scholarly journals The impact of the newly licensed dengue vaccine in endemic countries

2016 ◽  
Author(s):  
M. Aguiar ◽  
Nico Stollenwerk ◽  
Scott B. Halstead
Keyword(s):  
Disease Burden ◽  
Phase Iii ◽  
World Health ◽  
Severe Dengue ◽  
Dengue Vaccine ◽  
Endemic Region ◽  
Dengue Disease ◽  
Vaccination Strategies ◽  
Tetravalent Vaccine ◽  
The Impact

AbstractBackground:With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is only supportive and severe dengue cases require hospital intensive care. A vaccine now licensed in several countries and developed by Sanofi Pasteur (CYD-TDV, named Dengvaxia), is able to protect, in the first 25 months of the two Phase III, 66% of a subset of 9 − 16 year old participants. However, a significantly lower efficacy (including negative vaccine efficacy) was noted for children younger than 9 years of age.Methodology/Principal Findings:Analysis of year 3 results of phase III trials of Dengvaxia suggest high rates of protection of vaccinated partial dengue immunes but high rates of hospitalizations during breakthrough dengue infections of persons who were vaccinated when seronegative, with vaccine appearing to induce enhancing antibodies (ADE). An age structured model was developed based on Sanofi’s recommendation to vaccinate persons age 945 years in dengue endemic countries. The model was used to explore the clinical burden of two vaccination strategies: 1) Vaccinate 4 or 20% of individuals, ages 9 − 45 years, seropositives and seronegatives, and 2) vaccinate 4 or 20% of individuals, ages 9 − 45 years, who are dengue immune only.Conclusions/Significance:Our results show that vaccinating dengue monotypic immune individuals prevents dengue hospitalizations, but at the same time dengue infections of vaccine-sensitized persons increases hospitalizations. When the vaccine is given only to partial immune individuals, after immuno-logical screening of the population, disease burden decreases considerably.Author SummaryCaused by four antigenically related but distinct serotypes a tetravalent vaccine is needed to protect against the huge burden of dengue disease. Dengvaxia is a vaccine candidate now licensed in several countries for individuals 9 − 45 years of age living in endemic countries with least 70% of seroprevalence. Modelers from Sanofi Pasteur have predicted that this vaccine has the potential to reduce by about 50% the disease burden within 5 years when 20% of an endemic country population is vaccinated, thus achieving a World Health Organization dengue prevention goal.In this paper, mathematical modeling is used to investigate the impact of the newly licensed dengue vaccine using different scenarios. Our results show that to achieve significant reduction in disease bur-den, the vaccination program is most effective if it includes only individuals that have been already exposed to at least one dengue virus. Immunological screening of the population prior to vaccination is advised and vaccination strategies must be planned based on epidemiological disease dynamics for each specific endemic region.

scholarly journals Could Globalisation be Good for World Health?

1970 ◽  
Vol 1 ◽  
Author(s):  
Thomas Pogge
Keyword(s):  
Disease Burden ◽  
Pharmaceutical Innovation ◽  
World Health ◽  
Medical Treatments ◽  
Alternative Scheme ◽  
International Patent ◽  
Good For ◽  
The Impact ◽  
Perverse Effect ◽  
Global Disease Burden

Every day thousands of people die from poverty-related causes. Many of these deaths could be avoided if appropriate medical treatments were available to the world’s poor. Due to the current tructure of the international patent regime, they are not. Since the risks and costs associated with pharmaceutical innovation are extremely high, to incentivise research, inventor firms are granted a temporary monopoly over newly invented drugs. While allowing firms to make up for the costs of research, this has the morally perverse effect of raising the prices of pharmaceuticals to a level where they become unaffordable to the world’s poor. To correct this grievous flaw, the paper proposes a concrete and realistic alternative scheme which, by rewarding medical innovators in proportion to the impact of their drugs on the global disease burden, would incentivise the production and selling of crucial drugs for the world’s poor at prices accessible to them.

