1. Rickettsia

2. Rickettsia species
Small, intracellular parasites, transmitted to humans by arthropods (both vector and reservoir).
Clinical manifestation: fever, rashes, and vasculitis. They are grouped on the basis of clinical features, epidemiolgic aspects,immunologic characteristics.

3. Properties of Rickettsiae
1.Structure
The structure of the typical rickettsia is very similar to that of Gram-negative bacteria. The typical envelope consists of three major layers: an innermost cytoplasmic membrane, a thin electron dense rigid cell wall and an outer layer. The outer layer resembles typical membranes in its chemical composition and its trilaminar appearance. The cell wall is chemically similar to that of Gram-negative bacteria in that it contains diaminopimelic acid and lacks teichoic acid. Intracytoplasmic invaginations of the plasma membrane (mesosomes) and ribosomes are also seen. There are no discrete nuclear structures. 
2.Metabolism
In dilute buffered salt solutions, isolated rickettsia are unstable, losing both metabolic activity and infectivity for animal cells. If, however, the medium is enriched with potassium, serum albumin and sucrose, the isolated organisms can survive for many hours. If ATP is added to the solution, the organisms metabolize and consume oxygen. The basis for the obligate parasitism of these cells is that they require the rich cytoplasm to stabilize an unusually permeable cell membrane.
The rickettsia have many of the metabolic capabilities of bacteria, but require an exogenous supply of cofactors to express these capabilities. The response to exogenous cofactors implies an unusually permeable cytoplasmic membrane.

4. 3.Growth and Multiplication
Rickettsia normally multiply by transverse binary fission. Under poor nutritional conditions, the rickettsia cease dividing and grow into long filamentous forms, which subsequently undergo rapid and multiple division into the typical short rod forms when fresh nutrient is added. Immediately after division, the rickettsia engage in extensive movements through the cytoplasm of the cell. C. burnetii differs from other rickettsia in that it is enclosed in a persistent vacuole during growth and division. Six to ten daughter cells will form within a host cell before the cell ruptures and releases them.

5. 4.Pathogenicity
In their arthropod vectors, the rickettsia multiply in the epithelium of the intestinal tract; they are excreted in the feces, but occasionally gain access to the arthropods salivary glands. They are transmitted to man, via the arthropod saliva, through a bite. In their mammalian host, they are found principally in the endothelium of the small blood vessels, particularly in those of the brain, skin and heart. Hyperplasia of endothelial cells and localized thrombus formation lead to obstruction of blood flow, with escape of RBC's into the surrounding tissue. Inflammatory cells also accumulate about affected segments of blood vessels. This angiitis appears to account for some of the more prominent clinical manifestations, such as petechial rash, stupor and terminal shock. Death is ascribed to damage of endothelial cells, resulting in leakage of plasma, decrease in blood volume, and shock.

6. It is assumed that the observed clinical manifestations of a rickettsial infection are due to production of an endotoxin, although this endotoxin is quite different in physiological effects from that produced by members of the Enterobacteriaceae. This is inferred, although the toxin has not been isolated, from these facts:
1.    IV-injected rickettsia cause rapid death in experimental animals.
2.    UV-irradiation of rickettsia diminished their infectivity without reducing toxicity.
3.    The use of anti-rickettsial drugs does not prevent rapid death in experimental animals.
4.    Antiserum specific for cell wall antigens of the rickettsia prevents the toxic effect.
5.antigen
Agglutination of proteus vulgaris (Weil-Felix Reaction): Because rickettsial strains possess cell wall antigen that are similar to polysaccharide O antigens of the proteus strains. Give presumptive diagnosis of rickettsial disease.
S + OX19→ agg titer>1:160

7. The family Rickettsiaceae is taxonomically divided into following genera:
1. Rickettsia (11 species)--obligate intracellular parasites which do not multiply within vacuoles and do not  parasitize white blood cells.
2. Ehrlichia (2 species) – obligate intracellular parasites which do not multiply within vacuoles but do parasitize white blood cells.
3. Coxiella (1 species) – obligate intracellular parasite which grows preferentially in vacuoles of host cells.
4. Bartonella (3 species) – intracellular parasite which attacks the red blood cell.

8. Classification Group Disease Organism vector Typhus group
Epidemic Typhus
R. prowazekii
Lice
Endemic typhus
R. Typhi
Rat, flea
Spotted fever group
Rocky mountain spotted fever
R. Rickettsii
Tick
Trench fever
R.Quintana
Scrub typhus Group
Scrub typhus
R. Tsutsugamushi
Mite
Q fever group
Q fever
C. Burnettii
Ticks , lice
Rickettsial pox group
Rickettsial pox
R.Akari
mite

9. Why Rickettsia is called obligate parasite?
Obligate parasites mean those parasites which take nutrient from the host and unable to live without living cells or organisms.
Rickettsia can grow only in living cells.
They requires actively metabolized cell media for growth and they contain intracellular metabolic enzymes.
So, they are called obligate parasite.

10. Morphology Shape: Rod shaped Size: Diameter- 0.3- 0.5 µm
Length µm
Cell wall- multilayered and 7-10 nm thick.
Cell wall contains amino acids, polysaccharide .
Cytoplasm- It contains bacterial type of ribosome and variable quantities of RNA.
Nuclear membrane contains constant amount of DNA

12. Similarities with bacteria
Like bacteria Rickettsial cell contains cell wall and cytoplasmic membrane
Like bacteria, protein and phospholipid are present in the cell
Like bacteria, they reproduce by binary fission
Like bacteria, they contain intracellular metabolic enzymes
Like Gram negative bacteria they produce endotoxin

13. Difference with bacteria
Unlike bacteria, they are inactive and unstable outside the host cell
They do not forms spores
They do not show motility
They are not filterable
They are more resistant than bacteria

14. Transmission process

16. Pathogenesis
The Rickettsia are transmitted by various arthropod vectors
Q fever may also transmitted by aerosols
Within minutes organisms are engulfed by macrophage and endocytosed by vascular endothelial cells.
They are resistant to typical phagocyte degradation and actually begin to replicate within the cells causing lysis of the cells and spread to other cells.
Initial disease occurs at the site of the bite wounds and often produce local lesion
They frequently involve the skin and brain .

