Lecture #16 Bio3124
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Transcript Lecture #16 Bio3124
Medical Microbiology
Part II: genitourinary, CNS,
cardiovascular & systemic
infections
Lecture #16
Bio3124
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 uropathogenic E. 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
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
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
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
Bacterial Vaginosis
•
caused by Gardnerella vaginalis (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)
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
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
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
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)
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
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
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
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
Botulism
• Clostridium botulinum, obligate anerobic, endospore-forming, grampositive 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
Botulinum toxin
Synaptobrevin
SNAP-25
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
Animation: Botulinum toxin
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
Animation: tetanus toxin
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
Systemic infections
Septicemic infections that disseminate to
other organs
• Lyme disease (Borrelia burgdorfery)
• Plague (Yersinia pestis)
• Viral infections
– Hepatitis
Lyme Disease
• LD or Lyme borreliosis
• caused by Borrelia
burgdorferi,
B. garinii, and
B. afzelii
Lyme disease…
• transmitted from animal
reservoirs by ticks
– deer, field mice and woodrats
• clinical manifestations vary
with stage of disease
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
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
Cardiovascular infections
• Include septicemia, endocarditis, pericarditis and
atheroscelerotic infections
• Bacterial endocarditis
– S. mutans
• Atherosclerosis
– Chlamydophila pneumoniae
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
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
Extra slides for further study