Pertussis Infection in Fully Vaccinated Children in Day-Care Centers, Israel

Pertussis Infection in Fully Vaccinated Children in Day-Care Centers, Israel

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Isaac Srugo*Comments to Author , Daniel Benilevi*, Ralph Madeb*, Sara Shapiro†, Tamy Shohat‡, Eli Somekh§, Yossi Rimmar*, Vladimir Gershtein†, Rosa Gershtein*, Esther Marva¶, and Nitza Lahat†
Author affiliations: *Department of Clinical Microbiology, Bnai Zion Medical Center, Haifa, Israel; †Serology Laboratory, Carmel Medical Center, Haifa, Israel; ‡Israel Center for Disease Control, Tel Aviv, Israel; §Wolfson Medical Center, Tel Aviv, Israel; ¶Public Health Laboratories, Jerusalem, Israel

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Abstract

We tested 46 fully vaccinated children in two day-care centers in Israel who were exposed to a fatal case of pertussis infection. Only two of five children who tested positive for Bordetella pertussis met the World Health Organization’s case definition for pertussis. Vaccinated children may be asymptomatic reservoirs for infection.

Pertussis, an acute disease of the upper respiratory tract caused by the gram-negative bacillus Bordetella pertussis, lasts 6 to 8 weeks and has three clinical stages. The initial (catarrhal) stage resembles a common cold with a mild cough. The second (paroxysmal) stage is characterized by episodes of repetitive coughing during a single expiration, followed by a sudden inspiration that generates the typical “whoop.” The final (convalescent) stage, which lasts 1 to 2 weeks, marks a decrease in the severity and frequency of the cough.

Since the introduction of routine childhood vaccine, pertussis has been considered preventable, and pertussis-associated illness and deaths are uncommon (2). However, vaccine-induced immunity wanes after 5 to 10 years, making the vaccinated host vulnerable to infection (3). This susceptibility has been described in outbreaks of pertussis infection in highly vaccinated populations (36).

A recent study by Yaari et al. showed that infection in a vaccinated person causes milder, nonspecific disease, without the three classical clinical stages(7). Whooping cough is seen in only 6% of such cases; instead, the illness is characterized by a nonspecific, prolonged cough, lasting several weeks to months. Because of these atypical symptoms, pertussis infection is underdiagnosed in adults and adolescents, who may be reservoirs for infection of unvaccinated infants (810). In a study in France, up to 80% of infections in unvaccinated children were acquired from siblings and parents, suggesting that adults and even young siblings play a fundamental role in the transmission of pertussis (11).

We demonstrated B. pertussis infection in fully vaccinated children ages 2-3 years and 5-6 years who had contact with an infected child. We investigated whether younger or recently vaccinated children may be protected from classical clinical illness but remain susceptible to infection and become asymptomatic carriers.

The Study

We examined the family of a 4-month-old infant who died of pertussis in Israel, as well as children at two day-care centers that two siblings had attended during the infant’s illness. The two siblings, ages 2 and 5 years, attended different day-care centers, for ages 2-3 years and 5-6 years, respectively. Both siblings continued to attend the centers despite paroxysmal cough for 4 to 5 weeks. Thirty other children attended the day-care center for the 2- to 3-year-old group. Sixteen other children attended the center for the 5- to 6-year-old group.

Thumbnail of Timeline of pertussis infection in children in two day-care centers, IsraelFigure. Timeline of pertussis infection in children in two day-care centers, Israel

In the infant’s family, a third sibling, age 11 years, also had a paroxysmal cough of 4 to 5 weeks duration. The 35-year-old mother had a 3-month history of persistent cough. An 18-year-old aunt, who took care of the infant and lived in the same house, reported a mild respiratory illness without paroxysmal cough. None of the family members had a whooping episode, cyanosis, or pneumonia (Figure).

All the children in the day-care centers had been immunized in infancy with all four doses of Pasteur diphtheria-tetanus toxoid pertussis (DTP) vaccine, which includes a booster dose at 12 months of age. The Pasteur vaccine contains 1 immunization dose (ID) of purified diphtheria toxoid, 1 ID of purified tetanus toxoid, and >4 IU of B. pertussis. All family members of the infant were also fully vaccinated with four doses of DTP. The infant had received only the first dose of vaccine at 2 months of age.

