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BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 1
Introduction to Solving Clinical Cases
Steps in a Clinical Encounter
1.
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3.
4.
Patient History - Information gained by a healthcare professional by asking specific questions,
with the aim of obtaining information useful in formulating a diagnosis and providing medical
care.
Symptoms Signs -
A History may include:
 Identification and demographics: name, age, sex, height, weight
 The "chief complaint (CC)" — the major health problem or concern, and its time course.
 History of present illness (HOPI) - details about the complaints enumerated in the CC.
 History of past illness (HPI) (including major illnesses, any previous surgery/operations, any
current ongoing illness, e.g., diabetes, sickle cell)
 Review of systems(ROS) - Systematic questioning about different organ systems
 Family diseases
 Childhood diseases and immunizations
 Social history- including living arrangements, occupation, drug use (including tobacco,
alcohol, other recreational drug use), recent foreign travel and exposure to environmental
pathogens through recreational activities or pets.
 Regular medications (including those prescribed by doctors, and others obtained over the
counter or alternative medicine)
 Allergies
 Sex life, obstetric/gynecological history
 and so on as appropriate.
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 2
Physical Examination - Process by which a healthcare professional investigates the body of a
patient for signs of disease.
A physical examination usually starts with first observation of the patient and systematically
covers the patient head to extremities. It may include:
 General appearance – mobility, awareness, color, hydration, etc
 Basic biometrics – height, weight, pain
 Vital Signs – temperature, blood pressure, pulse, respiratory rate
 Organ systems – cardiovascular, lungs, breast, abdomen, genitalia, musculoskeletal, nervous,
including mental status, HEENT (head, eyes, ears, nose, throat), skin
History + Physical Examination  Presumptive Diagnosis (a working theory) and a
Differential (in our case, infectious disease, a list of specific microorganisms associated with the
presumptive diagnosis).
Presumptive + differential will guide your investigation, development of a strategy that will
allow you to eliminate (or not) the most likely candidates. Always start with the idea that this is
a “horse” and not a “zebra”.
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 3
Respiratory Tract
I. Overview
 nose to alveoli
 continuous operation is essential
 divided into 2 regions:
o upper –
o lower A. Generalizations
 Many cause local infections, some may spread systemically
 Professional invaders - normal healthy host, specific attachment mechanisms, specific
evasion tactics
 Secondary invaders - impaired host
 Most common infections seen by doctors
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 Upper - usually mild & self-limiting
 Lower - can be severe & life-threatening
 in children
 bacterial in adults
B. Clinical Syndromes
1. Upper Respiratory Tract Infections
itis = inflammation - surface infections
Exposed to 8 microbes/min or 10,000/day
Predisposing factors
 decreased humidity –
 viral infections –
 antibiotic therapy -
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 4
1. Rhinitis = cold
100% viral (see Table 18.4)
 rhinovirus and coronaviruses  115 different rhinoviruses  Other viruses (parainfluenza, enterovirus, respiratory synctial virus (RSV), etc)
 transmission  bind to and infect ciliated epithelial cells of nose
 incubation 
 diagnosed by clinical signs & symptoms (burning sensation in nose/throat, followed by
sneezing, runny nose, fatigue, malaise. Sore throat and cough generally due to post nasal
drip. No or low fever)
 treatment  control –
2. Pharyngitis (= sore throat) and tonsilitis
infected mucosa or inflammation of lymphoid tissue
70% viral – symptoms often include rhinorrhea, conjunctivitis, malaise or fatigue,
hoarseness, and low-grade fever
 rhinovirus, coronavirus, adenovirus, etc, see Table 18.5
 Cytomegalovirus (CMV) -clinically silent in URT esp. in infant/child – can spread
from blood to placenta and infect fetus; second only to Down’s as a cause of mental
retardation
 Epstein-Barr Virus (EBV) -2 peaks 1-6 years and 14-20 years (infectious
mononucleosis – fever, sore throat, petechiae on hard palate, lymphadenopathy and
splenomegaly, with anorexia and lethargy. Symptoms due to release of cytokines.
