Rickettsial Diseases Notes

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Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Rickettsial Diseases essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Rickettsial Diseases by visiting the associated Learn Page.
NOTES NOTES RICKETTSIAL DISEASES GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Vector-borne obligate intracellular bacteria; poor Gram staining, rod-shaped structure ▪ Common tropism for endothelial cells → variable amount of hemorrhage, edema, organ dysfunction SIGNS & SYMPTOMS ▪ Disease-specific; fairly consistent integument manifestations (e.g. rash) DIAGNOSIS LAB RESULTS ▪ Isolation of Rickettsiae ▫ Inoculation of animal/via cell culture ▪ Serology ▫ Enzyme-linked immunosorbent assay (ELISA), western blot, microimmunofluorescent antibody test (detection of bacterial-specific antigens) 514 OSMOSIS.ORG ▪ Immunologic detection in tissue ▫ Isolation in epithelial tissue (from integument involvement) ▫ Requires sophisticated laboratory capability (not common in endemic areas of disease) ▪ Polymerase chain reaction (PCR) ▫ Detection of rickettsial DNA OTHER DIAGNOSTICS ▪ Clinical presentation (disease-specific) TREATMENT MEDICATIONS ▪ Prompt antimicrobial therapy ▫ Doxycycline (preferred)
Chapter 95 Rickettsial Diseases ANAPLASMA osms.it/anaplasma PATHOLOGY & CAUSES ▪ Tick-borne, obligate intracellular bacteria, endemic to wooded areas in North America → self-resolving disease, AKA human granulocytic anaplasmosis (HGA) Vector ▪ Anaplasma phagocytophilum: Ixodes tick ▫ Ixodes scapularis: also transmits Borrelia burgdorferi, Babesia spp. in eastern United States (US) ▫ Ixodes pacificus: main vector in western US ▫ Ixodes ricinus: implicated in European disease Life cycle and transmission ▪ Reservoir hosts: deer, white-footed mice (source of disease, not affected by pathogen) ▪ Vector: Ixodes tick (connects organism from reservoir to target) ▪ Human transmission Pathogenesis ▪ Tick bite → blood circulation → leukocyte infection, membrane attachment → phagocytosis → replication (in early endosome of leukocyte) → dysfunctional vacuolization, immature lysosomal micelles → microcolony (AKA morulae) development → release into extracellular space after cell lysis/exocytosis ▫ P-selectin glycoprotein (identified binding domain for A. phagocytophilum) ▫ Ligand: P-selectin glycoprotein ligand-1 (PSGL-1) required on granulocytes for internalization Disease: HGA ▪ Direct leukocyte cell death ▪ Inflammatory response → perivascular inflammatory infiltrates in multiple organ systems (without organ failure/endothelial damage) RISK FACTORS ▪ Residence in/travel to wooded areas in North America ▫ Especially during peak tick activity (e.g. spring, summer) ▪ Direct contact with slaughtered deer ▪ Occupational exposure (e.g. military) COMPLICATIONS ▪ Co-infection with Borrelia burgdorferi, Babesia spp. ▪ Respiratory insufficiency, renal failure, septic shock ▪ Neurological ▫ Demyelinating polyneuropathy, brachial plexopathy ▪ Serious, fatal opportunistic infections ▫ Herpes simplex esophagitis, invasive aspergillosis, SIGNS & SYMPTOMS ▪ Onset 1–2 weeks after identified tick bite ▪ Fever, malaise, headache ▪ Rash ▫ Typically trunk (sparing hands, feet), maculopapular (more evident in children) ▪ Gastrointestinal (GI) symptoms infrequent ▪ Neurological (rare) ▫ Mental status change, meningismus, clonus DIAGNOSIS LAB RESULTS ▪ Leukopenia ▫ Specific to disease (neutropenia) ▪ ↑ hepatic enzymes, lactate dehydrogenase OSMOSIS.ORG 515
▪ Serology: indirect IFA ▫ Detection of IgG/IgM antibodies of Anaplasma species ▫ If negative on acute serum testing, repeat with convalescent serum (confirms diagnosis if ↑ fourfold in IgG antibody titer) ▪ Whole blood PCR ▫ Detects epank1 primers on genogroup A. phagocytophilum ▪ Wright stain: morulae of Anaplasma in leukocyte ▫ A. phagocytophila: peripheral blood neutrophils; 25–75% (highest among morulae-producing bacteria) OTHER DIAGNOSTICS ▪ History ▫ Tick bite in endemic area TREATMENT MEDICATIONS ▪ Prompt antibacterial management ▫ Doxycycline (if pregnant, rifampin); chloramphenicol OTHER INTERVENTIONS ▪ Prevention ▫ Avoid tick habitats ▫ Careful inspection after outside activity in wooded areas (esp. in spring, summer); rapid discovery, tick removal < 24–48 hours post bite → effective prophylaxis ▫ Skin application of insect repellants ▫ Proper clothing for outside work/play (light-colored, long pants tucked into socks, long-sleeved shirts) 516 OSMOSIS.ORG Figure 95.1 Mites of the genus Ixodes act as vectors for many rickettsial diseases.
