Severe Dengue Virus Infection in Travelers. Part 2
WHO definitions cause confusion when patients with otherwise uncomplicated dengue fever have severe thrombocytopenia or when patients suspected clinically to have DHF do not meet all 4 WHO criteria. Second, the DHF/DSS classification excludes severe dengue disease associated with “unusual manifestations.” Moreover, the term “dengue hemorrhagic fever” places undue emphasis on hemorrhage, when the most important “danger” sign that should be watched for and managed appropriately is plasma leakage leading to shock. Finally, the WHO classification is mainly based on studies in children and may therefore not be applicable to predominantly adult travelers. Shock and plasma leakage appear to be more common in children, whereas internal hemorrhage is more frequently a manifestation in adults. A new definition for severe dengue is now urgently needed. A large multicenter descriptive study is under way to obtain the evidence base to establish a more robust dengue classification scheme for use by clinicians, epidemiologists, public health authorities, vaccine specialists, and scientists involved in dengue pathogenesis research. The development of shock, altered consciousness, severe bleeding, unusual manifestations, or death would be considered an indication of severe dengue, the main outcome, and the data might then be used to construct an algorithm to predict this outcome.
Wichmann et al. also attempted to identify risk factors for more severe disease, because the risk factors and clinical findings in adult travelers may differ from those observed in the predominantly pediatric population in which dengue is endemic. They added laboratory parameters to their analysis to supplement the initial descriptive epidemiological studies by their network on dengue, published in 2002. The data are limited somewhat by the small number of travelers with serious complications—of 219 patients with imported dengue virus infections, only 17 had any spontaneous hemorrhage, the majority of which were epistaxis or gum bleeding, and none required blood or platelet transfusions. In addition, only 2 patients met the WHO criteria for DHF, and none had DSS. Despite these limitations, the data confirm previous studies suggesting that the secondary immune response increases the risk of more‐severe disease but is not the only factor associated with DHF.
In conclusion, dengue is increasingly a global problem that also affects international travelers. There are huge challenges—the clinical diagnosis is difficult; cocirculation of all 4 virus serotypes has increased the risk of more‐severe disease; vaccines remain a challenge; new hosts have appeared, with dengue having been transmitted to transplant recipients; nosocomial transmission without a mosquito vector has been reported; and there is the potential for increased spread with global climate change. Efforts such as those by TropNetEurop and GeoSentinel that allow for systematic aggregation of clinical and laboratory data on dengue in international travelers via formal data collection are to be commended, and it is hoped that similar efforts will arise in Asia. This will allow for greater collaboration in terms of surveillance, identification of risk factors, improved treatment, and, potentially, vaccine studies.