1. A natural pertactin deficient strain of Bordetella pertussis shows improved entry in human monocyte-derived dendritic cells
Abstract
“The invasion and the immunomodulatory effect of a Bordetella pertussis natural deficient strain 00141(PRN- ) on human dendritic cells (MDDC) and its in vivo infection ability in a mouse model were evaluated in comparison with the reference B. pertussis strain ATCC 97-97 (18323). The mutant was isolated from a case of pertussis which occurred in a 22-month-old infant with typical symptoms of the disease. The results showed that this natural B. pertussis PRN deficient strain presented higher invasion ability of human MDDC compared to the reference strain. This natural mutant similar to the B. pertussis reference strain had immunomodulatory properties, inducing maturation in the DC phenotype which resulted in the acquisition of potent T cell-activating properties and down-regulated IL-12 production, and secretion of IL-10. The ability of PRN- strain to infect the lungs of CD1 mice was comparable to the reference strain and no difference was observed in the kinetics of clearance. Overall, these results show that the enhanced ability of the PRN- strain to invade/infect MDCC suggest that the PRN antigen may play a role in survival of the microorganism in the host.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/19579693
Citations
Souder, Emily, Jennifer Vodzak, Alan T. Evangelista, and Sarah S. Long. "Antimicrobial Susceptibility and Molecular Detection of Pertactin-producing and Pertactin-Deficient Bordetella Pertussis." The Pediatric Infectious Disease Journal 36.1 (2017): 119-21.
“The invasion and the immunomodulatory effect of a Bordetella pertussis natural deficient strain 00141(PRN- ) on human dendritic cells (MDDC) and its in vivo infection ability in a mouse model were evaluated in comparison with the reference B. pertussis strain ATCC 97-97 (18323). The mutant was isolated from a case of pertussis which occurred in a 22-month-old infant with typical symptoms of the disease. The results showed that this natural B. pertussis PRN deficient strain presented higher invasion ability of human MDDC compared to the reference strain. This natural mutant similar to the B. pertussis reference strain had immunomodulatory properties, inducing maturation in the DC phenotype which resulted in the acquisition of potent T cell-activating properties and down-regulated IL-12 production, and secretion of IL-10. The ability of PRN- strain to infect the lungs of CD1 mice was comparable to the reference strain and no difference was observed in the kinetics of clearance. Overall, these results show that the enhanced ability of the PRN- strain to invade/infect MDCC suggest that the PRN antigen may play a role in survival of the microorganism in the host.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/19579693
Citations
Souder, Emily, Jennifer Vodzak, Alan T. Evangelista, and Sarah S. Long. "Antimicrobial Susceptibility and Molecular Detection of Pertactin-producing and Pertactin-Deficient Bordetella Pertussis." The Pediatric Infectious Disease Journal 36.1 (2017): 119-21.
2. Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model
Abstract
“Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.”
Links
http://www.pnas.org/content/111/2/787
Citations
Warfel, J. M., L. I. Zimmerman, and T. J. Merkel. "Acellular Pertussis Vaccines Protect against Disease but Fail to Prevent Infection and Transmission in a Nonhuman Primate Model." Proceedings of the National Academy of Sciences 111.2 (2013): 787-92.
“Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.”
Links
http://www.pnas.org/content/111/2/787
Citations
Warfel, J. M., L. I. Zimmerman, and T. J. Merkel. "Acellular Pertussis Vaccines Protect against Disease but Fail to Prevent Infection and Transmission in a Nonhuman Primate Model." Proceedings of the National Academy of Sciences 111.2 (2013): 787-92.
3. Asymptomatic transmission and the resurgence of Bordetella pertussis
Abstract
“Background:
The recent increase in whooping cough incidence (primarily caused by Bordetella pertussis) presents a challenge to both public health practitioners and scientists trying to understand the mechanisms behind its resurgence. Three main hypotheses have been proposed to explain the resurgence: 1) waning of protective immunity from vaccination or natural infection over time, 2) evolution of B. pertussis to escape protective immunity, and 3) low vaccine coverage. Recent studies have suggested a fourth mechanism: asymptomatic transmission from individuals vaccinated with the currently used acellular B. pertussis vaccines.
Methods:
Using wavelet analyses of B. pertussis incidence in the United States (US) and United Kingdom (UK) and a phylodynamic analysis of 36 clinical B. pertussis isolates from the US, we find evidence in support of asymptomatic transmission of B. pertussis. Next, we examine the clinical, public health, and epidemiological consequences of asymptomatic B. pertussis transmission using a mathematical model.
Results:
We find that: 1) the timing of changes in age-specific attack rates observed in the US and UK are consistent with asymptomatic transmission; 2) the phylodynamic analysis of the US sequences indicates more genetic diversity in the overall bacterial population than would be suggested by the observed number of infections, a pattern expected with asymptomatic transmission; 3) asymptomatic infections can bias assessments of vaccine efficacy based on observations of B. pertussis-free weeks; 4) asymptomatic transmission can account for the observed increase in B. pertussis incidence; and 5) vaccinating individuals in close contact with infants too young to receive the vaccine (“cocooning” unvaccinated children) may be ineffective.
Conclusions:
Although a clear role for the previously suggested mechanisms still exists, asymptomatic transmission is the most parsimonious explanation for many of the observations surrounding the resurgence of B. pertussis in the US and UK. These results have important implications for B. pertussis vaccination policy and present a complicated scenario for achieving herd immunity and B. pertussis eradication. ”
Links
http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-015-0382-8
Citations
Althouse, Benjamin M., and Samuel V. Scarpino. "Asymptomatic Transmission and the Resurgence of Bordetella Pertussis." BMC Medicine 13.1 (2015)
“Background:
The recent increase in whooping cough incidence (primarily caused by Bordetella pertussis) presents a challenge to both public health practitioners and scientists trying to understand the mechanisms behind its resurgence. Three main hypotheses have been proposed to explain the resurgence: 1) waning of protective immunity from vaccination or natural infection over time, 2) evolution of B. pertussis to escape protective immunity, and 3) low vaccine coverage. Recent studies have suggested a fourth mechanism: asymptomatic transmission from individuals vaccinated with the currently used acellular B. pertussis vaccines.
Methods:
Using wavelet analyses of B. pertussis incidence in the United States (US) and United Kingdom (UK) and a phylodynamic analysis of 36 clinical B. pertussis isolates from the US, we find evidence in support of asymptomatic transmission of B. pertussis. Next, we examine the clinical, public health, and epidemiological consequences of asymptomatic B. pertussis transmission using a mathematical model.
