Clinical Infectious Diseases Advance Access published June 9, 2015
1
Bordetella pertussis isolates circulating in China where whole cell vaccines have been used for 50 years
1
Xi’an Center for Disease Control and Prevention, Xi’an, China
2
rip t
Zengguo Wang1 and Qiushui He2,3,*
Department of Medical Microbiology, Capital Medical University, Beijing, China
3
an us c
*
Corresponding to Dr. Qiushui He, Department of Medical Microbiology and Immunology, University of
Ac
ce
pt
ed
M
Turku, Turku, Finland (Tel. +358 2 333 7429; Fax. +358 2 233 0008; Email. [email protected])
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].
Downloaded from http://cid.oxfordjournals.org/ at University of California, San Diego on June 12, 2015
Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland
2 TO THE EDITOR: Despite extensive vaccinations, whooping cough has resurged in industrial countries. The major explanations include wanning immunity associated with the acellular pertussis vaccines (ACVs) and Bordetella pertussis adaptation to vaccine-induced immunity. ACVs contain purified antigens in different combinations: pertussis toxin (Ptx), filamentous hemagglutin, pertactin (Prn), and fimbriae (Fim) 2 and
rip t
Fim3. However, divergence in vaccine antigens have been found between vaccine strains and circulating isolates [1-3]. Moreover, contiunous changes occur in B. pertussis genomes as determined by multi-locus
variable number of tandem repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE) [1-3]. Today the common allele profile and MLVA type found in the industrial countries are ptxA1/prn2/ptxP3/fim3-2
ptxA3/prn1/ptxP1/fim3-1.
Our current knowledge of B. pertussis adaptation is obtained from studies conducted in industrial countries where ACVs were introduced in 1990s. To better understand bacterial adaptation to ACVs induced selection pressure we need to compare B. pertussis in countries where WCVs have been continuously used.
In China, vaccination with WCVs was introduced in early 1960s. In 1982, a booster dose given
M
at 18-24 months was added [4]. The vaccination schedule has remained unchanged, although both WCVs and ACVs are used from 2007 on. The number of notified cases has been decreasing, and a total of 2,183
ed
and 1,712 cases were reported in 2012 and 2013 [5]. Most of reported cases were infants. We analyzed 16 B. pertussis isolates collected from 2012 to 2013 during a prospective study in Xi’an, China (Table 1) [6]. They were isolated throughout the study period and not from local small outbreaks. The analyses included sequencing of ptxA, prn, ptxP and fim3 genes, MLVA and PFGE using XbaI
pt
as the restriction enzyme [1]. PFGE profiles were analyzed at National Pertussis Reference Laboratory, Turku, Finland. The nomenclature was based on the profiles already defined for Finland (BpFINR) and
ce
Sweden (BpSR) [1]. Profiles assigned as BpCHR have been found only among the analyzed Chinese isolates. The 16 isolates produced 4 distinct PFGE profiles and 8 MLVA types (Table 1). The isolates wtih the PFGE profile BpFINR9 harbored 4 different MLVA types: MT55, MT76, MT195 and MT296. Only one isolate had
Ac
different allele combination prn2/ptxP3 from the vaccine strains. This isolate harbored the dominant MLVA type MT27 found in Europe and the USA and BpCHR23, a PFGE profile similar to BpSR10 recently observed in Europe [1-3].
In this study, the dominant PFGE profiles BpFINR9 and BpSR23 were prevalent in Europe
before 1990s and the common MLVA type MT55 was also found in Finland 1990s [1-4]. The genomic profiles determined by MLVA and PFGE are correlated with that obtained by genotyping of the vaccine antigens. Moreover, our finding is consistent with the earlier Chinese study in which isolates with
Downloaded from http://cid.oxfordjournals.org/ at University of California, San Diego on June 12, 2015
an us c
and MT27. The vaccine strains used for ACVs or whole cell vaccines (WCVs) are mostly with ptxA2 or
3 prn1/ptxP1/fim3-1 were dominant when 96 isolates collected during 1953-2005 were tested [4]. This study provides evidence that ACVs induce accelerated selection pressure for B. pertussis population compared to
rip t
WCVs.
