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Comparison of immunogenicity of combined DPT--inactivated injectable polio vaccine (DPT - IPV) and association of DPT and attenuated oral polio vaccine (DPT + OPV) in Pakistani children.

Two hundred children aged 2-24 months attending EPI Centre Rawalpindi General Hospital, were randomly assigned to two basic immunization schedules i.e. 3 doses of oral polio vaccine alongwith two doses of DPT (Conventional Schedule) and 2 doses of combined DPT - enhanced injectable polio vaccine (new simplified schedule). Comparison of the seroconversion results showed the presence of protective antibodies against all the 3 types of polio in 100% of the children in both the groups, but there was no statistical difference in the geometric mean antibody titre in the two immunization schedules. After two doses of DPT-IPV or DPT vaccine alone the results demonstrated antibody levels above the protective threshold in both the groups against Diphtheria, Pertussis and Tetanus.

Antibody Formation↗

[The effect of health care settings on children's immunization status].

The objective of this study was to determine the effect of practice settings (CLSC and private office) and family characteristics (mother's age and education, children's rank in families) on children's immunization status and adherence to the immunization schedule. The study population was composed of 209 children born in 1991 and residing in the Regional Municipal County of Montmagny, Quebec. After adjusting for mother's education, those children vaccinated in a private office were at 13.3 times higher risk for incomplete immunization than those vaccinated in a CLSC. A similar but nonsignificant result was obtained regarding adherence to the immunization schedule. The factors likely to account for the results are the first contact and follow-up mechanisms put into place by the CLSC. The effectiveness of such mechanisms seems to be related to their population-based rather than client-oriented responsibility.

Child↗

Efficacy of intramammary immunization with an Escherichia coli J5 bacterin.

Intramammary immunization was investigated as a procedure to reduce the clinical signs of coliform mastitis. Twenty-four cows were equally distributed to the following Escherichia coli J5 immunization schedules: 1) Subcutaneous injection 14 d prior to the end of lactation, intramammary immunization 7 d after drying off, and subcutaneous injection 30 d into the dry period; 2) subcutaneous injections at drying off, at 30 d into the dry period, and within 12 h after calving; and 3) unimmunized controls. Intramammary immunizations were the infusion of vaccine via the teat canal into each of the four mammary glands. Cows were challenged by infusion of E. coli 727 into one uninfected mammary quarter at approximately 30 d after calving. Intramammary immunization enhanced antibody titers against E. coli J5 and E. coli 727 compared with subcutaneous immunization. Immunoglobulin G titers against E. coli J5 and E. coli 727 in whey were greater at the time of challenge and 7 d after challenge for cows that received the intramammary immunization than for cows immunized by only subcutaneous injections. Serum IgG titers against E. coli 727 were enhanced at 7 d after challenge for cows receiving intramammary immunizations compared with conventionally immunized cows. Serum IgM titers against E. coli 727 were higher at calving for cows receiving intramammary immunization compared with conventionally immunized cows. Immunization schedule had minimal effect on systemic and local signs of clinical mastitis following challenge.

Animals↗

[Report on 5 years of expanded program of vaccination in an experimental zone in Ivory Coast].

Started in june 1978 in the Abengourou District (Ivory Coast) the expanded program on immunization (E.P.I.) was assessed in june 1983 by the mean of a vaccinal survey, after five years of implementation. This survey was conducted in both urban circle where E.P.I. was fully in operation from 1978, and rural circle where it was progressively implemented to reach about 3/4 of the villages by 1983. The authors report and compare the findings in terms of global vaccinal coverage towards the six diseases covered by the E.P.I. in town (71,7%) and in rural area (42,6%). Their report includes the results of a survey about the sanitary protection of the children and about the respect of the ideal immunization schedule and recommended in Ivory Coast (39,9% in town and 6,2% in rural area). In considering measles, they attempt to understand the true benefit of such a plan in terms of reduced mortality and morbidity rate from 15,8% to 0,9%. Considering their findings, the authors recommend to concentrate efforts in two directions for the coming years. To better cover the rural zones. To better respect the ideal immunization schedule.

BCG Vaccine↗

Communicating the benefits of combination vaccines to parents and health care providers.