Results:
We find that: 1) the timing of changes in age-specific attack rates observed in the US and UK are consistent with asymptomatic transmission; 2) the phylodynamic analysis of the US sequences indicates more genetic diversity in the overall bacterial population than would be suggested by the observed number of infections, a pattern expected with asymptomatic transmission; 3) asymptomatic infections can bias assessments of vaccine efficacy based on observations of B. pertussis-free weeks; 4) asymptomatic transmission can account for the observed increase in B. pertussis incidence; and 5) vaccinating individuals in close contact with infants too young to receive the vaccine (“cocooning” unvaccinated children) may be ineffective.
Conclusions:
Although a clear role for the previously suggested mechanisms still exists, asymptomatic transmission is the most parsimonious explanation for many of the observations surrounding the resurgence of B. pertussis in the US and UK. These results have important implications for B. pertussis vaccination policy and present a complicated scenario for achieving herd immunity and B. pertussis eradication. ”
Links
http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-015-0382-8
Citations
Althouse, Benjamin M., and Samuel V. Scarpino. "Asymptomatic Transmission and the Resurgence of Bordetella Pertussis." BMC Medicine 13.1 (2015)
4. Bordetella pertussis and Pertussis Vaccines
Abstract
“Bordetella pertussis is a human-specific pathogen that causes whooping cough. The use of pertussis whole-cell vaccines in infants and toddlers led to decreased circulation of the bacterium in the child population and a marked decrease in the incidence of the disease. However, vaccine does not result in life-long immunity; indeed, the circulation of the bacterium has not been controlled in the adult population. Universal adult booster immunization is now possible using pertussis acellular vaccines, which target—and are thus likely to control—the virulence of this bacterium.’
Links
http://cid.oxfordjournals.org/content/49/10/1565.full
Citations
Guiso, N., and D. Hozbor. "Bordetella Pertussis Polymorphism and Pertussis Vaccines." Clinical and Vaccine Immunology 15.2 (2008): 394-95
“Bordetella pertussis is a human-specific pathogen that causes whooping cough. The use of pertussis whole-cell vaccines in infants and toddlers led to decreased circulation of the bacterium in the child population and a marked decrease in the incidence of the disease. However, vaccine does not result in life-long immunity; indeed, the circulation of the bacterium has not been controlled in the adult population. Universal adult booster immunization is now possible using pertussis acellular vaccines, which target—and are thus likely to control—the virulence of this bacterium.’
Links
http://cid.oxfordjournals.org/content/49/10/1565.full
Citations
Guiso, N., and D. Hozbor. "Bordetella Pertussis Polymorphism and Pertussis Vaccines." Clinical and Vaccine Immunology 15.2 (2008): 394-95
5. Bordetella pertussis Strains with Increased Toxin Production Associated with Pertussis Resurgence
Abstract
“Before childhood vaccination was introduced in the 1940s, pertussis was a major cause of infant death worldwide. Widespread vaccination of children succeeded in reducing illness and death. In the 1990s, a resurgence of pertussis was observed in a number of countries with highly vaccinated populations, and pertussis has become the most prevalent vaccine-preventable disease in industrialized countries. We present evidence that in the Netherlands the dramatic increase in pertussis is temporally associated with the emergence of Bordetella pertussis strains carrying a novel allele for the pertussis toxin promoter, which confers increased pertussis toxin (Ptx) production. Epidemiologic data suggest that these strains are more virulent in humans. We discuss changes in the ecology of B. pertussis that may have driven this adaptation. Our results underline the importance of Ptx in transmission, suggest that vaccination may select for increased virulence, and indicate ways to control pertussis more effectively.”
Links
https://wwwnc.cdc.gov/eid/article/15/8/08-1511_article
Citations
Mooi, Frits R., Inge H.m. Van Loo, Marjolein Van Gent, Qiushui He, Marieke J. Bart, Kees J. Heuvelman, Sabine C. De Greeff, Dimitri Diavatopoulos, Peter Teunis, Nico Nagelkerke, and Jussi Mertsola. "Bordetella Pertussis Strains with Increased Toxin Production Associated with Pertussis Resurgence." Emerging Infectious Diseases 15.8 (2009): 1206-213.
“Before childhood vaccination was introduced in the 1940s, pertussis was a major cause of infant death worldwide. Widespread vaccination of children succeeded in reducing illness and death. In the 1990s, a resurgence of pertussis was observed in a number of countries with highly vaccinated populations, and pertussis has become the most prevalent vaccine-preventable disease in industrialized countries. We present evidence that in the Netherlands the dramatic increase in pertussis is temporally associated with the emergence of Bordetella pertussis strains carrying a novel allele for the pertussis toxin promoter, which confers increased pertussis toxin (Ptx) production. Epidemiologic data suggest that these strains are more virulent in humans. We discuss changes in the ecology of B. pertussis that may have driven this adaptation. Our results underline the importance of Ptx in transmission, suggest that vaccination may select for increased virulence, and indicate ways to control pertussis more effectively.”
Links
https://wwwnc.cdc.gov/eid/article/15/8/08-1511_article
Citations
Mooi, Frits R., Inge H.m. Van Loo, Marjolein Van Gent, Qiushui He, Marieke J. Bart, Kees J. Heuvelman, Sabine C. De Greeff, Dimitri Diavatopoulos, Peter Teunis, Nico Nagelkerke, and Jussi Mertsola. "Bordetella Pertussis Strains with Increased Toxin Production Associated with Pertussis Resurgence." Emerging Infectious Diseases 15.8 (2009): 1206-213.
6. Clinical and epidemiological picture of B pertussis and B parapertussis infections after introduction of acellular pertussis vaccines
Abstract
“Aims:
To investigate the clinical picture and frequency of Bordetella pertussis and B parapertussis infections after introduction of acellular pertussis (acP) vaccines in Germany.
Methods:
Prospective surveillance for B pertussis and B parapertussis in 14 144 toddlers. Pertussis vaccination coverage was 86%, either with acP (75%) or whole cell pertussis (wcP) vaccine (11%). All children presenting with cough for more than seven days were examined for B pertussis and B parapertussis by culture, PCR, and serology (for cough duration >21 days).
Results:
There were 180 Bordetella infections; 116 (64%) were caused by B pertussis and 64 (36%) by B parapertussis. Incidence rates were 4.8 and 2.8 per 1000 person-years, respectively. Paroxysmal cough, post-tussive whooping, and vomiting >21 days was found in 53%, 22%, and 8% of all B pertussis cases and in 22%, 5%, and 0% of all B parapertussis cases, respectively. A total of 81/116 (70%) B pertussis cases and 56/64 (87.5%) B parapertussis cases had received at least one dose of pertussis vaccine. Typical pertussis with paroxysmal cough >21 days was present in 29/35 (83%) unvaccinated B pertussis cases, in contrast to 33/81 (41%) vaccinated B pertussis cases.
