Pneumococcal Conjugate Research Articles

The association of ethnicity with antibody responses to pneumococcal vaccination among adults with HIV infection

Ethnicity may be associated with the incidence of pneumococcal infections and the frequency of protective vaccine responses. Earlier studies have suggested that HIV-infected persons of black ethnicity develop less robust immune responses to pneumococcal vaccination that may relate to their higher incidence of invasive disease. We evaluated the association of ethnicity with capsule-specific antibody responses to pneumococcal revaccination, with either the pneumococcal conjugate (PCV) or polysaccharide (PPV) vaccines among 188 HIV-infected adults. The proportion of the 77 African Americans (AA) and 111 Caucasians with comparable virologic and immunologic parameters who achieved a positive immune response (≥2-fold rise in capsule-specific IgG from baseline with post-vaccination value ≥1 μg/mL for ≥2 of 4 serotypes) at day 60 after revaccination was similar (43% vs. 49%, respectively, p = 0.65). Results were also similar when vaccine types (PPV and PCV) were examined separately. Mean changes in log 10 transformed IgG levels from baseline to days 60 and 180 post-vaccination were also not significantly different between AA and Caucasians. In summary, in this ethnically diverse cohort with equal access to care, we did not observe differential antibody responses between AA and Caucasian HIV-infected adults after pneumococcal revaccination.

Vaccinating premature infants in a Special Care Baby Unit in the UK: results of a prospective, non-inferiority based, pragmatic case series study

Premature infants are at greater risk of infections in part because of impaired functioning of external barriers, innate and adaptive systems. For similar immunological reasons, diminished responses to particular vaccines have also been reported. This study, utilising a prospective, pragmatic case series approach was designed to show non-inferiority of antibody response in premature infants to diphtheria, tetanus, Haemophilus influenzae type b conjugate (Hib), meningococcal C conjugate (MenC) and pneumococcal conjugate (PnC) vaccines between immunization in a routine clinical situation rather than a vaccine trial. A secondary objective was to determine the effect of gestational age on antibody response to these vaccines. The case series comprised 131 infants born at ≤ 32 weeks gestation and managed on the Special Care Baby Unit (SCBU) of a District General Hospital in Stockport, UK. For diphtheria and tetanus, 98.3% and 100% of premature infants respectively developed a minimum protective antibody response; 86.6% were protected against Men C. However, only 67.8% preterm infants achieved anti-polyribosylribitolphosphate (PRP) antibodies >0.15μg against Hib, with only 34.7% having a level ≥1.0μg, and responses to the different pneumococcal serogroups ranged from 67.5% against serotype 6B to 92.5% against serogroup 19F. In comparison to term infants, preterm infants were less likely to achieve protective levels against MenC and Hib: there were no significant differences in the proportions of infants protected against diphtheria and tetanus. Protection was inferior to expected based on published premature infant clinical trial data for Hib and particular pneumococcal serotypes; data for Men C were also lower than expected.

The effect of Haemophilus influenzae type b and pneumococcal conjugate vaccines on childhood pneumonia incidence, severe morbidity and mortality

Background With the aim of populating the Lives Saved Tool (LiST) with parameters of effectiveness of existing interventions, we conducted a systematic review of the literature assessing the effect of Haemophilus influenzae type b (Hib) and pneumococcal (PC) conjugate vaccines on incidence, severe morbidity and mortality from childhood pneumonia.Methods We summarized cluster randomized controlled trials (cRCTs) and case–control studies of Hib conjugate vaccines and RCTs of 9- and 11-valent PC conjugate vaccines conducted in developing countries across outcome measures using standard meta-analysis methods. We used a set of standardized rules developed for the purpose of populating the LiST tool with required parameters to promote comparability across reviews of interventions against the major causes of childhood mortality. The estimates could be adjusted further to account for factors such as PC vaccine serotype content, PC serotype distribution and human immunodeficiency virus prevalence but this was not included as part of the LiST model approach.Results The available evidence from published data points to a summary effect of the Hib conjugate vaccine on clinical pneumonia of 4%, on clinical severe pneumonia of 6% and on radiologically confirmed pneumonia of 18%. Respective effectiveness estimates for PC vaccines (all valent) on clinical pneumonia is 7%, clinical severe pneumonia is 7% and radiologically confirmed pneumonia is 26%.Conclusions The findings indicated that radiologically confirmed pneumonia, as a severe morbidity proxy for mortality, provided better estimates for the LiST model of effect of interventions on mortality reduction than did other outcomes evaluated. The LiST model will use this to estimate the pneumonia mortality reduction which might be observed when scaling up Hib and PC conjugate vaccination in the context of an overall package of child health interventions.