Potential conflicts of Interest. All authors: No potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
1. van Gent M, Heuvelman KJ, van der Heide HGJ, et al. Analysis of Bordetella pertussis clinical isolates circulating in European countries from 1998-2012. Eur J Clin Microbiol Infect Dis 2015;34:821-30. 2. Schmidtke AJ, Boney KO, Martin SW, Skoff TH, Tondella ML, Tatti KM. Population diversity among Bordetella pertussis isolates, United States, 1935-2009. Emerg Infect Dis 2012;18:1248-55. 3. Octavia S, Sintchenko V, Gilbert GL, et al. Newly emerging clones of Bordetella pertussis carrying prn2 and ptxP3 alleles implicated in Australian pertussis epidemic in 2008–2010. J Infect Dis
M
2012;205:1220-4.
4. Zhang L, Xu Y, Zhao J, et al. Effect of vaccination on Bordetella pertussis strains, China. Emerg Infect Dis 2010;16:1695-1701.
ed
5. World Health Organization. Immunization,vaccination and biologicals. Vaccine preventable disease monitoring system: 2014 global summary (cited 2015 May 13). http://apps.who.int/immunization_monitoring/globalsummary/countries?countrycriteria%5Bcount ry%5D%5B%5D=CHN
pt
6. Wang Z, Cui Z, Li Y, et al. High prevalence of erythromycin-resistant Bordetella pertussis in Xi’an
Ac
ce
China. Clin Microbiol Infect 2014;20:O825-30.
Downloaded from http://cid.oxfordjournals.org/ at University of California, San Diego on June 12, 2015
an us c
References
Downloaded from http://cid.oxfordjournals.org/ at University of California, San Diego on June 12, 2015
Table. Characterization of B. pertussis isolates from Xi’an, China*
4
Date of NP sampling
Age
Gender
Vaccination status
Pertactin allele
Fimbriae 3 allele
Pertussis toxin promoter allele
PFGE profile
MLAV type
12030
Feb 28, 2012
84 days
Male
No
prn1
fim3-1
ptxP1
BpFINR9
MT55
12072
May 14, 2012
86 days
Female
No
prn1
fim3-1
ptxP1
BpFINR9
MT256
12152
Aug 14, 2012
2 years
Male
4 doses
prn1
fim3-1
ptxP1
BpSR23
MT104
12182
Sep 20, 2012
5 mo
Female
No
prn1
fim3-1
ptxP1
BpFINR9
MT195
13030
Apr 25, 2013
3 mo
Male
1 dose
prn2
fim3-1
ptxP3
BpCHR23
MT27
13038
May 27, 2013
4 mo
Male
No
prn1
fim3-4
ptxP1
BpCHR16
MT92
13046
June 25, 2013
2 mo
Male
No
prn1
fim3-1
ptxP1
BpFINR9
MT55
13055
July 5, 2013
2 mo
Male
No
prn1
fim3-1
ptxP1
BpSR23
MT104
13068
July 30, 2013
9 years
Female
Unknown
prn1
fim3-1
ptxP1
BpFINR9
MT55
13091†
Aug 26, 2013
4 mo
Female
1 dose
prn1
fim3-1
ptxP1
BpSR23
MT293
13092†
Aug 26, 2013
4 mo
Male
1 dose
prn1
fim3-1
ptxP1
BpSR23
MT293
13114
Oct 24, 2013
5 mo
13115
Oct 30, 2013
3 mo
13116
Oct 31, 2013
3 mo
13118
Nov 4, 2013
13159
Dec 16, 2013
2 doses
pt
prn1
fim3-1
ptxP1
BpFINR9
MT55
Male
1 dose
prn1
fim3-1
ptxP1
BpFINR9
MT55
Female
No
prn1
fim3-1
ptxP1
BpFINR9
MT55
Ac
Male
ce
ed
M
an us cr ipt
Laboratory code
2 mo
Male
No
prn1
fim3-1
ptxP1
BpFINR9
MT55
7 mo
Male
No
prn1
fim3-1
ptxP1
BpFINR9
MT76
*All isolates tested had ptxA1. †The two patients are twins.
