Accelerating Policy Decisions to Adopt Haemophilus influenzae Type b Vaccine: A Global,Multivariable Analysis

Background

Adoption of new and underutilized vaccines by national immunization programs is an essential step towards reducing child mortality. Policy decisions to adopt new vaccines in high mortality countries often lag behind decisions in high-income countries. Using the case of Haemophilus influenzae type b (Hib) vaccine, this paper endeavors to explain these delays through the analysis of country-level economic, epidemiological, programmatic and policy-related factors, as well as the role of the Global Alliance for Vaccines and Immunisation (GAVI Alliance).

Methods and Findings

Data for 147 countries from 1990 to 2007 were analyzed in accelerated failure time models to identify factors that are associated with the time to decision to adopt Hib vaccine. In multivariable models that control for Gross National Income, region, and burden of Hib disease, the receipt of GAVI support speeded the time to decision by a factor of 0.37 (95% CI 0.18–0.76), or 63%. The presence of two or more neighboring country adopters accelerated decisions to adopt by a factor of 0.50 (95% CI 0.33–0.75). For each 1% increase in vaccine price, decisions to adopt are delayed by a factor of 1.02 (95% CI 1.00–1.04). Global recommendations and local studies were not associated with time to decision.

Conclusions

This study substantiates previous findings related to vaccine price and presents new evidence to suggest that GAVI eligibility is associated with accelerated decisions to adopt Hib vaccine. The influence of neighboring country decisions was also highly significant, suggesting that approaches to support the adoption of new vaccines should consider supply- and demand-side factors. Please see later in the article for the Editors'' Summary     

Factors affecting the introduction of new vaccines to poor nations: a comparative study of the Haemophilus influenzae type B and hepatitis B vaccines

Background

A major effort to introduce new vaccines into poor nations of the world was initiated in recent years with the help of the GAVI alliance. The first vaccines introduced have been the Haemophilus influenzae type B (Hib) and the hepatitis B (Hep B) vaccines. The introduction of these vaccines during the first phase of GAVI''s operations demonstrated considerable variability. We set out to study the factors affecting the introduction of these vaccines. The African Region (AFRO), where new vaccines were introduced to a substantial number of countries during the first phase of GAVI''s funding, was selected for this study.

Methodology/Principal Findings

GAVI-eligible AFRO countries with a population of 0.5 million or more were included in the study. Countries were analyzed and compared for new vaccine introduction, healthcare indicators, financial indicators related to healthcare and country-level Governance Indicators, using One Way ANOVA, correlation analysis and Qualitative Comparative Analysis (QCA). Introduction of new vaccines into AFRO nations was associated primarily with high country-level Governance Indicator scores. The use of individual Governance Indicator scores, as well as a combined Governance Indicator score we developed, demonstrated similar results.

Conclusions/Significance

Our study results indicate that good country-level governance is an imperative pre-requisite for the successful early introduction of new vaccines into poor African nations. Enhanced support measures may be required to effectively introduce new vaccines to countries with low governance scores. The combined governance score we developed may thus constitute a useful tool for helping philanthropic organizations make decisions regarding the type of support needed by different countries to achieve success.     

Evaluation of vaccines against enteric infections: a clinical and public health research agenda for developing countries

Enteric infections are a major cause of morbidity and mortality in developing countries. To date, vaccines have played a limited role in public health efforts to control enteric infections. Licensed vaccines exist for cholera and typhoid, but these vaccines are used primarily for travellers; and there are two internationally licensed vaccines for rotavirus, but they are mainly used in affluent countries. The reasons that enteric vaccines are little used in developing countries are multiple, and certainly include financial and political constraints. Also important is the need for more cogent evidence on the performance of enteric vaccines in developing country populations. A partial inventory of research questions would include: (i) does the vaccine perform well in the most relevant settings? (ii) does the vaccine perform well in all epidemiologically relevant age groups? (iii) is there adequate evidence of vaccine safety once the vaccines have been deployed in developing countries? (iv) how effective is the vaccine when given in conjunction with non-vaccine cointerventions? (v) what is the level of vaccine protection against all relevant outcomes? and (vi) what is the expected population level of vaccine protection, including both direct and herd vaccine protective effects? Provision of evidence addressing these questions will help expand the use of enteric vaccines in developing countries.     

