1. Chlamydiae &Rickettsiae Lecture 13

2. Chlamydiae Obligate intracellular bacteria Agents of common sexually transmitted diseases urethritis and cervicitis other infections: pneumonia psittacosis Trachoma - lymphogranuloma venereum.

3. Three species: C. trachomatis C. psittaci C. pneumoniae

4. Diseases Chlamydia trachomatis infections eye (conjunctivitis, trachoma) respiratory (pneumonia) genital tract (urethritis, lymphogranuloma venereum) Infection with C. trachomatis is also associated with Reiter’s syndrome, an autoimmune disease Chlamydia pneumoniae atypical pneumonia. Chlamydia psittaci Psittacosis -Parrot Fever flu-like, include chest pain, shortness of breath, and sensitivity to light.

5. C. trachomatis  C. trachomatis is found only in humans. This species causes the following diseases: 1. Trachoma, a chronic follicular keratoconjunctivitis. 2. Inclusion conjunctivitis in newborn children and swimming-pool conjunctivitis. 3. Nonspecific urogenital infections in both men and women (urethritis, cervicitis, salpingitis, etc.). 4. Lymphogranuloma venereum, a venereal disease observed mainly in countries with warm climates.

6. Chlamydiae of Medical Importance

7. Important Properties Obligate intracellular bacterium; can grow only inside host cells. lack ATP, biosynthetic pathways They have a rigid cell wall but do not have a typical peptidoglycan layer. Their cell walls resemble those of gram-negative bacteria but lack muramic acid

8. Life cycle of Chlamydia All chlamydiae share a common and unique biphasic developmental cycle. Th e environmentally stable infectious particle is a small cell called the elementary body (EB) The extracellular, inert elementary body enters an epithelial cell EB is reorganized into a larger metabolically active reticulate body (Initial bodies) A reticulate body divides many times by binary fission The daughter reticulate bodies change into elementary bodies and are released from the epithelial cell. The cytoplasmic inclusion body, which is characteristic of chlamydial infections, consists of many daughter reticulate and elementary bodies.

9. Life cycle of Chlamydi a

10. cytoplasmic inclusion body of C. trachomatis

11. Transmission & Epidemiology Reservoir—human genital tract and eyes C. trachomatis infects only humans and is usually transmitted by close personal contact (e.g., sexually or by passage through the birth canal). In trachoma, C. trachomatis is transmitted by finger-to-eye or fomite-to- eye contact. C. pneumoniae infects only humans and is transmitted from person to person by aerosol. C. psittaci infects birds (e.g., parrots, pigeons, and poultry, and many mammals). Humans are infected by inhalation of dust (from bird excrements) containing the pathogens, more rarely by inhalation of infectious aerosols Patients with a sexually transmitted disease are coinfected with both C. trachomatis and Neisseria gonorrhoeae in approximately 10% to 30% of cases

12. Pathogenesis & Clinical Findings Chlamydiae infect primarily epithelial cells of the mucous membranes or the lungs. Rarely cause invasive, disseminated infections. C. psittaci infects the lungs primarily. The infection may be asymptomatic (detected only by a rising antibody titer) or may produce high fever and pneumonia. C. pneumoniae causes upper and lower respiratory tract infections, especially bronchitis and pneumonia, in young adults.

13. Pathogenesis & Clinical Findings C. trachomatis exists in more than 15 immunotypes (A–L). Types A, B, and C cause trachoma, a chronic conjunctivitis endemic in Africa and Asia. Trachoma may recur over many years and may lead to blindness but causes no systemic illness. Types D–K cause genital tract infections, which are occasionally transmitted to the eyes or the respiratory tract. In men, it is a common cause of nongonococcal urethritis. In women, cervicitis develops and may progress to salpingitis and pelvic inflammatory disease

14. Pathogenesis & Clinical Findings Infants born to infected mothers often develop mucopurulent conjunctivitis Chlamydial conjunctivitis also occurs in adults as a result of the transfer of organisms from the genitals to the eye. Patients with genital tract infections caused by C. trachomatis have a high incidence of Reiter’s syndrome, which is characterized by urethritis, arthritis, and uveitis C. trachomatis L1–L3 immunotypes cause lymphogranuloma venereum, a sexually transmitted disease with lesions on genitalia and in lymph nodes