Three Decades of Dengue Surveillance in Five Highly Endemic South East Asian Countries

2016 ◽  
Vol 29 (1) ◽  
pp. 7-16 ◽  
Author(s):  
T. A. Wartel ◽  
A. Prayitno ◽  
S. R. S. Hadinegoro ◽  
M. R. Capeding ◽  
U. Thisyakorn ◽  
...  
Keyword(s):  
Disease Burden ◽  
Case Fatality ◽  
World Health ◽  
Asian Countries ◽  
Dengue Disease ◽  
Dengue Prevention ◽  
Health Organization ◽  
Integrated Or ◽  
And Control ◽  
Observation Period

We described and quantified epidemiologic trends in dengue disease burden in 5 Asian countries (Indonesia, Thailand, Malaysia, Philippines, and Vietnam) and identified and estimated outbreaks impact over the last 3 decades. Dengue surveillance data from 1980 to 2010 were retrieved from DengueNet and from World Health Organization sources. Trends in incidence, mortality, and case fatality rate (CFR) were systematically analyzed using annual average percent change (AAPC), and the contribution of epidemic years identified over the observation period was quantified. Over the 30-year period, incidence increased in all countries (AAPC 1980-2010: 6.7% in Thailand, 10.4% in Vietnam, 12.0% in Indonesia, 18.1% in Malaysia, 24.4% in Philippines). Mortality also increased in Indonesia, Malaysia, and Philippines (AAPC: 6.8%, 7.0%, and 29.2%, respectively), but slightly decreased in Thailand and Vietnam (AAPC: −1.3% and −2.5%), and CFR decreased in all countries (AAPC: −4.2% to −8.3%). Epidemic years, despite representing less than a third of the observation period, contributed from 1 to 3 times more cases versus nonepidemic years. Implementation of more sensitive surveillance methods over the study period may have contributed to a reporting or ascertainment bias in some countries. Nonetheless, these data support the urgent need for novel, integrated, or otherwise effective dengue prevention and control tools and approaches.

scholarly journals Comparison of Neutralizing Dengue Virus B Cell Epitopes and Protective T Cell Epitopes With Those in Three Main Dengue Virus Vaccines

2021 ◽  
Vol 12 ◽  
Author(s):  
Josilene Ramos Pinheiro ◽  
Esther Camilo dos Reis ◽  
Rayane da Silva Oliveira Souza ◽  
Ana Luíza Silva Rocha ◽  
Lincoln Suesdek ◽  
...  
Keyword(s):  
T Cell ◽  
Dengue Virus ◽  
B Cell ◽  
Public Health Problem ◽  
Phase Iii ◽  
World Health ◽  
Human Populations ◽  
T Cell Epitopes ◽  
Dengue Vaccine ◽  
B Cell Epitopes

The four serotypes of Dengue virus (DENV1-4) are arboviruses (arthropod-borne viruses) that belong to the Flavivirus genus, Flaviviridae family. They are the causative agents of an infectious disease called dengue, an important global public health problem with significant social-economic impact. Thus, the development of safe and effective dengue vaccines is a priority according to the World Health Organization. Only one anti-dengue vaccine has already been licensed in endemic countries and two formulations are under phase III clinical trials. In this study, we aimed to compare the main anti-dengue virus vaccines, DENGVAXIA®, LAV-TDV, and TAK-003, regarding their antigens and potential to protect. We studied the conservation of both, B and T cell epitopes involved in immunological control of DENV infection along with vaccine viruses and viral isolates. In addition, we assessed the population coverage of epitope sets contained in each vaccine formulation with regard to different human populations. As main results, we found that all three vaccines contain the main B cell epitopes involved in viral neutralization. Similarly, LAV-TDV and TAK-003 contain most of T cell epitopes involved in immunological protection, a finding not observed in DENGVAXIA®, which explains main limitations of the only licensed dengue vaccine. In summary, the levels of presence and absence of epitopes that are target for protective immune response in the three main anti-dengue virus vaccines are shown in this study. Our results suggest that investing in vaccines that contain the majority of epitopes involved in protective immunity (cellular and humoral arms) is an important issue to be considered.

scholarly journals Comparing the 2009 and 1997 World Health Organization dengue case classifications in a large cohort of South Asian patients

2020 ◽  
Vol 14 (07) ◽  
pp. 781-787 ◽  
Author(s):  
Umesh Jayarajah ◽  
Upul Dissanayake ◽  
Visula Abeysuriya ◽  
Pradeep K De Silva ◽  
Priyankara Jayawardena ◽  
...  
Keyword(s):  
World Health Organisation ◽  
Warning Signs ◽  
World Health ◽  
Severe Dengue ◽  
Dengue Case ◽  
Dengue Disease ◽  
Asian Patients ◽  
Resource Limited ◽  
Dengue With Warning Signs ◽  
Health Organization

