Understanding the impact of adult pertussis and current approaches to vaccination: A narrative review and expert panel recommendations.

Pertussis has several notable consequences, causing economic burden, increased strain on healthcare facilities, and reductions in quality of life. Recent years have seen a trend toward an increase in pertussis cases affecting older children and adults. To boost immunity, and protect vulnerable populations, an enduring approach to vaccination has been proposed, but gaps remain in the evidence surrounding adult vaccination that are needed to inform such a policy. Gaps include: the true incidence of pertussis and its complications in adults; regional variations in disease recognition and reporting; and incidence of severe disease, hospitalizations, and deaths in older adults. Better data on the efficacy/effectiveness of pertussis vaccination in adults, duration of protection, and factors leading to poor vaccine uptake are needed. Addressing the critical evidence gaps will help highlight important areas of unmet need and justify the importance of adult pertussis vaccination to healthcare professionals, policymakers, and payers.

Clinical definitions of pertussis: Summary of a Global Pertussis Initiative roundtable meeting, February 2011.

Existing clinical case definitions of pertussis are decades old and based largely on clinical presentation in infants and children, yet an increasing burden is borne by adolescents and adults who may manifest distinct signs/symptoms. Therefore, a "one-size-fits-all" clinical case definition is no longer appropriate. Seeking to improve pertussis diagnosis, the Global Pertussis Initiative (GPI) developed an algorithm that delineates the signs/symptoms of pertussis most common to 3 age groups: 0-3 months, 4 months to 9 years, and ≥10 years. These case definitions are based on clinical presentation alone, but do include recommendations on laboratory diagnostics. Until pertussis can be accurately diagnosed, its burden will remain underestimated, making the introduction of epidemiologically appropriate preventive strategies difficult. The proposed definitions are intended to be widely applicable and to encourage the expanded use of laboratory diagnostics. Determination of their utility and their sensitivity and/or specificity versus existing case definitions is required.

Vaccination in Pregnancy against Pertussis: A Consensus Statement on Behalf of the Global Pertussis Initiative.

Infants are at high risk for severe morbidity and mortality from pertussis disease during early infancy. Vaccination against pertussis in pregnancy has emerged as the ideal strategy to protect infants during these early, vulnerable, first months of life. On 30 November and 1 December 2021, the Global Pertussis Initiative held a meeting that aimed to discuss and review the most up-to-date scientific literature supporting vaccination against pertussis in pregnancy and outstanding scientific questions. Herein, we review the current and historically published literature and summarize the findings as consensus statements on vaccination against pertussis in pregnancy on behalf of the Global Pertussis Initiative.

The global pertussis initiative: Meeting report from the Regional Latin America Meeting, Costa Rica, 5-6 December, 2008.

Pertussis remains endemic across the world, with an estimated 279,000 deaths in 2002, the majority in infants under 1 year of age. Worldwide epidemiologic data indicates increasing infection rates in older children and adults, which act as a source of infection to young infants. The Global Pertussis Initiative (GPI) is an expert scientific forum, which has published consensus recommendations for the monitoring, prevention, and treatment of the disease. This paper reports the proceedings of a regional meeting, held in Costa Rica in December 2008. The meeting gathered information on regional epidemiological, diagnostic capabilities and the ability to introduce GPI recommended vaccine strategies in Latin America. The capacity of Latin American countries to conduct vaccination programs is high and there is considerable government support. Whole-cell pertussis vaccines are used across Latin America, which appear to be quite effective. A 4-dose schedule is typically used (2, 4, 6, and 18 months), and a booster given at 4 to 6 years of age, with coverage often above 90%, but with regions of low coverage due to political and geographical difficulties. Adequate surveillance is lacking in many countries, giving insufficient data to guide vaccination policy. Improvements are being made, with countries such as Costa Rica, Panama, and Argentina introducing polymerase chain reaction (PCR) diagnosis. Those countries that do not currently use a preschool booster should launch one. Implementing vaccination programs in adolescents and/or adults to reduce exposure to infants would be beneficial and possible in most countries, given their current infrastructure.

