The Topic of This Month Vol. 32, No. 2 (No. 372)
Japan previously used the one dose measles vaccine for routine immunization to children 12-90 months after birth. In 2006, the vaccine was changed to measles-rubella combined vaccine and the vaccination schedule was changed from the single dose to two doses at one year of age (the 1st vaccination) and one year preceding primary school entrance (the 2nd vaccination) (IASR 27: 85-86, 2006). In addition, to achieve the elimination before 2012, the first grade students of the junior high school (12-13 years of age) (the 3rd vaccination) and the high school third grade students and other individuals in the same birth cohort (17-18 years of age) (the 4th vaccination) were added to the target vaccination age groups as five-year temporal measures under the Preventive Vaccination Law (IASR 29: 189-190, 2008)*. The reporting under the National Epidemiological Surveillance of Infectious Diseases (NESID) in compliance with the Infectious Diseases Control Law was changed to notification of all cases in January 2008 (IASR 29: 179-181 & 189-190, 2008). In addition, the notification requires not just clinical diagnosis but laboratory diagnosis too on account of increasing “modified measles” cases among those who received a single dose (http://idsc.nih.go.jp/disease/measles/guideline/doctor_ver2.pdf).
*Note: The schedule does not intend to give four doses. With the age distance between the target groups and on account of the limited time span of the temporal measures, any person under age of 18 has a chance of receiving two shots but not more. Missing the chance of immunization during the target age, he/she misses the chance of vaccination under this regime entirely (though they are free to receive vaccination with their own expense).
Measles incidence under the NESID: From week 1 to week 52 of 2010, total 457 cases (3.58 per 1,000,000 population), 329 cases based on laboratory diagnosis (including 168 “modified” measles cases) and 128 cases based on clinical diagnosis, were reported (as of January 7, 2011). It was a significant decrease compared with 11,015 cases in 2008 and 739 cases in 2009 (Fig. 1).
The reports of measles cases in 2010 decreased relative to 2009 in forty prefectures (Fig. 2), though seven prefectures, Kanagawa (77), Tokyo (76), Chiba (43), Aichi (32), Osaka (31), Saitama (29) and Fukuoka (25), continued to report more than 20 cases. The reports from the metropolitan area, Kanagawa, Tokyo, Chiba and Saitama combined, occupied more than half of all the reports. Prefectures reporting zero cases were Akita (2 years in succession), Toyama, Ishikawa, Shimane, Tokushima, Kagawa, Kochi (2 years in succession), Oita and Okinawa. These nine prefectures together with Kumamoto, Yamaguchi, Shiga, Niigata, Miyazaki and Hokkaido have already achieved the measles elimination target (<1/1,000,000 population).
There were 232 male and 225 female patients. As for age distribution of the patients (Fig. 3), one year olds were the highest in number, 104 (136 in 2009), followed by zero year olds, 30 (74 in 2009), two years olds, 22 (43 in 2009) and three years olds, 20 (20 in 2009). The incidence among the zero year and two year olds was reduced by half in comparison with year 2009. Among the measles patients, 119 had zero dose, 200 one dose and 29 two doses. The vaccination history of the remaining 119 was unknown. None of the zero-year-old cases had received vaccination, while among 104 one-year-old cases, 36 received zero dose and 68 had one dose. Among the 2-5 year olds, five had zero dose and 51 had one dose.
School outbreaks: From January to December in 2010, there were no temporary closures of schools or classes due to measles outbreak. Aichi Prefecture, however, reported an outbreak in a primary school in November-December 2010 which related to a case returning from Philippines (see p. 45 of this issue).
Isolation and detection of measles virus: Genotype analyses of measles virus isolates are useful for determining whether the virus is indigenous or imported. In Japan, the epidemic in 2006-2008 was caused by D5. In 2009 and 2010, however, the indigenous D5 was detected in small numbers (3 and 1 in respective years) (Table 1). In 2010, strains with genotypes indicative of importation increased remarkably, i.e., 14 strains of D9 (4 from imported cases from Philippines and 10 from the contacts and outbreak cases) (see p. 45 of this issue and IASR 31: 271-272 &327-328, 2010), two strains of H1 (imported from China, IASR 31: 203, 2010), one strain of D4 (imported from India, see p. 44 of this issue) and one D8 (imported from India, IASR 31: 328-329, 2010). Six vaccine-derived genotype A strains were confirmed by PCR diagnosis from measles-suspected cases and exanthema cases (as of February 3, 2011).