Conclusion:
Following the increase of pertussis vaccination coverage, we observed a relative increase of B parapertussis cases in comparison to B pertussis cases. In vaccinated children B pertussis disease frequently presented as a mild disease, clinically difficult to distinguish from diseases associated with coughing caused by B parapertussis and other viral or bacterial infections.”
Links
http://adc.bmj.com/content/88/8/684.abstract
Citations
Liese, J. G. "Clinical and Epidemiological Picture of B Pertussis and B Parapertussis Infections after Introduction of Acellular Pertussis Vaccines." Archives of Disease in Childhood 88.8 (2003): 684-87.
“Aims:
To investigate the clinical picture and frequency of Bordetella pertussis and B parapertussis infections after introduction of acellular pertussis (acP) vaccines in Germany.
Methods:
Prospective surveillance for B pertussis and B parapertussis in 14 144 toddlers. Pertussis vaccination coverage was 86%, either with acP (75%) or whole cell pertussis (wcP) vaccine (11%). All children presenting with cough for more than seven days were examined for B pertussis and B parapertussis by culture, PCR, and serology (for cough duration >21 days).
Results:
There were 180 Bordetella infections; 116 (64%) were caused by B pertussis and 64 (36%) by B parapertussis. Incidence rates were 4.8 and 2.8 per 1000 person-years, respectively. Paroxysmal cough, post-tussive whooping, and vomiting >21 days was found in 53%, 22%, and 8% of all B pertussis cases and in 22%, 5%, and 0% of all B parapertussis cases, respectively. A total of 81/116 (70%) B pertussis cases and 56/64 (87.5%) B parapertussis cases had received at least one dose of pertussis vaccine. Typical pertussis with paroxysmal cough >21 days was present in 29/35 (83%) unvaccinated B pertussis cases, in contrast to 33/81 (41%) vaccinated B pertussis cases.
Conclusion:
Following the increase of pertussis vaccination coverage, we observed a relative increase of B parapertussis cases in comparison to B pertussis cases. In vaccinated children B pertussis disease frequently presented as a mild disease, clinically difficult to distinguish from diseases associated with coughing caused by B parapertussis and other viral or bacterial infections.”
Links
http://adc.bmj.com/content/88/8/684.abstract
Citations
Liese, J. G. "Clinical and Epidemiological Picture of B Pertussis and B Parapertussis Infections after Introduction of Acellular Pertussis Vaccines." Archives of Disease in Childhood 88.8 (2003): 684-87.
7. Epidemic Pertussis in 2012 — The Resurgence of a Vaccine-Preventable Disease
Abstract
“According to the Centers for Disease Control and Prevention, the United States is currently experiencing what may turn out to be the largest outbreak of reported pertussis (whooping cough) in 50 years. Why has this theoretically vaccine-preventable disease been on the upswing?”
Links
http://www.nejm.org/doi/full/10.1056/NEJMp1209051#t=article
Citations
Liese, J. G. "Clinical and Epidemiological Picture of B Pertussis and B Parapertussis Infections after Introduction of Acellular Pertussis Vaccines." Archives of Disease in Childhood 88.8 (2003): 684-87.
“According to the Centers for Disease Control and Prevention, the United States is currently experiencing what may turn out to be the largest outbreak of reported pertussis (whooping cough) in 50 years. Why has this theoretically vaccine-preventable disease been on the upswing?”
Links
http://www.nejm.org/doi/full/10.1056/NEJMp1209051#t=article
Citations
Liese, J. G. "Clinical and Epidemiological Picture of B Pertussis and B Parapertussis Infections after Introduction of Acellular Pertussis Vaccines." Archives of Disease in Childhood 88.8 (2003): 684-87.
8. Evolution of French Bordetella pertussis and Bordetella parapertussis isolates: increase of Bordetellae not expressing pertactin
Abstract
“Bordetella pertussis and Bordetella parapertussis are closely related bacterial agents of whooping cough. Whole-cell pertussis (wP) vaccine was introduced in France in 1959. Acellular pertussis (aP) vaccine was introduced in 1998 as an adolescent booster and was rapidly generalized to the whole population, changing herd immunity by specifically targeting the virulence of the bacteria. We performed a temporal analysis of all French B. pertussis and B. parapertussis isolates collected since 2000 under aP vaccine pressure, using pulsed-field gel electrophoresis (PFGE), genotyping and detection of expression of virulence factors. Particular isolates were selected according to their different phenotype and PFGE type and their characteristics were analysed using the murine model of respiratory infection and in vitro cell cytotoxic assay. Since the introduction of the aP vaccines there has been a steady increase in the number of B. pertussis and B. parapertussis isolates collected that are lacking expression of pertactin. These isolates seem to be as virulent as those expressing all virulence factors according to animal and cellular models of infection. Whereas wP vaccine-induced immunity led to a monomorphic population of B. pertussis, aP vaccine-induced immunity enabled the number of circulating B. pertussis and B. parapertussis isolates not expressing virulence factors to increase, sustaining our previous hypothesis.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/22717007
Citations
Hegerle, N., A.-S. Paris, D. Brun, G. Dore, E. Njamkepo, S. Guillot, and N. Guiso. "Evolution of French Bordetella Pertussis and Bordetella Parapertussis Isolates: Increase of Bordetellae Not Expressing Pertactin." Clinical Microbiology and Infection 18.9 (2012)
“Bordetella pertussis and Bordetella parapertussis are closely related bacterial agents of whooping cough. Whole-cell pertussis (wP) vaccine was introduced in France in 1959. Acellular pertussis (aP) vaccine was introduced in 1998 as an adolescent booster and was rapidly generalized to the whole population, changing herd immunity by specifically targeting the virulence of the bacteria. We performed a temporal analysis of all French B. pertussis and B. parapertussis isolates collected since 2000 under aP vaccine pressure, using pulsed-field gel electrophoresis (PFGE), genotyping and detection of expression of virulence factors. Particular isolates were selected according to their different phenotype and PFGE type and their characteristics were analysed using the murine model of respiratory infection and in vitro cell cytotoxic assay. Since the introduction of the aP vaccines there has been a steady increase in the number of B. pertussis and B. parapertussis isolates collected that are lacking expression of pertactin. These isolates seem to be as virulent as those expressing all virulence factors according to animal and cellular models of infection. Whereas wP vaccine-induced immunity led to a monomorphic population of B. pertussis, aP vaccine-induced immunity enabled the number of circulating B. pertussis and B. parapertussis isolates not expressing virulence factors to increase, sustaining our previous hypothesis.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/22717007
Citations
Hegerle, N., A.-S. Paris, D. Brun, G. Dore, E. Njamkepo, S. Guillot, and N. Guiso. "Evolution of French Bordetella Pertussis and Bordetella Parapertussis Isolates: Increase of Bordetellae Not Expressing Pertactin." Clinical Microbiology and Infection 18.9 (2012)
9. Imperfect vaccine-induced immunity and whooping cough transmission to infants
Abstract
“Whooping cough, caused by B. pertussis and B. parapertussis, has increased in incidence throughout much of the developed world since the 1980s despite high vaccine coverage, causing an increased risk of infection in infants who have substantial disease-induced mortality. Duration of immunity and epidemically significant routes of transmission across age groups remain unclear and deserve further investigation to inform vaccination strategies to better control pertussis burden. The authors analyze age- and species-specific whooping cough tests and vaccine histories in Massachusetts from 1990–2008. On average, the disease-free duration is 10.5 years. However, it has been decreasing over time, possibly due to a rising force of infection through increased circulation. Despite the importance of teenage cases during epidemics, wavelet analyses suggest that they are not the most important source of transmission to infants. In addition, the data indicate that the B. pertussis vaccine is not protective against disease induced by B. parapertussis.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/21034823
Citations
Lavine, Jennie, Hélène Broutin, Eric T. Harvill, and Ottar N. Bjørnstad. "Imperfect Vaccine-induced Immunity and Whooping Cough Transmission to Infants." Vaccine 29.1 (2010): 11-16.
