Smallpox Vaccination of Laboratory Workers at US Variola Testing Sites.

To evaluate the need to revaccinate laboratory workers against smallpox, we assessed regular revaccination at the US Laboratory Response Network's variola testing sites by examining barriers to revaccination and the potential for persistence of immunity. Our data do not provide evidence to suggest prolonging the recommended interval for revaccination.

Tuberculosis vaccine development at a divide.

PURPOSE OF REVIEW: Tuberculosis (TB) remains a major health threat that will only be defeated by a combination of better drugs, diagnostics and vaccines. The only licensed TB vaccine, bacille Calmette-Guérin (BCG), protects against extrapulmonary TB in infants. RECENT FINDINGS: Novel vaccine candidates that could protect against pulmonary TB either in TB naïve or in latent TB-infected healthy individuals have been developed and are currently being assessed in clinical trials. Subunit booster vaccines are either based on viral vectors expressing TB-specific antigens or on TB-protein antigens in adjuvants. Subunit vaccines are administered on top of BCG. Replacement vaccines for BCG are recombinant viable BCG or Mycobacterium tuberculosis. Several candidates are undergoing, or will soon start, phase IIb assessment for efficacy. The first vaccine candidate, MVA85A, to complete a phase IIb trial, unfortunately failed to show protection against TB in infants. Therapeutic vaccines composed of killed mycobacterial preparations target patients with complicated TB in adjunct to drug treatment. SUMMARY: With increasing numbers of TB vaccine candidates in clinical trials, financial, regulatory and infrastructural issues arise, which would be best tackled by a global strategy. In addition, selection of the most promising vaccine candidates for further clinical development gains increasing importance.

[Old problems and new strategies in the fight against pertussis]. / Vecchi problemi e nuove strategie nella lotta contro la pertosse.

Pertussis is still a major Public Health problem. In fact, despite high vaccination coverage, several outbreaks have occurred in the last years all over the world, with thousands of cases and several deaths. Waning immunity seems to be the origin of this phenomenon, causing the shift of the peak incidence of the disease from school-age children, typical of the pre-vaccination era, to adolescents and adults. From these subjects the infection spreads to infants who have not yet been vaccinated or who have not completed the vaccination cycle. To reduce the incidence and the complications of pertussis in infants and immune compromised persons, booster doses are recommended and a "cocoon" vaccination strategy has been proposed.

Annual report: Surveillance of adverse events following immunisation in Australia, 2011.

This report summarises Australian passive surveillance data for adverse events following immunisation (AEFI) reported to the Therapeutic Goods Administration (TGA) for 2011, and describes reporting trends over the 12-year period 2000 to 2011. There were 2,327 AEFI records for vaccines administered in 2011, a decrease of 40% from 3,894 in 2010. The decrease in 2011 was attributable to a decline in reporting following seasonal influenza (2,354 to 483) and pandemic H1N1 (pH1N1) influenza vaccines (514 to 2). However, reporting rates for some other vaccines were higher in 2011 compared with 2010. The 13-valent pneumococcal conjugate vaccine (13vPCV) replaced the 7-valent pneumococcal conjugate vaccine (7vPCV) and was suspected of involvement in 236 AEFI cases (48 per 100,000 doses). An increase in the number of reports following rotavirus (from 40 to 56 per 100,000 doses), and the hexavalent infant vaccine (from 27 to 40 per 100,000 doses), may have been due at least in part to co-administration with 13vPCV. Reports following DTPa-IPV also increased (from 94 to 139 per 100,000 doses), continuing a trend since 2009. AEFI reports following receipt of the 23-valent pneumococcal vaccine also increased markedly in those aged ≥65 years, from 155 to 288 records. In response to the increase in reports following 23vPPV, boosters are no longer recommended for those without medical risk factors. The most commonly reported reactions were injection site reactions, fever, allergic reactions and malaise. Only 7% of all the reported adverse events were categorised as serious, as per the database definitions, although some events classified as non-serious may have caused severe illness. Three deaths were temporally associated with vaccination; however, all were attributed to causes other than vaccination. The increase in 2011 was predominately due to reports of injection site reactions (49% increase in 2011). Increases in some instances may also be partly attributable to an increasing propensity to report AEFI.

Impact of the adolescent pertussis booster dose on the incidence of pertussis in British Columbia and Quebec, Canada.

