One limitation of this study is in the classification of disease severity as none of our patients developed neurologic or hemorrhagic complications previously reported in CHIKF patients. Nonetheless, our definition of severe illness would have included patients with sepsis, a serious form of infection commonly associated with a temperature of .38uC and heart rate of .90/ minute [24] . Furthermore, we included thrombocytopenia of ,100610 9 /L as a criteria for severe CHIKF. Marked thrombocytopenia is a common feature of sepsis [25] and has been identified as a predictor of mortality [26, 27] . The degree of thrombocytopenia is a determinant of survival and once the platelet count decreases below 100610 9 /L, mortality continues to increase, even though the risk of bleeding does not [28] . A wide spectrum of disease has been reported in CHIKF ranging from asymptomatic infections, to self-limiting febrile illness [8] , to neurologic complications, and death [17] . The ''severe illness'' cohort in our study possibly represents a more severe form of selflimiting febrile illness, an intermediate group with higher levels of viremia (data not shown) and distinctly more severe clinical features (i.e. high temperature, tachycardia, and severe thrombocytopenia). Using this clinical phenotype, we have shown in this study that immune mediators are able to distinguish very mild disease from more severe forms of CHIKF disease at the acute stage. Follow-up studies will be required to determine if long-term sequelae are indeed different between non-severe and severe clinical presentations. Elucidating the association of disease severity with two cytokines and one chemokine can be useful in order to provide early identification and monitoring of patients with severe disease. Although this study is limited by the size of the outbreak, nevertheless, based on these observations, measurement of immune mediators could be helpful for the management of future outbreaks. This study strongly suggests these biomarkers be used for measuring disease severity and be tested in outbreaks in different populations and different strains. Once confirmed, they will be useful for follow-up studies, association studies, and prognosis for public health management. More importantly, these biomarkers can potentially lead to the development of modulators to reduce disease severity and to halt disease progression. 