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.     

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 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.     

ST2859 serogroup A meningococcal meningitis outbreak in Nouna Health District, Burkina Faso: a prospective study

We analysed cerebrospinal fluid samples from suspected meningitis cases in Nouna Health District, Burkina Faso, during the meningitis seasons of 2004-2006. Serogroup A ST2859 meningococci belonging to the ST5 clonal complex of subgroup III meningococci were the predominant causative agent. ST2859 bacteria were associated with focal outbreaks in the north of the district. While >10% of the population of an outbreak village carried ST2859, the population in the south of the district was predominantly colonised by serogroup Y ST4375 meningococci, which were associated with only sporadic cases of meningitis. Colonisation with the less virulent Y meningococci may interfere with the spread of the ST2859 to the south of the district, but there are concerns that this serogroup A clone may cause a third wave of subgroup III meningococcal disease in the African Meningitis Belt.     

Prevention of bacterial meningitis: an overview of Cochrane systematic reviews

Acute bacterial meningitis (ABM) is an acute inflammation of leptomeninges caused by bacteria, and has a case fatality rate of 10-30%. Prevention strategies, such as vaccination and prophylactic antibiotics, can prevent ABM and have substantial public health impact by reducing the disease burden associated with it. The aim of this paper is to summarize the main findings from Cochrane systematic reviews that have considered the evidence for measures to prevent ABM. We assessed the evidence available in the Cochrane Library. We found five Cochrane reviews focused on the prevention of ABM; three with use of vaccination and two with prophylactic antibiotics. Polysaccharide serogroup A vaccine is strongly protective for the first year, against serogroup A meningococcal meningitis in adults and children over 5 years of age. Meningococcal serogroup C conjugate (MCC) vaccine is safe and effective in infants. Haemophilus influenzae type b (Hib) vaccine is safe and effective against Hib-invasive disease at all ages. Ceftriaxone, rifampicin and ciprofloxacin are the most effective prophylactic antibiotics against Neisseria meningitidis. There is sufficient evidence to use polysaccharide serogroup A vaccine to prevent serogroup A meningococcal meningitis, MCC conjugate vaccines to prevent meningococcal C meningitis and Hib conjugate vaccine to prevent Hib infections. More studies are needed to evaluate the effects of Hib conjugate vaccine on mortality. Further, studies are required to compare the relative effectiveness of ceftriaxone, ciprofloxacin and rifampicin in chemoprophylaxis against meningococcal infection.     

Outbreaks of serogroup X meningococcal meningitis in Niger 1995-2000

In the African meningitis belt, the recurrent meningococcal meningitis epidemics are generally caused by serogroup A. In the past 20 years, other serogroups have been detected, such as X or W135, which have caused sporadic cases or clusters. We report here 134 meningitis cases caused by Neisseria meningitidis serogroup X that occurred in Niamey between 1995 and 2000. They represented 3.91% of the meningococcal isolates from all CSF samples, whereas 94.4% were of serogroup A. Meningococcal meningitis cases were detected using the framework of the routine surveillance system for reportable diseases organized by the Ministry of Public Health of Niger. The strains were isolated and determined by the reference laboratory for meningitis in Niamey (CERMES) and further typed at the WHO collaborating center of the Pharo in Marseille and at the National Reference Center for the Meningococci at the Institut Pasteur. Reference laboratories in Marseille and Paris characterized 47 isolates having the antigenic formula (serogroup:serotype:sero-subtype) X:NT:P1.5. Meningitis cases due to meningococcus serogroup X did not present any clinical or epidemiological differences to those due to serogroup A. The seasonal incidence was classical; 93.3% of the cases were recorded during the dry season. The mean age of patients was 9.2 years (+/- 6 years). The sex ratio M/F was 1.3. Case fatality rate was 11.9% without any difference related to age or sex. The increasing incidence of the serogroup X was not related to the decrease of serogroup A, but seemed cyclic, and evolved independently of the recurrence of both serogroups A and C.     

Subacute septicemia caused by Meningococcus of serogroup Y and acquired deficiency of complement C3 fraction

The high frequency of meningococcal infections in patients with congenital deficiency of a component of the complement terminal pathway emphasizes the critical role of this system in host resistance against Neisseriaceae. We report the observation of a subacute septicaemia due to N. meningitidis serogroup Y. This girl had an acquired deficit of the C3 fraction of complement due to a high titre of C3 nephritic factor (C3NeF). There was no evidence of partial lipodystrophy or biological symptoms of glomerular disease. The meningococcal infection revealed this biological abnormality.     

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

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

Outbreak of infection caused by Neisseria meningitidis group C type 2 in a nursery

An outbreak of meningococcal infection which took place in a nursery in Rioja, Spain, is reported. Between November 1981 and February 1982, 11 patients had meningitis with or without septicaemia. Two died. Three meningococcal strains from the patients isolated were studied. All three were group C type 2 and were resistant to sulphadiazine (MIC 50 mg/l) but susceptible to penicillin, ampicillin, chloramphenicol, rifampicin and spiramycin. This outbreak took place during an epidemic in which serogroup B was the most prevalent in Spain. Two surveys before and after chemoprophylaxis were made to determine the carrier rate in the nursery population. The strain causing the outbreak was found in 2.5 and 4 per cent of persons respectively. Rifampicin was administered to all carriers after the first survey and to carriers of the virulent strain after the second survey. The remaining children were given polysaccharide C vaccine. No more cases arose after this last prophylactic measure.     