Comparative economic evaluation of Haemophilus influenzae type b vaccination in Belarus and Uzbekistan

Background

Hib vaccine has gradually been introduced into more and more countries during the past two decades, partly due to GAVI Alliance support to low-income countries. However, since Hib disease burden is difficult to establish in settings with limited diagnostic capacities and since the vaccine continues to be relatively expensive, some Governments remain doubtful about its value leading to concerns about financial sustainability. Similarly, several middle-income countries have not introduced the vaccine. The aim of this study is to estimate and compare the cost-effectiveness of Hib vaccination in a country relying on self-financing (Belarus) and a country eligible for GAVI Alliance support (Uzbekistan).

Methods and Findings

A decision analytic model was used to estimate morbidity and mortality from Hib meningitis, Hib pneumonia and other types of Hib disease with and without the vaccine. Treatment costs were attached to each disease event. Data on disease incidence, case fatality ratios and costs were primarily determined from national sources. For the Belarus 2009 birth cohort, Hib vaccine is estimated to prevent 467 invasive disease cases, 4 cases of meningitis sequelae, and 3 deaths, while in Uzbekistan 3,069 invasive cases, 34 sequelae cases and 341 deaths are prevented. Estimated costs per discounted DALY averted are US$ 9,323 in Belarus and US$ 267 in Uzbekistan.

Conclusion

The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden. Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus. However, when seen in the context of the relative ability to pay for public health, the vaccine can be considered cost-effective in both countries.     

Delivering vaccines to the people who need them most

Thanks to the Global Alliance for Vaccines and Immunization (GAVI), the Vaccine Fund and the Bill & Melinda Gates Foundation, the global health community has made enormous progress in providing already existing vaccines to developing countries. However, there still exists a gap to develop vaccines for which there is no market in the Western world, owing to low economic incentives for the private sector to justify the investments necessary for vaccine development. In many cases, industry has the technologies, but lacks the impetus to direct resources to develop these vaccine products. The present emergency with the Ebola vaccine provides us an excellent example where a vaccine was feasible several years ago, but the global health community waited for a humanitarian disaster to direct efforts and resources to develop this vaccine. In the beginning of 2015, the first large-scale trials of two experimental vaccines against Ebola virus disease have begun in West Africa. During the past few years, several institutions have dedicated efforts to the development of vaccines against diseases present only in low-income countries. These include the International Vaccine Institute, the Novartis Vaccines Institute for Global Health, the Hilleman Institute, the Sabin Vaccine Institute and the Infectious Disease Research Institute. Nevertheless, solving this problem requires a more significant global effort than that currently invested. These efforts include a clear policy, global coordination of funds dedicated to the development of neglected disease and an agreement on regulatory strategies and incentives for the private sector.     

Maintaining vaccine delivery following the introduction of the rotavirus and pneumococcal vaccines in Thailand

Although the substantial burdens of rotavirus and pneumococcal disease have motivated many countries to consider introducing the rotavirus vaccine (RV) and heptavalent pneumococcal conjugate vaccine (PCV-7) to their National Immunization Programs (EPIs), these new vaccines could affect the countries' vaccine supply chains (i.e., the series of steps required to get a vaccine from their manufacturers to patients). We developed detailed computational models of the Trang Province, Thailand, vaccine supply chain to simulate introducing various RV and PCV-7 vaccine presentations and their combinations. Our results showed that the volumes of these new vaccines in addition to current routine vaccines could meet and even exceed (1) the refrigerator space at the provincial district and sub-district levels and (2) the transport cold space at district and sub-district levels preventing other vaccines from being available to patients who arrive to be immunized. Besides the smallest RV presentation (17.1 cm3/dose), all other vaccine introduction scenarios required added storage capacity at the provincial level (range: 20 L-1151 L per month) for the three largest formulations, and district level (range: 1 L-124 L per month) across all introduction scenarios. Similarly, with the exception of the two smallest RV presentation (17.1 cm3/dose), added transport capacity was required at both district and sub-district levels. Added transport capacity required across introduction scenarios from the provincial to district levels ranged from 1 L-187 L, and district to sub-district levels ranged from 1 L-13 L per shipment. Finally, only the smallest RV vaccine presentation (17.1 cm3/dose) had no appreciable effect on vaccine availability at sub-districts. All other RV and PCV-7 vaccines were too large for the current supply chain to handle without modifications such as increasing storage or transport capacity. Introducing these new vaccines to Thailand could have dynamic effects on the availability of all vaccines that may not be initially apparent to decision-makers.     

