Unusual Bacterial Diseases

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					Unusual Bacterial Diseases

           BIOL2421
       Dr. Ann M. Davis
                Lecture Outline
• Small obligate intracellular pathogens
  – Rickettsia rickettsii
  – Chlamydia trachomatis
• Spirochetes
  – Treponema pallidum pallidum
• Vibrios
  – Vibrio cholerae
         Associated Readings
• Chapter 21
Small Obligate Intracellular
       Pathogens
       Rickettsia rickettsii
Morphology and Growth Characteristics

• Gram-negative
• Very little PG
• Slime layer
• Pleomorphic
• Obligate aerobe
• Obligate intracellular
  pathogen
• Slow growth


              http://www.sciencephoto.com/images/download_lo_res.html/B220245-Rickettsia_rickettsii_bacteria-SPL.jpg?id=662200245
      R. rickettsii is Visualized Using the
          Giemsa and Gimenez Stains
             GIEMSA STAIN    GIMENEZ STAIN




Figure 21.3 (2nd Ed.)            http://pathmicro.med.sc.edu/mayer/rocky-bact.jpg
                Mode of Infection

• Natural habitats:
   – Hard ticks (Dermacentor)
   – Rodents
   – Humans
• Routes of entry:
   – Parenteral route
• Modes of transmission:
   – Biological vector



                     http://www.sciencephoto.com/images/download_lo_res.html/Z445252-SEM_of_a_dog_tick-SPL.jpg?id=904450252
    The Life Cycle of R. rickettsii
Involves Transovarian Transmission




                         http://www.utmb.edu/gsbs/microbook/ch038.htm
R. rickettsii is an Obligate
 Intracellular Pathogen




                      http://www.utmb.edu/gsbs/microbook/ch038.htm
            R. rickettsii Hijacks the Host Cell’s
                 Cytoskeleton for Motility




http://pathmicro.med.sc.edu/mayer/rick3ml.jpg
                                                     Epidemiology
        • Susceptible groups:
                – Children under 15
        • Annual occurrence:
                – United States: 250-1200 cases/year (CDC)
                – Southern U.S. has the greatest incidence
        • No vaccine available




http://www.cdc.gov/ticks/diseases/rocky_mountain_spotted_fever/statistics.html
R. rickettsii is Most Common in the
       Southern United States




                                  Figure 21.4
            Infection with R. rickettsii is Most
            Common in the Summer Months




http://www.cdc.gov/ticks/diseases/rocky_mountain_spotted_fever/statistics.html
             Children Are Most Susceptible to
              Disease Caused By R. rickettsii




http://www.cdc.gov/ticks/diseases/rocky_mountain_spotted_fever/statistics.html
   Diseases Caused by R. rickettsii
• Rocky Mountain spotted fever
  – Early signs and symptoms: Fever, severe
    headache, chills, muscle pain, nausea, vomiting
  – Widespread, spotted rash
     • R. rickettsii infects and kills cells lining the blood vessels
  – Severe complications: Encephalitis, hearing loss,
    paralysis, gangrene, multi-organ failure
• Mortality rates:
  – Untreated: 20%
  – Treated: 5%
Rocky Mountain Spotted Fever
  Causes a Widespread Rash




                           Figure 21.5
          Diagnosis of R. rickettsii

• Initial diagnosis
   – Based on signs and
     symptoms, patient
     history
   – Early diagnosis is crucial
                                  http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mmed&part=A5451&rend
• Confirmatory diagnosis                                                              ertype=figure&id=A5456



   – Latex agglutination
   – Fluorescent antibody
     stain of skin sample
   – PCR testing of skin
     sample
                                                              http://pathmicro.med.sc.edu/mayer/rocky-ifa.jpg
      Treatment and Prevention
• Treatment:
  – Antibiotics (doxycycline, tetracycline,
    chloramphenicol)
• Prevention:
  – Wear tight-fitting clothing and use insect repellent
    when walking in wooded areas
  – Check for and promptly remove ticks
  – Avoid areas known to be infested with ticks
            Proper Tick Removal Can Prevent
                  R. rickettsii Infection
        • Ticks should be removed with
          tweezers, not fingers.
        • Grasp close to skin and pull
          straight up.
                – No twisting
                – Do not squeeze or crush body
        • Disinfect hands and bite after
          removal.
        • No hot matches!

http://www.cdc.gov/ticks/tick_removal.html
                                                          Rickettsia prowazekii is Another
                                                            Important Rickettsia Species
                                                        • Causative agent of epidemic typhus
                                                          – Vector = human body louse
                                                          – High fever + rash
                                                        • Category B bioterrorism agent (CDC)
http://emergency.cdc.gov/agent/agentlist-category.asp




                                                          – Easy to spread, modest/low morbidity & mortality,
                                                            would require modifications to SOP at CDC
                                                        • Proposed as a possible ancestor for
                                                          mitochondria
Nature 396: 133.




