国立感染症研究所

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The topic of This Month Vol.38 No.9(No.451)

HIV/AIDS in Japan, 2016

(IASR Vol. 38 p177-178: September, 2017)

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 are required to notify all the diagnosed cases (see http://www.niid.go.jp/niid/images/iasr/34/403/de4031.pdf for the reporting criteria).  The data in this article were derived from the annual report of the National AIDS Surveillance Committee for the year 2016 (reported by the Tuberculosis and Infectious Diseases Control Division, the Ministry of Health, Labour and Welfare (MHLW), http://api-net.jfap.or.jp/status/2016/16nenpo/16nenpo_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 manifestation of AIDS symptoms*.

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The topic of This Month Vol.38 No.8(No.450)

Japanese encephalitis, Japan, 2007-2016

(IASR Vol. 38 p151-152: August, 2017)

Japanese encephalitis (JE) is caused by JE virus (JEV) transmitted by Culex tritaeniorhynchus.  Most infections are asymptomatic, but when symptomatic, after 1-2 weeks of incubation, case fatality can be 20-40% and half of the survivors will have sequelae.  JE is a category IV notifiable infectious disease under the Infectious Diseases Control Law and all diagnosed cases shall be notified immediately (see http://www.nih.go.jp/niid/images/iasr/38/450/de4501.pdf for notification criteria).  Prefectural public health institutes (PHIs) measure JEV antibody levels among humans and JEV infection levels among farmed pigs on a periodic basis, annually or once every few years, under the National Epidemiological Surveillance of Vaccine-Preventable Diseases (NESVPD) system.  The collected data are collated and summarized at the National Institute of Infectious Diseases.  This article describes the trends in JE from 2007-2016 (see IASR 30: 147-148, 2009 for data prior to 2008).

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The topic of This Month Vol.38 No.7(No.449)

Adenovirus infections, 2008 to June 2017, Japan

(IASR Vol. 38 p133-135: July, 2017)

Adenovirus (human mastadenovirus: Ad), is a physicochemically stable non-enveloped double-stranded DNA virus.  Over 80 types have been described, and are currently grouped into 7 species from A to G.  Ads have been reported as serotypes up to Ad51 (denoted as, for example, Ad1), but Ads discovered later (i.e. Ad52 or greater) have been reported based on the whole genome sequencing (see p. 136 of this issue).

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The topic of This Month Vol.38 No.2(No.444)

Pertussis in Japan, as of January 2017

(IASR Vol. 38 p23.-24: February, 2017)

Pertussis is defined as “acute respiratory tract infection caused by Bordetella pertussis” in the Infectious Diseases Control Law (see http://www.niid.go.jp/niid/images/iasr/38/444/de4441.pdf for the notification criteria).  The main symptom is a prolonged cough.  As severity may be greater among neonates and infants, vaccination is important.

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The topic of This Month Vol.38 No.1(No.443)

Norovirus trends in Japan, 2015/16 season

(IASR Vol.38: 1-3, January, 2017)

Norovirus (NoV) is a single stranded RNA virus.  It is classified into genogroups GI-GVII, and human infection is primarily associated with GI and GII.  Since the 2015/16 season, a new coding system based on the nucleotide sequence of the VP1 region has been used replacing the previous one, which was based on the nucleotide sequence of the capsid N/S region (see the comparison table; http://www.niid.go.jp/niid/images/iasr/rapid/graph/Vol.36/graph/pt4274a.gif).

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The Topic of This Month Vol.37 No.3(No.433)

Severe fever with thrombocytopenia syndrome (SFTS) in Japan, as of February 2016

(IASR 37: 39-40, March 2016)

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne systemic infection caused by SFTS virus (SFTSV), which belongs to Genus Phlebovirus, Family Bunyaviridae.  SFTS was first reported from China in 2011 as a novel bunyavirus infection. Since then, SFTS has also been reported from Japan and South Korea.  Incubation period is 5-14 days.  The signs/symptoms in the early phase of the disease are fever, gastrointestinal symptoms (anorexia, nausea, vomiting, etc.), headache and myalgia, followed by neurological symptoms (impaired consciousness) and bleeding (gingival oozing, bloody diarrhea, hematuria) in the later phase of the disease.  Other somatic signs such as lymph nodes enlargement and epigastric tenderness are commonly observed.  Laboratory findings include lymphopenia and thrombocytopenia in total blood cell counts (TBC), and increased level of AST, ALT and LDH in the serum chemistry.  Among survivors, TBC begins to improve 1 week after onset, and becomes normal within approximately 2 weeks after onset.  In severe cases, however, no recovery signs are observed in the later stage of the disease and signs/symptoms such as impaired consciousness and bleeding tendency appear.  The pathophysiology of fatal SFTS patients are a combination of the disseminated intravascular coagulation and multiple organ failure.  So far, the case fatality rate of notified SFTS patients in Japan has been approximately 30% at the time of notification.

