Dengue is widespread throughout the tropics and local spatial variation in dengue virus transmission is strongly influenced by rainfall, temperature, urbanization and distribution of the principal mosquito vector Aedes aegypti. Currently, endemic dengue virus transmission is reported in the Eastern Mediterranean, American, South-East Asian, Western Pacific and African regions, whereas sporadic local transmission has been reported in Europe and the United States as the result of virus introduction to areas where Ae. aegypti and Aedes albopictus, a secondary vector, occur. The global burden of the disease is not well known, but its epidemiological patterns are alarming for both human health and the global economy. Dengue has been identified as a disease of the future owing to trends toward increased urbanization, scarce water supplies and, possibly, environmental change. According to the WHO, dengue control is technically feasible with coordinated international technical and financial support for national programmes. This Primer provides a general overview on dengue, covering epidemiology, control, disease mechanisms, diagnosis, treatment and research priorities.

Clinical sequelae after recovery from an acute dengue virus infection are common in the 2 years following infection. The results obtained in this study suggest that persistent symptoms are associated with alterations in some immunological parameters and FcγRIIa gene polymorphism. This could suggest an autoimmune-based disturbance.

Abstract. The role of human Fcγ receptors (FcγR) has been recognized considerably over the last years. These receptors vary in their affinity for IgG subclasses and the intracellular signals elicited by them. Allelic variants of FcγR genes may influence the biological phagocyte activity, accounting for an inherited pre-disposition to disease. The specific FcγRIIa (CD32) contains a polymorphic variant (H/R131) that has been associated to a reduced risk for developing dengue hemorrhagic fever (DHF). Here, we investigated the role of this polymorphism in a very well-characterized group of Cuban individuals with antecedents of DHF, dengue fever (DF), or subclinical dengue infection. The HH131 genotype was significantly associated with dengue disease, either DF (* P = 0.016; odds ratio = 4.425; 95% confidence interval = 1.10-20.52) or DHF ( P = 0.00018; odds ratio = 10.56; 95% confidence interval = 2.33-54.64) with respect to the subclinical infection.

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Previously, we reported the ability of the chimeric protein DIIIC-2 (domain III of the dengue envelope protein fused to the capsid protein of dengue-2 virus), to induce immunity and protection in mice, when it is highly aggregated with a non-defined oligodeoxynucleotide (ODN) and adjuvanted in alum. In this work, three different defined ODNs were studied as aggregating agents. Our results suggest that the nature of the ODN influences the capacity of protein DIIIC-2 to activate cell-mediated immunity in mice. Consequently, the ODN 39M was selected to perform further experiments in mice and nonhuman primates. Mice receiving the preparation 39M-DIIIC-2 were solidly protected against dengue virus (DENV) challenge. Moreover, monkeys immunized with the same preparation developed neutralizing antibodies, as measured by four different neutralization tests varying the virus strains and the cell lines used. Two of the immunized monkeys were completely protected against challenge, whereas the third animal had a single day of low-titer viremia. This is the first work describing the induction of short-term protection in monkeys by a formulation that is suitable for human use combining a recombinant protein from DENV with alum. Dengue virus (DENV) is a mosquito-borne flavivirus and the causative agent of dengue and severe dengue. It is estimated that nearly half of the world's population is at risk of infection, with up to 50 million people infected each year and frequent epidemic activity in Southeast Asia, South America and Western Pacific regions. 1,2 Infection with one serotype confers immunity to infection with the same dengue serotype, but does not prevent infection with the others. Viral and host factors have been proposed to have a role in the development of the severe disease, but epidemiological evidence has led to the realization that the majority of severe cases occur in individuals who suffer secondary or sequential DENV infections. 3,4 This implies that immunity to a heterotypic virus is not only ineffective in preventing secondary infection, but may also enhance the disease.Primary prevention through dengue vaccines is considered a research priority in the dengue agenda. Although a vaccine is feasible, its development faces several challenges: (a) a dengue vaccine must be able to protect against the four serotypes; (b) long-term protection is needed; (c) no suitable animal model exists for dengue; and (d) although the protective role of neutralizing antibodies is widely held, correlates of protection need to be defined.There are several dengue vaccine candidates at advanced preclinical and clinical stages, although no vaccine is licensed. The most advanced strategies (phase II-III) are based on live attenuated viruses and are led by the Sanofi Pasteur's ChimeriVax-dengue vaccine candidate (Paris, France). Despite the balanced reactogenicity and immunogenicity profile of the tetravalent ChimeriVax-dengue vaccine candidate, three doses are required during 1 year to induce high neutralizing antibody seroconversion...