· They are small Gram negative bacilli adapted to obligate intracellular parasitism, transmitted by arthropod vectors. They are primary parasites of arthropods such as lice, fleas, ticks, in which they are found in the alimentary canal. In vertebrates they infect vascular endothelium, reticuloendothelial cells.
· This pleomorphic coccobacilli are nonmotile, noncapsulated. They stain bluish purple with Giemsa stain. It has a 3 layered cell wal , a trilaminar plasma membrane and an outer slime layer.
· Growth occurs in the cytoplasm of infected cells, nucleus etc. the optimum temperature is 32-350C. they are readily cultivated in the yolksac of chick embryos, HeLa cells etc., in arthropods.
· They multiply by binary fission.
· They are inactivated by physical and chemical agents. They are rapidly destroyed at room temperature when seperated from host components, susceptible to tetracycline, chloramphenicol, ciprofloxacin, lysozyme. Sulfonamides enhance the growth and worsen the condition of patients.
· They possess both RNA and DNA.
· They are large enough to be seen under the light microscope and are held back by bacterial filters.
Antigenic structure - Rickettsia have 3 types of antigen :
· group specific antigens, such as surface protein antigen (SPA) and outer membrane proteins (OMP).
· A species-specific within the cell wall of the organisms.
· also a third surface antigen, ie., an alkali stable polysaccharide. This antigen is found in some Rickettsiae and in some strains of Proteus bacilli.
Weil- Felix Reaction- During World war I Austrian Bacteriologists Edmund Weil and Arthur Felix were in charge of diagnosing typhus fever, an arthropod borne, caused by Rickettsia in the Austrian army. In 1916 they developed the agglutination test for typhus. The Weil- Felix reaction is based on the detection of cross reactive antibodies. In this test, antibodies produced in response to a particular rickettsial infection, agglutinate bacterial strains of Proteus, such as OX-19, OX-2, OX-K. These cross reactions occurs because rickettsial strains possess cell wall antigen, ie., alkali stable polysaccharide, similar to the O cell wall antigen of Proteus strains. But Proteus species are normal flora of human beings and may cause urinary tract infections. Therefore the presence of antibodies to Proteus OX strains could not be considered an absolute criterion for the presence of rickettsial disease.
Pathogenicity – Rickettsias are named after Howard T. Ricketts, who identified them as the causative agents of Typhus and Rocky Mountain Spotted fevers [died of lab infections from these highly infectious microorganisms].
Typhus fever forms grow in the cytoplasm of infected cells. Rocky Mountain Spotted fever types grow in both nucleus and the cytoplasm. They are cultured only in cells, embryonated eggs. Despite improved laboratory designs and equipments, vaccine, the infection is common and fatal. The organisms invade, damage the cells of blood vessel linings and cause the linings to leak, which causes skin lesions and petechiae- pin point haemorrhages, common in skin folds. It also causes necrosis in brain and heart. It causes fever, painful headache, extreme weakness, liver and spleen enlargement, skin rashes.
The different types of diseases, based on the various species :
I. Typhus Fever – Epidemic typhus, Endemic typhus and Scrub typhus.
v Epidemic typhus – Classic, European, Louse borne typhus, caused by Rickettsia prowazekki. The disease is common during wars, overcrowding, poor sanitation. The disease is transmitted by human body louse, Pediculus humanis corporis. After a louse feeds on an infected person, rickettsias multiply in its digestive tract and are shed in its faeces. When a louse bites, it defaecates and the infected lice deposit organisms next to a bite and die of typhus in a few weeks. As victims scratch bites, they inoculate organisms into the wound. The infected lice abandon dead bodies or people with high fevers, moving to and infecting new hosts.
After 12 days’ incubation, fever and headache is abrupt and after 7 days a rash on the trunk and spread to extremities, but spares face, palm and soles.
Antibiotic therapy should be started immediately. The disease can be prevented by eradicating lice with insecticides and maintaining hygeinic living conditions. A vaccine is available. Recovery gives lifetime immunity, except in Brill-Zinser disease.
