in the Middle East and North Africa (MENA). While meningococcal disease remains an important cause of endemic and epidemic disease in many MENA countries, existing published epidemiological data appear limited, fragmented, and collected via disparate methodologies. Children aged 5 years and younger are predominantly affected, though outbreaks of the disease often affect older age groups. Whilst serogroup A remains a main cause of meningococcal disease in the region, cases of serogroup B, W-135, and Y have been increasingly reported over the last two decades in some countries. The Hajj pilgrimage is a key factor influencing outbreaks and transmission, and the use of vaccines has minimized the effects on the home countries of the pilgrims and has decreased global dissemination of disease. Wider use of available polyvalent meningococcal conjugate vaccines may provide broader protection against the range of serogroups causing disease or posing a threat in the region. In addition, strengthening regional surveillance systems and regularly publishing reports with reliable estimates of disease incidence, carriage, disease-related mortality, and sequelae may facilitate the development of appropriate interventions and public health strategies regarding meningococcal disease within the region.     

Meningococcal meningitis outbreak control strategies.

Meningococcal meningitis has been occurring worldwide in both endemic and epidemic forms. Serogroup A accounts for majority of cases of epidemic as well as endemic Meningococcal meningitis in developing nations, whereas group C and group B causes epidemic and endemic meningococcal meningitis in developed countries. Person to person spread of N. meningitides generally occurs through inhalation of droplets of infected nasopharyngeal secretions by direct or indirect oral contact. Incubation period varies from 2 to 10 days. N. meningitides typically causes acute infective illness characterized by sequential development of upper respiratory tract infection, meningococcemia, meningitis and focal neurological deficit. Over 90 per cent cases of adult meningococcal infections have cerebrospinal meningitis, whereas in children prevalence of meningitis is much lower (50 per cent). Acute meningitis manifests with fever, severe headache, vomiting and neck stiffness. Presentations may be non-specific in infants, elderly and in patients with fulminant meningococcemia. Diagnosis is confirmed with cerebrospinal fluid analysis. Overall mortality due to meningitis is usually around 10 per cent. In meningococcal septicemia, the case fatality rate may exceed 50 per cent. Preventive strategies include vaccination, chemoprophylaxis and early detection and treatment. Mass vaccination campaign, if appropriately carried out, has been documented to halt an epidemic of meningococcal disease due to serogroup A or C. In the present review we have discussed the available evidence with regards to prevention at primary, secondary and tertiary level. Public health approach to an outbreak of meningococcal meningitis in a community or an organization is also outlined.     

Meningococcal vaccine in travelers

PURPOSE OF REVIEW: New vaccines to prevent meningococcal disease have been licensed in recent years. It is therefore timely to discuss current vaccine strategies pertinent to international travelers in relation to the changing epidemiology. RECENT FINDINGS: Serogroup W135 achieved epidemic status in Africa in 2002, and then largely disappeared over a short time period. The year 2006 saw a marked epidemic rise in meningitis attack rates across the meningitis belt in Africa. This rise was mainly due to a new serogroup A strain, indicating that a new meningitis epidemic wave is beginning in Africa. Epidemics are also spreading south of the meningitis belt, including the Greater Lakes Area (Burundi, Rwanda, Republic of Tanzania). The new quadrivalent conjugate meningococcal vaccine is now licensed in North America but not elsewhere. In most other industrialized countries, the serogroup C conjugate vaccine is licensed. Plain polysaccharide quadrivalent vaccines are available almost worldwide. SUMMARY: Quadrivalent meningococcal vaccination is a visa requirement for Hajj and Umrah pilgrims to Saudi Arabia. Travelers to the meningitis belt during the dry season should be advised to receive meningococcal vaccine that covers all four serogroups. This recommendation should be extended to the Greater Lake Area, because of recent epidemics. Vaccine choices depend on availability.     

Invasive Meningococcal Disease: Patient and Strain Characteristics Set New Challenge for Prevention and Control

Summary Differences in the course of invasive meningococcal disease, in prevalence, case-to-carrier ratio, geographical pattern, age distribution and antibiotic resistance have been related to major serogroups and their serotypes. The relationship between Neisseria meningitidis serogroups and clinical manifestation, outcome and patient characteristics are assessed. All hospitalized patients in six major hospitals in central Isral with a verified meningococcal disease during 1990–1994 were included (n = 66). Their personal and clinical data and the results of bacteriological and serological tests of their blood and cerebrospinal fluid (CSF) were recorded. Meningococci were isolated from both blood and CSF, from blood alone, and from CSF alone in 60.6%, 18.2% and 21.2% of the cases, respectively. The highest proportion of isolations were from infants < 1 year (34.8%), followed by children aged 1 to 5 years (25.8%). Serogroup B prevailed in 62.1%, while group C and W135 accounted for 28.8% and 9.1%, respectively. Serogroup B predominated in children < 1 year, while in patients aged 5–22 years, C strains were the major pathogen (P < 0.001). Serogroup B accounted for 93% of the cases of meningitis, 58% of meningococcemia and 42% of fulminant meningococcemina, while group C strains were the major cause of fulminant meningococcemia (50%). The overall case fatality rate was 7.6%: fulminant meningococcemia 8.3%, and meningococcemia 10%. It was concluded that N. meningitidis group C continues to account for almost a third of the cases of meningococcal disease and is the major cause of fulminant meningococcemia. Received: August 17, 1998 · Revision accepted: January 24, 1999