Impact of an adolescent tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine program was assessed in the provinces of British Columbia and Quebec, Canada. In both provinces, the Tdap booster has been in place since 2004, targeting Grade 9 students (14-15-years-of-age). Incidence rate ratios (IRRs) standardizing notification rates among teens 15-19-years-old to infants <1-year-old decreased following introduction of the Tdap program and were significantly halved during the 2009-2012 post-Tdap versus 2000-2003 pre-Tdap period. This program impact, however, is tempered by the observation that pertussis incidence among 15-19-year-olds was already lower than any other pediatric age group, following gradual decline from pre-teen rates even before the Tdap program. The risk of hospitalization among adolescents 15-19-years-old was also low throughout at <1/100,000. Furthermore, IRRs increased in 2013-2017 when an increasing proportion of 15-19-year-olds were primed with acellular pertussis vaccine only, suggesting short-lived Tdap booster-dose effectiveness that warrants further monitoring.

Progress toward the global control of Neisseria meningitidis: 21st century vaccines, current guidelines, and challenges for future vaccine development.

The control of meningitis, meningococcemia and other infections caused by Neisseria meningitidis is a significant global health challenge. Substantial progress has occurred in the last twenty years in meningococcal vaccine development and global implementation. Meningococcal protein-polysaccharide conjugate vaccines to serogroups A, C, W, and Y (modeled after the Haemophilus influenzae b conjugate vaccines) provide better duration of protection and immunologic memory, and overcome weak immune responses in infants and young children and hypo-responsive to repeated vaccine doses seen with polysaccharide vaccines. ACWY conjugate vaccines also interfere with transmission and reduce nasopharyngeal colonization, thus resulting in significant herd protection. Advances in serogroup B vaccine development have also occurred using conserved outer membrane proteins with or without OMV as vaccine targets. Challenges for meningococcal vaccine research remain including developing combination vaccines containing ACYW(X) and B, determining the ideal booster schedules for the conjugate and MenB vaccines, and addressing issues of waning effectiveness.

Levels of diphtheria and tetanus specific IgG of Portuguese adult women, before and after vaccination with adult type Td. Duration of immunity following vaccination.

BACKGROUND: The need for tetanus toxoid decennial booster doses has been questioned by some experts. Several counter arguments have been presented, supporting the maintenance of decennial adult booster doses with tetanus and diphtheria toxoids (adult formulation of the vaccine: Td). This study aimed to evaluate the use of Td in Portuguese adult women under routine conditions. For that purpose we selected a group of women 30+ years of age to which vaccination was recommended. We intended to know if pre-vaccination antibody concentrations were associated with factors as age at first and last vaccination, number of doses and time since last revaccination. We also intended to assess the serological efficacy of Td booster. METHODS: Following the Portuguese guidelines 100 women were vaccinated with Td. Antitetanus toxin IgG (ATT IgG) and antidiphtheria toxin IgG (ADT IgG) levels were measured (mIU/ml) in 100 pre-vaccination and 91 post-vaccination sera. Detailed vaccination records were available from 88 participants. RESULTS: Twenty-two women (Group A) began vaccination with DPT/DT in their early childhood and their pre-vaccination ATT IgG levels increased with the number of doses received (p = 0.022) and decreased with time since last vaccination (p = 0.016). Among the 66 women who began vaccination in adolescence and adulthood (Group B), with monovalent TT, ATT IgG levels decreased with age at first dose (p < 0.001) and with time since last vaccination (p = 0.041). In Group A, antidiphtheria toxin IgG kinetics was very similar to that observed for ATT IgG. Among women not vaccinated with diphtheria toxoid, ADT IgG levels decreased with age. Serological response to both components of Td was good but more pronounced for ATT IgG. CONCLUSION: Our study suggests that, to protect against tetanus, there is no need to administer decennial boosters to the Portuguese adults who have complied with the childhood/adolescent schedule (6 doses of tetanus toxoid). The adult booster intervals could be wider, probably of 20 years. This also seems to apply to protection against diphtheria, but issues on the herd immunity and on the circulation of toxigenic strains need to be better understood.

[Who is it necessary to vaccine against whooping-cough?]. / Qui faut-il vacciner contre la coqueluche?