Brill- Zinser disease – is a recurrence of typhus infection, named after, Nathan Brill and Hans Zinsser in 1930s. this disease has milder symptoms, shorter duration and no skin rash. It is caused by reactivation of latent organisms harbored in lymph nodes. Despite rigorous treatment, some victims of typhus still develop this disease. It can be distinguished from epidemic typhus by the type of antibodies formed, ie., epidemic typhus first elicits IgM and then IgG antibodies, whereas Brill – Zinsser disease, eliciting IgG antibodies being a secondary response.
v Endemic typhus – Murine typhus- because of the association with rats, flea-borne typhus, caused by R. typhi . Rat flea Xenopsylla cheopis multiplies in the gut of the flea and shed in its faeces. The fleas defaecates while biting host, and as host scratches the organisms enter into through the wound. After 10-14 days’ incubation, fever, chills, headache, followed by a rash in 3-4 days. It lasts about 2 weeks if untreated.
v Scrub typhus – tsutsugamoshi disease, caused by R. tsutsugamoshi transmitted by a “bad little bug” or mite, that feeds on rats in Japan and Australia. After 10-12 days incubation, scrub typhus begins with fever, chills, headache. Many patients develop sloughing lesions at the bite sites and later a spotty rash. Infections can be prevented by controlling mite population.
II. Rocky Mountain Spotted fever – First recognized in Rocky Mountain states in 1900. The disease is caused by R. rickettsii, transmitted by the ticks of the genus, Dermacentor. Ticks are not harmed by the rickettsiae and remain infected for life. The organisms are shed in tick faeces but transmission to human beings primarily by a bite as the organisms invade the salivary glands of the ticks.
After 3-4 days’ incubation, onset of fever, headache, weakness in abrupts, followed in 2-4 days by a rash. The rash begins on ankles and wrists, prominent on palms and soles and progresses towards the trunk, just reverse of typhus fever. Spots are caused by blood leaking out of damaged blood vessels beneath the skin surface, they coalesce as blood leaks from many damaged sites. Blood vessels in the organs throughout the body are damaged.
Laboratory diagnosis – Rickettsial diseases may be diagnosed in the laboratory either by isolation of rickettsiae or by serology. They can be isolated in male guinea pigs or mice from patients. Blood clot ground in skimmed milk is also inoculated intraperitoneally. The animals are observed for 3-4 weeks and the temperature is recorded daily. Their response varies with rickettsial species. Some may die, smears from peritoneum, spleen of infected animals may be stained with Giemsa.
Serological diagnosis can be done by Weil- Felix reaction. The test is usually done as a tube agglutination or rapid slide agglutination. The most frequently used serological method using rickettsial antigens in the complement fixation test. This may be done using the group specific soluble antigen or the type specific rickettsial antigen.
Prophylaxis - The fever can be damaged by wearing protective clothing and by vigilantly inspecting clothing and skin during visits to tick infested areas. Inspecting children’s hair is important. Eventhough vaccine is available, it is not effective completely.
Coxiella burnetti is pleomorphic rods or spheres. It is filterable. In dried faeces, wool it survives for a year at 40C. It is not inactivated by 600C and 1% phenol. In milk it survive holding method pasteurization, while susceptible to flash method. It grows well in the chick embryo yolk sac. It has two forms – large and small variants. The large cell variant produces terminal endospore, thereby giving resistance.
C. burnetti causes Q- fever[ first described in Queensland, Australia, Q stands for query because determining which organism caused it , remained a question for a long time]. Unlike other rickettsias, this organism survives long periods outside cells and can be transmitted aerially or by ticks.
Once C. burnetti cells with endospore-like bodies inside them have been inhaled, they are phagocytized by host cells, and they grow in phagolysosomes of host cells. There they respond to the acidic conditions by increasing their metabolism and multipling rapidly until they almost fill infected cells. Eventually the cell ruptures releasing the pathogenic bacteria. These pathogens, when spread by the blood stream, infect other body cells.
C. burnetti exist all over the world, especially in cattle, sheep raising areas. Wild animals and cattle are normal hosts. The bacteria are transmitted via tick bites, faeces and genital secretions of infected animals. Humans become infected by inhaling aerosol droplets from infected domestic animals. Farmers become infected while attending a cow giving birth, or miscarrying if the placenta is laden with organisms. Slaughter house and tannary workers become infected by inhaling dried tick faeces from animal hides. Because of its resistance to drying, Coxiella remain viable in the environment for long periods of time. Transmission to humans also occur by the ingestion of milk from contaminated animals. Flash pasteurization eliminates the hazard.
Symptoms – Chills, fever, headache, malaise and severe sweats. The incubation period is 18-20 days. Diagnosis by serologic testing or by direct immunofluorescent antibody staining.
Treatment with antibiotics – tetracycline, fluoroquinolone. Life long immunity follows, a vaccine is available.
Untreated or inadequately treated Q fever, remits. Cortisone treatment reactivate it. In chronic cases, endocarditis and heart valve infections are seen.