1
Bordetella pertussis isolates circulating in China where whole cell vaccines have been used for 50 years
1
Xi’an Center for Disease Control and Prevention, Xi’an, China
2
rip t
Zengguo Wang1 and Qiushui He2,3,*
Department of Medical Microbiology, Capital Medical University, Beijing, China
3
an us c
*
Corresponding to Dr. Qiushui He, Department of Medical Microbiology and Immunology, University of
Ac
ce
pt
ed
M
Turku, Turku, Finland (Tel. +358 2 333 7429; Fax. +358 2 233 0008; Email. [email protected])
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].
Downloaded from http://cid.oxfordjournals.org/ at University of California, San Diego on June 12, 2015
Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland
2 TO THE EDITOR: Despite extensive vaccinations, whooping cough has resurged in industrial countries. The major explanations include wanning immunity associated with the acellular pertussis vaccines (ACVs) and Bordetella pertussis adaptation to vaccine-induced immunity. ACVs contain purified antigens in different combinations: pertussis toxin (Ptx), filamentous hemagglutin, pertactin (Prn), and fimbriae (Fim) 2 and
rip t
Fim3. However, divergence in vaccine antigens have been found between vaccine strains and circulating isolates [1-3]. Moreover, contiunous changes occur in B. pertussis genomes as determined by multi-locus
variable number of tandem repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE) [1-3]. Today the common allele profile and MLVA type found in the industrial countries are ptxA1/prn2/ptxP3/fim3-2
ptxA3/prn1/ptxP1/fim3-1.
Our current knowledge of B. pertussis adaptation is obtained from studies conducted in industrial countries where ACVs were introduced in 1990s. To better understand bacterial adaptation to ACVs induced selection pressure we need to compare B. pertussis in countries where WCVs have been continuously used.
In China, vaccination with WCVs was introduced in early 1960s. In 1982, a booster dose given
M
at 18-24 months was added [4]. The vaccination schedule has remained unchanged, although both WCVs and ACVs are used from 2007 on. The number of notified cases has been decreasing, and a total of 2,183
ed
and 1,712 cases were reported in 2012 and 2013 [5]. Most of reported cases were infants. We analyzed 16 B. pertussis isolates collected from 2012 to 2013 during a prospective study in Xi’an, China (Table 1) [6]. They were isolated throughout the study period and not from local small outbreaks. The analyses included sequencing of ptxA, prn, ptxP and fim3 genes, MLVA and PFGE using XbaI
pt
as the restriction enzyme [1]. PFGE profiles were analyzed at National Pertussis Reference Laboratory, Turku, Finland. The nomenclature was based on the profiles already defined for Finland (BpFINR) and
ce
Sweden (BpSR) [1]. Profiles assigned as BpCHR have been found only among the analyzed Chinese isolates. The 16 isolates produced 4 distinct PFGE profiles and 8 MLVA types (Table 1). The isolates wtih the PFGE profile BpFINR9 harbored 4 different MLVA types: MT55, MT76, MT195 and MT296. Only one isolate had
Ac
different allele combination prn2/ptxP3 from the vaccine strains. This isolate harbored the dominant MLVA type MT27 found in Europe and the USA and BpCHR23, a PFGE profile similar to BpSR10 recently observed in Europe [1-3].
In this study, the dominant PFGE profiles BpFINR9 and BpSR23 were prevalent in Europe
before 1990s and the common MLVA type MT55 was also found in Finland 1990s [1-4]. The genomic profiles determined by MLVA and PFGE are correlated with that obtained by genotyping of the vaccine antigens. Moreover, our finding is consistent with the earlier Chinese study in which isolates with
Downloaded from http://cid.oxfordjournals.org/ at University of California, San Diego on June 12, 2015
an us c
and MT27. The vaccine strains used for ACVs or whole cell vaccines (WCVs) are mostly with ptxA2 or
3 prn1/ptxP1/fim3-1 were dominant when 96 isolates collected during 1953-2005 were tested [4]. This study provides evidence that ACVs induce accelerated selection pressure for B. pertussis population compared to
rip t
WCVs.
