IASR

ISSN 0915-5813

Vol. 42 No. 6 (No. 496) June 2021
Infectious Agents Surveillance Reporthttps://www.niid.go.jp/niid/en/iasr-e.html

An infant with pertussis showing symptom recurrence and bacterial
reisolation after clarithromycin treatment.......................................... 111
A household outbreak of pertussis in Mie Prefecture............................ 112
Epidemiology of pertussis during COVID-19 epidemic in Japan ......... 113
Detection of macrolide-resistant Bordetella pertussis in Asia .............. 115
The first isolation and molecular epidemiology of macrolide-resistantBordetella pertussis in Japan................................................................ 116
Active epidemiological investigation of COVID-19 with novel SARS-CoV-2
variant in Japan (1st Report) : Epidemiological and clinical characteristics
of patients with SARS-CoV-2 variant....................................................... 117
Possible SARS-CoV-2 contact transmission among cleaners and healthcare workers during waste handling in Japan .................................... 119
Infection risk from handling of linens used by COVID-19 patients andmethods for safe and effective cleaning................................................ 121

National Institute of Infectious Diseases andTuberculosis and Infectious Diseases
Control Division,Ministry of Health, Labour and Welfare

Carbapenem-resistant Enterobacteriaceae (CRE) surveillance underthe Infectious Agents Surveillance System in Japan, 2019 ............... 123
Efforts to improve the detection of human sapovirus in sewage in
wastewater treatment plants and specimens from patients withgastroenteritis, Fukuoka Prefecture.................................................... 124
Comparison of RT-qPCR and antigen quantification methods for
SARS-CoV-2, Kobe City ........................................................................ 126
A simple method for estimating the effective reproduction number
based on the number of reported COVID-19 cases ............................. 128
Infectiousness profile distribution of COVID-19 based on informationfrom active epidemiological investigation in Fukuoka City ............... 129
Estimation of the incubation period of COVID-19 based on informationfrom active epidemiological investigation in Fukuoka City ............... 131
Suspected transmission of SARS-CoV-2 on an international flightin Japan, August 2020........................................................................... 132<THE TOPIC OF THIS MONTH>
Pertussis in Japan, as at January 2021
Figure 1. Number of notified pertussis cases by week of diagnosis, week 1 of 2018 to week 53 of 2020, Japan (n=31,909)
450

No. of notiified cases

400*Mean no. of weekly notifications: 203 (range: 4-473)

350
300
250
200
150
100
5001

5

9 13 17 21 25 29 33 37 41 45 49 1
20185

9 13 17 21 25 29 33 37 41 45 49 1
20195

9 13 17 21 25 29 33 37 41 45 49 53 Week
2020

Year

Week of diagnosis（National Epidemiological Surveillance of Infectious Diseases: as at 13 April 2021）

