Childhood immunisation: what is the future?

Improved immunisation programmes and the development of new vaccines provide unprecedented opportunities to improve and sustain the health of our children. There are major challenges ahead in communicating the benefits of immunisation to all populations and in delivering vaccines to those in greatest need. In this review on immunisation, I have asked international opinion leaders to comment on the present and the future of immunisation to provide signposts for the narrative.     

Childhood tuberculosis: old and new vaccines

The world is witnessing an escalation of the tuberculosis (TB) epidemic, particularly in sub-Saharan Africa and South-East Asia. The problem has been compounded by the evolution of the human immunodeficiency virus pandemic, the increase in multidrug-resistant TB and the emergence of extensively drug-resistant TB. This has led to renewed interest in vaccines aimed at preventing tuberculosis. The current Bacille Calmette-Guérin (BCG) vaccine prevents the invasive complications of childhood tuberculosis, such as meningitis and miliary disease, but provides variable protection against adult pulmonary disease. This review discusses the history of the BCG vaccine, the reasons for its variable efficacy, protective immunity and TB, and the evolution of and obstacles to development of new candidate vaccines. Several new TB vaccines have demonstrated promising results in animal models; a number have gone into phase I clinical trials in humans, and it is anticipated that phase III trials will commence by 2009. Licensing of an effective new TB vaccine by 2015 is thus a possibility.     

Pediatric combination vaccines

There will be an increasing demand for safe and effective combination vaccines as more paediatric vaccines are developed and licensed for new indications. The successful introduction of new combination vaccines into the childhood immunization schedule has the potential to improve vaccine coverage and thus reduce morbidity and mortality from childhood infections, and also possibly to reduce the cost of vaccines and their delivery. This article reviews the recent literature regarding new combination vaccines and discusses the main issues surrounding the simultaneous administration of multiple vaccine antigens to children.     

New, and some not-so-new, vaccines for adolescents and diseases they prevent

Adolescents in the United States now have the opportunity to receive new vaccines that prevent invasive meningococcal infections, pertussis (whooping cough), and cervical cancer. Except for their potential to cause serious illness, these infections could not be more different. Their incidence ranges from extremely low to quite high. Early clinical manifestations of infection range from none to life-threatening illness. Two of the vaccines are similar to those already in use, whereas 1 is completely new. In conjunction with the 4 vaccines previously recommended for adolescents (the tetanus and diphtheria booster, hepatitis B, measles-mumps-rubella, and varicella), the 3 new vaccines (meningococcal, human papillomavirus, and the tetanus-diphtheria-pertussis booster [which replaced the tetanus-diphtheria booster]) bring the number recommended for adolescents to 6. In this article, we describe key characteristics of the 3 new vaccines and infections they were designed to prevent. We also briefly discuss other vaccines recommended for all adolescents who have not already received them and new vaccines that are still under development.     

A step ahead. Infant protection through maternal immunization

The concept of maternal immunization to prevent infectious diseases during a period of increased vulnerability in infants is not new and is supported by historical experience and carefully conducted studies of various viral and bacterial vaccines. Candidate vaccines should be minimally reactogenic, immunogenic, and safe for maternal immunization to be considered as a disease prevention strategy. The possibilities increase as more potential candidate vaccines for use during pregnancy become available, including conjugate meningococcal vaccines, parainfluenza virus type 3 purified subunit vaccines, herpes simplex virus, cytomegalovirus, and HIV vaccines. Additional research on the safety and efficacy of maternal immunization must continue to effect the development of infectious diseases in neonates and infants.     

A critique of criteria for evaluating vaccines for inclusion in mandatory school immunization programs

Several new vaccines for children and young adults have been introduced recently and now appear on the Advisory Committee on Immunization Practices' recommended childhood and adolescent immunization schedule (meningococcal, rotavirus, human papillomavirus). As new vaccines are introduced, states face complex decisions regarding which vaccines to fund and which vaccines to require for school or child care entry. This complexity is evidenced by the current debate surrounding the human papillomavirus vaccine. We present a critique to the approach and criteria for evaluating vaccines for inclusion in mandatory school immunization programs that have been adopted by the Washington State Board of Health by illustrating how these criteria might be applied to the human papillomavirus vaccine. We conclude that these 9 criteria can help ensure a deliberate and informed approach to important public policy decisions, but we argue that several clarifications of the review process are needed along with the addition of a 10th criterion that ensures that a new vaccine mandate relates in some manner to increasing safety in the school environment.     