Whooping-cough is one of the rare diseases for which vaccine prevention has been available for many years. However, in spite of good vaccine coverage in the infant, the pertussis infection remains a frequent disease in the teenagers and adults partially immunized. The missing diagnosis of the infection, added to its often clinical banal expression, contributes to support the circulation of Bordetella pertussis and explains the contamination of the young infants in whom the disease remains a true danger as the few declared deaths show it every year. Control of the disease must go through reinforcement of vaccination as a practitioner of booster vaccine in preadolescents, teenagers and adults. Instituted since 1998 in the French vaccine calendar, the 2nd booster in preadolescence between 11-13 years olds or 5th dose of vaccine is not enough carried out and must be encouraged like the installation of another additional vaccine dose for adults and certain professional categories. The protection of infants too young to have received the 3 doses goes through the vaccination of their entourage, family and socio-professional alike. The new recommendations thus preach to begin vaccination in children from the age of 2 months, a reinforcement of the vaccine boosters in preadolescents, in adults likely to become parents and in the medical and paramedical personnel in contact with very young infants.

[Adult immunisation: General points, hot topics and perspectives]. / Vaccination de l'adulte : données générales, actualités et perspectives.

Vaccination in immunocompetent adult mainly concerns booster vaccination against diphtheria, tetanus, polio and pertussis. Some chronic diseases may also require the achievement of pneumococcal and influenza vaccines. In addition, from the age of 65, annual influenza vaccination as well as one dose of a live attenuated shingles vaccine between 64 and 75 years are recommended. Immunocompromised adults, due to the increased risk of serious infections responsible of significant morbidity and mortality, are particularly concerned by vaccination. Main issues in this population are the decreased immunogenicity and efficacy of vaccination and the risk of infection with live attenuated vaccines and. Depending on the type of immunosuppression, the recommended vaccines and vaccination schemes differ. Vaccination of healthy persons caring or residing with immunocompromised patients is an important point in the vaccine strategy. The current perspectives in vaccinology concern the development of vaccines against healthcare associated infections (Clostridium difficile and Staphylococcus aureus in particular), the strategy of vaccination during pregnancy to protect new-borns (respiratory syncytial virus, group B streptococcus) and the development of new adjuvants and new routes of immunization. With the overall decline in immunization coverage and increasing distrust of vaccination, the problem of vaccine hesitancy is also a hot topic. The reasons for doubt in the vaccine usefulness and the solutions to be applied are also crucial issues.

[Pentavalent vaccine and vaccination coverage in children aged less than one in Colombia 2000-2003]. / Vacuna pentavalente y coberturas de vacunación en menores de un año Colombia 2000-2003.

OBJECTIVE: Determining the impact of including pentavalent vaccine in third-dose immunisation coverage for children aged less than 1 (2002 and 2003) by geographic cluster. MATERIALS AND METHODS: This was an ecologic study using department, province, municipality and capital city as analysis units. It compared third-dose coverage, desertion index, number of places having more than 80% immunisation coverage and the number of children being immunised before and after vaccination was introduced. Having more than 80% immunisation coverage was compared to the number of children or places having unsatisfied basic needs, the presence of armed conflict or municipal category. RESULTS: Immunisation coverage increased from 23% to 26%, mainly for Hib3. Desertion index was 9.3-31.7% in 2000 and 0.3% in 2003. The number of municipalities having more than 80% immunisation coverage increased from 265 in 2000 to 627 in 2003. 462,000-584,000 third-doses were applied in 2000 and 805,000-813,000 in 2003. More municipalities having more than 80% coverage had high unsatisfied basic needs, low socioeconomic income or conflict. CONCLUSIONS: The introduction of the vaccine affected immunisation coverage. Financing should be sought for the vaccine to ensure its continuity and to implement studies for new vaccines or introducing combination vaccines.

Epidemiology of pertussis.