Pertussis is defined as an “acute respiratory tract infection caused by Bordetella pertussis (B. pertussis) ” in the reporting criteria
for physicians under the Infectious Diseases Control Law. The main symptom is prolonged coughing and the severity is greater in
infected newborns or infants. In Japan, the “adsorbed diphtheria-purified pertussis-tetanus combined (DPT) vaccine” has been usedin routine immunization, but in November 2012, DPT-IPV, consisting of DPT and inactivated polio combined vaccine (IPV), wasintroduced as a routine immunization. According to the immunization schedule for DPT-IPV in Japan, for the primary series, threesubcutaneous injections are administered (usually for those 3-12 months of age) with an interval of at least 20 days between each dose(the standard interval is 20-56 days). For the booster dose, after the initial dose a subcutaneous injection is administered at least 6months after three doses of the primary series (the standard interval is 12-18 months after completion of three doses of the primaryseries). Immunity acquired by vaccination wanes in 3-4 years, and those previously vaccinated may also become infected and develop
the disease. In developed countries, adolescents and adults being a source of infection, transmitting the disease to their families andunvaccinated children, sometimes resulting in severe illness, is of concern (see pp. 111&112 of this issue). As one of the measures toprotect infants from pertussis, some countries recommend vaccination of adolescents and adults, including pregnant women, with areduced quantity of pertussis and diphtheria antigens in DPT (Tdap; not approved in Japan) (IASR 40: 14-15, 2019). In Japan, DPT
can be vaccinated on a voluntary basis instead of Tdap.
Since January 1, 2018, pertussis has been a category V notifiable infectious disease under the Infectious Diseases Control Law(IASR 39: 13-14, 2018). As a result, pertussis cases notified to the National Epidemiological Surveillance of Infectious Diseases(NESID) are those with the clinical presentation of pertussis and, in principle, those confirmed by laboratory diagnosis (https://www.
mhlw.go.jp/bunya/kenkou/kekkaku-kansenshou11/01-05-23.html).
Laboratory diagnosis of pertussis: For the laboratory diagnosis of pertussis, bacterial isolation, serological tests, andbacterial gene detection are available (IASR 38: 33-34, 2017). Bacterial isolation has high specificity but requires a special culture
medium. In addition, the detection rate is low, at less than 60% even for infants who have relatively high levels of the bacteria in therespiratory tract during the course of infection. It is more difficult to isolate the bacteria from those previously vaccinated and fromadults and adolescents who have low levels of bacteria. Serological diagnosis using anti-PT IgG is used globally, but the World HealthOrganization (WHO) does not recommend its use for infants whose immune system is immature or for those who were vaccinatedwithin one year. In Japan, serodiagnostic tests that detect IgM and IgA antibodies against B. pertussis were approved in 2016 and arecovered by Health insurance. Bacterial gene detection has the highest sensitivity and the real-time PCR method is used globally. InJapan, the loop-mediated isothermal amplification method to detect B. pertussis was developed as a highly specific test, enabling afaster and simpler diagnosis than real-time PCR, and has been covered by Health insurance since November 2016. The recommendedlaboratory test method for pertussis depends on the time from the onset of symptoms, and it is important to select an appropriate1′（109′）（Continued on page 110′）IASR Vol. 42 No. 6（Jun. 2021） 2′（110′）（THE TOPIC OF THIS MONTH-Continued）

