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

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

2. 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

3. General characteristics • The organisms will not show up on Gram stain, but can be seen with Giemsastains • 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

4. Louse Scanning electron microscope (SEM) depiction of a flea

5. Electron micrograph of Rickettsia prowazekiiin experimentally infected tick tissue

6. Gimenez stain of tissue culture cells infected with Rickettsia rickettsii

7. 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. rickettsiiinvades 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

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

9. Arthropod Vector Rickettsia rickettsii

10. 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

11. 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)

12. Pathogenesis: Rickettsia cell-to-cell spread

13. 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

14. 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

15. 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

16. Rocky Mountain Spotted Fever

17. 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

18. 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

19. 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

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

21. 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

22. 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

23. Q fever Doughnut shaped non-caseating granuloma of Q fever

24. 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