Re-emergence Of Pertussis Research Articles

The Reemergence of Pertussis and Infant Deaths: Is It Time to Immunize Pregnant Women?

The Reemergence of Pertussis and Infant Deaths: Is It Time to Immunize Pregnant Women?

Pertussis after end of a mass vaccination project—End of the “vaccination honey-moon”

After 16 years of no vaccination against pertussis in Sweden, mass vaccination of infants and catch-up vaccination of children up to 10 years with a monocomponent pertussis toxoid vaccine was performed in the Greater Gothenburg area of Sweden between 1995 and 1999. At the end of the project in February 1999, 56% of all 10 year old children born in the Greater Gothenburg area had received 3 doses of the pertussis toxoid. No booster doses were given. This led to a temporary almost complete elimination of the disease. The aim of the present study was to follow the incidence of pertussis after end of the mass vaccination project (1999–2009) as it is reflected by laboratory verified cases (cultures and/or PCR) and pertussis hospitalizations. A reemergence of pertussis was seen from the end of 1999 with a peak in 2004 followed by a decrease when booster doses to both 6 and 10 year old children were introduced in 2005–2006. From July 1, 1999 through December 31, 2009 a total of 1973 cases were diagnosed with culture or PCR. The disease was prevalent in all age groups. The highest documented incidence was seen in infants younger than 12 months. 450 patients with verified pertussis had received 3 doses of the pertussis toxoid vaccine in the mass vaccination project and some other trials (comprising a total of 69,423 children). The mean time from the last dose to the laboratory verification of pertussis was 5 years in these 450 cases. There were 128 hospitalizations, 106 of which were in infants. In conclusion, pertussis is still not eliminated from the area. Booster doses are needed but the numbers and optimal timing are not known.

Pearl Kendrick, Grace Eldering, and the Pertussis Vaccine

In light of the reemergence of pertussis (whooping cough), the pioneering research of Pearl Kendrick and Grace Eldering is worth revisiting. In the 1930s, working in the Michigan Department of Health laboratory in Grand Rapids, Michigan, USA, they began researching a pertussis vaccine. Their research offers an instructive case study of the creative public health research performed in state health department laboratories during the interwar years. State department of health laboratory directors actively promoted research by supporting advanced education; making facilities and funding available for individual projects; and, when possible, procuring new facilities. Using Michigan Department of Health resources and local and federal funding, Kendrick and Eldering developed standardized diagnostic tools; modified and improved extant vaccines; conducted the first successful, large-scale, controlled clinical trial of pertussis vaccine; and participated in international efforts to standardize and disseminate the vaccine. Their model may again offer a promising avenue for groundbreaking research.

Synergic Effect of Genotype Changes in Pertussis Toxin and Pertactin on Adaptation to an Acellular Pertussis Vaccine in the Murine Intranasal Challenge Model

The Bordetella pertussis pertussis toxin and pertactin (Prn) are protective antigens and are contained in acellular pertussis vaccines. Polymorphisms in the A subunit of pertussis toxin (PtxA) and pertactin have been proposed to mediate vaccine resistance and contribute to pertussis reemergence. To test this hypothesis, previous studies compared clinical isolates expressing different alleles for the proteins. However, other virulence factors or virulence factor expression levels also may vary, confounding the analysis. To overcome these limitations, we constructed isogenic mutants of B. pertussis Tohama expressing the alleles ptxA1 or ptxA2 and prn1 or prn2 and compared the efficacies of an acellular pertussis vaccine against the mutants in a mouse model. While the vaccine was effective against all of the B. pertussis strains regardless of the allele expression pattern, the strain expressing ptxA1 and prn2 displayed a survival advantage over the other strains. These results suggest that an allele shift to the ptxA1 prn2 genotype may play a role in the emergence of pertussis in vaccinated populations.

Reducing the risk of pertussis in newborn infants.