Infants may receive as many as 5 separate injections at an office visit in order to comply with the 2002 childhood immunization schedule. Many parents and healthcare providers disagree with administering 4 or 5 injections at one visit, and therefore may delay some injections until another visit. This practice may lead to decreased compliance and can increase costs for the parent. New combination vaccines will help to simplify the immunization schedule, and health care providers will need to be able to address parental concerns regarding these vaccines. Nurses are often responsible for administering vaccines in the office setting, and therefore are also influential in deciding which vaccines should be ordered. The purpose of this article is to educate nurses on communicating the benefits of combination vaccines to parents and other healthcare providers.

Attitude of Health Personnel↗

Strategies for development of combination vaccines.

BACKGROUND: The increasing complexity of the recommended childhood immunization schedule has resulted in the need for combination vaccines. METHODS: Through an extensive review of the current literature, various strategies and issues related to the development of combination vaccines are discussed. RESULTS: Issues that should be considered when combining vaccine components include the current childhood immunization schedule, compatibility of components, availability of antigens for targeted diseases, safety, efficacy, immunogenicity and route of delivery. When choosing an appropriate combination of antigen(s)/serotype(s) for a global or national formulation, careful consideration must be made when selecting serotypes to combine depending on the market or area of use. It is important to know that potential interactions can involve other components of the vaccines, including buffers, adjuvants and preservatives. The Food and Drug Administration requires that the combination not only have immunogenicity comparable with those of the component vaccines, but that its safety profile be comparable with the most reactogenic component. The Food and Drug Administration also recommends that a test of noninferiority be performed, such that the combination performs similarly to the separate components with regard to antibody titers. CONCLUSIONS: Combination vaccines are critical to the success of vaccination programs, and each new combination must be carefully studied to ensure comparable safety and immunogenicity of the individual components.

Antigens↗

Immunization issues for the 21st century.

OBJECTIVE: Review and discuss major issues of vaccination and immunization. The development and application of vaccination and immunization is one of the most remarkable successes of the 20th century. This is true both in the United States and worldwide. In the United States, a number of vaccine-preventable diseases have been all but eliminated through the development of a recommended childhood immunization schedule by governmental and nongovernmental organizations, education of providers about these recommendations, and enforcement of these recommendations by school and day care entry mandates. Despite these successes, vaccine-preventable diseases continue to occur, in part because of missed opportunities by health care providers, antivaccine forces empowered by misguided mass media, and parental ignorance. Important aspects of the 2002 recommended childhood immunization schedule are reviewed, including: birth dose hepatitis B, diphtheria underimmunization and tetanus overimmunization, increasing pertussis disease, the success of conjugate vaccines, the change in poliovirus vaccines, measles vaccine and autism, the safety of varicella vaccine, and adult vaccination recommendations. Finally, future prospects for vaccination and immunization are discussed, including: combination vaccines, vaccines against new diseases such as rotavirus, new routes of delivery of immunizing agents, the use of computerized vaccine registries to prevent missed opportunities, and vaccines against bioterrorism agents. CONCLUSIONS: A careful analysis of risk and benefit suggests that the benefit of vaccination far outweighs the risks from the utilization of immunizing agents. Vaccination delayed may be protection denied. The bottom line is that vaccines are good and disease is bad.

Child Welfare↗

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

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.

Adolescent↗

How do caregivers know when to take their child for immunizations?

BACKGROUND: Childhood vaccinations help reduce and eliminate many causes of morbidity and mortality among children. The objective of this study was to compare 4:3:1:3:3 (4+ doses of diphtheria and tetanus toxoids and pertussis vaccine, 3+ doses of poliovirus vaccine, 1+ doses of measles-containing vaccine, 3+ doses of Haemophilus influenzae type b vaccine, and 3+ doses of hepatitis B vaccine) coverage among children whose caregivers learned by different methods when their child's most recent immunization was needed. METHODS: Between July 2001 and December 2002, a portion of households receiving the National Immunization Survey were asked how they knew when to take the child in for his/her most recent immunization. Responses were post-coded into several categories: 'Doctor/nurse reminder at previous immunization visit', 'Shot card/record', 'Reminder/recall', and 'Other'. Respondents could give more than one answer. Children who did not receive any vaccines, had < or = 1 visits for vaccinations, or whose caregiver did not provide an answer to the question were excluded from analyses. Chi-square analyses were used to compare 4:3:1:3:3 coverage among 19-35 month old children. RESULTS: Children whose caregivers indicated that a doctor/nurse told them at a previous immunization visit when to return for the next immunization had significantly greater 4:3:1:3:3 coverage than those who did not choose the response (77.2% vs. 70.1%, p < 0.01). However, no significant difference in coverage was found between households that did/did not indicate that reminder/recalls (71.0% vs. 75.5%, p = 0.24) helped them remember when to take their child for their most recent immunization visit; only borderline significance was found between those that did/did not choose shot cards (70.6% vs. 76.2%, p = 0.07). CONCLUSION: A doctor or nurse's reminder during an immunization visit of the next scheduled immunization visit effectively encourages caregivers to bring children in for immunizations, providing an inexpensive and easy way to effectively increase immunization coverage.

