Lecture #16 Bio3124

1. Lecture #16Bio3124 Medical Microbiology Part II: genitourinary, CNS, cardiovascular & systemic infections

2. Genitourinary tract infections • Genital (STI) and urinary tract infections (UTI) • UTI:Infection of kidneys, ureters, bladder, urethra • Normally sterile except for 1/3 distal urethra • UTI by uropathogenicE. coli (UPEC), 75% of UTI • STI:Sexually transmitted infections, infection of genitalia by sexual contact • Bacterial: Syphilis, Chlamydia, bacterial Vaginosis, Gonorrhea • Viral:HIV SARS, Genital Herpes

3. Urinary Tract Infections Many gram-negative bacteria grow in urine • Uropathogenic E. coli (UPEC), Klebsiella, Pseudomonas, Enterobacter • P-type pili (type I) adhere to cells expressing P-blood group antigen • Expressors more susceptible to recurrence • May grow in reservoir protected by biofilm • “Bladder pods” • High bacterial concentration on cell surface • Hide under uroplakin extracellular matrix • prevents antibiotic penetration

4. Urinary Tract Infections Signs and symptoms: frequent urination, dysuria (painful urination), back pain • Diagnosis: positive detection of UPEC in urine, detection of leukocytes, proteins in urine • Treatment: noting resistance, antibiotics of choice single or combination, • Trimethoprim-sulfamethoxazole • fluoroquinolones eg ciprofluxacin • Amoxicillin

5. Sexually Transmitted Infections • major worldwide public health problem • US: 19 million new cases yearly, ages 15-30 • Risk factors: Multiple partner sexual relationship, needle sharing among drug users • some also transmitted by nonsexual means eg. Obstetric infections, syringes • some cured easily, others difficult or impossible to cure

6. Bacterial Vaginosis • caused by Gardnerellavaginalis (gram variable, pleomorphic bacterium) • mild infection • risk factor for obstetric infections, adverse effect on pregnancy, pelvic inflammatory disease (PID) • Signs and Symptoms: lots of frothy, fishy smelling vaginal secretions, pain and itching • diagnosis • Observing signs and symptoms, and microscopic observation of clue cells in discharge • Clue cells: vaginal epithelial cells covered with bacteria • treatment, prevention, and control • antibiotic therapy, including drugs to kill anaerobes eg. Metronidazole (MetroGel Vaginal)

7. Gonorrhea • caused by Neisseria gonorrhoeae • gram-negative, oxidase-positive diplococcus • referred to as gonococcus, (pl. gonococci) • attaches to microvilli and then phagocytosed by mucosal cells • disease of mucous membranes of the genitourinary tract, eye, rectum and throat • mother to child transmission at birth, casues • ophthalmia neonatorum (conjunctivitis of the newborn) • clinical manifestations • symptoms in males (2-8 days post infection) • urethral discharge of yellow, creamy pus, and painful, burning urination • symptoms in females • vaginal discharge beginning 7 to 21 days after infection

8. Gonorrhea… • pelvic inflammatory disease (PID): infection of fallopian tubes and surrounding tissue • major cause of sterility and ectopic pregnancies • diagnosis • culture of bacterium followed by gram stain, oxidase test, and determination of cell and colony morphology; DNA probe test • treatment, prevention, and control • antibiotic therapy: new fluoroquinolones • penicillin resistance common • public education, diagnosis and treatment of asymptomatic individuals, condom use, and quick diagnosis and treatment of infected individuals

9. Genital Herpes • Herpes simplex type 2, linear dsDNA, enveloped virus • enters the external genitalia, urethra, cervix, rectal and pharyngeal epithelial cells by sexual contact • break in the tissue • Frequent STI in US, almost 20% of adult population • Upon entry, viral DNA replicates in nucleus • Incubation: 7 days • Active phase: virus replicates explosively, degrades host DNA • Cells die and typical Herpes blisters form around genitalia • Blisters: due to cell lysis and host inflammatory response

10. Genital herpes… • clinical manifestations • fever, burning sensation, genital soreness, and blisters in infected area • blisters heal spontaneously, but virus remains latent and is periodically reactivated • can be treated with antiviral drugs (e.g., acyclovir)

11. Infections of central nervous system • Infection of brain and spinal cord • Must traverse brain blood barrier • Bacterial infections • Meningitis • Botulism and Tetanus • Viral infections • Poliomyelitis • Rabies • Prion diseases

12. Meningitis • Inflammation of brain and spinal cord meninges (membranes) • Two types: • Septic: caused by many different bacteria • S. pneumonia, H. influenza, N. meningitis, L. monocytogenes, S. aureus, S. epidermidis etc. • Aseptic: also called meningitis syndrome, caused by agents other than bacteria • eg. Viruses, fungi, protozoa • identification etiological agent required for proper treatment • Septic meningitis, sever symptoms, responds to antibiotics • Aseptic syndrome, milder, difficult to treat

