Dengue is a major international public health concern and the number of outbreaks has escalated greatly. the ratio of clinically apparent to (R)-(+)-Corypalmine inapparent contamination could affect the interpretation of vaccine trials. We performed a literature search for inapparent DENV infections and provide an analytical review of their frequency and associated risk factors. Inapparent rates were highly variable but “inapparent” was the major outcome of contamination in all prospective studies. Differences in the epidemiological context and type of surveillance account for much of the variability in inapparent contamination rates. However one particular epidemiological pattern was shared by four longitudinal cohort studies: the rate of inapparent DENV infections was positively correlated with the incidence of disease the previous year strongly supporting an important role for short-term heterotypic immunity in determining the outcome of contamination. Primary and secondary infections were equally likely to be inapparent. Knowledge of the extent to which viruses from inapparent infections are transmissible to mosquitoes is usually urgently needed. Inapparent infections need to be considered for their impact on disease severity transmission dynamics and vaccine efficacy and uptake. genus in the family and mosquito vector to transmit the virus. This Asian tiger mosquito is the major potential vector of DENV in Europe although the (R)-(+)-Corypalmine most important vector world-wide A. aegypti was identified in Madeira Island Portugal in October 2005. A major epidemic occurred in Madeira in 2012 (13). Autochthonous transmission of DENV in the United States has also been reported intermittently over the past decade in Texas Hawaii and Florida (14 15 International travel will ensure importation (R)-(+)-Corypalmine of virus into non-endemic countries from regions endemic for dengue. Infected individuals may harbor sufficiently high viral loads to infect mosquitoes prior to the onset of symptoms and thereby introduce the virus into the population. Potentially more important is the epidemiological IB2 significance of inapparent subclinical infections. Travelers may import virus without showing overt clinical symptoms and thus will not be detectable either in the airports or once in the country. There is some suggestion that primary (1°) DENV infections can be majoritarily inapparent in certain outbreaks (16) whereas secondary (2°) infections lead to more severe symptoms even when occurring 20?years later (17). In fact the longer the interval between heterotypic DENV infections the higher the case fatality rate (18). The public health consequences of such inapparent infections are considerable because apparently na?ve populations may well have been previously exposed to infections and once hospital cases of dengue are detected the population as a whole may have already been primed with prior DENV infection. The frequency of inapparent infections is extremely variable year to year the risk factors poorly understood and the terminology not (R)-(+)-Corypalmine standardized. Subclinical inapparent and asymptomatic infections are often used as synonyms and the use of paucisymptomatic is used to designate a DENV contamination with few symptoms. We will use subclinical and inapparent to denote infections with insufficient symptoms to be detected by the research or national surveillance program and/or to incite the infected individual to consult but for which there is evidence either by seroconversion or detection of virus that the individual was infected with DENV. Asymptomatic infections will be used when there are no symptoms at all reported by the infected individual during an active contamination whether inferred by seroconversion or serology. We review the literature around the extent of inapparent DENV infections identify associated risk factors and highlight several important lacunae that need to be addressed to assess the extent of the epidemiological importance of inapparent infections. We combine a PubMed literature (R)-(+)-Corypalmine search approach with review of articles cited within PubMed hits plus a review of the classical pre-PubMed dengue literature. The search strategy was dengue?+?one of the.