Zoonoses: Emerging Rickettsial Diseases Sharon Altmann, PhD, RBP (ABSA), CBSP (ABSA) The science you expect. The people you know. Learning Objectives Review the major groups of rickettsioses and their clinical manifestations Identify risk factors for rickettsial infection Understand the considerations for rickettsial diagnostics and treatments 2 Rickettsioses and Their Clinical Manifestations 3 What Are Rickettsia? • Members of the Alphaproteobacteria Spotted Fever Group order Rickettsiales •Rickettsia rickettsia (Rocky Mountain Spotted Fever, RMSF) •R. parkeri (R. parkeri rickettsiosis) • Obligate endosymbionts of eukaryotic •R. conorii (Mediterranean spotted fever) cells •R. africae (African tick bite fever) Typhus Group • Gram negative bacilli •R. prowazekii (epidemic typhus) • Primarily transmitted by arthropod •R. typhi (murine typhus) vectors Transitional Group •R. akari (rickettsialpox) • Laboratory acquired infections •R. felis (flea-borne spotted fever) associated with aerosols, accidental Scrub Typhus Group parenteral inoculation •Orientia tsutsugamushi • One report of nosocomial A. •Candidatus Orientia chuto phagocytophilum transmission from •Candidatus Orientia chiloensis China (Zhang et al. JAMA. Anaplasma Group •Anaplasma phagocytophilum (Anaplasmosis, formerly human granulocytic 2008;300(19):2263-2270) ehrlichiosis (HGE)) • Anaplasmosis and ehrlichiosis have Ehrlichia Group been contracted though contaminated •Ehrlichia chaffeensis blood transfusion products or solid •E. ewingii organ transplant •E. muris eauclarensis 4 Transmission Vectors Spotted Fever Group, Anaplasmas, Ehrlichias • Hard body (ixodid) tick bites Typhus Group • R. prowazekii: bites from infected body lice (Pediculous humanus humanus) or ectoparasites from infected flying squirrels; inhalation or accidental mucosal or parenteral inoculation of body louse feces • R. typhi: accidental mucosal or parenteral inoculation of rat flea (Xenopsylla cheopsis) Transitional Group • R. akari: accidental mucosal or parenteral inoculation of mouse mite (Liponyssoides sanguineus) feces • R. felis: bites from cat fleas (Ctenocephalides felis) Scrub Typhus Group • Trombiculid mite larvae (chigger) bites 5 U.S. Geographical Distribution Reported incidence rate per 1,000,000 persons per year, by county, 2000-2013 Spotted fever rickettsiosis, Ehrlichia chafeensis ehrlichiosis Anaplasmosis including Rocky Mountain Spotted Fever Biggs HM et al. MMWR Recomm Rep. 2016;65(No. RR-2):1–44. 6 Vector (And Pathogen) Distribution Is Changing • Gulf Coast tick (Ambylomma maculatum) reported in Illinois for the first time during surveys in 2013 and 2019– 8 of 14 screened specimens were positive for R. parkeri (Phillips et al. J Parasitol. 2020;106(1):9-13) • Asian longhorned tick (Haemaphysalis longicornis) first confirmed in the U.S. in 2017, with archived samples suggesting introduction in 2010 or earlier; confirmed in 14 states as of August 2020. • Shown to carry at least 30 human pathogens naturally, including seven spotted fever group rickettsiae, three species of Ehrlichia, and seven species of Anaplasma (Zhao et al. Lancet Planet Health. 2020;4(8):e320-e329) • Shown experimentally to support R. rickettsia infection (Stanley et al. J Med Entomol. 2020;57(5):1635-1639) • Murine typhus is re-emerging in areas of Texas where it was previously eradicated (Ruiz et al. Emerg Infect Dis. 2020;26(5):1044-1046) Historical and current expanded distribution of A. americanum. • Lone Start tick (A. americanum), a key vector for Ehrlichia From Monzón et al. Genome Biol Evol. 2016:8(5):1351-1360 species, has markedly increased its range in the last 70 years (Monzón et al. Genome Biol Evol. 2016:8(5):1351-1360). 7 Clinical Manifestations- Tick-borne Rickettsioses Estimated Incubation Common initial signs and Disease Cutaneous signs Common laboratory findings Severe disease case-fatality period symptoms rate Rocky Mountain spotted 3–12 days Fever, headache, chills, Maculopapular rash Thrombocytopenia, slightly Meningoencephalitis, acute 5%–10% fever malaise, myalgia, nausea, approximately 2–4 days increased hepatic renal failure, ARDS, cutaneous (treated), vomiting, abdominal pain, after fever onset in most, transaminase levels, normal or necrosis, shock, arrhythmia, 25% photophobia, anorexia might become petechial slightly increased white blood seizure, focal neurologic (untreated) and involve palms and cell count with increased deficits, fulminant vasculitis, soles immature neutrophils, sudden transient hearing loss hyponatremia Rickettsia 2–10 days Fever, myalgia, headache Eschar, sparse Mild thrombocytopenia, mild Vasculitis —* parkeri rickettsiosis maculopapular or leukopenia, increased hepatic vesiculopapular rash that transaminase levels might involve palms and soles