Delivering new vaccines to adolescents: the role of school-entry laws

In the United States, state-based school-entry vaccination laws have been used effectively to rapidly increase vaccination rates among adolescents, in particular, for hepatitis B vaccine. New vaccines for adolescents raise the question of whether and under what circumstances school-entry laws may be used to increase coverage rates with these vaccines. The new vaccines differ somewhat from their predecessors and raise policy and legal issues. For example, some of the new vaccines prevent diseases for which the primary mode of transmission is sexual contact. Mandating these vaccines before school entry has been met with concern by those who believe that mandates for this type of vaccine not only intrude on parental decision-making rights but might also lead to sexual promiscuity among youth. In this article we explore (1) the possible utility of school-entry requirements to increase the delivery of the new vaccines for adolescents, including the legal basis for US school-entry laws, (2) arguments in favor and concerns about the adoption of laws for adolescent vaccination, and (3) the importance of including diverse stakeholders in the deliberative process and formulating and implementing laws in a way that maximizes their acceptance and effectiveness.     

Newer Haemophilus influenzae type b vaccines and passive prophylaxis

PRP-protein conjugate vaccines may prove to be a prototype of a new generation of bacterial vaccines for the prevention of diseases caused by encapsulated bacteria, such as pneumococci, meningococci and Group B streptococci, as well as Hib. These diseases often strike the very young, the very old and individuals with compromised immunity. These vaccines have been "engineered" to maximize immune recognition and response. It is hoped that these vaccines will be adequate to control or possibly eradicate Hib and other invasive bacterial diseases. For high risk populations unable to respond to the vaccines, passive prophylaxis may have a role.     

One for all: newer combination vaccines in practice

As new combination vaccines are approved, practices must consider whether to switch. The decision is likely to be complex, involving everything from re-education of staff to recalculating the bottom line. At some point, however, change will be inevitable, driven principally by the need to add new vaccines to the schedule. In fall 2004, practitioners will be adding two doses of inactivated influenza vaccine to the infant schedule. More communities will be adding two doses of hepatitis A vaccine, which may become routine for all children at some point. We can hope as well for a meningococcal conjugate vaccine series, which, like Hib and PCV-7, would be administered by an infant's first birthday. In addition, there's the pentavalent bovine reassortant rotavirus vaccine (Rotateq) which, although given orally, will further crowd the schedule. The sooner we become comfortable with combination vaccines, the better.     

Present status of vaccines in 1989

The authors describe 2 new vaccines now available in France: one is the GenHevac, an hepatitis B vaccine, the first virus recombinant vaccine; the other one is the Typhim Vi, a polysaccharide typhoid vaccine. Three other vaccines are currently used in foreign countries and will be soon available: the Hemophilus influenzae vaccine, the acellular pertussis vaccine and the varicella vaccine. Rotavirus and Cytomegalovirus vaccines are studied for their clinical efficacy.     

HIV vaccine development and clinical trials

The magnitude of HIV pandemic has made the development of HIV vaccines an urgent biomedical research priority. Although the biologic problems in designing a vaccine for a chronic viral infection like HIV are formidable, there has been encouraging progress. More than a dozen first generation prophylactic HIV vaccine candidates have completed phase I human trials that have established the safety and immunogenicity of these products in adults. A phase II trial of two HIV subunit envelope vaccines in adults at high risk of HIV infection is underway in the United States, and preparations for phase III efficacy trials have begun. Preliminary studies are under way to evaluate the potential application of active and passive immunization for preventing vertical transmission of HIV. Because of the higher rate of HIV transmission and a more abbreviated time course to disease, it may be more efficient to evaluate the efficacy of HIV vaccines in HIV infected pregnant women and their offspring than in adults who are exposed sexually to HIV.     

