Chamydiae/Rickettsiae/Anaplasmacetaceae: Obligate Intracellular Pathogens

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Robert Carpenter
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1 Chamydiae/Rickettsiae/Anaplasmacetaceae: Obligate Intracellular Pathogens These groups are degenerate highly specialized Gramnegative bacteria with very small genomes. Due to loss of essential biosynthetic capacities, they can grow only within mammalian cells and cannot be cultured on artificial media. Chlamydia generally cause infections of epithelial tissues and are transmitted by sexual contact or via aerosols. Rickettsiae colonize endothelia of the circulatory system, and depend on arthropod vectors for transmission. Erlichia and Anaplasma species are transmitted by ticks and colonize leukocytes.

2 Chlamydial Diseases Chlamydial diseases are generally diseases of epithelial tissue. C. pneumoniae pharyngitis, bronchitis, and atypical pneumonia. C. trachomatis most common sexually transmitted pathogen in the U.S. and causes urogenital tract infections of varying severity. infection of the epithelium of the eye and eye lids called trachoma. Rare in US. Transmission by flies attracted to ocular secretions. C. psittici transmitted to man as an aerosol generated by infected birds (usually psittacine birds (budgerigars, parrots, cockatiels) or domestic fowl, especially turkeys.

3 Life Cycle of Chlamydia and the generation of hardy, spore-like elementary bodies (EBs). Chlamydiae, but not Rickettsiae or Anaplasmacetacae, produce spore-like elementary bodies resistant to desication and are infectious. metabolically inactive must undergo transformation into a metabolically active form during infection

4 The Chlamydia Life Cycle

5 Chlamydia Invasion and Establishment

6 Maturing Inclusion: C. psittici and C. trachomatis

7 Inability to culture in a cell-free system has limited progress of investigation From: J. Cocchioro and R. Valdivia Cell Microbiol 11:

8 Inability to culture in a cell-free system has limited progress of investigation Chlamydia can be readily grown in the laboratory only within cultured mammalian cells This limits experimentation, and genetic manipulation in particular. Progress is slow.

9 An Advanced Case of Trachoma

10 Pelvic Inflammatory Disease Clinical syndrome associated with ascending spread of microorganisms from the vagina or cervix to the endometrium, fallopian tubes, ovaries, and contiguous structures. Comprises a spectrum of inflammatory disorders including any combination of endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis.

11 Pelvic Inflammatory Disease Most cases of PID are polymicrobial Most common pathogens: N. gonorrhoeae: recovered from cervix in 30%-80% of women with PID C. trachomatis: recovered from cervix in 20%-40% of women with PID N. gonorrhoeae and C. trachomatis are present in combination in approximately 25%-75% of patients

12 Normal Fallopian Tube Epothelium Patton, D.L. University of Washington

13 Fallopian Tube Epothelium Infected with C. trchomatis Patton, D.L. University of Washington

14 Pelvic Inflammatory Disease: Sequelae Approximately 25% of women with a single episode of PID will experience sequelae ectopic pregnancy infertility chronic pelvic pain Tubal infertility occurs in 50% of women after three episodes of PID

15 Q Fever Coxiella burnetii 50% of infected become symptomatic High fever ( C), severe headache, malaise, myalgia, confusion, sore throat, chills, sweats, cough, nausea, vomiting, diarrhea, abdominal pain, chest pain. Fever last 1-2 weeks. Weight loss is common. Recovery my require several months. 1-2% mortality. Chronic Q fever my develop as long as 20 years after initial infection. Endocarditis is a common complication. Mortality ~ 65%.

16 Coxiella burnetii Very like chlamydiae Highly infectious spore-like EB readily spread via aerosol. Reaches very high concentrations in placental tissue of animals. Human infection infection often associated with birth of livestock or pets. Has been used a a component of biological weapons intended to incapacitate rather then kill.

19 Severe Manifestations of Tick-borne Rickestsial Diseases (TBRD) Prolonged fever Renal failure Disseminated intravascular coagulopathy (DIC) Hemophagocytic syndrome Meningoencephalitis Acute respiratory distress syndrome (not HGA). RMSF is frequently severe (mortality 20% untreated and 5% treated)

21 In mid-august 2003, a male child aged 14 months was taken to a community health clinic in Arizona after 1 day of fever F (39.8 C). On physical examination, the child had a maculopapular rash that involved his palms and soles. On auscultation, abnormal breath sounds were detected in the right lower lung. The parent stated that they had not traveled out of the local area recently. No one else in the family was ill, and the child was up-to-date on vaccinations. Chest radiographic evaluation revealed a possible right lower lobe infiltrate. On the basis of clinical and radiographic findings, pneumonia and roseola infantum were diagnosed. The child was administered an intramuscular injection of ceftriaxone and sent home with a prescription for oral amoxicillin/clavulanate.

22 The next day, the child was taken back to the clinic with vomiting and rash that was petechial. His fever was F (41 C). He was admitted to the hospital, and antibiotic treatment for pneumonia was continued. On day 3 of hospitalization, the child developed DIC. Remarkable laboratory findings included: WBC count, 16.2 x 109 cells/l (normal: x 109 cells/l); platelet count, 46 x 109 platelets/l (normal: x 109 cells/l); aspartate aminotransferase (AST), 291 U/L (normal: U/L); and alanine aminotransferase (ALT), 99 U/L (normal: U/L). The child s condition worsened, and 7 days after the onset of illness, he died of pulmonary hemorrhage.

23 A serum sample collected 5 days before the child s death tested negative by IFA for IgM and IgG antibodies reactive with R. rickettsii. However, R. rickettsii DNA was detected in serum by PCR assay.

24 Growth Cycle of Rickettsiae in Endothelial Cells

25 Leaking and Occluded Arteriole in RMSF

29 Long-term health effects of severe RMSF Partial paralysis of lower extremities Gangrene requiring amputation of fingers, toes, arms, or legs Hearing loss Blindness Loss of bowel or bladder control Movement disorders Speech disorders

30 Risk factors associated with severe RMSF Partial paralysis of lower extremities Advanced age Male gender Black race Chronic alcohol abuse Glucose-6-phosphatedehydrogenase (G6PD) deficiency

31 Variable Frequency of RMSF

34 Tropsims R. rickettsii infects endothelial cells, causing vasculitis, which leads to rash and life-threatening damage to the brain, lungs, and other viscera. R. rickettsii is not evident in blood smears, and doesn t stain with the majority of conventional stains. Ehrlichia and Anaplasma species infect monocytes or granulocytes, respectively, and cytoplasmic vesicles containing the bacteria (morulae) might occasionally be observed on peripheral blood smears by using routine stains.

37 Diagnosis of TBRD is difficult Early symptoms are not specific Fever Headache Myalgia Malaise Clinical signs and symptoms Thorough history Laboratory diagnostic tests (rarely definitive in early disease)

38 Diseases Associations of Selected Rickettsiae and Related Organisms

Pelvic Inflammatory Disease (PID) Max Brinsmead PhD FRANZCOG July 2011

Pelvic Inflammatory Disease (PID) Max Brinsmead PhD FRANZCOG July 2011 This talk What is Pelvic Inflammatory Disease? Why it is important How it is spread Diagnosis Treatment Prevention What is PID? Inflammation