Chapter 20

• Rickettsia


  A genus or collective term for a group of vector-borne intracellular parasites
• Chlamydia


  Nonmotile, coccoid, Gram negative atypical bacteria that are obligate intracellular parasites with a unique developmental cycle

  
• Mycoplasma


  The smallest organisms that can be free-living, have no cell walls, are highly pleomorphic, and can reproduce in cell-free media
• Rickettsia, Chlamydia, and Mycoplasma are all atypical Gram-negative organisms because they don't Gram stain
• Rickettsia species

  • Rickettsia prowazekii - epidemic typhus
  • Rickettsia typhi - endemic typhus
  • Rickettsia rickettsii - Rocky Mountain spotted fever
  • Bartonella quintana - trench fever
  • Coxiella burnetii - Q fever

  
• Rickettsia


  • Rod-shaped, coccoid or pleomorphic
  • No flagella, typical Gram-negative cell wall
  • Very small, 0.3 to 0.5 by 0.8 to 2.0 µm
  • Do not stain well with Gram's stain, can use Giemsa & acridine orange
  • Either parasitic or mutualistic
  • Parasitic form depend on entry, growth, and replication within the cytoplasm of living eukaryotic host cells (typically endothelial cells) (obligate intracellular pathogen)
  • Can be classified into several groups, with the typus and spotted fever group being the most common

  
• Rickettsia metabolism and lifecycle

  • Have a very small genome 1.11 Mb and only 834 genes
  • Lack glycolytic pathway, do not use glucose as energy source, instead oxidize glutamate and TCA cycle intermediates
  • Take up and use ATP and other materials from host cell through carrier-mediated transport systems in plasma membrane
• Rickettsia

  • The typhus and spotted fever group contains LPS and surface proteins (OmpA/B – inherence to host and humoral response)
  • Most rickettsiae survive only for short periods of time outside of the vector or host
  • They are quickly destroyed by heat, drying, bactericidal chemicals
  • Dried feces of infected lice may contain infectious R. prowazekii for months at room temperature
  • Coxiella burnetii may survive pasteurisation and can survive for months in dried feces or milk, may be due to the formation of endospore-like structures

  
• Endemic


  A disease outbreak that is consistently present but limited to a particular region, making the disease spread and rates predictable
• Epidemic

  An unexpected increase in the number of disease cases in a specific geographical area
• Rickettsial infections - Typhus

  • General symptoms are fever, headache, malaise/prostration, skin rash and hepatomegaly (enlarged lived) splenomegaly (enlarged spleen)
  • Typhus group infections are characterised by a rash which starts centrally and spreads out
  • Typhus group organisms usually found in the cytoplasm of host

  
• Rickettsial infections - Epidemic Typhus


  • Transmitted by the body louse in the human-louse cycle
  • Fatality rate during epidemics = 6 – 30% (higher mortality in older people)
  • Systemic infection and prostration are severe
  • Fever lasts for about 2 weeks
  • Also called Camp/jail fever

  
• Rickettsial infections - Endemic Typhus


  • Flea-borne disease, primarily the fleas of rodents
  • Acute febrile illness, however, generally milder than epidemic typhus
  • Person can become infected when they scratch a louse bite and dried feces of infected lice enters the wound
  • Rarely fatal except in the elderly (disseminated multisystemic disease)
• Rickettsial infections - Spotted Fever Group


  • Resembles typhus clinically but rash appears first on extremities (hands and ankles) before spreading to trunk as well as the palms and soles (diagnostic feature)
  • Patients may also experience fever, nausea, vomiting, loss of appetite and conjunctival infection
  • Usually found in the nucleus of the host
  • Severity of illness depends on the strain involved, e.g. RMSF has fatality as high as 50% in elderly

  
• Rickettsial infection - Q fever

  • Causative agent is Coxiella burnetii, an obligate Gram negative organism
  • Found in ticks and transmitted to animals such as goats, sheep, and cattle (transmission to humans via ticks is rare)
  • Disease resembles influenza, nonbacterial pneumonia, encephalopathy, rather than typhus
  • Transmission involves inhalation of dust contaminated with dried feces, urine, milk

  
• Rickettsia species do not grow in artificial nutrient culture, they must be grown in either tissue/embryo cultures

  
• Additional features to consider for diagnosis of rickettsial diseases: history of tick bites/exposure, recent travel to endemic areas, similar illness in family/co-workers/pets

  
• Diagnosis of rickettsial diseases can be done through serology (immunohistochemical) or PCR

  
• The majority of pathogenic Rickettsia bacteria are susceptible to antibiotics of the tetracycline group
• Chlamydia


  • Nonmotile, coccoid, Gram negative atypical bacteria
  • Have very small genomes
  • Obligate intracellular parasite with unique developmental cycle
  • Metabolically appear to be energy parasites, obtaining ATP from host
• Chlamydia developmental cycle


  1. Elementary bodies have high affinity for host epithelial cell and rapidly enter them through endocytosis and form an entry vacuole

  2. Shortly after entry the elementary body is re-organised into a reticulate body (non infectious)

  3. Reticulate body grows and divides into elementary bodies

  4. Elementary bodies are released by cell lysis and cell starts again

  5. Cycle takes 24-48 hours

  
• Chlamydia trachomatis serotypes

  • A-C - Trachoma
  • D-K - Genital infections, infant conjunctivitis and pneumonia
  • L1-L3 - Lymphogranuloma venereum (STI)

  
• Chlamydia trachomatis - Trachoma

  • Leading cause of infectious blindness worldwide, highly contagious transmitted by direct contact, clothing and insects
  • Chronic keratoconjunctivitis (dry eye disease) leading to scarring and blindness
• Chlamydia trachomatis - Genital Infection (STI)

  • Globally chlamydia is one of the top two STIs in many countries
  • In men it causes urethritis and prostatisis, and in woman results in cervicitis and PID
  • Can also cause pneumonia and conjunctivitis in infants acquired during birth, might be most common cause of neonatal pneumonia
• Chlamydia trachomatis - Lymphogranuloma venereum

  • STD characterised by suppurative inguinal adenitis (inflammation of the lymph nodes – groin)
  • Small papule or vesicle develop on any part of the external genitalia, may or may not ulcerate and heals in a few days
  • Regional lymph nodes enlarge and are painful
• Other Chlamydia species


  • Chlamydophila psittaci infects humans and many other animals, causes psittacosis (parrot fever) in humans, zoonotic infection from birds
  • Chlamydophila pneumoniae is a common cause of human pneumonia, atypical pneumoniae
• Mycoplasma

  • Smallest organisms that can be free-living, have no cell walls, are highly pleomorphic, and can reproduce in cell-free media
  • Completely resistant to penicillin (no cell wall)
  • They can reproduce in cell-free media, on agar, the center of the colony is inverted, forming a characteristic "fried egg" form on agar
  • Growth is inhibited by specific antibodies
  • They have an affinity for mammalian cell membranes – they are a major contaminant in labs which work with mammalian cell cultures and very difficult to get rid of

  
• Mycoplasma pneumoniae


  • Important cause of pneumonia especially in persons 5-20 years old (colleges, military barracks and prisons)
  • Walking-pneumonia (atypical pneumonia – doesn't look like normal pneumococcal pneumonia)
  • Attaches to the respiratory epithelium and causes local tissue destruction
  • Unique virulence factor – CARDS toxin (community-acquired respiratory distress syndrome); aids in colonization, leading to inflammation and tissue destruction
  • Transmitted by respiratory droplets