Pathophysiology Of Infectious Diseases

There are a ton of infectious diseases we have to know and recognize.  While hopefully most of the following are a review of concepts learned in undergrad and medical school, there are some minutiae that I often will forget.  Some of these infectious diseases will be addressed in later articles, pertaining to the specific eye condition it may cause.  Not all infectious diseases will be discussed; only the ones where there were specific pathophysiology-related discussions listed.

Key Facts

  Infectious crystalline keratopathy.    S. viridans  is sequestered from the immune system due to its surrounding glycocalyx and biofilm production.  Image credit:  University of Iowa,  EyeRounds

Infectious crystalline keratopathy.  S. viridans is sequestered from the immune system due to its surrounding glycocalyx and biofilm production.

Image credit:  University of Iowa, EyeRounds

  • Staphylococcus bacteria:
    • Different species are differentiated by the production (or non-production) of coagulase, which induces blood clot formation.
    • Adherence of staphylococcus epidermidis to implants is caused by biofilm formation.
  • Streptococcus bacteria:
    • Different species are differentiated by the hemolysis of blood.
    • Streptococcus viridans, an α-hemolytic streptococci, is responsible for infectious crystalline keratopathy because of biofilm formation and has a surrounding glycocalyx.
  Blebitis.   H. influenzae , though waning in prevalence due to an effective vaccine based on its capsular polysaccharide antigens, remains the most common pathogen implicated in blebitis.  Image credit:  Review of Ophthalmology .

Blebitis. H. influenzae, though waning in prevalence due to an effective vaccine based on its capsular polysaccharide antigens, remains the most common pathogen implicated in blebitis.

Image credit: Review of Ophthalmology.

  • Haemophilus influenzae:
    • This bacterial infection, which has significantly decreased in prevalence in the U.S. due to the HiB vaccine, has 6 different serotypes, differentiated by capsular polysaccharide antigens.
    • It was previously the most common cause of orbital cellulitis (staph and strep species are now more common etiologic agents).
    • It is the most common cause of blebitis.
    • H. influenzae can invade the corneal stroma without epithelial breakdown.
  • Neisseria bacteria:
    • The virulence factor is based on a polysaccharide capsule.
    • Neisseria meningitidis releases an endotoxin that can cause cardiovascular collapse, shock, and disseminated intravascular coagulation (DIC).
    • Neisseria gonorrhoeae is a sexually-transmitted illness that can cause ophthalmia neonatorum and a hyperacute bacterial conjunctivitis.
    • Neisseria species can invade the corneal stroma without epithelial breakdown.
  • Pseudomonas aeruginosa:
    • Its virulence is mediated by a combination of exotoxins, endotoxins, and encapsulation.
    • It is a common cause of corneal ulcers and endophthalmitis.
    • Pseudomonas aeruginosa breaks down the corneal epithelium in order to invade the corneal stroma.
 Histopathology of syphilitic gumma. Note the area of necrotic tissue (top right) surrounded by lymphocytic inflammation (small round blue cells in the bottom left).  Image credit:  YouTube .

Histopathology of syphilitic gumma. Note the area of necrotic tissue (top right) surrounded by lymphocytic inflammation (small round blue cells in the bottom left).

Image credit: YouTube.

  • Treponema pallidum (syphilis):
    • Syphilis affects the body by causing obliterative endarteritis with perivascular infiltration of lymphocytes, monocytes, and plasma cells.
    • Gummas, which are typically considered in tertiary syphilis, have a histopathology similar to tuberculosis - granulomas with central caseating necrosis.
    • Depending on the stage of syphilis, there are multiple systemic and ocular manifestations possible.  A detailed list of these stages and their manifestations goes beyond the scope of this article.  I will post an article eventually discussing those stages.  Until then, if you have trouble remember the different manifestations, consult the BCSC or one of the many other resources available to you.
  • Borrelia burgdorferi (Lyme disease):
    • Lyme disease is the most common vectorborne infection in the United States.
    • It is typically transmitted by the Ixodes tick (white-tailed deer tick), which can also transmit babesiosis and human granulocytic ehrlichiosis.
    • At the cellular level, Lyme disease induces a perivascular lymphocytic tissue infiltration.
    • Like syphilis, Lyme disease has several stages that can cause very different systemic and ocular findings.  Discussion of these manifestations would take too much space in this already-too-long article, so for now I will have to refer you all to other resources.  Sorry!
  • Chlamydia trachomatis
    • Chlamydia is the most common sexually-transmitted infection.
    • It is a gram negative obligate intracellular parasitic bacteria (try saying that 5 times fast!).
    • On histopathology, Chlamydia forms basophilic intracytoplasmic inclusion bodies, which are called Halberstaedter-Prowasek bodies.
    • As you may recall from your microbiology classes, Chlamydia has an infectious and replicating body.  The elementary body is infectious, and the reticulate body is replicating (the vowels stick together, and r = replicating).

Sample Questions (answers at the bottom of the page)

  1. How are different species of streptococcus differentiated?

    A.  Pattern of hemolysis
    B.  Polysaccharide capsule
    C.  Presence or absence of coagulase
    D.  Biofilm formation
     
  2. How are different species of staphylococcus differentiated?

    A.  Pattern of hemolysis
    B.  Polysaccharide capsule
    C.  Presence or absence of coagulase
    D.  Biofilm formation
     
  3. What is the virulence factor of infectious crystalline keratopathy?

    A.  Biofilm formation
    B.  Endotoxin formation
    C.  Exotoxin formation
    D.  Polysaccharide capsule
     
  4. Which of the following organisms causes a granulomatous inflammation?

    A.  Haemophilus influenzae
    B.  Staphylococcus epidermidis
    C.  Streptococcus viridans
    D.  Treponema pallidum

Sample Question Answers

  1. AStreptococcus bacterial species are differentiated by hemolysis.
  2. CStaphylococcus bacterial species are differentiated by presence of coagulase.
  3. A.  Infectious crystalline keratopathy, which is caused by streptococcus viridans, occurs because the streptococcus bacteria secretes a biofilm that prevents immune cells from reaching the bacteria.  A YAG laser can disrupt the biofilm and allow the immune reaction to reach the bacteria.
  4. D.  Lyme, syphilis, Bartontella, and mycobacterial infections will all cause granulomatous inflammation.  Most bacteria trigger a normal immune reaction to bacteria (neutrophils and macrophages), without the formation of granulomas.

References and Additional Reading

  1. Basic and Clinical Science Course, Section 1:  Update on General Medicine.  American Academy of Ophthalmology, 2017-2018 edition.

Do you have any suggestions on what else might be important to know about infectious diseases?  Do you have any tips for helping to remember all of this information?  Do you have any requests for specific topics to cover?  Leave a comment or contact me!