The Topic of This Month Vol.26 No.2(No.300)
Meningococcal meningitis, a Category V notifiable disease under the National Epidemiological Surveillance of Infectious Diseases (NESID) (based on the Infectious Diseases Control Law that was amended in November 2003), is a nationally notifiable disease in Japan. While H. influenzae is by far the most common etiologic agent of bacterial meningitis in children, followed by S. pneumoniae , group B streptococcus, and Escherichia coli (see IASR 23: 31-32, 2002), N. meningitidis is recognized as a rare cause in Japan. However, cases of meningococcal meningitis are frequently seen abroad, either developing countries such as Africa or industrialized countries such as the Northern European nations and the United States. According to the World Health Organization (WHO), approximately 500,000 cases and 50,000 deaths attributed to meningococcal meningitis are reported worldwide each year. In today's borderless world, a result of advances in air travel, epidemics of meningococcal meningitis abroad should be regarded as equally threatening events in Japan. Therefore, monitoring trends in the incidence of meningococcal meningitis in Japan is necessary toward developing and implementing future prevention and control measures.
Annual trend of meningococcal meningitis: Prior to the enactment of the Infectious Diseases Control Law, cases had been notified as "epidemic cerebrospinal meningitis" under the Communicable Diseases Prevention Law. According to the "Statistics on Communicable Diseases in Japan," over 4,000 cases were reported around the end of World War II. Despite the fact that active control measures, such as vaccination, were not implemented at that time, the incidence of meningococcal meningitis fell sharply after the war to less than 100 cases per year after 1969. Subsequently, incidence decreased to less than 30 cases per year after 1978 and to single digits in the 1990s. Since the implementation of the Infectious Diseases Control Law in 1999, 8-22 cases have been reported annually (Fig 1).
Notified cases through NESID: From April 1999 to December 2004, 82 cases of meningococcal meningitis were reported through NESID. Of these, eight were fatal at the time of notification (Fig 2). All cases, except one with a history of travel to Australia (and five cases with no data available), were acquired domestically.
Serotyping of N. meningitidis : N. meningitidis species are classified into 13 serogroups based on differences in their capsular polysaccharides. Serogrouping provides important epidemiological information for vaccine planning. However, serogroup data was available for isolates from only nine cases at the time of reporting (group A 2 cases, group B 7 cases). Even after additional information was obtained from local municipalities, serogroup data remained unknown for approximately half of the cases. Of those with available serogroup information, serogroup B was the most prevalent with 22 cases, followed by serogroup Y with 15 cases (Fig 3).
Results of a retrospective survey conducted by a research group found that 70% or more of domestic isolates over the past 30 years were either from serogroups B or Y (see p. 36 of this issue). This serogroup distribution in Japan is unique, since serogroups A, B and C are the major ones circulating abroad (see p. 36 of this issue). On the other hand, although no serogroup A isolates were identified from 182 isolates of N. meningitidis over the past 30 years (see p. 36 of this issue), serogroup A was isolated from three cases after 1999. Of these three cases, one traveled to China prior to the illness and the other had relatives that traveled there. Molecular epidemiological classification using multilocus sequence typing (MLST) found that both isolates were genotypically indistinguishable from a recent epidemic strain in China (see p. 37 of this issue and IASR 24: 264, 2003). Only one case of group C was reported (Tokyo, 2003); serogroup C is rarely isolated from domestically infected cases (see IASR 25:207, 2004).
Seasonal variations: In the high-risk area of meningococcal meningitis, referred to as the African "meningitis belt" just the north of the equator, disease incidence is very high during the dry season (http://www.who.int/emc-documents/meningitis/ whoemcbac983c.html). In Japan, such large seasonal variations are not observed, although slight increases in case counts have occurred during the late winter (February-March) and rainy (June-July) seasons (Fig. 2). Data from the "Statistics on Communicable Diseases in Japan" show similar seasonal trends in the past. Therefore, these same trends may persist at present, even after drastic decreases in reported cases have occurred.
Age and gender of cases: Reported meningococcal meningitis cases in Japan have occurred most frequently in infants and children 0-4 years of age, followed those 15-19 years (Fig. 4). In other developed countries (e.g. UK, USA) with large numbers of cases, children 0-2 years of age and college students living in dormitories also represent the most frequently affected groups. Although male cases (59) largely outnumbered female cases (23) in Japan, no such gender differences have been observed in other countries. As such, this trend may be characteristic of Japan.
Incidence by prefecture: Meningococcal meningitis cases were reported from 23 out of 47 prefectures. Tokyo and Kanagawa reported the most cases with 20 and 15 cases, respectively, followed by Chiba (6), Aichi (5), and Fukuoka (5). The fact that more cases are reported from metropolitan and other populated areas, where active mixing of populations takes place, may be explained by the fact that N. meningitidis is only spread from person to person. Further accumulation and analysis of large numbers of cases will be necessary to help explain this regional difference.
The number of meningococcal meningitis cases worldwide is large, increasing the risk of contracting disease among Japanese who travel to endemic areas or have contact with imported cases. From the perspective of early detection of imported cases and prevention of further spread, it is important to obtain serogroup data on N. meningitidis isolates in Japan. Because not all isolates are currently serogrouped, it will be necessary to strengthen future pathogen surveillance. All medical institution and laboratories are asked to actively conduct serogrouping of N. meningitidis isolates. The National Institute of Infectious Diseases also performs detailed analyses of N. meningitidis using MLST (see p. 36 of this issue), and willingly accepts isolates, including those difficult to serogroup, for further identification.
Current reporting criteria for meningococcal meningitis are based on the judgment of the examining physician. If the disease is suspected, based on symptoms and physical findings, pathogen identification is performed by isolation of N. meningitidis from cerebrospinal fluid. The reporting criteria do not specify situations in which meningococcus is isolated from blood of patients with meningococcemia. However, a N. meningitidis strain causing septicaemia may subsequently cause meningitis. Revisions to the reporting criteria are under review in order to strengthen laboratory diagnostic systems to cover all meningococcal infections.
According to WHO's practical guidelines for "Control of Epidemic Meningococcal Disease," post-exposure chemoprophylaxis is appropriate for the prevention of secondary cases in small groups, such as household members and boarding school pupils@(http://www.who.int/emc-documents/meningitis/whoemcbac983c.html). CDC also recommends chemoprophylaxis with rifampin or other antimicrobial agents for household contacts and residents of treatment facilities, as the attack rate in these groups is 500-800 times higher than that of the general population (http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00046263.htm). In Japan, however, chemoprophylaxis is not implemented except under special direction from health centers or other authorities. This stems from the fact that administration of antimicrobial agents to healthy people is not recommended nor covered by health insurance. Future consideration toward developing national guidelines for post-exposure chemoprophylaxis will be necessary.
At present, due to the small number of cases in Japan, the probability of an urgent introduction of vaccination is felt to be low. Meningococcal vaccine is presently not commercially available in Japan, and is therefore administered in only a few institutions. Individuals traveling to areas with epidemic or endemic meningococcal meningitis activity may choose to be vaccinated either 1) with a vaccine personally imported by a physician prior to travel or 2) in the country of destination. With recent epidemics occurring in neighboring countries such as China and the Philippines, we must recognize that meningococcal meningitis is certainly not a rare disease any longer.
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