Factors affecting parents’ willingness to pay for dengue vaccination for children in endemic areas, Indonesia: A multicenter crosssectional study

IntroductionThere has been a dramatic global surge in dengue fever (DF) in recent years, with a projected 100-400 million cases annually and large outbreaks expected every 3-4 years. This concerning scenario is in sharp contrast to the very low availability of dengue vaccines to meet this spiraling demand, particularly affecting developing countries in Latin America and Africa. In our study, we aim to identify current vaccine development constraints, from a technological perspective, based on clinical trials and patent landscape data.MethodsThis study was conducted in a two-step methodology. First, candidates and launched products and methods used in the development or as part of DF vaccines were identified from the Cortellis Drug Discovery Intelligence (CDDI) platform. Second, the Derwent Innovation database was used to retrieve patent documents related to dengue vaccines. Data were collected in the period 2014-2024 (to identify the candidate and or launched vaccines) and 2018-2022 (to identify patent documents) with claims involving applications for dengue vaccine development. We presented these descriptive data in the following format: quantitative and qualitative assessments describing the vaccine development scenario and the claimed vaccine technologies.ResultsOur study indicated that 65% of dengue vaccines are still in phase 1 of development. The few current dengue vaccines that have reached phase 3 (1) and launched (2) have shown limited levels of individual protection for one or more dengue serotypes and there is an anemic pipeline of the next generation of more effective tetravalent dengue vaccines. Although the intelligent use of multiple dengue vaccine formulations in immunization campaigns can result in effective protection against all serotypes at the population level, the implementation of this is complex and challenging. The results of our study thus provide evidence of a worrisome global situation regarding the development of new dengue vaccine candidates.ConclusionTo reverse this scenario, there is an urgent need to implement new knowledge governance approaches and business models to stimulate an exponential increase in global vaccine development funding for dengue and several other vaccines.

Dengue is one of the most problematic vector-borne diseases in the Philippines, with an estimated 842,867 cases resulting in medical costs of $345 million U.S. dollars annually. In December 2015, the first dengue vaccine, known as chimeric yellow fever virus–dengue virus tetravalent dengue vaccine, was approved for use in the Philippines and is given to children 9 years of age. To estimate the cost-effectiveness of dengue vaccination in the Philippines, we developed an age-structured model of dengue transmission and vaccination. Using our model, we compared two vaccination scenarios entailing routine vaccination programs both with and without catch-up vaccination. Our results indicate that the higher the cost of vaccination, the less cost-effective the dengue vaccination program. With the current dengue vaccination program that vaccinates children 9 years of age, dengue vaccination is cost-effective for vaccination costs up to $70 from a health-care perspective and up to $75 from a societal perspective. Under a favorable scenario consisting of 1 year of catch-up vaccinations that target children 9–15 years of age, followed by regular vaccination of 9-year-old children, vaccination is cost-effective at costs up to $72 from a health-care perspective and up to $78 from a societal perspective. In general, dengue vaccination is expected to reduce the incidence of both dengue fever and dengue hemorrhagic fever /dengue shock syndrome. Our results demonstrate that even at relatively low vaccine efficacies, age-targeted vaccination may still be cost-effective provided the vaccination cost is sufficiently low.

Dengue virus can cause dengue fever,dengue hemorrhagic fever,and dengue shock syndrome.In recent years,dengue virus infection is posing a great threat to people's health.In order to research and develop safe and effective dengue vaccines,the updated biological characteristics and pathogenesis of dengue virus and research advance of dengue virus vaccines are summarized in this review. Key words: Dengue virus; Dengue vaccines; Dengue; Dengue hemorrhagic fever; Dengue shock syndrome

Dengue fever is caused by the dengue virus (DENV) which is transmitted to humans through mosquito bites (Aedes aegypti) with a high morbidity rate of up to 20% of those affected by dengue fever. In Indonesia, dengue fever has to get the serious attention from various parties because this disease is endemic and threatening the public health. A multicentre cross-sectional approach was carried out on 642 parents in Southeast Sulawesi. The technique sampling used simple random sampling technique. Research data analysis used descriptive and inferential analysis. Descriptive analysis was used to describe sociodemographic characteristics, experiences, knowledge and acceptance of parents in Southeast Sulawesi. Meanwhile, inferential analysis was used to find out the factors that influence the parents’ acceptance in Southeast Sulawesi. The average value of parents' acceptance and knowledge of the dengue vaccine was 77.1% respectively. The results of the chi square test showed that 4 factors directly influenced the acceptance of the dengue vaccine, those were income, experience of knowing about the vaccine, source of information, and level of knowledge of the respondent with p value of <0.05. It is necessary to increase knowledge of the health workers to the parents to increase the awareness of the benefits of dengue vaccine so that parents in Southeast Sulawesi received the dengue vaccine.

