Pertussis is caused by Bordetella pertussis.  It is an acute respiratory infection mainly affecting children.  The main symptom is protracted cough.  In Japan, children are recommended to receive four shots (including one supplementary injection) of pertussis-containing vaccine in their infancy.  Instead of “adsorbed diphtheria-tetanus-acellular pertussis (DTaP) combined vaccine”, inactivated poliovirus vaccine (IPV)-containing DTaP, DTaP-IPV, was introduced since November 2012 (see p. 323 of this issue).  It has been found recently that acquired immunity wanes in 4-12 years after vaccination, which permits infection among children and adults who were already vaccinated.  As being often asymptomatic, the infected adolescent and adults transmit the bacteria to unvaccinated infants whose infection tends to become severe.  This trend is a challenge to many developed countries. 

Incidence: Pertussis is a category V infectious disease to be reported by sentinel clinics under the National Epidemiological Surveillance of Infectious Diseases (NESID).  Clinical cases are reported every week from approximately 3,000 pediatric sentinels all over the country (criteria for reporting: http://www.mhlw.go.jp/bunya/kenkou/kekkaku-kansenshou11/01-05-23.html).  While weekly incidence was low during 2001-2007 (<0.040/sentinel), it increased in 2008 with a peak (0.115/sentinel) in week 20/May (Fig. 1).  Pertussis epidemic is known to occur at an interval of about four years (IASR 26: 61-62, 2005).  Year 2008 corresponded the epidemic year as the previous epidemics occurred in 1999-2000 and 2004.  The epidemic started in 2008 continued for three years until 2010.  

The 2008-2010 epidemic was nationwide (Fig. 2).  In 2007 one year before the epidemic, prefectures reporting ≥2.00 cases/sentinel/year were only two, Chiba and Tochigi.  After the onset of the epidemic, prefectures reporting ≥2.00 cases/sentinel/year increased to 16 in 2008, 7 in 2009 and 11 in 2010.  

Immunological status of Japanese population: National Epidemiological Surveillance of Vaccine-Preventable Diseases (NESVPD) conducted sero-prevalence of anti-pertussis antibodies (anti-pertussis toxin and anti-filamentous hemagglutinin antibodies) among people in all age groups in 2003 and 2008.  In 2008, antibody-positive rate was about 80% among children aged 6 months to 2 years, which was higher than in 2003, and early acquisition of immunity among this age group was confirmed (Fig. 5).  Meanwhile, sero-prevalence rates among other age groups remained as low as 50% from 2003 to 2008. 

Outbreaks: Japan experienced large scale pertussis outbreaks in universities and other facilities in 2007, which reconfirmed the easiness of pertussis transmission in enclosed spaces occupied by people for a long time (IASR 29: 65-66, 2008).  Later than 2008, outbreaks continued to occur in nursery schools and junior high schools (IASR 29: 201-202, 2008, and see pp. 325 & 326 of this issue).  In addition, local epidemics involving mainly primary and junior high school children occurred (IASR 32: 340-341, 2011, and see pp. 327 & 329 of this issue). 

Pathogens that cause pertussis-like clinical symptoms:B. pertussis-related microorganisms that cause cough and other pertussis-like symptoms are B. parapertussis and B. holmesii.  B. holmesii is a new species identified by US CDC in 1995.  In Japan, B. holmesii has been isolated since late 2000’s from pericarditis and “pertussis” patients (IASR 33: 15-16, 2012 and see pp. 329 & 332 of this issue).  

Microorganisms other than Bordetella that cause pertussis-like symptoms are Mycoplasma pneumoniae, Chlamydia pneumoniae and human bocavirus.  Rhinovirus primarily responsible of common cold was detected from a suspected pertussis outbreak in a medical college and its affiliated hospital in Japan, which warned necessity of differential diagnosis between B. pertussis and rhinoviruses (IASR 32: 234-236, 2011).  From a pertussis outbreak in a nursery school in 2012, rhinovirus and coxsackievirus A9 were detected together with B. pertussis, which indicates occasional double infection of these pathogens in children (see p. 326 of this issue).  

Laboratory diagnosis of pertussis: For laboratory diagnosis of pertussis, bacterial isolation, serological test, and gene detection are applicable.  In Japan, the bacterial agglutination test is widely used as a simple serological test.  However, it is of low precision, and its application to adult or vaccinated child cases is not always appropriate (IASR 32: 236-237, 2011).  Titration of anti-pertussis toxin IgG antibody can be used but is not useful as a rapid test, because IgG increases one week or later after the onset of cough.  Bacterial isolation is extremely difficult particularly from adolescent or adult patients whose bacterial load is low, on account of limited bacterial growth.  The genetic testing can detect B. pertussis genome with a high sensitivity and widely being used as rapid detection method in the United States and European countries.  In Japan, the loop-mediated isothermal amplification (LAMP) is only used by the prefectural and municipal public health institutes (PHIs) and some medical institutions for research purposes (IASR 33: 104-105, 2012).  

For B. holmesii, both bacterial isolation and genetic testing are feasible (see p. 330 of this issue), but only genome sequencing can give definitive diagnosis of the pathogen.  Therefore, its presence may have been overlooked in clinical settings.  National Institute of Infectious Diseases Japan (NIID) is currently developing a LAMP method specifically detecting B. holmesii as a part of its NIID-PHI joint activities in strengthening national laboratory pathogen surveillance system.

Additional comments: Pertussis cases are increasing among adults in developed countries including Japan.  In Japan, pertussis epidemic still persists among secondary school children and also in communities.  As clinical diagnosis of pertussis particularly among adolescents and adults is difficult, genetic testing instead of bacterial culture should be used more widely as in the United States and European countries.  Introduction of simple genetic testing with high accuracy is needed not only for surveillance but also for evaluating vaccine efficacy in Japan.