“Whooping cough, caused by B. pertussis and B. parapertussis, has increased in incidence throughout much of the developed world since the 1980s despite high vaccine coverage, causing an increased risk of infection in infants who have substantial disease-induced mortality. Duration of immunity and epidemically significant routes of transmission across age groups remain unclear and deserve further investigation to inform vaccination strategies to better control pertussis burden. The authors analyze age- and species-specific whooping cough tests and vaccine histories in Massachusetts from 1990–2008. On average, the disease-free duration is 10.5 years. However, it has been decreasing over time, possibly due to a rising force of infection through increased circulation. Despite the importance of teenage cases during epidemics, wavelet analyses suggest that they are not the most important source of transmission to infants. In addition, the data indicate that the B. pertussis vaccine is not protective against disease induced by B. parapertussis.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/21034823
Citations
Lavine, Jennie, Hélène Broutin, Eric T. Harvill, and Ottar N. Bjørnstad. "Imperfect Vaccine-induced Immunity and Whooping Cough Transmission to Infants." Vaccine 29.1 (2010): 11-16.
10. Lack of Cross-protection against Bordetella holmesii after Pertussis Vaccination
Abstract
“Bordetella holmesii, a species closely related to B. pertussis, has been reported sporadically as a cause of whooping cough–like symptoms. To investigate whether B. pertussis–induced immunity is protective against infection with B. holmesii, we conducted an analysis using 11 human respiratory B. holmesii isolates collected during 2005–2009 from a highly B. pertussis–vaccinated population in Massachusetts. Neither whole-cell (wP) nor acellular (aP) B. pertussis vaccination conferred protection against these B. holmesii isolates in mice. Although T-cell responses induced by wP or aP cross-reacted with B. holmesii, vaccine-induced antibodies failed to effi ciently bind B. holmesii. B. holmesii–specifi c antibodies provided in addition to wP were suffi cient to rapidly reduce B. holmesii numbers in mouse lungs. Our fi ndings suggest the established presence of B. holmesii in Massachusetts and that failure to induce cross-reactive antibodies may explain poor vaccine-induced cross-protection”
Links
https://wwwnc.cdc.gov/eid/article/18/11/11-1544_article
Citations
Zhang, Xuqing, Laura S. Weyrich, Jennie S. Lavine, Alexia T. Karanikas, and Eric T. Harvill. "Lack of Cross-protection against Bordetella Holmesii after Pertussis Vaccination." Emerging Infectious Diseases 18.11 (2012): 1771-779.
“Bordetella holmesii, a species closely related to B. pertussis, has been reported sporadically as a cause of whooping cough–like symptoms. To investigate whether B. pertussis–induced immunity is protective against infection with B. holmesii, we conducted an analysis using 11 human respiratory B. holmesii isolates collected during 2005–2009 from a highly B. pertussis–vaccinated population in Massachusetts. Neither whole-cell (wP) nor acellular (aP) B. pertussis vaccination conferred protection against these B. holmesii isolates in mice. Although T-cell responses induced by wP or aP cross-reacted with B. holmesii, vaccine-induced antibodies failed to effi ciently bind B. holmesii. B. holmesii–specifi c antibodies provided in addition to wP were suffi cient to rapidly reduce B. holmesii numbers in mouse lungs. Our fi ndings suggest the established presence of B. holmesii in Massachusetts and that failure to induce cross-reactive antibodies may explain poor vaccine-induced cross-protection”
Links
https://wwwnc.cdc.gov/eid/article/18/11/11-1544_article
Citations
Zhang, Xuqing, Laura S. Weyrich, Jennie S. Lavine, Alexia T. Karanikas, and Eric T. Harvill. "Lack of Cross-protection against Bordetella Holmesii after Pertussis Vaccination." Emerging Infectious Diseases 18.11 (2012): 1771-779.
11. Newly Emerging Clones of Bordetella pertussis Carrying prn2 and ptxP3 Alleles Implicated in Australian Pertussis Epidemic in 2008–2010
Abstract
“Australia is experiencing a prolonged epidemic of pertussis that began in 2008. A total of 194 Bordetella pertussis isolates collected from 2008 through 2010 were typed by single-nucleotide polymorphism (SNP) analysis, by multilocus variable number tandem repeats analysis, and by fim3, prn, and ptxP sequence analyses. Strains with 2 closely related SNP profiles carrying prn2 and ptxP3 from the recently emerged SNP cluster I predominated. The data suggest increasing selection among the B. pertussis population in Australia in favor of strains carrying prn2 and ptxP3 under the pressure of acellular vaccine–induced immunity.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/22416243
Citations
Octavia, S., V. Sintchenko, G. L. Gilbert, A. Lawrence, A. D. Keil, G. Hogg, and R. Lan. "Newly Emerging Clones of Bordetella Pertussis Carrying Prn2 and PtxP3 Alleles Implicated in Australian Pertussis Epidemic in 2008-2010." Journal of Infectious Diseases 205.8 (2012): 1220-224.