Caregivers↗

Measles update.

The incidence of measles in the United States dramatically increased in the 1980s, from a low of 1,497 cases in 1983 to over 17,000 cases in 1989. Family physicians can help reverse this trend by following the revised immunization schedule, which includes a measles-mumps-rubella (MMR) booster for preschool-age children. New guidelines also recommend that either the two-dose MMR schedule or serologic evidence of immunity be required for all persons entering college or employed in the medical field. Immunization policies for physician's offices should ensure that all office staff have acquired measles immunity and that a triage policy separating patients with rash from those with other illnesses is utilized. Mild upper respiratory illness, a history of seizures, nonanaphylactic egg allergy and asymptomatic human immunodeficiency virus infection are not contraindications to measles vaccine. All cases of measles should be reported to the local health department.

Adolescent↗

[Routine preventive vaccinations].

In 1996, a second measles, mumps and rubella (MMR) vaccination at the time of school entry was included in the Swiss Childhood Immunization schedule, and universal hepatitis B immunization will likely be added in 1998. An additional innovation is the possibility to use acellular pertussis vaccines which have a lower rate of side effects. Each physician who is involved in immunizations should be familiar with the arguments that support the official immunization recommendations in order to be able to provide competent advice to patients or their parents.

Adolescent↗

Comparative evaluation of measles, mumps & rubella vaccine at 9 & 15 months of age.

BACKGROUND & OBJECTIVES: Measles, mumps and rubella (MMR) contribute to significant amount of mortality and morbidity in our country. Though MMR vaccine has been a part of immunization schedule in the developed countries, it is yet to be included in our national immunization schedule. Hence this study was conducted to assess the serological status of measles, mumps and rubella in young children and to evaluate the seroconversion of measles, mumps and rubella vaccine at 9 and 15 months of age. METHODS: The cohort study was carried out at the out patient department of a tertiary care hospital in north India. A total of 240 normal children, 120 each in the age group 9-10 and 15-18 months attending the hospital for immunization were enrolled for the study. None of them had been vaccinated with MMR vaccine in the past, or gave any history of measles, mumps or rubella infection, or were on any immunosuppressive agent. The pre-vaccination blood sample was taken and each child was administered a single dose of trivalent MMR vaccine. The post-vaccination sample was taken 6-8 wk later. The paired serum samples were analysed for the presence of measles, mumps and rubella antibodies using commercially available ELISA kits. RESULTS: Of the 120 infants in the age group of 9-10 months, 102 (85%) were seronegative for measles and 96 (80%) were seronegative for both mumps and rubella. Following MMR vaccination, 102 infants came for post vaccination sampling of which 92 per cent were seropositive for measles, 100 per cent for mumps and 98 per cent for rubella. In the age group of 15-18 months, of the 120 children, 67 (56%) were seronegative for measles, 84 (70%) for mumps and 86 (71.6%) for rubella. In 50 per cent of the children, there was a history of measles immunization at 9 months of age. After MMR vaccination, 100 children came for post vaccination sampling and seropositivity of 92, 96 and 94 per cent was observed for measles, mumps and rubella, respectively. The rise in the pre- and post-immunization geometrical mean titre was significant (P < 0.05) for each component of the vaccine in both the age groups. INTERPRETATION & CONCLUSION: The MMR vaccine can be offered safely and with equal efficacy to children at 9 and 15 months of age.

Age Factors↗

Development of pediatric vaccine recommendations and policies.

A significant decrease in each vaccine-preventable disease has occurred since the introduction of the respective immunizations now included in the recommended childhood immunization schedule. The process through which a vaccine must travel from development to approval and implementation is complex. Hurdles include receiving approval from several advisory committees, government agencies, and professional organizations. At each step in the process, data regarding safety, immunogenicity, and efficacy are evaluated continuously and rigorously. Once a vaccine is approved by the Food and Drug Administration (FDA) and incorporated into the recommended childhood immunization schedule, continuing issues include those that deal with supply, safety, effectiveness, and financing. The logistics of development and implementation of pediatric vaccine recommendations and policies are reviewed.