15. Laboratory Diagnosis Chlamydiae form cytoplasmic inclusions, which can be seen with special stains (e.g., Giemsa stain) or by immunofluorescence In exudates, the organism can be identified within epithelial cells by fluorescent-antibody staining or hybridization with a DNA probe. Chlamydial antigens can also be detected in exudates or urine by enzyme-linked immunosorbent assay (ELISA) In culture, C. trachomatis forms inclusions containing glycogen, whereas C. psittaci and C. pneumoniae form inclusions that do not contain glycogen. The glycogen-filled inclusions are visualized by staining with iodine

16. Treatment susceptible to tetracyclines, such as doxycycline macrolides, such as erythromycin and azithromycin. The drug of choice for C. trachomatis is azithromycin. The drug of choice for neonatal inclusion conjunctivitis and pneumonia is oral erythromycin. The drug of choice for C. psittaci and C. pneumoniae infections and for lymphogranuloma venereum is a tetracycline, such as doxycycline.

17. Prevention There is no vaccine against any chlamydial disease Oral erythromycin given to newborn infants of infected mothers can prevent inclusion conjunctivitis and pneumonitis caused by C. trachomatis.

18. Your patient is a 20-year-old man with a urethral discharge. Gram stain of the pus reveals many neutrophils but no bacteria. You suspect this infection may be caused by Chlamydia trachomatis. Which one of the following is the laboratory result that best supports your clinical diagnosis? (A) Gram stain of the pus reveals small gram-positive rods. (B) The organism produces beta-hemolytic colonies on blood agar plates when incubated aerobically. (C) The organism produces alpha-hemolytic colonies on blood agar plates when incubated anaerobically. (D) Fluorescent-antibody staining of cytoplasmic inclusions in epithelial cells in the exudate (E) Fourfold or greater rise in antibody titer against C. trachomatis

19. Regarding chlamydiae, which one of the following is the most accurate? (A) Lifelong immunity usually follows an episode of disease caused by these organisms. (B) The reservoir host for the three species of chlamydiae that cause human infection is humans. (C) Their life cycle consists of elementary bodies outside of cells and reticulate bodies within cells. (D) They can only replicate within cells because they lack the ribosomes to synthesize their proteins

20. Rickettsiae Rickettsiae are obligate intracellular bacteria;. They are the agents of typhus, spotted fevers, and Q fever.

21. Diseases  Rocky Mountain spotted fever, caused by Rickettsia rickettsii,  Q fever, caused by Coxiella burnetii.  Epidemic typhus, caused by Rickettsia prowazeki  Other rickettsial diseases such as endemic and scrub typhus occur primarily in developing countries

22. Important Properties Very short rods that are non flagellated, non-motile, non-spore forming, highly pleomorphic bacteria. Structurally, their cell wall resembles that of gram-negative rods, but they stain poorly with the standard Gram stain. Rickettsiae are obligate intracellular parasites Rickettsiae divide by binary fission within the host cell

23. Transmission 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. burnetii, 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.

24. Selected Rickettsial Diseases

25. Pathogenesis Localized in the vascular endothelial cells and multiply to cause thrombosis lead to rupture & necrosis. The typical lesion caused by the rickettsiae is a vasculitis Damage to the vessels of the skin results in the characteristic rash and in edema and hemorrhage caused by increased capillary permeability.

26. Clinical Findings & Epidemiology 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 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 tick is an important reservoir of R. rickettsii as well as the vector;

27. Clinical Findings & Epidemiology Q fever is the one rickettsial disease that is not transmitted to humans by the bite of an arthropod. The important reservoirs for human infection are cattle, sheep, and goats. The agent, C. burnetii, which causes an inapparent infection in these reservoir hosts, is found in high concentrations in the urine, feces, placental tissue, and amniotic fluid of the animals. It is transmitted to humans by inhalation of aerosols of these materials.

28. EPIDEMIC TYPHUS (CLASSICAL TYPHUS) Cause: Rickettsia prowazekii Vector: Human body louse and Human head louse Incubation period – 5-21 days Mortality rate is 20-30% in untreated cases.

29. Laboratory Diagnosis 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 A fourfold or greater rise in titer between the acute and convalescent serum samples is the most common way the laboratory diagnosis is made

30. Treatment The treatment of choice for all rickettsial diseases is tetracycline, with chloramphenicol as the second choice.

31. Prevention Vector control Live vaccine & killed vaccine are available but not much effective