Pertussis vaccines: The first hundred years.

Vaccines against pertussis have been used for more than a hundred years. This review describes the development of whole-cell (wP) and acellular pertussis (aP) vaccines, which, as DTP combination vaccines, have significantly reduced morbidity and mortality from pertussis, and which currently serve as the building blocks for a variety of vaccines used to immunize all infants worldwide. Two series of efficacy trials done in the 1950s for wP vaccines and in the 1990s for aP-vaccines have established standards for studying vaccine effectiveness. However, irrespective of their longtime use, critical aspects of pertussis vaccines remain unknown, including the exact mechanisms of protective immunity and a correlate of protection. Research to improve on the effectiveness and the duration of protection is ongoing, but although the vaccines are not perfect, only their continued use with a high coverage will ensure that infants and children are being protected from pertussis.

The epidemiology of pertussis in Germany: past and present.

BACKGROUND: Current and past pertussis epidemiology in the two parts of Germany is compared in the context of different histories of vaccination recommendations and coverage to better understand patterns of disease transmission. METHODS: Available regional pertussis surveillance and vaccination coverage data, supplemented by a literature search for published surveys as well as official national hospital and mortality statistics, were analyzed in the context of respective vaccination recommendations from 1964 onwards. RESULTS: Routine childhood pertussis vaccination was recommended in the German Democratic Republic (GDR) from 1964 and in former West German states (FWG) from 1969, but withdrawn from 1974-1991 in FWG. Pertussis incidence declined to <1 case/100,000 inhabitants in GDR prior to reunification in 1991, while in FWG, where pertussis was not notifiable after 1961, incidence was estimated at 160-180 cases/100,000 inhabitants in the 1970s-1980s. Despite recommendations for universal childhood immunization in 1991, vaccination coverage decreased in former East German States (FEG) and increased only slowly in FWG. After introduction of acellular pertussis vaccines in 1995, vaccination coverage increased markedly among younger children, but remains low in adolescents, especially in FWG, despite introduction of a booster vaccination for 9-17 year olds in 2000. Reported pertussis incidence increased in FEG to 39.3 cases/100,000 inhabitants in 2007, with the proportion of adults increasing from 20% in 1995 to 68% in 2007. From 2004-2007, incidence was highest among 5-14 year-old children, with a high proportion fully vaccinated according to official recommendations, which did not include a preschool booster until 2006. Hospital discharge statistics revealed a ~2-fold higher pertussis morbidity among infants in FWG than FEG. CONCLUSION: The shift in pertussis morbidity to older age groups observed in FEG is similar to reports from other countries with longstanding vaccination programs and suggests that additional booster vaccination may be necessary beyond adolescence. The high proportion of fully vaccinated cases in older children in FEG suggests waning immunity 5-10 years after primary immunisation in infancy. The higher incidence of pertussis hospitalisations in infants suggests a stronger force of infection in FWG than FEG. Nationwide pertussis reporting is required for better evaluation of transmission patterns and vaccination policy in both parts of Germany.

Pertussis in Latin America: Recent epidemiological data presented at the 2017 Global Pertussis Initiative meeting.

The Global Pertussis Initiative (GPI) is an expert scientific forum that publishes consensus recommendations for pertussis monitoring, prevention, and treatment across many regions of the world. Here, we report on the regional 2017 GPI meeting on the Americas, focusing on Latin America. Information on current pertussis epidemiology, surveillance, vaccine strategies, diagnostic capabilities, disease awareness, and major local obstacles was presented by researchers from Argentina, Brazil, Colombia, Costa Rica, El Salvador, Mexico, Peru, Puerto Rico, Uruguay, and Venezuela. Pertussis outbreaks have occurred during the last decade in the majority of participant countries and have been followed by improvements in surveillance. In the countries that introduced maternal immunization during pregnancy, a reduction in the infant case fatality rate has been detected. All countries need to maintain and improve pertussis surveillance to reach primary vaccination coverage >90%. Moreover, countries without maternal immunization programs should strongly consider them.

Controlling pertussis: how can we do it? A focus on immunization.

