(Abstract) Infection with dengue virus is a major public health problem in the Asia-Pacific region and throughout tropical and sub-tropical regions of the world. Vaccination represents a major opportunity to control dengue and several candidate vaccines are in development. Experts in dengue and in vaccine introduction gathered for a two day meeting during which they examined the challenges inherent to the introduction of a dengue vaccine into the national immunisation programmes of countries of the Asia-Pacific. The aim was to develop a series of recommendations to reduce the delay between vaccine licensure and vaccine introduction. Major recommendations arising from the meeting included: ascertaining and publicising the full burden and cost of dengue; changing the perception of dengue in non-endemic countries to help generate global support for dengue vaccination; ensuring high quality active surveillance systems and diagnostics; and identifying sustainable sources of funding, both to support vaccine introduction and to maintain the vaccination programme. The attendees at the meeting were in agreement that with the introduction of an effective vaccine, dengue is a disease that could be controlled, and that in order to ensure a vaccine is introduced as rapidly as possible, there is a need to start preparing now.
In 2012, dengue is the most important vector-borne viral disease of humans and likely more important than malaria globally in terms of morbidity and economic impact.
(Abstract) Dengue is a systemic arthropod-borne viral disease of major global public health importance. At least 2.5 billion people who live in areas of the world where dengue occurs are at risk of developing dengue fever (DF) and its severe complications, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Repeated reemergences of dengue in sudden explosive epidemics often cause public alarm and seriously stress healthcare systems. The control of dengue is further challenged by the lack of effective therapies, vaccines, and point-of-care diagnostics. Despite years of study, even its pathogenic mechanisms are poorly understood. This article discusses recent advances in dengue research and identifies challenging gaps in research on dengue clinical evaluation, diagnostics, epidemiology, immunology, therapeutics, vaccinology/clinical trials research, vector biology, and vector ecology. Although dengue is a major global tropical pathogen, epidemiologic and disease control considerations in this article emphasize dengue in the Americas.
(Abstract) BACKGROUND: Dengue is a growing problem both in its geographical spread and in its intensity, and yet current global distribution remains highly uncertain. Challenges in diagnosis and diagnostic methods as well as highly variable national health systems mean no single data source can reliably estimate the distribution of this disease. As such, there is a lack of agreement on national dengue status among international health organisations. Here we bring together all available information on dengue occurrence using a novel approach to produce an evidence consensus map of the disease range that highlights nations with an uncertain dengue status. METHODS/PRINCIPAL FINDINGS: A baseline methodology was used to assess a range of evidence for each country. In regions where dengue status was uncertain, additional evidence types were included to either clarify dengue status or confirm that it is unknown at this time. An algorithm was developed that assesses evidence quality and consistency, giving each country an evidence consensus score. Using this approach, we were able to generate a contemporary global map of national-level dengue status that assigns a relative measure of certainty and identifies gaps in the available evidence. CONCLUSION: The map produced here provides a list of 128 countries for which there is good evidence of dengue occurrence, including 36 countries that have previously been classified as dengue-free by the World Health Organization and/or the US Centers for Disease Control. It also identifies disease surveillance needs, which we list in full. The disease extents and limits determined here using evidence consensus, marks the beginning of a five-year study to advance the mapping of dengue virus transmission and disease risk. Completion of this first step has allowed us to produce a preliminary estimate of population at risk with an upper bound of 3.97 billion people. This figure will be refined in future work.
(Abstract) The incidence of dengue fever and dengue hemorrhagic fever in Brazil experienced a significant increase since the emergence of dengue virus type-3 (DENV-3) at the early 2000s. Despite the major public health concerns, there have been very few studies of the molecular epidemiology and time-scale of this DENV lineage in Brazil. In this study, we investigated the origin and dispersion dynamics of DENV-3 genotype III in Brazil by examining a large number (n = 107) of E gene sequences sampled between 2001 and 2009 from diverse Brazilian regions. These Brazilian sequences were combined with 457 DENV-3 genotype III E gene sequences from 29 countries around the world. Our phylogenetic analysis reveals that there have been at least four introductions of the DENV-3 genotype III in Brazil, as signified by the presence of four phylogenetically distinct lineages. Three lineages (BR-I, BR-II, and BR-III) were probably imported from the Lesser Antilles (Caribbean), while the fourth one (BR-IV) was probably introduced from Colombia or Venezuela. While lineages BR-I and BR-II succeeded in getting established and disseminated in Brazil and other countries from the Southern Cone, lineages BR-III and BR-IV were only detected in one single individual each from the North region. The phylogeographic analysis indicates that DENV-3 lineages BR-I and BR-II were most likely introduced into Brazil through the Southeast and North regions around 1999 (95% HPD: 1998-2000) and 2001 (95% HPD: 2000-2002), respectively. These findings show that importation of DENV-3 lineages from the Caribbean islands into Brazil seems to be relatively frequent. Our study further suggests that the North and Southeast Brazilian regions were the most important hubs of introduction and spread of DENV-3 lineages and deserve an intense epidemiological surveillance.