“Australia is experiencing a prolonged epidemic of pertussis that began in 2008. A total of 194 Bordetella pertussis isolates collected from 2008 through 2010 were typed by single-nucleotide polymorphism (SNP) analysis, by multilocus variable number tandem repeats analysis, and by fim3, prn, and ptxP sequence analyses. Strains with 2 closely related SNP profiles carrying prn2 and ptxP3 from the recently emerged SNP cluster I predominated. The data suggest increasing selection among the B. pertussis population in Australia in favor of strains carrying prn2 and ptxP3 under the pressure of acellular vaccine–induced immunity.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/22416243
Citations
Octavia, S., V. Sintchenko, G. L. Gilbert, A. Lawrence, A. D. Keil, G. Hogg, and R. Lan. "Newly Emerging Clones of Bordetella Pertussis Carrying Prn2 and PtxP3 Alleles Implicated in Australian Pertussis Epidemic in 2008-2010." Journal of Infectious Diseases 205.8 (2012): 1220-224.
12. Pathogen adaptation under imperfect vaccination: implications for pertussis
Abstract
“Mass vaccination campaigns have drastically reduced the burden of infectious diseases. Unfortunately, in recent years several infectious diseases have re-emerged. Pertussis poses a well-known example. Inspired by pertussis, we study, by means of an epidemic model, the population and evolutionary dynamics of a pathogen population under the pressure of vaccination. A distinction is made between infection in immunologically naive individuals (primary infection) and infection in individuals whose immune system has been primed by vaccination or infection (secondary infection). The results show that (i) vaccination with an imperfect vaccine may not succeed in reducing the infection pressure if the transmissibility of secondary infections is higher than that of primary infections; (ii) pathogen strains that are able to evade the immunity induced by vaccination can only spread if escape mutants incur no or only a modest fitness cost and (iii) the direction of evolution depends crucially on the distribution of the different types of susceptibles in the population. We discuss the implications of these results for the design and use of vaccines that provide temporary immunity”
Links
https://www.ncbi.nlm.nih.gov/pubmed/16048777
Citations
Boven, M. Van, F. R. Mooi, J. F.p Schellekens, H. E De Melker, and M. Kretzschmar. "Pathogen Adaptation under Imperfect Vaccination: Implications for Pertussis." Proceedings of the Royal Society B: Biological Sciences 272.1572 (2005): 1617-624.
“Mass vaccination campaigns have drastically reduced the burden of infectious diseases. Unfortunately, in recent years several infectious diseases have re-emerged. Pertussis poses a well-known example. Inspired by pertussis, we study, by means of an epidemic model, the population and evolutionary dynamics of a pathogen population under the pressure of vaccination. A distinction is made between infection in immunologically naive individuals (primary infection) and infection in individuals whose immune system has been primed by vaccination or infection (secondary infection). The results show that (i) vaccination with an imperfect vaccine may not succeed in reducing the infection pressure if the transmissibility of secondary infections is higher than that of primary infections; (ii) pathogen strains that are able to evade the immunity induced by vaccination can only spread if escape mutants incur no or only a modest fitness cost and (iii) the direction of evolution depends crucially on the distribution of the different types of susceptibles in the population. We discuss the implications of these results for the design and use of vaccines that provide temporary immunity”
Links
https://www.ncbi.nlm.nih.gov/pubmed/16048777
Citations
Boven, M. Van, F. R. Mooi, J. F.p Schellekens, H. E De Melker, and M. Kretzschmar. "Pathogen Adaptation under Imperfect Vaccination: Implications for Pertussis." Proceedings of the Royal Society B: Biological Sciences 272.1572 (2005): 1617-624.
13. Patterns of Bordetella parapertussis Respiratory Illnesses: 2008–2010
Abstract
“Clinical specimens from 9 states during 2008–2010 were tested by PCR for Bordetella pertussis and Bordetella parapertussis. Of the positive samples, 13.99% were identified as B. parapertussis. It was concluded that B. parapertussis infections are more common than previously realized and contribute to cases thought to be vaccine failures.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/22156857
Citations
Cherry, J. D., and B. L. Seaton. "Patterns of Bordetella Parapertussis Respiratory Illnesses: 2008-2010." Clinical Infectious Diseases 54.4 (2011): 534-37.
“Clinical specimens from 9 states during 2008–2010 were tested by PCR for Bordetella pertussis and Bordetella parapertussis. Of the positive samples, 13.99% were identified as B. parapertussis. It was concluded that B. parapertussis infections are more common than previously realized and contribute to cases thought to be vaccine failures.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/22156857
Citations
Cherry, J. D., and B. L. Seaton. "Patterns of Bordetella Parapertussis Respiratory Illnesses: 2008-2010." Clinical Infectious Diseases 54.4 (2011): 534-37.
14. Pertactin-negative Bordetella pertussis strains in Canada: characterization of a dozen isolates based on a survey of 224 samples collected in different parts of the country over the last 20 years
Abstract
“Objective:
To detect and characterize pertactin-negative Bordetella pertussis in Canada, especially for isolates collected in recent years. Methods: A total of 224 isolates from the years 1994–2013 were screened by Western immuno-blot for expression of pertactin. Pertactin-negative isolates were characterized by serotyping, pulsed-field gel electrophoresis (PFGE), and genotyping of their pertactin, fimbriae 3, pertussis toxin subunit 1, and pertussis toxin gene promoter region, as well as the complete sequence of the pertactin gene.
Results:
Twelve isolates were pertactin-negative, giving an overall prevalence of 5.4%. However, no such isolate was found prior to 2011 and 17.8% of 62 isolates examined in 2012 were pertactin-negative. Ten pertactin-negative isolates contained a significant mutation in their pertactin (prn) genes. IS481 was found in the prn genes of eight isolates, while a single point mutation occurred either in the coding region (resulting in a premature stop codon) or in the promoter region (preventing gene transcription) in two other isolates. PFGE analysis also showed multiple profiles suggesting that several independent genetic events might have led to the emergence of these pertactin-negative strains rather than expansion of a single clone.