INTRODUCTION: Pertussis is a highly contagious disease of the respiratory tract which is caused by the bacterium Bordetella pertussis and is most severe in those <1 year of age. A vaccine against pertussis, introduced in the 1950's, led to a significant decrease in incidence of the disease, but recent increases in outbreaks have been attributed to insufficient vaccine uptake, suboptimal protection conferred by vaccines, and waning immunity after immunization. Areas covered: In this review we discuss the major challenges for controlling pertussis, and what we believe the best strategies are to overcome these challenges, focusing on immunization against pertussis in Europe, but with recommendations that are relevant worldwide. Expert commentary: To provide maximum vaccine coverage we propose a schedule that incorporates immunization of infants, preschoolers, adolescents, adults, and pregnant women. Uptake of vaccines may also vary between populations due to a variety of causes, including hesitancy to vaccinate, so any national strategy to control pertussis should also include sustaining public and healthcare provider confidence in vaccination. Addressing and improving regional variations in surveillance will also help better monitor annual incidence and outbreaks. Looking towards the future, the development of new pertussis vaccines with longer duration of protection would be advantageous.

Surveillance of pertussis: methods and implementation.

INTRODUCTION: Pertussis or whooping cough is a respiratory disease caused by Bordetella pertussis or, to a lesser extent, by B. parapertussis. Vaccines against pertussis have been widely used for more than 50 years and have led to a significant reduction of morbidity and mortality. However, even in countries with a high vaccine coverage, the disease is still not well controlled. Surveillance is urgently needed. AREAS COVERED: This review summarizes surveillance methods and gives examples that may be used when setting up a surveillance program or analyzing an outbreak. Expert commentary: Pertussis surveillance is urgently required in order to define the burden of disease, to adapt vaccine strategies according to the type of pertussis vaccine used and to follow the evolution of the bacteria.

Highlights of the 11th International Bordetella Symposium: from Basic Biology to Vaccine Development.

Pertussis is a severe respiratory disease caused by infection with the bacterial pathogen Bordetella pertussis The disease affects individuals of all ages but is particularly severe and sometimes fatal in unvaccinated young infants. Other Bordetella species cause diseases in humans, animals, and birds. Scientific, clinical, public health, vaccine company, and regulatory agency experts on these pathogens and diseases gathered in Buenos Aires, Argentina from 5 to 8 April 2016 for the 11th International Bordetella Symposium to discuss recent advances in our understanding of the biology of these organisms, the diseases they cause, and the development of new vaccines and other strategies to prevent these diseases. Highlights of the meeting included pertussis epidemiology in developing nations, genomic analysis of Bordetella biology and evolution, regulation of virulence factor expression, new model systems to study Bordetella biology and disease, effects of different vaccines on immune responses, maternal immunization as a strategy to prevent newborn disease, and novel vaccine development for pertussis. In addition, the group approved the formation of an International Bordetella Society to promote research and information exchange on bordetellae and to organize future meetings. A new Bordetella.org website will also be developed to facilitate these goals.

Pertussis immunization in the global pertussis initiative European region: recommended strategies and implementation considerations.

Approaches to pertussis diagnosis, surveillance and immunization vary widely across Europe. Nonetheless most countries report high levels of vaccine coverage in infants and toddlers, and significant reductions in infant morbidity and mortality have been achieved. As a consequence of the effective protection of infants and toddlers, the absolute incidence of pertussis has substantially decreased, but the relative proportion of older age groups, adolescents and adults in particular, has increased. These groups, however, are a relevant source of infection of unimmunized or incompletely immunized infants. In addition to efficient childhood vaccination, other approaches to pertussis immunization are required. Among the various strategies evaluated, 3 were recommended by the European participants in the Global Pertussis Initiative that might be adapted to each country's specific needs: the reinforcement of implementation of current schedules, the addition of an extra dose of vaccine to current immunization schedules and the selective immunization of health care workers, which is already included in a European Commission directive. The main barriers to the acceptance of these strategies are low awareness of pertussis in immunized populations, poor recognition of the disease in adults and adolescents, lack of standardized diagnostic criteria and poor access to laboratory confirmation of the diagnosis. These obstacles have led to underreporting of pertussis and an underestimation of the disease burden. Actions to overcome these issues are crucial to the implementation of new or improved immunization strategies to combat pertussis in Europe.