Controversy and debate on dengue vaccine series—paper 1: review of a licensed dengue vaccine: inappropriate subgroup analyses and selective reporting may cause harm in mass vaccination programs

Background and Objectives: Mass immunization program with the recently approved dengue vaccine among grade 4 students of public elementary schools commenced in April 2016. Whether an individual had prior dengue infection or not is the most important aspect when implementing this vaccine since through the mechanism of antibody-dependent enhancement (ADE), those who are seronegative or never had dengue prior that are immunized can have their first natural dengue infection to be of higher severity. Thus, this study aims to determine if immunization with the newly-licensed live, attenuated, tetravalent dengue vaccine is associated with the occurrences of hospitalization due to dengue infection. Methodology: This unmatched case control study was conducted in three tertiary hospitals within and near Pasig City, an area tagged as hotspot for dengue infection. Cases (n=112) were Filipino children, 9-12 years of age, confined to a tertiary hospital due to dengue infection and supported with a positive confirmatory test. Controls (n=112) were Filipino children of the same age group with a medical record as an outpatient or inpatient whose final diagnosis is not dengue. Chi-square test was used to determine the association between the dependent and independent variables. All statistical analysis in this study was done using SPSS 20. Results: The proportions of cases and controls that were vaccinated with dengue vaccine were 1/56 for both (only 2 out of 112). Among children of 9-12 years of age, dengue vaccine is not associated with dengue infection hospitalization (p=1.000). Only age is found to be significant among the confounders (p=0.010; 95% CI: 1.134-1.863). Conclusions: There is no significant association between dengue vaccination status and hospitalization due to dengue infection. Further evaluation of the association may require an increase in sample size, and conduct of the study a few more years after the implementation of the mass immunization program.

PurposeEnhancing vaccine coverage among children is crucial to preventing the long-term consequences of dengue fever (DF) infections. This study aims to identify sociodemographic factors influencing parents’ willingness to pay (WTP) for future dengue vaccine products in Southeast Sulawesi.Materials and MethodsAn observational study design with a multicentred cross-sectional approach was employed, involving 510 parents participating in integrated health service activities (Posyandu) across 5 regencies/cities in Southeast Sulawesi. Data were collected using a modified questionnaire from previous studies, covering sociodemographic factors and WTP for the dengue vaccine. The questionnaire first asked about willingness to pay, followed by reasons if respondents were unwilling. Conversely, for respondents willing to pay, the contingent valuation method was applied, utilizing direct inquiries about the amount they were willing to pay. This involved a bidding technique followed by an open-ended question to determine the exact value respondents were willing to pay for the vaccine. The data were processed and analysed using IBM SPSS version 26. To identify the factors influencing WTP for the vaccine, a χ2 test was conducted using IBM SPSS version 26.ResultsThe average WTP among parents was IDR 134,686 (USD 8.27), which decreased to IDR 108,108 (USD 6.64) when government subsidies were considered. Five factors significantly influenced the WTP for the vaccine: sex, education level, monthly income, previous experience with the disease, and prior knowledge of the dengue vaccine.ConclusionThe government and related health institutions need to improve public awareness and knowledge about DF and dengue vaccination.

Dengue is considered the most important emerging, human arboviruses, with worldwide distribution in the tropics. Unfortunately, there are no licensed dengue vaccines available or specific anti-viral drugs. The development of a dengue vaccine faces unique challenges. The four serotypes co-circulate in endemic areas, and pre-existing immunity to one serotype does not protect against infection with other serotypes, and actually may enhance severity of disease. One foremost constraint to test the efficacy of a dengue vaccine is the lack of an animal model that adequately recapitulates the clinical manifestations of a dengue infection in humans. In spite of this limitation, non-human primates (NHP) are considered the best available animal model to evaluate dengue vaccine candidates due to their genetic relatedness to humans and their ability to develop a viremia upon infection and a robust immune response similar to that in humans. Therefore, most dengue vaccines candidates are tested in primates before going into clinical trials. In this article, we present a comprehensive review of published studies on dengue vaccine evaluations using the NHP model, and discuss critical parameters affecting the usefulness of the model. In the light of recent clinical data, we assess the ability of the NHP model to predict immunological parameters of vaccine performances in humans and discuss parameters that should be further examined as potential correlates of protection. Finally, we propose some guidelines toward a more standardized use of the model to maximize its usefulness and to better compare the performance of vaccine candidates from different research groups.

