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Home , Rickettsia, Rickettsia rickettsii

APPENDIX 2

Rickettsia rickettsii Common Human Exposure Routes:

Disease Agent: • Adult stage of feed on humans, to whom they transmit the agent during a prolonged period of • rickettsii feeding (usually for 1 to 2 weeks). • Rickettsiae are injected from salivary glands of an Disease Agent Characteristics: infected into the human bloodstream only after 6 to 10 hours that the tick is feeding (the so-called grace • Rickettsia are obligate intracellular Gram-negative period). . • A few cases describing infection by aerosols in the • Order: ; Family: laboratory exist. • Size: 0.3 ¥ 1.0 mm intracellular bacteria that stain • Only one case reported by blood transfusion poorly • Nucleic acid: Rickettsial are among the Likelihood of Secondary Transmission: smallest of bacteria at 1000-1600 kb. • Physicochemical properties: Susceptible to 1% •Low sodium hypochlorite, 70% ethanol, glutaraldehyde, formaldehyde and quaternary ammonium disinfec- At-Risk Populations: tants. Sensitive to moist heat (121°C for at least 15 min) and dry heat (160-170°C for at least 1 hour). • Initially restricted to rural residents The organism is stable in tick tissues or blood under • More recently, urban populations exposed to open ambient environmental conditions, surviving up to 1 spaces (parks, open sports areas, fishing ponds) sur- year; sensitive to drying; feces of infected ticks quickly rounded by bushes, domestic animals, and large lose their infectivity on drying. rodents Disease Name: • Animal care workers (dogs, horses, cattle), agri- cultural workers in open fields, and ecological tourists • Rocky Mountain (RMSF) • A threat as a bioterrorist weapon for susceptible • Brazilian spotted fever or São Paulo fever (Brazil), populations Tobia fever (Colombia), Fiebre manchada (Mexico) Vector and Reservoir Involved: Priority Level: • Ticks (primarily ) are the main • Scientific/Epidemiologic evidence regarding blood vectors in the US. safety: Very low • Ticks also are the agent reservoir, given that there are • Public perception and/or regulatory concern regard- tick-to-tick mechanisms of transmission, allowing ing blood safety: Very low infection to all four tick life-cycle stages (, larvae, • Public concern regarding disease agent: Absent/Low, nymphs, and adults). but higher in selected areas • Usually, only 1-5% of ticks are infected by Rickettsia Background: rickettsii, even in high incidence areas. • The main tick species involved in transmission are: • First described in the Snake River Valley (Idaho) in ᭺ (American dog tick)— 1896 eastern and far west US. Dogs and medium-sized • First available test was the Weil-Felix test (agglutina- mammals are preferred hosts. tion of certain vulgaris strains), described in ᭺ (Rocky mountain wood 1921 tick)—western US states and southwestern • Endemic in the US and in several other parts of the Canada. Small rodents and large mammals are Western hemisphere: Canada, Mexico, Costa Rica, preferred hosts. Panama, Colombia, Brazil, and Argentina; in the US, ᭺ (Brown dog tick)— has become more common in the Mexico, US (Arizona) and Europe. This is a newly central southwest and south Atlantic states than in recognized vector in the US. the Rocky Mountains. ᭺ Amblyomma cajennense— • In many parts of the world, it is considered as an • Other reservoirs include wild rodents (e.g., capyba- emergent or re-emergent disease. ras), dogs, horses and donkeys • Classified (Category B) as bioterrorism agent by the • Humans are not considered as reservoirs, only acci- CDC. dental hosts.

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Blood Phase: Primary Disease Symptoms:

• Bacteremia is present for up to 9 days, including • Classical triad includes fever, severe headache, and several days during the incubation period prior to the rash. onset of symptoms. • The main targets for infection are vascular endothe- lial cells, responsible for the typical maculopapular Survival/Persistence in Blood Products: rash. • Rash is fully present up to 5 days after the onset of • Viability in blood at 4°C for at least 9 days is demon- fever, though cases without rash can be observed in strated by transmission of RMSF in the single elderly or African-American patients, and usually reported case. A fraction of this unit kept refrigerated associated with more severe cases, probably because to 21 days did not transmit to three male guinea pigs. of the late diagnosis in the absence of typical rash.

