Lecture #16 Bio3124

Download Report

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