RICKETTSIA

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

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

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.

Morphology Shape: Rod shaped Size: Diameter- 0.3- 0.5 µm Length - 0.3- 0.4 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

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

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

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

Explain - biologically Rickettsia are intermediate between bacteria and virus

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.

Transmission process

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 .

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

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

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

Epidemic Typhus

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

Transovarian cycle Rocky Mountain spotted fever

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

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.

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

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

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

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 .

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 -