A biocompatible microdevice for core body temperature monitoring in the early diagnosis of infectious disease

Abstract

The early diagnosis of microbial infection is critical to the clinical instigation of effective post-exposure prophylaxis or therapy. However, diagnosis of infection is often attempted only when there are overt clinical signs, and for some of the serious human pathogens, this may jeopardise the efficacy of therapy. We have used a miniaturised sealed, implantable transponder incorporating a calibrated temperature sensor with an external receiver system, to monitor core body temperature (Tc) remotely. We have observed early changes in the diurnal rhythm of Tc, after infection of mice with bacterial pathogens. Changes in Tc preceded overt clinical signs by 3–10 h following challenge with Yersinia pestis, which causes acute infection, In contrast, changes in Tc were detected 11 days before clinical signs in mice exposed to Burkholderia pseudomallei, which causes a chronic syndrome. Significantly, mice pre-vaccinated against Y.pestis infection showed only slight and transient disruption to the diurnal rhythm for Tc, in the absence of clinical signs, when challenged with 10⁶ median lethal doses of Y.pestis. This remote monitoring technology could be used to monitor changes in more than one physiological parameter and extrapolation of these data to the clinic would define the available therapeutic window in which diagnosis and post-exposure prophylaxis could be instigated, after a suspected exposure.