Advisory Committees↗

Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska.

BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive bacterial disease and pneumonia among children. Antimicrobial resistance among pneumococci has increased in recent years and complicates treatment. The introduction of heptavalent pneumococcal conjugate vaccine (PCV7) could reduce acquisition of antimicrobial-resistant pneumococci. METHODS: We obtained 1350 nasopharyngeal swabs for culture from 1275 children aged 3-59 months presenting at 3 clinics in Anchorage, Alaska, during the winters of 2000, 2001, and 2002, as PCV7 was being introduced into the routine immunization schedule. We recorded the frequency of use of antibiotics as well as the dates of doses of PCV7 for enrolled children. We used multivariate logistic regression modeling to identify independent risk factors for overall carriage of pneumococci and carriage of PCV7-type pneumococci, cotrimoxazole-nonsusceptible (COT-NS) pneumococci, or penicillin-nonsusceptible (PCN-NS) pneumococci. RESULTS: The proportion of children who were up-to-date for age, with respect to PCV7 vaccination, increased from 0% in 2000 to 55% in 2002. Carriage of PCV7-type pneumococci decreased by 43% (P<.0001). Risk of carriage of PCV7-type pneumococci was lower in 2002 than in 2000, independent of vaccination status, suggesting an indirect effect of vaccination. Carriage of COT-NS, but not PCN-NS, pneumococci also decreased (38%; P=.02), not only among vaccinated children but also among unvaccinated children without recent use of antibiotics. CONCLUSIONS: Introduction of PCV7 into the routine infant immunization schedule in a community with a high prevalence of antimicrobial-resistant pneumococci appears to reduce transmission of PCV7 vaccine serotypes and COT-NS pneumococci but has no impact on overall carriage of pneumococci or carriage of PCN-NS pneumococci.

Alaska↗

Responses of antibody titers to intramammary immunization with Escherichia coli J5 bacterin.

The effect of an immunization schedule on responses of antibody titers was tested following vaccination with an Escherichia coli J5 bacterin. Eighteen cows were equally distributed among three immunization schedules: 1) subcutaneous injection at 14 d prior to the end of lactation, intramammary immunization at 7 d after drying off, and subcutaneous injection at 30 d into the dry period; 2) subcutaneous injections at drying off, at 30 d into the dry period, and within 12 h after calving; and 3) unimmunized controls. The E. coli J5 bacterin consisted of 5 ml of 10(9) boiled cells/ml of 0.9% NaCl plus 0.005% phenol emulsified with 5 ml of Freund's incomplete adjuvant. Subcutaneous injections were administered on the upper part of the rib cage, posterior to the scapula. Intramammary immunizations of 2.5 ml of bacterin were infused via the teat canal into each of the four mammary glands. Intramammary immunization increased rectal temperatures at 12 h after infusion, but subcutaneous injections did not induce febrile responses. Intramammary immunization enhanced immunoglobulin G titers in serum and whey on d 0 of lactation compared with subcutaneous immunizations. Immunoglobulin G titers in serum also were greater at d 30 of the dry period and at d 14 and 21 of lactation for cows that received intramammary immunization than for cows that were vaccinated by subcutaneous injections only. Immunoglobulin M titers in whey and serum on d 21 of lactation were greater for cows that received intramammary immunizations than for cows that were immunized by subcutaneous injections only.

Animals↗

An edible vaccine for malaria using transgenic tomatoes of varying sizes, shapes and colors to carry different antigens.