CDC Issues Recommendations for a New Pneumococcal Conjugate Vaccine

Target Population: Infectious diseases specialists, as well as physicians, nurses, and public health workers who care for children Sponsoring Organization: CDC Type: Recommendations of the Advisory Committee on Immunization Practices. This report is consistent with recommendations by the American Academy of Pediatrics Committee on Infectious Diseases. Key Points: In February 2000, a 7-valent pneumococcal polysaccharide-protein conjugate vaccine (Prevnar [PCV7]) was licensed for infants and young children in the U.S. Subsequently, the rates of pneumococcal sepsis and meningitis in children fell, but infections caused by nonvaccine serotypes have persisted, and the prevalence of nonvaccine serotypes may be increasing. On February 24, 2010, a 13-valent pneumococcal polysaccharide-protein conjugate vaccine …

Immunogenicity of a Heptavalent Conjugate Pneumococcal Vaccine Administered Concurrently with a Combination Diphtheria, Tetanus, Five-Component Acellular Pertussis, Inactivated Polio, and Haemophilus influenzae Type b Vaccine and a Meningococcal Group C Conjugate Vaccine at 2, 3, and 4 Months of Age

The immunogenicities of conjugate pneumococcal vaccines have been demonstrated when they are administered at 2, 3, and 4 months of age. There is a paucity of data on the immunogenicity of this vaccine when it is administered concurrently with other vaccines in the primary immunization schedule of the United Kingdom. We immunized 55 term infants at 2, 3, and 4 months of age with the seven-valent pneumococcal conjugate vaccine (PCV7), the meningococcal group C conjugate (MCC) vaccine, and the diphtheria, tetanus, five-component acellular pertussis, inactivated polio, and Haemophilus influenzae type b (DTaP(5)/IPV/Hib-TT) vaccine. The immune responses to the H. influenzae type b (Hib), MCC, and tetanus vaccines were measured at 2, 5, and 12 months of age; and the immune responses to PCV7 were measured at 2 and 5 months and then either at 12 months or following a 4th dose of PCV7. There were increases in the geometric mean concentrations (GMCs) of all antigens postimmunization. Greater than or equal to 90% of the infants achieved putatively protective levels postimmunization for all vaccine antigens except pneumococcal serotype 6B and Hib. The GMCs of the PCV7 serotypes increased following a 4th dose, although one infant had not reached putative levels of protection against serotype 6B. In conclusion, when infants were vaccinated according to the schedule described above, they had lower postprimary immunization responses to Hib, meningococcus group C capsular polysaccharide, and pneumococcal serotype 6B than the responses demonstrated by use of the other schedules. Despite this finding, there was a good response following a 4th dose of PCV7.