No. of notified cases

diagnostic method for an accurate diagnosis.
Figure 2. Proportion of notified pertussis cases＊ by age group, week 1 of 2018 to week
53 of 2020, Japan (n=29,833)
Pertussis notifications under the NESID
0102030405060708090
100％ No. ofsystem: Trends in the number of cases reportedYear
notified cases
2018
11,190weekly in Japan from 2018 to 2020 are presented(Fig. 1 on p.109). There were 31,909 cases
2019
15,972
notified to NESID during the three years from2018 to 2020 when notifications of all cases began.
1-4
5-9
10-14
40-49
30-39
≧60
2,671
2020
In 2018, the number of notified cases started to6-11months
15-19 20-29
50-59
increase around week 16, and the cumulative
Age group (year)
0-5 months＊Restricted to cases that meet the definition described in the Pertussis Reporting Guidelines basesd on the Infectious Diseases
number of notifications reached 12,116 for theControl Law (1st edition)
year. In the following year, 16,846 cases werehttps://www.niid.go.jp/niid/ja/id/610-disease-based/ha/pertussis/idsc/7994-pertussis-guideline-180425.html
reported, but in 2020, when the COVID-19(National Epidemiological Surveillance of Infectious Diseases: as at 8 January 2021)
pandemic occurred, only 2,947 cases were
Figure 3. Number of notified pertussis cases＊ by age and immunization status, weekreported (see p. 113 of this issue).
1 of 2018 to week 53 of 2020, Japan (n=29,833)
The median age of the notified cases from
3,000
January 2018 to 2020 was 10 years (range 0-98),
2,800
No record
2,600
with patients aged 5-9 years representing 36% of
Unknown vaccination history
2,400
Dose unknown
the total, followed by those aged 10-14 years
2,200
4 doses(26%). Patients younger than one year of age
2,000
3 doses
accounted for approximately 5% of the total (Fig.
1,800
2 doses2). There were many patients aged 6 to 13 years,
1,600
1 dosean age group corresponding to elementary andNot vaccinated1,400
junior high school students (Fig. 3). The number
1,200
1,000
of patients under 6 months of age who are prone
800
to severe disease when infected with pertussis
600
was 1,398 cases (4.7%). Moreover, there were400
pertussis patients in the adult population, whose
200
number was hitherto unclear from pediatric00 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 61 63 65 67 69 71 73 75 77 79 81 83 85 87 89 91 93 95 97
sentinel surveillance, with many being in their11Age (year)＊＊＊＊M refers to months
late 30s to 40s.
0 year＊Restricted to cases that meet the definition described in the Pertussis Reporting Guidelines basesd on the Infectious Diseases
Of the notified pertussis cases, 29,833 cases
Control Law (1st edition)
met the notification guidelines, 57% (17,062
https://www.niid.go.jp/niid/ja/id/610-disease-based/ha/pertussis/idsc/7994-pertussis-guideline-180425.html(National Epidemiological Surveillance of Infectious Diseases: as at 8 January 2021)
cases) had four doses of a pertussis-containing
vaccine, and 73% (16,646/22,822 cases) of thoseaged 20 years or younger and 80% (15,243/18,929 cases) of those aged 5 to 15 years had been vaccinated, revealing that most pediatricpatients were those previously vaccinated (Fig. 3). These proportions have changed little since 2018.
Outbreaks: In 2007, Japan experienced multiple outbreaks of pertussis in universities, suspected to have involved more than 200cases (IASR 29: 70-71, 2008). In recent years, reports of pertussis outbreaks have included those that began in primary and juniorhigh schools that led to an increase in pertussis in the local community (IASR 38: 25-26 & 26-28, 2017) and outbreaks in urban
settings (IASR 40: 7-9 & 10-12, 2019). As pertussis is now a notifiable disease with reporting of more detailed patient information,
earlier outbreak detection and response are expected.
Pertussis Seroprevalence in the Japanese population: According to the 2018 seroprevalence survey, i.e., National
Epidemiological Surveillance of Vaccine-Preventable Diseases (NESVPD), the proportion positive for anti-pertussis toxin (PT) IgG
antibody was 80% among those 6-11 months of age (https://www.niid.go.jp/niid/ja/y-graphs/8815-pertussis-yosoku-year2018.html).
Seroprevalence decreased with age, reaching the lowest level among 7-12-year-olds, but subsequently increased with age. There is noadditional pertussis vaccination in Japan after 90 months (7.5 years) of age, suggesting the possibility of natural infection in schoolage children. In addition, the decrease in seroprevalence among 4-7-year-olds confirmed in the previous survey (2013) shifted overtime to 7-12-year-olds, suggesting that vaccine effectiveness was lower in this group, but the cause of this change is unknown.
Pathogenic agents of pertussis and molecular epidemiology: As for B. pertussis, in recent years, MT27 strains, which arestrains circulating in Europe and the United States, have been increasing in Japan (IASR 40: 3-4, 2019), but due to the widespreaduse of gene detection tests and the decrease in bacterial culture tests, the number of clinical isolates obtained has decreased, making
it difficult to determine the epidemic strains. Macrolide antimicrobial agents are the first choice for treatment. However, in recentyears, macrolide-resistant strains in Asia continue to be reported (see p. 115 of this issue). Macrolide-resistant B.pertussis has also
been clinically isolated in Japan (see p. 116 of this issue), and it is important to continue to collect clinical isolates and to monitor forresistant strains. Bordetella species, such as Bordetella parapertussis and Bordetella holmesii, also cause symptoms similar to thoseof pertussis, but case reports of infection with these species are rare in Japan.
Conclusion: Due to the introduction of all-case notifications to NESID for pertussis since January 1, 2018, more detailed
epidemiological information, such as symptoms among those younger than 6 months of age, the number of cases among adults, andvaccination history, has become available. It is hoped that this information will lead to the early detection of and response to pertussis
outbreaks, along with assessment and implementation of effective prevention and response measures.
6 -M
5-M

The statistics in this report are based on 1) the data concerning patients and laboratory findings obtained by the National Epidemiological
Surveillance of Infectious Diseases undertaken in compliance with the Act on the Prevention of Infectious Diseases and Medical Care for Patientswith Infectious Diseases, and 2) other data covering various aspects of infectious diseases. The prefectural and municipal health centers andpublic health institutes (PHIs), the Department of Environmental Health and Food Safety, the Ministry of Health, Labour and Welfare, andquarantine stations, have provided the above data.

Infectious Disease Surveillance Center, National Institute of Infectious Diseases
Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, JAPAN Tel (+81-3)5285-1111