The Topic of This Month Vol. 31, No. 2 (No. 360)
Japan formerly used the one dose measles vaccine for routine immunization to children 12-90 months after birth. In 2006, the vaccination schedule was revised and measles-rubella combined vaccine was introduced. Now the target age of the first vaccination is one year, and that of the second vaccination is one year preceding primary school entrance (5-6 years of age). Namely, two doses of measles-containing vaccine (MCV) are requested before entrance to the primary school (IASR 27: 85-86, 2006). In addition, in 2007, in response to the outbreak of measles among young populations in their 10s and 20s (IASR 28: 239-240, 2007), vaccination to the first grade students of the junior high school (12-13 years of age) and those aged 17-18 years (including the third grade students of the high school) were added as five-year temporal measures under the Preventive Vaccination Law so as to increase the immunity level among this population.
The measles case reporting under the National Epidemiological Surveillance of Infectious Diseases (NESID) in compliance with the Infectious Diseases Control Law was also changed to notification of all cases in January 2008 (IASR 29: 179-181 & 189-190, 2008). Formerly, the sentinel clinics and hospitals reported cases based on clinical symptoms. But, now the doctors are requested to report measles cases not only on clinical but also on laboratory diagnosis on account of the recent increase of the “modified measles” among those receiving one dose of MCV (http://idsc.nih.go.jp/disease/measles/guideline/doctor_ver2.pdf).
Measles incidence under the NESID: From week 1 to week 53 of 2009, total 741 cases (5.80 per 1,000,000 population), 438 cases based on laboratory diagnosis (including 193 “modified” measles cases) and 303 cases based on clinical diagnosis, were reported (as of January 7, 2010). It was a remarkable decrease compared with 11,015 cases in 2008. The largest number reported per week was 30 cases in week 29 (Fig. 1), and the number of reports tended to decline from week 34 on.
When prefectures were compared for the incidence of measles (Fig. 2), Chiba (116), Tokyo (112), Kanagawa (97) and Osaka (57) were the top four. The reports from the metropolitan area, Kanagawa, Tokyo, Chiba and Saitama (44) combined, occupied half of all the reports. Other prefectures where more than 20 cases were reported were Aichi, Fukuoka, and Hiroshima. There were no prefectures whose report exceeded 10 cases/week. Akita, Kochi, and Kumamoto reported zero cases. These prefectures together with Ishikawa achieved the measles elimination target (<1/1,000,000 population).
There were 371 male and 370 female patients. As for age distribution of the patients (Fig. 3), 140 were one year old, 74 were zero year old, and 42 were two years old. The age peak observed in 2008 for 15-16 year olds disappeared. Among the patients, 176 cases had no vaccination history, 352 had received one dose, and 32 had received two doses. The vaccination history of the remaining 181 was unknown. None of the zero-year-old cases (except one case with unknown vaccination history) had received vaccination, while many of the one-year-old cases (96/140) had received one dose.
In 2009, there was no report of measles encephalitis that requires reporting of all the cases in contrast to 9 cases each in 2007 and 2008.
School outbreaks: From April to December in 2009, there were no temporary closures of schools or classes due to measles outbreak reported to the Ministry of Health, Labour and Welfare (MHLW).
Isolation and detection of measles virus: Measles virus has 8 clades from A to H, and further divided into 23 genotypes. The epidemic of 2001 in Japan was caused by D5. In 2002-2003, H1 was predominant (IASR 25: 60-61, 2004), and in 2006-2008, D5 became predominant again (IASR 30: 29-30, 2009). In 2009, prefectural and municipal public health institutes (PHIs) isolated/detected eight strains (as of January 29, 2010), i.e., three strains of D5 detected in Okinawa (two in February and one in April), one strain of D9 isolated in March in Yamagata from a case who came back from Thailand (see p. 47 of this issue), one strain of D8 isolated in Okinawa in September, which was the first isolation of genotype D8 from the domestic case in Japan (IASR 30: 299-300, 2009), and three vaccine-derived strains of genotype A (one each from a chickenpox case in Tokyo in April, a herpangina case in Osaka in April and an exanthem subitum case in Fukuoka in June) (http://idsc.nih.go.jp/iasr/measles-e.html).