Life cycle in nature and transmission route of SFTSV to humans:  In nature, SFTSV is maintained in ticks and mammals through the tick-tick cycle (vertical transmission from adult ticks to their offspring through transovarial transmission) and tick-mammal cycle (transmission from infected ticks to mammals and then from mammals to ticks).  SFTSV genome has been detected in several tick species in Japan, i.e., Takasago testudinarium (Amblyomma testudinarium), Haemaphysalis longicornis, Haemaphysalis flava, Haemaphysalis megaspinosa, and Haemaphysalis kitaokai.  High prevalence of SFTSV seropositivity has also been demon-strated among deer, wild boars, dogs, and raccoon dogs (see pp. 50 & 51 of this issue), and indicates that the tick-mammal infection cycle is already established in Japan.  While the main infection route of SFTSV to humans is via SFTSV-carrying tick-bite, transmission through direct contact with blood and/or body fluid of the SFTS patient to the patient’s family members or medical providers has been reported in China and South Korea (see p. 48 of this issue).

Molecular epidemiology: SFTSV isolates in Japan, China, and South Korea are classified into two major clades, i.e., a Chinese clade consisting of 5 genotypes, C1 to C5, and a Japanese clade consisting of 3 genotypes, J1 to J3. In Japan, majority of the Japanese SFTSV isolates detected belonged to genotype J1.  However, genotypes C3 to C5 have been detected from some Japanese SFTSV isolates on rare occasions, and conversely, genotype J3 has been detected from some Chinese and South Korean SFTSV isolates (see p. 44 of this issue).

SFTS patients in Japan: Since March 4, 2013, SFTS has been designated as a category IV infectious disease under the Infectious Diseases Control Law in Japan (see http://www.niid.go.jp/niid/images/iasr/35/408/de4081.pdf for notification criteria). Therefore, a physician, who diagnoses a patient as having SFTS, must notify the case within 24 hours to a local health center. SFTSV must be handled as a class III pathogen under the Infectious Diseases Control Law.

A total of 170 SFTS patients have been notified in Japan as of February 24, 2016 (Table).  Among them, 162 had onset in 2013 or afterwards (Fig. 1), while 8 had onset before 2013 (2, 1, and 5 cases in 2005, 2010, and 2012, respectively).  Majority of patients were reported during May to August (Fig. 1) and were from 20 prefectures located mostly in western Japan (Fig. 2).  Among 162 patients reported since 2013, 77 (45%) were male and 93 (55%) were female.  The majority were older than 60 years of age (range 5-95 years; median 74 years) (Fig. 3).  A pediatric case was reported in 2015 for the first time in Japan (see p. 42 of this issue).  Forty-six patients (27%) were fatal at the time of notification (Fig. 3).  Majority of patients had fever (168 cases, 99%) and gastrointestinal symptoms including abdominal pain, diarrhea, vomiting, and anorexia (150 cases, 88%). Thrombocytopenia and leukopenia were found in 162 (95%) and 150 (88%) patients, respectively (see p. 41 of this issue).

SFTS in other countries (China and South Korea) (see p. 47 of this issue): In China, approximately 3,500 SFTS patients have been reported through 2014, with the case fatality rate ranging from 7.8-12.2%.  In South Korea, since a fatal SFTS patient was confirmed in August 2012, 36 cases (17 fatal) and 55 cases (15 fatal) have been reported in 2013 and 2014, respectively.  The estimated case fatality rate in South Korea ranged from 27-47%.

Laboratory diagnosis in Japan: Virological tests for SFTS include detection/isolation of SFTSV from patients’ blood or other body fluids (throat swab, urine, etc.), and/or demonstration of a significant rise in IgG antibody titer against SFTSV in paired sera.  Prefectural and municipal public health institutes (PHIs) conduct the conventional one-step RT-PCR (see p. 43 of this issue), while the National Institute of Infectious Diseases (NIID) conducts the quantitative one-step RT-PCR upon request (see p. 45 of this issue).  Physicians who are concerned regarding laboratory tests should consult their local health center.

Challenges for the future: The first SFTS patient in Japan was reported in January 2013, and SFTS infections are expected to continue to occur.  Studies such as those conducted by NIID and PHIs and the Ministry of Health, Labour and Welfare-funded program, “Comprehensive studies for the control of SFTS”, have increased our knowledge and understanding of the SFTS patients’ geographical distribution, clinical picture, and pathology, and also regarding the lifecycle of SFTSV in nature, transmission route(s), and risk factors of SFTSV infection.