Polyclonal activation of B cells; WBC dif shows at least 10% atypical lymphocytes)
EBV infections can re-activate, see Fig. 18.6.
30% bacterial – usually no rhinorrhea, no cough, no conjunctivitis
 S. pyogenes
o age –
o onset –
o symptoms –
o complications  N. gonorrhoeae –
 C. diphtheria –.
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 5
3. Otitis media and sinusitis = ear and sinus
 ear infections are second most common infection of childhood (after colds) and most
common cause of visits to pediatricians
 50% viral
 respiratory syncytial virus (RSV), influenza, parainfluenza, rhinovirus, adenovirus
 50% bacteria - secondary invaders
 S. pneumoniae, Haemophilus influenzae, Moraxella
4. Epiglottitis
 H. influenzae type B (vaccination = Hib)
 Severe inflammation with edema  life-threatening respiratory obstruction
 Age –
 Symptoms -
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 6
2. Lower Respiratory Tract Infections
Lower RT is a sterile site, there are no normal microbiota
1. Laryngitis and tracheitis
 Viruses (symptoms – hoarseness, burning retrosternal pain)
 Parainfluenza virus – croup (dry cough and inspiratory stridor)
 RSV, Influenza virus, Adenovirus
 Bacteria
 GAS, H. influenzae, S. aureus
 C. diphtheria - life threatening, rare in U.S. due to vaccination (DaPT)
2. Whooping cough
 Org - Bordetella pertussis (GNR, ox +, obligate aerobe)
 Humans are sole reservoir
 Highly contagious
 Transmission - person - person airborne droplets
 Colonization - attach to ciliated mucosa in trachea using fimbriae & hemagglutinin also
spreads to bronchi
 Several toxic factors -affect inflammation or damage ciliated epithelium
1. pertussis toxin - A-B structure exotoxin; A unit is an ADP-ribosylase, disrupts signal
transduction in affected epithelial cell - prod massive amts mucoid secretions
2. Adenylate cyclase toxin - enters neutrophils & causes them to incr. cAMP - inhibits
chemotaxis, phagocytosis, & killing
3. Tracheal cytotoxin - kills tracheal epithelial cells
4. Endotoxin
 Incubation - 1-3 weeks
 Pathology - ciliated epithelium of trachea becomes covered w/ massive purulent exudate
 Presentation
early - runny nose, sneezing, fever, mild dry cough
week later - mucus & bact fill lower trachea, cough becomes paroxysmal - violent
coughing fits, 5-20X w/ no breath in btwn - as air rushes back in - whoop
also vomiting, epistaxis, periorbital edema, conjunctival hemorrhage
 Complications - CNS anoxia, secondary pneumonia
 Immunization - DaPT
 Rate of infection in unvaccinated exposed - 90-95%; Mortality - up to 14%
3. Acute bronchitis - Inflammation of the tracheal/bronchial tree assoc w/ infection
 Orgs
 Professional pathogens; Viruses (rhino-, corona-, adeno-, influenzae,) and
Mycoplasma pneumoniae
 Secondary invaders - S. pneumoniae, H. influenzae
 Presentation - cough - treatment is symptomatic - antibiotics? usually recommended
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 7
4. Influenza = the Flu
 Org - Influenzavirus types A, B, C; A - segmented RNA, 3 major HA types, 2 major NA
types; antigenic epitopes change from yr-yr (antigenic drift & shift)
 Transmission - person - person small airborne droplets
 Colonization - attaches via HA to sialic acid receptors on ciliated epithelium of
trachea/bronchi, RME
 Incubation - 1-3 days
 Pathology - impair mucociliary clearance, tracheobronchitis, bronchospasms; cytokines
released from damaged cells & WBC may symptoms
 Presentation - fever 102-104, chills, severe headache w/ retro-orbital pain, muscular
aches (esp backache), dry cough, weakness (prostration).
