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.