The most important preventive measure against SFTS is avoidance of tick-bite.  During spring to autumn when ticks are most active, exposed areas of the skin should be minimized when entering areas inhabited by ticks.  Repellents containing DEET are effective to some extent.  Other information regarding tick-bite prevention is available at http://www.niid.go.jp/niid/ja/sfts/2287-ent/3964-madanitaisaku.html

No vaccines or specific therapeutics against SFTS are currently available.  While there has been progress in developing therapeutics against SFTSV (see p. 49 of this issue), as the prognosis of SFTSV infection is quite poor, further research is imperative.

 

 

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The Topic of This Month Vol.37 No.2(No.432)

Poliomyelitis as of 2016

(IASR 37: 17-18, February 2016)

Poliomyelitis, also known as infantile paralysis, is caused by poliovirus that infects the central nervous system. Typically, the infection irreversibly damages motor neurons causing acute flaccid paralysis (AFP).  As no specific therapeutic is available, vaccination is the basic strategy for preventing polio disease occurrence and epidemic.  Acute poliomyelitis is a notifiable Category II infectious disease under the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (the Infectious Diseases Control Law); physicians who have diagnosed symptomatic or asymptomatic cases (excluding vaccine strain carriers) must notify the case immediately (see http://www.niid.go.jp/niid/images/iasr/37/432/de4321.pdf for clinical characteristics and notification criteria).  Vaccine-associated paralytic polio (VAPP) and those caused by secondary transmission of vaccine strain(s) derived from vaccinees are also notifiable.  As AFP can be caused by causes other than polio, confirmation of poliovirus by isolation from stool specimens, identification and genetic analysis of the isolates are indispensable for polio surveillance.

Current situation of the global polio eradication program
Since WHO launched the global polio eradication initiative in 1988, the total number of reported polio cases and areas considered endemic steadily decreased.  Globally, wild poliovirus (WPV) type 2 has not been isolated since the last detection in India in 1999 and the Global Commission for the Certification of the Eradication of Poliomyelitis declared eradication of WPV type 2 in September 2015.  WPV type 3 has not been reported for ≥3 years since the last detection in Nigeria in 2012.  The remaining WPV circulating in the world is poliovirus type 1; while still circulating in Pakistan and Afghanistan (Figure, see p. 19 of this issue), it is likely no longer circulating in the African continent after the last detection in Nigeria in July 2014, a country where polio had been endemic for a long time (see p. 29 of this issue).  In 2015, 72 wild polio cases were reported globally, a considerable decline from 359 cases in 2014 (Table).  As the remaining polio-endemic countries are afflicted by numerous social problems, however, polio eradication in the near future will not be easy.

The Western Pacific Region (WPR) of WHO declared eradication of indigenous WPV in 2000.  Since then, it has not experienced an epidemic of WPV except the WPV type 1 epidemic in Xinjiang province in China, which was imported from Pakistan.  More recently, however, vaccine-derived poliovirus (VDPV) epidemics have been reported from various parts of the world, and in the WPR, a type 1 VDPV epidemic was reported from Laos in 2015 (see pp. 20 & 24 of this issue).

VDPV has thus become an impediment to the completion of global polio eradication (see p. 24 of this issue). In addition to VDPV, VAPP has also been a public health concern; approximately 40% of the 250-500 VAPP cases reported annually from countries that use oral polio vaccine (OPV) have been caused by type 2 OPV (http://www.who.int/immunization/diseases/poliomyelitis/inactivated_polio_vaccine/learn/en/index2.html).  Accordingly, WHO requested all countries to stop using trivalent OPV (tOPV) within the period of 17 April - 1 May of 2016, and it further requested for countries that will continue to use OPV that they should be prepared to replace tOPV with type 1 and type 3 bivalent OPV (bOPV).  After replacement of tOPV with bOPV, however, risk of poliomyelitis due to type 2 VDPV may increase.  In order to minimize such a consequence, at least one dose of the trivalent inactivated polio vaccine (IPV) should be incorporated into routine vaccination, which necessitates manufacturing a larger supply of IPV (see pp. 19, 20 & 30 of this issue). 