 Most cases resolve 1-2 wks
 Complications - 1º influenza pneumonia (1% of cases but 30% fatality, pregnant women
↑ risk), 2º bacterial pneumonia (H. influenzae, S. pneumonia, S. aureus, S. pyogenes)
 Epidemics are indicated by the number of unexpected deaths due to influenza, when #
exceeds 10,000-50,000 = epidemic
5. Bronchiolitis
 children less than 2
 swollen by inflammation, passage of air is restricted
 necrosis of epithelial cells lining the bronchioles
 Orgs
 75% RSV
 Respiratory Syncytial Virus - paramyxovirus (RNA), enveloped
 Most common cause of fatal bronchiolitis & pneumonia in infants (1/100
hospital) - humans only reservoir
 Transmission - resp. droplets to hands
 Colonization - nasopharynx - surface spikes are fusion proteins that fuse host cells
to cause "syncytia", then virus invades LRT by surface spread in secretions
 Incubation 4-5 days
 Immunopathology - maternal Ab in infant react w/ virus Ag, liberate histamine &
other inflammatory mediators
 Presentation - cough, rapid respiration, cyanosis
 25% other viruses
6. Pneumonia
 4,000,000 people/yr. Most common cause of infection related death in the US. 6th leading
cause of death
 wide range of microbes
 Transmission - inhalation or aspiration
 Colonization - attach to resp epithelium
 Pathology - respiratory distress from the interference of gas exchange in lungs, systemic effects
 Orgs
 children - viral or bacteria secondary to viruses
 adults - bacterial, kind depends on risk factors, age, other diseases - in hospitals GN
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 8
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Bacterial - acute onset, high fever
Typical - classic bacteria of acute, community-acquired - S. pneumoniae (25-60%),
H. influenzae (5-15%), others - S. aureus, Klebsiella, E. coli, Pseudomonas
Atypical - M. pneumoniae, Chlamydia pneumoniae, Legionella pneumophila,
Coxiella burnetii
Chest exam
 rales (abnormal crackles)
 evidence of consolidation
 chest x-ray
Viral
Transmission - inhaled or from blood
Colonization - attach specifically
Orgs
 RSV - children
 Parainfluenza virus types 1 & 2 – children; hemagglutinin & neuraminidase &
fusion proteins
 Adenovirus - 41 types; 5% of acute resp. illness
 Influenzavirus
7. Chronic Infections of the lungs
 Tuberculosis - review
 Fungi
 Aspergillus fumigatus – aspergillosis - Predisposing condition - asthma, pre-existing
lung cavities, chronic pulmonary disorders - fungal ball aspergilloma doesn’t invade
but in immunosuppressed - invade lungs to produce disseminated disease
 Histoplasma capsulatum - histoplasmosis
 Coccidiodes immitis - San Joaquin Valley Fever
 Blastomyces dermititidis - blastomycosis
 Pneumocystis jiroveci (formerally P. carinii) - pneumocystis pneumonia
8. Cystic fibrosis
 very viscous bronchiol secretions leads to fluid stasis in the lungs & infections w/ P.
aeruginosa (S. aureus, H. influenzae, B. cepacia)
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 9
Urinary Tract Infections and Sexually Transmitted Infections
I. Overview Urinary
A. General info
 Function - transport products from inside of body to outside
 Free of microbes (sterile) except where the outflow meets the skin
Urinary Tract Infections (UTI)
 Almost always bacterial
 Usually acquired as ascending infections
 Most originate from fecal microbiota - self-inoculation
 Differential lists varies depending on whether infection is acquired in the community or in
the hospital, and whether the infection is uncomplicated or complicated (e.g., persons with
abnormal UT)
Community- acquired
1. E. coli (80-90%)
2. S. saprophyticus (5-15%)
3. Proteus mirabilis
4. Klebsiella, Enterobacter, Serratia,
Pseudomonas aeruginosa
viruses - rare
Hospital-acquired
1. E. coli (40%)
2. Klebsiella, Enterobacter, Serratia,
Pseudomonas aeruginosa (25%)
3.GPC
