DENGUE FEVER All four distinct dengue viruses (dengue 1-4) have A.

aegypti as their principal vector, and all cause a similar clinical syndrome. In rare cases, second infection with a serotype of dengue virus different from that involved in the primary infection leads to dengue H with severe shoc! (see "elow). #poradic cases are seen in the settings of endemic transmission and epidemic disease. $ear-round transmission "etween latitudes %& ' and %&# has "een esta"lished, and seasonal forays of the viruses to points as far north as (hiladelphia are thought to have ta!en place in the )nited #tates. *ith increasing spread of the vector mos+uito throughout the tropics and su"tropics, large areas of the world have "ecome vulnera"le to the introduction of dengue viruses, particularly through air travel "y infected humans, and "oth dengue fever and the related dengue H are "ecoming increasingly common. ,onditions favora"le to dengue transmission e-ist in the southern )nited #tates, and "ursts of dengue fever activity are to "e e-pected in this region, particularly along the .e-ican "order, where water may "e stored in containers and A. aegypti num"ers may therefore "e greatest/ this mos+uito, which also is an efficient vector of the yellow fever and chi!ungunya viruses, typically "reeds near human ha"itation, using relatively fresh water from sources such as water 0ars, vases, discarded containers, coconut hus!s, and old tires. A. aegypti usually inha"its dwellings and "ites during the day. After an incu"ation period of % to 1 days, the typical patient e-periences the sudden onset of fever, headache, retroor"ital pain, and "ac! pain along with the severe myalgia that gave rise to the collo+uial designation 2"rea!-"one fever.2 3here is often a macular rash on the first day as well as adenopathy, palatal vesicles, and scleral in0ection. 3he illness may last a wee!, with additional symptoms usually including anore-ia, nausea or vomiting, mar!ed cutaneous hypersensitivity, and near the time of defervescencea maculopapular rash ( ig. %44-,51) "eginning on the trun! and spreading to the e-tremities and the face. 6pista-is and scattered petechiae are often noted in uncomplicated dengue, and pree-isting gastrointestinal lesions may "leed during the acute illness. 7a"oratory findings include leu!openia, throm"ocytopenia, and, in many cases, serum aminotransferase elevations. 3he diagnosis is made "y Ig. 67I#A or paired serology during recovery or "y antigen-detection 67I#A or 83-(,8 during the acute phase. 9irus is readily isolated from "lood in the acute phase if mos+uito inoculation or mos+uito cell culture is used. DENGUE HEMORRHAGIC FEVER/DENGUE SHOCK SYNDROME A syndrome of H noted in the 1:&4s among children in the (hilippines and #outheast Asia was soon associated with dengue virus infections, particularly those occurring against a "ac!ground of previous e-posure to another serotype. 3he transient heterotypic protection after dengue virus infection is replaced within several wee!s "y the potential for heterotypic infection resulting in typical dengue fever (see a"ove) oruncommonlyfor enhanced disease (secondary 5H ;5##). In rare instances, primary dengue infections lead to an H syndrome, "ut much less is !nown a"out pathogenesis in this situation. In the past %4 years, A. aegypti has progressively reinvaded 7atin America and other areas, and fre+uent travel "y infected individuals has introduced multiple strains of dengue virus from many geographic areas. 3hus the pattern of hyperendemic transmission of multiple dengue serotypes has now "een esta"lished in the Americas and the ,ari""ean and has led to the emergence of 5H ;5## as a ma0or pro"lem there as well. .illions of dengue infections, including many thousands of cases of 5H ;5##, occur annually. 3he severe syndrome is unli!ely to "e seen in ).#. citi<ens since few children have the dengue anti"odies that can trigger the pathogenetic cascade when a second infection is ac+uired. .acrophage;monocyte infection is central to the pathogenesis of dengue fever and to the origin of 5H ;5##. (revious infection with a heterologous dengue-virus serotype may result in the production of nonprotective antiviral anti"odies that nevertheless "ind to the virion=s surface and through interaction with the c receptor focus secondary dengue viruses on the target cell, the result "eing enhanced infection. 3he host is also primed for a secondary anti"ody response when viral antigens are released and immune comple-es lead to activation of the classic complement pathway, with conse+uent phlogistic effects. ,ross-reactivity at the 3 cell level results in the release of physiologically active cyto!ines, including interferon and tumor necrosis factor alpha. 3he induction of vascular permea"ility and shoc! depends on multiple factors, including the following/ 1. Presence of enhancing and nonneutralizing antibodies 3ransplacental maternal anti"ody may "e present in infants <: months old, or anti"ody elicited "y previous heterologous dengue infection may "e present in older individuals. %. Age#uscepti"ility to 5H ;5## drops considera"ly after 1% years of age. >. Sex emales are more often affected than males.

4. Race,aucasians are more often affected than "lac!s. &. Nutritional status.alnutrition is protective. ?. Sequence of infection or e-ample, serotype 1 followed "y serotype % is more dangerous than serotype 4 followed "y serotype %. 1. Infecting serotype3ype % is apparently more dangerous than other serotypes. In addition, there is considera"le variation among strains of a given serotype, with #outheast Asian serotype % strains having more potential to cause 5H ;5## than others. 5engue H is identified "y the detection of "leeding tendencies (tourni+uet test, petechiae) or overt "leeding in the a"sence of underlying causes such as pree-isting gastrointestinal lesions. 5engue shoc! syndrome, usually accompanied "y hemorrhagic signs, is much more serious and results from increased vascular permea"ility leading to shoc!. In mild 5H ;5##, restlessness, lethargy, throm"ocytopenia (<144,444;u7), and hemoconcentration are detected % to & days after the onset of typical dengue fever, often at the time of defervescence. 3he maculopapular rash that often develops in dengue fever may also appear in 5H ;5##. In more severe cases, fran! shoc! is apparent, with low pulse pressure, cyanosis, hepatomegaly, pleural effusions, ascites, and in some cases severe ecchymoses and gastrointestinal "leeding. 3he period of shoc! lasts only 1 or % days, and most patients respond promptly to close monitoring, o-ygen administration, and infusion of crystalloid orin severe casescolloid. 3he mortality rates reported vary greatly with case ascertainment and the +uality of treatment@ however, most 5H ;5## patients respond well to supportive therapy, and overall mortality in an e-perienced center in the tropics is pro"a"ly as low as 1 percent. A virologic diagnosis can "e made "y the usual means, although multiple flavivirus infections lead to a "road immune response to several mem"ers of the group, and this situation may result in a lac! of virus specificity of the Ig. and IgA immune responses. A secondary anti"ody response can "e sought with tests against several flavivirus antigens to demonstrate the characteristic wide spectrum of reactivity. 3he !ey to control of "oth dengue fever and 5H ;5## is the control of A. aegypti, which also reduces the ris! of ur"an yellow fever and chi!ungunya virus circulation. ,ontrol efforts have "een handicapped "y the presence of nondegrada"le tires and long-lived plastic containers in trash repositories, insecticide resistance, ur"an poverty, and an ina"ility of the pu"lic health community to mo"ili<e the populace to respond to the need to eliminate mos+uito "reeding sites. 7ive attenuated dengue vaccines are in the late stages of development and have produced promising results in early tests. *hether vaccines can provide safe, dura"le immunity to an immunopathologic disease such as 5H ;5## in endemic areas is an issue that will have to "e tested, "ut it is hoped that vaccination will reduce transmission to negligi"le levels.