An outbreak of dengue fever occurred in the Caribbean island of St. Croix, USVI during June 2005. This is the largest recorded dengue outbreak to date in St. Croix and a high incidence of laboratory-positive infections was observed. In comparison to the recent large island-wide hyperendemic dengue outbreak in Puerto Rico, 
the incidence observed in this outbreak was 2.7 times greater. Additionally, a high proportion of suspected cases (5%) met WHO criteria for DHF. In comparison, during the 1981 DENV-2 outbreak in Cuba, the proportion of DHF among reported cases was approximately 3%. 
More recently, the proportion of DHF among reported dengue cases during the hyperendemic outbreaks of 2007 in the Caribbean states of Martinique, Guadeloupe, and the Dominican Republic similarly ranged from 2–3%. 
In this investigation, the enhancement of dengue surveillance at the hospital in St. Croix may have accounted for the increased proportion of DHF. It may also be explained by the high proportion of secondary infections, 
as well as by the virulence of the circulating strain of dengue. 
During this outbreak, the circulating dengue genotype was the southeast Asian strain of DENV-2, which has been previously demonstrated to be associated with more severe illness. 
To our knowledge, this is the first report of an investigation of the risk factors of DHF in the USVI. In this investigation, age was the only factor associated with DHF. The higher proportion of DHF cases in those above the age of 40 suggests that more of these individuals may have preexisting immunity to another dengue serotype after a past outbreak in St. Croix. An association between DHF and age has also been demonstrated using data from Brazil and Thailand. 
Additionally, there was a protective trend for Afro-Caribbean race in this study, but this was not statistically significant. Previous studies have noted that, despite hyperendemic transmission, DHF is not as prevalent in Haiti (where the majority of the population is of African descent) or in the African continent when compared to other tropical areas. 
This may be partially explained by the lack of consistent surveillance or by the under-diagnosis of DHF in these areas. In the Cuban dengue epidemics of 1981 and 2001, Afro-Cubans were at a reduced risk of severe manifestations of dengue when compared to whites. 
More recently, it was reported that Afro-Colombians, in comparison with Mestizos, were less likely to be hospitalized, had higher platelet counts and lower hematocrit levels. 
African ancestry has also been reported to be protective for DHF in Brazil. 
Other studies have suggested that, in addition to race, there are other genetic determinants for severe dengue, ranging from blood group to expression of human leukocyte antigen (HLA) class I and II molecules on virus-infected cells. 
It is very difficult to assess race, and there are inconsistencies between different studies (e.g
., researchers in Brazil used genetic ancestry as a proxy for race/ethnicity 
while others in Colombia determined it by observing the hair type, facial features and skin color of study participants 
). This study utilized self-reported race and, though an imperfect measure, this may be the most appropriate means of assigning it, 
especially in the absence of ancestral genetic markers.
The major limitation of this investigation is the small sample size and consequent lack of power to detect significant associations. Moreover, 53% of suspected cases lacked a convalescent serum specimen and thus yielded indeterminate results from laboratory testing. Thus, in light of the small population size of St. Croix and the fact that only 37% of suspected cases were confirmed, any epidemiologic study on laboratory-positive cases seeking care at the hospital would be limited by a small sample size. There were inadequate resources to perform IgG testing on all specimens; thus the primary/secondary infection status of all cases and controls could not be ascertained, and this could not be assessed as a risk factor for DHF. However, increasing age may have acted as a proxy for secondary infection status. Additionally, a dengue seroprevalence study was not performed in response to this outbreak and the true incidence rate of dengue infection could not be calculated.
Severe dengue disease does occur along a spectrum but clinical data was insufficient for the non-hospitalized cases and inaccessible for those who sought care from private physicians during this outbreak. Thus, comparisons between severe and mild dengue cases were not possible. Other limitations include the high degree of under-reporting due to the passive method of dengue surveillance in the USVI. As all dengue testing is conducted outside of the territory, this may act as a further disincentive to report. Being unable to include data on laboratory-positive outpatients with dengue fever and the limited sample size and power of the study may have biased the results of this analysis towards the null. Conversely, the major strength of the case-control study was that it focused entirely on hospital-based, laboratory-positive patients which, through chart review, allowed for appropriate classification of disease severity.
This investigation provided an excellent opportunity to investigate the epidemiology of a circumscribed dengue outbreak in a Caribbean island – despite the increasing frequency of reported outbreaks in the region, there are few published reports documenting the unique nature of each outbreak. This is the first report addressing risk factors for DHF in the USVI, a multi-ethnic Caribbean territory. While it has been reported that persons of African descent are at reduced risk of DHF, clearly, as reported here, the population is still at risk of severe dengue and potentially death. HLA and other markers associated with altered risk of DHF have been identified, but the reason for this reduced risk among Afro-Caribbean persons remains elusive. The Caribbean is a dengue-endemic region and investigating outbreaks in its more populous multi-ethnic countries (such as Trinidad and Tobago, Cuba, and the Dominican Republic) would provide an excellent opportunity to conduct further research on the question of a dengue resistance gene in those of African descent.