4. Proteus mirabilis
Predisposing Factors
Anything that:
 Disrupts urine flow
 Prevents complete emptying of bladder
 Promotes microbial access
Females
Pregnancy
Intercourse
Females & males
Renal stones
Tumors
Neurological disorders
Catheters
Males
Enlarged prostate
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 10
Virulence Factors of Urinary Pathogens (examples):
E. coli – uropathogenic strains (O and K serotypes) = UPEC
 pathogenicity island
 P fimbriae (attachment)
 capsular acid polysaccharide (resist phagocytosis)
 membrane active cytotoxins
S. saprophyticus
 adherence to uroepithelium (high proportion of bladder cells w/ adherent bacteria)
 microbistatic to GP and GN
 urease
P. mirabilis
 flagella (motility)
 urease
B. Clinical Syndromes
Lower UTI
1. urethritis (urethra)
Symptoms - dysuria
2. cystitis (bladder)
Symptoms - rapid onset of dysuria; increased urgency/frequency
Urine - cloudy - pyuria (inflammation) or bacteriuria (bacteria); blood (hematuria)
3. prostatitis (prostate)
Symptoms - dysuria, increased frequency, low back pain, systemic indications (fever)
Upper UIT
1. pyelonephritis (renal parenchyma)
Symptoms - cystitis + more severe systemic indications (fever)
Complications - septicemia, loss of renal function
Collecting Urine Samples
 Voiding (Midstream clean-catch)
 Urinary catheter
 Suprapubic bladder aspiration
Laboratory Diagnosis of Urinary Tract Infections
 Read in text pages 257-259 carefully, especially pay attention to how to tell what is
significant bacteriuria
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 11
II. Genital/Reproductive
A. General info
 Only system that is significantly different in males & females
 Largely free of microbes, except for the vagina
Sexually Transmitted Infection (STI) ( = Sexually Transmitted Disease (STD) = venereal
disease (VD)
 Incidence is increasing
 Almost no vaccines
 Rampant on college campuses
 Often asymptomatic
Sexually Transmitted Diseases - Top Ten in US By Occurrence
Pathogen
1. Human Papillomavirus (HPV)
2. *Chlamydia trachomatis D-K.
C. trachomatis L1, L2, L3
3. Candida albicans
4. Trichomonas vaginalis
5. Herpes simplex virus (HSV)
6. *Neisseria gonorrhoea
7. HIV
8. *Treponema pallidum
9. *Hepatitis B virus
10. Haemophilus ducreyi
Disease
genital warts; associated w/ cervical cancer
non-specific or non-gonococcal urethritis
lymphogranuloma venereum
vaginal thrush, balanitis
vaginitis, urethritis
genital herpes
gonnorhea
AIDS
syphilis
hepatitis
chancroid
B. Clinical Syndromes
#1 Human Papilloma Virus (HPV)
 Transmission – sexually
 Entry – attach to target cell via capsid protein, enter via RME
 Incubation – 1-6 months
 Pathology – dyplasia = abnormal growth
 Symptoms – warts on penis, vulva, perianal regions (types 6 or 11) – BUT majority
asymptomatic
 Complications – high-risk HPV types 16, 18, 31, 33, and 35 are strongly associated with
cervical neoplasia
 Treatment (Txt) – asymptomatic and subclinical not treated; warts treated
 Prevention - vaccine
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 12
#2. Non-gonococcal urethritis - Chlamydia trachomatis - Obligate intracellular bacterium –
 Transmission – sexual
 Entry – abrasions
 Attachment - to receptors on host cell, parasite-induced endocytosis
 Incubation – 2-6 weeks or longer
 Pathology – cells destruction & inflammation
 Symptoms – asymptomatic infection is common, esp. in women OR urethritis
 Complications –systemic dissemination, infertility – in women also PID, ectopic pregnancy –
in infants pneumonia, trachoma.
 Treatment (Txt) – tetracycline, doxycycline, azithromycin
#3. Yeast infection or Candida vulvovaginitis - Candida albicans – yeast, part of normal
microbiota
 Transmission – normal microbiota of female vagina - disruptions to bacterial vagina
community can result in an overgrowth with yeast.
