we conducted a retrospective cohort analysis of trends in dengue diagnoses among hospitalized patients using the national inpatient sample , the largest all - payer database of hospital discharges in the united states .
the database is maintained as part of the healthcare cost and utilization project by the agency for healthcare research and quality and consists of a 20% stratified sample of discharges from nonfederal acute care hospitals ( 11 ) .
we first extracted all discharges from the national inpatient sample for hospital admission ( i.e. , the denominator of the incidence rate ) from 2000 through 2007 . among this population , we then identified cases of dengue fever coded as either a primary or secondary diagnosis ( i.e. , code 061 , dengue fever ) , according to the international classification of diseases , ninth revision , clinical modification .
for each yearly incidence rate , we calculated a 95% exact binomial confidence interval . to determine whether a significant trend in hospitalizations of patients with dengue fever occurred during the study period , we fit a logistic regression model using yearly incidence as the dependent variable and year as the independent variable .
in addition , to accommodate the temporal association in the yearly incidence , we fit the model using generalized estimating equations , assuming an autoregressive correlation structure .
we also calculated the ratio of the yearly incidence rates at the beginning and the end of the study period ( i.e. , rates in 2000 and 2007 ) .
we tested whether this incidence ratio is significantly different from one using the fisher exact test and computed a 95% exact confidence interval for the corresponding odds ratio using the hypergeometric distribution .
( because the incidence rates are fairly low , the odds ratio closely approximates the incidence ratio . )
finally , we used the monte carlo variant of the fisher exact test to investigate possible geographic variation in the incidence rate among the 4 us census regions .
all statistical analyses were performed by using r version 2.10.1 ( r foundation for statistical computing ; www.r-project.org ) and sas version 9.2 ( sas institute inc . , cary , sc , usa . ) .
the length of stay for these patients ranged from 0 to 35 days ( median 3 days ) . for the monte carlo variant of the fisher exact test
, we found the incidence rates for the 4 us census regions were homogenous for all years , except for 2004 and 2007 . in these 2 years , the northeast region had the highest incidence rate ( p<0.0001 for each year ) . over the study period ,
the estimated number of dengue cases more than tripled from 81 cases in 2000 to 299 cases in 2007 .
the trend in the incidence of patients hospitalized with dengue during the study period was upward and significant ( trend estimate 0.1313 , model - based se 0.0258 ; p<0.0001 ) ( figure ) .
the increase from 2000 to 2007 was also significant ( incidence ratio 3.5641 , 95% confidence interval 2.02936.6232 ; p<0.0001 ) .
national estimates of dengue yearly incidence rates and 95% exact binomial confidence intervals ( error bars ) , calculated by using data from the national inpatient sample , united states , 20002007 .
the trend ( dotted line ) is based on a logistic regression model fit by using generalized estimating equations .
note that the trend is curvilinear in the incidence rate , yet linear in the log odds of the incidence .
we found a dramatic increase in the number of hospitalizations for patients with dengue fever in the united states .
this increase is not surprising considering that 1 ) the number of cases in disease - endemic regions has increased in recent years , and 2 ) a substantial number of travelers annually enter the united states from the tropics and subtropics ( 12 ) .
although infrequent , severe consequences of dengue infection may occur in returning travelers . as individual travelers increasingly make multiple visits to dengue - endemic areas , the risk for severe dengue infections may similarly increase .
a survey of 219 travelers who received treatment for dengue in europe showed that 23 ( 11% ) had severe clinical manifestations , including internal hemorrhage , plasma leakage , shock , and marked thrombocytopenia ( 13 ) .
we were unable to ascertain whether mosquito - borne hemorrhagic fever ( international classification of diseases , ninth revision , code 065.4 ) also increased because the code appears quite infrequently , making statistical inferences unreliable .
we also attempted to use deaths as a marker for disease severity , but we could not detect an increase in disease severity in our analysis because number of deaths was insufficient to accurately estimate a mortality rate . dengue and dengue hemorrhagic fever have been described as potential public health threats for residents of the us mainland ( 14 ) . despite the proximity of circulating dengue virus to the continental united states and the spread of the vector mosquitoes ( aedes aegypti and ae .
albopictus ) to at least 26 states ( 15 ) , autochthonous cases in the continental united states have been relatively rare ( 5 ) until the recent florida outbreak . the increase in reported cases that we have documented highlights a potential risk for dengue spread within the united states .
although dengue fever was previously classified as reportable in some states , it did not become a reportable illness at the national level until 2010 .
thus , some time is required before cases reported to public health departments can be used to establish reliable statistical estimates of national trends .
furthermore , the number of cases may not be linked to other relevant clinical data .
the major limitation to our study is that we used administrative data , and thus we did not have access to laboratory data or patients travel histories .
nevertheless , our results indicate that the decision to make dengue fever a reportable disease in the united states was warranted and that increased vigilance focused on these new surveillance data is needed .
in addition , administrative data , as we describe here , can be used to estimate the effects and severity of illness attributable to dengue .
 international travel and a global expansion of dengue fever have the potential to increase the incidence of dengue in the united states . 
 we conducted a retrospective cohort analysis of trends in dengue among hospitalized patients by using the national inpatient sample ( 20002007 ) ; the number of cases more than tripled ( p<0.0001 ) . 