PMID- 26378973 OWN - NLM STAT- MEDLINE DCOM- 20170417 LR - 20191210 IS - 1557-7759 (Electronic) IS - 1530-3667 (Linking) VI - 15 IP - 9 DP - 2015 Sep TI - Development of an Orientia tsutsugamushi Lc-1 Murine Intraperitoneal Challenge Model for Scrub Typhus: Determination of Murine Lethal Dose (MuLD50), Tissue Bacterial Loads, and Clinical Outcomes. PG - 539-44 LID - 10.1089/vbz.2015.1773 [doi] AB - Currently, no vaccine has been developed to protect humans from naturally acquired heterologous Orientia tsutsugamushi infections. To enhance the validity of vaccine candidates, we are developing a murine chigger challenge model with the O. tsutsugamushi Lc-1-infected Leptotrombidium chiangraiensis Line-1. To this end, an intraperitoneal (i.p.) murine challenge model using an O. tsutsugamushi Lc-1 isolate was developed for eventual validation of the chigger challenge model. We have determined that the murine lethal dose that kills 50% of the challenged mice (MuLD50) of a liver/spleen homogenate developed from O. tsutsugamushi Lc-1-infected ICR Swiss mice to be 10(-6.9). Employing different inoculum doses of this homogenate, the bacterial load using quantitative real-time PCR (qPCR) was determined to range from 60 to 1.6 x 10(5) genome equivalent copies (GEC)/muL of liver and 33.4 to 2.2 x 10(5) GEC/muL of spleen tissue. The clinical outcomes relative to homogenate dose levels followed a dose-dependent pattern. The successful development and characterization of the O. tsutsugamushi Lc-1 i.p. challenge model will assist in the development and validation of a mouse chigger challenge scrub typhus model. FAU - Lurchachaiwong, Woradee AU - Lurchachaiwong W AD - 1 Department of Entomology, US Army Medical Component, Armed Forces Research Institute of Medical Sciences , Bangkok, Thailand . FAU - McCardle, Wesley AU - McCardle W AD - 1 Department of Entomology, US Army Medical Component, Armed Forces Research Institute of Medical Sciences , Bangkok, Thailand . FAU - Chan, Teik-Chye AU - Chan TC AD - 2 Viral and Rickettsial Diseases Department, Naval Medical Research Center , Silver Spring, Maryland. FAU - Schuster, Anthony L AU - Schuster AL AD - 1 Department of Entomology, US Army Medical Component, Armed Forces Research Institute of Medical Sciences , Bangkok, Thailand . FAU - Richards, Allen L AU - Richards AL AD - 2 Viral and Rickettsial Diseases Department, Naval Medical Research Center , Silver Spring, Maryland. AD - 3 Preventive Medicine and Biometrics Department, Uniformed Services University of the Health Sciences , Bethesda, Maryland. LA - eng PT - Journal Article PT - Validation Study PL - United States TA - Vector Borne Zoonotic Dis JT - Vector borne and zoonotic diseases (Larchmont, N.Y.) JID - 100965525 SB - IM MH - Animals MH - Bacterial Load MH - Disease Models, Animal MH - Female MH - Humans MH - Injections, Intraperitoneal MH - Lethal Dose 50 MH - Liver/microbiology MH - Mice MH - Mice, Inbred ICR MH - Orientia tsutsugamushi/genetics/*physiology MH - Scrub Typhus/*microbiology MH - Spleen/microbiology MH - Trombiculidae/*microbiology OTO - NOTNLM OT - Chigger mite OT - Modeling OT - Rickettsia OT - Scrub typhus OT - Tsutsugamushi EDAT- 2015/09/18 06:00 MHDA- 2017/04/18 06:00 CRDT- 2015/09/18 06:00 PHST- 2015/09/18 06:00 [entrez] PHST- 2015/09/18 06:00 [pubmed] PHST- 2017/04/18 06:00 [medline] AID - 10.1089/vbz.2015.1773 [doi] PST - ppublish SO - Vector Borne Zoonotic Dis. 2015 Sep;15(9):539-44. doi: 10.1089/vbz.2015.1773.