 Symptoms – UTI, intensely itchy/burning, cottage cheesy discharge
 Balanitis (inflammation of glans penis) in 10% of male partners
 Txt – antifungals like micronazole or nystatin (topical) or oral fluconazole
#4. Vaginitis - Trichomonas vaginalis - protozoa
 Transmission – sexual
 Entry – vagina in women; urethra and prostate in men
 Symptoms – vaginitis – copious, yellow/green frothy discharge, rise in vaginal pH
 Txt - metranidazole
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 13
#5. Genital herpes - Herpes simplex viruses types 1 and 2 (HSV1, HSV2)
 Transmission – sexual
 Entry - by membrane fusion
 Incubation – 3-7 days
 Pathology The herpes virus causes the membranes of host cells to
fuse together to form “giant” cells. This picture was taken
of PAP smear material and the arrow indicates a giant cell.
 Symptoms - First sign – primary genital lesion vesicles
 ulcer w/tender, swollen nodes, fever, headache,
malaise
The herpes virus travels up sensory nerve
endings to the root ganglion neurons where it
remains in a latent stage for the life of the host.
The herpes virus can not be eliminated by the
immune system or by anti-viral drugs.
Herpes infections can re-activate. Virus travels
back down the nerve fibers and causes new
lesions at the surface of the skin or mucosal
membranes. Re-activations are common and are
triggered by trauma, stress, and sun.
I it is believed that herpes infected individuals may always be somewhat infectious.
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Complications (in addition to reactivation) – aspetic meningitis or encephalitis in adults.
Neonatal disseminated herpes or encephalitis.
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Txt – acyclovir (Zovirax), famciclovir, valacyclovir (Valtrex)
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 14
#6. Gonorrhea - Neisseria gonorrhoea – 260,530 U.S. in 2009/ 14,471 cases MI
 Transmission – direct, usually sexual, person-person
If the woman has gonorrhea there is a 20% chance during each sexual encounter that she will
transmit to her male partner. If the man has gonorrhea, there is a 50-90% chance he will transmit
to his partner (female or male).
 Asymptomatically infected individuals, almost always women, form a major reservoir of
infection.
 Entry – vaginal or mucosa of penis – or other mucous membranes (pharynx, conjunctiva)
 Attachment - via common pilus (which undergoes antigenic variation), Opa proteins. Invade
non-ciliated epithelial cells
 Incubation – 2-7 days
 Pathology – see picture– what process causes the damage?
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 15
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Symptoms - First sign in
men – dysuria, purulent
discharge (shown center and
a Gram stain of shown right,
see the GNC engulfed by the
PMNs).
First sign in woman –
vaginal discharge if
symptomatic, BUT 50%
asymptomatic
Complications – similar to Chlamydia – pelvic
inflammatory disease (PID) and/or damage to the
fallopian tubes resulting in infertility in 10-20%,
disseminated infection (1-3%), opthalmia
neonatorum (neonate blindness shown at right –
this is what newborns get silver nitrate drops to
prevent, mandated in MI).
 Txt – Cefixime, Ciprofloxacin PLUS treat for Chlamydia – very often people who have
gonorrhea have Chlamydia and visa versa.
#7. Acquired Immune Deficiency Syndrome (AIDS) - Human Immunodeficiency Virus
(HIV) – globally, 2.7 million new infections in 2008
 Transmission - Sexually transmitted (but not a disease of the reproductive tracts but of the
immune cells, specifically CD4+ cells like macrophages and TH), also transmitted by blood.
 Incubation – 2 weeks to 3 months, sometimes 6 months.
 Read in text pages 275-283.
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 16
#8. Syphilis ((#3 bacterial STI in U.S.) - Treponema pallidum – 12,833 U.S. in 2009/ 231
cases MI
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Transmission – close physical contact; usually sexual, saliva, blood - 1/3 of those exposed to
the syphilis spirochete will become infected.
Entry – small abrasions
Incubation – 10-90 days, 3 weeks is average
Symptoms - First sign – chancre –
develops after 2-4 weeks apparently not painful!
Primary – the bacteria multiply in regional lymph nodes and cause swelling.
Secondary – after 3-6 weeks, the bacteria multiply and produce lesions in many sites.
Symptoms include myalgia, headache, fever, and rash (in 75-100% of cases).