The World Health Organization recommended that a pertussis incidence of <1 case per 100,000 population be achieved in Europe by 2000. Available data indicate that this goal has generally not been achieved, and the incidence is actually rising in some countries. Understanding the reasons for this increased incidence may lead to better global control of pertussis. In the majority of countries where pertussis is a notifiable disease, a case-based national surveillance system is in place. However, different case definitions, methods of diagnosis and reporting and surveillance systems make direct intercountry comparisons difficult, and pertussis is not a statutory notifiable disease in every country. Nevertheless the general consensus is that reported incidences are probably considerably lower than the actual incidence of pertussis; underreporting is common. Prolonged cough may be the only clinical feature in adolescents or adults, who may present for diagnosis late (precluding laboratory confirmation) or not at all. When they do present, their condition is often misdiagnosed because, in part, clinicians continue to perceive pertussis as a childhood disease. Despite underreporting, an increased incidence of infant, adolescent and adult pertussis has been observed worldwide since the introduction of widespread vaccination. This is of concern because adolescents and adults have been identified as a source of transmission of pertussis to very young infants who are unimmunized or partially immunized and thus more vulnerable to disease-related complications and higher mortality. In recent years, acellular pertussis vaccines have been incorporated into the immunization schedules of many developed countries, gradually replacing whole cell vaccines. Dosing schedules vary between countries, although primary immunization with 3 doses of the pertussis vaccine within the first 6 months of life exists in most countries. Only Australia, Austria, Canada, France and Germany have incorporated an adolescent booster dose into their current immunization schedules, in recognition of the rising incidence of pertussis in adolescents and adults. Despite high coverage rates for primary immunization in infants and children, pertussis continues to be a global concern, with increased incidence widely noted. This global epidemiologic summary highlights differences worldwide in pertussis reporting, incidence and approaches to prevention. It underscores a general shift in the age distribution of pertussis toward older groups. Understanding the link between these observations may lead to better informed global control strategies, especially those pertaining to immunization schedules and use of pertussis vaccine.

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.

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

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.

Economic evaluation of an extended acellular pertussis vaccine program for adolescents in Québec, Canada.

OBJECTIVE: Pertussis is a frequent cause of cough illness in adolescents. In Canada, immunization against pertussis in public programs has been restricted to children under 7 years of age. The purpose of this analysis was to estimate the health and economic impact of an additional booster dose of the acellular vaccine in adolescents in Québec. METHOD: We performed a cost-effectiveness analysis, based on a predictive spreadsheet dynamic model following a cohort of 90,929 adolescents in Québec from the age of 14 years over a 10-year period from the Québec Ministry of Health (MOH) and societal (SOC) perspectives. The model was used to compare costs (2003 values) and benefits of an adolescent vaccination program (AVP), including a diptheria, tetanus, and acellular pertussis (dTacp) vaccine administered at age 14 years, with current practice. RESULTS: From the MOH perspective, a booster vaccination of dTacp at age 14 years via the AVP would produce a yearly additional expected cost of Can dollars 1.06 per adolescent with an incremental cost-effectiveness ratio (ICER) of Can dollars 480 per pertussis case avoided based on a 10-year period. When outcomes are discounted at 3%, the ICER rises to Can dollars 527 per discounted pertussis case avoided. From the SOC perspective, the AVP would cost Can dollars 0.83 per adolescent per year with an additional cost per avoided pertussis case of Can dollars 377 (Can dollars 414 per additional discounted case of pertussis avoided). Over the 10-year period, 2012 non-discounted cases of pertussis would be prevented with approximately two hospital admissions averted. CONCLUSION: This study suggests that administering a booster dose of dTacp at age 14 years to replace the diptheria and tetanus vaccination will slightly increase the economic burden from MOH and SOC perspectives; however, the number of pertussis cases and the number of hospital admissions will decrease.

An assessment of the interval between booster doses of Japanese encephalitis vaccine in the Torres Strait.

OBJECTIVE: Japanese encephalitis (JE) emerged for the first time in the Torres Strait, north Australia, in 1995. The inactivated mouse-brain derived JE vaccine was offered to all residents of the outer Torres Strait Islands prior to the 1996 wet season. This study was undertaken to determine the appropriateness of the recommended three-year interval between booster doses of the vaccine. METHODS: JE neutralising antibody was measured in residents of Badu Island for whom 30-36 months had passed since either a previous booster or the completion of the primary immunisation series. RESULTS: Only 70 (32%) of 219 eligible individuals had protective antibodies; 50 (37%) of the adults were immune, compared with 20 (24%) of the children (odds ratio (OR) 1.93; 95% confidence interval (CI) 1.01-3.74). CONCLUSIONS: This low level of immunity suggests that there is little in the way of natural boosting from either JE or other closely related viruses. Given the apparent low level of risk of exposure to the JE virus in the Torres Strait, and the logistical complexities involved in delivering the booster doses, the current recommendation of a three-year interval is not inappropriate. IMPLICATIONS: It would be advantageous to have a JE vaccine that is not only safer but also more immunogenic, so that it might be possible to further increase the booster dose interval.

