Return to: Scandals: Vaccine Effectiveness - An ineffective argument

addition of references still in progress - 04/14/06

 
Acellular pertussis vaccine booster combined with diphtheria and tetanus toxoids for adolescents.

Pichichero ME, Blatter MM, Kennedy WA, Hedrick J, Descamps D, Friedland LR.

University of Rochester Medical Center, Rochester, NY 14642, USA. michael_pichichero@urmc.rochester.edu

BACKGROUND: The incidence of pertussis is increasing, especially in adolescents, attributed in part to waning of immunity after childhood immunization. Recently licensed in the United States for use in adolescents, acellular pertussis vaccines will provide an immunogenic and safe option for booster immunization against pertussis. METHODS: This prospective, randomized, observer-blinded, multicenter, comparative study evaluated the safety and immunogenicity of a vaccine formulated with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis antigens (Tdap) compared with tetanus and diphtheria toxoids vaccine (Td) for booster immunization in adolescents. There were 4114 healthy adolescents aged 10 to 18 years who completed childhood vaccination against diphtheria, tetanus, and pertussis who were enrolled, randomized, and received study vaccine. RESULTS: Local and general symptoms were comparable between the Tdap and Td groups. The immune response of Tdap was comparable with Td vaccine for tetanus and diphtheria seroprotection and booster responses. In addition, geometric mean concentrations of antibody to pertussis antigens, pertussis toxoid, filamentous hemagglutinin, and pertactin exceeded the antibody response elicited after infant immunization with diphtheria and tetanus toxoids and acellular pertussis antigens (DTaP) that had proven efficacy against pertussis. CONCLUSIONS: In adolescents, the studied Tdap was safe and immunogenic and induced pertussis antibodies that were higher than those associated with efficacy in infants.

PMID: 16585302 [PubMed - in process]

 
Immunogenicity and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine as a single-dose booster in Singaporean adults.

Chan SH, Tan PT, Han HH, Bock HL.

Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD4, 5 Science Drive 2, Singapore 117597. hans.l.bock@gsk.com.

Introduction: Older children and adults, susceptible to pertussis because of waning immunity, may serve as a reservoir of infection, leading to severe disease among young unvaccinated infants. Booster diphtheria-tetanus-acellular pertussis (dTpa) vaccination in older age groups is rare in Singapore, one reason being the increase in reactogenicity with each successive dose. The aim of this study was to assess the immunogenicity, safety and reactogenicity of a reduced antigen, combined dTpa vaccine as a single booster dose in healthy adults aged 18 years or older. Methods: A total of 150 healthy adults, 18 to 60 years of age, received a single dose of GlaxoSmithKline Biologicals' dTpa vaccine with reduced content for diphtheria and pertussis, with measurement of pre- and post-vaccination antibody titres. Results: Prior to vaccination, 71.6 percent and 92.6 percent of the subjects had anti-diphtheria and anti-tetanus antibody levels greater than or equal to 0.1 IU/mL, respectively. 46.7 percent, 98.5 percent and 44.4 percent of subjects were seropositive for pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) antibodies, respectively. One month after vaccination, there was an increase in geometric mean titres from pre-vaccination to post-vaccination blood samples for anti-diphtheria (greater than seven-fold), anti-tetanus (greater than five-fold), anti-PT (greater than 11-fold), anti- FHA (greater than 25-fold) and anti-PRN (greater than 31-fold) antibodies. Solicited grade three local symptoms (pain, redness and swelling) were reported in 14.1 percent, 8.1 percent and 10.4 percent of subjects, respectively. No serious adverse events were reported. Conclusion: In summary, the dTpa vaccine is immunogenic, safe and well-tolerated in Singaporean adults.

PMID: 16572239 [PubMed - in process]

 
Relative efficacy of different immunization schedules for the prevention of serogroup C meningococcal disease: A model-based evaluation.

De Wals P, Trottier P, Pepin J.

Faculty of Medicine, Laval University, Canada; Quebec National Institute of Public Health, Canada.

Different immunization strategies have been implemented for the control of serogroup C meningococcal disease (CMD) in Canada and in other developed countries. Results from effectiveness studies of conjugate vaccines in the UK and Spain indicate waning immunity over time. To estimate the life-time protection conferred by different immunization schedules, a simulation model was constructed based on the current epidemiologic situation in Canada. Results showed that the efficacy of any immunization schedule was highly influenced by the rate at which immunity waned and that the benefit of a booster dose increased with increasing rates of waning immunity. Schedules including several doses in early infancy provided little additional benefit over programs starting with 1 dose at the age of 12 months. One-dose programs provided low levels of protection, unless the vaccine was administered at the age of 12 months, and a waning immunity rate of 1% per year or less was assumed. The most effective schedule was 5 doses given at age 2 months, 4 months, 1 year, 12 years, and 18 years, but was only marginally better than 2 doses provided at 12 months and 12 years of age. Existing routine immunization schedules may not be optimal and should be designed to achieve the highest level of protection using the lowest number of doses.

PMID: 16517032 [PubMed - in process]

 
Modelling the effect of a booster vaccination on disease epidemiology.

