Although N. meningitidis serogroup C is a prominent serogroup in many regions of the world and has occasionally caused epidemics and frequently causes outbreaks , only sporadic cases and no epidemics of meningococcal disease due to serogroup C occurred in China before 2002. In this study, we report the emergence of endemic serogroup C meningococcal disease and epidemiological characteristics in China. The rate of invasive meningococcal disease in Hefei increased 2.5 times from 2000 to 2003, and the incidence peaked at 8.43 cases per 100,000 in 2005. This increase was mostly because of the emergence and increase in the incidence of serogroup C disease.
The reasons for the emergence and increase in serogroup C disease in Anhui Province and parts of China (while other potentially epidemic strains have remained relatively quiescent) are not fully understood. It is well-known that molecular mechanisms likely play an important role in the epidemiology of meningococcal disease. N. meningitidis uses several mechanisms to change its characteristics, such as antigenic structure and resistance to antibiotics. Many of these changes occur through horizontal gene transfer, by which the organism obtains large DNA sequences from other meningococcal strains or other species . Capsular switching is a genetic mechanism that allows N. meningitidis to change its capsular phenotype, permiting immunologic escape [12, 13]. N. meningitidis outbreaks can be started or sustained when this occurs. Capsular switching appears to have been responsible for an outbreak of serogroup W-135 disease during the 2000 Hajj in Mecca, Saudi Arabia. Subsequent to this outbreak, the epidemic strain spread globally and, in one example, caused an epidemic in Burkina Faso [14, 15]. Selected isolates of the serogroup C clone from Hefei and the rest of Anhui Province were found to belong to ST-4821, a unique clone of serogroup C that does not belong to any of the previously reported sequence types . For this reason, capsular switching may have been a cause for the emergence of serogroup C in Anhui Province. Published data showed that this unique ST-4821 clone was first identified in Anhui Province during 2003–04, and the same ST clones were also identified in 11 other provinces in China during 2004–2005 [7, 16, 17].
The overall case-fatality rate in Hefei tripled from 2000 to 2003. We report that the rate of case-fatality with serogroup C was 2.2 times that of serogroup A during the period covered. This was of borderline statistical significance and factors associated with death in univariate analysis were age of 15–24 years, infection with serogroup C, and meningococcemia. The results of this study confirm the severity of serogroup C disease [18, 19]. The reason for the high virulence of this particular strain of N. meningitidis is unknown, but the strain is associated with a high frequency of meningococcemia with severe complications, which was of statistical significance in multivariable analysis. Meningococcemia was also independently associated with serogroup C disease and with increased risk of death. Meningococcemia has a higher case-fatality rate than meningitis .
Few published papers discuss the clinical characteristics of serogroup C meningococcal disease [18–20]. We reviewed the detailed clinical information and found serogroup C disease more likely to cause meningococcemia, decreased platelet counts, and serious complications. Our findings provide valuable information to understand the severity of serogroup C disease. Several scoring systems have been developed for assessing the prognosis and mortality of meningococcal disease [21–24]. The Glasgow Meningococcal Septicemia Prognostic Score is a good example of a clinical prediction tool for assessing the mortality of meningococcal disease [21, 22]. Most of those scoring systems are based on easily available clinical and laboratory parameters such as age distribution, period between onset of disease and admission, absence of meningitis, presence of widespread skin lesions, hypotension, metabolic acidosis, normal C-reactive protein level, absence of leukocytosis, presence of thrombocytopenia, and hypofibrinogenemia [21–24]. However, some of the above factors (e.g., C-reactive protein and fibrinogen levels) were not routinely checked in our cases.
Of note, the age distribution of patients shifted from younger to older age categories in the Hefei area during the study period. From 1989 to 1999, 78% of cases of meningococcal disease occurred in children younger than 14 years . However, the proportion of cases in this age group decreased to 31% from 2000 to 2010, while the proportion in 15–24 year olds increased from 22% (1989–1999) to 52.6% (2000–2010). The elevated incidence of meningococcal disease among adolescents and young adults has also been noted in previous studies [15, 25]. Some reports indicated that the age distribution was not uniform for all serogroups, and disease caused by serogroup C was more likely to affect older children than disease caused by serogroup B . However, another study regarded the shift toward older age as a characteristic of a meningococcal disease epidemic, and suggested that the age distribution of the disease would return to “normal” after the epidemic . Possible explanations for the change in age group affected include: N meningitidis of serogroup C was antigenically new to the entire population; adolescents and young adults have enhanced risk factors for meningococcal transmission and invasion, such as crowding, active or passive smoking, and exposure to oral secretions. Understanding the age distribution of meningococcal disease is necessary to devise control and preventive measures such as vaccinations for high-risk populations. Because serogroup C is a vaccine-preventable strain, our findings stress the importance of further study of the age distribution of this disease. In the early days of an outbreak of serogroup C meningococcal disease (2003–2004) in Anhui Province, serogroup C vaccine was only recommended for children younger than two years. In 2005 serogroup C meningococcal conjugate vaccine was introduced to all those who were younger than 25 years, especially for those populations such as middle school students, college freshmen and service personnel. From September 2003 to July 2007, 627,000 doses of serogroup A and C vaccine were used in Hefei, providing an estimated 37–51% coverage of the population aged 2–24 years. After the immunization campaign in Hefei, the incidence of serogroup C meningococcal disease decreased. In addition, serogroup C meningococcal pharyngeal carriage has likely been reduced, which has likely led to a reduction in serogroup C meningococcal disease in the unimmunized population.