Safety of adjuvants and excipients in vaccines

Vaccines are named either for the antigen that they contain or the disease that they prevent, but they contain a number of excipients that serve to maintain proper pH, prevent microbial growth, act as stabilizers, or enhance the immune response to the vaccine. The objective of this article is to provide information for pharmacists who address patient concerns related to the safety of vaccine adjuvants and excipients and to offer suggestions and resources to address these issues in the community. Vaccine adjuvants improve the potency of vaccines, allowing for decreased doses of antigens or fewer doses in a vaccine series. Aluminum salts are the only vaccine adjuvant currently licensed in the United States and are included in vaccines such as Haemophilus influenzae type b, diphtheria–tetanus–acellular pertussis (DTaP), pneumococcal conjugate, hepatitis A, and hepatitis B. Aluminum adjuvants enhance phagocytosis of the vaccine antigen and inflammation that recruits immune cells.1 Aluminum is the most common metal found in nature. Aluminum can be neurotoxic and has been linked to dementia in patients with renal failure who receive large amounts of aluminum-containing antacids used as phosphate binders.2 This has led to the question of whether the amount of aluminum given to infants and children with the current vaccination schedule could lead to developmental delay or decreases in learning and memory. Patients can be assured that the amount of aluminum received during several vaccinations is well below the minimum risk level for daily intake. The aluminum exposure from vaccines in the first 6 months of life is about 4 mg. During this same time, the infant can be exposed to 10 mg aluminum in breast milk, about 40 mg in infant formula, or about 120 mg in soy-based formula. The aluminum exposure from a dose of vaccine is about 1,000 times less than the amount of aluminum from a dose of antacid.2 Aluminum has been used in vaccines for more than 75 years with hundreds of millions of doses given. Parents should be told that the aluminum can cause pain or redness around the injection site and in rare cases a harmless lump under the skin, but no long-term effects have been associated with aluminum in vaccines.3,4 Other compounds may be added to vaccines that are not adjuvants. For example, thimerosal is a preservative containing ethyl mercury that is no longer used as a preservative in childhood vaccines. It was reviewed in a previous installment of Vaccine Update.5 Formaldehyde is used during the manufacture of some vaccines to inactivate the pathogens. Although formaldehyde can cause cancerous changes to cells in vitro at certain doses, it does not have that property in either animals or humans. It is most widely known for its use as an embalming agent and as a component of cigarette smoke, which may alarm some patients. After manufacture and dilution, some vaccines (e.g. DTaP, hepatitis A, hepatitis B, polio) contain 0.1 mg formaldehyde or less per dose. This amount is 600 times less than has been given safely to animals and will not increase the patient’s risk for cancer or other ill effects.6 Some components of vaccines can elicit allergic responses ranging from mild to severe reactions, including anaphylaxis. Patients should be properly screened for all medication, food, and substance allergies using both openended questions and those that are vaccine specific. Latex can be found in some syringe plungers and in the rubber stoppers of some vaccine vials. For patients with a documented latex allergy, remove the rubber stopper of the vaccine or consider an alternate delivery technique to avoid adverse reactions. Latex content is described in prescribing information. Yellow fever and all influenza vaccine preparations are manufactured by using cellular components from chicken eggs that act as a viral growth medium during production. The final vaccine products contain measurable quantities of egg protein and should not be administered to any patient with a history of anaphylactic reaction to eggs. Influenza vaccine can be administered to individuals who can eat eggs.7 Gelatin is used in vaccines as a stabilizing agent and can be found in many commonly administered vaccines, including influenza (Fluzone brand), measles–mumps–rubella, varicella (Varivax), zoster (Zostavax), and DTaP (Tripedia brand). Gelatin has been estimated to cause immediate hypersensitivity reactions in approximately one person in every 2 million doses administered and is typically the responsible component when such reactions occur. Although immunizers can ask patients about allergies to food, the predictive value of this correlation is not very high.8 Another feature of vaccines that raises questions with patients is the presence of antibiotics. Many vaccines contain trace amounts of antibacterials such as neomycin, polymixin B, and streptomycin. These are used to prevent

Discordant immunization schedules can complicate vaccine evaluation for Europe

Background: Most of the world’s vaccines are produced in Europe. Although vaccine licensure can becentralized through the EMEA, immunization recommendations are established at the national levels,reimbursement policies vary widely (ranging from regional to national, from private to public) and the lag timecan be long between licensure and eventual introduction into a national immunization program.Methods: An example of this discordance is the paediatric combination vaccines. Young infants in some EUcountries receive a whole-cell pertussis vaccine, in a three- to five-vaccine combination (“DTPw | IPV | Hib”).Acellular pertussis vaccines have been introduced over the last decade in many other EU countries, with four-to six-vaccine combinations (“DTPa | IPV | HBV | Hib”). Either of these combinations may be administered witha “3 + 1” schedule, with the first dose given between the age of 2 to 3 months, a spacing of 1 to 2 monthsbetween doses, and the final (booster) dose usually given at anywhere between 12 and 24 months of age, butin a handful of countries as late as the age of 3 to 5 years. By contrast, a “2 + 1” schedule is applied in somecountries for the “DTPa | IPV | Hib” or “DTPa | IPV | HBV | Hib” vaccines: first dose, 3 months old; spacing, 2months between doses; final (booster) dose, 11 to 14 months of age.Results: Differing national policies in the EU may have led to delays in the introduction of the newest vaccines(e.g., pneumococcal conjugate, meningococcal conjugate, rotavirus, influenza, varicella-zoster, etc.) thatmust be shown to be compatible with the various infant immunization programs across Europe. This coulddelay the likelihood, in some EU countries, of the public health advancements that these new vaccines canprovide.Conclusions: Sharing of best practices from vaccination schedules might rationalize vaccine development,streamline the introduction of novel vaccines into the national immunization programs, and facilitate theevaluation of the impact of new vaccines in Europe.