Vaccination rate (see p. 39 of this issue): The vaccination rate as of the end of 2009 fiscal year (the end of March 2010) was 94%, 92%, and 86% and 77% for the 1st (1 year), the 2nd (5-6 years), the 3rd (12-13 years) and the 4th (17-18 years) vaccinations, respectively, where the denominator for the 1st vaccination was number of one-year-old children as of 1 October 2009 and for the rest it was the number of the respective target populations. Yamagata, Fukui, both similarly as in 2009, and Iwate Prefectures attained vaccination coverage higher than 90% in all the four target cohorts (they did not exceed 95%, however). Compared with other prefectures, Kanagawa and Osaka were of low coverage in the 3rd and the 4th vaccinations, and Tokyo, Chiba and Saitama in the 4th vaccination.
The National Epidemiological Surveillance of Vaccine-Preventable Diseases (see p. 36 of this issue): Titers higher than 1:16 in the gelatin particle agglutination assay (PA) are judged as antibody positive. It is considered that measles elimination requires antibody positives among more than 95% of the population. In 2010, the rate of antibody positives was 67% in 1-year-old children, while it was 96% in 2-year-old children reflecting high coverage of the 1st vaccination. The age groups that did not reach 95% antibody positives were 0 year, 1 year, 3 year and 10-12 year olds. It should be noted that protection of individuals from measles infection requires titer 1:128 or higher. It should be noted that more than 16% of the population in age groups of 0-1 year, 10-12 years, and 15-17 years had antibody titer less than 1:128.
Measures needed to increase vaccine coverage: Although the number of measles cases has remarkably decreased since 2009, measles elimination necessitates further increase of the vaccine coverage all over the country. Akita Prefecture has conducted “Akita measles elimination month” since April from 2010 and has been providing “information on the next scheduled vaccination” on the internet and portable phones (see p.46 of this issue).
For fiscal year 2010, three target cohorts of the 2nd to the 4th vaccinations will not be covered by public expense after March 31 2011, before which date unvaccinated persons are advised to receive vaccination. During the Children's Immunization Week, from March 1 (Tuesday) to March 7 (Monday) in 2011, in some areas, local medical association will open clinics on holidays and/or evenings for vaccination.
For protection from measles infection when visiting endemic countries, vaccination should be completed prior to the visit. It is important to note that some measles-eliminated countries requires a certificate of vaccination for entry.
Importance of laboratory diagnosis: As the vaccination program progresses, clinical diagnosis alone is inappropriate in view of increasing number of “modified measles” cases. Differential diagnosis from other diseases becomes increasingly important. Actually, WHO requests the link between laboratory diagnosis and epidemiological investigation in evaluating measles elimination (WHO, WER 85: 490-495, 2010) (see p. 33 & 34 of this issue). In 2010, however, 28% of reported measles cases were clinically diagnosed without laboratory confirmation. In addition, laboratory confirmation is mostly made by IgM antibody test only. The IgM data may have to be scrutinized for false positives resulting from non-specific cross reaction or from partially shared antigenicity with measles antigen, such as in case of erythema infectiosum (parvovirus B19), exanthem subitum (HHV6, 7) and other feverish infections (IASR 31: 265-271, 2010). In principle, every measles-suspected case should be diagnosed by virus isolation or PCR detection. Prefectural and municipal public health institutes (PHIs) and National Institute of Infectious Diseases (NIID) established the collaboration network for PCR and antibody testing (see p. 41 of this issue). During January-August 2010, PHIs tested 461 measles-suspected cases and confirmed 10 cases as positive (p. 42 of this issue). It should be noted, however, that false negative results are often caused by inappropriate timing of clinical specimen sampling and also by inappropriate specimen shipment to PHIs (see p. 41 of this issue). Such a situation prompted MHLW to issue an announcement “On laboratory diagnosis of measles” on 11 November 2010 (see p. 44 of this issue).
Future strategy toward measles elimination: Almost all the measles viruses detected in Japan in 2010 were imported strains. In 2011, detection of genotype D9 (imported from Philippines and Singapore/Sri Lanka) and D4 (imported from UK) were reported one after another and importation-related outbreaks occurred (http://idsc.nih.go.jp/iasr/measles-e.html). To prevent the spread of measles, the active surveillance combined with the laboratory diagnosis and keeping high herd immunity by high vaccine coverage are crucial. Collaborative mechanism among medical institutions, health centers, PHIs and NIID should be further strengthened, so that all suspected cases are actively investigated by epidemiologists and laboratory experts.
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