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

RICKETTSIACEAE FAMILY

General characteristicsConsists 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

Scanning electron microscope (SEM) depiction of a flea

Louse

Electron micrograph of Rickettsia prowazekii in experimentally infected tick tissue

Gimenez stain of tissue culture cells infected with Rickettsia rickettsii

Rickettsia

TransmissionRickettsia 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 specieschanges in the host cell phagocytosisbacterial surface protein

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

Arthropod Vector

Rickettsia rickettsii

Pathogenesis

During the first few days of incubation periodlocal 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 disseminatereplicate in the nucleus or cytoplasm of endothelial cells

causing vasculitis

Infected cells show intracytoplasmic inclusions & intranuclear inclusions

Endothelial damage & vasculitis progress causingdevelopment of maculopapular skin rashesperivascular tissue necrosisthrombosis & 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 TyphusEtiologic 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 withleucopeniathrombocytopeniaelevations of aminotransferase levels

Rash is infrequent

Vasculitis is rare

Coxiella burnetiiThe only species of Coxiella genus

Causal agent of Q-fever

Found in infected animals, arthropods or humans and highly infectious

TransmissionInhalation of airborne organisms

infected dusts in farm and slaughterhousesContact 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 feverQ 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 Rickettsiae1. Culture & isolation

Difficult & dangerous because of the highly infectious nature of rickettsiae

2. Serologic testA. Weil-Felix test: based on cross-reactivity between some

strains of Proteus & RickettsiaB. Complement fixation: not very sensitive & time

consumingC. 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