2/3 are cured at this point but 1/3 develop go into a latent phase that can last 3-30 years, which
can then progress to tertiary.
Tertiary – bacteria again multiply and spread. Host cell-mediated response causes progressive
destruction of neuro-, cardio-, skin, and/or joints.
Complications – congenital syphilis (intrauterine death, congenital abnormalities)
Txt – arsenic (historical), penicillin (modern) or doxycycline for pen-sensitive patients.
If you haven’t seen the movie “Miss Evers’ Boys” you could watch this for extra credit (I know
some rental places carry it, in the “true stories” section). It is about the Tuskegee experiments on
syphilis conducted by the U.S. government. Relate presentation of syphilis in the movie with
info from Medical Microbiology.
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 17
Infections of the GI and Diarrheal Illness
Clinical Syndromes
1. Gastritis - inflammation of the stomach - pain in the upper abdomen, sometimes bleeding
2. Gastroenteritis - inflammation of stomach & intestines - primarily diarrhea, sometimes nausea,
vomiting, crampy abdominal pain
3. Colitis - intestinal syndrome that primarily involves the colon or large intestines.
4. Enterocolitis - inflammation of mucosa of both large & small intestine = dysentery - diarrhea often
contains blood & mucus.
5. Hepatitis - liver damage causes a clinical syndrome called hepatitis. Patients with hepatitis become
jaundiced because bilirubin builds up in their bodies.
Pathogens
Cause disease by 3 mechanisms:
a. action of toxins
b. adherence to & effacement of microvilli  inflammation
c. invasion of intestinal epithelial cells
A. Toxins cause disease – microbes are not present in the body
Toxin types
Action on intestine/intestinal cells
Enterotoxin
results in net secretion w/out intestinal damage
Cytoskeleton-altering toxin
alters cell shape, may injure cells but is not lethal
Cytotoxin
causes cell damage and ultimately cell death
Neural toxin
alters smooth muscle activity in intestines
1. Bacterial Food Poisoning - Intoxications NOT infections –
a. Clostridium botulinum - botulism - canned foods, spores survive 5 hrs boiling & germinate under
anaerobic conditions in can  neural toxin  gut – binds to epithelial cell and is transported across 
bloodstream  presynaptic regions (disease of CNS, symptoms begin 12-48h)
b. Staphylococcus aureus - most common – 2 different heat [100ºC for 30 min] & enz stable
enterotoxins stimulate vegus nerve (so also a neural toxin) of stomach lining  emetic response
(vomiting),w or w/o diarrhea 30 min to 8 hrs after ingestion. These toxins also function as
superantigens and stimulate T cells to over secrete IL2. 1ug of toxin is enough to induce symptoms, can
be achieved when # of Staph in food reaches 1,000/gram. Resolves within 24h.
c. Bacillus cereus - 2 distinct presentations caused by two different toxins – only one is a true
intoxication
 emetic – cereulide (an enterotoxin) targets vagus nerve (also a neural toxin)  nausea & vomiting 1-5
hrs after ingestion of toxin - lasts ~1-6 hrs. can be difficult to distinguish from S. aureus food
poisoning.
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 18
B. True infections – microbes enter and then colonize the GI - 3 mechanisms for damage
1. Pathogens colonize epithelial surfaces of small intestine (do not enter) & then release toxins
Vibrio cholera - cholera
Source Pathology
1. Ingestion of large numbers (> 108); only 0.001% survive passage through stomach
2. Flagella & mucinase allow Vibrio to reach epithelial cells
3. Attachment by way of fimbriae to receptors on brush border & crypt cells of small intestine
4. Damage due to production of toxin called cxt that is an ADP ribosyl transferase. Toxin binds to
receptors for the glycolipid GM1 ganglioside by the B subunit & A enters epithelial cells  disrupts
adenylate cyclase (cxt - enterotoxin, cytotoxin, & neural toxin)
5. Secretion of large quantities of Cl- into intestine, causing H2O & and Na+ to follow  hypersecretion
of fluids & electrolytes
Incubation –
Symptoms -
Txt -
Other pathogens that cause disease by similar mechanism:
Enterotoxigenic E. coli strains (ETEC) - traveler’s diarrhea – 2 enterotoxins – LT-1 similar to
cholera toxin. ST – activates guanylate cyclase activity  increase in cGMP  increased fluid
secretion.