The present and future of tuberculosis vaccinations.

The clinical, social, and economic burden of tuberculosis (TB) remains high worldwide, thereby highlighting the importance of TB prevention. The bacilli Calmette-Guérin (BCG) vaccine that is currently available can protect younger children but is less effective in adults, the major source of TB transmission. In addition, the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) strains and the high prevalence of HIV infection have significantly complicated TB prognosis and treatment. Together, these data highlight the need for new and more effective vaccines. Recently, several vaccines containing multiple antigens, including some of those specific for dormant Mtb strains, have been developed. These vaccines appear to be the best approach for satisfactory Mtb prevention. However, until a new vaccine is proven more effective and safe than BCG, BCG should remain part of the immunization schedules for neonates and children at risk for TB as a fundamental prophylactic measure.

Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2020 / Immunisation schedule of the Spanish Association of Paediatrics: 2020 recommendations

El CAV-AEP publica anualmente el calendario de vacunaciones que estima idóneo para los niños residentes en España, teniendo en cuenta la evidencia científica disponible. Se mantiene el esquema 2 + 1 (2, 4 y 11 meses) con vacunas hexavalentes (DTPa-VPI-Hib-HB) y con antineumocócica conjugada 13-valente. Se aconseja un refuerzo a los 6 años, preferentemente con DTPa (si está disponible), junto a una dosis de polio para aquellos que recibieron esquemas 2 + 1, así como vacunación con Tdpa en adolescentes y en cada embarazo, preferentemente entre las 27 y las 32 semanas. La vacuna del rotavirus debería ser sistemática para todos los lactantes. Se sigue proponiendo la incorporación en el calendario de la vacuna antimeningocócica B, con esquema 2 + 1 en lactantes. Además de la inclusión de la vacuna antimeningocócica conjugada tetravalente (MenACWY) a los 12 años con rescate hasta los 18 años, inclusive, el CAV recomienda que esta vacuna sea introducida también a los 12 meses de edad, sustituyendo a MenC. Igualmente, se recomienda en los mayores de 6 semanas de edad con factores de riesgo o que viajen a países de elevada incidencia de estos serogrupos. Se emplearán esquemas de 2 dosis para triple vírica (12 meses y 3-4 años) y varicela (15 meses y 3-4 años). La segunda dosis se podría aplicar como vacuna tetravírica. Se recomienda la vacunación sistemática universal frente al VPH, tanto a chicas como a chicos, preferentemente a los 12 años, debiendo realizar un mayor esfuerzo para mejorar las coberturas. La de 9 genotipos amplía la cobertura para ambos sexos

The CAV-AEP annually publishes the immunisation schedule considered optimal for all children resident in Spain, taking into account the available evidence. The 2 + 1 schedule is recommended (2, 4, and 11 months) with hexavalent vaccines (DTPa-VPI-Hib-HB) and with 13-valent pneumococcal conjugate. A 6-year booster is recommended, preferably with DTPa (if available), with a dose of polio for those who received 2 + 1 schemes, as well as vaccination with Tdpa in adolescents and in each pregnancy, preferably between 27 and 32 weeks. Rotavirus vaccine should be systematic for all infants. Meningococcal B vaccine, with a 2+1 schedule, should be included in routine calendar. In addition to the inclusion of the conjugated tetravalent meningococcal vaccine (MenACWY) at 12 years of age with catch up to 18 years, inclusive, the CAV recommends this vaccine to be also included at 12 months of age, replacing MenC. Likewise, it is recommended in those over 6 weeks of age with risk factors or who travel to countries with a high incidence of these serogroups. Two-dose schedules for MMR (12 months and 3-4 years) and varicella (15 months and 3-4 years) will be used. The second dose could be applied as a tetraviral vaccine. Universal systematic vaccination against HPV is recommended, both for girls and boys, preferably at 12 years, and greater effort should be made to improve coverage. The 9 genotype extends coverage for both genders