Introduction: Due to the shortcomings in the 1997-World Health Organisation (WHO) dengue case classification (DCC), a revised classification was proposed in 2009. This study was aimed to assess the clinical usefulness of the two classifications during a large dengue epidemic. Methodology: Clinical data of dengue patients admitted to selected units at National Hospital of Sri Lanka, Panadura Base Hospital and Nawaloka Hospital Colombo between June and August 2017 were collected prospectively. Cases were classified using the 1997 and 2009 WHO DCCs. Results: 1,878 patients [adult = 1,573 (83.8%)] were studied. Based on 1997-WHO-DCC-DF (Dengue Fever): 1,316 (70.1%), DHF (Dengue Haemorrhagic Fever) -1: 468 (24.9%), DHF-2: 86 (4.6%) and DHF-3: 8 (0.4%). Based on 2009-WHO-DCC–Dengue with warning signs (WS): 1647 (87.7%), Dengue without WS: 231 (12.3%) and severe dengue (SD): 41 (2.18%). A total of 1,088 (82.7%) DF and 559 (99.5%) DHF patients developed WS. Of those without WS, 228 (17.3%) were DF patients and 3 (0.5%) were DHF patients. Three (0.23%) DF and 38 (6.76%) DHF patients had SD. All SD patients had WS. The level of agreement between the two systems of classification was poor (Kappa = - 0.035, p < 0.001). Conclusions: The 2009-WHO-DCC was more useful than 1997-WHO-DCC in predicting dengue disease severity as few DF patients also had SD. Furthermore, the presence of WS identified patients with SD. However, the 2009-WHO-DCC may not suit the resource limited countries as WS are non-specific, and lack of diagnostic tests can result in case overload.

scholarly journals 1389. Economic Evaluation of Universal Varicella Vaccination in Mexico

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S704-S704
Author(s):  
Enrique Chacon-Cruz ◽  
Estelle Meroc ◽  
Sue Ann Costa-Clemens ◽  
Thomas Verstraeten
Keyword(s):  
Cost Effectiveness ◽  
Cost Saving ◽  
Economic Burden ◽  
Disease Burden ◽  
Varicella Vaccine ◽  
Cost Effective ◽  
Varicella Vaccination ◽  
Published Data ◽  
Vaccination Strategies ◽  
The Impact

Abstract Background Universal varicella vaccination (UVV) has proven to be cost-effective in countries where implemented. However, this has not yet been evaluated for Mexico. We assessed the cost-effectiveness of UVV in the Mexican Immunization Program from both healthcare and societal perspectives. Methods The annual disease burden (varicella cases/deaths, outpatient visits, and hospitalizations) were derived from Mexican seroprevalence-published data adjusted to the 2020 country’s population. The annual economic burden was calculated by combining disease with Mexican published unit cost data. Four different vaccination strategies were evaluated: 1. One dose of a single varicella vaccine at 1 year old; 2. Two doses of single varicella vaccine at 1 and 6 years; 3. One dose of a single varicella vaccine at 1 year, and quadrivalent measles-mumps-rubella-varicella vaccine (MMRV) at 6 years; 4. Two doses of MMRV at 1 and 6 years. We developed an economic model for each vaccination strategy where 20 consecutive birth cohorts were simulated. The impact of vaccination (number of avoided cases/deaths) was evaluated for a 20 years follow-up period based on vaccine effectiveness (87% and 97.4%), and assuming a 95% coverage. Subsequently, we estimated net vaccination costs, benefit-cost ratio (BCR), annual costs saved, cost-effectiveness ratio. Results From annual disease burden estimation, avoided cases with one dose, and two doses were of 20,570,722 and 23,029,751, respectively. From the 20 years cohort, the yearly number of varicella cases was estimated at 2,041,296, and total costs at $115,565,315 (USD) (healthcare perspective) and $165,372,061 (healthcare and societal perspectives). Strategies 1 and 2 were found to be cost-saving (BCR &gt;1) (Figure 1), and strategy 3 to be cost-effective (CE) ($1539 per Life Year Gained). Strategy 4 was not CE. Strategies 1 and 2 would allow saving annually $53.16 million and $34.41 million, respectively, to the Mexican society. FIGURE 1 Conclusion 1.The disease and economic burden of varicella in Mexico are high. 2.UVV with four different vaccination strategies results in a high reduction of cases. 3.From healthcare and societal perspectives, UVV was shown to be cost-effective (with strategy 3), and cost-saving (with strategies using one dose or two doses separately). Disclosures All Authors: No reported disclosures

scholarly journals Commentary on Article: Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents (NEJM, Nov 21 2019)

