国立感染症研究所

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The Topic of This Month Vol.34 No.10 (No.404)

Chickenpox/varicella zoster and vaccine in Japan

(IASR 34: 287-289, October 2013)

 

Chickenpox is caused by the primary infection of varicella-zoster virus (VZV).  It is category V infectious disease under the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (Infectious Diseases Control Law) (http://www.niid.go.jp/niid/images/iasr/34/404/de4041.pdf) and category II school infectious disease under the School Health and Safety Act.  VZV latently infects nerve ganglia, and is reactivated by immunosuppression causing herpes zoster.

Incidence of chickenpox:  Number of cases increases from winter to spring, and then gradually decreases towards the autumn.  Estimatedly about 1,000,000 chickenpox patients, mostly infants, occur every year, though the overall incidence is decreasing (though slightly) in the recent three years (Fig. 1).  While 80% of the patients used to be under 4 years of age, since 2010 the percentage of this age group has been decreasing possibly owing to the increased vaccination coverage of this age group (Fig. 2).  When chickenpox and rubella, both sentinel reportable infectious diseases, are compared, however, while rubella decreased dramatically after starting of rubella routine vaccination to infants of the both genders in 1995, the incidence of chickenpox, to which immunization has been conducted on voluntary basis, remained continuously high. 

Severe cases:  Transmissibility of VZV is strong.  It spreads by the air-borne infection, and subclinical infection is very rare.  On estimation, one in 400 natural chickenpox infections among unvaccinated children require hospitalization, and nearly 20 in 1,000,000 infections are fatal (Chickenpox fact sheet, National Institute of Infectious Diseases).  The incidence of deaths due to chickenpox is the highest among all the deaths caused by vaccine preventable diseases including measles, rubella, mumps and chickenpox that have been reported since 2004.

Hospital infection of chickenpox is a serious problem in pediatric hospitals in Japan.  It cannot be prevented even in hospitals using aggressive infection control, and it sometimes results in ward closure (http://www.theidaten.jp/journal_cont/20130328J-41-2.htm).

As chickenpox infection can be fatal to infants who are under immune-suppression, infection control including outpatient services should be further strengthened.  Currently, utility of post-operative varicella vaccination to infant organ recipients is under study (see p.289 of this issue). Very often, among immune-compromised individuals with leukemia and other malignancies, etc., the first sign of chickenpox infection is abdominal or back or low back pain in place of rash, and may follow poor clinical consequence like multiple organ failure, disseminated intravascular coagulation, etc.  (see p.290 of this issue).  Adults as well as infants at high risk tend to follow severe clinical course, such as, pneumonia (see pp. 292 & 293 of this issue).

If a mother is infected during the first 20 weeks of gestation, infection causes in 1-2% of the cases serious damages to the fetus, which is known as congenital varicella syndrome.  Stillbirth, though rare, may also occur (see p. 294 of this issue).  When a mother catches chickenpox within 5 days before or 2 days after delivery, trans-placental infection occurs and the infected newborn often follows a serious consequence due to the lack of maternal antibody.

Prevention and therapy:  Varicella vaccine is the best for prevention of chickenpox.  When a person without immunization or infection history is exposed to varicella, immediate vaccination within 3 days after exposure can prevent disease onset or aggravation of symptoms.  As a post-exposure treatment, anti-herpes drugs, such as, acyclovir (ACV) and valacyclovir (VCV), or anti-chickenpox/varicella zoster immunoglobulin (VZIG) is administered.  ACV and VCV are not covered by the health insurance in Japan, and VZIG is primarily used abroad.  As treatment of infants at high risk needs VZIG, clinicians request its approval and supply in Japan.

Varicella vaccine:  The Oka strain varicella live vaccine is recognized by WHO as the most desirable varicella vaccine.  In Japan, vaccination targets are people older than 12 months who have no history of chickenpox, people having risk of developing severe form of chickenpox, people having risk individuals in their family, or health care providers.  As the vaccination has been conducted on the voluntary basis, exact coverage rate is unknown; so far, coverage rate has been calculated on the basis of number of shipped lots and number of births, which was 30-40%.  From 2009 to 2012, the vaccine production doubled probably thanks to increased public recognition and local governments’ expanded subsidy to vaccination (Fig. 3).  The vaccination dose, which used to be one dose, is now becoming two doses under the influence of the world trend.  Therefore, the increased shipment can’t be translated directly into increased number of children receiving the vaccine.  A system of more precise estimation of vaccine coverage is needed.  The amount of the vaccine shipped dose 1-year-old children population is quite variable among prefectures in Japan (Fig. 4).

