The Topic of This Month Vol.20 No.2(No.228)

The incidence of measles in Japan is followed by the National Epidemiological Surveillance of Infectious Diseases (NESID). The immune status against measles of the people is followed by the National Epidemiological Surveillance of Vaccine-Preventable Diseases (NESVPD). This topic will summarize the present status of measles in Japan on the basis of the information provided by the above programs.

Since 1978, when regular vaccination program against measles started, the incidents of measles epidemics have been reduced. According to NESID, the weekly reports of measles patients during 1987-1998 (Fig.1) have shown a relatively large-scale epidemic occurring in 1991. Since then, the number of patients has decreased (Fig. 3, see cases in each year). The largest number of patients is reported in April-May of each year. When past measles epidemics are reviewed by geographical region (Fig. 2), the 1991 epidemic occurred throughout the country. Small-scale epidemics have consistently occurred in some regions in Japan (see IASR, Vol. 19, Nos. 2 & 7).

The age distribution of patients is shown in Fig. 3. In 1998, patients aged 1 year (<24 months) were numbered the largest, followed by those aged <1 year (<12 months). During 1992-1997, of 79 deaths from measles (53 males and 26 females), those aged 1 year (<24 months) were the largest in number, followed by those aged <1 year (<12 months) (Table 1).

The measles antibody prevalence among general population in 1996-1997 is shown in Figs. 4 and 5. In NESVPD, the hemagglutination-inhibition (HI)-antibody test with fresh green monkey erythrocytes used to be performed (11 times in total during 1978-1994). Recently, however, it has become difficult to obtain green monkey erythrocytes, so a gelatin particle agglutination (PA) test kit, which is more sensitive than HI test and easy to perform, has been implemented (Sato et al. Arch. Virol. 142:1971-1977, 1997). The PA test detects antibodies to not only hemagglutinin (H) protein but also fusion (F) protein. In 1996 and 1997, PA-antibody was assayed with this kit. Fig. 4 shows the rate of PA-antibody positives by age group. In the group of <1-year of age, those with low antibody titers suggestive of the maternal antibody were seen. The antibody-positive rate of the 1-year group was 50%, that of 2-year group 80%, and those of 5-year and older groups 90-100%. The antibody-positive rates were compared by vaccination history (Fig. 5a, ��, ��). The vaccinees of any age group gave a rate close to 100%, but the difference from those of non-vaccinees particularly of younger generations is conspicuous. Non-vaccinees may acquire the immunity through natural infection before the age of 7 years. The difference between vaccinees and non-vaccinees in the geometric mean antibody titer (GMT) of antibody-positives was found to be small (Fig. 5b). The rate of those having such high antibody titers that exceeding 1:512 of both vaccinees and non-vaccinees (Fig. 5a, ��, ��) and GMT of antibody positives (Fig. 5b) were slightly low at the age over 10 years, but it was increased again at the age over 30 years.

Recently, highly susceptible B95a cells (established at the National Institute of Infectious Diseases) suitable for measles virus isolation have come into wide use. The reports on measles virus isolation from prefectural and municipal public health institutes to the Infectious Disease Surveillance Center have markedly increased; 309 isolates were reported during 1991-1998 (30 isolates during 1982-1990, see IASR, Vol. 14, No. 9). Measles viruses used to be isolated from nasopharyngeal specimens. Nevertheless, recently, measles virus isolation from blood specimens has been on the increase because of the use of B95a cells (see IASR, Vol. 16, No. 7). Nucleotide sequence analyses conducted at the Department of Viral Disease and Vaccine Control, NIID (see p. 31 of this issue) found that the viruses currently prevailing in Japan are mainly genotypes D3 and D5 based on the WHO genotyping nomenclature (see WHO, WER 73:265-269, 1998).

The current difficulties concerning measles and the future anti-measles strategy may be as follows:

1. Promoting vaccination and encouraging early vaccination: The survey conducted by a study group on immunization of the Ministry of Health and Welfare disclosed that the average rate of vaccination against measles was 75% in 1996 (see p. 30 of this issue). The procedure to increase the rate is being reviewed (a preliminary report of the Committee for Immunization Program: see p. 33 of this issue). The age of vaccination recommended by Preventive Vaccination Law is 12-24 months old. Since patients and deaths were predominantly aged 1 year, the children 12 months old should receive vaccination at the earliest possible time.

2. Monitoring the people's immune status: In 1998, an outbreak of measles occurred in Alaska, USA among senior high school students, having received only the first-dose-measles vaccine. A child visiting from Japan was considered to be the source of infection. The second-dose-measles vaccination was given by an emergency order (see CDC MMWR, 47, Nos. 51 & 52, 1109, 1998). To strengthen the individual protective immunity, more countries are giving booster injections with live measles vaccine to cope with the wild-type viruses (see WHO, WER 73, No. 50, 389, 1998).

If the vaccine coverage increases and natural measles decreases in Japan in future, decrease in chances of the boosting of immunity by infection with wild-type virus (Whittle et al., Lancet, 353: 98-102, 1999) accompanying decrease in antibody titer among adults is anticipated. If the antibody titer of pregnant women is lowered, the maternal antibody will also decrease. The infants under the recommended age for vaccination are more susceptible to wild-type virus if ever exposed, and the appearance of measles in infants tends to be serious. Monitoring the immune status as the levels of antibody titer of general population by NESVPD will be continued to investigate the necessity for the second-dose vaccination and the adequate age for the injection.

3. Surveillance for adult measles patients: To understand the incidence of measles among adults, which is not clear at present, surveillance for adult measles patients is undertaken in compliance with the new Infectious Diseases Control Law. In addition to reports of measles patients from about 3,000 pediatric sentinel clinics, about 500 sentinel hospitals are soon reporting adult inpatients of measles from April 1999.

4. Global surveillance of wild-type measles virus: WHO is aiming at eliminating measles by propagating the vaccines after the success in polio eradication. For long-term and effective vaccine strategy, international cooperation is necessary for isolating the viruses that are prevailing and analyzing their antigen structures and nucleotide sequences (see p. 31 of this issue).



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