Kevin Forsyth

Recommendations are needed for adolescent and adult pertussis immunisation: rationale and strategies for consideration

Pertussis vaccination of infants has dramatically reduced disease, complications and deaths in infancy and early childhood. But there is still a major public health challenge--to deal with the morbidity and economic burden of illness in older children, adolescents and adults. Furthermore, it is these groups that form a major source of infection for non-immunised and partially immunised infants who are at high risk of severe complications. Adult-type acellular pertussis vaccine confers safe and effective protection against pertussis. There are several strategies to consider for immunising older individuals. Universal vaccination of all age groups would be the best available strategy for protecting individuals. It would also reduce the potential for transmitting the disease to other susceptibles, particularly infants. However, such a policy may be difficult both logistically and economically at this time. More easily achievable as a first step would be a strategy of universal adolescent booster vaccination combined with a programme targeted at adults most likely to have contact with very young babies including healthcare and childcare workers, parents and close family contacts. There is also potential for offering vaccination to adults (and their carers and close contacts) whose medical conditions or advanced age may place them at increased risk of more severe pertussis disease. Specific details of immunisation programmes must be made on a country by country basis depending on local circumstances.

New Pertussis Vaccination Strategies beyond Infancy: Recommendations by the Global Pertussis Initiative

BACKGROUND The Global Pertussis Initiative, an expert scientific forum, was established to address the ongoing problems associated with pertussis disease worldwide. METHODS The group analyzed pertussis disease trends, developed recommendations to improve disease control through expanded vaccination strategies, and proposed solutions to barriers to implementation and support of research activities. RESULTS Bordetella pertussis infection is endemic and continues to be a serious problem among unvaccinated or incompletely vaccinated infants. In addition, the reported incidence of pertussis disease is increasing in adolescents and adults, who not only experience a considerable health burden themselves but also infect vulnerable infants. CONCLUSIONS Current vaccination strategies need to be reinforced. Expanded vaccination should include adding booster doses to existing childhood schedules (preschool or adolescent) and booster doses for those specific adult subgroups that have the highest risk of transmitting B. pertussis infection to infants (i.e., new parents, other contacts of newborns, and health care workers). More epidemiological studies and studies of disease transmission and the cost-effectiveness of vaccination would be valuable, and surveillance, diagnostic improvements, and educational campaigns are needed for implementation. However, as a prelude to universal adult vaccination, immediate universal adolescent vaccination should be instituted in countries in which it is economically feasible.

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.

Potential strategies to reduce the burden of pertussis.

Pertussis continues to be a significant cause of morbidity and mortality among nonimmunized young infants. Although the inception of childhood pertussis immunization programs has significantly reduced the occurrence of the disease in children, waning vaccine-induced immunity permits the disease to affect adolescents and adults, who in turn transmit the disease to unimmunized or incompletely immunized infants. The Global Pertussis Initiative brought together experts from 17 countries around the world to evaluate strategies to improve disease control. Seven strategies were considered: (1) universal adult immunization; (2) selective immunization of mothers and close family contacts of newborns; (3) selective immunization of health care workers; (4) selective immunization of child care workers; (5) universal immunization of adolescents; (6) preschool booster at 4–6 years of age; and (7) reinforcement and/or improvement of current infant and toddler immunization strategies. Because immunization programs vary widely from country to country, no single strategy is likely to be appropriate for all. Moreover it would be helpful to have additional data to support the strategies and provide a better understanding of the disease so that new approaches can be monitored effectively. However, certain steps can be taken now to reduce the incidence of pertussis.

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.