Antibody Response to Polysaccharide Conjugate Vaccines after Nonmyeloablative Allogeneic Stem Cell Transplantation

After allogeneic stem cell transplantation with reduced-intensity conditioning regimens (allo-RIST) patients are susceptible to bacterial and viral infections for a period that may last several years. The efficacy of the recommended vaccination schedules, in terms of induction of a protective antibody response, is unknown. In this study, the reconstitution of humoral immunity after allo-RIST is determined by measuring the vaccination-induced antibody response against Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and tetanus toxoid (TT) 1 year posttransplantation. Patients who underwent allo-RIST were vaccinated according to a schedule starting at 12 months following transplantation with conjugated vaccines against S. pneumoniae, Hib, and TT. Of twenty-six patients both pre- and postvaccination sera were available. Patients were required to be off immunosuppression at the time of vaccination, and, therefore, 9 of the 26 patients did not start vaccination at 12 months post-stem cell transplantation but rather at a median range of 15 (12-36 months) posttransplantation. Except for pneumococcal serotype 6B, more than 73% of the patients developed antibody levels >or=0.35 microg/mL for all pneumococcal serotypes included in the vaccine. For Hib and TT, protective antibody levels were found in 77% and 96% of the patients, respectively. Vaccination of patients at a median of 15 months post-allo-RIST leads to significant rise in concentrations of pneumococcal, Hib, and TT antibodies in the majority of patients.

Antimicrobial Resistance among Isolates Causing Invasive Pneumococcal Disease before and after Licensure of Heptavalent Conjugate Pneumococcal Vaccine

BackgroundThe impact of the pneumococcal conjugate vaccine (PCV-7) on antibiotic resistance among pneumococcal strains causing invasive pneumococcal disease (IPD) has varied in different locales in the United States. We assessed trends in IPD including trends for IPD caused by penicillin non-susceptible strains before and after licensure of PCV-7 and the impact of the 2008 susceptibility breakpoints for penicillin on the epidemiology of resistance.Methodology/Principal FindingsWe performed a retrospective review of IPD cases at Morgan Stanley Children's Hospital of NewYork-Presbyterian, Columbia University Medical Center. Subjects were ≤18 years of age with Streptococcus pneumoniae isolated from sterile body sites from January 1995–December 2006. The rate of IPD from 1995–1999 versus 2002–2006 significantly decreased from 4.1 (CI95 3.4, 4.8) to 1.7 (CI95 1.3, 2.2) per 1,000 admissions. Using the breakpoints in place during the study period, the proportion of penicillin non-susceptible strains increased from 27% to 49% in the pre- vs. post-PCV-7 era, respectively (p = 0.001), although the rate of IPD caused by non-susceptible strains did not change from 1995–1999 (1.1 per 1,000 admissions, CI95 0.8, 1.5) when compared with 2002–2006 (0.8 per 1,000 admissions, CI95 0.6, 1.2). In the multivariate logistic regression model controlling for the effects of age, strains causing IPD in the post-PCV-7 era were significantly more likely to be penicillin non-susceptible compared with strains in the pre-PCV-7 era (OR 2.46, CI95 1.37, 4.40). However, using the 2008 breakpoints for penicillin, only 8% of strains were non-susceptible in the post-PCV-7 era.Conclusions/SignificanceTo date, there are few reports that document an increase in the relative proportion of penicillin non-susceptible strains of pneumococci causing IPD following the introduction of PCV-7. Active surveillance of pneumococcal serotypes and antibiotic resistance using the new penicillin breakpoints is imperative to assess potential changes in the epidemiology of IPD.