Introduction of IPV and polio surveillance in Japan
In September 2012, Japan replaced tOPV with tIPV for routine immunization, and two months later, ahead of other countries, it introduced DPT-IPV into routine immunization, which included Sabin-derived tIPV and diphtheria-pertussis-tetanus antigens.  Though vaccine coverage and seropositivity were low in 2011-2012 when OPV was still used (for infants 1 year old and younger, vaccine coverage was 76%, and seropositivity for type 1, type 2, and type 3 were 80%, 78% and 48%, respectively), high levels of vaccine coverage (≥95% among children under 5 years of age) and high seropositivity (≥95% among children under 5 years of age for both type 1 and type 2 antigens) were obtained after switching to IPV-DPT, which has been maintained since then (see p. 26 of this issue).

Reporting under the Infectious Disease Control Law and surveillance activities under the National Epidemiological Surveillance of Vaccine-Preventable Diseases (NESVPD) ensured absence of importation and/or circulation of WPV and VDPV.  To complement disease surveillance, infectious agent surveillance under the NESVPD has been examining stool specimens from healthy children for the presence of poliovirus.  This system was replaced by the more sensitive environmental surveillance system in 2014, and in October 2014, Sabin type 3 poliovirus strain was isolated from concentrated sewage water (see p. 27 of this issue).

Laboratory diagnosis of poliovirus
Laboratory diagnosis consists of isolation of poliovirus in cultured cells.  According to WHO’s standard recommendations, intratypic differentiation should be conducted by real time RT-PCR.  All isolates identified as non-Sabin-like by intratypic differentia-tion should be sequenced for the whole VP1 region to differentiate between WPV, VDPV and vaccine types.  Isolates with nucleotide substitutions in ≥1% of the VP1 gene for types 1 and 3 and ≥0.6% of the VP1 gene for type 2 are classified as VDPV, which should be reported immediately to WHO (see p. 24 of this issue).

Biorisk management of poliovirus
WHO, in its Global Action Plan, 3rd edition (GAPIII), requests Member States to limit the use of poliovirus to the diagnosis, research and vaccine production conducted in certified facilities, where poliovirus is handled according to the Biorisk Management Standards delineated in GAPIII.  In addition, GAPIII requests that the Sabin type 2 OPV strains be destroyed or handled under biosafety conditions designated for wild type poliovirus within three months after the global introduction of bOPV (see p. 22 of this issue).

Accordingly, the Ministry of Health, Labour and Welfare (MHLW) issued a national announcement requesting the destruction of unnecessary poliovirus and requested institutions that will continuously retain poliovirus materials to notify the Tuberculosis and Infectious Diseases Control Division of MHLW (Ken-kan-hatsu 1211 No.1) (see p. 22 of this issue).

Issues to be considered
WHO deems the global polio eradication program as the number one priority among public health programs, and is striving to interrupt the spread of WPV type 1 in endemic countries.  As an endgame strategy, WHO is planning to replace tOPV with bOPV globally within the first half of year 2016.

As high vaccine coverage has been maintained after introduction of IPV, the occurrence of polio and the risk of transmission is believed be low in Japan.  However, as IPV does not confer mucosal immunity sufficient enough for preventing the intestinal replica-tion of the virus, importation of WPV or VDPV should be vigilantly monitored.  As the Sabin type 2 strain will be controlled from the second half of 2016, MHLW is taking the necessary measures regarding further use or destruction of the poliovirus specimens in biomedical research facilities and other institutions.

 

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The Topic of This Month Vol.37 No.1(No.431)

Erythema infectiosum (Human parvovirus B19 infection)

(IASR 37: 1-3, January 2016)

Erythema infectiosum is a contagious exanthematous disease affecting mainly infants and young children.  The causative agent is human parvovirus B19 (PVB19), a single-stranded DNA virus, which belongs to the genus Erythrovirus, the subfamily Parvovirinae, the family Parvoviridae.  It is known to infect only humans.  It infects the erythroid precursor cells through specific binding to the P antigen present on these cells and destroys the cells through apoptosis.  The typical manifestation is butterfly-shaped erythema on the cheeks, and is thus called “apple disease” in Japan.  However, the erythema, often taking lacy, mesh-like form, may extend to the extremities and the trunk (see p. 3 of this issue). 

National Epidemiological Surveillance of Infectious Diseases (NESID)
Erythema infectiosum is a category V infectious disease (notification criteria are found in http://www.niid.go.jp/niid/images/iasr/37/431/de4311.pdf), and approximately 3,000 pediatric sentinel sites report patients diagnosed as erythema infectiosum on a weekly basis.  The reported number of erythema infectiosum cases shows a seasonal trend in epidemic years, with a peak in June-July (Fig. 1).  The annual number of patients reported from 2010 to 2014 was 50,061, 87,010, 20,966, 10,118 and 32,352, respectively. In the 2015 season, a total of 92,625 patients were reported as of week 50 (Table 1), the highest in the last ten years.  Since the current national surveillance system was established, epidemic years (years where the peak in the weekly number of reported cases per sentinel site exceeded one) occurred in 2001, 2007, 2011, and 2015; epidemic years occurred every 4 to 6 years (Fig. 2, IASR 19: 50-51, 1998; https://idsc.niid.go.jp/iasr/19/217/tpc217.html).  In the 2015 season, the epidemic that started in the Kanto region spread nationwide and peaked in week 28 (Fig. 3).  It then subsided but the patient number has again been increasing since autumn (Fig. 1). 

