A high seroprevalence of antibodies to pertussis toxin among Japanese adults: Qualitative and quantitative analyses

In 2013, national serosurveillance detected a high seroprevalence of antibodies to pertussis toxin (PT) from Bordetella pertussis among Japanese adults. Thus, we aimed to determine the cause(s) of this high seroprevalence, and analyzed the titers of antibodies to PT and filamentous hemagglutinin (FHA) among adults (35–44 years old), young children (4–7 years old), and older children (10–14 years old). Our quantitative analyses revealed that adults had higher seroprevalences of anti-PT IgG and PT-neutralizing antibodies, and similar titers of anti-FHA IgG, compared to the young and older children. Positive correlations were observed between the titers of PT-neutralizing antibodies and anti-PT IgG in all age groups (rs values of 0.326–0.522), although the correlation tended to decrease with age. The ratio of PT-neutralizing antibodies to anti-PT IgG was significantly different when we compared the serum and purified IgG fractions among adults (p = 0.016), although this result was not observed among young and older children. Thus, it appears that some adults had non-IgG immunoglobulins to PT. Our analyses also revealed that adults had high-avidity anti-PT IgG (avidity index: 63.5%, similar results were observed among the children); however, the adults had lower-avidity anti-FHA IgG (37.9%, p < 0.05). It is possible that low-avidity anti-FHA IgG is related to infection with other respiratory pathogens (e.g., Bordetella parapertussis, Haemophilus influenzae, or Mycoplasma pneumoniae), which produces antibodies to FHA-like proteins. Our observations suggest that these adults had been infected with B. pertussis and other pathogen(s) during their adulthood.

[1]  C. Rizzo,et al.  Evidence of increased circulation of Bordetella pertussis in the Italian adult population from seroprevalence data (2012-2013). , 2016, Journal of Medical Microbiology.

[2]  Y. Arakawa,et al.  A Novel IgM‐capture enzyme‐linked immunosorbent assay using recombinant Vag8 fusion protein for the accurate and early diagnosis of Bordetella pertussis infection , 2016, Microbiology and immunology.

[3]  R. Saito,et al.  Concentrations of Immunoglobulin G Antibodies Against Pertussis Toxin Does Not Decrease Over a Long Period of Time in Japan , 2015, Internal medicine.

[4]  K. Shibayama,et al.  Laboratory-based surveillance of pertussis using multitarget real-time PCR in Japan: evidence for Bordetella pertussis infection in preteens and teens , 2015, New microbes and new infections.

[5]  Meng Chen,et al.  Seroepidemiology of diphtheria and pertussis in Beijing, China: A cross-sectional study , 2015, Human vaccines & immunotherapeutics.

[6]  F. Mooi,et al.  Seroprevalence of Pertussis in The Gambia , 2015, The Pediatric infectious disease journal.

[7]  I. Lutsar,et al.  Seroprevalence of IgG antibodies to pertussis toxin in children and adolescents in Estonia. , 2014, Vaccine.

[8]  S. Lambert,et al.  Waning vaccine immunity in teenagers primed with whole cell and acellular pertussis vaccine: recent epidemiology , 2014, Expert review of vaccines.

[9]  S. Lee,et al.  Pertussis Seroprevalence in Korean Adolescents and Adults Using Anti-Pertussis Toxin Immunoglobulin G , 2014, Journal of Korean medical science.

[10]  T. Clark Changing pertussis epidemiology: everything old is new again. , 2014, The Journal of infectious diseases.

[11]  K. Shibayama,et al.  Genetic Analysis of Bordetella pertussis Isolates from the 2008–2010 Pertussis Epidemic in Japan , 2013, PloS one.

[12]  G. Amirthalingam Strategies to control pertussis in infants , 2013, Archives of Disease in Childhood.

[13]  C. Kenyon,et al.  Waning Immunity to Pertussis Following 5 Doses of DTaP , 2013, Pediatrics.

[14]  J. Liese,et al.  Assessment of IgG avidity against pertussis toxin and filamentous hemagglutinin via an adapted enzyme-linked immunosorbent assay (ELISA) using ammonium thiocyanate. , 2013, Journal of immunological methods.

[15]  J. Liese,et al.  Differences of IgG antibody avidity after an acellular pertussis (aP) booster in adolescents after a whole cell (wcP) or aP primary vaccination. , 2013, Vaccine.

[16]  J. Mertsola,et al.  Differences in avidity of IgG antibodies to pertussis toxin after acellular pertussis booster vaccination and natural infection. , 2012, Vaccine.

[17]  K. Krogfelt,et al.  Pertussis serology: assessment of IgG anti-PT ELISA for replacement of the CHO cell assay* , 2010, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[18]  F. Mooi,et al.  Seroprevalence of Pertussis in the Netherlands: Evidence for Increased Circulation of Bordetella pertussis , 2010, PloS one.

[19]  G. Berbers,et al.  What to do and what not to do in serological diagnosis of pertussis: recommendations from EU reference laboratories , 2010, European Journal of Clinical Microbiology & Infectious Diseases.

[20]  K. Krogfelt,et al.  Problem solved: a modified enzyme-linked immunosorbent assay for detection of human antibodies to pertussis toxin eliminates false-positive results occurring at analysis of heat-treated sera. , 2009, Diagnostic microbiology and infectious disease.

[21]  I. Srugo,et al.  What is new in pertussis? , 2007, European Journal of Pediatrics.

[22]  E. Hewlett,et al.  Pertussis — Not Just for Kids , 2005 .

[23]  E. Hewlett,et al.  Clinical practice. Pertussis--not just for kids. , 2005, The New England journal of medicine.

[24]  P. van Damme,et al.  Seroprevalence of Bordetella pertussis antibodies in Flanders (Belgium). , 2003, Vaccine.

[25]  S. Halperin,et al.  Pertussis of adults and infants. , 2002, The Lancet. Infectious diseases.

[26]  M. Iwaki,et al.  Distribution of pertussis antibodies among different age groups in Japan. , 2002, Vaccine.

[27]  L. Salleras,et al.  The seroepidemiology of B. pertussis infection in Catalonia, Spain , 2001, Epidemiology and Infection.

[28]  J. Gornbein,et al.  Prolonged afebrile nonproductive cough illnesses in American soldiers in Korea: a serological search for causation. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[29]  S. Barenkamp,et al.  Cloning, expression, and DNA sequence analysis of genes encoding nontypeable Haemophilus influenzae high-molecular-weight surface-exposed proteins related to filamentous hemagglutinin of Bordetella pertussis , 1992, Infection and immunity.

[30]  R. Möllby,et al.  Evaluation of serology and nasopharyngeal cultures for diagnosis of pertussis in a vaccine efficacy trial. , 1991, The Journal of infectious diseases.

[31]  H. Sato,et al.  An improved ELISA system for the measurement of IgG antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) in human sera. , 1991, Developments in biological standardization.

[32]  I. Krantz,et al.  Toxin-neutralizing antibodies in patients with pertussis, as determined by an assay using Chinese hamster ovary cells. , 1988, The Journal of infectious diseases.

[33]  H. Sato,et al.  Effect of monoclonal antibody to pertussis toxin on toxin activity , 1987, Infection and immunity.