Introduction
  Meningococcal infection (Neisseria meningitidies) is a disease that is not commonly encountered in Japan. However, it should not be forgotten that this disease is endemic all over the world and that over 100,000 people die of it every year. Compared to other countries, its incidence is low in Japan. Nevertheless, since no special precautions are taken, there could be outbreaks at any time. Measures such as surveillance and preparedness to make a vaccine available should be taken on a regular basis in order to be prepared against sudden outbreaks. Since meningococcal infection is a vaccine-preventable disease, travelers to endemic regions are advised to get immunized for their own protection. Since the meningococcal vaccine has not yet been approved in Japan, there is an urgent need for putting in place a system of immunization for travelers to endemic regions and in case of sudden epidemics.
Meningococcal infection
  The bacterium is a gram-negative diplococcus that infects humans who are the only carriers. The source of infection is discharges from the airways of humans, and the disease is spread by inhalation of droplets. The incubation period is 1~10 days, and 3~4 days in many cases. Small children aged 6 months and over can contract easily the disease, and approximately one-third of the cases are observed in adults. The disease takes the following forms: meningitis, bacteremia, septicemia, pneumonia, arthritis, urethritis, endocarditis, etc. The infection can occur in all the organs of the body. Septicemia is called in particular Waterhouse-Friedrichsen syndrome, and its mortality is extremely high (18~55%). The disease begins by sudden fever, muscular pain, and headache, and it is accompanied by convulsions, vomiting, diarrhea and rash. Following consciousness disorders, DIC, multiple organ insufficiency and death eventually occur in a short period of time (6~36 hours) after the onset. The mortality rate of meningococcal meningitis is on the order of 5% in Japan. There are at least 13 serogroups (A,B,C,D,X,Y,Z,E,W-135,H,I,K,L), of which five serogroups, namely A,B,C,Y,W-135, account for no less than 90% of meningococcal infections in the world. What is particularly notable with meningococcal meningitis is that it causes epidemics. In Japan, meningococcal infection is classed under Infectious Diseases Category Five in the Infectious Diseases Control Law. It is a disease in which all the cases should be identified. Clinicians who have encountered patients with this disease are under the obligation of reporting it to health centers within seven days.
  The diagnosis for meningococcal infection is made by isolation of the meningococcus from the site of infection , the blood and the cerebrospinal fluid by culture. However, its isolation is difficult if the test specimens are not handled properly. Precautions are required, such as avoiding to store the specimens in refrigerators and bringing them rapidly to laboratories for tests. The sensitivity of the cerebrospinal fluid culture may also be affected if the handling of the specimens is not adequate. Besides, the culture may often be negative in case antimicrobials have been already administered. In many cases the diagnosis is made by Gram staining of the cerebrospinal fluid whereas the culture is negative. The sensitivity and specificity of the latex agglutination technique are poor. Therefore, in the United Kingdom where the number of patients is about 100 times higher than in Japan, the PCR technique endowed with a highly sensitive serogrouping is used for routine laboratory tests.
  The treatment of meningococcal infection is shown in Table 1. The duration of the administration is 5~7 days. Strains mildly resistant to penicillin (MIC; 0.1\1 m.g/ml ) have been increasing in recent years in Europe, the US and Africa, and the number of regions where penicillin-based antimicrobials cannot be an option is growing.
Carriers and risk of secondary infection
  The meningococcus carriage rate has reached 0~5% in Japan, 5~15% in foreign countries, and 20-50% in endemic regions. Since the number of carriers is small in Japan compared to other countries, the incidence is apparently low. Whether one becomes a carrier or contracts the disease after being infected is influenced by the primary immunity. Immunity to meningococcus is apparently acquired gradually with age due to antigen cross-over with enteric bacteria and other Neisseria spp.. There are few cases of disease onset before the age of six months due to maternal antibodies. Factors increasing the carriage rate are epidemics, smoking, viral infection, living in cramped places such as barracks or dormitories, etc. The risk of secondary infection rises 500-4,000 times when there are close contacts in households and communities such as day care nurseries, etc.
Prevention of meningococcal infection
  Meningococcal infection can be prevented by a vaccine and antimicrobial agents. Prevention by administration of antimicrobials is targeted at household members with a high risk of secondary infection and persons having close contacts with the patient less than seven days before onset. Since over 50% of cases of secondary infection occur within seven days, the treatment should be initiated within 24 hours whenever possible. The drugs are listed in Table 2.
  Two types of purified capsular polysaccharide vaccines are primarily marketed in the world (two-valence A,C and four-valence A,C,Y,W-135). Immunity acquisition is good in adults and older children, but the efficacy cannot be expected in children under two years of age. The efficacy appears 7~10 days after one shot. The protective efficacy is 79~100%. A conjugate vaccine efficacious also in children below two years of age is currently under development in Europe and in the United States. Cases where immunization with the meningococcal vaccine is recommended are shown in Table 3.
Situation in Japan and in the world
  The incidence per 100,000 population is 0.01, 1 and 10~70 in Japan, Western countries and the African meningitis belt (Figure 1), respectively. The incidence is over 100 times that of Japan in Western countries and over 1,000 times in the African meningitis belt. In Japan, around 10 cases are reported every year, while the number is far higher in the United States, approximately 3,000. Although over 4,000 cases were notified each year around 1950 in Japan, the incidence has fallen to the present level since 1980. In the African meningitis belt, epidemics occur in ten-year cycles, and the incidence per 100,000 population exceeds 500 during outbreaks. Vaccination with the meningococcal vaccine is recommended to those who are traveling to Africa, the Middle East, Nepal and other countries where the prevalence is very high. Immunization with this vaccine is mandatory when entering Saudi Arabia, since in recent years there have been many cases involved in world large epidemics through the pilgrimage of Muslims to the city of Mecca.
Future actions
  Table 4 shows the standard plan of actions in case of epidemics. Since the meningococcal vaccine has not yet been licensed in Japan, there is an urgent need to set up a system allowing to import and store the vaccine for administration to travelers to endemic regions and in case of sudden outbreaks.