Abstract
Brill-Zinsser disease, the relapsing form of epidemic typhus, typically occurs in a susceptible host years or decades after the primary infection; however, the mechanisms of reactivation and the cellular reservoir during latency are poorly understood. Herein we describe a murine model for Brill-Zinsser disease, and use PCR and cell culture to show transient rickettsemia in mice treated with dexamethasone >3 months after clinical recovery from the primary infection. Treatment of similarly infected mice with cyclosporine failed to produce recrudescent bacteremia. Therapy with doxycycline for the primary infection prevented recrudescent bacteremia in most of these mice following treatment with dexamethasone. Rickettsia prowazekii (the etiologic agent of epidemic typhus) was detected by PCR, cell culture, and immunostaining methods in murine adipose tissue, but not in liver, spleen, lung, or central nervous system tissues of mice 4 months after recovery from the primary infection. The lungs of dexamethasone-treated mice showed impaired expression of β-defensin transcripts that may be involved in the pathogenesis of pulmonary lesions. In vitro, R. prowazekii rickettsiae infected and replicated in the murine adipocyte cell line 3T3-L1. Collectively these data suggest a role for adipose tissue as a potential reservoir for dormant infections with R. prowazekii.
Highlights
Epidemic, or louse-borne typhus, caused by Rickettsia prowazekii, is a potentially fatal disease that typically occurs as large, explosive outbreaks associated with war, famine, and overcrowding during periods of civil turmoil [1,2,3]
Rickettsemias of 28 BALB/c mice infected with R. prowazekii were determined by quantative real-time PCR
Using a recently described murine model for infection with R. prowazekii [24], we induced a transient rickettsemia .3 months after the primary infection by long-term treatment with dexamethasone. This reactivation was accompanied by a robust and specific IgG antibody response, without detectable IgM antibodies, similar to the humoral response associated with Brill-Zinsser disease [16,17,19,20], and pulmonary lesions similar to, but generally less extensive than the lesions observed in the lungs of mice following primary infection with R. prowazekii [24]
Summary
Louse-borne typhus, caused by Rickettsia prowazekii, is a potentially fatal disease that typically occurs as large, explosive outbreaks associated with war, famine, and overcrowding during periods of civil turmoil [1,2,3]. The disease has occurred recently as smaller outbreaks, in Russia in 1997 [7] Peru in 1998 [8], and as isolated sporadic cases in Algeria [9,10] the United States [11] and Europe [12]. Stress or waning immunity are likely to reactivate this persistent infection, and cause a recrudescent form of typhus known as Brill-Zinsser disease [14,15]. Brill-Zinsser disease is considered a milder illness than classical epidemic typhus, and the case-fatality rate of non-treated recrudescent disease is approximately 1.2%– 2.5% [22,23]; many patients with Brill Zinsser disease are moderately to severely ill [14,22,23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