Chapter 95 Rickettsial Diseases COXIELLA BURNETII (Q FEVER) osms.it/coxiella-burnetii PATHOLOGY & CAUSES ▪ Coxiella burnetii: primarily zoonotic pathogen → febrile illness (after contact with animal amniotic fluid/placental contents) Taxonomy ▪ Order: Legionellales ▪ Family: Coxiellaceae Morphology ▪ Short, pleomorphic rod ▫ Strict intracellular bacterium Life cycle ▪ Source of human infections ▫ Farm animals (e.g. cattle, goats, sheep) ▫ Wild animals (e.g. birds, rabbits, reptiles) ▫ Arthropods (e.g. ticks) ▪ Main reservoir ▫ Ticks Transmission ▪ Inhalation of spores/bacteria ▫ Animal feces, milk, products of conception ▪ Ingestion of contaminated milk ▪ Percutaneous ▫ Crushing of ticks near skin breaks ▪ Vertical spread (transplacental) Pathogenesis ▪ Host cell ▫ Macrophage ▪ Antigenic variation (AKA phase variation) important in virulence ▫ Lipopolysaccharide capsule modifications underly antigenic variation RISK FACTORS ▪ Occupation involving animal contact (e.g. veterinarian, farmer) ▪ ↑ age ▪ Unpasteurized milk consumption COMPLICATIONS ▪ Q fever pneumonia, chronic hepatitis, osteomyelitis ▪ Infective endocarditis ▫ Pre-existing heart/valve disease predisposes to endocarditis development ▫ May have secondary, septic embolic manifestation SIGNS & SYMPTOMS ▪ Q fever (sudden onset) ▫ Fever, headache (often frontal), general malaise, cough, anorexia, myalgia ▪ Pneumonia ▫ Cough, pleural effusion ▪ Hepatitis ▫ Hepatomegaly DIAGNOSIS LAB RESULTS ▪ ↑ serum hepatic enzymes, leukopenia/ leukocytosis, thrombocytopenia ▪ Immunofluorescent antibody assays: detect IgM/IgG antibodies; differentiate between acute, chronic infection ▫ IgM: detectable 4 days after symptom onset ▫ IgG: detectable 9–14 days after symptom onset ▫ Concentration of serum samples can assist in diagnosis (esp. if vague clinical presentation) OSMOSIS.ORG 517
▪ PCR ▫ Blood/serum detection possible before IgM serology peak ▪ Immunohistochemistry ▪ Culture OTHER DIAGNOSTICS ▪ History ▫ Animal contact, occupation ▫ Trimethoprim-sulfamethoxazole: pregnant individuals; treat even if asymptomatic ▪ Chronic infection: prolonged therapy ▫ 18 months doxycycline, hydroxychloroquine (monitor serologic response across therapeutic intervention; biannual ophthalmic examinations required) OTHER INTERVENTIONS TREATMENT MEDICATIONS ▪ Prompt antimicrobial treatment ▫ Doxycycline: effectiveness of antibacterial agent, severity of complications warrants use despite side effects; shorter therapy for children (14 day course) ▪ Management ▫ Individuals with pre-existing valvulopathy/cardiomyopathy; echocardiogram ▪ Prevention ▫ Whole cell vaccine; recommended for individuals working with farm animals (e.g. farmers, slaughterhouse workers) EHRLICHIA osms.it/ehrlichia PATHOLOGY & CAUSES ▪ Tick-borne, obligate intracellular bacteria with leukocytic tropism, associated with febrile disease with rare, serious neurologic complication ▫ AKA human monocytic ehrlichiosis (HME) ▪ Characteristics ▫ Small (0.5–1.5 micrometer) gramnegative cocci, (1.8 megabases) genome TYPES ▪ Ehrlichia ewingii ▫ Southeastern, central United States ▪ Ehrlichia chaffeensis ▫ Northeastern, midwestern United States ▪ Ehrlichia sennetsu ▫ Western Japan 518 OSMOSIS.ORG Vector ▪ Amblyomma americanum (AKA lone star tick) ▫ Ehrlichia ewingii, Ehrlichia chaffeensis Life cycle ▪ Tick bite → blood circulation → leukocyte infection, membrane attachment → phagocytosis → replication (in early endosome of leukocyte) → dysfunctional vacuolization, immature lysosomal micelles → microcolony (AKA morulae) development → release into extracellular space after cell lysis/exocytosis Pathogenesis ▪ Direct leukocyte cell death ▪ Inflammatory response → perivascular inflammatory infiltrates in multiple organ system without organ failure/endothelial damage Disease: Sennetsu fever
Chapter 95 Rickettsial Diseases RISK FACTORS ▪ Residence in/travel to western Japan ▪ Occupational exposure (e.g. military) COMPLICATIONS ▪ Co-infection with Babesia spp./B. burgdorferi ▪ Encephalitis, seizure ▫ Associated most with E. chaffeensis ▫ May result in persistent neurologic deficit (rare; seen especially in children) ▪ Heart failure, respiratory insufficiency, renal failure, shock SIGNS & SYMPTOMS ▪ Sennetsu fever ▫ Abrupt-onset fever, chills, headache, malaise, sore throat, myalgias, arthralgias ▪ Atypical rash ▫ Maculopapular with occasional petechiae; located on trunk (sparing hands, feet) ▪ Generalized lymphadenopathy ▫ Most associated with E. sennetsu; includes hepatosplenomegaly ▪ GI ▫ Associated with E. chaffeensis ▫ Anorexia, diarrhea, nausea, vomiting ▪ Leukopenia, thrombocytopenia, anemia, hyponatremia ▪ Hepatic transaminitis: most common in E. chaffeensis infection ▪ Cerebrospinal fluid (CSF) analysis: pleocytosis (mononuclear cells with morulae), ↑ protein OTHER DIAGNOSTICS ▪ History ▫ Tick bite in endemic area TREATMENT MEDICATIONS ▪ Prompt antibacterial management: poxycycline, chloramphenicol OTHER INTERVENTIONS Prevention ▪ Avoidance of tick habitats ▪ Careful inspection after outside activity (esp. in spring, summer) ▫ Rapid discovery, removal < 24–48 hours after bite → effective prophylaxis ▪ Proper skin application of insect repellants DIAGNOSIS LAB RESULTS ▪ Serology: indirect IFA ▫ Detection of IgG/IgM antibodies (Ehrlichia species) ▫ If negative on acute serum testing, repeat with convalescent serum (confirms diagnosis if fourfold increase in IgG antibody titer) ▪ Whole blood PCR: detects 16S rRNA gene ▪ Wright stain: morulae (Ehrlichia) in leukocyte ▫ E. ewingii: in peripheral blood granulocyte ▫ E. chaffeensis: in peripheral blood monocyte OSMOSIS.ORG 519
RICKETTSIA RICKETTSII (ROCKY MOUNTAIN SPOTTED FEVER) osms.it/rickettsia-rickettsii PATHOLOGY & CAUSES ▪ Tick-borne, obligate intracellular, Gramnegative bacteria endemic to parts of North America → potentially lethal febrile disease ▪ Characteristics ▫ Weakly gram-negative, nonmotile coccobacillus; 0.7–2.0 micrometers: cannot be visualized by traditional staining methods/direct fluorescent antibody techniques ▫ Bacterial contents: ribosome; single, circular chromosome; microcapsule surrounding cell wall (may be important in pathogenicity) Vectors ▪ Dermacentor variabilis (American dog tick) ▫ Eastern, South-central US ▪ Dermacentor andersoni (Rocky Mountain wood tick) ▫ West of Mississippi River ▪ Rhipicephalus sanguineus (common brown dog tick) ▫ Southwestern US ▪ Virulence of strain depends on tick’s feeding status ▫ ↑ feeds → ↑ incubation at high temperatures → ↑ extracellular slime → ↑ virulence (AKA reactivation phenomenon) Life cycle ▪ Tick bite (requires 6–10 hours of feeding) → proliferates by binary fission ▪ Grows in nucleus, cytoplasm of host cells Pathogenesis ▪ Tropism for endothelial cells, downstream systemic effects as sequelae ▪ Endothelial cell entry: rickettsial outer membrane proteins (rOmps) interact with 520 OSMOSIS.ORG ▪ ▪ ▪ ▪ ▪ ▪ lipopolysaccharides, surface-exposed proteins (SEPs) for entry ▫ rOmps bind Ku70 (membrane protein) → activate Ku70 → recruit ubiquitin ligase → ubiquitination of Ku70 → act upon cAMP receptors protein kinase A, Epac (exchange protein) → rearrangement of host cell actin filaments → rickettsial endocytosis Bacterial spread: R. rickettsii express phospholipase D, tlyC → lyse phagosomal membrane → entry into cytosol → polymerization of host cell monomeric actin filaments → invagination of host cell membranes → passage into neighboring cells Further bacterial spread ▫ Filopodia (from host cell membranes) assist in intercellular movement ▫ Bloodstream, lymphatic spread assist in more distant infection sites Small blood vessel injury (not entirely elucidated) ▫ Associated with phospholipase A activity, protease activity, free radicalinduced lipid peroxidation ▫ Cell necrosis (from other infected cells) → CD8+ T-cell response → endothelial cell injury → immune, phagocytic cellular response → lymphohistiocytic vasculitis Sequelae of small vessel injury: ↑ fluid in interstitial space → exposes brain, lung parenchyma to devastating pathophysiologic consequences Ability to spread cell-to-cell without causing obvious damage ▫ Rarely accumulate in large numbers inside cells Speeds of 4.8m/min ▫ Achieves speed via rapid recruitment, polymerization of host cell actin filaments
Chapter 95 Rickettsial Diseases RISK FACTORS ▪ Residence in/travel to endemic areas (esp. in spring, summer) ▪ ↑ age (peak: 40–64) ▪ Individuals who are biologically male ▪ Glucose-6-phosphate dehydrogenase (G6PD) deficiency COMPLICATIONS ▪ Skin necrosis at sites of terminal arterial supply (e.g. fingers, toes, nose, ears, genitals) ▪ Interstitial pneumonitis, myocarditis, encephalitis SIGNS & SYMPTOMS ▪ Early infection ▫ Fever, headache, malaise, myalgias, arthralgias, nausea (without vomiting), edema (esp. in children) ▪ Rash development (hallmark of infection) ▫ Blanching, erythematous rash ▫ Macules (1–4mm) → petechiae ▫ Ankles, wrist → truncal spread → palms, soles rash (characteristic of late-stage disease) ▪ Confusion, conjunctival erythema, seizures, focal neurologic deficit ▪ Fundoscopic examination ▫ Retinal vein engorgement, arterial occlusion, flame hemorrhage DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray ▪ Interstitial infiltrates Echocardiogram ▪ Minimal myocardial dysfunction with normal capillary wedge pressure ▪ Consistent with noncardiogenic nature of pulmonary edema (commonly present) ▪ Advanced disease ▫ Hyponatremia (sign of central nervous system involvement); transaminitis; ↑ bilirubin; azotemia (due to hypovolemia); ↑ prothrombin, partial thromboplastin times ▪ CSF ▫ Pleocytosis (monocytic, polymorphonuclear predominance possible), ↑ protein OTHER DIAGNOSTICS ▪ History ▫ Residence in/travel to endemic area; recollection of tick bite (only 30% of individuals recollect bite) TREATMENT MEDICATIONS ▪ Early treatment: prompt, empiric antimicrobial therapy with doxycycline (first-line), chloramphenicol (second-line) ▫ Even if mild symptoms (due to potential lethality of bacterial strain); recommended for pregnant individuals, children ▫ Goal: initiate < five days after symptom onset ▫ Duration: until three days after resolution of febrile illness; minimum seven days ▪ Antiemetics, antimotility agents (individuals intolerant of doxycycline) OTHER INTERVENTIONS ▪ Hemodynamic monitoring in ICU setting; respiratory support; renal replacement therapy, blood transfusions ▪ Prevention ▫ Vigilant detection, early removal of ticks, proper clothing LAB RESULTS ▪ Thrombocytopenia (worsens with progression of disease) OSMOSIS.ORG 521
RICKETTSIA TYPHI (MURINE TYPHUS) osms.it/rickettsia-typhi PATHOLOGY & CAUSES ▪ Rat-borne zoonotic disease transmitted to humans via flea; flu-like illness; minority of individuals require ICU-level care ▫ AKA murine, endemic, flea-borne typhus Transmission ▪ Zoonotic reservoir: Rattus typhi ▪ Vector: Xenopsylla cheopis (AKA Oriental rat flea) Life cycle ▪ Flea feeds on infected rodent → lifetime infection → fecal bacterial shedding → human contact with flea feces through breaks in skin barrier/inhalation → human disease ▫ Further human infection occurs via body lice passed human-to-human ▪ Replicates in high titers in yolk sacs of embryonated chicken eggs Pathogenesis (not well elucidated) ▪ Perivascular infiltration with lymphocytes, macrophages, plasma, mast cells (on biopsy) ▪ Vasculitis (rare) ▫ Accompanied by mural/intimal thrombi; heart, lungs, kidneys, central nervous system (CNS) ▪ Disease ▫ Mild, flu-like illness RISK FACTORS ▪ Warmer climates, seaports, major commercial areas COMPLICATIONS ▪ Shock, sepsis, myocarditis, renal/respiratory failure, severe hemolysis (associated with 522 OSMOSIS.ORG G6PD deficiency) ▪ Neurological ▫ Meningitis, meningoencephalitis, facial paralysis, hearing loss, ocular abnormalities SIGNS & SYMPTOMS ▪ Fever (8–16 days after exposure), chills, headache (commonly frontal), myalgia, rash (concurrent with fever; maculopapular, less commonly petechial; spares face, palms, soles), nausea, vomiting DIAGNOSIS LAB RESULTS ▪ ↑ erythrocyte sedimentation rate (ESR) ▪ Left shifted leukocyte count (absolute neutropenia/lymphopenia possible) ▪ Abnormal hepatic enzymes ▪ Electrolytes ▫ Hyponatremia, hypokalemia, ↑ serum creatinine TREATMENT MEDICATIONS ▪ Prompt doxycycline antimicrobial therapy ▪ Ciprofloxacin (viable alternative) OTHER INTERVENTIONS Prevention ▪ Rodent, flea eradication ▪ Rat-proofing homes, food service areas ▪ Protective clothing for occupational exposure to rats

Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Rickettsial Diseases essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Rickettsial Diseases by visiting the associated Learn Page.