Kinetics of changes of Histamine throughout the course of illness
In order to determine the changes in urinary histamine throughout the illness, we measured histamine in 16 patients DF and 16 patients with DHF throughout the course of illness (Fig 7a) . In patients with both DF and in those who proceeded to develop DHF, urinary histamine levels gradually declined from illness day 3 onwards. We also investigated possible diurnal variation in urinary histamine levels in 9 patients with DF and 7 patients with DHF (Fig 7b) . In patients with both DF (p = 0.004) and DHF (p = 0.01) the urinary histamine levels significantly decreased in the afternoon (3pm) samples compared to the morning samples, although there was wide inter-individual variation(Fig 7b). Similar diurnal variations were seen with serum viral loads in patients with both DF and DHF (Fig 7c ).