                                                          – Genome sequence of R. prowazekii more similar
                                                            to mitochondrial DNA than to other bacteria
Small Obligate Intracellular
       Pathogens
     Chlamydia trachomatis
Morphology and Growth Characteristics


•   Gram-negative
•   No PG cell wall
•   Coccus
•   Cannot make ATP
•   Obligate intracellular
    pathogen



                http://www.sciencephoto.com/images/download_lo_res.html/C0049506-Chlamydia_infection,_SEM-SPL.jpg?id=670049506
            Mode of Infection
• Natural habitats:
  – Human mucous membranes
• Routes of entry
  – Mucous membranes
  – Conjunctiva of the eyes
• Modes of transmission
  – Direct contact
  – Indirect contact (fomites)
  – Droplet transmission
  – Mechanical vector (flies)
        Life Cycle of C. trachomatis
• Elementary body
   –   Small (0.2 – 0.4 mm)
   –   Dormant
   –   Infective
   –   Resistant
• Reticulate body
   – Larger (0.6 – 1.5 mm)
   – Replicating
   – Non-infective




                                       Figure 21.6b
                                                  Epidemiology
         • Susceptible groups:
                – Sexually active individuals (LGV)
                – Newborns (trachoma)
         • Annual incidence:
                – ~1.2 million cases reported in U.S. in 2008 (CDC)
                – ~92 million estimated cases worldwide in 1999
                  (WHO)
                – Most common STD in U.S. and worldwide
         • Experimental vaccine in Phase I clinical trials
http://www.cdc.gov/std/stats08/chlamydia.htm
http://www.who.int/vaccine_research/diseases/soa_std/en/index1.html
      Rates of Sexually Transmitted Chlamydia
          Have Been Increasing in the U.S.




http://www.cdc.gov/std/stats08/figures/1.htm
                  Sexually Transmitted Chlamydia is
                     Most Common in the South




http://www.cdc.gov/std/stats08/figures/3.htm
         Trachoma is a Major Global Health
                     Problem




http://gamapserver.who.int/mapLibrary/Files/Maps/global%20active%20may%202006.jpg
         Diseases Caused by C. trachomatis
       • Different strains of C. trachomatis cause
         distinct diseases
               – Trachoma – Strains A-C
               – Lymphogranuloma venereum (LGV) – Strains
                 LGV1-LGV3




http://pathmicro.med.sc.edu/mayer/chlamyd.htm
 Lymphogranuloma Venereum is a
   Sexually-Transmitted Disease
• 3 progressive stages of disease
  – Stage 1: Painless genital lesion
  – Stage 2: Buboes (swollen lymph nodes), fever and
    chills, muscle pain, loss of appetite
  – Stage 3: Genital sores, urethral constriction/
    inflammation, genital elephantitis
• 85% asymptomatic in women
  – Can cause PID leading to infertility
Lymphogranuloma Venereum Involves
  Swelling of Regional Lymph Nodes




                             Figure 21.7
            Trachoma Leads to Inflammation
                 and Scarring of the Eye
       • Initial infection kills cells of conjunctiva
               – Production of pus results in scarring
               – Repeated infections are common
               – Causes eyelashes to turn inward  corneal
                 scarring and blindness
       • Most common cause of infectious blindness
         worldwide



PLoS Neglected Tropical Diseases 3: e460.
          Ocular Immune Responses Are
         Dampened to Prevent Eye Damage




http://www.streilein-foundation.org/ocular_immunology.html
Trachoma Can Result in Irreversible
           Blindness




                                Figure 21.8
       Diagnosis of C. trachomatis



• Fluorescent antibody
  stain of specimen taken
  from infected site




                                     Figure 21.9
      Treatment and Prevention
• Treatment:
  – Oral antibiotics (LGV)
  – Antibiotic eye cream (trachoma)
  – Surgical correction of eyelid damage
• Prevention:
  – Sexual abstinence/monogamy
  – Condom use (?)
                               C. trachomatis Vaccine
       • Two groups working toward C. trachomatis
         vaccine
               – Merck/UTSA partnership
               – Novartis




http://www.utsa.edu/today/2009/04/merck.cfm
      Spirochetes

Treponema pallidum pallidum
                                                            Morphology and Growth Characteristics


                                                            •   Gram-negative
                                                            •   Spirochete
http://www.mansfield.ohio-state.edu/~sabedon/biol2020.htm




                                                            •   Microaerophilic
                                                            •   Axial filaments
                                                            •   Extremely difficult to
                                                                culture



                                                                              http://www.sciencephoto.com/images/download_lo_res.html/B2201601-Treponema_Pallidum-SPL.jpg?id=662201601
  Virulence Factors – External Factors
• Glycocalyx
  – Inhibits phagocytosis