B. cereus – ingested diarrheal toxin produced in the small intestine (cytotoxin targets villi  villus
necrosis)  diarrhea 8-16.5 hrs after ingestion (note, this is the other presentation for B. cereus, not the
food poisoning)
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2. Pathogens attach to and enter epithelial cells, multiply intracellularly & destroy (efface)
microvilli of epithelial cells (may release toxins), and induce diarrhea.
Shigella spp. (dysenteriae, boydii, flexneri, sonnei) – shigellosis - 14,581 U.S. / 212 MI
Source Pathology – a descending infection of the intestine – small intestine then colon
1. Ingestion - only 10-100 organisms required, 55% survive passage through stomach - most effective of
bacterial pathogens of GI
2. Secrete enterotoxins during passage through small intestine  profuse, watery diarrhea
3. Adhere specifically to epithelial cells of colon by way of outer membrane proteins (OMP)
4. Induce parasite-directed endocytosis by enterocytes and by M cells of GALT (Gut Associated
Lymphoid Tissue) that transport Shigella across intestinal epithelium
5. Phagocytized by macrophages but escape from phagolysosome into cytoplasm
6. Trigger macs to produce IL-1, also triggers apoptosis
7. IL-1 induces inflammation & stimulates edema & extravasation of neutrophils (PMNs) across
epithelial barrier.
8. Movement of PMNs across destroys the epithelial barrier & Shigella can now move across in massive
number.
9. Further induce prod. of cytokines & intense inflammation w/ destruction of epithelium  ulcerations
 blood in stool
S. flexneri and S. sonnei secrete enterotoxins (shET1 and shET2) S. dystenteriae secretes a cytotoxin
(shiga toxin, stx)
Incubation –
Symptoms Txt –
Complications -
Other pathogens that cause disease by similar mechanism:
Enterohemorrhagic E. coli (EHEC) including E. coli O157:H7 4(toxins stx1 and stx2)
Campylobacter  enteritis + diarrhea
Yersinia enterocolitis
Entamoeba histolytica  amoebic dysentery
Human diarrhoeal viruses (rotavirus, Norwalk virus) - gastroenteritis
Virus replicates in intestinal epithelial cells, damages transport mechanisms in the gut, leads to loss of
water, salt, glucose  diarrhea. Infected cells are destroyed but no inflammation, no blood. Shed at rate
of 1,000 million virus particles/g feces.
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 21
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 22
3. Pathogen attaches to, enters, & multiplies in deep tissues that are normally sterile - submucosal
or subepithelial tissues – sometimes will spread systemically.
Salmonella enteritidis, S. typhimurium  salmonellosis 44,468 U.S. / 911 MI
Salmonella typhi, paratyphi – invasive species  typhoid fever
Sources
S. enteritidis S. typhi Pathology
1. Ingestion of large numbers (105-1010); 0.001% survive passage through stomach
2. Attach specifically to fibronectin of epithelial cells of small intestine
3. Transported by M cells of GALT
4. Invade gut wall  ulcerations & hemorrhage. Also spread to intestinal lymphatics & are
phagocytized by macs but escape from phagolysosome into cytoplasm
5. Produces toxin that increase cAMP & fluid secretion  loose, watery diarrhea & nausea (enterotoxin
and cytoskeletal altering toxin)
6. Causes influx of PMN (nontyphoid species) that confines infection to GI
7. OR influx of macrophages (typhoid species) and systemic spread
S typhi organisms spread through the reticuloendothelial system, mainly to the liver, spleen, and bone
marrow. Within 14 days, the bacteria appear in the bloodstream, facilitating secondary metastatic foci
(eg, spleen, heart). In some patients, gallbladder infection leads to long-term carriage of S typhi or S
paratyphi in bile and secretion to the stool
Salmonellosis
Incubation –
Symptoms –
Txt Complications –
Other pathogens that cause disease by similar mechanism:
Hepatitis A virus - 1,849 cases U.S. / 70 MI
Reoviruses
Enteroviruses (includes poliovirus)
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 23
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 24
Nervous System = peripheral nerves + central nervous system (CNS)
