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 when either Gimenez or Giemsa stains are used. Require growth co-factors (acetyl-CoA, NAD, ATP). 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 lice, ticks, fleas and/or mites.

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). Rickettsiae multiply in endothelial cells of microvessels. Incubation period: ~1 week Virulence factors of Rickettsial species: Induced phagocytosis Recruitment of actin for intracellular spread

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 drainage - 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

Pathogenesis: - Infected cells show intracytoplasmic inclusions & intranuclear inclusions - Endothelial damage & vasculitis progress causing the 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 ---> DIC

Pathogenesis: Rickettsia cell-to-cell spread 1

Rocky Mountain Spotted Fever: Etiologic agent: Rickettsia rickettsiae Most common rickettsial disease At risk: individuals younger than 19 years old. Males affected twice as often as females Disease 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 and 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 1

Endemic Typhus: Etiologic agent: Rickettsia typhi Incubation period: 5-18 days. Transmitted to man by rat fleas. 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 Parsitize 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 via: Inhalation of airborne organisms (infected dusts in barnyards and slaughterhouses). Ingestion of milk from infected animals. It has spore-like form that resists heat and dryness allowing it to survive extracellulary.

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

Doughnut shaped noncaseating granuloma of Q fever

Laboratory Diagnosis: 1. Culture & isolation: difficult & dangerous because of the highly infectious nature of rickettsiae 2. Serologic test: widely used 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