Transmission by Blood Transfusion: Severity of Clinical Disease:

• The only known case was from a donor who donated • High, especially when recognition and appropriate blood 3 days before the clinical onset of RMSF. treatment are delayed ᭺ The donor reported tick removal 18 hours after a • Because of endothelial injury with increased vascular whole blood donation and subsequently died permeability, the resulting outcome is , hypo- after 7 days. Rickettsia rickettsii was identified in volemia, hypotension, and several tissues by IFA. • Main target organs for serious disease are: ᭺ The recipient became mildly ill 6 days after trans- ᭺ Lungs (leading to noncardiogenic pulmonary fusion and fully recovered after appropriate edema, interstitial , pleural infusion, treatment (starting at the fourth day of and adult respiratory distress) illness). ᭺ Heart () • In 1997, an investigation of 377 National Guard blood ᭺ Central nervous system (focal neurologic donors at Fort Chaffee, AR, identified 10 recipients of deficits, transient deafness, meningismus, and units from donors later identified as probable RMSF photophobia) cases. No recipient was infected, although the infec- ᭺ Gastrointestinal tract (nausea, vomiting, tion status of the donors at the time they were bled is abdominal pain, diarrhea, sometimes resem- unknown. bling an acute gastroenteritis or acute surgical abdomen) Cases/Frequency in Population: ᭺ Pancreas ᭺ • Between 1996 and 2000, the number of cases of RMSF Liver (hepatomegaly and jaundice) ᭺ reported in the US was between 400 and 600 cases per Kidneys (prerenal kidney failure and acute year. The number of recognized cases increased to tubular necrosis) ᭺ over 1000 in 2002. is observed in approximately • More than 90% of cases in the US are reported during 50% of cases. ᭺ April through September Activation of coagulant cascade due to endothe- • Despite the name “Rocky Mountain Spotted Fever,” lial damage is also observed in the most severe during recent decades cases have predominated in cases, usually after a long period between onset the southern Atlantic states (especially N. and S. of symptoms and diagnosis. ᭺ Carolina) and lower Midwest (especially Missouri, Damage to the microcirculation may evolve to Arkansas, and Oklahoma). necrosis and gangrene of digits or limbs.

Incubation Period: Mortality:

• Median of 7 days (range: 2-14 days), Partially related • Approximately 65% in untreated patients to the inoculum size • Decreased since the advent of and (especially ), but still Likelihood of Clinical Disease: remains around 5% in the US • Usually occurs after 8-15 days, especially when there • Seroprevalence studies demonstrate that there are is a late diagnosis with delay of appropriate therapy many asymptomatic cases (up to 95% in some areas). • Patients with glucose-6-phosphate dehydrogenase • Mild symptoms are also frequent, but not recognized (G6PD) deficiency are more susceptible to fulminant as RMSF. disease.

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• A recent outbreak in Brazil, with absence or late onset Currently Recommended Donor Deferral Period: of rash in most cases and other classical symptoms • No FDA Guidance or AABB Standard exists. led to late diagnosis and treatment with a mortality • Prudent practice would be to defer the donor until rate up to 42%. signs and symptoms are gone and a course of treat- • Other predictive factors for poor outcome include ment is completed. older age, and failure to recognize tick bites. • In focal outbreaks a different policy may be appropri- Chronic Carriage: ate. At the time of the recognition of the events at Fort Chaffee, AR, in 1997, a recall of components collected •No during the deployment was undertaken, and FDA rec- ommended that exposed individuals not donate Treatment Available/Efficacious: blood for 4 weeks after departure from the area.