The incidence of dengue fever (DF) is steadily increasing in Mexico [1], [2], as it is in the rest of Latin America [3], burdening health systems with the consequent morbidity and mortality [4]–[6]. The incidence of DF in Mexico has increased from 1.7 cases per 100,000 inhabitants in 2000 to 43.03 cases per 100,000 inhabitants in 2012 (Table 1) [1], [2]. Growing urbanization, human migration, climate change, and ecological disruption have facilitated the expansion of dengue's vectors, Aedes aegypti and A. albopictus [3], [4]. This increase, which could be solely attributed to an improvement in epidemiological surveillance, in reality has a much more complex explanation. According to reports from the Mexican Secretariat of Health, DF in Mexico follows a cyclical pattern of approximately five years per cycle, characterized by a sudden and dramatic rise in cases subsequently followed by a period of decrement that ultimately results in years with a low number of cases. This pattern seems to have its origin in the introduction/reintroduction of new serotypes among the population [2]. Table 1 Evolution of the incidence of dengue fever cases in Mexico between 2000 and 2012. Globally, an estimated 2,500,000,000 to 3,000,000,000 individuals are at risk of infection. Each year 50 million people fall ill, and 20,000 people die as a result of dengue [5]–[7]. These trends will continue to worsen in the foreseeable future [3], [7]. Even at its current level, dengue overloads healthcare systems, particularly in developing countries in which resources are scarce [4]. The direct and indirect costs of dengue are high and impose a considerable financial burden on those affected [2], [8]. The most commonly used dengue control measure—vector control programs—have had poor effects on dengue incidence and are difficult to implement in a sustainable fashion [9]–[11]. Also, these programs are costly and have limited effect because of the difficulty of destroying all mosquitoes in an area [9]. Additionally, there are no effective antivirals available to treat the disease. However, as a result of much progress in research and development over the last decade [12], there is a prospect of a safe and effective preventive vaccine becoming available soon [13]–[16]. In 2012, Sanofi-Pasteur (SP) published the results of a Phase IIB clinical trial carried out in Thailand to test the efficacy of its recombinant, live-attenuated, tetravalent dengue vaccine. The authors reported that although the vaccine showed less efficacy than projected, this was not significant, and the vaccine resulted immunogenic for the four dengue serotypes and protected against serotypes 1, 3, and 4 [17]. Irregardless of the results, the authors of the present report consider that this exercise has been successful and a step forward in the process towards obtaining a much-needed dengue vaccine. Nevertheless, it will be important to assess further data, particularly from the ongoing Phase III studies in Latin America and Asia, in which Mexico is participating with several clinical sites [18]. A dengue vaccine would change the paradigm of dengue control by providing invaluable support to currently available prevention and control measures. Importantly, as a disease most prevalent in developing regions, a dengue vaccine would be primarily aimed at low- and middle-income countries (LMICs) [2], [16], a reversal of the traditional situation. Historically, LMICs wait for vaccines to become available and licensed in developed countries before adopting it themselves once an evidence base is generated and prices have come down to affordable levels [19], [20]. The prospect of a dengue vaccine presents LMICs, like Mexico, with an opportunity to strengthen their decision-making capacity in order to make timely and well-informed decisions about the introduction of new interventions for disease prevention and control. Improving the decision-making process will help LMICs become early adopters of public health interventions [21] and help close the time gap between innovation and access to new vaccines in such countries [22]. For early access to the dengue vaccine, countries will need to be proactive, since early access entails the timely development of adoption plans with active involvement of all sectors of society, including academic institutions, nonprofit organizations, ministries of health and finance, and health service providers [21]. Consequently, LMICs will need to prepare early and engage with all stakeholders to accelerate the process of making the vaccine available to their populations.

Investigation of selenium nutritional status and dietary pattern among children in Kashin-Beck disease endemic areas in Shaanxi Province, China using duplicate portion sampling method.

Dengue fever is a type of disease with a high and fast transmission rate, especially in tropical and subtropical regions. One of the dengue fever vaccines developed by Sanofi Pasteur (CYD-TDV) and has undergone phase III clinical trials is the tetravalent dengue vaccine. This study aims to conduct a meta-analysis and review analysis of the effectiveness of the dengue vaccine on the level of efficacy at various age levels based on previously published research results. This research uses a quantitative approach through a meta-analysis study. The data in this study were obtained from multiple sources of scientific literature in the form of research articles published in national and international journals. Data was collected online through Google Scholar, PubMed, ProQuest, Cochrane Library, and Scopus—a literature search from various sources using the keyword dengue vaccine. Data analysis was performed with the distinct stages of the study sample, effect size heterogeneity testing, calculating summary effects, calculating p-values, and determining and plotting publication bias/trim-fill analysis. The research results showed that administration of the tetravalent vaccine (CYD-TDV) to children aged 2-16 years had a moderate relationship with a Random Effect value (r ̅_RE)=0.400. The efficacy level of the CYD-TDV dengue vaccine significantly impacts patients who are given the vaccine regularly at certain time intervals (I2=4.46%).