13. Bacterial (septic) Meningitis • Associated with • S. pneumonia, H. influenza, N. meningitis • Neisseria meningitis (Meningococcus), a gram negative bacterium, is normal inhabitant of nasopharynx • Serotype A is associated with epidemics • transmitted in respiratory secretions • Colonize nasopharyngeal epithelia • Cross the epithelium by endocytosis, enter blood (meningococcemia) • Proliferate and cross to cerebrospinal fluid (CSF) leading to meningitis • clinical manifestations • initial respiratory illness or sore throat • vomiting, headache, lethargy, confusion, stiffness in neck and back • If not treated can kill the patient

14. Meningitis… • Diagnosis: • Isolation of bacteria from CSF • identification by rapid tests • Symptoms and signs • treatment, prevention, and control • antibiotic therapy: immediate administration of penicillin, chloramphenicol, cefotaxime, ceftriaxone, ofloxacin • Prophylactic administration to patient contacts • Control: vaccination using meningococcal polysaccharide vaccine (MCPV4), ages 2-10 and adults over 55 who are at risk

15. Botulism • Clostridium botulinum, obligate anerobic, endospore-forming, gram-positive rod • Source: insufficiently heated home-canned food • endospores not killed, germinate, produce toxin • inadequately cooked food, toxin remains and causes disease • botulinum toxin • neurotoxin that binds to synapses of motor neurons • Prevents neurotransmitter (Ach) release, flaccid paralysis • diagnosis • demonstration of toxin in patient’s serum, stools or vomitus or C.botulinum in stool cultures • infantile botulism • endospores ingested, germinate, reproduce, and produce exotoxin Signs/symptoms:constipation, general weakness, and poor appetite; death may result from respiratory failure • treatment, prevention and control • symptomatic/supportive therapy and administration of antitoxin • safe food processing practices and not feeding honey to babies under one year of age

16. Botulinum toxin SNAP-25 Synaptobrevin Syntaxin • H(heavy chain 100 kD, ligand), L(light chain 50 kD protease) • H binds presynaptic memb, internalize HL by endocytosis • L moves out of endocytic vesicles , • cleaves proteins involved in cholinergic vesicle-axon membrane fusion ie synaptobrevin and/or SNAP-25 • no acetylcholine released, flaccid paralysis, death in 12-72 hrs

17. Animation: Botulinum toxin

18. Tetanus toxin • Mechanism of tetanus toxin similar to botulinum • different -> cause spastic instead of flaccid paralysis • delivery of toxin to inhibitory neurons • GABA not produced • Excitatory signal overwhelms • muscles go to extreme spasm

19. Animation: tetanus toxin

20. Poliomyelitis • polio (infantile paralysis) • caused by poliovirus • plus strand RNA, naked virus of Picornaviridae • very stable in food and water • multiplies in throat and intestinal mucosa • Transmission: contaminated food and water sources • Upon entry infects tonsils, lymph nodes and intestine • Sometimes transiently enters blood (viremia) • clinical manifestations • usually asymptomatic or brief, mild illness • fever, headache, sore throat, vomiting, loss of appetite • viremia sometimes occurs • usually transient; no clinical disease • sometimes persists and virus enters central nervous system causing paralytic polio • prevented by immunization with live vaccine and killed vaccine • likely to be the next human disease to be completely eradicated

21. Systemic infections Septicemic infections that disseminate to other organs • Lyme disease (Borreliaburgdorfery) • Plague (Yersiniapestis) • Viral infections • Hepatitis

22. Lyme Disease • LD or Lyme borreliosis • caused by Borrelia burgdorferi, B. garinii, and B. afzelii

23. Lyme disease… • transmitted from animal reservoirs by ticks • deer, field mice and woodrats • clinical manifestations vary with stage of disease

24. Stages of Lyme disease • localized stage • develops 1 week to 10 days after infection • expanding, ring-shaped, skin lesion • flu-like symptoms • disseminated stage • occurs weeks or months after infection • neurological abnormalities, heart inflammation, and arthritis • late stage • occurs years later • demyelination of neurons, behavioral changes, and symptoms resembling Alzheimer’s disease and multiple sclerosis

25. Lyme disease… • diagnosis • isolation of bacterium, PCR, and serological tests • treatment, prevention, and control • antibiotic therapy most effective in early stages, Amoxicillin • Later stages: ceftriaxone, passes through BBB • tick control and avoiding ticks

26. Cardiovascular infections • Include septicemia, endocarditis, pericarditis and atheroscelerotic infections • Bacterial endocarditis • S. mutans • Atherosclerosis • Chlamydophilapneumoniae

27. Bacterial endocarditis • Streptocccus mutans, normal oral cavity microflora, opportunist viridans pathogen • Subacute infections; acute if S. aureus • Viral endocarditis, usually asymptomaic • Septicemia following dental procedures • Prevalent among, • Patients with mitral valve prolapse • injection drug abusers • Enters blood (Bacterimia), colonizes on the mitral valve (vegetation) • Damaging valve further, • Fatal if not treated

28. Bacterial endocarditis • Diagnosis: positive blood culturing for pathogen, viridans hemolysis • Signs/Symptoms: lasting fever, cough, shortness of breath, diarrhea, abdominal pain, joint pain • Treatment: difficult due to glycocalyx • require hospitalization, intravenous high dose combination anitbiotherapy eg penicillin G & Erythromycin • Prevention: prophylatic antibiotic prior to dental visits

29. Extra slides for further study