Oral vaccines: new needs, new possibilities

Vaccination is an important tool for handling healthcare programs both in developed and developing countries. The current global scenario calls for a more-efficacious, acceptable, cost-effective and reliable method of immunization for many fatal diseases. It is hoped that the adoption of oral vaccines will help to provide an effective vaccination strategy, especially in developing countries. Mucosal immunity generated by oral vaccines can serve as a strong first line of defense against most of the pathogens infecting through the mucosal lining. Advances in elucidating the mechanism of action of oral vaccines will facilitate the design of more effective, new generation vaccines. There are promising developments in the use of different agents to effectively deliver the vaccine candidate. It is hoped that ongoing research may be able to set another cardinal point, after polio vaccine, in eradicating infectious diseases.     

Process development of a New Haemophilus influenzae type b conjugate vaccine and the use of mathematical modeling to identify process optimization possibilities

Vaccination is one of the most successful public health interventions being a cost‐effective tool in preventing deaths among young children. The earliest vaccines were developed following empirical methods, creating vaccines by trial and error. New process development tools, for example mathematical modeling, as well as new regulatory initiatives requiring better understanding of both the product and the process are being applied to well‐characterized biopharmaceuticals (for example recombinant proteins). The vaccine industry is still running behind in comparison to these industries. A production process for a new Haemophilus influenzae type b (Hib) conjugate vaccine, including related quality control (QC) tests, was developed and transferred to a number of emerging vaccine manufacturers. This contributed to a sustainable global supply of affordable Hib conjugate vaccines, as illustrated by the market launch of the first Hib vaccine based on this technology in 2007 and concomitant price reduction of Hib vaccines. This paper describes the development approach followed for this Hib conjugate vaccine as well as the mathematical modeling tool applied recently in order to indicate options for further improvements of the initial Hib process. The strategy followed during the process development of this Hib conjugate vaccine was a targeted and integrated approach based on prior knowledge and experience with similar products using multi‐disciplinary expertise. Mathematical modeling was used to develop a predictive model for the initial Hib process (the ‘baseline’ model) as well as an ‘optimized’ model, by proposing a number of process changes which could lead to further reduction in price. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:568–580, 2016     

Carriage burden,multiple colonization and antibiotic pressure promote emergence of resistant vaccine escape pneumococci

Pneumococcal conjugate vaccines target the limited subset of the more than 90 known serotypes of Streptococcus pneumoniae responsible for the greatest burden of pneumococcal disease and antibiotic resistance. Following the introduction of these vaccines, serotypes not targeted were able to expand and resistance became more common within these types. Here we use a stochastic dynamic model of pediatric pneumococcal carriage to evaluate potential influences on the emergence of new resistant lineages following the introduction of a vaccine targeting more common resistant types. Antibiotic pressure was the strongest driver, with no emergence at low levels and universal emergence at high levels. At intermediate levels of antibiotic pressure, higher carriage burden and a greater degree of dual carriage promoted emergence. This may have implications for current plans to introduce childhood pneumococcal vaccination in several high-burden countries.     