Malaria, a disease caused by protozoan parasites of genus Plasmodium, is one of the world's biggest scourges. Over two billion individuals reside in the malaria endemic areas and the disease affects 300-500 million people annually. As a result of malarial-infection, an estimated three million lives are lost annually, among them over one million children (majority under 5 years of age). The mortality due to malaria has increased because of the spread of drug-resistant strains of the parasite, the breakdown of health services in many affected areas, the interaction of the disease with human immunodeficiency virus (HIV) infection, and possibly the effects of climate change. Infants and young children with malaria often die from severe anemia, cerebral involvement,or prostration caused by overwhelming infection; many new borns die from complications of low birth weight caused by maternal malaria during pregnancy. The scarce economic resources and lack of communication, infrastructure and adequate means of travel in the endemic areas make it extremely difficult to implement traditional infection control measures (i.e., mosquito control, preventive anti-malarial drugs and nets). To make the matter worse, both malarial parasites and its insect vectors are increasingly becoming resistant to anti-malarial agents (chloroquine) and insecticides (both DDT and melathione and related chemicals), respectively. By conventional wisdom, the immune mechanisms responsible for protection against malaria will require a multiple of 10-15 antigen targets for proper protection against various stages of malarial infection. By standard vaccination protocols, such a large number of targets would not be appropriate to be used for vaccination as a single dose due to antigenic competition. It would be almost impossible to immunize over two billion individuals who live in malaria susceptible areas with several carefully crafted immunization schedules delivered 4-6 weeks apart in the form of two different antigens as a single dose. Besides, if immunization schedules could be arranged, the stability of vaccines carrying different malarial antigens, their transport, and the logistics of vaccination would be an almost impossible task to achieve under the current fiscal constraints. We are proposing a unique way to circumvent these logistical difficulties to deliver the malaria vaccines to every susceptible home at a small fraction of a cost. We hypothesize that the anti-malaria edible vaccines in transgenic tomato plants where different transgenic plants expressing different antigenic type(s). Immunizing individuals against 2-3 antigens and against each stage of the life cycle of the multistage parasites would be an efficient, inexpensive and safe way of vaccination. Tomatoes with varying sizes, shapes and colors carrying different antigens would make the vaccines easily identifiable by lay individuals.

Administration, Oral↗

A live attenuated recombinant chimeric parainfluenza virus (PIV) candidate vaccine containing the hemagglutinin-neuraminidase and fusion glycoproteins of PIV1 and the remaining proteins from PIV3 induces resistance to PIV1 even in animals immune to PIV3.

Using a reverse genetics system for PIV3, we previously recovered recombinant chimeric PIV3-PIV1 virus bearing the major protective antigens of PIV1, the hemaglutinin-neuraminidase and fusion proteins, on a background of PIV3 genes bearing temperature sensitive (ts) and attenuating mutations in the L gene. Immunization of hamsters with this virus, designated rPIV3-1.cp45L, induced a high level of resistance to replication of wild type (wt) PIV1 and, surprisingly, also induced a moderate amount of restriction of the replication of PIV3 challenge virus. This suggested that some immunity is conferred by the internal PIV3 proteins shared by the two viruses. In the present study, we found that the immunity to PIV3 conferred by infection with rPIV3-1.cp45L is short-lived and completely disappeared four months after immunization, whereas resistance to replication of PIV3 induced by prior infection with PIV3 remains high even after an interval of four months. Since a live attenuated PIV1 vaccine such as the chimeric rPIV3-1.cp45L virus will likely be given to infants after a live attenuated PIV3 vaccine in a sequential immunization schedule, we examined the immunogenicity and efficacy of rPIV3-1.cp45L against PIV1 challenge in animals with and without prior immunity to PIV3. rPIV3-1.cp45L efficiently infected hamsters previously infected with wt or attenuated PIV3, but there was approximately a five-fold reduction in replication of rPIV3-1. cp45L virus in the PIV3-immune animals. This reduction in replication of rPIV3-1.cp45L in PIV3-immune animals was accompanied by a significant decrease in efficacy against PIV1 challenge. However, rPIV3-1.cp45L immunization of PIV3-immune animals induced a vigorous serum antibody response to PIV1 and reduced replication of PIV1 challenge virus 1000-fold in the lower respiratory tract and 25 to 200-fold in the upper respiratory tract. This study demonstrated that the recombinant chimeric rPIV3-1.cp45L candidate vaccine can induce immunity to PIV1 even in animals immune to PIV3. This establishes the feasibility of employing a sequential immunization schedule in which a recombinant chimeric rPIV3-1.cp45L vaccine is given following a live attenuated PIV3 vaccine.

Animals↗

The use of ammonium sulphate precipitation method for the determination of antigen-binding capacity and affinity of anti-tetanus antibodies in human serum.

Radioimmunoassay of anti-tetanus antibodies produced in human serum in response to tetanus toxoid immunization was carried out by employing the non-specific precipitation effect of ammonium sulphate described by Farr (1958). The results showed that the method was sensitive and was able to differentiate between immune and non-immune persons. The effects of booster dose injection on the quantity and quality of antibodies produced during immunization were discussed, and the possible use of the method to predict the amount of immunogen, the timing and number of injections required for optimal host response in immunization schedules was suggested.

Ammonium Sulfate↗