APPENDIX 2 Orientia tsutsugamushi • “Tsutsugamushi” = “dangerous mite” in Japanese • Infection provides prolonged immunity to the spe- Disease Agent: cific strain of O. tsutsugamushi causing infection. Recurrent disease only occurs with other strains. • Orientia tsutsugamushi (Rickettsia tsutsugamushi until 1995) Common Human Exposure Routes: • The bite of larval trombiculid mites (chiggers) Disease Agent Characteristics: • Chiggers attach, take a blood meal over several hours, • Rickettsiae are obligate intracellular, Gram-negative and then detach, often leaving a pruritic rash. bacteria. The organism exhibits extensive genomic • Chiggers acquire infection transovarially or from and antigenic heterogeneity that may lead to the defi- rodent reservoirs. nition of multiple species in the genus. Likelihood of Secondary Transmission: • Order: Rickettsiales; Family: Rickettsiaceae • Size: 0.5-0.8 ¥ 1.2-3 mm intracellular bacteria • Vertical transmission during pregnancy has been • Nucleic acid: Rickettsial genomes are among the alleged based on clinical illness and serology in the smallest of bacteria. The Orientia genome is approxi- mother and the presence of IgM antibody in the mately 2000 kb. infant. • Physicochemical properties: Information specific to At-Risk Populations: Orientia was not found. The rickettsiae are suscep- tible to 1% sodium hypochlorite, 70% ethanol, • Residents of endemic areas, military personnel, and glutaraldehyde, formaldehyde, and quaternary tourists ammonium disinfectants. Sensitive to moist heat Vector and Reservoir Involved: (121°C for at least 15 min) and dry heat (160-170°C for at least 1 h). • O. tsutsugamushi is maintained in nature by highly efficient transovarial transmission in larval trombicu- Disease Name: lid mites (chiggers). • Scrub typhus, tsutsugamushi fever, mite-borne • Rodent reservoirs can also harbor the bacterium. typhus fever Blood Phase: Priority Level: • Bacteremia occurs during the symptomatic phase and for 1-3 days before symptom onset. • Scientific/Epidemiologic evidence regarding blood • Although chronic infection of lymph nodes occurs, safety: Theoretical there is no evidence of bacteremia during this phase. • Public perception and/or regulatory concern regard- ing blood safety: Low, but absent in the US Survival/Persistence in Blood Products: • Public concern regarding disease agent: Absent • Persistence and survival of O. tsutsugamushi in whole Background: blood is well established. • Survival in RBCs for 10, but not 30 days, and survival • Endemic across extensive parts of Asia, South Asia, for at least 45 days in frozen and deglycerolized RBCs Australia, and the Pacific demonstrated in spiking studies. • Clinically described in the Far East more than 1500 Transmission by Blood Transfusion: years ago • Scrub typhus may be the most prevalent human rick- • Theoretical; a case report alleges transfusion- ettsial infection, with over 1 billion people living in transmission, but proof is lacking. endemic areas and as many as 1 million infections Cases/Frequency in Population: annually. • Localized, rural foci of risk are recognized where the • Estimated 1 million cases per year in endemic areas vector (larval stages of trombiculid mites, referred to • Rare introduction into the US as chiggers) occurs and where natural environments Incubation Period: are disturbed, as well as in rice paddies, atolls, and plantations. • Usually 10-12 days; abrupt onset of illness 6-21 days • US experience related to exposure of military person- after infected larval mite bite nel during World War II, the Korean conflict, and the Likelihood of Clinical Disease: Vietnam war • Disease prevalence is stable in endemic areas • Assumed to be very high 178S TRANSFUSION Volume 49, August 2009 Supplement APPENDIX 2 Primary Disease Symptoms: Laboratory Tests Available: • Abrupt onset of febrile illness • No FDA-licensed blood donor screening test exists. • Headache, myalgia, sweats, conjunctival injection, • Serologic tests are the mainstay of laboratory diagno- lymphadenopathy (may be tender), and mental sis, but antibody appears after clinical illness and changes (cognitive dysfunction to delirium and would not be useful for donor screening. coma) ᭺ Specific IgM identified by IFA is the test of choice. • Eschar develops at the site of mite bite and lymphad- ᭺ An immunoperoxidase test is available as an enopathy in nodes draining area may be prominent. alternative. The recognition of cutaneous findings varies greatly. ᭺ EIA tests have been developed, and these have • Late in first week, a transient (few days) pale macular been found to be closely equivalent to IFA for to maculopapular rash may be observed, most promi- early detection of antibody. nent on the trunk and spreading to the extremities. ᭺ The