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Home , Rickettsia prowazekii

APPENDIX 2

Rickettsia prowazekii Common Human Exposure Routes:

Disease Agent: • Exposure to the feces of infected body lice. The lice are infected by a human blood meal. The rickettsiae • prowazekii reproduce in the louse gut epithelium. Infection occurs when louse feces are scratched into the skin, Disease Agent Characteristics: inoculated onto mucous membrane or inhaled. • As a bioweapon, the agent can be aerosolized, with • Rickettsiae are obligate intracellular Gram-negative intent of infection through inhalation. . • Sporadic cases occur after exposure to flying squir- • Order: ; Family: rels, most likely as a result of exposure to squirrel flea • Size: 0.3 ¥ 1.0 mm intracellular bacteria that take up feces. The organism has also been identified in ticks Gram stain poorly feeding on livestock in Africa. • Nucleic acid: Rickettsial genomes are among the Likelihood of Secondary Transmission: smallest of bacteria at 1000-1600 kb. The R. prowazekii genome is 1100 kb. • No evidence of direct person-to-person transmission • Physicochemical properties: Susceptible to 1% • Under crowded conditions, where bathing and sodium hypochlorite, 70% ethanol, glutaraldehyde, washing clothes are difficult, and where lice are formaldehyde and quaternary ammonium disinfec- present, can spread explosively. tants. Sensitive to moist heat (121°C for at least • Recent outbreaks have occurred in a number of areas 15 min) and dry heat (160-170°C for at least 1 hour). in the world under conditions of war and population The organism is stable in tick tissues or blood under displacement. ambient environmental conditions, surviving up to 1 year; sensitive to drying (feces of infected ticks At-Risk Populations: quickly lose their infectivity on drying). • Any population in which weather and living condi- Disease Name: tions favor the presence and activity of infected body lice • Typhus, , louse-borne typhus, • A threat as a bioterrorist weapon for susceptible typhus exanthematicus populations • Brill-Zinsser disease is recrudescent human typhus, occurring up to many years after initial infection as a Vector and Reservoir Involved: result of chronic subclinical infection. • The , Pediculus humanus corporis,isthe • A related disease, occurs worldwide vector and chronically infected humans are the most and is milder than epidemic typhus and is caused by important reservoir. R. typhi. It is a zoonosis maintained in rodents and • Lice live in clothing take multiple blood meals per transmitted via fleas. day, acquire infection from their blood meal, excrete R. prowazekii in feces, and abandon febrile hosts for Priority Level: other hosts. Infected body lice eventually succumb to their R. prowazekii infections so do not function as a • Scientific/Epidemiologic evidence regarding blood major reservoir. safety: Theoretical • Other reservoirs for R. prowazekii include Southern • Public perception and/or regulatory concern regard- flying squirrels (Glaucomys volans) in the Americas ing blood safety: Absent and ticks feeding on livestock in Africa. • Public concern regarding disease agent: Absent Blood Phase: Background: • R. prowazeckii infects endothelial cells releasing • Can cause devastating human epidemics by progeny into the blood, from which they can be iso- louse-borne transmission under appropriate lated. Data are lacking regarding bacteremia during conditions. the incubation period of acute infection. • Typhus rickettsiae were studied as agents of biowar- • The blood phase is the source of infection of the lice fare before and during World War II. and subsequent transmission to other humans. • Classified (Category B) as agent by the • Acute disease is symptomatic, but clinically recovered CDC. individuals may have persistent infection for years.

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• R. prowazekii has been isolated from otherwise • Spontaneous recovery is associated with rapid defer- healthy individuals whose infection could only have vescence at 2 weeks, with similar but earlier response been remote. with antibiotic treatment. • Brill-Zinsser disease, recrudescent typhus, is usually a Survival/Persistence in Blood Products: milder disease with similar symptoms. • No data are available. • Naturally acquired disease from the flying squirrel reservoir is milder, and the rash may be more Transmission by Blood Transfusion: maculopapular. • Theoretical; experimentally transmitted to non- Severity of Disease: human primates and other animals