The five family members of the infant and the 46 children in the two day-care centers were tested for B. pertussis. Two nasopharyngeal specimens were taken with Dacron swabs (Medical Wire, MEDECO, Corsham, UK); one specimen was used for culture and the other for polymerase chain reaction (PCR) testing. The culture specimen was immediately spread on charcoal agar plates (Hy Labs, Rehovot, Israel), which were incubated at 37°C for 14 days. Serum samples were also taken from every study participant for specific testing for immunoglobulin (Ig) M, IgA, and IgG antibodies to B. pertussis by an enzyme immunoassay (EIA) with whole-cell antigens (Panbio, East Brisbane, Australia) (12). Primers for the repeated insertion sequences were used in a semi-nested PCR assay (1314). The upstream primer sequence gATTCAATAggTTgTATgCATggTT and downstream primer AATTgCTggACCAT TCgAgTCgACG were used in the first PCR, which included 5 µL sample DNA, reaction buffer (10 mM Tris-HCl, 50 mM KCl, 1.5 mM MgCl2, 0.1% Triton X-100), 1 µM of each primer, 200 µM deoxynucleotide triphosphate, and 1 U Taq polymerase (Boehringer Mannheim, Germany) in a 25-µL volume (14). Statistical analysis was performed by the two-tailed Fischer’s exact test.

A person with positive PCR results was considered to have B. pertussis colonization of the nasopharynx. A person with positive IgM serum antibodies was considered to have had a recent infection. There were no culture-positive results, and nasopharyngeal aspirates were not available from the infant. Positivity by PCR or IgM did not indicate presence of symptoms.

Information on clinical symptoms was obtained from each person by a detailed questionnaire. The children in the day-care centers were followed clinically for 8 weeks after laboratory testing. All family members had been treated with erythromycin before testing, but no antibiotics were administered to the children in the day-care centers.

Eleven percent of the children in the two day-care centers were PCR positive, indicating nasopharyngeal colonization: 4 (25%) of the 16 5- to 6-year-old and 1 (3%) of the 30 2- to 3-year-old children (p <.05). Nine (55%) 5- to 6-year-old children were positive for serum IgM antibodies, and 4 (25%) were IgA positive. Three (10%) of the 2- to 3-year-old children were IgM positive, and 1 (3%) had IgA antibodies. Nasopharyngeal colonization was found more frequently in the 5- to 6-year-old than in the 2- to 3-year-old children (4/16 vs. 1/30, p <.05). This trend was also constant with IgM and IgA serum antibodies (9/16 vs. 3/30, p <.001 and 4/16 vs. 0/30, p <.01, respectively). In the index family, four of five members were positive by PCR, including all three siblings of the infant and the 18-year-old aunt. The 35-year-old mother, who was treated with erythromycin before testing, was negative by PCR. All five family members, including the mother, had high levels of IgM antibodies, indicating recent infection. The 4-month-old infant was seronegative for all subclasses of Ig antibodies to B. pertussis. No cultures were grown from the three groups.

According to a modified World Health Organization (WHO) case definition, two (11%) of the five children colonized with B. pertussis in the two day-care centers had the typical course of pertussis infection, with 3 weeks of paroxysmal cough (Table) (1). The other three children who were positive by PCR had only a mild, nonspecific cough during follow-up.

Conclusions

The effects of whole-cell pertussis vaccine wane after 5 to 10 years, and infection in a vaccinated person causes nonspecific symptoms (37). Vaccinated adolescents and adults may serve as reservoirs for silent infection and become potential transmitters to unprotected infants (311). The whole-cell vaccine for pertussis is protective only against clinical disease, not against infection (1517). Therefore, even young, recently vaccinated children may serve as reservoirs and potential transmitters of infection.

We used PCR, EIA, and culture to confirm B. pertussis infection in two highly vaccinated groups of children in two day-care centers. Three (10%) of 30 2- to 3-year-old children were seropositive for recent infection; one had nasopharyngeal colonization and a clinical illness that met the modified WHO case definition. In the day-care center for the 5- to 6-year-old group, 9 (55%) of 16 children were IgM positive, 4 (25%) of whom had nasopharyngeal colonization. Of these four children, three had nonspecific cough, and only one met the modified WHO definition for pertussis. None of the children in our study, including those who met the WHO definition, had been examined by a physician before our investigation.