The National Epidemiological Surveillance of Vaccine-Preventable Diseases (see p. 36 of this issue): While titers higher than 1:16 in the gelatin particle agglutination assay (PA) are judged as antibody positive, protection from measles requires titer 1:128 or higher.
In 2009, the rate of antibody positives (≥1:16) was low (73%) in one-year-old children, while it was 96% in two-year-old children which reflected high coverage of the first vaccination. The age groups that did not reach 95% antibody positives were 0, 1, 10 and 15 years. The percentage of the population with high antibody titers (≥1:256) among 12-14-year-old and 17-19-year-old age groups were higher in 2009 than in 2008 reflecting the second vaccinations introduced in 2008. However, more than 10% of the population whose age was over twenty years had antibody titer lower than 1:128.
Vaccination rate (see p. 39 of this issue): The vaccination rate as of the end of 2008 fiscal year (the end of March) was 94% for the first vaccination and 92%, 85%, and 77% for the second vaccinations for age groups of 5-6 years, 12-13 years and 17-18 years, respectively, where the denominator for the first vaccination was number of one-year old children as of 1 October 2008, and those for the second vaccinations were number of the respective target populations. The prefectures that accomplished vaccination coverage over 90% were only three, Yamagata, Fukui and Saga.
In Tokyo, Kanagawa and Osaka, where the incidence of measles was high, the second vaccination rate was low for the both 12-13 years and 17-18 years.
Measures needed to increase vaccine coverage: For measles elimination, the vaccine coverage has to be increased further (see p. 48 of this issue). Akita Prefecture is planning to have “Akita measles elimination month” in April from 2010 on, using the lessons learned during the experience of the large measles epidemic in 1987-1988 involving 10 deaths and a local outbreak in 2007-2008 (see p. 41 of this issue). A high school, through contribution of nurse-teachers, achieved the second vaccination to the third grade students with coverage higher than 95% (see p. 42 of this issue).
For eliminating measles in zero-year-old infants, there is no other means than elimination of measles from Japan. For fiscal year 2009, the second vaccinations to the three target cohorts will not be covered by public expense after May 31, before which date unvaccinated persons are advised to receive vaccination. During the 2010 Children's Immunization Week from March 1 (Monday) to March 7 (Sunday), in some areas, local medical association will open clinics on holidays and/or evenings for vaccination.
Importance of laboratory diagnosis: As the vaccination program progresses, “modified measles” increases particularly among those with previous vaccination history. As the “modified measles” cannot be correctly diagnosed by clinical symptoms alone, the laboratory diagnosis is becoming more and more important. In 2009, the patients diagnosed using laboratory data were 60%, and the rest of the patients were diagnosed on clinical symptoms alone. Most of the laboratory diagnosis was IgM test done in commercial laboratories. However, interpretation of IgM antibody test needs caution because the borderline data are difficult to judge and often result in false-positives or false-negatives (see p. 43&44 of this issue).
The Special Infectious Disease Prevention Guidelines on Measles (MHLW, December 28, 2007) requests laboratory diagnosis for all the measles cases once the measles case number is reduced to a certain level. Japan is now a member of global measles-rubella laboratory network (see p. 35 of this issue), and in June 2008, PHIs and National Institute of Infectious Diseases (NIID) established the Measles-Rubella Reference Centers for PCR and antibody testing (IASR 30: 45-47, 2009). However, many of the specimens are not sent to PHIs (see p. 46 of this issue).
Future strategy toward measles elimination: To prevent the spread of measles, the active surveillance for investigating each suspected case should be more facilitated and more strengthened. Collaborative mechanism among medical institutions, health centers, PHIs and NIID should be further strengthened, so that all suspected cases are laboratory diagnosed. It is also necessary to start discussion on possible reclassification of measles, i.e., its move from the current category V into category IV, III or II in the categorization under the Infectious Diseases Control Law.
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