Pertussis (whooping cough) is a respiratory tract infection characterised by a paroxysmal cough, caused by Bordetella pertussis, a gram negative coccobacillus. The disease can affect individuals of all ages, even though the most severe complications and mortality occur more frequently in early infancy. Bordetella pertussis is an exclusively human pathogen; hence elimination of the disease by mass vaccination should theoretically be an achievable objective, even though neither natural infection nor vaccination confer permanent immunity. The implementation of well-conducted vaccination strategies in various countries has not prevented the re-emergence of pertussis [1, 2] particularly in 2 age groups: those over 10 years and infants aged less than 5 months [3]. This is the reason why many countries, including Italy, have introduced antipertussis vaccinations for adolescents into the national immunisation schedule. Among the strategies proposed to control pertussis and decrease pathogen circulation, with the aim of reducing the burden of disease in children that have not yet been vaccinated, the international literature presents a number of strategies. Besides the vaccination of adolescents and the replacement of decennial antitetanus and antidiphtheria booster vaccinations with a trivalent diphtheria, tetanus and pertussis vaccine, the “cocoon” strategy is proposed, with the aim to indirectly protect newborn infants through the immunisation of a target population of adults, represented by parents and other potential close contacts, such as grandparents and healthcare workers [4-6]. The goal of this paper is to evaluate the rationale and potential of “cocooning” as a complementary strategy to universal infant and adolescent’s antipertussis vaccination in order to reduce the risk of pertussis in newborn infants, highlighting which healthcare providers are expected to be involved in its implementation.

Estimating the Duration of Pertussis Immunity Using Epidemiological Signatures

Case notifications of pertussis have shown an increase in a number of countries with high rates of routine pediatric immunization. This has led to significant public health concerns over a possible pertussis re-emergence. A leading proposed explanation for the observed increase in incidence is the loss of immunity to pertussis, which is known to occur after both natural infection and vaccination. Little is known, however, about the typical duration of immunity and its epidemiological implications. Here, we analyze a simple mathematical model, exploring specifically the inter-epidemic period and fade-out frequency. These predictions are then contrasted with detailed incidence data for England and Wales. We find model output to be most sensitive to assumptions concerning naturally acquired immunity, which allows us to estimate the average duration of immunity. Our results support a period of natural immunity that is, on average, long-lasting (at least 30 years) but inherently variable.

Re-emergence of pertussis in Slovenia: Time to change immunization policy

The introduction of childhood vaccination has dramatically reduced morbidity and mortality of pertussis in Slovenia. However, despite high vaccination coverage for many decades, reported incidence has increased recently, to the highest incidence of 27.5/100,000 in 2006, a 6.5-times increase in comparison to the previous year. Marked shift in age distribution among reported cases was observed in recent years. In 2006, reported age-specific incidence was relatively high in children 8-12 years old, the highest among 9 years old. Similar to other countries, where children are given pre-school boosters, we also have to consider the revision of the national vaccination policy. A booster dose at school entrance or latest at 8 years of age should be introduced to decrease the transmission of disease among school children and to further reduce the burden of disease among infants.

The Bordetella type III secretion system: its application to vaccine development

B. pertussis is a causative agent of whooping cough (pertussis) in humans. Despite wide-scale vaccination in many countries, there is serious concern about pertussis as a re-emerging disease. Re-emergence of pertussis may be explained by several factors: the short duration of protection by the currently available acellular pertussis vaccine, an increase in asymptomatic adult carriers and expansion of strains with certain antigenic variations which are not covered by currently available vaccines. To develop safer and more efficacious vaccines which confer more prolonged protection, researchers are focusing on identification and characterization of new virulence factors. One candidate for protective antigens is the type III secretion system and its secreted proteins.

The re-emergence of pertussis: implications for diagnosis and surveillance

Pertussis, or whooping cough, a highly contagious disease caused by Bordetella pertussis, is making a comeback globally and nationally in spite of reasonable vaccination coverage. This paper provides an update on laboratory testing methods that assist the confirmation of clinical disease and investigation of outbreaks. Laboratory confirmation of the diagnosis by polymerase chain reaction or serology should be attempted, especially when atypical pertussis is suspected clinically. Genetic and antigenic variations in virulence factors of strains circulating in the population should also be monitored.

