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Rickettsiae

Date: 09. January 2018

Introduction
Rickettsiae are obligate intracellular bacteria; that is, they can grow only within cells. They are the agents of typhus, spotted fevers, and Q fever.

Classification: In the United States, there are two rickettsial diseases of significance:

  • Rocky Mountain spotted fever, caused by Rickettsia rickettsia.
  • Q fever, caused by Coxiella burnetii.
  • Epidemic typhus, caused by Rickettsia prowazekii, is an important disease that occurs mainly in crowded, unsanitary living conditions during wartime.
  • Other rickettsial diseases such as endemic and scrub typhus occur primarily in developing countries.
  • Rickettsial pox, caused by Rickettsia akari, is a rare disease found in certain densely populated cities in the United States.

General Characteristics of Rickettsia: Rickettsiae are very short rods that are barely visible in the light microscope. Structurally, their cell wall resembles that of gram-negative rods, but they stain poorly with the standard Gram stain.

Rickettsiae are obligate intracellular parasites, because they are unable to produce sufficient energy to replicate extracellularly. Therefore, rickettsiae must be grown in cell culture, embryonated eggs, or experimental animals. Rickettsiae divide by binary fission within the host cell, in contrast to chlamydiae, which are also obligate intracellular parasites but replicate by a distinctive intracellular cycle. Several rickettsiae, such as Rickettsia prowazekii, Rickettsia tsutsugamushi, and R. urnetiid, possess antigens that cross-react with antigens of the OX strains of Proteus vulgaris. The Weil-Felix test, which detects antirickettsial antibodies in a patient’s serum by agglutination of the Proteus organisms, is based on this cross reaction.

Coxiella Burnetti: C. Burnetii has a sporelike stage that is highly resistant to drying, which enhances its ability to cause infection. It also has a very low ID50 estimated to be approximately one organism. C. urnetiid exists in two phases that differ in their antigenicity and their virulence: phase I organisms are isolated from the patient, are virulent, and synthesize certain surface antigens, whereas phase II organisms are produced by repeated passage in culture, are non-virulent, and have lost the ability to synthesize certain surface antigens. The clinical importance of phase variation is that patients with chronic Q fever have a much higher antibody titer to phase I antigens than those with acute Q fever.

Transmission: The most striking aspect of the life cycle of the rickettsiae is that they are maintained in nature in certain arthropods such as ticks, lice, fleas, and mites and, with one exception, are transmitted to humans by the bite of the arthropod. The rickettsiae circulate widely in the bloodstream (bacteremia), infecting primarily the endothelium of the blood vessel walls. The exception to arthropod transmission is C. urnetiid, the cause of Q fever, which is transmitted by aerosol and inhaled into the lungs. Virtually all rickettsial diseases are zoonoses (i.e., they have an animal reservoir), with the prominent exception of epidemic typhus, which occurs only in humans. It occurs only in humans because the causative organism, R. prowazekii, is transmitted by the human body louse.

 

Pathogenesis
The typical lesion caused by the rickettsiae is a vasculitis, particularly in the endothelial lining of the vessel wall where the organism is found. Damage to the vessels of the skin results in the characteristic rash and in edema caused by increased capillary permeability. The basis for pathogenesis by these organisms is unclear. There is some evidence that endotoxin is involved, which is in accord with the nature of some of the lesions such as fever and petechiae, but its role has not been confirmed. No exotoxins or cytolytic enzymes have been found.

 

Diseases
Rocky Mountain Spotted Fever: This disease is characterized by the acute onset of nonspecific symptoms (e.g., fever, severe headache, myalgias, and prostration). The typical rash, which appears 2 to 6 days later, begins with macules that frequently progress to petechiae. The rash usually appears first on the hands and feet and then moves inward to the trunk. In addition to headache, other profound central nervous system changes such as delirium and coma can occur. Disseminated intravascular coagulation, edema and circulatory collapse may ensue in severe cases. The diagnosis must be made on clinical grounds and therapy started promptly, because the laboratory diagnosis is delayed until a rise in antibody titer can be observed. The name of the disease is misleading, because it occurs primarily along the East Coast of the United States (in the south-eastern states of Virginia, North Carolina, and Georgia), where the dog tick, Dermacentor variabilis, is located. The name “Rocky Mountain spotted fever” is derived from the region in which the disease was first found. The tick is an important reservoir of R. urnetiid as well as the vector; the organism is passed by the transovarian route from tick to tick, and a lifetime infection results. Certain mammals, such as dogs and rodents, are also reservoirs of the organism.