Contribution of the GAVI Alliance to improving health and reducing poverty

The Global Alliance for Vaccines and Immunization (GAVI), now 10 years old, was established as a successful and innovative public-private partnership to deal with a fundamental inequity. The poorest children in the poorest parts of the world were being denied access to life-saving vaccines simply on the basis of cost. GAVI has been successful in mobilizing significant funding from donors and through innovative financing instruments, immunizing large numbers of children. GAVI has been less successful, at least in the time frames first envisaged, at quickly reducing the prices of new and under-used vaccines to levels affordable by the poorest countries. Vaccines remain some of the most cost effective of public health interventions. As GAVI seeks to introduce a new set of vaccines to tackle major killers such as pneumonia and diarrhoea, and emerging threats such as cervical cancer, it needs to raise significant additional funds. There is no single solution. Multiple and new instruments will be required to raise finance both globally and at the country level, and also to incentivize industry and others to provide vaccines at affordable prices to the poorest countries.     

Mutual interactions between DTaP-IPV and Haemophilus influenzae type b (Hib)-conjugated vaccines in laboratory animal models.

Potency and/or immunogenicity of three different Haemophilus influenzae type b-conjugated vaccines (Hib) and a DTaP-IPV vaccine alone, and their mutual interactions in DTaP-IPV-Hib combination was tested. In a mouse model, only combination of Act-Hib, in which tetanus toxoid (TT) was as active as non-conjugated TT, significantly increased the immunogenicity and potency of TT component of DTaP-IPV vaccine. Also, only combination of Hib-TITER, in which CRM197 was used as the carrier with DTaP-IPV, increased the potency of diphtheria toxoid (DT) component of DTaP-IPV vaccine significantly. It shows that the additive effect of tested Hib vaccines on immunogenicity and/or potency of TT and DT was mostly due to the existence of TT and CRM197, respectively, as the carrier in the mentioned Hib vaccines. No difference was shown in inoculation of DTaP-IPV and Hib conjugated vaccines in the same syringe or at separate sites. DTaP-IPV had dual effects on anti-Hib capsular polysaccharide (HibCP) responses to Hib vaccines in the mouse model. This duality was probably related to the carrier B-cell epitopes activity of Hib conjugated vaccines. The immunogenicity of TT component of Act-Hib and Amvax Hib-TT in the guinea pig model was shown and combination of mentioned Hib vaccines with DTaP-IPV, remarkably increased anti-TT antibody responses to the TT component of DTaP-IPV vaccine. These confirmed our results in the mouse model. Using two different protocols to evaluate the guinea pig model for induction of anti-HibCP immunity showed that a "long interval" protocol does not have any advantage over the "short interval" protocol. Also, combination of DTaP-IPV with Hib vaccines did not have any noticeable effect on anti-HibCP antibodies in the guinea pig model. Taken together, our observations in laboratory animal models may facilitate a better understanding of the mutual interactions between the different antigen components of a combined vaccine such as DTaP-IPV-Hib vaccine.     

Evaluation of a guinea pig model to assess interference in the immunogenicity of different components of a combination vaccine comprising diphtheria, tetanus and acellular pertussis (DTaP) vaccine and haemophilus influenzae type b capsular polysaccharide conjugate vaccine.