Alexander ME, Moghadas SM, Rohani P, Summers AR.

Institute for Biodiagnostics, National Research Council Canada, R3B 1Y6, Winnipeg, Manitoba, Canada, Murray.Alexander@ncr-cnrc.gc.ca.

Despite the effectiveness of vaccines in dramatically decreasing the number of new infectious cases and severity of illnesses, imperfect vaccines may not completely prevent infection. This is because the immunity afforded by these vaccines is not complete and may wane with time, leading to resurgence and epidemic outbreaks notwithstanding high levels of primary vaccination. To prevent an endemic spread of disease, and achieve eradication, several countries have introduced booster vaccination programs. The question of whether this strategy could eventually provide the conditions for global eradication is addressed here by developing a seasonally-forced mathematical model. The analysis of the model provides the threshold condition for disease control in terms of four major parameters: coverage of the primary vaccine; efficacy of the vaccine; waning rate; and the rate of booster administration. The results show that if the vaccine provides only temporary immunity, then the infection typically cannot be eradicated by a single vaccination episode. Furthermore, having a booster program does not necessarily guarantee the control of a disease, though the level of epidemicity may be reduced. In addition, these findings strongly suggest that the high coverage of primary vaccination remains crucial to the success of a booster strategy. Simulations using estimated parameters for measles illustrate model predictions.

PMID: 16283412 [PubMed - in process]

 
Adolescent and adult pertussis: disease burden and prevention.

Edwards K, Freeman DM.

Division of Infectious Diseases, CCC-5323 Medical Center North, Vanderbilt University Medical Center, Nashville, Tennessee 37223, USA. Kathryn.Edwards@vanderbilt.edu

PURPOSE OF REVIEW: According to surveillance data provided by the Centers for Disease Control and Prevention, the rates of pertussis disease in adolescents and adults have been increasing. This is likely due to increased recognition and waning vaccine-induced immunity. RECENT FINDINGS: The presentation of pertussis in adolescents and adults is generally a persistent cough, but more serious complications have been reported. In addition, adolescents and adults often serve as sources of pertussis infection in infants and young children. SUMMARY: Acellular pertussis vaccines combined with diphtheria and tetanus toxoids have proven to be well tolerated, immunogenic and effective in reducing pertussis disease in adolescents and adults. These vaccines are currently being recommended to replace the booster diphtheria and tetanus toxoid vaccines in adolescents. Recommendations for the use of these vaccines in adults are still being formulated.

PMID: 16470167 [PubMed - in process]

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

Godfroid F, Denoel P, Poolman J.

DAP Bacterial Vaccine Preclinical Immunology, Research & Development, GlaxoSmithKline Biologicals, Rue de l'Institut 89, 1330 Rixensart, Belgium. fabrice.godfroid@gskbio.com

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.

PMID: 16221076 [PubMed - in process]

 
Prevention of pertussis among adolescents: recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine.

America Academy of Pediatrics Commitee on Infectious Diseases.

The purpose of this statement is to provide the rationale and recommendations for adolescent use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines. Despite universal immunization of children with multiple doses of pediatric diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine, pertussis remains endemic with a steady increase in the number of reported cases. Two peaks in the incidence of pertussis occur in pediatric patients: infants younger than 6 months of age who are inadequately protected by the current immunization schedule and adolescents 11 through 18 years of age whose vaccine-induced immunity has waned. Significant medical and public health resources are being consumed in postexposure management of adolescent cases, contacts, and outbreaks with little beneficial effect on individuals or the epidemiology of disease. Two Tdap products were licensed in 2005 for use in people 10 through 18 years of age (Boostrix) and 11 through 64 years of age (Adacel). The American Academy of Pediatrics recommends the following: 1. Adolescents 11 to 18 years of age should receive a single dose of Tdap instead of tetanus and diphtheria toxoids (Td) vaccine for booster immunization. The preferred age for Tdap immunization is 11 to 12 years. 2. Adolescents 11 to 18 years of age who have received Td but not Tdap are encouraged to receive a single dose of Tdap. An interval of at least 5 years between Td and Tdap is suggested to reduce the risk of local and systemic reactions; however, intervals of less than 5 years can be used, particularly in settings of increased risk of acquiring pertussis, having complicated disease, or transmitting infection to vulnerable contacts. Data support acceptable safety with an interval as short as approximately 2 years. 3. Tdap and tetravalent meningococcal conjugate vaccine (MCV4 [Menactra]) should be administered during the same visit if both vaccines are indicated. If this is not feasible, MCV4 and Tdap can be administered using either sequence. When not administered simultaneously, the American Academy of Pediatrics suggests a minimum interval of 1 month between vaccines. The rationale for this strategy is to provide direct protection of immunized adolescents. With implementation of vaccine recommendations, indirect benefitalso is likely to extend to unimmunized peers and other age groups. The strategy of universal Tdap immunization at 11 to 12 years of age is cost-effective.

Publication Types:

• Practice Guideline

PMID: 16382131 [PubMed - indexed for MEDLINE]

J Adolesc Health. 2005 Dec;37(6):517. Related Articles, Links
 

 
Immunogenicity and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine in healthy Taiwanese children and adolescents.