The interaction of neutrophils with respiratory epithelial cells in viral infection

Viral respiratory infection is very common. Respiratory syncytial virus (RSV) infects almost all children during the first 2 years of life. Respiratory syncytial virus is the most frequent cause of bronchiolitis, which is strongly linked with asthma. However, the pathophysiology of RSV bronchiolitis is unclear. Neutrophils are the predominant airway leucocytes in RSV bronchiolitis and other viral infections. Neutrophils and their products are likely to play an important role in viral infection. Current evidence indicates that: (i) viral infection of epithelial cells increases the production of neutrophil chemoattractants or chemokines, which induce neutrophil migration into the inflammatory sites; (ii) the expression of adhesion molecules on neutrophils and epithelial cells is up‐regulated in viral infection, and neutrophil‐epithelial adhesion is increased; (iii) neutrophils augment epithelial damage and detachment induced by viral infection and contribute to the pathophysiology of viral disease; (iv) neutrophil apoptosis is up‐regulated in RSV infection, which may be an in vivo mechanism to limit neutrophil‐induced epithelial damage; (v) inhibitors of chemokines, adhesion molecules or neutrophil proteases may be useful in prevention of neutrophil‐induced epithelial damage. In conclusion, neutrophils play an important role in viral infection, and intervention to prevent neutrophil‐induced epithelial damage may be a potential clinical therapy.

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.

Immunomodulatory constituents of human milk change in response to infant bronchiolitis.

Although epidemiological evidence is generally supportive of a causal association between respiratory syncytial virus (RSV) bronchiolitis during infancy and the development of persistent wheeze/asthma, if not allergy, the mechanism by which this occurs and an explanation for why all children do not succumb remains to be elucidated. Breast feeding has been found to confer a protective effect against respiratory infections such as RSV bronchiolitis and allergy; however, again there is little direct evidence and no clear mechanism. In this study, we examined whether human milk immunomodulatory factors (cells, cytokines) change in response to clinically diagnosed, severe bronchiolitis in the recipient breast‐fed infant. We examined milk from 36 breast feeding mothers of infants hospitalized with bronchiolitis and compared them with milk from 63 mothers of postpartum age‐matched healthy controls. Milks from mothers of infants hospitalized with bronchiolitis had significantly greater numbers of viable cells when compared with the milks obtained from mothers of healthy infants (1.3 ± 0.4 vs. 0.3 ± 0.03 × 106 cells/ml, mean ± s.e.m.; p ≤ 0.001). Further, the cells obtained from the mothers of infants hospitalized with bronchiolitis were found to produce a skewed cytokine profile ex vivo in response to stimulation by live RSV but not when cultured with a non‐specific mitogen (concanavalin A). This study provides preliminary evidence for an immunological link between mothers and their breast‐fed infants during severe respiratory infections as well as a possible contributing factor to the development of persistent wheeze in these infants.

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

Despite widespread immunization programs in most countries, pertussis disease continues to be a threat to public health. In particular, there has been a resurgence of pertussis disease in older children, adolescents and adults, creating a reservoir of infection, which poses a significant threat to infants who are either unimmunized or incompletely immunized. Global Pertussis Initiative participants from Argentina, Australia, Brazil and Japan considered the relative merits of several strategies to reduce the burden of pertussis disease and suggested strategies that might be implemented in these countries. Infants in these countries receive an initial course of 3 doses of vaccine in the first year of life followed by a fourth dose in the second year. Only children in Japan are not given a preschool booster (age 3–5 years). Of the strategies considered, the addition of a preschool booster is therefore a priority in Japan to overcome the problem of waning vaccine-induced immunity to pertussis in school children. Waning immunity also affects adolescents; Australia introduced an adolescent booster in 2003, and the addition of a booster in this age group was suggested for Argentina and Japan. Immunization of new mothers and other close contacts of young infants, such as child care and health care workers, might be appropriate in Australia in the future. Argentina also suggested a future possibility of immunizing health care and child care workers. Obstacles to new immunization strategies include poor access to standardized laboratory diagnostic techniques, inadequate resources to fund new immunization programs, low awareness of pertussis disease in adults and adolescents and inadequate surveillance techniques to assess the full extent of the problems caused by pertussis or the impact new vaccination strategies might have.

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.