A guinea pig model to assess the immunogenicity of a combination vaccine containing diphtheria, tetanus and acellular pertussis (DTaP) vaccine and Haemophilus influenzae type b (Hib) capsular polysaccharide conjugated to tetanus toxoid (HibT) was evaluated comparatively with the mouse immunogenicity test to study the effect of combining these antigens on the immunogenicity of various components. The immunogenicity test in mice was performed by subcutaneous injection of groups of 10 animals twice at an interval of four weeks with 1/10 of a single human dose of various formulations of combination vaccines, DTaP or HibT vaccine. The animals were bled at 4 and 6 weeks and IgG or total antibodies to various components were determined by ELISA or RIA. The guinea pig immunogenicity model included groups of animals injected subcutaneously twice at an interval of six weeks with 1.5 times the single human dose of various formulations. The animals were bled at 4, 6 and 8 weeks and serum samples were tested for antibodies to various components by ELISA, RIA and/or neutralization tests. Additionally, potency of tetanus and diphtheria components was assessed as per the US Food and Drug Administration's regulations. Aluminium phosphate (AIPO(4)) adsorbed HibT vaccine or HibT as a combination with AIPO(4)adsorbed DTaP vaccine showed significant increases in IgG antibodies to tetanus toxin in mice as well increased tetanus antitoxin levels in guinea pigs as compared to soluble HibT vaccine. In general, combining DTaP and HibT vaccines did not affect the antibody levels to tetanus and diphtheria toxoids whereas DTaP-HibT combination vaccine elicited significantly lower IgG antibodies to pertussis toxin and filamentous haemagglutinin than DTaP vaccine alone, particularly after first injection. Mice showed similar Hib antibody responses for the combination and HibT alone whereas guinea pigs consistently showed lower anamnestic responses to Hib for combination formulations than for HibT alone. Reducing the amount of HibT and/or tetanus toxoid in the combination formulations reduced this suppression of Hib antibody response in guinea pigs. Suppression of Hib antibody response in combination vaccines has also been reported from recent clinical trials. Based on the results from this study, it appears that the guinea pig model may be able to predict the human response to various components of combination vaccines.     

The Impact of Residency and Urbanicity on Haemophilus influenzae Type b and Pneumococcal Immunization in Shanghai Children: A Retrospective Cohort Study

Background

Haemophilus influenzae type b (Hib) vaccine and pneumococcal conjugate vaccine (PCV) are relatively expensive, newly introduced vaccines in China. This study evaluates the impact of residency and urbanicity on Hib vaccine and PCV coverage for children aged 2 to 7 years living in Shanghai, China, in August 2012.

Methods

In this exploratory cohort study, a sample of children aged 2 to 7 years, all of whom were eligible to have received the complete series of Hib vaccine and PCV, was obtained from the Shanghai Immunization Program Information System. Three measures of vaccination coverage for Hib vaccine and PCV were examined: dose 1 coverage, series completion, and timeliness of dose 1 vaccination. Multivariable binomial regression was used to estimate the difference in vaccination coverage between locals and the floating population.

Results

Dose 1 coverage was 50.9% for Hib vaccine and 11.4% for PCV for the 28,141 abstracted pediatric records. For both vaccines, dose 1 coverage was higher in locals than in the floating population. The disparity in coverage between locals and the floating population was greater in suburban areas than urban areas. Of all children who received dose 1, 79.7% completed the Hib vaccine series, and 91.3% completed the PCV series. Timely dose 1 coverage was 8.2% for Hib vaccine and 0.5% for PCV.

Conclusion

Low vaccination coverage and extremely low levels of timely dose 1 vaccination indicate that current vaccination efforts are inadequate to reduce the burden of Hib and pneumococcal disease among Chinese children, especially infants. Government funding of the Hib vaccine and PCV through the Expanded Program on Immunization would increase uptake and could also ensure that improvement in the timeliness of administration and series completion is targeted for all demographic groups.     

Polyosides (encapsulated bacteria)

The polysaccharide capsule which surrounds bacterial species such as Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis and Salmonella typhi is a potent virulence factor by protecting the bacteria from phagocytosis. The host responds with antibody production and specific antibodies plus complement binding to the capsule facilitate opsonization of the micro-organism, which is phagocytized and eliminated. Purified capsular polysaccharides elicit T-independent antibody responses without a memory function, but are often poorly immunogenic in infants where much of the invasive H. influenzae type b (Hib) and pneumococcal infections is seen. Therefore purified polysaccharides have found limited use as vaccines. However, covalent linkage of the capsular polysaccharide, or fractions thereof, to immunogenic carrier proteins creates glycoconjugates which are T-dependent antigens and which elicit antibodies also in infants and which prime for boosting either with the glycoconjugate or the capsular polysaccharide. In the last decade Hib glycoconjugate vaccines have been successfully introduced and in countries with very high immunization coverage the disease has been virtually eliminated and a decline of over 95% has been seen in countries with slightly lower vaccine rates. World-wide use of Hib glycoconjugate vaccines offers the possibility of elimination of invasive Hib disease. Pneumococcal (11 serotypes with coverage of approximately 85% of invasive disease), meningococcal (A, C, W 135, Y but not B) and S. typhi glycoconjugates are in advanced development and offer the prospect of being as successful as the Hib glycoconjugates.     