A completed clinical trial of vaccine efficacy should be cause for celebration for the billions of people who live in the 128 countries where dengue viruses (DENV) are transmitted. However, the celebration will be muted this time, as was the case after announcement of results of early clinical trials of vaccines for malaria and HIV.
(Abstract) BACKGROUND: Roughly half the world's population live in dengue-endemic countries, but no vaccine is licensed. We investigated the efficacy of a recombinant, live, attenuated tetravalent dengue vaccine. METHODS: In this observer-masked, randomised, controlled, monocentre, phase 2b, proof-of-concept trial, healthy Thai schoolchildren aged 4-11 years were randomly assigned (2:1) to receive three injections of dengue vaccine or control (rabies vaccine or placebo) at months 0, 6, and 12. Randomisation was by computer-generated permuted blocks of six and participants were assigned with an interactive response system. Participants were actively followed up until month 25. All acute febrile illnesses were investigated. Dengue viraemia was confirmed by serotype-specific RT-PCR and non-structural protein 1 ELISA. The primary objective was to assess protective efficacy against virologically confirmed, symptomatic dengue, irrespective of severity or serotype, occurring 1 month or longer after the third injection (per-protocol analysis). This trial is registered at ClinicalTrials.gov, NCT00842530. FINDINGS: 4002 participants were assigned to vaccine (n=2669) or control (n=1333). 3673 were included in the primary analysis (2452 vaccine, 1221 control). 134 cases of virologically confirmed dengue occurred during the study. Efficacy was 30·2% (95% CI -13·4 to 56·6), and differed by serotype. Dengue vaccine was well tolerated, with no safety signals after 2 years of follow-up after the first dose. INTERPRETATION: These data show for the first time that a safe vaccine against dengue is possible. Ongoing large-scale phase 3 studies in various epidemiological settings will provide pivotal data for the CYD dengue vaccine candidate. FUNDING: Sanofi Pasteur.
(Abstract) OBJECTIVE: Dengue fever is endemic in Malaysia and poses a significant problem to the national health system. Because of its nonspecific clinical features, it creates clinical and administrative uncertainties. We evaluated the role of an emergency department short-stay ward (EDSSW) in the management of dengue fever in the Universiti Kebangsaan Malaysia Medical Centre (UKMMC). METHODS: A retrospective study was carried out on suspected dengue patients who were admitted to UKMMC EDSSW, between January and March 2010. Data were retrieved from the EDSSW Monthly Census Book and patients' medical records. Patients were categorized as follows: group 1, which included patients who received treatment in the EDSSW only, and group 2, which included patients who received initial treatment in EDSSW and were subsequently admitted to the inpatient (IP) wards. RESULTS: A total of 147 patients' records were available. The total length of stay was 32.2 h in group 1 and 100.5 h in group 2. For group 2 patients, a median of 21.8 h was spent in EDSSW and 78.8 h was spent in IP. All patients in group 1 and group 2 were discharged well. The total EDSSW stay was 4309 patient-hours; IP stay totalled 5137 patient-hours. The use of the EDSSW reduced the IP burden in managing dengue by 45.6%. CONCLUSION: EDSSW limit the number and burden of dengue patients requiring formal IP admissions while acting as a 'safety net' for inappropriate discharges and unnecessary admissions.
(Abstract) Objective: To estimate the seroincidence of dengue in children living in Salvador, Bahia, Brazil and to evaluate the factors associated. Methods: A prospective serological survey was carried out in a sample of children 0-3 years of age. A multilevel logistic model was used to identify the determinants of seroincidence. Results: The seroprevalence of dengue was 26.6% in the 625 children evaluated. A second survey detected an incidence of 33.2%. Multilevel logistic regression showed a statistically significant association between the seroincidence of dengue and age and the premises index. Conclusion In Salvador, the dengue virus is in active circulation during early childhood; consequently, children have heterotypic antibodies and run a high risk of developing dengue haemorrhagic fever, because the sequence and intensity of the three dengue virus serotypes currently circulating in this city are very similar to those that were circulating in Rio de Janeiro, Brazil, in 2008. Therefore, the authors strongly recommend that the health authorities in cities with a similar epidemiological scenario be aware of this risk and implement improvements in health care, particularly targeting the paediatric age groups. In addition, information should be provided to the population and actions should be implemented to combat this vector.
(Abstract) Dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) is an enigmatic and growing public health problem which is confined at present to countries of South-East Asia. Epidemiological studies in South-East Asia clearly link DHF/DSS to individuals who have had a previous dengue infection or who have acquired maternal dengue antibody. There is an urgent need for a comprehensive identification of "risk factors" in DHF/DSS. This research could be approached by undertaking comparative prospective epidemiological studies in dengue-endemic areas with and without DHF/DSS.