Rickettsia, Coxiella, Ehrlichia and Anaplasma

Rickettsia Family rickettsiaceae: R. rickettsii R. prowazekii R. typhi Orientia tsutsugamushi All are transmitted by arthropod vectors as fleas, ticks, mites and lice. Rickettsia is named after Howard Ricketts, who studied Rocky Mountain spotted fever, and died of typhus after studying that disease.

Geographical distribution Specie Disease Mode of transmission Geographical distribution R. Rickettsii Rocky Mountain spotted fever Bite of tick North & South America R. prowazekii Epidemic typhus Louse faeces Africa, North& South America R. typhi Murine (endemic) typhus Flea faeces Tropics O. tsutsugamushi Scrub typhus Bite of mite Asia & Australia

Mite Body louse Tick flea

General characteristics All are obligate intracellular bacteria. Small coccobacilli (0.3-0.5 um) All except orientia have cell wall similar to gram negative bacteria with LPS & peptidoglycan. They can be seen by Giemsa stain but not Gram stain. Do not grow on artificial media. Can be isolated in tissue culture but rarely done because aerosol transmission can easily occur.

Giemsa stain of tissue culture cells infected with Rickettsia rickettsii

Pathogenesis Enter the body through the bite or faeces of arthropod vectors. Attach to endothelial cells, enter by induced phagocytosis, multiply intracellularly. Endothelial damage either due to accumulation of large numbers of bacteria (R. prowazekii, R. typhi) or due to cell membrane damage by formation of actin tails and filopodia (R.rickettsii). This result in widespread microvascular injury; increased vascular permeability with encephalitis and pulmonary edema.

Formation of actin tails and leaving the cells through filopodia (R Formation of actin tails and leaving the cells through filopodia (R. rickettsii). Large number of rickettsiae in endothelial cells (R. prowazekii, R. typhi)

Clinical features Epidemic typhus (R. prowazekii) : Epidemics with high mortality. Fever & macular rash first appear on the trunk then the extremities. Mild cases resolve within 1-2 days. Sever cases: the rash become hemorrhagic with hypotension, renal failure and coma. Early treatment is life saving. Reactivation of latent infection may happen years later.

Murine (endemic) typhus (R. typhi): The same symptoms of epidemic typhus but rarely fatal. Scrub Typhus (O. tsutsugamushi): Fever, myalgia, maculopapular rash, eschar and enlarged lymph nodes in the site of the bite. Death occurs due to encephalitis and respiratory failure.

Rocky Mountain Spotted Fever: Fever, myalgia, vomiting, diarrhea, cough and maculopapular rash develop first in the extremities. Most of the cases are mild. Sever disease is more seen in old patient with hemorrhagic rash, encephalitis, hypovolemia, shock and death.

Laboratory Diagnosis Timely and accurate diagnosis and appropriate treatment may mean the difference between death and recovery. However laboratory diagnosis is difficult in the beginning of the disease. Isolation is difficult & hazardous. PCR tests are not always available. Serology will give positive results late in the disease. Rocky mountain spotted fever can be diagnosed by skin biopsies.

Treatment & prevention Impossible to be eradicated because they are zoonotic diseases. Using of repellents, delousing and removing of ticks from skin reduce transmission. Respond well to antibiotics that enter the cells esp. doxycycline and tetracycline.

Coxiella (Q fever) World wide distribution. Reservoir: cattle, sheep and goats. Causative agent. C. burnetii; an intracellular, coccobacilli with gram negative cell wall. Transmission: by inhalation of aerosols leading to infection of alveolar macrophages. Acute Q fever: fever, myalgia and pneumonia which is usually self limiting. Chronic Q fever: reactivation of latent bacteria in the cardiac valves leading to endocarditis. Diagnosis: antibodies detection and PCR.

Ehrlichiosis & anaplasmosis Caused by ehrlichia and anaplasma respectively. Transmitted by ticks bite. Infect monocytes, macrophages and neutrophils (low TWBC & platelets). Clinically similar to rocky mountain spotted fever. 50% of patients need hospitalization for renal failure, meningoencephalitis and DIC and about 3% die. Diagnosis: Antibodies detection, Giemsa stain of neutrophils or PCR.