• Adhesion proteins
  – Mediate attachment
    Virulence Factors – Enzymes
• Hyaluronidase
  – Breaks down protein matrix between cells




                                               Figure 14.9a
            Mode of Infection
• Natural habitat:
  – Human genital tract
• Routes of entry:
  – Mucous membranes
• Modes of transmission:
  – Direct contact (intercourse)
  – Mother-to-fetus transmission
                                                   Epidemiology
        • Susceptible groups:
                – Individuals engaging in frequent casual sex
        • Annual incidence:
                – ~46,000 cases reported in U.S. in 2008 (CDC)
                – ~12 million cases/year worldwide (WHO)
        • Active syphilis increases HIV infection and
          transmission
        • No vaccine available
http://www.cdc.gov/std/stats08/syphilis.htm
http://www.who.int/reproductivehealth/publications/rtis/9789241595858/en/index.html
Clinical Microbiology Reviews 19: 29.
Rates of T. pallidum Infection in the
    U.S. Have Been in Decline




                                  Figure 21.11a
          T. pallidum Infection is Most Common
                    in the Southern U.S.




http://www.cdc.gov/std/stats08/figures/33.htm
   Diseases Caused by T. pallidum
• Syphilis
   – Primary syphilis: Chancre (extremely contagious)
   – Secondary syphilis: Widespread rash (extremely
     contagious)
   – Latent syphilis: Signs and symptoms disappear, T. pallidum
     still present
   – Tertiary syphilis: Gummas, organ damage, heart failure,
     dementia, blindness
• Congenital syphilis occurs via transmission of T.
  pallidum across the placenta
   – Primary/secondary syphilis  fetal death
   – Latent syphilis  mental retardation, deformities
             Syphilis Lesions
                          Chancre




Secondary Syphilis Rash             Gummas




                                             Figure 21.12
         Diagnosis of T. pallidum
• Microscopy of infected
  sample
   – Must be done
     immediately
• Agglutination test of
  patient serum                                                     Figure 21.10

• Tertiary syphilis is
  extremely difficult to
  diagnose


                           http://bmtjournal.blogspot.com/2007/11/treponemal-test-tppa.html
      Treatment and Prevention
• Treatment:
  – Antibiotics (penicillin)
• Prevention
  – Sexual abstinence/monogamy
  – Condom use
  – Prophylactic antibiotics
             Syphilis in the Context of History
       • 1494 – New venereal disease appeared among French soldiers
         during a war with Naples
              – May have been imported from the Americas
              – Much more virulent
       • 1530 – Disease named “syphilis” by Girolamo Fracastoro
              – Also called “French disease”
              – Believed to be the same as gonorrhea
       •    1800’s – Efforts to regulate prostitution to control spread
       •    1905 – T. pallidum isolated
       •    1908 – Ehrlich/Hata – Salvarsan (arsenic compound)
       •    1943 – Penicillin for syphilis

http://ocp.hul.harvard.edu/contagion/syphilis.html
http://std.wustl.edu/IM/stdweb.nsf/0/0A65E02DB7948E3586257465005CCFD9/$File/Syphilis+History+and+Epidemiology.pdf
                        The Tuskegee Experiment
       • 1932 – Tuskegee Study of Untreated Syphilis in the Negro
         Male
              – Joint project of Public Health Service and Tuskegee Institute (Alabama)
              – 600 African-American men (399 infected, 201 healthy)
       • Participants told they were being treated for “bad blood”
              – Treatment for syphilis was deliberately denied/prevented for 40 years
              – No informed consent obtained
       • 1972 – News reports of the study caused public outcry
              – Led to major improvements in ethical requirements for research
              – Class action suit obtained compensation for victims and their families



http://www.brown.edu/Courses/Bio_160/Projects2000/Ethics/TUSKEGEESYPHILISSTUDY.html
http://www.cdc.gov/tuskegee/timeline.htm
                          Facebook Causes Syphilis?
         Or, The Dangers of Equating Correlation and Causation




   The Telegraph
   March 24, 2010




   The Telegraph
   March 25, 2010


http://www.telegraph.co.uk/technology/facebook/7508945/Facebook-linked-to-rise-in-syphilis.html
http://www.telegraph.co.uk/technology/facebook/7519772/Facebook-dismisses-syphilis-link.html
  Vibrios

Vibrio cholerae
                                                                  Morphology and Growth Characteristics


                                                                  •   Gram-negative
                                                                  •   Vibrio
http://pathport.vbi.vt.edu/pathinfo/pathogens/V_cholerae_2.html




                                                                  •   Facultative anaerobe
                                                                  •   Pili
                                                                  •   Single polar flagellum
                                                                  •   2 chromosomes



