The infectivity of P. berghei-infected TO mice to mosquitoes declines
rapidly 2 to 5 days after blood inoculation, in spite of rising number
s of gametocytes in the blood. This pattern is typical of many malaria
infections and various factors, particularly specific and nonspecific
immune responses, have previously been implicated in the decline. Her
e we report that (1) simple physiological changes in the mouse blood n
amely, falling pH and bicarbonate levels induced by high parasitaemias
, are responsible for the sustained inhibition of infectivity; (2) the
inhibition is reversible in vivo by the addition of sodium bicarbonat
e alone; (3) the inhibition occurs at the point of exflagellation; (4)
contrary to previous observations (Kawamoto et al. 1992), exflagellat
ion in P. berghei, like that in P. gallinaceum (Bishop and McConnachie
1956; Nijhout and Carter 1978; Nijhout 1979) and P. falciparum (Ogwan
'g et al. 1993), is dependent on extracellular bicarbonate; and (5) in
duction of exflagellation by a mosquito factor is bicarbonate dependen
t. These new observations are critical to the design and interpretatio
n of experiments on other transmission blocking phenomena. (C) 1996 Ac
ademic Press, Inc.