• Tetracyclines (e.g., doxycycline) and chloramphenicol Impact on Blood Availability: have reduced the mortality from 65% to 5% in the US. • Agent-specific screening question(s): Not applicable; Agent-Specific Screening Question(s): in response to a bioterrorism threat, impact of a local deferral would be significant. • No specific question is in use. • Laboratory test(s) available: Not applicable • Not indicated because transfusion transmission is limited to a single reported case. Impact on Blood Safety: • No sensitive or specific question is feasible. In • Agent-specific screening question(s): Not applicable; endemic areas, a question on exposure to tick bites unknown impact in response to a bioterrorism threat has been shown to be ineffective in distinguishing • Laboratory test(s): Not applicable Babesia-infected from Babesia-uninfected donors. This question probably also lacks sensitivity and Leukoreduction Efficacy: specificity for Rickettsia rickettsii. • Unknown, but may be useful as leukoreduction has • Under circumstances of a bioterrorism threat, the been shown to have some efficacy in vitro in the case need for, and potential effectiveness of, specific donor of tsutsugamushi. screening questions would need to be addressed. Reduction Efficacy for Plasma Derivatives: Laboratory Test(s) Available: • No data available for this organism, but fractionation • No FDA-licensed blood donor screening test exists. and inactivation techniques in use for plasma deri- • Antibodies are detected only after the second week of vatives should be robust against an intracellular illness. All available tests show a considerable cross- bacteria reactivity among different rickettsiae and different Other Prevention Measures: bacteria (e.g., Proteus species, Brucella species). • Available tests include the following: • Tick avoidance measures (e.g., long pants, long ᭺ Complement fixation sleeves, insect repellant) ᭺ IFA • Riboflavin/light has been effective in vitro in inacti- ᭺ Latex agglutination vating , a related organism. ᭺ EIA Suggested Reading: ᭺ Western blot ᭺ NAT—both for whole blood samples (limit of 1. Arguin PM, Singleton J, Rotz LD, Marston E, Treadwell detection: 50-500 organism/mL) or fresh skin TA, Slater K, Chamberland M, Schwartz A, Tengelsen biopsies (higher sensitivity) L, Olson JG, Childs JE. An investigation into the • Given that antibodies develop only after the onset of possibility of transmission of tick-borne disease, asymptomatic infected donors will not be via blood transfusion. Transfusion-Associated Tick- detected by serology. Borne Illness Task Force. Transfusion 1999;39:828-33. • Should a screening procedure be required, molecular 2. Centers for Disease Control and Prevention. Rocky methods (NAT) will be the strongest candidates, mountain spotted fever. [cited 2009 May]. Available however, sensitivity is still inadequate. from: http://www.cdc.gov/ticks/diseases/rocky_ • Direct identification of the agent includes isolation of mountain_spotted_fever/ R. rickettsii in embryonic hen’s eggs, cell culture, and 3. Dumler JS, Walker DH. Rocky Mountain spotted by the shell vial culture technique. These methods fever—changing ecology and persisting . N take days or weeks to detect organisms. Eng J Med 2005;353:551-3.

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4. Leiby DA, Chung AP, Cable RG, Trouern-Trend J, 7. Rotz LD, Khan AS, Lillibridge SR, Ostroff SM, Hughes McCullough J, Homer MJ, Reynolds LD, Houghton JM. Public health assessment of potential biological RL, Lodes MJ, Persing DH. Relationship between tick terrorism agents. Report summary. Emerg Infect Dis bites and the seroprevalence of Babesia microti and 2002;8:225-30. phagocytophila (previously sp.) 8. Walker DH, Raoult D. Rickettsia rickettsii and other in blood donors. Transfusion 2002;42:1585-91. spotted fever group rickettsiae (Rocky mountain 5. Leiby DA, Gill JE. Transfusion-transmitted tick-borne spotted fever and other spotted fevers). In: Mandell infections: a cornucopia of threats. Transf Med Rev GL, Bennet JE, Dolin R, editors. Principles and prac- 2004;8:293-306. tice of infectious diseases, 5th ed. Philadelphia: 6. McQuiston JH, Childs JE, Chamberland ME, Tabor E Churchill Livingstone; 2000. p. 2035-43. for the Working Group on Transfusion Transmission 9. Wells GM, Woodward TE, Fiset P, Hornick RB. Rocky of Tick-borne Diseases. Transmission of tick-borne Mountain spotted fever caused by blood transfusion. agents of disease by blood transfusion: a review of JAMA 1978;239:2763-5. known and potential risks in the United States. Transfusion 2000;40:274-84.

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