Among reported cases through week 50 of 2015, those 9 years of age or under occupied 93%, and those aged 5 years made up the highest proportion (17% of total cases) (Fig. 4).  Though the epidemiology of erythema infectiosum among adults is unclear as surveillance is based on the pediatric sentinel notifications, local epidemics among adults have been reported (see p. 5 of this issue).  Information on the epidemiological situation abroad is limited, but outbreaks and fatal fetal cases have been reported (see p. 11 of this issue).

Transmission route and clinical picture
The incubation period of PVB19 is 4-15 days. It is transmitted through droplet or contact infection and is transmissible before clinical onset, but generally noninfectious post onset of the typical erythema (see p. 3 of this issue).  As the blood derived from PVB19-infected patients pre-onset poses a risk for infection, raw plasma materials have been all screened for PVB19 by the agglutination method (receptor-mediated hemagglutination assay) since 1997 (IASR 19: 52, 1998).  During the 11 year period till 2007, 9 infections due to transfusion blood-derived prod-ucts were reported.  In 2008, the CLEIA method (chemiluminescent enzyme immunoassay), whose sensitivity was as high as 106 copies/ml, was introduced, and since 2008 to 2015, only one blood product-derived infection was reported (see p. 9 of this issue).

One in four PVB19 infection cases is asymptomatic.  While PVB19 infection confers lifelong immunity, the virus may cause persistent infection among immunocompromised persons.

Among adults, differential diagnosis is difficult due to variety of manifestations.  In one study, about 30% of measles-suspected cases older than 20 years of age were found positive for the PVB19 genome (see p. 4 of this issue).  Among adults (particularly women), PVB19 infection frequently manifests as arthritis.  Other complications include transient aplastic crisis among hemolytic anemia patients and chronic anemia among immunocompromised persons.

When pregnant women are infected with PVB19, transplacental infection occurs in about 20% of the cases (see p. 7 of this issue), and about 10% of them experience miscarriage or stillbirth.  Fetal hydrops is a frequent complication when mothers are infected before 20 weeks of gestation (particularly 9 to 16 weeks), but the risk decreases after 28 weeks of gestation.  As transplacental infection can occur from asymptomatic cases, pregnant women who have frequent contact with children (such as those with young children or in occupational settings that involve children) should take particular care to reduce the chance of infection.

Laboratory diagnosis of PVB19
Routine laboratory diagnosis includes the titration of IgM and IgG antibodies using enzyme immunoassay and the detection of PVB19 DNA by PCR test.  In case of primary infection, IgM antibody can be detected about 2 weeks post infection, when the erythema appears.  IgM remains positive for about 3 months.  IgG antibody is detectable a few days after the appearance of the IgM antibody, and is maintained lifelong.  To determine whether an infection is primary or not, one needs to take into account the clinical picture, the PVB19 IgM antibody data and PVB19 DNA data (see p. 9 of this issue).  

The real-time PCR test can be used for estimating the clinical stage or the time course of infection.  Utilization of a laboratory test for a “pregnant woman with erythema, who is strongly suspected of PVB19 infection” is covered by the national health insurance. 

Measures to be taken against erythema infectiosum
Erythema infectiosum is generally a pediatric disease with good prognosis.  However, PVB19 infection may become serious among immunocompromised persons and may cause fetal infection with serious outcome.  It is important to note that preventing disease spread is challenging due to several reasons, e.g. differential diagnosis is difficult due to diverse manifestations, asymptomatic cases are infectious, and the virus is shed 1 week before the appearance of symptoms.  In epidemic seasons and epidemic areas, special measures, such as intensified hospital infection control and hygienic practices in the family setting, should be implemented so as to protect persons at risk.

 
 
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The topic of This Month Vol.36 No.12(No.430)

Middle East Respiratory Syndrome (MERS), as of November 2015

(IASR 36: 231-232, December 2015)

Middle East Respiratory Syndrome (MERS) is an acute respiratory infectious disease caused by MERS coronavirus (MERS-CoV) that was first detected in Saudi Arabia in 2012.  MERS-CoV is classified in the family Coronaviridae, genus β-coronavirus, which includes Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) that appeared in China in 2003 (see p. 236 of this issue). 

