Rickettsial (Spotted & Typhus Fevers) & Related Infections (Anaplasmosis & Ehrlichiosis)

RICKETTSIACEAE FAMILY General characteristics Consists of 3 genera Rickettsia Ehrlichia Coxiella Obligate intracellular parasites. Small Gram (-) coccobacilli (0.3-0.5 um) Cell membrane similar to Gram (-) bacteria with LPS & peptidoglycan

General characteristics The organisms will not show up on Gram stain, but can be seen with Giemsa stains Require growth co-factors Will not grow on artificial media Grown in embryonated eggs or tissue culture Cultivation is costly and hazardous because aerosol transmission can easily occur All, except Coxiella, are transmitted by arthropod vectors as fleas, ticks, mites and lice

Louse Scanning electron microscope (SEM) depiction of a flea

Electron micrograph of Rickettsia prowazekii in experimentally infected tick tissue

Gimenez stain of tissue culture cells infected with Rickettsia rickettsii

Rickettsia Transmission Rickettsia are usually introduced into human skin by the bite of an insect (flea or louse) or an arachnid (tick or mite) R. rickettsii invades the endothelial cells that line the blood vessels Incubation period: ~1 week Virulence factors of Rickettsial species changes in the host cell phagocytosis bacterial surface protein

Engorged tick attached to back of toddler's head Engorged tick attached to back of toddler's head. Adult thumb shown for scale. Castor bean tick, Ixodes ricinus

Arthropod Vector Rickettsia rickettsii

Pathogenesis During the first few days of incubation period local reaction caused by hypersensitivity to tick or vector products Bacteria multiply at the site & later disseminate via lymphatic system Bacteria is phagocytosed by macrophages (1st barrier to rickettsial multiplication) After 7-10 days organisms disseminate replicate in the nucleus or cytoplasm of endothelial cells causing vasculitis

Endothelial damage & vasculitis progress causing Infected cells show intracytoplasmic inclusions & intranuclear inclusions Endothelial damage & vasculitis progress causing development of maculopapular skin rashes perivascular tissue necrosis thrombosis & ischemia Disseminated endothelial lesion lead to increased capillary permeability, edema, hemorrhage & hypotensive shock Endothelial damage can lead to activation of clotting system ---> Disseminated intravascular coagulation (DIC)

Pathogenesis: Rickettsia cell-to-cell spread

Rocky Mountain Spotted Fever Etiologic agent: Rickettsia rickettsiae Most common rickettsial disease Individuals younger than 19 years old are usually at risk Males affected twice as often as females It is common during summer months

Serious disease with 35% mortality rate Transmitted by ticks that must remain attached for hours in order to transmit the disease Incubation of 2-6 days Followed by a severe headache, chills, fever, aching, and nausea

After 2-6 days, a maculopapular rash develops, first on the extremities, including palms, foot soles, and spreading to the chest and abdomen If left untreated, the rash will become petechial with hemorrhages in the skin and mucous membranes due to vascular damage as the organism invades the blood vessels Death may occur during the end of the second week due to kidney or heart failure

Rocky Mountain Spotted Fever

Endemic Typhus Etiologic agent: Rickettsia typhi Incubation period: 5-18 days Transmitted to man by rat fleas  cat fleas and mouse fleas are less common modes of transmission The disease occurs sporadically

Symptoms: severe headache, chills, fever, and after a fourth day, a maculopapular rash caused by subcutaneous hemorrhaging as Rickettsia invade the blood vessels The rash begins on the upper trunk and spread to involve the whole body except the face, palms of the hands, and the soles of the feet The disease lasts about 2 weeks and the patient may have a prolonged convalescence

Ehrlichia Disease: Ehrlichiosis Transmitted via tick vectors Etiologic agent: E. chaffeensis Invade leukocytes and grow in cytoplasmic vacuoles making characteristic inclusions known as morulae Symptoms resemble Rocky Mountain spotted fever

Clinically manifests as acute fever with leucopenia thrombocytopenia elevations of aminotransferase levels Rash is infrequent Vasculitis is rare

Coxiella burnetii The only species of Coxiella genus Causal agent of Q-fever Found in infected animals, arthropods or humans and highly infectious Transmission Inhalation of airborne organisms infected dusts in farm and slaughterhouses Contact with the milk, urine, feces, of infected animals It has spore-like form that resists heat and dryness allowing it to survive in extracellular environment

Q fever Q for “query” or mysterious febrile illness Occurs in veterinarians, ranchers, and animal researchers who are in contact with infected placenta from sheep, cattle, or goats (no arthropod vector for C. burnetii) Incubation period: 10-28 days Disease characterized by fever, influenza-like syndromes; but no skin rash Some patients present with bronchopneumonia with patchy interstitial infiltrates Rare complications: hepatitis, endocarditis, and meningoencephalitis

Q fever Doughnut shaped non-caseating granuloma of Q fever

Laboratory Diagnosis of Rickettsiae 1. Culture & isolation Difficult & dangerous because of the highly infectious nature of rickettsiae 2. Serologic test A. Weil-Felix test: based on cross-reactivity between some strains of Proteus & Rickettsia B. Complement fixation: not very sensitive & time consuming C. Indirect fluorescence (EIA): more sensitive & specific; allows discrimination between IgM & IgG antibodies which helps in early diagnosis D. Direct immunofluorescence: the only serologic test that is useful for clinical diagnosis, 100% specific & 70% sensitive allowing diagnosis in 3-4 days into the illness