Analysis of Bordetella pertussis pertactin and pertussis toxin types from Queensland, Australia, 1999–2003

BackgroundIn Australia two acellular Bordetella pertussis vaccines have replaced the use of a whole cell vaccine. Both of the licensed acellular vaccines contain the following three components; pertussis toxoid, pertussis filamentous haemagglutinin and the 69 kDa pertactin adhesin. One vaccine also contains pertussis fimbriae 2 and 3. Various researchers have postulated that herd immunity due to high levels of pertussis vaccination might be influencing the makeup of endemic B. pertussis populations by selective pressure for strains possessing variants of these genes, in particular the pertactin gene type. Some publications have suggested that B. pertussis variants may be contributing to a reduced efficacy of the existing vaccines and a concomitant re-emergence of pertussis within vaccinated populations. This study was conducted to survey the pertactin and pertussis toxin subunit 1 types from B. pertussis isolates in Queensland, Australia following the introduction of acellular vaccines.MethodsForty-six B. pertussis isolates recovered from Queensland patients between 1999 and 2003 were examined by both DNA sequencing and LightCycler™ real time PCR to determine their pertactin and pertussis toxin subunit 1 genotypes.ResultsPertactin typing showed that 38 isolates possessed the prn1 allele, 3 possessed the prn2 allele and 5 possessed the prn3 allele. All forty-six isolates possessed the pertussis toxin ptxS1A genotype. Amongst the circulating B. pertussis population in Queensland, 82.5% of the recovered clinical isolates therefore possessed the prn1/ptxS1A genotype.ConclusionThe results of this study compared to historical research on Queensland isolates suggest that B. pertussis pertactin and pertussis toxin variants are not becoming more prevalent in Queensland since the introduction of the acellular vaccines. Current prevalences of pertactin variants are significantly different to that described in a number of other countries with high vaccine coverage. Relative paucity of recovered isolates compared to notified infections, due primarily to non culture based pertussis diagnostics is however a confounding factor in the assessment of variant prevalence.

Differences of circulating Bordetella pertussis population in Argentina from the strain used in vaccine production

In Argentina, as in other countries, the number of pertussis cases has been increasing, even in highly vaccinated zones. Many reports suggest that the decline of vaccine efficacy due to antigenic shifts in the circulating Bordetella pertussis might be among the factors that contribute to pertussis re-emergence in different parts of the world. To evaluate the incidence of this factor in Argentina, we decided to characterize the circulating bacteria of an important demographic area of this country in comparison with the strain used for vaccine production. From 1997 to 2003 we collected nasopharyngeal samples from pediatric patients with signs of Bordetella infection hospitalized in the metropolitan area of Buenos Aires and La Plata, Argentina. From these samples we identified 28 B. pertussis, which were characterized by biochemical techniques, PCR, DNA fingerprint, prn and ptx genes sequencing, and lipopolysaccharides (LPS) pattern. BOX-PCR from B. pertussis isolates yielded one cluster containing 13 isolates and some smaller ones, being all fingerprints different from the vaccine strain. Differences between Argentinean circulating bacteria and the vaccine strain were also observed for the Prn and Ptx variants as well as for the LPS pattern. Moreover, this last pattern seemed to change over the years. In addition, we identified two B. bronchiseptica. The presence of this Bordetella species together with the observed differences between circulating B. pertussis and the strain used in vaccine production should be considered for the development of an improved vaccine.

Are vaccination programs and isolate polymorphism linked to pertussis re-emergence?

Whooping cough remains an endemic disease, and the re-emergence of pertussis in older children and adolescents has been reported in several countries, despite high vaccine coverage. Polymorphism of Bordetella pertussis has been observed over time, and some characteristics of pertussis isolates have gradually diverged from the vaccine strains. The present review summarizes the current knowledge on B. pertussis variability in countries with different vaccination programs and discusses its potential impact on the recently observed increased incidence of whooping cough. No direct association between B. pertussis isolate variability and vaccination programs has been observed to date, except for shifts from fimbriae Fim2 to Fim3. More likely explanations for the re-emergence of pertussis include the change in the epidemiology and transmission patterns of pertussis in highly vaccinated populations, and a shift of disease from young children to adolescents and adults due to waning protective immunity.