MERS-CoV is transmitted principally via droplet or contact.  The incubation period is 2-14 days (median 5 days).  Clinical manifestation is variable, ranging from mild upper respiratory infection to severe lower respiratory infection such as pneumonia, gastrointestinal syndromes such as diarrhea, to multiple organ failure.  Asymptomatic infection is known.  In severe cases, pneumonia exacerbates about 1 week after disease onset, which is accompanied by acute respiratory distress syndrome.  The exacerbation may be followed by acute respiratory and/or multiple organ failure.  The case fatality ratio among reported cases has been 20-40%.  There are no specific therapeutics or vaccines, although they are currently under development.

Since September 2012, Ministry of Health, Labour and Welfare (MHLW) has been requesting the bureau of hygiene of prefectural governments to provide information on patients suspected of the new coronavirus infection.  In July 2014, concerned by the increasing number of MERS-CoV patients in the Middle East and importations of MERS-CoV in various countries after April 2014, MHLW designated MERS as a “designated infectious disease” under the Infectious Diseases Control Law and a quarantinable infectious disease under the Quarantine Act.  Accordingly, MHLW developed a legal framework for the quarantine and treatment of MERS patients.  With further amendments to the Infectious Diseases Control Law in November 2014, MERS-CoV was classified as a Category II infectious disease (21 January 2015) (see p. 242 of this issue).  Notification criteria are found in http://www.niid.go.jp/niid/images/iasr/36/430/de4301.pdf.

Reservoir of MERS-CoV
Dromedary camels are considered as the most likely reservoir of MERS-CoV, mainly because (i) a fatal case reported from Saudi Arabia in November 2013 had close contact with a MERS-CoV-infected camel, and (ii) a sero-prevalence study conducted in Saudi Arabia indicated that people who had contact with camels had higher anti-MERS-CoV antibody levels.  In Middle East, dromedary camels are closely related to the daily life of the local population and are important not only as a source of meat but also for tourism and amusement (see p. 234 of this issue).

A survey of camels living in Japan indicated that none of the examined camels had MERS-CoV antibody or genetic material detected (see p. 238 of this issue).

Epidemiological situation of MERS
There were 1,618 laboratory-confirmed MERS-CoV cases reported from 26 countries to the World Health Organization (WHO) from 2012 to 13 November 2015, among whom 579 were fatal (case fatality ratio 36%) (Figure). More than 70% of the reported cases were from Saudi Arabia (Table).  History of contact with camels was unknown for most of the cases.  Person-to-person transmission was observed in several nosocomial outbreaks (see p. 233 of this issue). 

Outside of Saudi Arabia, Republic of Korea (ROK) reported the largest number of MERS-CoV cases.  In the ROK, majority of the transmissions was nosocomial, following a male index case who returned from the Middle East.  Between May and July 2015, 186 cases were reported from 16 hospitals.  The age of patients ranged from 16 to 87 years (median 55 years).   Thirty-seven patients died (case fatality proportion 20%), among whom 33 (89%) were either elderly or had underlying disease, such as malignancy, heart disease, respiratory disease, renal disease, diabetes, or immunodeficiency.  A total 39 cases (21% of the total patients) were medical workers but none of them developed fatal outcomes (see p. 235 of this issue).

Person-to-person transmission
Risk of person-to-person transmission of MERS-CoV in case of an importation to a non-endemic country was assessed by a mathematical model using the data of 36 events reported to WHO.  The assessment suggested that secondary transmission was absent in most of the importation events, and the spreading potential of MERS-CoV was found to be modest, although the risk of an event with multiple generations as seen in ROK should be kept always in mind (see p. 244 of this issue).

Laboratory diagnosis of MERS-CoV (see p. 239 of this issue)
For laboratory diagnosis, detection of the viral genome(s) by real-time RT-PCR is used.  On account of less virus materials in the upper respiratory tract, the lower respiratory tract specimens, such as sputa, tracheal aspirate, or bronchoalveolar lavage fluid, should be used.  According to the WHO’s criteria, detection of at least 2 different viral genomic regions is required for confirmatory diagnosis. 

In Japan, prefectural and municipal public health institutes (PHIs), quarantine stations and the National Institute of Infectious Diseases (NIID) are prepared to conduct laboratory diagnosis.  NIID has distributed the necessary diagnostic materials (e.g. upE primers, probes, positive control specimens) to PHIs and quarantine stations, and has also recently developed an RT-LAMP method that detects nucleocapsid protein region of MERS-CoV within 30 minutes.