complement fixation (CF) test for O. tsut- • Hepatomegaly and splenomegaly may occur. sugamushi antibodies is strain specific, so all • Cough and x-ray evidence of pneumonia are suspect strains must be included in the reagent. common. ᭺ Dot blot assays for antibody are available but are • Leukopenia/lymphopenia and thrombocytopenia also strain specific. are common. • Direct detection: • In severe disease, multiple organ involvement and ᭺ Isolation in cell culture, animals, and embryo- disseminated intravascular coagulation with hemor- nated chicken eggs rhage may occur. ᭺ Immunofluorescence and immunoperoxidase • Febrile illness lasts for approximately 2 weeks without staining can demonstrate organisms in tissue. specific treatment. Prompt clinical response to ᭺ Monoclonal antibodies are now available for tetracyclines strain identification. • Relapse is common but less severe. ᭺ PCR has been used to detect O. tsutsugamushi in skin biopsies, peripheral mononuclear cells, Severity of Clinical Disease: whole blood, blood clots, and serum. • The severity is very dependent on the particular strain • Nested PCR with specific primers allows of O. tsutsugamushi, area of acquisition, previous determination of particular strains. exposure, and host characteristics. • PCR is the only potentially rapid and specific practical approach to early diagnosis. Mortality: Currently Recommended Donor Deferral Period: • Case-fatality rates vary from less than 1% with appro- priate treatment to 60%. • No FDA Guidance or AABB Standard exists, but malaria deferral will exclude many at-risk donors. Chronic Carriage: • Prudent practice would be to defer donor until signs and symptoms are gone and a course of treatment is • Viable organisms can be isolated from lymph nodes completed. for up to 1-2 years after untreated infection. • There is no evidence of long-term persistence after Impact on Blood Availability: adequate therapy. Treatment Available/Efficacious: • Agent-specific screening question(s): Not applicable • Laboratory test(s) available: Not applicable • Prompt clinical response to tetracyclines (e.g., doxy- cycline) or alternatively chloramphenicol, even with Impact on Blood Safety: short courses • Clinical evidence of antibiotic resistance is being • Agent-specific screening question(s): Not applicable described in South Asia. • Laboratory test(s) available: Not applicable Agent-Specific Screening Question(s): Leukoreduction Efficacy: • No specific question is in use. • A mouse model suggests current filters can remove as • Not indicated because transfusion transmission has many as 105 O. tsutsugamushi organisms from packed not been definitively demonstrated. red blood cells spiked with infected mononuclear • No sensitive or specific question is feasible. cells. Volume 49, August 2009 Supplement TRANSFUSION 179S APPENDIX 2 Pathogen Reduction Efficacy for Plasma Derivatives: to military medicine and international public health. Clin Infect Dis 2002;34 Suppl 4:S145-69. • No specific data are available for this organism, but 6. Khaisuwan S, Kantipong P,Watt G, Burnouf T. Trans- fractionation and inactivation techniques in use for mission of scrub typhus by blood transfusion? Trans- plasma derivatives should be robust against intracel- fusion 2001;41:1454-5. lular bacteria. 7. La Scola B, Raoult D. Laboratory diagnosis of Other Prevention Measures: rickettsioses: current approaches to diagnosis of old and new rickettsial diseases. J Clin Microbiol 1997;35: • Tick avoidance measures (e.g., long pants, long 2715-27. sleeves, insect repellant) 8. Mettille FC, Salata KF,Belanger KJ, Casleton BG, Kelly • Riboflavin and light have been demonstrated to DJ. Reducing the risk of transfusion-transmitted rick- reduce infectivity by a factor of 105 in RBCs, platelets, ettsial disease by WBC filtration, using Orientia tsut- and plasma in a mouse model. sugamushi in a model system. Transfusion 2000;40: • Amotosalen and UV light (INTERCEPT) used to treat 290-6. platelet concentrates reduced infectivity in mice by a 9. Raoult D, RouxV.Rickettsioses as paradigms of new or similar amount. emerging infectious diseases. Clin Microbiol Rev Suggested Reading: 1997;10:694-719. 10. Rentas F, Harman R, Gomez C, Salata J, Childs J, Silva 1. Belanger KJ, Kelly DJ, Mettille FC, Hanson CV, Lippert T, Lippert L, Montgomery J, Richards A, Chan C, Jiang LE. Psoralen photochemical inactivation of Orientia J, Reddy H, Li J, Goodrich R. Inactivation of Orientia tsutsugamushi in platelet concentrates. Transfusion tsutsugamushi in red blood cells, plasma, and plate- 2000; 40:1503-7. lets with riboflavin and light, as demonstrated in an 2. Casleton BG, Salata K, Dasch GA, Strickman D, Kelly animal model. Transfusion 2007;47:240-7. DJ. Recovery and viability of Orientia tsutsugamushi