title: Inactivation of Orientia tsutsugamushi in red blood cells, plasma, and platelets with riboflavin and light, as demonstrated in an animal model.
abstract: BACKGROUND
  Treatment of blood products with riboflavin and light has been used to reduce the number of certain pathogens. Orientia (formerly Rickettsia) tsutsugamushi, the scrub typhus agent, is an obligate intracellular bacterium that grows free in the cytoplasm of infected cells. This study evaluated the capability of riboflavin and light to inactivate O. tsutsugamushi in red blood cells (RBCs), platelets (PLTs), and plasma, as measured by mouse infectivity.
  
  
  METHODS
  A total of 108 mice, equally divided into groups receiving RBCs, plasma, and PLTs, received untreated products infected with 10(0) to 10(5) organisms. Eighteen mice received products infected with 10(5) organisms and were subsequently treated with riboflavin and light. Mice were monitored daily for up to 17 days for signs and symptoms of infection (e.g., lethargy, labored breathing, rough coat) and killed upon appearance of symptoms or on Day 17 after infection. Real-time polymerase chain reaction (PCR) on blood and Giemsa stains from peritoneal exudates were performed.
  
  
  RESULTS
  A total of 102 of 108 mice receiving the untreated products developed signs and symptoms of infection and had positive PCR and Giemsa stain results. None of the 18 animals receiving riboflavin and light-treated blood products exhibited signs or symptoms of infection, nor was infection observed by PCR testing or Giemsa staining.
  
  
  CONCLUSIONS
  Riboflavin and light are effective in reducing O. tsutsugamushi. Mice injected with blood products inoculated with 10(5) organisms and treated with riboflavin and light did not experience any signs or symptoms of infection, 17 days after inoculation. A 5-log reduction of this organism in blood was achieved as assayed in an animal model.
authors.affiliation: Walter Reed Army Institute of Research, and the Naval Medical Research Center, Silver Spring, MD, USA. frank.rentas@us.army.mil
authors.forename: Francisco
authors.initials: F
authors.lastname: Rentas
authors.forename: Ronald
authors.initials: R
authors.lastname: Harman
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gomez
authors.forename: Jeanne
authors.initials: J
authors.lastname: Salata
authors.forename: Joseph
authors.initials: J
authors.lastname: Childs
authors.forename: Tonya
authors.initials: T
authors.lastname: Silva
authors.forename: Lloyd
authors.initials: L
authors.lastname: Lippert
authors.forename: Joshua
authors.initials: J
authors.lastname: Montgomery
authors.forename: Allen
authors.initials: A
authors.lastname: Richards
authors.forename: Chye
authors.initials: C
authors.lastname: Chan
authors.forename: Ju
authors.initials: J
authors.lastname: Jiang
authors.forename: Heather
authors.initials: H
authors.lastname: Reddy
authors.forename: John
authors.initials: J
authors.lastname: Li
authors.forename: Raymond
authors.initials: R
authors.lastname: Goodrich
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D001681:Biological Assay; D000094902:Blood Banking / Q000379:methods; D001792:Blood Platelets / Q000382:microbiology; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000382:microbiology; D006801:Humans; D008027:Light; D051379:Mice; D012285:Orientia tsutsugamushi / Q000187:drug effects* / Q000254:growth & development / Q000528:radiation effects; D017319:Photosensitizing Agents; D010949:Plasma / Q000382:microbiology; D012256:Riboflavin; D012612:Scrub Typhus / Q000097:blood / Q000517:prevention & control* / Q000635:transmission; D065227:Transfusion Reaction
chemical_list: D017319:Photosensitizing Agents; D012256:Riboflavin