Lecture 14: Rickettsial Infections

Rickettsial Infections

Obligate intracellular bacterial- Survive for only short time outside

Phagocytosed by host cells

Escape phagosome early in infection and grows in host cell cytoplasm

gram-negative, alpha-proteobacteria

Orientia → scrub typhus

Rickettsia

Gram-negative, pleomorphic coccobacilli

Very thin peptidoglycan layer → do not Gram stain well

Arthropod vectors (Ectoparasites)

Rickettsioses Clinical Manifestations

Rickettsial triad: fever, headache, rash

Rickettsiae multiply in endothelial cells of small blood vessels of the skin and other organs

Increased microvascular permeability

Consequences: edema, hypovolemia, hypoalbuminemia, thrombo-cytopenia, hypotension, reduced perfusion, multi-organ dysfunction

Resulting damage leads to necrotizing vasculitis

Consequences: rash; encephalitis; nephritis; myocarditis; lesions in lungs, liver, GI walls

Rickettsioses Diagnosis

Immunofluorescence Assay (IFA): ≥7–10 days after symptom onset

Detects IgG/IgM antibodies

≥4-fold IgG rise = diagnostic

Cross-reactivity between species

PCR (blood or tissue): ≤7 days of illness

Detects rickettsial DNA BEFORE seroconversion

Skin or Eschar Biopsy: PCR or immunohistochemistry (IHC)

Useful when serology or blood PCR are negative

Rickettsioses Treatment

Doxycycline (DOC)

Chloramphenicol only if true DOC allergy

Orientia tsutsugamushi

Scrub typhus

Orientia lack LPS → less immunogenic

Arthropod vector: Chigger mite- larvae are parasitic

Reservoir: Chigger mite, rodents, and birds

Asia-Pacific

Increased incidence in the Middle East and Americas

Eschar at bite site

High mortality

Rickettsia rickettsii

Rocky Mountain Spotted Fever

Arthropod vector: Hard ticks – Am. & Brown dog tick, and Rocky Mtn. Wood tick

Reservoir: Wild rodents and small mammals; Ticks – transovarial transmission

Western Hemisphere

2–4 days after onset of fever, rash develops (macular → petechial)

Begins on wrists, forearms & ankles then spreads to trunk

1/4 of untreated cases will be fatal by the 7th–9th day of illness

Rickettsia prowazekii

Epidemic typhus

Arthropod vector: Human body louse (and squirrel flea)

Transmitted via louse bite and feces scratched into skin

Reservoir: Humans and flying squirrels

Worldwide

Outbreaks associated with overcrowding and poor hygiene

Rash appears several days after fever

Begins on trunk & spreads to extremities

High mortality rate

Brill-Zinnser disease and Sylvatic typhus

Rickettsia prowazekii

Brill-Zinnser disease (recrudescent typhus):

Recurrent form, can develop decades after initial infection

History of primary epidemic typhus

Symptoms less severe; rarely fatal

Adipocytes the reservoir

Sylvatic epidemic typhus (aka sylvatic typhus):

Symptoms less severe; no reported fatalities

Reservoir = Flying squirrel

Vector = Squirrel flea

Rickettsia typhi

Murine (endemic) typhus

Arthropod vector: Fleas

Transmitted via flea feces scratched into skin at bite site or other wounds

Reservoir: Rats, mice, cats, opossums

Worldwide- Urban & coastal port regions

USA: primarily in TX, CA, and Hawaii

Symptoms less severe than epidemic typhus

Low mortality

Rickettsia akari

Rickettsialpox

Arthropod vector: House mouse mite

Reservoir: Rodents (house mouse)

Worldwide

USA in urban areas

Biphasic rickettsioses:

Phase 1: Red papule at bite site that proceeds to eschar

Phase 2: 3–7 day after, abrupt onset of fever & other non-specific symptoms

Rash: 1–9 days after fever; “pox-like” on face, trunk, & extremities

20-25% patients have oral enanthem

Anaplasmataceae

Anaplasma phagocytophilum

Ehrlichia chaffeensis

Gram-negative, pleomorphic coccobacilli

Lacks peptidoglycan layer → do not Gram stain well

Lack LPS → less immunogenic

Obligate intracellular lifestyle

Phagocytosed by host cells

Modifies phagosome and grows in a membrane-bound vacuole (morulae)

Biphasic developmental cycle: Infectious + Non-infectious form

Arthropod vectors (Ectoparasites)

Fever, chills, headache, myalgia

Rash more common in ehrlichiosis, especially in children

Replicate in Granulocytes and monocytes (WBC)

Leukopenia, thrombocytopenia, and elevated liver enzymes

Multi-organ failure, disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), meningoencephalitis and internal bleeding

Anaplasmataceae Diagnosis

PCR (whole blood): ≤7 days of illness

Detects pathogen DNA; can differentiate organisms

Peripheral blood (Buffy coat) smear: ID morulae

Immunofluorescence Assay (IFA): ≥7–10 days after symptom onset

≥4-fold IgG rise= diagnostic

Cross-reactivity between genera

Cannot always distinguish Ehrlichia spp.

Anaplasmataceae Treatment

Doxycycline (DOC)

Rifampin only if true DOC allergy

Anaplasma phagocytophilum

Human granulocyte anaplasmosis

Arthropod vector: Blacklegged ticks

Reservoir: Small mammals (white-footed mouse) and ruminants (white-tailed deer)- Wild & domestic animals

Worldwide

NE USA, northern Europe, & SE Asia

Low mortality

High risk groups: elderly, immunocompromised, & those where treatment was delayed

Ehrlichia chaffeensis

Human monocyte ehrlichiosis

Arthropod vector: Lone Star tick

Reservoir: Small mammals (white-footed mouse) and ruminants (white-tailed deer)- Wild & domestic animals

Worldwide

SE and SC USA

Rash 5 days after fever- more common in children

Low mortality

Sepsis, seizures, and coma