Q fever: Unlike other rickettsial diseases, the main organ involved in Q fever is the lungs. It begins suddenly with fever, severe headache, cough, and other influenza like symptoms. This is all that occurs in many patients, but pneumonia ensues in about half. Hepatitis is frequent enough that the combination of pneumonia and hepatitis should suggest Q fever. A rash is rare, unlike in the other rickettsial diseases. In general, Q fever is an acute disease, and recovery is expected even in the absence of antibiotic therapy. Rarely, chronic Q fever characterized by life-threatening endocarditis occurs.

Typhus: There are several forms of typhus, namely, louse-borne epidemic typhus caused by R. prowazekii, flea-borne endemic typhus caused by Rickettsia typhi, chigger-borne scrub typhus caused by R. tsutsugamushi, and several other quite rare forms. Cases of flea-borne endemic typhus, also called murine typhus, occur in small numbers in the southern regions of California and Texas. The following description is limited to epidemic typhus, the most important of the typhus group of diseases. Typhus begins with the sudden onset of chills, fever, headache, and other influenza like symptoms approximately 1 to 3 weeks after the louse bite occurs. Between the fifth and ninth days after the onset of symptoms, a maculopapular rash begins on the trunk and spreads peripherally. The rash becomes petechial and spreads over the entire body but spares the face, palms, and soles. Signs of severe meningoencephalitis, including delirium and coma, begin with the rash and continue into the second and third weeks. In untreated cases, death occurs from peripheral vascular collapse or from bacterial pneumonia. Epidemic typhus is transmitted from person to person by the human body louse, Pediculus. When a bacteremic patient is bitten, the organism is ingested by the louse and multiplies in the gut epithelium. It is excreted in the feces of the louse during the act of biting the next person and auto inoculated by the person while scratching the bite. The infected louse dies after a few weeks, and there is no louse-to-louse transmission; therefore, human infection is an obligatory stage in the cycle. Epidemic typhus is associated with wars and poverty. A recurrent form of epidemic typhus is called Brill-Zinsser disease.


Laboratory Diagnosis
Culturing: Laboratory diagnosis of rickettsial diseases is based on serologic analysis rather than isolation of the organism. Although rickettsiae can be grown in cell culture or embryonated eggs, this is a hazardous procedure that is not available in the standard clinical laboratory.

Serological tests: Of the serologic tests, the indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA) tests are most often used. The Weil-Felix test is of historic interest but is no longer performed because its specificity and sensitivity are too low. The basis of the Weil-Felix test is described below. A fourfold or greater rise in titer between the acute and convalescent serum samples is the most common way the laboratory diagnosis is made. This is usually a retrospective diagnosis, because the convalescent sample is obtained 2 weeks after the acute sample. If the clinical picture is typical, a single acute-phase titer of 1:128 or greater is accepted as presumptive evidence. If the test is available, a diagnosis can be made during the acute phase of the disease by immunofluorescence assay on tissue obtained from the site of the petechial rash. The Weil-Felix test is based on the cross-reaction of an antigen present in many rickettsiae with the O antigen polysaccharide found in P. vulgaris OX-2, OX-19, and OX-K. The test measures the presence of antirickettsial antibodies in the patient’s serum by their ability to agglutinate Proteus bacteria. The specific rickettsial organism can be identified by the agglutination observed with one or another of these three different strains of P. vulgaris. However, as mentioned, this test is no longer used in the United States.

 

Treatment and Prevention
Treatment of Rickettsial Diseases: The treatment of choice for all rickettsial diseases is tetracycline, with chloramphenicol as the second choice.

Prevention of Rickettsial Diseases: Prevention of many of these diseases is based on reducing exposure to the arthropod vector by wearing protective clothing and using insect repellent. Frequent examination of the skin for ticks is important in preventing Rocky Mountain spotted fever; the tick must be attached for several hours to transmit the disease. There is no vaccine against Rocky Mountain spotted fever. Prophylactic antibiotics are not recommended in the asymptomatic person bitten by a tick. Prevention of typhus is based on personal hygiene and “delousing” with DDT A typhus vaccine containing formalin-killed R. prowazekii organisms is effective and useful in the military during war time but is not available to civilians in the United States. Persons at high risk of contracting Q fever, such as veterinarians, shepherds, abattoir workers, and laboratory personnel exposed to C. urnetiid, should receive the vaccine that consists of the killed organism.

Khurshid, Aqsa
  • Academics: MS
  • Specialization: Industrial Biotechnology
  • Current: Senior Technologist
  • Hospital: AFIP
  • Location: Islamabad, Pakistan
  • Clinical / Teaching Years: 2 / 1
  •  
  • Course: Microbiology
  •  

Ms. Aqsa Khurshid did her Masters of science in 2014 from National University of Science and Technology. And after that, she is serving at Armed Forces Institute of Pathology (AFIP) as senior technologist.

She also has publications in Global Journal of Medical Research.

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