Vaccine-resistant pertussis strains found in Philadelphia

WASHINGTON – Vaccine-resistant isolates of Bordetella pertussis have appeared in Philadelphia – the first such strains to be seen in the United States.

Of 30 samples analyzed, 18 (60%) showed a variant that conferred resistance to the current vaccine formulation, Dr. Jennifer Vodzak said at the annual meeting of the Pediatric Academic Societies. The strains had developed two different mutations, each of which deleted their expression of pertactin, an outer membrane protein that helps the bacteria adhere to respiratory epithelium. Pertactin is used as an antigen in the acellular pertussis component of the Tdap vaccine.

"It seems that, responding to vaccine pressure, B. pertussis has acquired several adaptations to halt the production of pertactin," said Dr. Vodzak, an infectious disease specialist at St. Christopher’s Hospital for Children, Philadelphia.

For the past decade, pertactin-negative strains have been reported in Japan, France, and Finland. Although the bacteria lack pertactin, French studies have shown that they are just as virulent as the nonmutated strains. The bacteria have simply found a way to cause disease without that particular protein.

Dr. Vodzak and her colleagues first reported their findings in a brief correspondence to the New England Journal Medicine in February. At that time, 11 of 12 isolates cultured from 2011 and 2012 expressed the pertactin variants. Seven expressed stop codons that truncated the protein, and four expressed insertion sequences that disrupted the pertactin coding region. The investigators also noted that these mutations appeared to be unique and not related to those seen in other countries.

Since then, the team has expanded its search, attempting to pinpoint the time these variants first appeared. To do that, they randomly selected 70 samples taken from Philadelphia patients who had culture-proven pertussis from 2007 to 2012. Most (80%) of the samples were from hospitalized patients, the majority of whom (87%) were younger than 1 year. More than half of the patients were younger than 3 months old. So far, 30 of the isolates have been molecularly examined.

After pertussis immunization became widespread in the 1940s, the disease incidence dropped dramatically in the United States. But in the mid-1990s – shortly after the acellular vaccine was introduced in 1991 – a gradual resurgence began. The incidence really picked up in the early 2000s, when annual case reports jumped into the tens of thousands. There were 18,719 cases reported in 2011; in 2012, that number more than doubled, to 41,880 – the highest since 1955.

The rise in cases was temporally related to the initiation of the acellular vaccine, which carries the pertactin antigen. The acellular vaccine also confers a limited immunogenicity. This limited protection and increased surveillance and reporting – not the acellular pertactin-containing vaccine –have caused the rise in cases, according to the Centers for Disease Control and Prevention.

"It does not appear that these strains are the reason the United States has experienced a dramatic increase in the number of reported pertussis cases recently," the agency says on its pertussis pages. "But CDC will continue to closely monitor the situation before drawing any conclusions. There is also no suggestion that these new strains are causing more severe cases of pertussis," or that the mutated strains carry any antibiotic resistance.

The appearance of pertactin-negative strains does seem to parallel the recent jump in cases, but as yet there are no hard data linking these three occurrences, Dr. Vodzak said.

Right now, she added, there’s no way to know if – or when – similar pertactin-negative strains have developed elsewhere in the United States. She and her team are encouraging public health agencies to test their stored samples so a more complete picture can be drawn.

"It will be important to consider the pathogen’s adaptations as we consider both the decreased vaccine effectiveness and vaccine development," she said. "I think the next step is to look at the clinical picture of these variants."

Dr. Vodzak said she had no relevant financial disclosures. Her coauthor, Anne Marie Queenan, Ph.D., is an employee of Janssen Research and Development.

msullivan@frontlinemedcom.com

WASHINGTON – Vaccine-resistant isolates of Bordetella pertussis have appeared in Philadelphia – the first such strains to be seen in the United States.

Of 30 samples analyzed, 18 (60%) showed a variant that conferred resistance to the current vaccine formulation, Dr. Jennifer Vodzak said at the annual meeting of the Pediatric Academic Societies. The strains had developed two different mutations, each of which deleted their expression of pertactin, an outer membrane protein that helps the bacteria adhere to respiratory epithelium. Pertactin is used as an antigen in the acellular pertussis component of the Tdap vaccine.

"It seems that, responding to vaccine pressure, B. pertussis has acquired several adaptations to halt the production of pertactin," said Dr. Vodzak, an infectious disease specialist at St. Christopher’s Hospital for Children, Philadelphia.

For the past decade, pertactin-negative strains have been reported in Japan, France, and Finland. Although the bacteria lack pertactin, French studies have shown that they are just as virulent as the nonmutated strains. The bacteria have simply found a way to cause disease without that particular protein.

Dr. Vodzak and her colleagues first reported their findings in a brief correspondence to the New England Journal Medicine in February. At that time, 11 of 12 isolates cultured from 2011 and 2012 expressed the pertactin variants. Seven expressed stop codons that truncated the protein, and four expressed insertion sequences that disrupted the pertactin coding region. The investigators also noted that these mutations appeared to be unique and not related to those seen in other countries.

Since then, the team has expanded its search, attempting to pinpoint the time these variants first appeared. To do that, they randomly selected 70 samples taken from Philadelphia patients who had culture-proven pertussis from 2007 to 2012. Most (80%) of the samples were from hospitalized patients, the majority of whom (87%) were younger than 1 year. More than half of the patients were younger than 3 months old. So far, 30 of the isolates have been molecularly examined.