Child and adolescent immunisation in the UK: current issues

The childhood immunisation programme in UK is highly successful and constantly under review. Changes are frequent with new vaccines introduced or alterations to the timing or number of doses of existing vaccines. It is important for child healthcare professionals to keep up to date with the programme, as parents will often turn to them for advice. In this article we outline recent changes to the vaccine programme and the impact of recently introduced vaccines on disease. Current issues, including increases in measles cases and addressing parents’ concerns about vaccines, are discussed.     

Health care providers’ and parents’ attitudes toward administration of new infant vaccines—a multinational survey

The New Vaccinations of Infants in Practice online survey in seven countries evaluated vaccination-related attitudes and concerns of parents of infants and health care providers (HCPs) who provide pediatric medical care. The survey showed that HCPs and parents were open to adding new vaccines to the immunization schedule, even if it requires co-administration with current vaccines or introduction of new office visits. Parental disease awareness campaigns would be helpful to achieve widespread acceptance of changes to vaccination schedules. In addition, HCPs would ideally provide disease education to parents to accompany recommendations for a new vaccine.     

-Vaccination against hepatitis B-.

Although relatively uncommon among French children, hepatitis B virus infection is a major problem of public health which deserves coordinated strategies of prevention and immunization, in order to eliminate chronic carriers among groups at risk. The participation of pediatricians to these strategies is essential, knowing that transmission of hepatitis B virus from asymptomatic carrier mothers to their newborns contributes to new generation of chronic carriers who will be exposed to cirrhosis and hepatocellular carcinoma. Four hepatitis B vaccine are presently available in France with equal good efficiency and tolerance. These vaccines allow a protection against hepatitis B in 90 to 95% of the vaccinated subjects. Active search for new vaccines, particularly DNA vaccines, is in progress to extend the protection to the 5-10% non or low responders. The current recommended strategy of immunization in France associates immunizations of infants, preadolescents and groups at risk. In addition newborns from carrier mothers must receive combined passive and active immunization at birth.     

Indian Academy of Pediatrics (IAP) recommended immunization schedule for children aged 0 through 18 years — India, 2013 and updates on immunization

Justification

There is a need to review/revise recommendations about existing vaccines in light of recent developments in the field of vaccinology where new developments are taking place regularly at short intervals.

Process

Following an IAP ACVIP meeting on 3rd and 4th August, 2013, a draft of revised recommendations for the year 2013 and updates on certain new vaccine formulations was prepared and circulated among the meeting participants to arrive at a consensus.

Objectives

To review and revise recommendations for 2013 Immunization timetable for pediatricians in office practice and issue statements on new vaccine formulations.

Recommendations

The major change in the 2013 Immunization timetable was made in the recommendations pertaining to pertussis immunization. Taking in to the consideration of recent outbreaks of pertussis in many industrialized countries using acellular pertussis (aP) vaccines and subsequent finding of faster waning of the same in comparison to whole-cell pertussis (wP) vaccines and superior priming with wP vaccines than aP vaccines, the committee has now recommended wP vaccines for the primary series of infant vaccination. Guidelines are now also issued on the preference/selection of a particular aP vaccine in case it is not feasible to use wP vaccine, and use of Tdap vaccine during pregnancy. The administration schedule of monovalent human rotavirus vaccine, RV1 has been revised to 10 and 14 weeks from existing 6 and 10 weeks. Recommendation is made for the need of booster dose of live attenuated SA-14-14-2 JE vaccine. Updates and recommendations are issued on new typhoid conjugate vaccine, inactivated vero-cell culture derived SA-14-14-2 JE vaccine, inactivated vero-cell derived Kolar strain, 821564XY JE vaccine, and new meningococcal conjugate vaccines. This year the recommended immunization schedule with range for persons aged 0 through 18 years is being published together instead of two separate schedules. A subcategory of ‘general instruction’ is added in footnotes. The comments and footnotes for several vaccines are revised and separate instructions for ‘routine vaccination’ and ‘catch-up vaccination’ are added in the footnotes section wherever applicable.     