A global health partnership's use of time-limited support to catalyze health practice change: the case of GAVI's Injection Safety Support

This paper presents the findings of a study to assess the effectiveness and sustainability of a GAVI (Global Alliance of Vaccines and Immunization) sponsored, time-limited Injection Safety (INS) support. The support came in two forms: 1) in-kind, in the form of AD syringes and safety boxes, and 2) in cash, for those countries that already had a secure, multi-year source of AD syringes and safety boxes, but proposed to use INS support to strengthen their injection safety activities. In total, GAVI gave INS support for a three-year period to 58 countries: 46 with commodities and 12 with cash support. To identify variables that might be associated with financial sustainability, frequencies and cross-tabulations were run against various programmatic and socio-economic variables in the 58 countries. All but two of the 46 commodity-recipient countries were able to replace and sustain the use of AD syringes and safety boxes after the end of their GAVI INS support despite the fact that standard disposable syringes are less costly than ADs (10-15 percent differential). In addition, all 12 cash-recipient countries continued to use AD syringes and safety boxes in their immunization programs in the years following GAVI INS assistance. At the same time, countries were often not prepared for the increased waste management requirements associated with the use of the syringes, suggesting the importance of anticipating challenges with the introduction of new technologies. The sustained use of AD syringes in countries receiving injection safety support from GAVI, in a majority of cases through government financing, following the completion of three years of time-limited support, represents an early indication of how GHPs can contribute to improved health outcomes in immunization safety in the world's poorest countries in a sustainable way.     

The Economic Impact of Eradicating Peste des Petits Ruminants: A Benefit-Cost Analysis

Peste des petits ruminants (PPR) is an important cause of mortality and production loss among sheep and goats in the developing world. Despite control efforts in a number of countries, it has continued to spread across Africa and Asia, placing an increasing burden on the livelihoods of livestock keepers and on veterinary resources in affected countries. Given the similarities between PPR and rinderpest, and the lessons learned from the successful global eradication of rinderpest, the eradication of PPR seems appealing, both eliminating an important disease and improving the livelihoods of the poor in developing countries. We conducted a benefit-cost analysis to examine the economic returns from a proposed programme for the global eradication of PPR. Based on our knowledge and experience, we developed the eradication strategy and estimated its costs. The benefits of the programme were determined from (i) the averted mortality costs, based on an analysis of the literature, (ii) the downstream impact of reduced mortality using a social accounting matrix, and (iii) the avoided control costs based on current levels of vaccination. The results of the benefit-cost analysis suggest strong economic returns from PPR eradication. Based on a 15-year programme with total discounted costs of US$2.26 billion, we estimate discounted benefits of US$76.5 billion, yielding a net benefit of US$74.2 billion. This suggests a benefit cost ratio of 33.8, and an internal rate of return (IRR) of 199%. As PPR mortality rates are highly variable in different populations, we conducted a sensitivity analysis based on lower and higher mortality scenarios. All the scenarios examined indicate that investment in PPR eradication would be highly beneficial economically. Furthermore, removing one of the major constraints to small ruminant production would be of considerable benefit to many of the most vulnerable communities in Africa and Asia.     

A novel Enzyme-Linked Immuno-Sorbent Assay (ELISA) for the quantification of total and free polysaccharide in Haemophilus influenzae b–Tetanus toxoid conjugate vaccines in monovalent and combined vaccine formulations

Current Haemophilus influenzae b conjugate vaccines (Hib), which are made of purified capsular polysaccharide (poly-ribosyl-ribitol-phosphate; PRP) conjugated to a carrier protein, are almost completely evaluated by physico-chemical methods to ensure the integrity and stability of the vaccine and consistency of manufacture of batches. The absence of a potency assay makes the quantification of total PRP content (in SI units) and of % free polysaccharide in final fills or bulk components of Hib vaccines critical release tests for both manufacturers and national control authorities. Here we describe a simple and sensitive Enzyme-Linked Immuno-sorbent Assay (ELISA) which has been developed to quantify total and free PRP content in Hib–TT vaccine alone or when in combination with other vaccines. The assay is robust, specific and highly sensitive.     