Huang LM, Chang LY, Tang H, Bock HL, Lu CY, Huang FY, Lin TY, Lee CY.

Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.

PURPOSE: Disease caused by Bordetella pertussis is increasingly being identified among older children and adults in immunized populations, indicating a waning of the vaccine-induced immunity. These findings suggest the need for booster immunization of older children and adults. Modern acellular reduced-antigen-content vaccines have been developed, which can be given as a booster in individuals more than 4 years of age. This study was to assess the immunogenicity and reactogenicity of Boostrix, GlaxoSmithKline Biologicals' reduced-antigen-content diphtheria-tetanus acellular pertussis (dTpa) vaccine, when administered as a booster in healthy subjects previously primed with DTP vaccine. METHODS: Healthy Taiwanese children and adolescents aged 6-8 years and 15-20 years, previously primed with DTP vaccine, were enrolled. All received one dose of Boostrix. Two blood samples were taken from each of them, one before vaccination and one at 1 month after vaccination. Serum antibodies to diphtheria and tetanus toxoids and immunoglobulin G (IgG) antibodies against the pertussis components PT, FHA and PRN were measured by enzyme-linked immunosorbent assay (ELISA) technique. Adverse reactions following vaccination were recorded. RESULTS: A total of 180 subjects were recruited. The vaccine response rates to the pertussis antigens ranged between 89.0-100%. There were no serious adverse events reported during the study period. CONCLUSIONS: The results of this study suggest that Boostrix may be safely and effectively administered as a booster dose to children previously primed with DTP vaccine.

Publication Types:

• Clinical Trial

PMID: 16310132 [PubMed - indexed for MEDLINE]

 
Pertussis: increasing disease as a consequence of reducing transmission.

Aguas R, Goncalves G, Gomes MG.

Instituto Gulbenkian de Ciencia, Oeiras, Portugal.

Since the 1980s, the occurrence of pertussis cases in developed countries has increased and shifted towards older age groups. This resurgence follows 30 years of intense mass vaccination, and has been attributed primarily to three factors: (1) more effective diagnosis of the disease, (2) waning of vaccine-induced immunity, and (3) loss of vaccine efficacy due to the emergence of new Bordetella pertussis strains. Here we develop and analyse a mathematical model to assess the plausibility of these hypotheses. We consider that exposure to B pertussis through natural infection or vaccination induces an immune response that prevents severe disease but does not fully prevent mild infections. We also assume that these protective effects are temporary due to waning of immunity. These assumptions, describing the mode of action of adaptive immunity, are combined with a standard transmission model. Two distinct epidemiological scenarios are detected: under low transmission, most infections lead to severe disease; under high transmission, mild infections are frequent, boosting clinical immunity and maintaining low levels of severe disease. The two behaviours are separated by a reinfection threshold in transmission. As a result, the highest incidence of severe disease is expected to occur at intermediate transmission intensities--near the reinfection threshold--suggesting that pertussis resurgence may be induced by a reduction in transmission, independently of vaccination. The model is extended to interpret the outcomes of current control measures and explore scenarios for future interventions.

PMID: 16439331 [PubMed - indexed for MEDLINE]

 
Emerging diseases: measles.

Ota MO, Moss WJ, Griffin DE.

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA. mota@jhsph.edu

High vaccination coverage rates and the administration of a second dose of measles vaccine have resulted in a significant decline in the incidence of measles and neurologic diseases due to measles in many countries. However, intermittent outbreaks of measles still occur even in countries with excellent vaccination coverage, suggesting the existence of high rates of measles virus introduction from endemic regions and/or waning of vaccine-induced immunity. Strategies to sustain high levels of global immunity to measles virus by increasing vaccine coverage with routine and supplementary vaccination campaigns must be supported.

Publication Types:

• Review

PMID: 16287686 [PubMed - indexed for MEDLINE]

 
Pertussis vaccination for adolescents and adults.

Franco E, Giambi C, Ialacci R, Maurici M.

University Tor Vergata, Department of Public Health, Via Montpellier, 1 00133 Rome, Italy. franco@med.uniroma2.it

Following the introduction of vaccines, the incidence of pertussis declined; however, since 1990, a progressive increase was noted, even in highly immunised populations. Periodic pertussis outbreaks are due to suboptimal efficacy of the vaccine and waning immunity with increasing age. A significant proportion of adolescents and adults with a prolonged cough present Bordetella pertussis, and infection is often transmitted to infants too young to be vaccinated. A high vaccination coverage in the whole population would be necessary to interrupt the circulation of B. pertussis, but immunisation programmes for adolescents and adults have been introduced recently and are accepted with difficulty. The lack of cost-benefit analysis and consistent epidemiological data makes it difficult to assess the role of pertussis elimination among public health priorities. At present, programmes targeted at risk groups for close contacts with infants are the most convenient for adult population, as more epidemiological and economic evidence is needed before a universal strategy can be discussed.

Publication Types:

• Review

PMID: 15461578 [PubMed - indexed for MEDLINE]

 
Health and economic consequences of an outbreak of pertussis among healthcare workers in a hospital in France.