Prevention and treatment
Contact with dromedary camels in MERS-CoV endemic countries should be avoided.  Information on MERS-CoV, such as endemic countries and regions, notification criteria, response measures in case of MERS-CoV importation, is available on the MHLW home page [http://www.mhlw.go.jp/stf/seisakunitsuite/bunya/kenkou/kekkaku-kansenshou19/mers.html (in Japanese)].  NIID continuously assesses MERS risk in Japan using the best available epidemiological and virological information.  The assessment is updated in a timely manner, according to the epidemiological situation abroad [http://www.niid.go.jp/niid/ja/diseases/alphabet/mers.html (in Japanese)].

For aspects regarding MERS treatment, a study group, “Investigation on clinical intervention of MERS and other emerging and re-emerging infections”, was established in 2015 so as to collect information useful for treating MERS and to share the obtained information widely in Japan (see p. 241 of this issue).

The MERS outbreak in ROK reminded us of the importance of preparedness for infectious disease outbreaks, careful information collection of travel history of febrile patients, rapid contact investigation of suspected cases, and risk communication.  It is important to ensure that these measures are well implemented in Japan.

 

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The topic of This Month Vol.36 No.11(No.429)

Influenza 2014/15 season, Japan

(IASR 36: 199-201, November 2015)

The 2014/15 influenza season (week 36 in September 2014 to week 35 in August 2015), which peaked in January 2015, was characterized by the predominance of AH3, after observing relatively low AH3 activity during the previous season.  From week 12 of 2015, influenza virus B was the dominant type for the remainder of the season. 

Epidemiology of the 2014/15 Influenza season:  Under the National Epidemiological Surveillance of Infectious Diseases (NESID), approximately 5,000 influenza sentinel sites (approximately 3,000 paediatric and 2,000 internal medicine healthcare facility sites) report patients diagnosed as influenza on a weekly basis (http://www.niid.go.jp/niid/images/iasr/34/405/de4051.pdf).  In the 2014/15 season, the number of reported patients per sentinel in Japan exceeded 1.0 (indicator of the nationwide start of influenza season) in week 48 of 2014 and weekly influenza activity remained at or above this level until week 18 of 2015; the peak was the week 4 of 2015 (39.4 patients/sentinel) (Fig. 1) (http://www.niid.go.jp/niid/en/10/2096-weeklygraph/2572-trend-week-e.html). Iwate prefecture was the first prefecture to attain the alert level of 10.0 patients/sentinel/week in week 48 of 2014. In week 2 of 2015, all 47 prefectures exceeded the alert level.  For the 2014/15 season, cumulatively there was a total of 289.8 patients/sentinel (301.0 patients/sentinel in the 2013/14 season).

Soon after the start of the 2014/15 season, outbreaks in healthcare facilities were reported from several prefectures, such as Hiroshima prefecture (see p. 207 of this issue).  Okinawa prefecture had reported influenza activity during the summer months every year since 2005; however, during the 2012/13 and 2013/14 seasons, such summer influenza activity was no longer observed. However, in the 2014/15 season, Okinawa again reported influenza activity during the summer, and was the only prefecture that continuously reported at least 1.0 influenza patient/sentinel/week from week 47 of 2014 to week 42 of 2015. In addition, Okinawa reported an influenza outbreak in a healthcare facility in July 2015 (see p. 209 of this issue).

Based on sentinel surveillance, the estimated number of medically attended influenza patients nationwide was approximately 15,030,000 from week 36 of 2014 to week 20 of 2015 (September 1, 2014-May 17, 2015).  Hospitalized influenza surveillance, which collects data for hospitalized influenza patients from 500 designated sentinel hospitals with ≥300 beds (initiated in September 2011), reported a total of 12,705 hospitalized influenza patients in the 2014/15 season, which was higher than the previous season by 28% (9,905 in 2013/14) (see p. 210 of this issue).  From the surveillance system for acute encephalitis, a category V notifiable infectious disease, 101 influenza acute encephalitis cases (tentative statistic that is not officially final) were notified during the 2014/15 season, relative to 96 cases in the previous season (see p. 212 of this issue).  In addition, during the 2014/15 season, the total number of deaths exceeded the excess mortality threshold in January 2015, with an estimated excess of 5,000 deaths (see p. 213 of this issue).

Isolation/detection of influenza virus:  In the 2014/15 season, prefectural and municipal public health institutes (PHIs) reported a total of 6,170 samples with isolation/detection of influenza viruses (4,456 isolations and 1,714 detections without isolation) (Table 1).  Among them, 5,100 were reported from influenza sentinels, and 1,070 from the other facilities (Table 2 in p.201 of this issue).