A dengue vaccine effective against all four serotypes is urgently needed. However, safety and immunogenicity could be affected by prior exposure to flaviviruses. This open, controlled, phase IIa study was conducted in 35 healthy adults who had received monovalent, live attenuated Vero cell-derived dengue vaccine against dengue virus 1 (VDV1) or 2 (VDV2) or yellow fever (YF) vaccine 1 year before or who were flavivirus-naïve. All participants received one subcutaneous injection of tetravalent dengue vaccine (TDV) and were followed for 180 days. Previous vaccination did not increase reactogenicity, laboratory abnormalities, or incidence of vaccine viremia, but it did increase the neutralizing antibody response to dengue virus that persisted at day 180. There was no increase in YF antibodies in participants previously immunized with YF vaccine. Prior exposure to YF or monovalent dengue vaccines had no adverse effects on the safety or incidence of viremia associated with this TDV, but it increased immunogenicity.

BackgroundThe incidence of dengue fever (DF) is steadily increasing in Mexico, burdening health systems with consequent morbidities and mortalities. On December 9th, 2015, Mexico became the first country for which the dengue vaccine was approved for use. In anticipation of a vaccine rollout, analysis of the cost-effectiveness of the dengue vaccination program that quantifies the dynamics of disease transmission is essential.MethodsWe developed a dynamic transmission model of dengue in Yucatán, Mexico and its proposed vaccination program to incorporate herd immunity into our analysis of cost-effectiveness analysis. Our model also incorporates important characteristics of dengue epidemiology, such as clinical cross-immunity and susceptibility enhancement upon secondary infection. Using our model, we evaluated the cost-effectiveness and economic impact of an imperfect dengue vaccine in Yucatán, Mexico.ConclusionsOur study indicates that a dengue vaccination program would prevent 90% of cases of symptomatic DF incidence as well as 90% of dengue hemorrhagic fever (DHF) incidence and dengue-related deaths annually. We conclude that a dengue vaccine program in Yucatán, Mexico would be very cost-effective as long as the vaccination cost per individual is less than $140 and $214 from health care and societal perspectives, respectively. Furthermore, at an exemplary vaccination cost of $250 USD per individual on average, dengue vaccination is likely to be cost-effective 43% and 88% of the time from health care and societal perspectives, respectively.

Background: Knowledge, attitude, and practice (KAP) of in-patients with dengue fever (DF) through hospital-based surveillance has not been done. This study aimed to assess and compare the KAP, identify its predictors, correlation, and protective factors among pediatric and adult patients with DF and community-based controls to structure proactive community-wide DF prevention and control programs. Methods: This case-control study involved clinically or serologically confirmed patients (pediatrics n = 233; adults n = 17) with DF admitted in three public hospitals and community-based controls in Metro Manila, Philippines. A pretested structured KAP questionnaire was administered to participants to assess their KAP. Results: Pediatric and adult patients had significantly lower mean scores in the practice (p < 0.001) domain compared with the pediatric and adult controls. Being in senior high school, having had days in hospital, and rash were predictors of KAP among pediatric patients. Knowledge and attitude of patients with DF did not correlate with their practices against DF. Use of mosquito-eating fish, screen windows, and dengue vaccine were protective factors against DF. Conclusion: The study highlights the importance of behavioral change for knowledge and attitude to have significant effect to practices against DF. Thus, we recommend two comprehensive health programs, Communication for Behavioral Impact (COMBI) and Health Belief Model (HBM).

To explore and understand the attitude towards dengue vaccination and its modifiable determinants among inhabitants of Aceh (northern Sumatra Island, Indonesia), the region that was most severely affected by the earthquake and tsunami of 26 December 2004. A community-based, cross-sectional study was conducted among 535 healthy inhabitants in nine regencies (Kabupaten or Kotamadya) of Aceh that were selected randomly from November 2014 to March 2015. A set of validated, pre-tested, structured questionnaires was used to guide the interviews. The questionnaires covered a range of explanatory variables and one outcome variable (attitude to dengue vaccination). Multi-step logistic regression analysis and Spearman's rank correlation were used to test the role of explanatory variables for the outcome variable. More than 70% of the participants had a poor attitude towards dengue vaccination. Modifiable determinants associated with poor attitude to dengue vaccination were low education level, working as farmers and traditional market traders, low socioeconomic status and poor knowledge, attitude and practice regarding dengue fever (P<0.05). The KAP domain scores were correlated strongly with attitude to dengue vaccination, rs=0.25, rs=0.67 and rs=0.20, respectively (P<0.001). Multivariate analysis found that independent predictors associated with attitude towards dengue vaccination among study participants were only sex and attitude towards dengue fever (P<0.001). This study reveals that low KAP regarding dengue fever, low education level and low socioeconomic status are associated with a poor attitude towards dengue vaccination. Therefore, inhabitants of suburbs who are working as farmers or traditional market traders with low socioeconomic status are the most appropriate target group for a dengue vaccine introduction program.