Meningococcal Disease: Shifting Epidemiology and Genetic Mechanisms That May Contribute to Serogroup C Virulence

During the past decade, monovalent serogroup C and quadrivalent (serogroups A, C, W135, Y) meningococcal vaccination programs have been introduced in multiple industrialized countries. Many of these programs have been successful in reducing the burden of disease due to vaccine-preventable serogroups of Neisseria meningitidis in target age groups. As a result, disease burden in these countries has decreased and is primarily serogroup B, which is not vaccine preventable. Despite the success of these programs, meningococcal disease continues to occur and there is always concern that serogroup C organisms will adapt their virulence mechanisms to escape pressure from vaccination. This review highlights the current epidemiology of meningococcal disease in Europe and United States, as well as genetic mechanisms that may affect virulence of serogroup C strains and effectiveness of new vaccines.     

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.     

Management of acute meningococcal septicaemia in Al-Nasser Paediatric Hospital: a retrospective cohort study

Background

Acute meningococcal septicaemia is a fulminant disease, and mortality and long-term morbidity can be very high if not treated appropriately. We aimed to evaluate case fatality rate of all children admitted with acute meningococcal septicaemia.

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 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.     

Antigenic shift and increased incidence of meningococcal disease

BACKGROUND: The incidence of serogroup C and Y meningococcal disease increased in the United States during the 1990s. The cyclical nature of endemic meningococcal disease remains unexplained. The purpose of this study was to investigate the mechanisms associated with the increase in the incidence of meningococcal disease. METHODS: We characterized an increasing incidence of invasive serogroup C and Y meningococcal disease using population-based surveillance from 1992 through 2001. Isolates were characterized by multilocus sequence typing and antigen sequence typing of 3 outer membrane protein (OMP) genes: porA variable regions (VRs) 1 and 2, porB, and fetA VR. RESULTS: For both serogroups, OMP antigenic shifts were associated with increased incidence of meningococcal disease. For serogroup Y, antigenic shift occurred through amino acid substitutions at all 3 OMPs--PorA VR 1 and 2, PorB, and FetA VR. For serogroup C, antigenic shift involved amino acid substitutions at FetA VR and, in some cases, deletion of the porA gene. On the basis of deduced amino acid sequences, the antigenic changes likely occurred by horizontal gene transfer. CONCLUSIONS: Antigenic shifts were associated with increased incidence of serogroup C and serogroup Y meningococcal disease. For serogroup Y, the changes involved all OMP genes that were studied. Increases in the incidence of meningococcal disease may be caused, in part, by antigenic shift.     

Meningococcal disease

Due to a high complication and case fatality rate, meningococcal diseases are important health problems both in tropical countries experiencing severe epidemics as well as in countries of moderate climate zones. Worldwide N. meningitidis of sero-groups A, B, and C are predominant and to a lesser extent serogroups W (135) and Y play a role, whereas in Europe more than 90 % of meningococcal diseases are caused by serogroups B and C of N. meningitidis. In Germany and other developed countries the majority of cases occur in very young children and adolescents. Since many years, meningococcal polysaccharide vaccines against diseases due to N.meningitidis serogroup A, C, Y and W (135) are commercially available. Unfortunately, a vaccine against diseases caused by N. meningitidis serogroup B is still under development. The recently developed and licensed conjugated meningococcal vaccines against N. meningitidis serogroup C are also protective against disease in very young children. Eight countries in Western Europe as well as Australia have already established country-wide immunization programs for children and adolescents. Within only 2 to 3 years, well managed programs have achieved far-reaching control of meningococcal C disease in UK and the Netherlands. In Germany, the Advisory Committee on Immunization (STIKO recommends immunization for selected risk groups. The current increase of the percentage of meningococcal C diseases to 28 - 30 % gives reason for further discussion regarding immunization strategies. How-ever, the STIKO expressively declares, that in addition to the recommendation for risk groups, the physician can use all vaccines licensed in Germany without any restriction. It is his/her responsibility to advice the patients regarding immunization possibilities against the life-threatening meningococcal disease, particularly if cases are occurring.     

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.     

Advances with vaccination against Neisseria meningitidis

In the last decade, meningococcal serogroup C conjugate vaccination programs have been demonstrated to be hugely successful with a truly impressive public health impact. In sub‐Saharan Africa, with the implementation of an affordable serogroup A conjugate vaccine, it is hoped that a similar public health impact will be demonstrated. Challenges still remain in the quest to develop and implement broadly protective vaccines against serogroup B disease. New, broad coverage vaccines against serogroup B are for the first time becoming available although little is known about their antibody persistence, effectiveness or effect on nasopharyngeal carriage. Enhanced surveillance following any potential vaccine introduction against serogroup B needs to be thoroughly implemented. The future now holds a distinct possibility, globally, for substantially decreasing meningococcal disease, regardless of infecting serogroup.