Real-time monitoring of disease progression in rhesus macaques infected with Borrelia turicatae by tick bite

Abstract

The hallmark of disease caused by tick- and louse-borne relapsing fever due to Borrelia infection is cyclic febrile episodes, which in humans results in severe malaise and may lead to death. To evaluate the pathogenesis of relapsing fever due to spirochetes in an animal model closely related to humans, disease caused by Borrelia turicatae after tick bite was compared in 2 rhesus macaques in which radiotelemetry devices that recorded body temperatures in 24-hour increments were implanted. The radiotelemetry devices enabled real-time acquisition of core body temperatures and changes in heart rates and electrocardiogram intervals for 28 consecutive days without the need to constantly manipulate the animals. Blood specimens were also collected from all animals for 14 days after tick bite, and spirochete densities were assessed by quantitative polymerase chain reaction. The complexity of disease caused by relapsing-fever spirochetes was demonstrated in the nonhuman primates monitored in real time. The animals experienced prolonged episodes of hyperthermia and hypothermia; disruptions in their diurnal patterns and repolarization of the heart were also observed. This is the first report of the characterizing disease progression with continuous monitoring in an animal model of relapsing fever due to Borrelia infection.

Keywords: Borrelia; Borrelia turicatae; relapsing fever; rhesus macaques; spirochetes.

Figure 1.

Experimental design for infecting rhesus macaques with Borrelia turicatae. A and B, JD03 (A) and IN57 (B) were implanted with radiotelemetry devices 2 weeks before ticks fed on the animals. C, After the feeding, body temperatures of the 2 animals were recorded manually (black horizontal arrow) in 24-hour intervals. Horizontal white arrows indicate the time line for collecting blood specimens by ear or tail prick, and black vertical arrows indicate time points for serum specimen collection and performing complete blood count and blood chemistry analyses.

Figure 2.

A and B, Ornithodoros turicata ticks feeding on JD03. The duration between tick placement (A) and repletion (B) was between 20–30 minutes. C, Subdermal hemorrhage on JD03 was seen at the site where ticks fed. D, Spirochetes were visualized in the blood within 6 days after the transmission-associated blood meal (D), and a 25-µm scale is shown. These results from JD03 were representative of those for the 3 other animals.

Figure 3.

A–D, Comparisons of Borrelia turicatae densities in the blood with daily temperature readings for JB23 (A), JB60 (B), JD03 (C), and IN57 (D). Box and whisker plots indicate the lower and upper quartiles, median, and lower and upper extremes of spirochete densities, while the asterisks represent the temperature at the time of blood specimen collection.

Figure 4.

Real-time measured physiological responses of JD03 and IN57. JD03 was fed upon by uninfected ticks (red data points) as a sham infection. A–C, After Borrelia turicatae challenge by tick bite, changes in body temperature (A), corrected QT interval (defined as the duration of ventricular depolarization and repolarization; B), and heart rate (C) are displayed as hourly means for JD03 (blue) and IN57 (green). The period when temperature data were not collected for IN57, on day 6, was a result in temporary unavailability of the hard drive of the data-acquisition unit.