Strategies to decrease pertussis transmission to infants.

The Global Pertussis Initiative (GPI) is an expert scientific forum addressing the worldwide burden of pertussis, which remains a serious health issue, especially in infants. This age cohort is at risk for developing pertussis by transmission from those in close proximity. Risk is increased in infants aged 0 to 6 weeks, as they are too young to be vaccinated. Older infants are at risk when their vaccination schedules are incomplete. Infants also bear the greatest disease burden owing to their high risk for pertussis-related complications and death; therefore, protecting them is a high priority. Two vaccine strategies have been proposed to protect infants. The first involves vaccinating pregnant women, which directly protects through the passive transfer of pertussis antibodies. The second strategy, cocooning, involves vaccinating parents, caregivers, and other close contacts, which indirectly protects infants from transmission by preventing disease in those in close proximity. The goal of this review was to present and discuss evidence on these 2 strategies. Based on available data, the GPI recommends vaccination during pregnancy as the primary strategy, given its efficacy, safety, and logistic advantages over a cocoon approach. If vaccination during pregnancy is not feasible, then all individuals having close contact with infants <6 months old should be immunized consistent with local health authority guidelines. These efforts are anticipated to minimize pertussis transmission to vulnerable infants, although real-world effectiveness data are limited. Countries should educate lay and medical communities on pertussis and introduce robust surveillance practices while implementing these protective strategies.

Pertussis Across the Globe: Recent Epidemiologic Trends From 2000 to 2013.

Pertussis has reemerged as a problem across the world. To better understand the nature of the resurgence, we reviewed recent epidemiologic data and we report disease trends from across the world. Published epidemiologic data from January 2000 to July 2013 were obtained via PubMed searches and open-access websites. Data on vaccine coverage and reported pertussis cases from 2000 through 2012 from the 6 World Health Organization regions were also reviewed. Findings are confounded not only by the lack of systematic and comparable observations in many areas of the world but also by the cyclic nature of pertussis with peaks occurring every 3-5 years. It appears that pertussis incidence has increased in school-age children in North America and western Europe, where acellular pertussis vaccines are used, but an increase has also occurred in some countries that use whole-cell vaccines. Worldwide, pertussis remains a serious health concern, especially for infants, who bear the greatest disease burden. Factors that may contribute to the resurgence include lack of booster immunizations, low vaccine coverage, improved diagnostic methods, and genetic changes in the organism. To better understand the epidemiology of pertussis and optimize disease control, it is important to improve surveillance worldwide, irrespective of pertussis vaccine types and schedules used in each country.

Pertussis diagnostics: overview and impact of immunization.

In all vaccinated populations, infections with Bordetella pertussis and Bordetella parapertussis continue to cause infections in unvaccinated infants and children, as well as in adolescents and adults with waning immunity. Thus in patients with longer lasting coughs a diagnosis of pertussis should be entertained irrespective of their vaccination status. Due to the non-specific clinical symptoms, clinically suspected cases of pertussis must be verified by laboratory methods. Hyperleukocytosis may be helpful in diagnosis for young infants, but in most cases, nonspecific laboratory tests have no role in pertussis diagnosis. Specific laboratory tests include direct detection of the bacteria or their DNA by culture or PCR, whereas serology serves as an indirect method to diagnose pertussis in those patients who present late in the development of the disease. Serology results can be interpreted in relation to reference values for different populations, but serology is unable to distinguish between vaccination and infection.

The Global Pertussis Initiative: report from a round table meeting to discuss the epidemiology and detection of pertussis, Paris, France, 11-12 January 2010.

