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Observations on the Mechanism of the Parasite Cycle in Falciparum Malaria¹

Persis Putnam
The Rockefeller Foundation, New York, N. Y.

A study of the mechanism of the parasite cycle has been made through an analysis of its component trophozoite and gametocyte waves in fifty-five Negro patients, thirty-four of whom were naturally inoculated and twenty-one artificially infected with a single strain of P. falciparum.

The day of modal density proves to be a reasonably good centering point for the trophozoite and gametocyte waves to which curves are fitted. Computed densities on the modal day are utilized.

Key points in the parasite cycle, the days of first appearance (microscopic detection) of trophozoites and gametocytes following inoculation and the days of maximum or of modal density, are surprisingly constant. Failure of quinine to affect these points and of artificial inoculation to alter greatly the lengths of the segments between them supplies further evidence of the stable nature of the cycle.

The timing of certain key points may be altered in individual patients by natural resistance, acquired immunity, or treatment but all points are not similarly affected. The correlations between adjacent segments are predominantly negative indicating that when one is lengthened the other becomes shorter and vice versa so that the cycle is brought back into line.

This stability leads to the belief that the events in the parasite cycle are determined prior to the appearance of trophozoites in the peripheral blood and possibly at the time of inoculation.

Significant positive correlation exists between the computed densities of trophozoites and gametocytes on the modal day. This relationship supports the thesis that sexual forms arise from the segmenting asexual parasites.

The negative relationships between adjacent segments of trophozoite and gametocyte waves indicate, we believe, that production of gametocytes begins prior to the end of the prepatent period and possibly soon after inoculation of the patient. Consequently, the interval of approximately ten days between the first appearance of trophozoites and gametocytes and between their peak densities indicates that a period for development is required by gametocytes over and above that needed for them to accumulate sufficiently to reach microscopic visibility.

¹ The studies and observations on which this paper is based were conducted with the support and under the auspices of the International Health Division of The Rockefeller Foundation, in cooperation with the Florida State Board of Health and the Florida State Hospital.