Ward A, Caro J, Bassinet L, Housset B, O'Brien JA, Guiso N.

Caro Research Institute, Concord, Massachusetts, USA. alexward@caroresearch.com

BACKGROUND: Bordetella pertussis is highly contagious, and because immunity wanes after vaccination, it continues to be a cause of cough among adults. OBJECTIVE: To describe the healthcare services used and productivity losses accrued by healthcare workers (HCWs) missing work due to pertussis. METHODS: After 3 pertussis cases were confirmed among HCWs, all hospital employees and patients with a cough were screened between November 2000 and March 2001. Each potential case underwent diagnostic tests and received antibiotics (spiramycin or azithromycin) when appropriate. Symptomatic employees were not allowed to return to work until they received an antibiotic for at least 5 days. Services used (physician visits and calls, antibiotics, diagnostic tests, hospitalization, and treatment provided to their contacts) were combined with cost estimates (in 2002 euros) for these services in France. RESULTS: Ninety-one potential cases were identified (77 HCWs, 12 patients, and 2 family members). Of them, 89% received antibiotics and 22% had at least one contact who was also treated. Approximately half (55%) of the HCWs who were cases missed 5 days of work. Four patients were admitted to the hospital as a result of the infection. The average medical cost was 297 euros per potential case: diagnostic tests accounted for 32% and hospitalization for 31%. Total cost (medical and productivity) was 46,661 euros for 91 cases, 42% from productivity losses. An investigation to identify these potential cases also accrued additional costs. CONCLUSION: Serious adverse health and economic consequences arose from transmission of pertussis among HCWs, their families, and patients.

PMID: 15796282 [PubMed - indexed for MEDLINE]

 
Prevention of hepatitis B in nonresponders to initial hepatitis B virus vaccination.

Sjogren MH.

Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, District of Columbia 20307, USA.

Although vaccination against hepatitis B virus (HBV) is highly successful, 5% to 10% of individuals do not experience a response with an adequate antibody level to hepatitis B surface antigen (anti-HBs). Contributing causes for nonresponse to the vaccine are genetic predisposition, immunosuppression, and certain chronic illnesses. The distinction between true nonresponse (after adequate immunization) and waning anti-HBs levels is important. The latter is not uncommon in populations in areas of the world with low endemicity for HBV infection. Data from subjects with waning anti-HBs levels show that immunologic memory may still protect these individuals against acute HBV infection or may prevent chronic infection with HBV for < or =10 years after immunization. Recent reports from Asia and Alaska describe cases of chronic HBV infection 15 years after immunization in subjects who have very low levels of anti-HBs. Thus, nonresponders or those with waning immunity who may be at risk of HBV infection in subsequent years may require a booster dose. Clinical algorithms to reimmunize nonresponders have been described and are discussed in this article. Experimental hepatitis B vaccines have shown some promise in nonresponders but are not commercially available in the United States.

Publication Types:

• Review

PMID: 16271539 [PubMed - indexed for MEDLINE]

 
Diagnosis and management of pertussis.

Tozzi AE, Celentano LP, Ciofi degli Atti ML, Salmaso S.

Epidemiology Unit, Bambino Gesu Hospital, Rome, Italy. alberto.tozzi@opbg.net

Pertussis is increasing in frequency among children too young to be vaccinated and among adolescents and adults. This increase is due mainly to waning immunity among vaccinated individuals, who become susceptible during adolescence and adulthood and maintain the circulation of Bordetella pertussis. Infants are at highest risk of severe illness requiring hospital admission, complications and death. The clinical presentation in adolescents, adults and vaccinated individuals may be atypical, with paroxysmal cough of short duration or simply a persistent cough. Culture and polymerase chain reaction may be used to identify B. pertussis infection, but their sensitivity is high only in the early phase of the disease. Serologic tests are not standardized for the diagnosis of pertussis, and their clinical application is limited. Erythromycin is still considered in some countries to be the "gold standard" for therapy and prophylaxis; however, azithromycin and clarithromycin seem equally efficacious and are associated with fewer side effects.

Publication Types:

• Review

PMID: 15710944 [PubMed - indexed for MEDLINE]

 
Pertussis sources of infection and routes of transmission in the vaccination era.

Schellekens J, von Konig CH, Gardner P.

Diagnostic Laboratory for Infectious Diseases and Perinatal Screening, RIVM, Bilthoven, the Netherlands. j.schellekens@infectielab.nl

Vaccination against pertussis has resulted in reduction of the infection pressure of Bordetella pertussis (partial herd immunity), but the circulation of B. pertussis has persisted as a consequence of waning of vaccine-induced and naturally acquired immunity. An increase in the reported incidence of B. pertussis infection in older children, adolescents and young adults has been noted, resulting in a perceived resurgence of the disease in these age groups. Regardless of whether this resurgence is real or not, older groups are increasingly recognized as playing an important role in transmitting B. pertussis infection to incompletely immunized infants, in whom pertussis disease continues to cause severe and fatal illness, albeit at much lower levels than in the prevaccine era. Several studies have suggested that mothers, in particular, are a significant source of infection for infants. Adolescents, grandparents and health care workers can also play a role. By contrast, most adolescents acquire the infection from schoolmates and friends, whereas for adults the main sources are children and work colleagues. Furthermore teachers, child care workers and health care workers could be at increased risk of being exposed to, and transmitting, B. pertussis infection. Current immunization strategies inadequately control the circulation of B. pertussis, in part because of suboptimal adherence to current pediatric immunization guidelines. In addition to efforts to improve pertussis immunization rates in children, the expansion of pertussis immunization to target specific groups should be considered. Besides reducing morbidity in the targeted groups, these strategies could decrease the residual burden of pertussis morbidity and mortality in infants.