Conclusions:
As reported elsewhere, pertactin-negative B. pertussis has emerged in Canada in recent years, notably in 2012. This coincided with an increase in pertussis activity in Canada. A further systematic study with a larger geographical representative sample is required to determine how these vaccine-negative strains may contribute to the overall changing epidemiology of pertussis in Canada.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/25244999
Citations
Tsang, Raymond S.w., Michelle Shuel, Frances B. Jamieson, Steven Drews, Linda Hoang, Greg Horsman, Brigitte Lefebvre, Shalini Desai, and Monique St-Laurent. "Pertactin-negative Bordetella Pertussis Strains in Canada: Characterization of a Dozen Isolates Based on a Survey of 224 Samples Collected in Different Parts of the Country over the Last 20 Years." International Journal of Infectious Diseases 28 (2014): 65-69.
“Objective:
To detect and characterize pertactin-negative Bordetella pertussis in Canada, especially for isolates collected in recent years. Methods: A total of 224 isolates from the years 1994–2013 were screened by Western immuno-blot for expression of pertactin. Pertactin-negative isolates were characterized by serotyping, pulsed-field gel electrophoresis (PFGE), and genotyping of their pertactin, fimbriae 3, pertussis toxin subunit 1, and pertussis toxin gene promoter region, as well as the complete sequence of the pertactin gene.
Results:
Twelve isolates were pertactin-negative, giving an overall prevalence of 5.4%. However, no such isolate was found prior to 2011 and 17.8% of 62 isolates examined in 2012 were pertactin-negative. Ten pertactin-negative isolates contained a significant mutation in their pertactin (prn) genes. IS481 was found in the prn genes of eight isolates, while a single point mutation occurred either in the coding region (resulting in a premature stop codon) or in the promoter region (preventing gene transcription) in two other isolates. PFGE analysis also showed multiple profiles suggesting that several independent genetic events might have led to the emergence of these pertactin-negative strains rather than expansion of a single clone.
Conclusions:
As reported elsewhere, pertactin-negative B. pertussis has emerged in Canada in recent years, notably in 2012. This coincided with an increase in pertussis activity in Canada. A further systematic study with a larger geographical representative sample is required to determine how these vaccine-negative strains may contribute to the overall changing epidemiology of pertussis in Canada.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/25244999
Citations
Tsang, Raymond S.w., Michelle Shuel, Frances B. Jamieson, Steven Drews, Linda Hoang, Greg Horsman, Brigitte Lefebvre, Shalini Desai, and Monique St-Laurent. "Pertactin-negative Bordetella Pertussis Strains in Canada: Characterization of a Dozen Isolates Based on a Survey of 224 Samples Collected in Different Parts of the Country over the Last 20 Years." International Journal of Infectious Diseases 28 (2014): 65-69.
15. Pertactin-Negative Variants of Bordetella pertussis in the United States
Abstract
“Global vaccination of children has dramatically reduced the incidence of illness and deaths from Bordetella pertussis, the causative agent of whooping cough. However, increased numbers of cases of whooping cough have recently been reported in several countries, including the United States. Although much attention has been given to the waning immunity associated with the introduction of acellular vaccines,1 another factor contributing to the outbreaks may be the adaptation of B. pertussis to vaccine selection pressure. Pertactin is a component of acellular vaccines. Pertactin-negative variants of B. pertussis have recently been reported in clinical isolates from Japan, France, and Finland. The variants from Japan and Finland had deletions or insertion sequences in prn1, an allelic variant of the gene encoding pertactin (prn); the French isolates had deletions or truncations in the prn2 allele.2,3 Pertactin mutants retain lethality in mouse models of infection and are transmissible in humans”
Links
https://www.ncbi.nlm.nih.gov/pubmed/23388024
Citations
Queenan, Anne Marie, Pamela K. Cassiday, and Alan Evangelista. "Pertactin-Negative Variants OfBordetella Pertussisin the United States." New England Journal of Medicine 368.6 (2013): 583-84.
“Global vaccination of children has dramatically reduced the incidence of illness and deaths from Bordetella pertussis, the causative agent of whooping cough. However, increased numbers of cases of whooping cough have recently been reported in several countries, including the United States. Although much attention has been given to the waning immunity associated with the introduction of acellular vaccines,1 another factor contributing to the outbreaks may be the adaptation of B. pertussis to vaccine selection pressure. Pertactin is a component of acellular vaccines. Pertactin-negative variants of B. pertussis have recently been reported in clinical isolates from Japan, France, and Finland. The variants from Japan and Finland had deletions or insertion sequences in prn1, an allelic variant of the gene encoding pertactin (prn); the French isolates had deletions or truncations in the prn2 allele.2,3 Pertactin mutants retain lethality in mouse models of infection and are transmissible in humans”
Links
https://www.ncbi.nlm.nih.gov/pubmed/23388024
Citations
Queenan, Anne Marie, Pamela K. Cassiday, and Alan Evangelista. "Pertactin-Negative Variants OfBordetella Pertussisin the United States." New England Journal of Medicine 368.6 (2013): 583-84.
16. Pertussis: Challenges Today and for the Future
Abstract
“Pertussis is a truly unique contagious respiratory disease [1–4]. It is mainly caused by Bordetella pertussis, but similar cough illnesses can be caused by B. parapertussis in young children and B. holmesii in adolescents and adults. (The remainder of this communication will be restricted to B. pertussis infection and illness.)”
Links
http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003418
Citations
Cherry, James D. "Pertussis: Challenges Today and for the Future." PLoS Pathogens 9.7 (2013)
“Pertussis is a truly unique contagious respiratory disease [1–4]. It is mainly caused by Bordetella pertussis, but similar cough illnesses can be caused by B. parapertussis in young children and B. holmesii in adolescents and adults. (The remainder of this communication will be restricted to B. pertussis infection and illness.)”
Links
http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003418
Citations
Cherry, James D. "Pertussis: Challenges Today and for the Future." PLoS Pathogens 9.7 (2013)
17. Population Diversity among Bordetella pertussis Isolates, United States, 1935–2009
Abstract
“Since the 1980s, pertussis notifi cations in the United States have been increasing. To determine the types of Bordetella pertussis responsible for these increases, we divided 661 B. pertussis isolates collected in the United States during 1935–2009 into 8 periods related to the introduction of novel vaccines or changes in vaccination schedule. B. pertussis diversity was highest from 1970–1990 (94%) but declined to ≈70% after 1991 and has remained constant. During 2006–2009, 81.6% of the strains encoded multilocus sequence type prn2-ptxP3-ptxS1A-fi m3B, and 64% were multilocus variable number tandem repeat analysis type 27. US trends were consistent with those seen internationally; emergence and predominance of the fi m3B allele was the only molecular characteristic associated with the increase in pertussis notifi cations. Changes in the vaccine composition and schedule were not the direct selection pressures that resulted in the allele changes present in the current B. pertussis population.”