Prospects for elimination of childhood tuberculosis: the role of new vaccines

Control of childhood tuberculosis must be considered in the context of active tuberculosis disease among adults, who form the main reservoir of transmission. The elimination target of the Stop TB Partnership is a reduction of global incidence to less than one case per million per year by 2050. There is an urgent need for a new, safe and effective tuberculosis vaccine that prevents all forms of tuberculosis, in all age groups and in HIV-infected people. Bacillus Calmette-Guérin (BCG) vaccination protects against disseminated forms of childhood tuberculosis, but protection is variable against pulmonary tuberculosis and adult disease. 14 new tuberculosis vaccines have entered human clinical trials, including viral-vectored vaccines, recombinant fusion proteins, recombinant BCG vaccines and inactivated whole or fragmented mycobacteria. Effective pre-exposure and postexposure vaccination, in conjunction with mass campaigns, is the most promising tuberculosis control strategy to approach the elimination target by the middle of the 21st century.     

Childhood immunization schedule of the Spanish Association of Pediatrics 2003

In this document the Advisory Committee on Vaccines of the Spanish Association of Pediatrics provides recommendations for the immunization schedule for the 2003-2004 season. The use of inactivated poliovirus vaccine is again stressed for children of any age. Moreover, the introduction of the varicella vaccine and the pneumococcal conjugated vaccine, as well as the option of dTpa in adolescents, is highly recommended due to the availability of safe and effective products. Because of the increasing number of new vaccines in the immunization schedule, strategies with combined vaccines must be used.     

Adolescent immunizations and other clinical preventive services: a needle and a hook?

Advances in technology have led to development of new vaccines for adolescents, but these vaccines will be added to a crowded schedule of recommended adolescent clinical preventive services. We reviewed adolescent clinical preventive health care guidelines and patterns of adolescent clinical preventive service delivery and assessed how new adolescent vaccines might affect health care visits and the delivery of other clinical preventive services. Our analysis suggests that new adolescent immunization recommendations are likely to improve adolescent health, both as a "needle" and a "hook." As a needle, the immunization will enhance an adolescent's health by preventing vaccine-preventable diseases during adolescence and adulthood. It also will likely be a hook to bring adolescents (and their parents) into the clinic for adolescent health care visits, during which other clinical preventive services can be provided. We also speculate that new adolescent immunization recommendations might increase the proportion and quality of other clinical preventive services delivered during health care visits. The factor most likely to diminish the positive influence of immunizations on delivery of other clinical preventive services is the additional visit time required for vaccine counseling and administration. Immunizations may "crowd out" delivery of other clinical preventive services during visits or reduce the quality of the clinical preventive service delivery. Complementary strategies to mitigate these effects might include prioritizing clinical preventive services with a strong evidence base for effectiveness, spreading clinical preventive services out over several visits, and withholding selected clinical preventive services during a visit if the prevention activity is effectively covered at the community level. Studies are needed to evaluate the effect of new immunizations on adolescent preventive health care visits, delivery of clinical preventive services, and health outcomes.     

Vaccination schedule of the Spanish Association of Pediatrics: recommendations 2005

The Advisory Committee on Vaccines of the Spanish Association of Pediatrics provides information and comments on the new developments in vaccines that have taken place in 2004 and recommends a few modifications to the Immunization Schedule for 2005. Concerning the meningococcal C vaccine, no change is made to the possibility of administering two doses for the first vaccination with one of the available formulations. The existence of immunization failure in children who have received a first vaccination with three vaccine doses before the age of 12 months is discussed, and the health authorities will probably include a booster dose in the second year of life throughout 2005. The recommendations of the European Medicines Evaluation Agency (EMEA) on hexavalent vaccines continue to be valid and consequently the use of these vaccines should not be stopped. This year the need for adolescents to receive a booster dose of the pertussis vaccine, with administration of an acellular, low antigenic load preparation together with the adult diphtheria and tetanus vaccine is stressed.     

Immunization and transplantation – What is new and what is coming?

Abstract:  Infections represent an important risk for pediatric transplant recipients. Many infections are preventable through immunization, and ongoing studies are working on increasing the number of available vaccines for these children either before or after transplantation. We examine new immunization schedules (such as pertussis vaccines in teenagers) and newly available vaccines (such as human papillomavirus vaccine), and suggest how to deliver them in pediatric transplant candidates or recipients. We also review less common vaccines (such as encephalitis vaccines), and possible vaccines of the future that could have an important clinical impact in these children, such as CMV or EBV vaccines.