Publication Types:

• Review

PMID: 15876919 [PubMed - indexed for MEDLINE]

 
Measles in Minsk, Belarus, 2001-2003: clinical, virological and serological parameters.

Atrasheuskaya AV, Blatun EM, Neverov AA, Kameneva SN, Maksimov NL, Karpov IA, Ignatyev GM.

Laboratory of Immunology Safety, Institute of Molecular Biology, State Research Center of Virology and Biotechnology Vector, Koltsovo, Novosibirsk Region 630559, Russia. ignat@vector.nsc.ru

BACKGROUND: A number of cases of measles have been reported in the Republic of Belarus despite vaccine coverage of 98%. The absence of information on measles virus genotypes circulating in the Republic of Belarus has made it difficult to asses the situation. OBJECTIVES: The purpose of this study was to isolate and sequence measles virus strains from clinical cases in Minsk, Belarus, and to estimate the role of vaccine failure in those cases. STUDY DESIGN: Between 2001 and 2003 years, 14 measles cases admitted to the Hospital of Infectious Diseases of Minsk were enrolled in our study. Clinical, routine laboratory, as well as serological and virological examinations were carried out. Detection of measles antibodies and IgG avidity testing was performed using commercial test kits. All measles cases were confirmed by RT-PCR and phylogenetically characterized. RESULTS: Only 42.9% of the cases met the WHO laboratory criteria for measles, however, all cases were confirmed by RT-PCR. Most of the measles cases were attributed to secondary vaccine failure (SVF). Phylogenetic analysis revealed the presence of genotype A virus strains in 2001 and 2002 with D6 and D7 genotypes in 2003. CONCLUSIONS: For the first time, MVs were genetically characterized in Belarus. Our results suggest that in a highly vaccinated population, most of measles cases represent vaccine failures and are vaccine-modified. Our results also indicate that confirmation of a clinical diagnosis of vaccine-modified measles requires a combination of serological and virological tests.

PMID: 16214679 [PubMed - indexed for MEDLINE]

 
Duration of immunity against pertussis after natural infection or vaccination.

Wendelboe AM, Van Rie A, Salmaso S, Englund JA.

Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA. awendelboe@unc.edu

Despite decades of high vaccination coverage, pertussis has remained endemic and reemerged as a public health problem in many countries in the past 2 decades. Waning of vaccine-induced immunity has been cited as one of the reasons for the observed epidemiologic trend. A review of the published data on duration of immunity reveals estimates that infection-acquired immunity against pertussis disease wanes after 4-20 years and protective immunity after vaccination wanes after 4-12 years. Further research into the rate of waning of vaccine-acquired immunity will help determine the optimal timing and frequency of booster immunizations and their role in pertussis control.

Publication Types:

• Review

PMID: 15876927 [PubMed - indexed for MEDLINE]

 
Potential strategies to reduce the burden of pertussis.

Forsyth K, Tan T, von Konig CH, Caro JJ, Plotkin S.

Flinders University, Adelaide, Australia. Kevin.Forsyth@flinders.edu.au

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.

Publication Types:

• Review

PMID: 15876930 [PubMed - indexed for MEDLINE]

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

Tan T, Halperin S, Cherry JD, Edwards K, Englund JA, Glezen P, Greenberg D, Rothstein E, Skowronski D.

Division of Infectious Diseases, Northwestern University's Feinberg School of Medicine, The Children's Memorial Hospital, Chicago, IL 60614, USA. titan@childrensmemorial.org

In North America, children currently receive 5 doses of a combined diphtheria-tetanus-acellular pertussis vaccine between the ages of 2 months and 6 years. Although this schedule has reduced the incidence of childhood pertussis, it has not led to the development of herd immunity in the total population, largely because pertussis immunity wanes with time. The time course over which immunity wanes is uncertain; however, high pertussis antibody titers in adolescents and adults indicate unrecognized infection in these groups. There is evidence that this group serves as a source of infection for young infants who are not fully immunized. Therefore, of the potential strategies reviewed by the North American Global Pertussis Initiative group, universal adolescent immunization would in theory reduce the risk of pertussis in this age group and may reduce transmission to young infants. However, because immunity probably wanes at the same rate in adolescents and children, the burden of disease will likely shift to older age groups, including young adults (parents of vulnerable infants). Therefore the ideal would be immunization of adolescents and adults, particularly those who are in contact with young infants. Adolescent immunization is already recommended in Austria, France, Germany and Canada, and participants in the Global Pertussis Initiative recommend that this strategy be implemented across North America with a view to eventually extending immunization to include adults. The final decision to implement such a strategy will depend on pertussis surveillance studies and analysis of the effectiveness and tolerability of adolescent and adult pertussis immunization as well as program considerations related to feasibility and economics.

