The Topic of This Month Vol. 33, No. 2 (No. 384)
Currently, Japan uses measles-rubella combined vaccine. The vaccination schedule consists of 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 the end of 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, which was taken as five-year (FY 2008-FY 2012) temporal measures under the Preventive Vaccination Law (IASR 29: 189-190, 2008).
Measles incidence under the National Epidemiological Surveillance of Infectious Diseases: Infectious Diseases Control Law requests notification of all measles cases since January 2008 (IASR 29: 179-181, 2008 & 29: 189-190, 2008). From week 1 to week 52 of 2011, total 434 cases (3.58 per million population) were reported (Fig. 1), among which 311 cases were supported by laboratory diagnosis (including 110 “modified”measles cases) but 123 cases were not (as of January 5, 2012).
The reports of measles cases in 2011 decreased relative to 2010 in twenty-four prefectures (Fig. 2). Now, four prefectures within the metropolitan area, Tokyo (see p. 31 of this issue), Kanagawa, Saitama and Chiba occupy 63% of the reported cases. Fourteen prefectures reported zero cases, and total 19 prefectures reported less than 1/million population, a criterion of measles elimination.
Two hundred and thirty-one male and 203 female patients were reported. As for age distribution of the patients (Fig. 3), one year olds were the highest in number (50), followed by zero year olds (25), three years olds (17) and four years olds (16). The incidence among 0-4 year olds was reduced from 183 in 2010 to 119 in 2011, but that among 20-49 year olds rather increased. Among the measles patients, 126 had had zero dose, 141 one dose and 26 two doses. The vaccination history was obscure for the remaining 141. None of the zero-year-old cases had received vaccination. Among 50 one-year-old cases, 20 had had zero dose and 29 one dose. Among the 2-5 year olds, 12 had had zero dose and 35 one dose.
There was no temporary closing of classes or schools due to measles outbreak from January to December 2011.
Isolation and detection of measles virus: Genotype analyses of virus isolates are useful for determining whether the virus is indigenous or imported. In Japan, the epidemic in 2006-2008 was caused by D5, which has not been detected later than May 2010 (see p. 29 of this issue). In contrast, strains with genotypes prevalent abroad are increasing (Table 1 & Table 2), such as, D9 that was isolated already in 2010 (see p. 31 of this issue and IASR 32: 144-145, 2011), D4 that surged in spring of 2011 (see p. 31 of this issue and IASR 32: 145-146, 2011), G3 that was isolated for the first time in Japan in 2011 (IASR 32: 79-80, 2011), and D8 (IASR 32: 197, 2011). Vaccine-derived genotype A strains were detected by PCR diagnosis from post-vaccination febrile patients and exanthema cases (IASR 32: 299-300, 2011).
Vaccination rate (see p. 33 of this issue): As of March 31, 2011 (the end of FY 2010), the vaccination rate of measles-containing vaccines (M, MR) for the 1st (1 year), the 2nd (5-6 years), the 3rd (12-13 years) and the 4th (17-18 years) vaccination in FY 2010 was respectively 96% (94% in FY 2009), 92% (92% in FY 2009), and 87% (86% in FY 2009) and 79% (77% in FY 2009). Here, the denominator for the 1st vaccination is number of one-year-old children as of October 1, 2010. For the rest it was the number of the respective target populations. The 1st vaccination attained the target vaccination rate >95% for the first time in the national level, and prefectures attaining >95% for the 1st, 2nd and 3rd vaccinations are increasing in number.
The National Epidemiological Surveillance of Vaccine-Preventable Diseases (see p. 35 of this issue): WHO considers that measles elimination requires antibody positives among more than 95% of the population. From the interim report of the 2011 survey, the antibody-positive rate (titer 1:16 or higher in gelatin particle agglutination assay) became >95% in age groups 2 years or older for the first time. However, the antibody-positive rate in 1-year age group was 74%. To increase the immune status among 1-year age group, earliest vaccination after attaining 12 months of age is desired. While protection of individuals from symptomatic measles infection requires titer 1:128 or higher, more than 10% of the population in age groups of 0-1 year, 4 years, 10-12 years, 16-17 years, 50-54 years and 60 years or older had antibody titer <1:128, meaning that no small number of individuals among the target populations of the 1st to 4th vaccinations in FY 2011-FY 2012 had insufficient level of antibody.