Children who were seropositive and remained both asymptomatic and PCR negative probably had sufficient immunity from vaccines or natural boosters to protect them against persistent colonization and clinical disease. Their seropositivity could not be due to vaccine because the children were tested more than a year after having been vaccinated. Yet not all the children were protected from infection and from colonization with the bacteria. Whether a child who is serologically or PCR positive for pertussis and is clinically asymptomatic is a potential transmitter of infection has not been established. What is certain, however, is that vaccine-induced immunity against infection does not persist throughout adulthood. In France, booster vaccinations have been recommended for adolescents and teenagers (18). We found that immunity does not even persist into early childhood in some cases. We also observed that DPT vaccine does not fully protect children against the level of clinical disease defined by WHO. Our results indicate that children ages 5-6 years and possibly younger, ages 2-3 years, play a role as silent reservoirs in the transmission of pertussis in the community. More studies are needed to find the immunologic basis of protection against infection and colonization and thus an effective way to eradicate pertussis.

Dr. Srugo is a senior lecturer and director of the Clinical Microbiology and Pediatric Infectious Disease unit at the Bnai Zion Medical Center, Haifa, Israel.

References

  1. WHO meeting on case definition of pertussis: Geneva 10-11 January, 1991. Geneva: World Health Organization, 1991:4-5 (issue no. MIN/EPI/PERT/91.1)

  2. Cherry JD. The epidemiology of pertussis and pertussis immunization in the United Kingdom and the United States: a comparative study. Curr Probl Pediatr. 1984;14:178. DOIPubMed

  3. Jenkinson D. Duration of effectiveness of pertussis vaccine: evidence from 10-year community study. [Clin Res Ed]. BMJ. 1988;296:6124.DOIPubMed

  4. Christie CD, Marx ML, Marchant CD, Reising SF. The 1993 epidemic of pertussis in Cincinnati: resurgence of disease in a highly immunized population of children. N Engl J Med. 1994;331:1621. DOIPubMed

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  8. Aoyama T, Takeuchi Y, Goto A, Iwai H, Murase Y, Iwata T. Pertussis in adults. Am J Dis Child. 1992;146:1636.PubMed

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  14. Lichtinghagen R, Diedrich-Glaubitz R, von Horsten B. Identification of Bordetella pertussis in nasopharyngeal swabs using a polymerase chain reaction: evaluation of detection methods. Eur J Clin Chem Clin Biochem. 1994;32:1617.PubMed

  15. Fine PEM, Clarkson JA. The recurrence of whooping cough: possible implications for assessment of vaccine efficacy. Lancet. 1982;l:6669.DOIPubMed

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  17. Minh NNTM, He Q, Edelman K, Olander RM, Viljanen MK, Arvilommi H, Cell-mediated immune response to antigens of Bordetella pertussis and protection against pertussis in schoolchildren. Pediatr Infect Dis J. 1999;18:36670. DOIPubMed

  18. Grimprel E, Baron S, Levy-Bruhl D, Garnier JM, N’jamkepo E, Guiso N, Influence of vaccination coverage on pertussis transmission in France.Lancet. 1999;354:1699700. DOIPubMed

Figure

Table

Suggested citation: Srugo I, Benilevi D, Madeb R, Shaprio S, Shohat T, Somekh E, et al. Pertussis Infection in Fully Vaccinated Children in Day-Care Centers, Israel. Emerg Infect Dis [serial on the Internet]. 2000, Oct [date cited]. Available from http://wwwnc.cdc.gov/eid/article/6/5/00-0512

DOI: 10.3201/eid0605.000512

Table of Contents – Volume 6, Number 5—October 2000

Article copied from CDC.GOV

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British Court Throws Out Conviction of Autism/Vaccine MD: Andrew Wakefield’s Co-Author Completely Exonerated

British Court Throws Out Conviction of Autism/Vaccine MD: Andrew Wakefield’s Co-Author Completely Exonerated

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Autism Action Network

In a stunning reversal, world renowned pediatric gastroenterologist Prof. John Walker-Smith won his appeal against the United Kingdom’s General Medical Council regulatory board that had ruled against both him and Andrew Wakefield for their roles in the 1998 Lancet MMR paper, which raised questions about a link to autism. The complete victory means that Walker-Smith has been returned to the status of a fully licensed physician in the UK, although he had already retired in 2001 — six years before the GMC trial even began.

Justice John Mitting ruled on the appeal by Walker-Smith, saying that the GMC “panel’s determination cannot stand. I therefore quash it.” He said that its conclusions were based on “inadequate and superficial reasoning and, in a number of instances, a wrong conclusion.” The verdict restores Walker-Smith’s name to the medical register and his reputation to the medical community. This conclusion is not surprising, as the GMC trial had no actual complainants, no harm came to the children who were studied, and parents supported Walker-Smith and Wakefield through the trial, reporting that their children had medically benefited from the treatment they received at the Royal Free Hospital.