Publication Types:

• Review

PMID: 15876933 [PubMed - indexed for MEDLINE]

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

Forsyth K, Nagai M, Lepetic A, Trindade E.

Department of Paediatrics, Flinders Medical Centre, Flinders University, Adelaide, Australia. Kevin.Forsyth@flinders.edu.au

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.

Publication Types:

• Review

PMID: 15876935 [PubMed - indexed for MEDLINE]

 
Erratum in:

• Pediatr Infect Dis J. 2005 Nov;24(11):983.

Pertussis in adolescents: increasing incidence brings attention to the need for booster immunization of adolescents.

Greenberg DP.

Scientific and Medical Affairs, sanofi pasteur, Swiftwater, PA 18370, USA. david.greenberg@sanofipasteur.com

As a result of waning immunity and improved awareness, the reported incidence of pertussis is increasing among adolescents in the United States. Symptoms of pertussis are often mild and difficult to diagnose in adolescents, but these individuals can transmit the infection to schoolmates and family members, including high risk infants. Improvements in diagnosis and prevention of pertussis in adolescents are needed.

Publication Types:

• Review

PMID: 16094229 [PubMed - indexed for MEDLINE]

 
[Vaccinations in adults--who? when? why?]

[Article in German]

Hofmann F.

Fachgebiet Arbeitsphysiologie, Arbeitsmedizin und Infektionsschutz, Bergische Universitat Wuppertal. fhofmann@uni-wuppertal.de

Despite the success of childhood vaccinations in Europe, many infectious diseases pose a threat to adults, particularly because immunity induced by vaccination is not life long in some cases. This paper presents the rationale for adult boosters for diphtheria, hepatitis B, pertussis, poliomyelitis and tetanus. Moreover indication for adult-vaccinations against measles, mumps, German measles and varicella is discussed, as a significant part of the population in Germany is susceptible or without known immunity/vaccination history. Finally, immunisation of the elderly against infections with influenza-virus and S. pneumoniae will be described.

PMID: 15655680 [PubMed - indexed for MEDLINE]

 
Overview of pertussis: focus on epidemiology, sources of infection, and long term protection after infant vaccination.

Edwards KM.

Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-2573, USA. Kathryn.Edwards@vanderbilt.edu

BACKGROUND: Pertussis, or whooping cough, is a bacterial disease characterized by paroxysmal cough often accompanied by inspiratory whoop and posttussive emesis. Although the introduction of whole-cell pertussis vaccine in the 1940s led to a significant decline in the incidence of pertussis, there has been a gradual increase in reported pertussis cases since 1980. Some of these cases are in infants too young to have received routine pertussis vaccination, and many are in adolescents immunized previously as young children. METHODS: Based on a literature review, an overview of pertussis is provided, focusing on epidemiology, sources of infection, and trends in incidence patterns, particularly among adolescents. Issues surrounding long-term protection after infant vaccination are also discussed. RESULTS: The most dramatic increase in pertussis incidence has been among adolescents and young adults. Waning vaccine-induced immunity and refinements in the diagnosis of pertussis have contributed to the rise in the occurrence of pertussis in older age groups. Disease rates in infants have also increased. Determining the source of infection in infants can be challenging, but studies have demonstrated that many infant cases are attributable to infections in adolescent or adult family members. CONCLUSIONS: Pertussis is on the rise, particularly in adolescents. Booster vaccination of adolescents with less-reactogenic acellular pertussis vaccines appears to be the most logical approach to disease prevention in adolescents and reduced transmission to young infants.

Publication Types:

• Historical Article

PMID: 15931137 [PubMed - indexed for MEDLINE]

 
Immunogenicity of a combined diphtheria-tetanus-acellular pertussis vaccine in adults.

Van Damme P, Burgess M.

Centre for the Evaluation of Vaccination, Faculty of Medicine, University of Antwerp, Universiteitsplein, 1 B-2610 Antwerp, Belgium. pierre.vandamme@ua.ac.be

Two clinical studies were undertaken to evaluate the immunogenicity of an adult-type dTpa booster vaccine (Boostrix by GlaxoSmithKline Biologicals). Blood samples taken prior to vaccination showed that 24.4 and 13.0% of subjects were seronegative for diphtheria and tetanus antibodies, respectively. Moreover, about one-third of the vaccinees had no detectable levels of antibodies to pertussis toxoid (PT) or pertactin (PRN). One month post-vaccination, more than 93% of all individuals, regardless of age or type of vaccine received, had seroprotective antibody levels for diphtheria and tetanus (> or = 0.1IU/ml). In those individuals vaccinated with the adult-type dTpa vaccine (Boostrix), more than 98% were found to be seropositive for antibodies to all three pertussis antigens (PT, filamentous haemogluttin (FHA), and PRN). These data suggest that immunity to diphtheria, tetanus and pertussis (DTP) in adults wanes and that booster vaccination with an adult-type combined dTpa vaccine would boost the serological response to diphtheria antitoxin, tetanus antitoxin and antibodies to Bordetella pertussis PT, FHA and PRN.