After pertussis immunization became widespread in the 1940s, the disease incidence dropped dramatically in the United States. But in the mid-1990s – shortly after the acellular vaccine was introduced in 1991 – a gradual resurgence began. The incidence really picked up in the early 2000s, when annual case reports jumped into the tens of thousands. There were 18,719 cases reported in 2011; in 2012, that number more than doubled, to 41,880 – the highest since 1955.

The rise in cases was temporally related to the initiation of the acellular vaccine, which carries the pertactin antigen. The acellular vaccine also confers a limited immunogenicity. This limited protection and increased surveillance and reporting – not the acellular pertactin-containing vaccine –have caused the rise in cases, according to the Centers for Disease Control and Prevention.

"It does not appear that these strains are the reason the United States has experienced a dramatic increase in the number of reported pertussis cases recently," the agency says on its pertussis pages. "But CDC will continue to closely monitor the situation before drawing any conclusions. There is also no suggestion that these new strains are causing more severe cases of pertussis," or that the mutated strains carry any antibiotic resistance.

The appearance of pertactin-negative strains does seem to parallel the recent jump in cases, but as yet there are no hard data linking these three occurrences, Dr. Vodzak said.

Right now, she added, there’s no way to know if – or when – similar pertactin-negative strains have developed elsewhere in the United States. She and her team are encouraging public health agencies to test their stored samples so a more complete picture can be drawn.

"It will be important to consider the pathogen’s adaptations as we consider both the decreased vaccine effectiveness and vaccine development," she said. "I think the next step is to look at the clinical picture of these variants."

Dr. Vodzak said she had no relevant financial disclosures. Her coauthor, Anne Marie Queenan, Ph.D., is an employee of Janssen Research and Development.

msullivan@frontlinemedcom.com

WASHINGTON – Vaccine-resistant isolates of Bordetella pertussis have appeared in Philadelphia – the first such strains to be seen in the United States.

Of 30 samples analyzed, 18 (60%) showed a variant that conferred resistance to the current vaccine formulation, Dr. Jennifer Vodzak said at the annual meeting of the Pediatric Academic Societies. The strains had developed two different mutations, each of which deleted their expression of pertactin, an outer membrane protein that helps the bacteria adhere to respiratory epithelium. Pertactin is used as an antigen in the acellular pertussis component of the Tdap vaccine.

"It seems that, responding to vaccine pressure, B. pertussis has acquired several adaptations to halt the production of pertactin," said Dr. Vodzak, an infectious disease specialist at St. Christopher’s Hospital for Children, Philadelphia.

For the past decade, pertactin-negative strains have been reported in Japan, France, and Finland. Although the bacteria lack pertactin, French studies have shown that they are just as virulent as the nonmutated strains. The bacteria have simply found a way to cause disease without that particular protein.

Dr. Vodzak and her colleagues first reported their findings in a brief correspondence to the New England Journal Medicine in February. At that time, 11 of 12 isolates cultured from 2011 and 2012 expressed the pertactin variants. Seven expressed stop codons that truncated the protein, and four expressed insertion sequences that disrupted the pertactin coding region. The investigators also noted that these mutations appeared to be unique and not related to those seen in other countries.

Since then, the team has expanded its search, attempting to pinpoint the time these variants first appeared. To do that, they randomly selected 70 samples taken from Philadelphia patients who had culture-proven pertussis from 2007 to 2012. Most (80%) of the samples were from hospitalized patients, the majority of whom (87%) were younger than 1 year. More than half of the patients were younger than 3 months old. So far, 30 of the isolates have been molecularly examined.

After pertussis immunization became widespread in the 1940s, the disease incidence dropped dramatically in the United States. But in the mid-1990s – shortly after the acellular vaccine was introduced in 1991 – a gradual resurgence began. The incidence really picked up in the early 2000s, when annual case reports jumped into the tens of thousands. There were 18,719 cases reported in 2011; in 2012, that number more than doubled, to 41,880 – the highest since 1955.

The rise in cases was temporally related to the initiation of the acellular vaccine, which carries the pertactin antigen. The acellular vaccine also confers a limited immunogenicity. This limited protection and increased surveillance and reporting – not the acellular pertactin-containing vaccine –have caused the rise in cases, according to the Centers for Disease Control and Prevention.

"It does not appear that these strains are the reason the United States has experienced a dramatic increase in the number of reported pertussis cases recently," the agency says on its pertussis pages. "But CDC will continue to closely monitor the situation before drawing any conclusions. There is also no suggestion that these new strains are causing more severe cases of pertussis," or that the mutated strains carry any antibiotic resistance.

The appearance of pertactin-negative strains does seem to parallel the recent jump in cases, but as yet there are no hard data linking these three occurrences, Dr. Vodzak said.

Right now, she added, there’s no way to know if – or when – similar pertactin-negative strains have developed elsewhere in the United States. She and her team are encouraging public health agencies to test their stored samples so a more complete picture can be drawn.

"It will be important to consider the pathogen’s adaptations as we consider both the decreased vaccine effectiveness and vaccine development," she said. "I think the next step is to look at the clinical picture of these variants."

Dr. Vodzak said she had no relevant financial disclosures. Her coauthor, Anne Marie Queenan, Ph.D., is an employee of Janssen Research and Development.

msullivan@frontlinemedcom.com