Circadian Temperature Rhythm and Circadian-Circaseptan (about 7-Day) Aspects of Murine Death from Malaria 1

Abstract

About-7-day (circaseptan) and circadian rhythms were sought and found in host-parasite relations of mice infected with Plasmodium berghei. Five inbred male DBA mice, about 18 weeks of age, were implanted with transsensors for temperature telemetry. Core temperature, monitored every 10 min for 3 days before the intravenous or intraperitoneal inoculation of 10⁵ infected erythrocytes and thereafter until death, was analyzed by cosinor. A statistically highly significant circadian rhythm exhibited similarly synchronized acrophases. Core temperatures on the days immediately after malarial infection were mostly within the range of temperatures observed before injection. A mesor-hypothermic stage preceded death by several days. In a second study, 24 male BALB/c and 42 male DBA mice, 12 weeks of age, housed in three rooms on different regimens of light and darkness (alternating at 12-hr intervals), staggered by 8 hr, were inoculated ip with 10⁴ infected erythrocytes, one-half at noon, the other half at midnight, within 0.5 hr of blood withdrawal. Thus, one endeavored to cover six circadian host stages (02, 06, 10, 14, 18, and 22 hr after light-on). At 54 and 51% overall mortality (irrespective of inoculation time), a circadian rhythm in susceptibility to malaria was demonstrated in these mice by the single cosinor fit of a 24-hr period (P < 0.003 and < 0.020, respectively). The single cosinor fit of a 7-day period further demonstrated a circaseptan rhythm (P = 0.014) in the mortality of both strains following the inoculation of P. berghei. The acrophase (360° = 168 hr) was at −325° from the inoculation time with 95% confidence limits extending from −276 to −378°. Such predictable time relations of P. berghei to its murine host await the exploration of mechanisms underlying the circadian and infradian (7-day) rhythmicities here demonstrated and quantified with their uncertainties.