Publication Types:

• Clinical Trial

PMID: 14670310 [PubMed - indexed for MEDLINE]

  
Identification of primary and secondary measles vaccine failures by measurement of immunoglobulin G avidity in measles cases during the 1997 Sao Paulo epidemic.

Pannuti CS, Morello RJ, Moraes JC, Curti SP, Afonso AM, Camargo MC, Souza VA.

Instituto de Medicina Tropical de Sao Paulo-LIM-HC, Departamento de Molestias Infecciosas e Parasitarias, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil. cpannuti@usp.br

Despite almost universal use of measles vaccines in recent decades, epidemics of the disease continue to occur. Understanding the role of primary vaccine failure (failure to seroconvert after vaccination) and secondary vaccine failures (waning immunity after seroconversion) in measles epidemics is important for the evaluation of measles control programs in developing countries. After a measles epidemic in Sao Paulo, Brazil, 159 cases previously confirmed by detection of specific immunoglobulin M (IgM) antibodies were tested for IgG avidity, and a secondary immune response, defined by an IgG avidity index of at least 30%, was established in 30 of 159 (18.9%) patients. Among the 159 patients, 107 (67.3%) had not been vaccinated and 52 (32.7%) had received one or more doses of measles vaccine. Of the 107 unvaccinated patients, 104 (97.2%) showed a primary immune response, defined as an IgG avidity index of less than 30%. Among the 52 patients with documented vaccination, 25 (48.1%) showed a primary immune response and 27 (51.9%) showed a secondary immune response, thereby constituting a secondary vaccine failure. Primary vaccine failure was observed in 13 of 13 patients vaccinated prior to 1 year of age and in 43.5 and 12.5%, respectively, of patients receiving one or two doses after their first birthdays. These results provide evidence that measurement of IgG avidity can be used to distinguish between primary and secondary vaccine failures in vaccinated patients with measles; the method can also be a useful tool for the evaluation of measles control programs.

PMID: 14715557 [PubMed - indexed for MEDLINE]

 
Waning immunity and subclinical measles infections in England.

Glass K, Grenfell BT.

National Centre for Epidemiology and Population Health, Australian National University, Canberra 0200, Australia. kathryn.glass@anu.edu.au

Following the introduction of vaccination against measles, levels of clinical infection have dropped markedly. As we move further into the vaccine era, increasingly many individuals owe their measles immunity to vaccination and have had few (if any) exposures to wild virus. A number of recent reports suggest that vaccinated individuals with low levels of immunity may be at risk of subclinical measles infection. We explore the interplay between levels of infection and immunity over time using a mathematical model that simulates infection, waning and boosting of immunity. We focus particularly on the situation in England, where vaccination has been in place since 1966. Simulations of our model demonstrate a rise in the levels of subclinical measles infection over time, and a corresponding rise in clinical measles infections if vaccination levels are too low. We compare the impact of intervention strategies, and find that the rise in cases is most effectively reduced by 'catch-up' vaccination of children. In recent years, vaccination levels in England have dropped from above 90% in the 1990s to 84% in 2001/2002. We discuss the impact of declining vaccination levels on clinical and subclinical infections.

PMID: 15364464 [PubMed - indexed for MEDLINE]

 
The challenge of improving the efficacy of measles vaccine.

Garly ML, Aaby P.

Projecto de Saude Bandim, Apartado 861, Bissau, Guinea-Bissau. mlg@ssi.dk

Despite a safe and effective measles vaccine, measles still claims an estimated 800,000 lives per year mostly among children in developing countries. This paper deals with strategies to improve vaccine efficacy and prevent unnecessary deaths, including considerations of one dose at 9 months strategy for developing countries, strain of vaccine, potency and number of doses of measles vaccine. After more than 20 years of measles immunisation in the developing world, the epidemiology of measles is radically changed, and the absence of measles epidemics might lead to waning immunity due to less clinical and subclinical infections boosting the antibody level. An increasing proportion of mothers are vaccinated, thus transferring a lower maternal antibody level to their infants who will be susceptible to measles at a younger age. The strategies to limit nosocomial measles infection and spread of measles epidemics are reviewed. Though the measles elimination programmes have been very effective in the Americas, it seems unlikely that they will be equally effective in the rest of the world. Even if eradication should be possible, it might be unwise to stop measles vaccination because the vaccine apparently has beneficial effects and because it would make measles a likely weapon for bio-terrorism. If we are unlikely to get rid of measles and measles vaccine, it might be wise to study further some of the many unanswered questions regarding the long-term effects of measles and measles vaccination. Copyright 2002 Elsevier Science B.V.

Publication Types:

• Review

PMID: 12505179 [PubMed - indexed for MEDLINE]

 
Antibody dynamics in childhood diseases: waning and boosting of immunity and the impact of vaccination.

Glass K, Grenfell BT.