Safety and efficacy of vaccine:  No serious side effects have been observed among the healthy vaccinees since gelatin, an allergen, was removed from vaccine in 2000.  Secondary infection of vaccine strain is very rare; so far only 10 cases have been reported in the world.  Its efficacy is evidenced by the drastic decrease of patients, hospitalizations and deaths in the United States, which adopted routine immunization of chickenpox in 1995 (see p. 295 of this issue).  For those having received one dose, the probability of reinfection during an epidemic is 15-20%, and that of acquiring moderate to severe chickenpox is <5%.  As the reinfection can be prevented by two doses (see p. 296 of this issue), implementation of two vaccine doses is desirable from the public health viewpoint.  Comparison of costs of vaccination and patient care including burden on patient’s family has indicated the cost-effectiveness of routine varicella vaccination.  Currently, Vaccine Panel established by Health Science Council is working on incorporation of varicella vaccine into the routine immunization.

Varicella zoster (VZ):  According to a survey in Miyazaki prefecture (see p. 298 of this issue), one in three persons acquires VZ if they live for 80 years.  The risk of developing VZ can be assessed by an intradermal skin test (see p. 300 of this issue).  VZ reduces quality of life on account of the skin rash and prodromal pain as well as postherpetic neuralgia.  Ramsay Hunt syndrome occasionally observed is refractory to therapeutic intervention (see p.301 of this issue).  Though early clinical intervention can alleviate associated complications, varicella control by vaccine is of prime importance.

As VZ development and decreased host cellular immunity are closely correlated, the United States considered use of varicella vaccine for control of VZ reactivation by taking advantage of its capacity to augment cellular immunity, and the FDA approved an Oka strain based VZ vaccine in 2006.  Clinical trials in the United States revealed that incidence of VZ, postherpetic neuralgia and severe cases were decreased by more than 50% each. 

As Japan’s VZV vaccine for routine immunization has titer comparable to that of the United States’ VZ vaccine, since 2004 the VZV vaccines sold in Japan have been attached with a package insert informing that, under “pharmacology”, the vaccine can enhance cellular immunity to VZ when applied to persons with decreased immunity due to aging and other reasons.

Diagnosis:  Clinical diagnosis of chickenpox and VZ is easy.  Laboratory diagnosis using antibody test is available in the commercial laboratories, and is used as a confirmatory test.  Virus genome can be detected from vesicles as they contain large amount of virus particles, but the test is not covered by the health insurance.  Pathological characteristics of severe VZV infection cases are detailed in p. 302 of this issue. 

For monitoring of efficacy and safety of varicella vaccine, a VZV pathogen surveillance system should be established. Differential diagnosis of wild type VZV and vaccine type VZV that is required for the surveillance is described in the “Pathogen Detection Manual: National Institute of Infectious Diseases”.

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The Topic of This Month Vol.37 No.4(No.434)

Measles and Rubella/Congenital Rubella Syndrome in Japan, as of March 2016

(IASR 37: 59-61, April 2016)

The World Health Organization (WHO) proposed to achieve regional measles and rubella/congenital rubella syndrome (CRS) elimination goals by the end of 2015, and achieve measles and rubella elimination in at least five of the six WHO regions by 2020 (Global Measles and Rubella Strategic Plan, WHO, 2012).  These measles and rubella elimination goals were included in the global vaccine action plan (GVAP) endorsed at the 65th World Health Assembly in 2012.  Here, “elimination” is defined as the absence of endemic transmission of measles or that of rubella/CRS in a defined geographical area (e.g. region or country) for ≥12 months in the presence of a well performing surveillance system.  WHO’s Western Pacific Regional Office started the measles elimination program in 2003, and verified the elimination status of Australia, Macao SAR (China), Mongolia and the Republic of Korea in 2014, and that of Brunei Darussalam, Cambodia and Japan in 2015 (see p. 62 of this issue).  Japan, while maintaining measles elimination status under the “Guidelines for the Prevention of Specific Infectious diseases: Measles (Ministry of Health, Labour and Welfare notice No. 442, December 28, 2007; http://www.mhlw.go.jp/bunya/kenkou/kekkaku-kansenshou21/dl/241214a.pdf)”, now targets attaining rubella elimination status by FY2020 under the “Guidelines for the Prevention of Specific Infectious diseases: Rubella (Ministry of Health, Labour and Welfare notice No. 122, March 28, 2014; http://www.mhlw.go.jp/file/06-Seisakujouhou-10900000-Kenkoukyoku/0000041928.pdf.pdf)”(see p. 81 of this issue).

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The topic of This Month Vol.37 No.5(No.435)

Enterohemorrhagic Escherichia coli infection, as of April 2016, Japan

(IASR 37: 85-86, May 2016)

Enterohemorrhagic Escherichia coli (EHEC) infection is a systemic infection of pathogenic E. coli that produces Verotoxin/Shiga toxin (VT/Stx) or possesses the VT encoding genes.  Main signs and symptoms consist of abdominal pain, watery diarrhea, and bloody diarrhea. High fever (38°C) and/or vomiting are occasionally observed.  Hemolytic uremic syndrome (HUS), which can be fatal for the young and the elderly, can be caused by VT that causes thrombocytopenia, hemolytic anemia and/or acute renal failure.