17. Pathogenesis (cont.) Lesions of the blood vessels produce microemboli
These lesions may become nercotic causing permanent damage anywhere in the body
Symptoms of these diseases may be a combination of
actual organism virulence factors such as endotoxins.
Characteristics symptoms include
- Fever
- headache
- rash

18. Diseases
1. Louse-borne: European epidemic typhus (Rickettsia prowazekii), Brill's disease (Rickettsia prowazekii), Trench fever (Bartonella quintana) 2. Flea-borne Endemic murine typhus (Rickettsia typhi), Cat scratch fever /Bacilliary angiomatosis/ (Bartonella henselae) 3. Mite-borne Scrub typhus (Orientia /Rickettsia tsutsugamushi), Rickettsialpox (Rickettsia akari)

19. Diseases
4. Tick-borne Rocky Mountain Spotted Fever (Rickettsia rickettsii), North Asian tick typhus (Rickettsia siberica), Fievre boutonneuse (Rickettsia conorii), Queensland tick typhus (Rickettsia australis), Q-fever (Coxiella burnetii), Spotted fever (Rickettsia rhipicephali), Ehrlichiosis (Ehrlichia canis, Ehrlichia chaffeensis) 5. Fly-borne Oroyo fever / Verruga peruana (Bartonella bacilliformis)

20. Epidemic Typhus Causative agent: R. prowazekii
Epidemic during war and during first world war approx. 3 million deaths resulted from infection by this bacterium.
Human is the only natural vibratae host
Vector : Human louse
Disease is a consequence of overcrowding and poor hygiene
Lice infected by feeding on Rickettsial patient.
Rickettsia multiply in the gut and appear in the faeces after 3 – 5 days.
Infection transmitted when contaminated louse faeces is rubbed through the minute abrasion caused by scratching

21. Epidemic Typhus(cont.)
Incubation period : 5-15 days
Symptoms starts with fever and chills
Rash on 4th or 5th day in the trunk and limb
Patient become stuporous & delirious during 2nd week
Case fatality 40%
In those who recover from the disease , Rickettsia remain dormant for years in the lymphoid tissue or organs

22. Epidemic Typhus

23. Rocky Mountain spotted fever
Causative agent: R. rickettsii
R. rickettsii discovered by Rickets in 1906
Spotted fever transmitted by ticks
This disease relatively common in USA .
Cases are usually related to those with increased opportunities for exposure – hiking, camping, rural and wooded areas where ticks are commonly found
The disease begins with a fever and rash which forms on the extremities and progresses toward the trunk
Patient treated within the first 5 days of illness are likely to progress fatal disease

25. Transovarian cycle Rocky Mountain spotted fever

26. Q fever Agent: C. burnetti
Q fever relatively common in the USA primarily in domestic animals such as cattle, sheep and goats.
Q fever also transmitted by the ticks and it can be highly contagious
It may also be transmitted through milk or other excreta of infected animals.
Q fever may cause asymptomatic disease or a generalized febrile illness which may include granulomatous hepatitis .
Inhalation may cause Pneumonia
Rash is rare in Q fever

28. Diagnosis
These diseases present as febrile illnesses after exposure to arthropods or animal hosts or aerosols in endemic areas
These disease are easily misdiagnosed and these delays may be the reason for the high fatality rate of spotted fever
The spread of the rash is often characteristic, spread from the trunk to the extremities is typical for typhus ; spread from extremities to trunk is typical for spotted fever.

29. Serology
Serology is the scientific study of blood serum and other bodily fluids.
In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given microorganism)
Serology available in the following methods-
- The Weil-felix test
- Complement fixation
- Immunofluoroscent antibody
- Latex agglutination
- ELISA
- Hemagglutination

30. Complement Fixation Test
Complement: A normal thermo labile protein constituent of blood which participate in antigen antibody reaction is called a complement.
Complement Fixation : Literally means the binding of complement to an antigen- antibody complex so that complement is unavailable for subsequent reaction

31. Complement Fixation Test
The complement fixation test is widely used in the laboratory diagnosis of many infectious disease including Rikettsial etiology
In this process patient’s blood serum , Rickettsial suspension( antigen) and complement are mixed
Sheep red blood cells (sRBCs) which have been pre-bound to anti-sRBC antibodies are added to the serum
If the complement is fixed by reacting with antigens and its homologous antibody, lysis of sheep red cells does not occur , even though antibodies against the sheep red cells are present

32. Complement Fixation Test(cont.)
It is called positive complement fixation test and the patient is infected by Rickettsial organism
But hemolysis of sheep red cells occur , it indicates a negative test and the patient is not infected by rickettsial organism
Complement fixation test is specific and more generally acceptable than non specific Weil-felix test .

33. Chemotherapy
The drugs of choice for the treatment of rickettsial diseases are chloramphenicol and tetracycline. Each of these is highly toxic, especially in children, and must be used with care. The sulfonamides stimulate rickettsial growth and thus are contraindicated in the treatment of these diseases.