University of Cambridge, Department of Zoology, Downing Street, Cambridge CB2 3EJ, UK. katie@zoo.cam.ac.uk

The introduction of vaccination against acute diseases such as measles induced a dramatic decline in the prevalence of the disease, and a more gradual rise in the proportion of the population whose immunity is derived solely from vaccination. These two factors combine to constitute an important shift in the dynamics of immunity, especially in highly vaccinated populations. We develop a general model to describe both loss of immunity in the absence of disease, and boosting of immunity corresponding to subclinical infection in individuals whose immunity has waned. We consider the interaction between infection and immunity and identify the key parameters that determine the eradication threshold. We explore the dynamics in the years following the introduction of vaccination using a stochastic version of the model, and consider the effect of different assumptions concerning the nature of immunity. A comparison of the model results with recently published data suggests that heterogeneity in host immune response is an important feature of the antibody dynamics.

PMID: 12634049 [PubMed - indexed for MEDLINE]

 
Modelling measles re-emergence as a result of waning of immunity in vaccinated populations.

Mossong J, Muller CP.

Laboratoire National de Sante, P.O. Box 1102, L-1011 Luxembourg, Luxembourg. joel.mossong@lns.etat.lu

An age-structured mathematical model of measles transmission in a vaccinated population is used to simulate the shift from a population whose immunity is derived from natural infection to a population whose immunity is vaccine-induced. The model incorporates waning of immunity in a population of vaccinees that eventually will become susceptible to a milder form of vaccine-modified measles with a lower transmission potential than unvaccinated classical measles. Using current estimates of duration of vaccine-derived protection, measles would not be expected to re-emerge quickly in countries with sustained high routine vaccine coverage. However, re-emergence is possible to occur several decades after introduction of high levels of vaccination. Time until re-emergence depends primarily on the contagiousness of vaccine-modified measles cases in comparison to classical measles. Interestingly, in a population with a high proportion of vaccinees, vaccine-modified measles and classical measles would occur essentially in the same age groups. Although waning of humoral immunity in vaccinees is widely observed, re-emergence of measles in highly vaccinated populations depends on parameters for which better estimates are needed.

PMID: 14575773 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11066183&dopt=Abstract

 

JAMA 2000 Nov 8;284(18):2334-40

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Antibody concentration and clinical protection after Hib conjugate vaccination in the United Kingdom.

Heath PT, Booy R, Azzopardi HJ, Slack MP, Bowen-Morris J, Griffiths H, Ramsay ME, Deeks JJ, Moxon ER.

Department of Child Health and St. George's Vaccine Institute, St George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, England. pheath@sghms.ac.uk

CONTEXT: The schedule for Haemophilus influenzae type b (Hib) vaccination of infants in the United Kingdom consists of 3 doses given at 2, 3, and 4 months of age. Many countries include a fourth dose (booster) of Hib vaccine in the second year of life on the basis of declining Hib antibody concentrations after the primary series. Few data are available to show that this fourth dose is actually necessary. OBJECTIVE: To evaluate long-term clinical protection against Hib disease and Hib antibody concentrations following primary Hib vaccination without a booster dose. DESIGN, SETTING, AND SUBJECTS: Clinical protection study conducted between October 1992 and March 1999 in the United Kingdom, in which children developing invasive Hib disease despite vaccination in infancy with 3 doses of Hib conjugate vaccine were reported by pediatricians through an active, prospective, national survey. Separate antibody studies were conducted among 2 cohorts of children (n = 153 and n = 107) vaccinated at 2, 3, and 4 months of age with Hib conjugate vaccine and followed up to 43 and 72 months of age. MAIN OUTCOME MEASURES: Age-specific vaccine effectiveness, derived from the observed number of true vaccine failures after 3 Hib vaccine doses compared with the number of cases expected based on the age-specific rates of invasive Hib disease obtained prior to the introduction of Hib vaccines; and proportion of children in the 2 cohorts with Hib antibody concentrations of less than 0.15 and less than 1.0 microg/mL. RESULTS: Ninety-six true vaccine failures occurring after 3 vaccine doses were detected. During the study period, an estimated 4,368,200 infants in the United Kingdom received 3 doses of vaccine; therefore, the vaccine failure rate was 2.2 per 100,000 vaccinees (95% confidence interval, 1.8-2.7 per 100,000). Although vaccine effectiveness declined significantly after the first year of life (P<.001), it remained high until the sixth year of life (99.4% in children aged 5-11 months vs 97.3% in those aged 12-71 months). The proportion of cohorts 1 and 2 with anti-PRP antibody levels of less than 0.15 microg/mL increased between 12 and 72 months of age (6% at 12 months, 8% at 43 months, and 32% at 72 months; chi(2)(1) = 18.25; P<.001 for trend). CONCLUSIONS: Our results suggest that anti-PRP antibody levels and clinical protection against Hib disease wane over time after Hib vaccination at 2, 3, and 4 months of age without a booster dose at 2 years of age. The decline in clinical protection is minimal, however, suggesting that a booster dose of Hib vaccine following infant vaccination is not essential. JAMA. 2000;284:2334-2340.

PMID: 11066183 [PubMed - indexed for MEDLINE]