Enhancing vaccine coverage: The number of measles cases has remarkably decreased after introduction of the 3rd and 4th vaccinations in FY 2008 (Fig. 1 & Fig. 3). For measles elimination, further efforts should be made to enhance and maintain the vaccine coverage at high level; intensive vaccination among FY 2011-FY 2012 target populations will be important in this respect.
It has been indicated that the cooperation between schools, families, school doctors, city office health departments, board of education, and related bodies is an important element in increasing the vaccine coverage. In response to this requirement, vaccine campaign is being conducted involving 19 junior high schools in Yamagata City (see p. 38 of this issue), for example. A high school in Shimane Prefecture attained 100% vaccine coverage through a school nurse-led school-wide measles campaign in collaboration with parents and teachers (see p. 39 of this issue). Ministry of Education, Culture, Sports, Science and Technology produced leaflets and posters destined to the first grade junior high school students and the third grade high school students (see p. 40 of this issue).
Unvaccinated persons belonging to target cohorts of the 2nd, 3rd and 4th vaccinations in FY 2011 are advised to receive vaccination before March 31, 2012, as public expense will not cover the vaccination after this date. During the Children's Immunization Week, from March 1 (Thursday) to March 7 (Wednesday) in 2012, in some areas, local medical association will open clinics on Saturday, Sunday and evenings for vaccination. As the coming FY 2012 is the last chance of receiving the 3rd and 4th immunizations, the eligible persons are advised to be vaccinated at the earliest occasion after April of this year.
Importance of laboratory diagnosis: As the vaccination program progresses, clinical diagnosis alone becomes insufficient on account of increasing number of “modified measles” cases among vaccinated persons. WHO's requirement for evaluation of measles elimination includes confirmation by laboratory diagnosis or by epidemiological link with a laboratory-confirmed case. Clinically suspected measles or weakly positive IgM cases are often cases of rubella (see p. 43 of this issue), erythema infectiosum or exanthem subitum (IASR 31: 265-271, 2010). Therefore, direct detection of measles virus, such as by PCR or virus isolation, is now indispensable. Prefectural and municipal public health institutes (PHIs) and National Institute of Infectious Diseases (NIID) have established the collaboration network for laboratory diagnosis based on PCR testing (see p. 41 of this issue). In 2011, however, as in the previous year, laboratory confirmed cases were only 70%, and 60% of them was diagnosed by IgM test only. It is important to obtain clinical specimens in appropriate timing and send them to PHIs. Establishment of appropriate specimen collection and transport system is urgently needed.
Measures to be taken from now: Almost all the measles viruses detected in Japan in 2010-2011 were imported strains, i.e. Japan has become an importer of measles. Outbreaks caused by D8 and D9 of overseas origin are continuously reported in 2012 (Table 1 and http://idsc.nih.go.jp/iasr/measles-e.html). Prevention of such importation requires vaccination of travelers before trip abroad. For FY 2011, immunization to the second grade high school students going abroad as school excursion are covered by public expense for 4th vaccination. Further increase of the vaccine coverage and strengthening of cooperation between medical institutions, health centers, PHIs and NIID are required. Active surveillance combined with the laboratory investigation should be conducted to all the suspected measles cases. Principle of “instantaneous response once found” is a key for stopping the spread of measles.
PCR negatives are not necessarily indicative of measles negative. Diagnosis should be established for each case taking into account clinical pictures, PCR and IgM results and epidemiological data. In addition, to demonstrate measles elimination status of Japan, it is necessary to have sufficient data that indicate there is no endemic measles circulation. For this, the genomic data of isolates are indispensable.
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