Links
https://wwwnc.cdc.gov/eid/article/18/8/12-0082_article
Citations
Schmidtke, Amber J., Kathryn O. Boney, Stacey W. Martin, Tami H. Skoff, M. Lucia Tondella, and Kathleen M. Tatti. "Population Diversity among Bordetella Pertussis Isolates, United States, 1935-2009." Emerging Infectious Diseases 18.8 (2012)
“Since the 1980s, pertussis notifi cations in the United States have been increasing. To determine the types of Bordetella pertussis responsible for these increases, we divided 661 B. pertussis isolates collected in the United States during 1935–2009 into 8 periods related to the introduction of novel vaccines or changes in vaccination schedule. B. pertussis diversity was highest from 1970–1990 (94%) but declined to ≈70% after 1991 and has remained constant. During 2006–2009, 81.6% of the strains encoded multilocus sequence type prn2-ptxP3-ptxS1A-fi m3B, and 64% were multilocus variable number tandem repeat analysis type 27. US trends were consistent with those seen internationally; emergence and predominance of the fi m3B allele was the only molecular characteristic associated with the increase in pertussis notifi cations. Changes in the vaccine composition and schedule were not the direct selection pressures that resulted in the allele changes present in the current B. pertussis population.”
Links
https://wwwnc.cdc.gov/eid/article/18/8/12-0082_article
Citations
Schmidtke, Amber J., Kathryn O. Boney, Stacey W. Martin, Tami H. Skoff, M. Lucia Tondella, and Kathleen M. Tatti. "Population Diversity among Bordetella Pertussis Isolates, United States, 1935-2009." Emerging Infectious Diseases 18.8 (2012)
18. Prevalence and Genetic Characterization of Pertactin Deficient Bordetella pertussis in Japan
Abstract
“The adhesin pertactin (Prn) is one of the major virulence factors of Bordetella pertussis, the etiological agent of whooping cough. However, a significant prevalence of Prn-deficient (Prn2) B. pertussis was observed in Japan. The Prn2 isolate was first discovered in 1997, and 33 (27%) Prn2 isolates were identified among 121 B. pertussis isolates collected from 1990 to 2009. Sequence analysis revealed that all the Prn2 isolates harbor exclusively the vaccine-type prn1 allele and that loss of Prn expression is caused by 2 different mutations: an 84-bp deletion of the prn signal sequence (prn1DSS, n = 24) and an IS481 insertion in prn1 (prn1::IS481, n = 9). The frequency of Prn2 isolates, notably those harboring prn1DSS, significantly increased since the early 2000s, and Prn2 isolates were subsequently found nationwide. Multilocus variable-number tandem repeat analysis (MLVA) revealed that 24 (73%) of 33 Prn2 isolates belong to MLVA-186, and 6 and 3 Prn2 isolates belong to MLVA-194 and MLVA-226, respectively. The 3 MLVA types are phylogenetically closely related, suggesting that the 2 Prn2 clinical strains (harboring prn1DSS and prn1::IS481) have clonally expanded in Japan. Growth competition assays in vitro also demonstrated that Prn2 isolates have a higher growth potential than the Prn+ back-mutants from which they were derived. Our observations suggested that human host factors (genetic factors and immune status) that select for Prn2 strains have arisen and that Prn expression is not essential for fitness under these conditions.”
Links
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031985
Citations
Otsuka, Nao, Hyun-Ja Han, Hiromi Toyoizumi-Ajisaka, Yukitsugu Nakamura, Yoshichika Arakawa, Keigo Shibayama, and Kazunari Kamachi. "Prevalence and Genetic Characterization of Pertactin-Deficient Bordetella Pertussis in Japan." PLoS ONE 7.2 (2012)
“The adhesin pertactin (Prn) is one of the major virulence factors of Bordetella pertussis, the etiological agent of whooping cough. However, a significant prevalence of Prn-deficient (Prn2) B. pertussis was observed in Japan. The Prn2 isolate was first discovered in 1997, and 33 (27%) Prn2 isolates were identified among 121 B. pertussis isolates collected from 1990 to 2009. Sequence analysis revealed that all the Prn2 isolates harbor exclusively the vaccine-type prn1 allele and that loss of Prn expression is caused by 2 different mutations: an 84-bp deletion of the prn signal sequence (prn1DSS, n = 24) and an IS481 insertion in prn1 (prn1::IS481, n = 9). The frequency of Prn2 isolates, notably those harboring prn1DSS, significantly increased since the early 2000s, and Prn2 isolates were subsequently found nationwide. Multilocus variable-number tandem repeat analysis (MLVA) revealed that 24 (73%) of 33 Prn2 isolates belong to MLVA-186, and 6 and 3 Prn2 isolates belong to MLVA-194 and MLVA-226, respectively. The 3 MLVA types are phylogenetically closely related, suggesting that the 2 Prn2 clinical strains (harboring prn1DSS and prn1::IS481) have clonally expanded in Japan. Growth competition assays in vitro also demonstrated that Prn2 isolates have a higher growth potential than the Prn+ back-mutants from which they were derived. Our observations suggested that human host factors (genetic factors and immune status) that select for Prn2 strains have arisen and that Prn expression is not essential for fitness under these conditions.”