Wyeth's pneumococcal 7-valent CRM197 conjugate vaccine [Prevenar] has been added to Saudi Arabia's national immunisation programme

Wyeth's pneumococcal 7-valent CRM197 conjugate vaccine [Prevenar] has been added to Saudi Arabia's national immunisation programme

The Turkish Government has added Wyeth's pneumococcal 7-valent CRM197 vaccine conjugate [Prevenar] to its National Immunisation Schedule

The Turkish Government has added Wyeth's pneumococcal 7-valent CRM197 vaccine conjugate [Prevenar] to its National Immunisation Schedule

Antibiotics for bacterial pneumonia in children

Pneumonia remains the leading cause of mortality in children. Diagnosis depends on a combination of factors, including clinical assessment, radiological and laboratory findings. Although Streptococcus pneumoniae remains the most important cause of childhood bacterial pneumonia, the great majority of cases of community-acquired pneumonia (CAP) are of viral etiology. A new, rapid, and inexpensive test that differentiates viral from bacterial pneumonia is needed to decide empiric antibiotic treatment. Antibiotics effective against the expected bacterial pathogens should be instituted where necessary. The role of emerging pathogens and the effect of pneumococcal resistance and heptavalent conjugate pneumococcal vaccines are to be considered in practice. There are reports supporting the valid and highly efficacious use of penicillin as a first-line drug for treating CAP. This review raises the issue of the overuse of unnecessary antibiotics in viral CAPs and the use of second or third-line antibiotics for non-complicated pneumonias in most clinical settings.

Adjuvants LT‐K63 and CpG Enhance the Activation of Dendritic Cells in Neonatal Mice

Dendritic cells (DC) play a major role in the priming of T cells and initiating specific immune responses. We assessed the effects of the adjuvants LT-K63 and CpG on neonatal DC in vivo and in vitro. Cytokine levels (IL-10, IL-12p70 and IL-12p40/IL-23p40) were measured and the expression of the activation markers CD86, CD40 and MHCII on CD11c+ DC was analysed by using FACS. The proportion of MHCII high CD11c+ DC was higher in neonatal mice immunized with a pneumococcal conjugate (PncTT) and LT-K63 or CpG compared with that when PncTT was alone. In vitro stimulation with LT-K63 enhanced the expression of CD86 more on CD11c+ DC from spleens of mice immunized as neonates than those immunized as adults, whereas in vitro stimulation with CpG enhanced the expression of CD86 and CD40 on CD11c+ DC similarly in both age groups. CpG stimulation in vitro enhanced IL-10 and IL-12(p70) production in mice immunized as neonates with PncTT and either adjuvant, but not PncTT alone. The adjuvants LT-K63 and CpG enhance the activation of CD11c+ DC in mice immunized as neonates and can thereby overcome one of the limiting factors in the initiation of the immune response to conjugate vaccines in early life. The fact that neonatal DC are more susceptible to stimulation with either adjuvant, LT-K63 or CpG, could imply that neonatal CD11c+ DC are more easily activated than adult CD11c+ DC, and /or be a consequence of the predominance of different DC subsets in neonatal and adult mice.

South Africa plans to phase in routine vaccination with pneumococcal 7-valent CRM197 vaccine conjugate [Prevenar

South Africa plans to phase in routine vaccination with pneumococcal 7-valent CRM197 vaccine conjugate [Prevenar

The changing epidemiology of pneumococcal pulmonary disease in the era of the heptavalent vaccine

Since the pediatric pneumococcal 7-valent conjugate vaccine was licensed in the United States, dramatic changes have taken place in the occurrence of pneumococcal disease among children and adults. Incidence of invasive pneumococcal disease including bacteremic pneumonia has declined, but changes in noninvasive pulmonary disease have been more difficult to assess. This paper reviews evidence of the epidemiologic features of invasive pneumococcal disease and community-acquired pneumonia among children and adults since 2000. Despite some increases in non-vaccine-type disease, its use has resulted in major reductions in incidence of invasive pneumococcal disease in all age groups, particularly that of antibiotic-resistant disease and of pediatric pneumococcal pneumonia. Several studies show that changes in circulating pneumococcal strains may be producing differential changes in disease incidence and disease presentation in several populations, including HIV-infected individuals and Alaska Natives.

Can the burden of pneumonia among HIV-infected children be reduced?