Public Acceptance and Willingness-to-Pay for a Future Dengue Vaccine: A Community-Based Survey in Bandung,Indonesia

Background

All four serotypes of dengue virus are endemic in Indonesia, where the population at risk for infection exceeds 200 million people. Despite continuous control efforts that were initiated more than four decades ago, Indonesia still suffers from multi-annual cycles of dengue outbreak and dengue remains as a major public health problem. Dengue vaccines have been viewed as a promising solution for controlling dengue in Indonesia, but thus far its potential acceptability has not been assessed.

Methodology/Principal Findings

We conducted a household survey in the city of Bandung, Indonesia by administering a questionnaire to examine (i) acceptance of a hypothetical pediatric dengue vaccine; (ii) participant''s willingness-to-pay (WTP) for the vaccine, had it not been provided for free; and (iii) whether people think vector control would be unnecessary if the vaccine was available. A proportional odds model and an interval regression model were employed to identify determinants of acceptance and WTP, respectively. We demonstrated that out of 500 heads of household being interviewed, 94.2% would agree to vaccinate their children with the vaccine. Of all participants, 94.6% were willing to pay for the vaccine with a median WTP of US$1.94. In addition, 7.2% stated that vector control would not be necessary had there been a dengue vaccination program.

Conclusions/Significance

Our results suggest that future dengue vaccines can have a very high uptake even when delivered through the private market. This, however, can be influenced by vaccine characteristics and price. In addition, reduction in community vector control efforts may be observed following vaccine introduction but its potential impact in the transmission of dengue and other vector-borne diseases requires further study.     

Vaccines and future global health needs

Increased international support for both research into new vaccines and their deployment in developing countries has been evident over the past decade. In particular, the GAVI Alliance has had a major impact in increasing uptake of the six common infant vaccines as well as those against hepatitis B and yellow fever. It further aims to introduce pneumococcal and rotavirus vaccines in the near future and several others, including those against human papillomavirus, meningococcal disease, rubella and typhoid not long after that. In addition, there is advanced research into vaccines against malaria, HIV/AIDS and tuberculosis. By 2030, we may have about 20 vaccines that need to be used in the developing world. Finding the requisite funds to achieve this will pose a major problem. A second and urgent question is how to complete the job of global polio eradication. The new strategic plan calls for completion by 2013, but both pre-eradication and post-eradication challenges remain. Vaccines will eventually become available beyond the field of infectious diseases. Much interesting work is being done in both autoimmunity and cancer. Cutting across disease groupings, there are issues in methods of delivery and new adjuvant formulations.     

Technology transfer of Sabin-IPV to new developing country markets.

The Netherlands Vaccine Institute (NVI) developed the micro-carrier technology for large-scale production of IPV in the late 1960s and has used this technology successfully to produce IPV as well as DTP-IPV for the national immunization program in the Netherlands. As a public sector organization, and as one of the Millennium Development Goals, NVI has supported over the years access to vaccine technology like DTP and Hib for vaccine manufacturers in developing countries. In line with this role as a resource institute, NVI has recently been approached by a number of vaccine manufacturers, predominantly from developing countries, for transfer of IPV technology to meet the anticipated increase in demand for IPV following OPV cessation. Since WHO encourages new manufacturers to use the attenuated Sabin virus instead of wild polio strains in the production of IPV, NVI decided to respond positively to this WHO policy. The existing NVI experience in large-scale production of IPV and OPV using Vero cell based micro-carrier technology and its experience with experimental Sabin-IPV is an attractive start for the development of Sabin-IPV. This paper discusses the approach followed and the experience already gained in the project, as well as factors critical to its success.