While John Walker-Smith received funding to appeal the GMC decision from his insurance carrier, his co-author Andrew Wakefield did not — and was therefore unable to mount an appeal in the high court. This year, however, Dr. Wakefield, who now conducts his research in the US, has filed a defamation lawsuit against Brian Deer, Fiona Godlee and the British Medical Journal for falsely accusing him of “fraud.” The suit is currently underway in Texas, where Wakefield now lives. The ruling today bodes well for Dr. Wakefield’s suit against Deer, on whose reporting the entire GMC hearing was based.

In 1998 the Lancet published a case series on twelve children receiving treatment for bowel dysfunction at the Royal Free Hospital in London. The paper called for further study of a possible association between bowel disease and developmental delay, including cases of autism. It also noted that eight of the children’s gastrointestinal and autistic symptoms began shortly after they received the MMR vaccination. The verdict today raises questions about whether or not the Lancet should have retracted the paper after the GMC decision, as the reasons for its retraction have now been contradicted by the judge’s decision.

The thirteen original co-authors of the 1998 Lancet case series were members of the Royal Free’s Inflammatory Bowel Disease Study Group. In 2004, under pressure from the British medical establishment, ten of the co-authors signed a letter retracting an interpretation of the paper that it proved that vaccines caused autism, which the paper never actually claimed in the first place. John Walker-Smith, Andrew Wakefield and Dr. Simon Murch were subsequently brought up on misconduct charges before the GMC. The proceedings resulted in Walker-Smith and Wakefield being found guilty and being “struck off” the medical register, while Dr. Murch retained his status as a physician. Wakefield was then vilified by corporate media and by bloggers eager to repeat scandal and engage in industry protectionism, rather than investigate the complicated facts of the story.

Today, almost 14 years after the paper was published, the high court determined that John Walker-Smith was innocent of the wrongdoing alleged by the GMC. Judge Mitting reported that the GMC, “on the basis of sensible instructions, does not invite me to remit it to a fresh Fitness to Practice panel for redetermination. The end result is that the finding of serious professional misconduct and the sanction of erasure are both quashed.”

British parents from the group CryShame, which includes parents of the Lancet 12, issued a statement saying that they “welcome with immense relief the end of the eight year ordeal of Prof John Walker-Smith and the quashing of all substantive charges against him in the High Court, and wish him their heartfelt congratulations at finally clearing his name.”

“Though justice has finally prevailed for Prof. Walker-Smith, the damage done to him and his colleagues has been incalculable,” said Mark Blaxill, chairman of the Canary Party. “The UK government must investigate the corruption in the GMC, which has severely damaged the reputations of good, honest doctors. Most of all, it’s outrageous that Dr. Andrew Wakefield has been vilified by government officials, vaccine manufacturers and physician organizations, and that the media has accepted these unfounded accusations uncritically.”

“It’s time that we started treating responsible parents as reliable witnesses to serious adverse reactions to medical procedures such as vaccination,” said Jennifer Larson, president of the Canary Party. “The work that Walker-Smith and his colleagues at the Royal Free Hospital did with the Lancet 12 was medically necessary and above reproach. No patient complained, and the charges against the Royal Free team came only from a freelance journalist writing for a Rupert Murdoch newspaper. Meanwhile, the findings reported in the Lancet paper have been replicated in numerous scientific publications and reported by thousands of parents all over the world.”

“It is quite obvious to me that James Murdoch, Brian Deer and GlaxoSmithKline orchestrated the smear attack on Dr. Andrew Wakefield,” said Ginger Taylor, executive director of the Canary Party. “A judge has now ruled that the GMC hearings were a farce. Parents are waiting for journalists to find their spine and start some honest reporting on the character assassination of doctors that is blocking medical treatments for vaccine injured children, and the role that GSK and Merck may be playing to protect their profits on the MMR vaccine. The Canary Party honors and stands by doctors of integrity like Prof. Walker-Smith, who continue to fight and defend their hard-won reputations for going the extra mile to investigate and improve the chronic, difficult-to-treat cases that now permeate our society.”

– See more at: http://healthimpactnews.com/2012/british-court-throws-out-conviction-of-autismvaccine-md-andrew-wakefields-co-author-completely-exonerated/#sthash.kzD9hwbK.BxpyaB7I.dpuf

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