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 ( 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 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

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

5. Electron micrograph of Rickettsia prowazekii in 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. 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

8. 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

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. 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)

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: 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