                                                                                  http://www.sciencephoto.com/images/download_lo_res.html/B2201544-Cholera_bacterium,_TEM-SPL.jpg?id=662201544
         Virulence Factors: External Factors
                     and Toxins
        • External factors
                – Pili – Mediate attachment


        • Toxins
                – Cholera toxin – Causes loss of electrolytes and
                  water from intestinal epithelial cells


        • Both acquired by phage transduction

Current Opinion in Microbiology 6: 35.
            Mode of Infection
• Natural habitats:
  – Fresh and salt water
  – Human gastrointestinal tract
• Routes of entry:
  – Gastrointestinal mucous membranes
• Modes of transmission:
  – Fecal-oral route
     • Waterborne
     • Foodborne
                                                   Epidemiology
       • Susceptible groups:
               – Individuals without access to clean water
       • Annual incidence:
               – 0-5 cases/year in U.S. (CDC)
               – ~190,000 reported cases and ~5000 deaths
                 worldwide in 2008 (WHO)
                       • Estimates of true case numbers: 500,000 – 700,000
       • Vaccine available but not widely used


http://www.cdc.gov/nczved/divisions/dfbmd/diseases/cholera/technical.html
http://www.who.int/wer/2009/wer8431.pdf
            Worldwide V. cholerae Infections




http://gamapserver.who.int/mapLibrary/Files/Maps/global_cholera_cases_2009.jpg
 2008-2009 Outbreak in Zimbabwe Was
   One of the Worst in Recent History




    98, 591 cases
     4,288 deaths
  Aug 2008 – Jul 2009

Weekly Epidemiological Record 84: 309.
        A Recent Outbreak Has Affected
      Large Regions of Papua New Guinea




http://gamapserver.who.int/mapLibrary/Files/Maps/PG_Cholera_20100629.png
       Central Africa Outbreak
• http://www.who.int/csr/don/2010_10_08/en/
  index.html
   Diseases Caused by V. cholerae
• Cholera
   – Watery diarrhea and vomiting
   – Fluid loss results in low blood volume, cardiac arrhythmias,
     kidney failure, death
• Two exceptionally virulent strains:
   – O1 El Tor
   – O139 Bengal
• Mortality rate
   – Untreated: Up to 60%
   – Treated: 1%
• Category B bioterrorism agent (CDC)
        Diagnosis of V. cholerae
• Typically done by characteristic signs and
  symptoms
  – Watery diarrhea with white mucus flecks
• Stool samples can be cultured to determine
  strain
  – Sample from early in disease
      Treatment and Prevention
• Treatment:
  – Fluid/electrolyte replacement
  – Antibiotics (doxycycline)


• Prevention:
  – Proper sewage treatment
  – Careful attention to hygiene
  – Sanitary food preparation techniques
  – Vaccination (?)
            A Cholera Vaccine is Available But
             Not Routinely Used in the U.S.
        • Three vaccines available:
                – Live attenuated
                – Killed whole-cell
                – Modified killed whole-cell
        • All three provide protection for minimum of 3-
          8 months following vaccination
        • Main uses:
                – Control of outbreaks
                – Travelers
http://www.who.int/topics/cholera/vaccines/current/en/index.html
                 References
• Centers for Disease Control and Prevention
  – http://www.cdc.gov
• Food and Drug Administration
  – http://fda.gov
• World Health Organization
  – http://who.int
                  References
• Rickettsia rickettsii
   – http://pathmicro.med.sc.edu/mayer/ricketsia.htm
   – Lancet Infectious Diseases 7: 724.
   – Nature 396: 133.
• Chlamydia trachomatis
   – http://www.utsa.edu/today/2009/04/merck.cfm
   – http://pathmicro.med.sc.edu/mayer/chlamyd.htm
   – PLoS Neglected Tropical Diseases 3: e460.
                 References
• Vibrio cholerae
  – http://pathport.vbi.vt.edu/pathinfo/pathogens/V_
    cholerae_2.html
  – Current Opinion in Microbiology 6: 35.
  – Weekly Epidemiological Record 84: 309.
                      References
• Treponema pallidum pallidum
   – http://www.mansfield.ohio-state.edu/~sabedon/biol2020.htm
   – http://ocp.hul.harvard.edu/contagion/syphilis.html
   – http://std.wustl.edu/IM/stdweb.nsf/0/0A65E02DB7948E35862574650
     05CCFD9/$File/Syphilis+History+and+Epidemiology.pdf
   – http://www.brown.edu/Courses/Bio_160/Projects2000/Ethics/TUSKE
     GEESYPHILISSTUDY.html
   – http://www.telegraph.co.uk/technology/facebook/7508945/Facebook
     -linked-to-rise-in-syphilis.html
   – http://www.telegraph.co.uk/technology/facebook/7519772/Facebook
     -dismisses-syphilis-link.html
   – Clinical Microbiology Reviews 19: 29.

				
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