Pertussis remains endemic worldwide and is an important public health problem, even in countries with sustained high vaccination coverage. Resurgence of pertussis in the post-vaccination era has been reported in many areas of the world. The Global Pertussis Initiative (GPI) was established in 2001 to evaluate the ongoing problem of pertussis worldwide and to recommend appropriate pertussis control strategies. In addition to primary vaccinations, the GPI currently recommends a pertussis booster vaccination to pre-school children, adolescents and those adults at risk of transmitting Bordetella pertussis infection to infants. At a meeting in Paris, France, in January 2010, GPI members discussed pertussis surveillance and testing then prepared recommendations on the implementation and utilisation of these activities. Issues and projects discussed included: national surveillance systems and their suitability for other countries; seroprevalence studies; ideal surveillance methodologies; ongoing efforts in obtaining biological samples; standardisation of sample treatment; culture; real-time polymerase chain reaction (PCR); and likely future advances such as antibody detection in saliva. Previous regional meetings of the GPI have confirmed that many countries have limited laboratory facilities for the detection of pertussis. The GPI hopes that the future introduction of increased laboratory capabilities and greater harmonisation of clinical definitions and detection methods will lead to enhanced surveillance and a better estimate of the burden of pertussis infection worldwide. This article provides a current guide on the appropriate use of laboratory diagnostics and optimal surveillance methodologies to assist countries in the control of pertussis disease.

Post-pandemic seroprevalence of pandemic influenza A (H1N1) 2009 infection (swine flu) among children <18 years in Germany.

BACKGROUND: We determined antibodies to the pandemic influenza A (H1N1) 2009 virus in children to assess: the incidence of (H1N1) 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children. METHODOLOGY/PRINCIPAL FINDINGS: Eight pediatric hospitals distributed over Germany prospectively provided sera from in- or outpatients aged 1 to 17 years from April 1(st) to July 31(st) 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT) and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1-4 and 5-17 years the prevalence of HI titers (≥1∶10) was 27.1% (95% CI: 23.5-31.3) and 53.5% (95% CI: 50.9-56.2) compared to 1.7% and 5.5%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1) 2009 during the season 2009/2010 of 25,4% (95% CI : 19.3-30.5) in children aged 1-4 years and 48.0% (95% CI: 42.6-52.0) in 5-17 year old children. Of children with HI titers ≥1∶10, 25.5% (95% CI: 22.5-28.8) reported no history of any infectious disease since June 2009. Among vaccinated children, 92% (95%-CI: 87.0-96.6) of the 5-17 year old but only 47.8% (95%-CI: 33.5-66.5) of the 1-4 year old children exhibited HI titers against influenza A virus (H1N1) 2009. CONCLUSION: Serologically determined incidence of influenza A (H1N1) 2009 infections in children indicates high infection rates with older children (5-17 years) infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03(B)-adjuvanted split virion vaccine need further scrutiny.

Characterization of reference materials for human antiserum to pertussis antigens by an international collaborative study.

Enzyme-linked immunosorbent assay (ELISA) has been widely used to evaluate antibody responses to pertussis vaccination and infection. A common reference serum is essential for the standardization of these assays. However, no internationally recognized reference serum is available. At the request of the Expert Committee on Biological Standardization (ECBS) of the World Health Organization (WHO), a set of four candidate international standards has been prepared. These candidate materials have been assessed for suitability and compared to the widely used U.S. reference pertussis antiserum (human) lot 3, lot 4, and lot 5 by 22 laboratories from 15 countries in an international collaborative study. Laboratories measured immunoglobulin G (IgG) and IgA antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (Fim2&3) using their established immunoassays. The results of this study showed each of the four candidates to be suitable as an international standard. With the agreement of the participants, a recommendation has been made to the ECBS that the candidate material coded 06/140 be established as the First International Standard for pertussis antiserum (human), with the following assigned international units (IU): IgG anti-PT, 335 IU/ampoule; IgA anti-PT, 65 IU/ampoule; IgG anti-FHA, 130 IU/ampoule; IgA anti-FHA, 65 IU/ampoule; IgG anti-PRN, 65 IU/ampoule; and IgA anti-PRN, 42 IU/ampoule. No formal units have been proposed for anti-Fim2&3 because most assays used a mixture of fimbrial antigens. In addition, the candidate material coded 06/142 has been proposed as a WHO working preparation for characterization of assay systems.