Links
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031985
Citations
Otsuka, Nao, Hyun-Ja Han, Hiromi Toyoizumi-Ajisaka, Yukitsugu Nakamura, Yoshichika Arakawa, Keigo Shibayama, and Kazunari Kamachi. "Prevalence and Genetic Characterization of Pertactin-Deficient Bordetella Pertussis in Japan." PLoS ONE 7.2 (2012)
19. Small Mutations in Bordetella pertussis Are Associated with Selective Sweeps
Abstract
“Bordetella pertussis is the causative agent of pertussis, a highly contagious disease of the human respiratory tract. Despite high vaccination coverage, pertussis has resurged and has become one of the most prevalent vaccine-preventable diseases in developed countries. We have proposed that both waning immunity and pathogen adaptation have contributed to the persistence and resurgence of pertussis. Allelic variation has been found in virulence-associated genes coding for the pertussis toxin A subunit (ptxA), pertactin (prn), serotype 2 fimbriae (fim2), serotype 3 fimbriae (fim3) and the promoter for pertussis toxin (ptxP). In this study, we investigated how more than 60 years of vaccination has affected the Dutch B. pertussis population by combining data from phylogeny, genomics and temporal trends in strain frequencies. Our main focus was on the ptxA, prn, fim3 and ptxP genes. However, we also compared the genomes of 11 Dutch strains belonging to successful lineages. Our results showed that, between 1949 and 2010, the Dutch B. pertussis population has undergone as least four selective sweeps that were associated with small mutations in ptxA, prn, fim3 and ptxP. Phylogenetic analysis revealed a stepwise adaptation in which mutations accumulated clonally. Genomic analysis revealed a number of additional mutations which may have a contributed to the selective sweeps. Five large deletions were identified which were fixed in the pathogen population. However, only one was linked to a selective sweep. No evidence was found for a role of gene acquisition in pathogen adaptation. Our results suggest that the B. pertussis gene repertoire is already well adapted to its current niche and required only fine tuning to persist in the face of vaccination. Further, this work shows that small mutations, even single SNPs, can drive large changes in the populations of bacterial pathogens within a time span of six to 19 years.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/23029513
Citations
Gent, Marjolein Van, Marieke J. Bart, Han G. J. Van Der Heide, Kees J. Heuvelman, and Frits R. Mooi. "Small Mutations in Bordetella Pertussis Are Associated with Selective Sweeps." PLoS ONE 7.9 (2012)
“Bordetella pertussis is the causative agent of pertussis, a highly contagious disease of the human respiratory tract. Despite high vaccination coverage, pertussis has resurged and has become one of the most prevalent vaccine-preventable diseases in developed countries. We have proposed that both waning immunity and pathogen adaptation have contributed to the persistence and resurgence of pertussis. Allelic variation has been found in virulence-associated genes coding for the pertussis toxin A subunit (ptxA), pertactin (prn), serotype 2 fimbriae (fim2), serotype 3 fimbriae (fim3) and the promoter for pertussis toxin (ptxP). In this study, we investigated how more than 60 years of vaccination has affected the Dutch B. pertussis population by combining data from phylogeny, genomics and temporal trends in strain frequencies. Our main focus was on the ptxA, prn, fim3 and ptxP genes. However, we also compared the genomes of 11 Dutch strains belonging to successful lineages. Our results showed that, between 1949 and 2010, the Dutch B. pertussis population has undergone as least four selective sweeps that were associated with small mutations in ptxA, prn, fim3 and ptxP. Phylogenetic analysis revealed a stepwise adaptation in which mutations accumulated clonally. Genomic analysis revealed a number of additional mutations which may have a contributed to the selective sweeps. Five large deletions were identified which were fixed in the pathogen population. However, only one was linked to a selective sweep. No evidence was found for a role of gene acquisition in pathogen adaptation. Our results suggest that the B. pertussis gene repertoire is already well adapted to its current niche and required only fine tuning to persist in the face of vaccination. Further, this work shows that small mutations, even single SNPs, can drive large changes in the populations of bacterial pathogens within a time span of six to 19 years.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/23029513
Citations
Gent, Marjolein Van, Marieke J. Bart, Han G. J. Van Der Heide, Kees J. Heuvelman, and Frits R. Mooi. "Small Mutations in Bordetella Pertussis Are Associated with Selective Sweeps." PLoS ONE 7.9 (2012)
20. Tdap Vaccine Effectiveness in Adolescents During the 2012 Washington State Pertussis Epidemic
Abstract
“BACKGROUND:
Acellular pertussis vaccines replaced whole-cell vaccines for the 5-dose childhood abstract vaccination series in 1997. A sixth dose of pertussis-containing vaccine, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap), was recommended in 2005 for adolescents and adults. Studies examining Tdap vaccine effectiveness (VE) among adolescents who have received all acellular vaccines are limited.
METHODS:
To assess Tdap VE and duration of protection, we conducted a matched case-control study during the 2012 pertussis epidemic in Washington among adolescents born during 1993–2000. All pertussis cases reported from January 1 through June 30, 2012, in 7 counties were included; 3 controls were matched by primary provider clinic and birth year to each case. Vaccination histories were obtained through medical records, the state immunization registry, and parent interviews. Participants were classified by type of pertussis vaccine received on the basis of birth year: a mix of whole-cell and acellular vaccines (1993–1997) or all acellular vaccines (1998–2000). We used conditional logistic regression to calculate odds ratios comparing Tdap receipt between cases and controls.
RESULTS:
Among adolescents who received all acellular vaccines (450 cases, 1246 controls), overall Tdap VE was 63.9% (95% confidence interval [CI]: 50% to 74%). VE within 1 year of vaccination was 73% (95% CI: 60% to 82%). At 2 to 4 years postvaccination, VE declined to 34% (95% CI: 20.03% to 58%).
CONCLUSIONS:
Tdap protection wanes within 2 to 4 years. Lack of long-term protection after vaccination is likely contributing to increases in pertussis among adolescents.”
Links
http://pediatrics.aappublications.org/content/early/2015/04/28/peds.2014-3358
Citations
"Tdap Vaccine Effectiveness in Adolescents During the 2012 Washington State Pertussis Epidemic." Pediatrics 135.6 (2015)
“BACKGROUND:
Acellular pertussis vaccines replaced whole-cell vaccines for the 5-dose childhood abstract vaccination series in 1997. A sixth dose of pertussis-containing vaccine, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap), was recommended in 2005 for adolescents and adults. Studies examining Tdap vaccine effectiveness (VE) among adolescents who have received all acellular vaccines are limited.
METHODS:
To assess Tdap VE and duration of protection, we conducted a matched case-control study during the 2012 pertussis epidemic in Washington among adolescents born during 1993–2000. All pertussis cases reported from January 1 through June 30, 2012, in 7 counties were included; 3 controls were matched by primary provider clinic and birth year to each case. Vaccination histories were obtained through medical records, the state immunization registry, and parent interviews. Participants were classified by type of pertussis vaccine received on the basis of birth year: a mix of whole-cell and acellular vaccines (1993–1997) or all acellular vaccines (1998–2000). We used conditional logistic regression to calculate odds ratios comparing Tdap receipt between cases and controls.
RESULTS:
Among adolescents who received all acellular vaccines (450 cases, 1246 controls), overall Tdap VE was 63.9% (95% confidence interval [CI]: 50% to 74%). VE within 1 year of vaccination was 73% (95% CI: 60% to 82%). At 2 to 4 years postvaccination, VE declined to 34% (95% CI: 20.03% to 58%).
CONCLUSIONS:
Tdap protection wanes within 2 to 4 years. Lack of long-term protection after vaccination is likely contributing to increases in pertussis among adolescents.”
Links
http://pediatrics.aappublications.org/content/early/2015/04/28/peds.2014-3358
Citations
"Tdap Vaccine Effectiveness in Adolescents During the 2012 Washington State Pertussis Epidemic." Pediatrics 135.6 (2015)