Potential conflicts of Interest. All authors: No potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
1. van Gent M, Heuvelman KJ, van der Heide HGJ, et al. Analysis of Bordetella pertussis clinical isolates circulating in European countries from 1998-2012. Eur J Clin Microbiol Infect Dis 2015;34:821-30. 2. Schmidtke AJ, Boney KO, Martin SW, Skoff TH, Tondella ML, Tatti KM. Population diversity among Bordetella pertussis isolates, United States, 1935-2009. Emerg Infect Dis 2012;18:1248-55. 3. Octavia S, Sintchenko V, Gilbert GL, et al. Newly emerging clones of Bordetella pertussis carrying prn2 and ptxP3 alleles implicated in Australian pertussis epidemic in 2008–2010. J Infect Dis
M
2012;205:1220-4.
4. Zhang L, Xu Y, Zhao J, et al. Effect of vaccination on Bordetella pertussis strains, China. Emerg Infect Dis 2010;16:1695-1701.
ed
5. World Health Organization. Immunization,vaccination and biologicals. Vaccine preventable disease monitoring system: 2014 global summary (cited 2015 May 13). http://apps.who.int/immunization_monitoring/globalsummary/countries?countrycriteria%5Bcount ry%5D%5B%5D=CHN
pt
6. Wang Z, Cui Z, Li Y, et al. High prevalence of erythromycin-resistant Bordetella pertussis in Xi’an
Ac
ce
China. Clin Microbiol Infect 2014;20:O825-30.
Downloaded from http://cid.oxfordjournals.org/ at University of California, San Diego on June 12, 2015
an us c
References
Downloaded from http://cid.oxfordjournals.org/ at University of California, San Diego on June 12, 2015
Table. Characterization of B. pertussis isolates from Xi’an, China*
4
Date of NP sampling
Age
Gender
Vaccination status
Pertactin allele
Fimbriae 3 allele
Pertussis toxin promoter allele
PFGE profile
MLAV type
12030
Feb 28, 2012
84 days
Male
No
prn1
fim3-1
ptxP1
BpFINR9
MT55
12072
May 14, 2012
86 days
Female
No
prn1
fim3-1
ptxP1
BpFINR9
MT256
12152
Aug 14, 2012
2 years
Male
4 doses
prn1
fim3-1
ptxP1
BpSR23
MT104
12182
Sep 20, 2012
5 mo
Female
No
prn1
fim3-1
ptxP1
BpFINR9
MT195
13030
Apr 25, 2013
3 mo
Male
1 dose
prn2
fim3-1
ptxP3
BpCHR23
MT27
13038
May 27, 2013
4 mo
Male
No
prn1
fim3-4
ptxP1
BpCHR16
MT92
13046
June 25, 2013
2 mo
Male
No
prn1
fim3-1
ptxP1
BpFINR9
MT55
13055
July 5, 2013
2 mo
Male
No
prn1
fim3-1
ptxP1
BpSR23
MT104
13068
July 30, 2013
9 years
Female
Unknown
prn1
fim3-1
ptxP1
BpFINR9
MT55
13091†
Aug 26, 2013
4 mo
Female
1 dose
prn1
fim3-1
ptxP1
BpSR23
MT293
13092†
Aug 26, 2013
4 mo
Male
1 dose
prn1
fim3-1
ptxP1
BpSR23
MT293
13114
Oct 24, 2013
5 mo
13115
Oct 30, 2013
3 mo
13116
Oct 31, 2013
3 mo
13118
Nov 4, 2013
13159
Dec 16, 2013
2 doses
pt
prn1
fim3-1
ptxP1
BpFINR9
MT55
Male
1 dose
prn1
fim3-1
ptxP1
BpFINR9
MT55
Female
No
prn1
fim3-1
ptxP1
BpFINR9
MT55
Ac
Male
ce
ed
M
an us cr ipt
Laboratory code
2 mo
Male
No
prn1
fim3-1
ptxP1
BpFINR9
MT55
7 mo
Male
No
prn1
fim3-1
ptxP1
BpFINR9
MT76
*All isolates tested had ptxA1. †The two patients are twins.