Pertussis: a concise historical review including diagnosis, incidence, clinical manifestations and the role of treatment and vaccination in management

Pertussis (whooping cough) is a highly contagious acute bacterial disease involving the respiratory tract and is caused mainly by Bordetella pertussis. Since the last decade many developed countries experience a re-emergence of pertussis, even countries that have had high vaccination coverage for ma

Comparison of acellular pertussis vaccines-induced immunity against infection due to Bordetellapertussis variant isolates in a mouse model

A significant increase in the incidence of pertussis in adolescents and adults has been observed in vaccinated populations. Concomitantly, emergence of novel pertussis toxin and pertactin types in circulating Bordetella pertussis isolates was noticed. In this study, immunity induced by acellular vaccines against infection due to isolates expressing different pertactin types and fimbriae was monitored in a mouse model. In accordance with previous studies, the effect of a bicomponent DTPa vaccine on bacterial clearance was lower when compared with tri- or pentavalent DTPa vaccines. Whatever the isolates used to infect mice, the tri- or pentavalent DTPa vaccines were both efficacious in inducing immunity that resulted in clearance of infection. These findings suggest that re-emergence of pertussis might not be related to emergence of isolates escaping vaccine protection. The present study reduces potential concerns about acellular vaccine efficacy, but frequent monitoring of protection and surveillance of the evolution of the B. pertussis population remains of particular importance.

Bordetella pertussisIsolates, Finland

<i>Bordetella pertussis</i>Isolates, Finland

The reemergence of pertussis in immunized populations: a case study.

To present a case of classical pertussis occurring in previously vaccinated male siblings, 11 and 13 years of age, living in El Paso TX; also to present an overview and update of the changing epidemiology of pertussis including pathophysiology, diagnosis, and treatment. Nasopharyngeal swabs and blood samples were collected from two male siblings, 11 and 13 years of age, presenting with cold-like symptoms and persistent cough during the second week of infection. Nasopharyngeal swabs were plated onto Bordet-Gengou agar plates and incubated for 48 hours. Blood samples were analyzed for the presence of antibodies (IgM and IgA) against Bordetella pertussis antigens using indirect enzyme linked immunosorbent assay (ELISA). Cultures and serological analysis was conducted at the University of Texas at El Paso, Clinical Laboratory Science Program Research facility. Bacterial cultures of both children were positive for Bordetella pertussis and the sera revealed positive IgM and IgA antibodies (> 11 PANBIO UNITS) against a mixture of antigens including: pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae. Pertussis immunity wanes overtime, leaving most adolescents and adults susceptible to infection. Physicians must be prepared to diagnose and treat pertussis in any age group regardless of vaccination status.

Temporal trends in circulating Bordetella pertussis strains in Australia.

Australia experienced a resurgence of pertussis in the 1990s despite improved vaccine coverage. Although much of the increase was attributable to increased detection of cases in older persons with waning immunity by serology, vaccine changes or alterations in circulating Bordetella pertussis strains may also have contributed. We determined the frequency of variants of B. pertussis pertactin (prn), and pertussis toxin subunit 1 (ptxS1) genes, restriction fragment length polymorphism (RFLP) types and fimbrial serotypes prevalent in Australia prior to, and during the 1990s. Ampoules of the whole-cell vaccine in use prior to 1999 and 84 B. pertussis isolates stored between 1967 and 1998 by laboratories around Australia were analysed. One pertactin allele, Prn3, not detected before 1985, was found in 24 out of 57 (42%) isolates between 1989 and 1998 (P<0.0001). PtxS1A was found in all isolates. IS1002 type 29, found in 17 out of 31 (55%) isolates tested, was the predominant RFLP type. The only difference in fimbrial serotype distribution between the time-periods was an increase in serotype 3 (P=0.054). The whole-cell vaccine contained only the alleles prn1 and ptxS1A. Antigenic shift in B. pertussis may have contributed to the re-emergence of pertussis in Australia. Monitoring these trends will be important as acellular vaccines are introduced and changes are made to pertussis vaccine schedules.

Which strategy for pertussis vaccination today?