Cases/Frequency in Population: • Acute infection appears to be uniformly symptom- atic, but seroconversion without definite history of • Rare in the US typhus is recognized in endemic areas. • Occasional cases arising from exposure to flying • Chronic infection generally asymptomatic, except for squirrels, usually during the colder months development of Brill–Zinsser syndrome • Outbreaks in Africa and the republics of the former USSR Mortality: • Active foci in South and Central America • Untreated mortality ranges between 10 and 40% and • Potential occurrence in jails, refugee camps, and any- correlates with age. With treatment, case mortality where people are crowded under poor sanitary and ranges from 2 to 4%. hygienic conditions • Mortality from Brill–Zinsser disease and typhus of • Used as a biologic weapon, a focal outbreak with flying squirrel origin is rare. narrow epidemic curve would be expected. Chronic Carriage: Incubation Period: • Up to 40 years or longer • Range of 5-23 days, usually 10-14 days • Onset often sudden, but may vary Treatment Available/Efficacious: • Incubation period for recrudescent Brill-Zinsser disease can be decades after apparent recovery from • Antibiotic treatment with a , such as doxy- acute infection. cycline, is effective at lowering acute mortality from 10-40% to <5%. Chloramphenicol is an alternative Likelihood of Clinical Disease: agent. A 7-10 day course of appropriate antibiotic • Experimental infections in humans suggest clinical therapy is curative. Relapses or chronic disease may illness is nearly universal following infection. occur with shorter courses of treatment. • If bacteremia is present during an asymptomatic pro- Agent-Specific Screening Question(s): drome (before the onset of acute disease), the likeli- hood of clinical disease in a nonimmune recipient • No specific question is in use. seems high. • Not indicated because transfusion transmission has not been demonstrated. Primary Disease Symptoms: • No sensitive or specific question is feasible. • Fever, chills, headache, and severe myalgia are • Under specific circumstances of exposure in an epi- prominent. demic environment, the need for, and potential effec- • Macular rash, with onset at 4-6 days, starting on the tiveness of specific donor screening questions would trunk and spreading centrifugally, but usually sparing need to be addressed the palms and soles. Not recognized in 30-70% of Laboratory Test(s) Available: cases • Conjunctival injection and conjunctivitis common • No FDA-licensed blood donor screening test exists. • Primary symptoms often accompanied by dry mouth, • Serologic tests are used for diagnosis: nausea and vomiting, and constipation ᭺ Antibodies are measurable at 2 weeks. • Patient may appear toxic, with apathy, delirium, ᭺ Cross-reactions on antibody tests for R. cough, and hemorrhagic rash (microvascular injury), prowazekii occur, especially with R. typhi (up to leading to coma and death in the untreated. 50%). • Complications include pneumonitis and myocarditis. ᭺ Cross-absorption studies can differentiate Cough is frequent, and chest x-ray may demonstrate between R. prowazekii and R. typhi antibodies, infiltrates. but are very resource intensive.

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᭺ IFA remains the standard test for diagnosing Pathogen Reduction Efficacy for Plasma Derivatives: infection with R. prowazekii; specific IgM can be • No data available for this organism, but fractionation identified by this method. and inactivation techniques in use for plasma deriva- ᭺ Latex fixation assays are also available. tives should be robust against an intracellular ᭺ EIA tests have been developed and these are sen- bacterium. sitive and specific and allow differentiation of IgG and IgM antibodies. Other Prevention Measures: ᭺ Serologic tests utilizing specific monoclonal antibodies for epitope saturation are under • Measures to maintain hygiene and prevent or control development. louse infestations are critical. • Direct detection: • Riboflavin/light has been effective in inactivating Ori- ᭺ Isolation in cell culture, animals, and embryo- entia tsutsugamushi, a related organism. nated chicken eggs • The agent would likely be susceptible to inactivation ᭺ Immunofluorescence and immunoperoxidase strategies designed to remove WBCs and kill bacteria. staining can demonstrate organisms in tissue. Suggested Reading: ᭺ Shell vial culture techniques have been pro- posed. However, utilization of culture techniques 1. Azad AF, Radulovic S. Pathogenic Rickettsiae as biot- is limited by the requirement for biosafety level 3 errorism agents. Ann NY Acad Sci 2003;990:734-8. conditions. 2. Birg ML, La Scola B, Roux V, Brouqui P, Raoult D. Iso- • NAT for whole blood, blood clots and serum lation of Rickettsia prowazekii from blood by shell vial ᭺ Nested PCR with specific primers performed on cell culture. J Clin Microbiol 1999;37:3722-4. skin biopsies has allowed determination of rick- 3. Fang R, Lin WP, Chao PS, Kuo NT, Chen CM. Haema- ettsial species. tological studies in . Asian J Med 1974; ᭺ NAT is the only potentially rapid and specific 10:198-200. practical approach to early diagnosis. 4. Fournier PE, Raoult D. Suicide PCR on skin biopsy specimens for diagnosis of rickettsioses. J Clin Micro- Currently Recommended Donor Deferral Period: biol 2004;42:3428-34. • No FDA Guidance or AABB Standard exists. 5. Kelly DJ, Richards AL, Temenak J, Strickman D, Dasch • If optimal therapy was administered, prudent prac- GA. The past and present threat of rickettsial diseases tice would be to defer the donor until signs and to military medicine and international public health. symptoms are gone, and the treatment course is com- Clin Infect Dis 2002;34 Suppl 4:S145-69. pleted. However, in light of the chronicity of infection 6. La Scola B, Raoult D. Laboratory diagnosis of (i.e., Brill–Zinsser disease), a permanent deferral rickettsioses: current approaches to diagnosis of old should be considered for infected persons without and new rickettsial diseases. J Clin Microbiol 1997;35: documentation of optimal therapy. 2715-27. 7. Lutwick LI. Brill-Zinsser disease. Lancet 2001;357: Impact on Blood Availability: 1198-200. • Agent-specific screening question(s): Not applicable; 8. Raoult D, Roux V. Rickettsioses as paradigms of new in response to a bioterrorism threat, impact of a local or emerging infectious diseases. Clin Microbiol Rev deferral would be significant. 1997;10:694-719. • Laboratory test(s) available: Not applicable 9. Walker DH. Principles of the malicious use of infec- tious agents to create terror: reasons for concern for Impact on Blood Safety: organisms of the genus Rickettsia. Ann NY Acad Sci • Agent-specific screening question(s): Not applicable; 2003;990:739-42. unknown impact in response to a bioterrorism threat 10. Wells GM, Woodward TE, Fiset P, Hornick RB. Rocky • Laboratory test(s) available: Not applicable Mountain caused by blood transfusion. JAMA 1978;239:2763-5. Leukoreduction Efficacy: 11. Zinsser H. Rats, lice, and history. New York: Black Dog • No data are available. & Leventhal; 1996.

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