RMSF maculopapular rash, late-stage petechial Ehrlichia 5–14 days Fever, headache, malaise, Rash in approximately Leukopenia, thrombocytopenia, Anemia, ARDS, DIC-like 1% (treated), purpuric rash, and late-stage gangrene of the digits. chaffeensis ehrlichiosis myalgia, nausea, diarrhea, 30% of adults and 60% of increased hepatic coagulopathies, central 3% Photos/CDC (human monocytic vomiting children, variable rash transaminase levels, nervous system involvement, (untreated) ehrlichiosis) pattern that might involve hyponatremia, anemia renal failure palms and soles, appears a median of 5 days after illness onset Ehrlichia —† Fever, headache, malaise, Rash rare Leukopenia, thrombocytopenia, —* ewingii ehrlichiosis myalgia increased hepatic transaminase levels Ehrlichia muris-like agent —† Fever, headache, malaise, Rash in approximately Thrombocytopenia, —* ehrlichiosis myalgia 12% lymphopenia, leukopenia, increased hepatic transaminase levels, anemia Human anaplasmosis 5–14 days Fever, headache, malaise, Rash rare, in <10% Thrombocytopenia, leukopenia, ARDS, peripheral <%1 (human granulocytic myalgia, chills mild anemia, increased hepatic neuropathies, DIC-like (treated), 1% anaplasmosis) transaminase levels, increased coagulopathies, hemorrhagic (untreated) numbers of immature manifestations, neutrophils rhabdomyolysis, pancreatitis, R. parkeri rickettsiosis eschars and acute renal failure, secondary vesiculopapular rash. Photos/CDC opportunistic infections *No known deaths. †Not documented. Adapted from Biggs et al. MMWR Recomm Rep. 2016;65(No. RR-2):1-44. 8 Clinical Manifestations- Other Rickettsioses Estimated Incubation Common initial signs Disease Cutaneous signs Common laboratory findings Severe disease case-fatality period and symptoms rate Murine typhus 7-14 days Fever, headache, Rash in 20-80% Thrombocytopenia, Cough, anorexia, nausea, 1-4% arthralgia hyponatremia, increased vomiting, myalgia, encephalitic hepatic transaminase levels, signs, acute kidney injury dissociated cholestasis, haematuria Epidemic typhus 10-14 days Fever, headache, Erythematous rash Thrombocytopenia, increased ARDS, splenomegaly, <5% tachypnoea, chills, myalgia progressing to petechial hepatic transaminase levels, hypotension, vascular (treated), and purpuric lesions increased blood urea collapse, renal insufficiency, 60% encephalitic signs, ecchymosis (untreated) with gangrene, pneumonia, multiple organ failure Diffuse rash in murine typhus patient. Gorchynski et al. West J Emerg Med. 2009;10(3);207 Rickettsialpox 7-10 days Fever, chills, sore throat, Eschar, papulovesicluar Leukopenia with relative —† __* rigor and profuse sweating, rash developing 2-3 days lyphocytosis and mild myalgia, anorexia after symptom onset that proteinuria, thrombocytopenia might involve palms and soles, occasional oropharyngeal enanthem Flea-borne spotted fever —† Fever, fatigue, headache, Eschar in 13%, Increased aspartate and Acute meningoencephalitis __* myalgia maculopapular rash in alanine aminotransferase 75% levels *No known deaths. †Not documented. Blanton et al. Am J Trop Med. 2017;96(1):53-56. Rickettsialpox eschar and papulovesicles. Hun et al. Res Rep Trop Med. 2012;3:47-55. Photos/CDC https://www.ecdc.europa.eu/en/epidemic-louse-borne-typhus/facts https://emedicine.medscape.com/article/227956-overview#a5 9 Risk Factors for Rickettsial Infection 10 Risk Factors for Severe Rickettsiosis Epidemic Risk Factor RMSF Murine typhus Anaplasmosis Ehrlichiosis typhus Age (< 10) XX Age (≥ 40) X Age (≥ 60) XX X X Race (Black) XX X Glucose 6-phosphate dehydrogenase XX deficiency Immunosuppression XX Diabetes XX Hepatic and/or renal dysfunction X Lung infiltrates on admission XX Leukocytosis on admission XX Treatment with sulfa antibiotics XX Delayed treatment XX X X X (onset-to-treatment ≥ 5 days) Blood product transfusion XXX Solid organ transplantation XXX Alcoholism XX 11 Environmental And Behavioral Risk Factors For Exposure • Occupational or recreational exposure to brushy or wooded areas with tall Examples of at-risk populations: grasses or shrubs •Hunters •Surveyors • Lack of use of appropriate tick • Outdoor enthusiasts • Pet / livestock owners repellents • Utility workers • Agricultural workers • Lack of appropriate clothing worn in high-risk areas • Veterinarians / animal • Scientists / students control involved in fieldwork • Exposure to animals and birds (wild, livestock, and/or peridomestic) • International travelers • Unhomed individuals • Those working or living in • Those working with or near • International travel refugee / detention camps unhomed populations • Exposure to individuals living with • Forestry / park workers • Military personnel poor sanitation and hygiene availability 12 Considerations for Diagnostics and Treatment 13