at risk for developing dengue fever. The disease occurs most often during the rainy season in tropical countries in Southeast Asia, South Asia and South America, with high numbers of infected mosquitoes. The virus is transmitted to humans through the bites of infected female mosquitoes, though humans are not capable of transmitting the disease and are not contagious. The incubation period is 3 to 14 days, while the period of the illness is 3–7 days. Signs and symptoms may include severe headache; retro-orbital pain; muscle, joint, and bone pain; macular or maculopapular rash; and minor hemorrhagic manifestations, including petechiae, ecchymosis, purpura, epistaxis, bleeding gums, hematuria, or a positive tourniquet test result. A recent systematic review and meta-analysis showed that allergic symptoms are one of the core symptoms that are highly associated with dengue severity. Mechanism of infection Dengue virus (DENV) E envelope protein binds to a cellular receptor. The exact nature of the cellular receptor has not been fully elucidated. DENV undergoes endocytosis. Acidification of the endosome leads to a conformational change of E, exposing a fusion peptide sequence that facilitates fusion of the envelope with the endosomal membrane, releasing the virion capsid into the cytoplasm. Uncoating occurs in the cytoplasm Host translational machinery (ribosomes) translates the (+)ssRNA into a single polypeptide Cellular and viral proteinases cleave the polypeptide into 10 proteins (E, M, C and 7 nonstructural/enzymatic proteins) while embedded on the ER membrane. As soon as functional RNA-dependent RNA polymerase is synthesized, RNA replication can commence. Synthesis is asymmetrical, making 10 times more of the positive-sense strand than the negative. Assembly occurs on intracellular membranes, which bud into the ER (forming the envelope from the ER membrane). Subsequent budding from the ER through the Golgi and into vesicles allows maturation via posttranslational modifications, e.g. glycosylation and pH transformational rearrangements Egress occurs via exocytosis Severe disease Some people develop more severe forms of dengue, such as dengue hemorrhagic fever. Different strains of viruses interacting with people with different immune backgrounds lead to a complex interaction. Among the possible causes are cross-serotypic immune response, through a mechanism known as antibody-dependent enhancement, which happens when a person who has been previously infected with dengue gets infected for the second, third, or fourth time. The previous antibodies to the old strain of dengue virus now interfere with the immune response to the current strain, leading paradoxically to more virus entry and uptake.