1. RICKETTSIA

2. General Concepts
The Rickettsia are Gram negative, obligate intracellular organism that infect mammals and arthropods .
They are primarily transmitted to humans through the bite of ticks, mite, flea or lice.
Rickettsia replicate in the cytoplasm and nucleus of the host cell .
They are small, pleomorphic coccobacilli about 2 micron in length.
The cell wall structure is typical of Gram-negative bacteria.
They are non-motile and non-spore forming
They are reproduced by binary fission

4. 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

5. 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.

6. 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

7. 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) structures.  and ribosomes are also seen. There are no discrete nuclear

9. 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

10. 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

11. Explain - biologically Rickettsia are intermediate between bacteria and virus

12. 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.

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. 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

19. 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

20. Epidemic Typhus

21. 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

23. Transovarian cycle Rocky Mountain spotted fever

24. 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

26. 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.

27. 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

28. 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

29. 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

30. 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 .

31. Treatment / Management
Rickettsia is susceptible to chemical disinfection and are destroyed by heat and dehydration
In order to inhibit their growth specific antibiotics are used, such as-
- tetracycline
- doxycicline
-Sulphonamides
Chloramphenicol