THE RELATION TO THE COURSE OF AVIAN MALARIA OF BIOTIN AND A FAT-SOLUBLE MATERIAL HAVING THE BIOLOGICAL ACTIVITIES OF BIOTIN.

Biotin deficiency produced by a synthetic biotin-deficient diet was as effective in decreasing the resistance of chickens to infection with Plasmodium lophurae as biotin deficiency produced by a diet high in egg white. In moderately biotin-deficient ducks Plasmodium cathemerium at first multiplied more slowly than in adequately fed controls. The parasitemia in the deficient animals later overtook that in the controls and attained higher peak parasite numbers. The multiplication of P. cathemerium was notably inhibited in ducks inoculated when they were approaching death from biotin deficiency. The total and differential leucocyte count of biotin-deficient chickens did not differ significantly from that of adequately fed controls. During infection of chickens with P. lophurae and ducks with either P. lophurae or P. cathemerium significant changes occur in the concentration in the plasma of free biotin and of a material which on hydrolysis yields a fat-soluble substance (FSF) having the biological activities of biotin but differing chemically from it. In ducks which survived infections with P. cathemerium or P. lophurae the biotin concentration rose very early in the course of the infection, before there was any anemia. It fell slightly, rose to a peak at about the time of the peak parasite number, and then returned to normal. The concentration of bound FSF, which was determined in terms of its biotin activity, increased at first, then decreased, then rose and continued at a high level throughout the period of decline in parasitemia. In most of the animals which died of either infection the free biotin, instead of returning to normal, rose to very high values Just before death, while the bound FSF, instead of remaining at a high value, fell to very low values, reaching zero in several animals. Greater resistance seemed to be associated with a greater excess of bound FSF over free biotin. In animals about to die the free biotin exceeded the bound FSF. The biotin content of the liver of ducks and chickens fed an adequate diet and killed just after having undergone an infection with either P. lophurae or P. cathemerium was much less than that of control uninfected animals. When P. lophurae was cultured in vitro in suspensions of duck erythrocytes a very wide range in biotin concentration in the culture fluid did not affect its rate of multiplication. Plasma protein fractions relatively rich in FSF at a concentration of 0.75 per cent inhibited multiplication, while comparable concentrations of plasma fractions poor in FSF did not. The results obtained fit the assumption that the substance in plasma which yields FSF is directly concerned in resistance to avian malaria.