2020 ◽  
pp. 21-28
Author(s):  
A. M. Meer Ahmad
Keyword(s):  
Adverse Events ◽  
Children And Adolescents ◽  
Phase Iii ◽  
Severe Dengue ◽  
Healthy Children ◽  
Additional Observation ◽  
Dengue Vaccine ◽  
Serious Adverse Events ◽  
Phase Iii Trial ◽  
Chimeric Vaccine

In this Letter to the Editor, this author comments on the article in the NEJM (Nov 21 2019) in the above title on the TAK-003 Dengue vaccine Phase III trial from a point of comparing with the predecessor, the CYD-TDV, beside comparing the TAK-003 and Severe dengue, and the TAK-003 and hospitalizations. The author also queries why the vaccine must be a chimeric-vaccine, questions the sample-size in the Phase III trial and questions the Serious Adverse Events reported observed in the trial. He write on Antibody Directed Enhancement in a relation to the TAK-003. The author make Additional Observation and seek certain Explanation.

scholarly journals Viral Toxin ns1 as Pivotal Target in Development of Efficient Dengue Vaccine

2021 ◽  
Author(s):  
Grégorie Lebeau ◽  
Alisé Lagrave ◽  
Eva Ogire ◽  
Lauriane Grondin ◽  
Soundary Seriacaroupin ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Nonstructural Protein ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Public Health Problem ◽  
Severe Dengue ◽  
Global Public Health ◽  
Dengue Vaccine ◽  
Dengue Disease ◽  
Nonstructural Protein 1

Mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often associated to fatality. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of the four related antigenically distinct serotypes, DENV-1 to DENV-4. The growing burden that represents the four DENV serotypes has intensified both basic and applied researches to better understand the dengue physiopathology. It has been proposed a significant role for the secreted soluble DENV nonstructural protein 1 (sNS1) glycoprotein in the pathogenesis of severe dengue. Here, we provided an overview on current knowledge about the role of sNS1 in the immunopathogenesis of dengue disease. The reasons for the consideration of sNS1 in the design of future dengue vaccine candidates will be discussed.

scholarly journals A study to evaluate the impact of a 21-day school brushing intervention on the knowledge, behaviour and oral health of schoolchildren (Preprint)

2019 ◽  
Author(s):  
Paulo Melo ◽  
Sinead Malone ◽  
Arathi Rao ◽  
Charlotte Fine
Keyword(s):  
Oral Health ◽  
Oral Care ◽  
Cluster Randomized Trial ◽  
Day School ◽  
Phase Iii ◽  
World Health ◽  
Control Group ◽  
Fluoride Toothpaste ◽  
Health Organization ◽  
The Impact

BACKGROUND The World Health Organization reports that dental cavities affect 60-90% of children globally. FDI World Dental Federation and Unilever Oral Care have developed public health programmes to improve brushing habits over their 12-year partnership. The last of these (Phase III) named Brush Day & Night aimed to educate children in brushing twice daily with a fluoride toothpaste. OBJECTIVE In Phase IV of the partnership, we aim to evaluate the impact on the knowledge, behaviour and toothbrushing habits in schoolchildren aged 6-9 years old, after a 21-day school programme and compare with baseline and a control group. The enduring nature of the programme will be determined by the inclusion of 8 and 24-week time points. METHODS The study is a two-arm, parallel, stratified, cluster randomized trial. Clusters in this study are infant and junior schools in Indonesia and Nigeria. The study aims to recruit 20 schools in each country. At baseline, children in both intervention and control schools will complete questionnaires and have their oral health assessed via the Simplified Oral Hygiene Index (OHIs) and Decayed Missing and Filled Teeth (DMFT). Children in the intervention schools will then take part in a structured 21-day Brush Day & Night intervention. The Brush Day & Night programme is an intense education activity designed to establish the habit of brushing day and night with a fluoride toothpaste. The programme involves daily brushing instruction and includes free toothpaste and toothbrushes. Children in the control schools will be provided with free toothpaste and toothbrushes but will not receive the 21-day intervention. The questionnaires and OHIs assessment are repeated after 21 days and then again at 8 weeks and 24 weeks later for all participating children. Parents/Carers/Guardians of all children will complete questionnaires on their own experience and attitudes to oral health and toothbrushing routine at each of the four times points (baseline, 21-day, 8 weeks and 24 weeks). The study will be conducted by the National Dental Associations of Indonesia and Nigeria. RESULTS The study is ongoing. Recruitment of schools started in Indonesia in February 2018 and in Nigeria in April 2018 for the first part of the study. This concluded in Indonesia in September 2018 and in Nigeria in November 2018. The second part of the study (the second half of the schools) started in November 2018 in Indonesia and December 2018 in Nigeria. CONCLUSIONS We expect to publish findings from the study by March 2020.

Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593.

1998 ◽  
Vol 16 (9) ◽  
pp. 2906-2912 ◽  
Author(s):  
H S Koops ◽  
M Vaglini ◽  
S Suciu ◽  
B B Kroon ◽  
J F Thompson ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Regional Lymph Node ◽  
Phase Iii ◽  
World Health ◽  
Isolated Limb Perfusion ◽  
Primary Cutaneous Melanoma ◽  
European Organization ◽  
Limb Perfusion ◽  
The Impact

PURPOSE Patients with primary cutaneous melanoma > or = 1.5 mm in thickness are at high risk of having regional micrometastases at the time of initial surgical treatment. A phase III international study was designed to evaluate whether prophylactic isolated limb perfusion (ILP) could prevent regional recurrence and influence survival. PATIENTS AND METHODS A total of 832 assessable patients from 16 centers entered the study; 412 were randomized to wide excision (WE) only and 420 to WE plus ILP with melphalan and mild hyperthermia. Median age was 50 years, 68% of patients were female, 79% of melanomas were located on a lower limb, and 47% had a thickness > or = 3 mm. RESULTS Median follow-up duration is 6.4 years. There was a trend for a longer disease-free interval (DFI) after ILP. The difference was significant for patients who did not undergo elective lymph node dissection (ELND). The impact of ILP was clearly on the occurrence-as first site of progression - of in-transit metastases (ITM), which were reduced from 6.6% to 3.3%, and of regional lymph node (RLN) metastases, with a reduction from 16.7% to 12.6%. There was no benefit from ILP in terms of time to distant metastasis or survival. Side effects were higher after ILP, but transient in most patients. There were two amputations for limb toxicity after ILP. CONCLUSION Prophylactic ILP with melphalan cannot be recommended as an adjunct to standard surgery in high-risk primary limb melanoma.

scholarly journals A Dengue Vaccine: Will It be Accepted and Is It Feasible? Lessons from Barranquilla, Colombia, and Merida, Venezuela

2019 ◽  
Vol 7 (10) ◽  
pp. 458
Author(s):  
Elizabeth McMahon ◽  
Liliana Encinales ◽  
Carlos Navarro Encinales ◽  
Silvana Vielma ◽  
Nelly Pacheco ◽  
...  
Keyword(s):  
Disease Burden ◽  
World Health ◽  
Dengue Vaccine ◽  
Government Officials ◽  
Policy Makers ◽  
Severe Problem ◽  
Social Unrest ◽  
Vaccination Programs ◽  
Vaccine Introduction ◽  
Health Organization

With one vaccine on the market and others in clinical trials, policy makers in dengue endemic regions face the decision of whether to introduce a dengue vaccine in their communities. The World Health Organization (WHO) recommends that individualized assessments be conducted before any vaccine introduction to evaluate disease burden and the strength of current vaccination programs. This study seeks to aid in that decision-making process by examining the acceptability and feasibility of dengue vaccine introduction in Barranquilla, Colombia, and Merida, Venezuela. Surveys were administered February–June of 2018 for three groups: patients (n = 351), health professionals (n = 197), and government officials (n = 26). In Barranquilla, most respondents reported dengue to be a moderate-severe problem, that a dengue vaccine would be useful in their communities, and that their current vaccination programs could handle the addition of a new vaccine. In Venezuela, respondents were less likely to view dengue as a major concern and listed multiple barriers to not just dengue vaccine introduction, but to providing current vaccines as well. Further work is needed in Colombia to more objectively assess the country’s readiness as a whole for a future dengue vaccine. As political and social unrest continues in Venezuela, however, future initiatives should focus on trust and capacity building. This study can serve as a framework for future assessments of the acceptability and feasibility of a dengue vaccine in both targeted areas and on larger scales.

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