Pertussis (whooping cough) remains an epidemic disease responsible for infant and child morbidity and mortality, and is perceived as a serious public health problem. Since the widespread use of whole-cell pertussis vaccines in the 1940s, vaccination programs have varied greatly between countries. National specificity is a function of several factors. The most important are: vaccine efficacy and tolerability;vaccine coverage and distribution; and vaccine acceptance by parents and professionals. During the 1970s, Sweden, England, Wales and Japan provided contrasting examples of the attitude of health authorities to the use of whole-cell vaccines. The increase in pertussis incidence was noted as a consequence of active opposition to this vaccine. The re-emergence of pertussis in the 1990s, in countries with high vaccination coverage and increased incidence of disease in individuals >15 years and <6 months of age, has drawn attention to the role of booster doses of pertussis vaccines and their introduction into regular vaccination programs. The use of acellular vaccines for booster doses for adolescents and adults would seem unambiguous because of their decreased reactogenicity, although the exact schedule has yet to be established. The choice between the two kinds of vaccines is more difficult for primary courses, where safety and efficacy profiles are similar, and the attitude towards acellular vaccines varies from country to country. In this case, the strategy adopted results from the national history of pertussis infection and from the quality of the available whole-cell vaccine. Two contrasting examples are the US, where acellular vaccines were licensed for the primary series in the 1990s, and the UK, where whole-cell vaccines are exclusively used for primary immunization. The changing epidemiology of pertussis, and its local diversification, would suggest that at present it is difficult to define a single worldwide strategy with only one kind of vaccine and one schedule. In order to control pertussis incidence, each country should continue to determine the best national vaccination program established in very close relation to the past and present epidemiological situation and available healthcare resources.

Role of the polymorphic region 1 of the Bordetella pertussis protein pertactin in immunity.

In several countries pertussis is re-emerging, despite a high vaccination coverage. It is suggested that antigenic divergence between Bordetella pertussis vaccine strains and circulating strains, in particular with respect to pertactin, has contributed to pertussis re-emergence. Polymorphism in pertactin is essentially limited to region 1, which is composed of repeats and is located adjacent to an Arg-Gly-Asp motif implicated in adherence. Evidence is provided for the immunological relevance of polymorphism in region 1. Region 1 was found to contain a B-cell epitope recognized in both humans and mice. Furthermore, variation in region 1 affected antibody binding and, in a mouse respiratory infection model, the efficacy of a whole-cell vaccine. Moreover, passive and active immunization indicated that region 1 confers protective immunity. An mAb directed against a linear conserved epitope conferred cross-immunity against isolates with distinct pertactin variants. The results indicate an important role of region 1 of pertactin in immunity.

Genotypic variation in the Bordetella pertussis virulence factors pertactin and pertussis toxin in historical and recent clinical isolates in the United Kingdom.

The reemergence of pertussis has been reported in several countries despite high vaccination coverage. Studies in The Netherlands and Finland have investigated polymorphism in the genes coding for two important virulence factors of Bordetella pertussis, pertactin and pertussis toxin, and identified the emergence and subsequent dominance in circulating strains of pertactin and toxin variants not found in the whole-cell vaccine (WCV). The study described here investigated whether such variation had occurred in the United Kingdom, which presently has low levels of pertussis. Sequence analysis of the genes for pertactin (prnA) and the pertussis toxin S1 subunit (ptxA) among isolates of B. pertussis from 285 United Kingdom patients, from 1920 to 1999, revealed three prnA variants, prnA(1), prnA(2), and prnA(3), and two ptxA variants, ptxA(1) and ptxA(2), showing differences in nucleic acid sequence. The proportion of pertactin gene types not included in the United Kingdom WCV, i.e., prnA(2) and prnA(3), has increased in recent years and was found in 21 of 86 (24%) strains from the 1980s and 56 of 105 (53%) strains from the 1990s. To date, the presence of these nonvaccine prnA types has not been associated with a resurgence of pertussis in the United Kingdom. The distribution of prnA and ptxA types in The Netherlands, Finland, and the United Kingdom in the 1990s is distinct. The most striking difference in the United Kingdom isolates is that all 105 of the most recent circulating strains (from 1998 to 1999) are of a pertussis toxin type found in the United Kingdom WCV, i.e., ptxA(1).