The Topic of This Month Vol.25 No.12(No.298)

Chickenpox 1982-2004

(IASR 2004; 25 : 318-320)

Varicella-zoster virus (VZV) is a DNA virus that belongs to the family Herpesviridae , subfamily Alphaherpesvirinae . Primary infection frequently manifests as chickenpox (varicella). Life-long latent infection then develops in sensory nerves and ganglia, and herpes zoster, or shingles, occurs when latent VZV reactivates in association with immunosuppressed conditions or aging. Chickenpox generally occurs more often in children with good prognosis, although complications such as secondary bacterial infections (including sepsis), meningoencephalitis, cerebellar ataxia, pneumonia, or hepatitis can occur. Adults or pregnant women who become infected often develop severe disease. Although effective antiviral drugs have improved prognosis, even at present, fatal disease often occurs in those who are immunosuppressed. The disease is highly contagious, with transmission occurring by droplet or airborne spread of respiratory secretions, and less commonly by contact with skin lesions. The virus initially invades the upper respiratory tract and subsequently causes viremia. After an incubation period of about two weeks, a rash appears, first on the trunk and face, then over the entire body. The rash progresses rapidly from erythema to papules to vesicles, ending in crusting. In the acute phase, lesions exist at all stages of development and are infectious until crusted over. Because the diagnosis can be easily made by the characteristic rash, virus isolation is seldom attempted. However, if disease develops in adults or immunosuppressed individuals, unusual clinical course may sometimes follow, thereby necessitating an etiological diagnosis by methods which include virus isolation.

Incidence of chickenpox: The number of chickenpox case reports per pediatric sentinel from the National Epidemiological Surveillance of Infectious Diseases (NESID) is shown in Fig. 1. Although a slight decrease in numbers of cases has been observed since 1988, there were 275,036 cases (92.36 per sentinel) in 2000, 271,409 (89.90) in 2001, 263,308 (86.73) in 2002, 250,561 (82.39) in 2003 and 220,543 (72.59) from weeks 1-49 in 2004, fairly constant figures from year to year.

Among the ages of the cases reported (Fig. 2), those younger than 10 years of age have accounted for more than 95% of all cases every year over the past 20 years. Although the proportion of cases 5-9 years of age have decreased gradually while the proportion 1-4 years of age have increased, after 1995, cases 5 years of age and younger have consistently accounted for approximately 90% of all cases. Infants have consistently accounted for slightly less than 10% of all cases over the past 20 years. The proportion of cases one-, two-, three-, and four years of age were approximately equal to each other, while proportions 0 and 5 years of age were slightly lower.

Figure 3 depicts the pediatric population (0-9 years old) along with number of case reports of chickenpox and exanthem subitum per sentinel site. Exanthem subitum has been included as an indicator disease from the inception of the NESID because there are no yearly or seasonal changes in disease incidence per sentinel. Case reports of exanthem subitum had been decreasing concomitantly with the declining pediatric population. Although increases and decreases in the number of case reports of chickenpox occur annually, a decreasing trend in the number of case reports has accompanied a declining pediatric population as similarly seen with exanthem subitum. However, after the enactment of the Infectious Diseases Control Law in 1999, sentinel sites shifted to medical institutions centered on pediatric care, leading to a slight increase in numbers of case reports of both diseases. Approximately twice as many cases of chickenpox as of exanthem subitum have been reported every year.

A regular trend is seen yearly in which weekly numbers of case reports decrease from week 25, reach a low during weeks 36-38, then increase from week 45 on. Regionally (see Fig. 4 on p. 320), the Hokkaido, Tohoku (see Yamagata P.) and Hokuriku (see Fukui P.) districts show bimodal epidemic patterns, while districts south of and including Kanto (see Tokyo M. and below) demonstrate ambiguous or unimodal epidemic patterns. In Kyushu (see Miyazaki P.) and Okinawa, unimodal patterns exist, with the difference in numbers of case reports between periods with many cases and periods with few cases being larger than that in other districts.