Of the approximately 2.1 million children who are infected with human immunodeficiency virus type 1 (HIV-1),1 more than 80% will develop a respiratory illness sometime during the course of their disease.2 The prevalence of HIV-1 infection among African children admitted for very severe pneumonia (under the WHO case definition) varies from 55% to 65% and is associated with a case fatality rate of 20% to 34%; three- to six-times higher than children who are not infected with HIV.3,4 In infancy, pneumonia caused by Pneumocystis jiroveci is often the first HIV/AIDS indicator disease that prompts HIV testing and, consequently, early antiretroviral treatment for those infected.5 Approximately 2 million children less than 5 years of age die of pneumonia each year in countries with a high prevalence of HIV. The standard case management guidelines for pneumonia recommended by WHO for use in areas with low HIV burdens are less effective in areas where HIV burdens are high.6 Modifications to these guidelines have been suggested, but their use, as reported in a recently published study of children with very severe pneumonia, resulted in a 45% treatment failure rate among HIV-infected infants in tertiary care settings.4 Polymicrobial infections with Staphylococcus aureus, nontyphoidal Salmonella spp. and other Gram-negative pathogens, Mycobacterium tuberculosis, P. jiroveci, cytomegalovirus and other viruses were commonly seen among the treatment failures and carried a greater than 10-fold risk of a poorer outcome. Randomized controlled studies of alternative antimicrobial agents that are active against some of the pathogens identified among these treatment failures are urgently required. A second major challenge for standard case management in the HIV era is to develop a management guideline to care for the largest group of HIV-affected children: HIV-exposed but HIV-uninfected children, who are at increased risk of acquiring pneumonia. Such children, who live in close contact with HIV-infected persons who persistently harbour a multitude of different pathogens, are at higher risk of pneumonia treatment failure than HIV-unexposed control children; however, the risk of an adverse outcome is lower than for HIV-infected children.7 Studies on the impact of pneumonia on HIV-exposed but HIV-uninfected children are essential. The other major intervention to reduce pneumonia-related morbidity and mortality among HIV-infected children requires the implementation of preventive strategies. Routine immunizations against Streptococcus pneumoniae, Haemophilus influenzae and varicella are safe and effective in HIV-infected children, even though their primary immunological response is inferior and they experience faster decay in immunological memory. Despite the lower efficacy of the conjugate pneumococcal (65% versus 83%) and H. influenzae type b vaccines (55% versus 91%) against invasive disease in HIV-infected and HIV-uninfected control children, respectively, introduction of these vaccines would considerably reduce the 1.6 million pneumococcal and 300 000 H. influenzae deaths that occur each year.8–10 Other preventive strategies, such as the provision of co-trimoxazole prophylaxis against bacterial and P. jiroveci infections, improvement in the provision of prevention of mother-to-child transmission (PMTCT) interventions and early use of highly active antiretroviral therapy (HAART) require urgent scaling-up. In a randomized controlled study of co-trimoxazole prophylaxis versus placebo in HIV-infected older Zambian children, a significant reduction in the hazards ratio for death of 0.57 (95% confidence interval: 0.43–0.77) was seen in the treated group.11 Although there is undoubted benefit in providing co-trimoxazole prophylaxis to HIV-infected children, its widespread implementation does carry risks such as development of resistance to a drug used for treating P. jiroveci pneumonia. This needs to be studied urgently as ineffective treatment of these conditions could increase mortality substantially. The effective implementation of PMTCT programmes, involving at least dual antiretroviral therapy and effective nutritional advice, will help to reduce to less than 4% the incidence of transmission of HIV to newborns and infants.12 Such a reduction is likely to have a significant impact on cutting the prevalence of pneumonia among HIV-infected children. Furthermore, use of HAART with HIV-infected children has been associated with a fourfold reduction in the rate of opportunistic infections and a threefold reduction in hospitalizations.13 The role of nutritional inventions, such as exclusive breastfeeding and zinc supplements, in the prevention of pneumonia among HIV-infected children needs to be explored more thoroughly. In conclusion, significant attention has to be paid to revising the standard case management guidelines for HIV-infected children with pneumonia through properly conducted randomized controlled studies. The implementation of preventative strategies that include co-trimoxazole prophylaxis, pneumococcal and H. influenzae type b vaccinations, PMTCT programmes and early introduction of HAART carry the greatest immediate hope for helping these children. There is a need to rapidly scale up these measures globally. ■