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The topic of This Month Vol.37 No.6(No.436)

Leptospirosis in Japan, January 2007-April 2016

(IASR 37: 103-104, June 2016)

Leptospirosis is a zoonotic infectious disease caused by Leptospira spp. (IASR 29: 5-7, 2008).  The bacteria colonize the renal tubules of rodents and other mammals and are excreted in urine.  Humans are infected by the bacteria through direct contact with the urine of the carrier animal or indirectly through contact with contaminated water and/or soil; occasionally, infection may occur through ingestion of contaminated food and/or water.

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The topic of This Month Vol.37 No.7(No.437)

Mosquito-borne viral infections: Zika virus infection, Chikungunya fever and Dengue fever, 2011 to June 2016, Japan

(IASR 37: 119-120, July 2016)

All mosquito-borne infectious diseases are classified as category IV infectious diseases under the Infectious Diseases Control Law (Table 1).  This article focuses on Zika virus infection, Chikungunya fever and Dengue fever.  As these are associated with acute febrile illness and clinically similar in manifesting syndromes such as fever, rash, and arthralgia, and as there are many asymptomatic cases, differential diagnosis solely based on clinical information is difficult (see notification criteria for each disease described below).  In Japan, majority of the reported cases for these three diseases have been acquired abroad (i.e. imported cases), but an autochthonous dengue fever outbreak was confirmed in Japan in 2014 for the first time in nearly 70 years (IASR 36: 33-35, 2015).

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The topic of This Month Vol.37 No.8(No.438)

Acute hepatitis B, April 2006-December 2015

(IASR 37: 147-148, August 2016)

Acute hepatitis B is caused by infection with hepatitis B virus (HBV) of Hepadnaviridae.  After an incubation period of approximately 3 months, the disease starts with general malaise, flu-like symptoms, anorexia, chills, and vomiting, often followed by brown urine or jaundice.  Infection among infants is usually symptomless but often lapses into a carrier state.  Infection among adults generally resolves within 1-2 months.  However, fulminant hepatitis occurs in 1% of adult cases and approximately 60-70% among them are fatal.  A proportion of infants and adult cases who are carriers can develop chronic hepatitis; adults with competent immunity rarely become carriers (see p. 157 of this issue).

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The topic of This Month Vol.37 No.9(No.439)

HIV/AIDS in Japan, 2015

(IASR 37: 167-168, September, 2016)

HIV/AIDS surveillance in Japan started in 1984.  It was conducted under the AIDS Prevention Law from 1989 to March 1999 and since April 1999, has been operating under the Infectious Diseases Control Law. Physicians who have made a diagnosis of HIV/AIDS are required to notify all such cases (see http://www.niid.go.jp/niid/images/iasr/34/403/de4031.pdf for the reporting criteria).  The data used in this article were derived from the annual report of the National AIDS Surveillance Committee for the year 2015 (released by the Tuberculosis and Infectious Diseases Control Division, the Ministry of Health, Labour and Welfare (MHLW), http://api-net.jfap.or.jp/status/2015/15nenpo/15nenpo_menu.html).  HIV/AIDS cases are classified into two categories: as an “HIV case” if HIV infection was detected before clinical manifestation of AIDS, and as an “AIDS case” if the infection was detected after manifes-tation of AIDS symptoms*.

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The topic of This Month Vol.37 No.10(No.440)

Mumps (infectious parotitis) in Japan, as of September 2016

(IASR 37: 185-186, October, 2016)

Mumps is a common viral infection frequent among children.  The causative agent is mumps virus (MuV) belonging to the family Paramyxoviridae, genus Rubulavirus.  While there is only one serotype, there are 12 genotypes from A to N (E and M are lacking) based on the variation of the SH gene (IASR 34: 224-225, 2013).

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The topic of This Month Vol.37 No.11(No.441)

Influenza  2015/16 season, Japan

(IASR 37: 211-212, November, 2016)

The 2015/16 influenza season (from week 36 in September 2015 to week 35 in August 2016) was characterized by the return of A/H1pdm09 as the predominant strain after being relatively absent in the previous season.  Influenza virus B, consisting of both Yamagata and Victoria lineages, started increasing from week 2 of 2016.

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The topic of This Month Vol.37 No.12(No.442)

Amebiasis in Japan, week 1 of 2007-week 43 of 2016

(IASR 37: 239-240, December, 2016)

Amebiasis is caused by the protozoan parasite Entamoeba histolytica, transmitted through the fecal-oral route.  The parasite is released in the feces as cysts, which may contaminate drinking water or foods.  Once the cysts are ingested and reach the small intestine, they undergo excystation and become trophozoites.  Trophozoites migrate to the colon and cause mucosal ulcers in 5-10% of infected persons, resulting in “intestinal amebiasis”.  This condition is associated with dysenteric signs or symptoms, such as mucous and bloody stool, diarrhea, tenesmus (feeling of incomplete defecation) and abdominal pain.  Occasionally, the trophozoites migrate hematogenously further to the liver, lung, brain or skin and produce local abscesses resulting in “extraintestinal amebiasis”, which is clinically more serious.  The World Health Organization estimates that globally several tens of thousands of people die of amebiasis annually.

Copyright 1998 National Institute of Infectious Diseases, Japan

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