Detection of VZV: From January 1982 to October 2004, there were 737 reports of VZV detection from prefectural and municipal public health institutes (PHIs) (as of October 25, 2004). Because chickenpox is not a targeted disease in infectious agent surveillance, reports from PHIs are based on surveys at the research level. Prior to introduction of the varicella vaccine, there were 50-100 isolation reports annually; since then, the number of reports has decreased to 6-11 yearly. PCR has been the primary method of detection.

Varicella vaccine: The Oka strain varicella vaccine is a live attenuated vaccine first developed in the world by Takahashi and others (see p. 320 of this issue). It is recognized by WHO as the most desirable varicella vaccine and is administered to children one year of age and older in many countries (see p. 330 of this issue). Prevention of naturally acquired chickenpox is expected to reduce the later incidence of zoster. Furthermore, in 2004, application of the vaccine has expanded to include boosting VZV-specific cellular immunity, which in turn is expected to prevent zoster in the elderly. The seroconversion rate after one dose of vaccine is greater than 95% in healthy children and greater than 90% in children with leukemia. Vaccine efficacy has been estimated at 80%-85% against infection, including mild disease, and 95%-100% against moderate and severe disease (see p. 320 of this issue). Post-vaccine adverse reactions were occasionally seen when the vaccine contained gelatine, but have become rare since its removal. When administered to immunocompromised patients, vesicles may develop after 2-3 weeks. As of 2004, countries beside the USA that have recommended vaccine to all children include Korea, Canada, Australia, and Finland (see p. 330 of this issue). Countries where routine immunization has been introduced have observed declines not only in chickenpox cases, but also chickenpox-related hospitalizations, medical costs and deaths [Pediatrics 114 (3): 786-792, 2004 and Pediatr. Infect. Dis. J. 23 (6): 498-503, 2004]. On the other hand, as depicted in Table 1, Japan has produced between 200,000- 300,000 doses of varicella vaccine annually, about one-fourth the number of measles doses, ever since the introduction of varicella vaccine in 1987 as voluntary immunization for children one year of age and over. The estimated vaccine coverage rate is approximately 25-30% (see p. 322 of this issue).

Current problems: According to results from two surveys in Sakai City and Kanazawa City, the vaccine coverage rate of nursery school children is as low as 7.6-13%. Once infection occurs in a group, a large-scale outbreak may follow which includes infants not old enough to receive vaccine (see p. 324&326 of his issue). The average duration of nursery school absence is about one week, and the burden on their guardians who take off from work to provide nursing care is indicated (see p. 326 of this issue). Based on a study in Izumo City, the total direct medical costs and indirect costs of family nursing (social disease burden) was estimated at \43.9 billion nationwide for a hypothetical 840,000 annual cases, about 5 times the social disease burden of measles in 2003 (see p. 331 of his issue). Approximately 80% of the social disease burden is a result of family nursing cost, although the ratio of the total cost of disease /total cost of vaccination is high, between 4.4-5.9 (see p. 331 of his issue). Nosocomial infection of VZV occur every year, and the impact that susceptible health care workers may have (on nosocomial spread) could be significant although the antibody prevalence in adults is high at 95% (see p. 328 of this issue). Considering the impact of secondary infection on immunocompromised people, as well as the costs and labor required for infection control of nosocomially acquired infections, vaccination of medical staff is also important (see p. 328 of this issue).

Future countermeasures: The present vaccine coverage rate in Japan is not sufficient to control an epidemic, and reports of cases from 3,000 pediatric sentinels throughout Japan exceed 200,000 every year. In addition to the marked decrease in cases of severe disease in countries where routine immunization has already been adopted, Euro Var, an organization of US and European researchers, reached a consensus toward routine immunization in Europe this year. This consensus is considered important toward the planning of future countermeasures in Japan. The health economic effects have been shown, and considering the scale of current epidemics and the actual conditions of serious cases, elevating the vaccine coverage rate will be necessary. Because insufficient vaccine coverage rates may lead to a rise in the ages of the cases, high vaccination coverage should be attained. With the advancement of transplant medicine, patients being treated with immunosuppressive agents have increased, and the number of patients receiving corticosteroids for renal or autoimmune diseases is not minimal. For those who are unable to receive vaccination due to their underlying disease, control and prevention of an epidemic itself is the only method of chickenpox prevention. Therefore, increasing vaccination coverage is desired.

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