Estimating teh costs of achieving the WHO-UNICEF Global Immunization Vision and Strategy, 2006-2015

To estimate the cost of scaling up childhood immunization services required to reach the WHO-UNICEF Global Immunization Vision and Strategy (GIVS) goal of reducing mortality due to vaccine-preventable diseases by two-thirds by 2015. A model was developed to estimate the total cost of reaching GIVS goals by 2015 in 117 low- and lower-middle- income countries. Current spending was estimated by analysing data from country planning documents, and scale-up costs were estimated using a bottom-up, ingredients-based approach. Financial costs were estimated by country and year for reaching 90% coverage with all existing vaccines; introducing a discrete set of new vaccines (rotavirus, conjugate pneumococcal, conjugate meningococcal A and Japanese encephalitis); and conducting immunization campaigns to protect at-risk populations against polio, tetanus, measles, yellow fever and meningococcal meningitis. The 72 poorest countries of the world spent US$ 2.5 (range: US$ 1.8-4.2) billion on immunization in 2005, an increase from US$ 1.1 (range: US$ 0.9-1.6) billion in 2000. By 2015 annual immunization costs will on average increase to about US$ 4.0 (range US$ 2.9-6.7) billion. Total immunization costs for 2006-2015 are estimated at US$ 35 (range US$ 13-40) billion; of this, US$ 16.2 billion are incremental costs, comprised of US$ 5.6 billion for system scale-up and US$ 8.7 billion for vaccines; US$ 19.3 billion is required to maintain immunization programmes at 2005 levels. In all 117 low- and lower-middle-income countries, total costs for 2006-2015 are estimated at US$ 76 (range: US$ 23-110) billion, with US$ 49 billion for maintaining current systems and $27 billion for scaling-up. In the 72 poorest countries, US$ 11-15 billion (30%-40%) of the overall resource needs are unmet if the GIVS goals are to be reached. The methods developed in this paper are approximate estimates with limitations, but provide a roadmap of financing gaps that need to be filled to scale up immunization by 2015.

Direct and Indirect Effects of Pneumococcal Protein Conjugate Vaccine

Direct and Indirect Effects of Pneumococcal Protein Conjugate Vaccine

Pneumococcal Otopathogen Not Vulnerable to Approved Antibiotics and Vaccine

Introduction of a pneumococcal 7-valent conjugate vaccine (PCV7) in the U.S. in 2000 decreased the incidence of invasive pneumococcal disease by 69% to

Can Hexavalent Vaccines Be Simultaneously Administered with Pneumococcal or Meningococcal Conjugate Vaccines?

BackgroundLocal immunization programs may include hexavalent and conjugate pneumococcal or meningococcal vaccines administered in the same vaccination visit. Information based on evidence is necessary for correctly planning schedules and for parents who often fear the administration of too many vaccines. We reviewed the available literature to assess the effects on immunogenicity and safety of simultaneous administration of hexavalent and conjugate pneumococcal and meningococcal C vaccines in healthy children.MethodsWe searched for papers including a comparison of coadministration and single administration of hexavalent with conjugate pneumococcal or meningococcal C vaccines. Data sources included Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. Immunogenicity and safety results were extracted and compared. We calculated the absolute risk increase of being a non responder to any antigen and of experiencing common adverse events.ResultsFour relevant articles were included in the review. Immunogenicity of components included in the hexavalent vaccines was maintained with coadministration of conjugate pneumococcal and meningococcal C vaccines. However individuals who received hexavalent vaccine with conjugate pneumococcal vaccines were 18% more likely to have anti-PRP < 1 μg/mL after the third dose although this difference disappeared after the fourth dose, and titres against meningococcal C antigens were higher when vaccines were administered separately. Children who received simultaneous administration of hexavalent vaccines with conjugate pneumococcal vaccines had a 13-17% additional risk of experiencing fever compared with single administration.ConclusionFew studies deal with coadministration of vaccines. Hexavalent and conjugate pneumococcal or meningococcal vaccines may however be administered simultaneously without noteworthy negative effects on immunogenicity or safety profile. Parents of vaccinees should be appropriately informed on the effects of coadministration to improve their compliance. Studies on vaccine coadministration should be promoted and unpublished studies realized for vaccine registration should be made available.