Background The result of previous dengue computer virus (DENV) exposure about subsequent heterologous infection can be beneficial or detrimental depending on many factors including timing of infection. Of 38 740 DENV infections two or more infections were recognized in 502 individuals; 14 experienced three infections. The mean age groups at the time of the 1st and second recognized infections were 7.6?±?3.0 and 11.2?±?3.0?years. The shortest time between sequential infections was 66?days. A longer time interval between sequential infections was associated with dengue hemorrhagic fever (DHF) in the second detected illness (OR 1.3 95 CI 1.2-1.4). All possible sequential serotype pairs were observed among 201 subjects with DHF at the second detected illness except DENV-4 followed by DENV-3. Among DENV infections recognized in cohort subjects by active study surveillance and subsequent non-study hospital-based passive surveillance hospitalization in the 1st detected illness increased the likelihood of hospitalization at the second detected illness. Conclusions Increasing time between sequential DENV infections was associated with Angiotensin 1/2 (1-6) higher severity of the second detected illness supporting the part of heterotypic immunity in both safety and enhancement. Hospitalization was positively associated between the 1st and second recognized infections suggesting a possible predisposition in some individuals to more severe dengue disease. Electronic supplementary material The online version of this article (doi:10.1186/s12889-015-1590-z) contains supplementary material which is available to authorized users. Background Dengue is definitely a globally important re-emerging infectious disease caused by one of four dengue computer virus serotypes (DENV-1 to DENV4) with a high degree of antigenic cross-reactivity. It is estimated that 390 LRRC15 antibody million infections happen yearly with approximately 96 million resulting in clinically apparent disease . DENV infections can lead to diverse results including subclinical illness clinically nonspecific illness dengue fever (DF) and dengue hemorrhagic fever (DHF). Many studies have shown that the risk of DHF in non-infant individuals is higher when an initial DENV illness is followed by a second illness having a different serotype [2-7]. All possible orders of infecting serotypes have been documented in individuals with DHF except DENV-4 followed by DENV-1 or DENV-3 . In some populations reports indicate that DHF happens more frequently with DENV-2 or DENV-3 infections in DENV-1 revealed individuals [9 10 One mechanism underlying this observation has been postulated to be antibody-dependent enhancement (ADE) during the second illness mediated by non-protective heterotypic antibodies arising from the 1st illness. However the timing of the second illness seems to be important since some degree of short-term safety may Angiotensin 1/2 (1-6) be Angiotensin 1/2 (1-6) conferred against subsequent heterologous illness from the Angiotensin 1/2 (1-6) preceding illness . Inside a population model of children hospitalized with dengue in Bangkok Thailand the space of this short-term heterologous safety was estimated to be one to three years . Longer intervals between heterologous infections seem to increase susceptibility to DHF. An evaluation of dengue instances from outbreaks in Cuba in 1981 and 1997 suggest that a longer period between infections increases the risk of DHF . In an analysis of repeat DENV infections from a prospective cohort study of children in Kamphaeng Phet Thailand the percentage of symptomatic to subclinical infections was found to be higher when the time from first to second illness was longer . Some studies have suggested that sequential illness with two different serotypes may induce adequate cross-immunity to confer some degree of safety from a third or fourth serotype. Primate studies have suggested that multivalent neutralizing antibodies after two DENV infections reduce the risk of detectable viremia from subsequent heterologous illness [15-18]. Among thousands of children hospitalized with dengue in Bangkok Thailand the number of known third and fourth infections was found to be less than the number of known second infections indicating some level of multivalent safety after two heterologous infections . Interestingly with this same populace of.