Distribution of influenza viruses isolated/detected in the 2014/15 season was 85% AH3, 14% type B (Yamagata lineage to Victoria lineage ratio 9:1) and 1% AH1pdm09 (Table 2).  AH3 began increasing in week 46 of 2014 and peaked in week 2 of 2015.  Influenza B began increasing in week 2 of 2015 and peaked in week 12, surpassing influenza A thereafter (Figs. 1 and 2).  Among AH3 isolates, 26% were isolated from patients 5-9 years old and 24% from those 10-14 years old (Fig. 3 and http://www.niid.go.jp/niid/images/iasr/rapid/inf2/2015_35w/innen5e_150924.gif).  Among type B isolates, 32% were isolated from patients 5-9 years old.

Antigenic characteristics of 2014/15 isolates (see p. 202 of this issue): The National Institute of Infectious Diseases (NIID) conducts antigenic analysis of isolates submitted from Japan and other Asian countries.  All the 99 AH1pdm09 isolates, except two isolated in Taiwan, were antigenically similar to the 2014/15 vaccine strain A/California/7/2009.  Most of the 366 AH3 isolates belonged to the genetic lineage clade 3C.2a; clades 3C.3a and 3C.3b were few.  Antigenicity determined by neutralization test (the isolates’ hemagglutination activity was too low for the HI test) revealed that more than 70% of the AH3 isolates were antigenically different from the 2014/15 vaccine strain A/New York/39/2012 (clade 3C.3).  The 205 B/Yamagata-lineage isolates had antigenicity similar to that of the 2014/15 vaccine strain B/Massachusetts/02/2012, and all the 39 B/Victoria-lineage isolates were antigenically similar to that of the 2011/12 vaccine strain B/Brisbane/60/2008.

Antiviral resistance of 2014/15 isolates (see p. 202 of this issue):  Except for one AH3 isolate that was resistant to oseltamivir and peramivir and with low sensitivity to zanamivir, 42 AH1pdm09 and 353 AH3 isolates from Japan were all sensitive to oseltamivir, zanamivir, peramivir and laninamivir.  All Influenza B isolates from Japan and abroad were sensitive to all four antiviral drugs.

Immunological status of the Japanese population:  Sero-surveillance for influenza has been conducted under the Preventive Vaccination Law (revised on April 1, 2013) (see p. 214 of this issue).  According to approximately 7,000 serum samples collected before the 2014/15 season (from July to September in 2014), the age-group specific HI antibody positive prevalence (titer higher than 1:40) to A/California/7/2009 [A(H1N1)pdm09] was ≥75% among 10-24 year olds and <40% among 0-4 year olds and those older than 60 years.  For A/New York/39/2012 [A(H3N2)], age-group specific HI antibody positive prevalence was ≥80% among 10-14 year olds, <30% among 0-4 year olds, and 40-60% among those older than 30 years; for B/Brisbane/60/2008 (B/Victoria-lineage), the seroprevalence was 50% for 40-44 year olds and <30% for those aged 0-4, 25-29 and ≥60 years.

Influenza vaccine:  Approximately 33,460,000 vials (calculated as 1mL/vial) of trivalent vaccines were produced in the 2014/15 season, of which an estimated 26,490,000 vials were used for vaccination.

The 2015/16 season tetravalent vaccine consists of two strains of type A and one strain each for B/Yamagata and B/Victoria (see p. 217 of this issue).  The AH1 strain was A/California/7/2009pdm09 (X-179A), same as for 2010/11-2014/15 seasons.  The AH3 and influenza B/Yamagata strains were changed, respectively, to A/Switzerland/9715293/2013 (NIB-88) [previously A/New York/ 39/2012 (X-233A)] and B/Phuket/3073/2013 [previously B/Massachusetts/2/2012 (BX-51B)].  The newly added B/Victoria lineage strain was B/Texas/2/2013.

Conclusion:  Trends in influenza activity should be monitored continuously by sentinel surveillance, school closure surveillance, hospitalized influenza surveillance and other systems.  Virus isolation should be conducted throughout the year and antigenic and genetic changes should be monitored to select vaccine candidate strains. Monitoring of antiviral resistance and influenza seroprevalence in the Japanese population should also be continued.  These measures are all important for future risk management measures. The epidemiology of the 2014/15 influenza season is described in http://www.niid.go.jp/niid/ja/flu-m/flutoppage/2066-ids/related/5647-fludoko-2914.html, in Japanese, and isolation and detection of influenza viruses in the 2015/16 season in see pp. 223, 224 & 225 of this issue; http://www.niid.go.jp/niid/en/iasr-inf-e.html.

 

 

Copyright 1998 National Institute of Infectious Diseases, Japan

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