I. Generalities:
A. Structure of
B. Protection of
C. How do microbes get to the central nervous system (CNS)?
**1. from the bloodstream - cross the Blood-Brain-Barrier (ex. bacterial meningitis, polio)
*2. from the peripheral nerves (ex. herpes, VZV, rabies)
3. invasion from:
bone
sinuses
middle ear
4. trauma
II. Clinical Syndromes
A. meningitis - of meninges
Characterized by high fever, headache, stiff neck (classic triad)
Pathology due to acute inflammation:
Vascular permeability  ↑WBC, ↑fluids
Fluids  swelling
Swelling  ↑pressure  headache
Inflammation affects muscles  stiff neck
Inflammation  fever
Causes:
clogging of blood vessels (DIC)  necrosis of tissue
↓ CSF flow
impaired CNS function
In bacterial meningitis, death occurs from shock & other serious complications within hours
as a result of release of peptidoglycan + endotoxins (GN) or teichoic acid (GP)
B. encephalitis - of the brain
Characterized by acute febrile illness + changes in mental state, consciousness, behavior
C. myelitis - of spinal cord
Symptoms vary depending on where damage to cord occurs
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 25
III. Infections of the Meninges
A. Bacterial meningitis
Acute - nearly always fatal
Strong correlation of microbe with age of patient – influences the top R/O:
Neonates – E. coli, Group B streptococci
1 month to 5 yrs - Haemophilus influenzae type B (Hib)
5 to 40 - Neisseria meningitidis
30 and over - Streptococcus pneumoniae
Pathogenesis
1. colonization and invasion of nasopharynx
2. nasopharynx  bloodstream  BBB to subarachnoid
3. replicate and induce inflammation in subarachnoid space  increased permeability of
BBB, cerebral edema, increased intracranial pressure, decreased cerebral blood flow.
Pathology
Subarachnoid space purulent exudates, vein distension, focal necrosis
Diagnosis
CSF examination – elevated opening pressure, very ↑neutrophils, very ↑ protein, ↓glucose
Prognosis
Serious to grave
Mortality rates
Hib
N. meningitides
S. pneumoniae
without txt = near 100%
without txt = near 100%
without txt = near 100%
All can be present in humans in an asymptomatic carrier state
with txt = 5%
with txt = 7-10%
with txt = 20-30%
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 26
1. Haemophilus influenzae type B (Hib) (1 month – 5)
GNR
Normal upper RT microbiota
Inactivate IgA using IgA protease
Colonize the nasopharynx using common pili
Penetrate submucosa (invasive) bloodstream (capsule to avoid phagocytosis)
Incubation - 5-6 days
Symptoms develop over 1-2 days
Endotoxin:
1. inflammation
2. DIC
Complications – hearing loss, delayed language development, mental retardation
Prevention – Vaccination
2. Neisseria meningitidis (5-40)
GNdC
Person-person in respiratory droplets; 20% carriers (as high as 60-80%)
Inactivate IgA using IgA protease
Colonize the nasopharynx using pili  sore throat
Endocytized  bloodstream (capsule to avoid phagocytosis)
Incubation 1-3 days
Symptoms develop over 6-24 hours
Endotoxin:
1. affects blood vessel permeability  cross BBB (attach to dura mater w/ pili)
2. drop in blood pressure  shock
3. clotting of blood  hemorrhage (rash = petichiae and purpura), also DIC
Complications – amputations, permanent hearing loss
Prevention - Vaccination
3. Streptococcus pneumoniae (30+)
GPC
Normal upper RT microbiota
sinuses or middle ear  brain
or
pneumonia in lungs  bloodstream  brain
Capsule
Teichoic acid  inflammation
Prevention - Vaccination
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 27
B. Viral meningitis = aseptic meningitis
Most common
Self-limiting, non-fatal
Many different viruses:
1. Enteroviruses - 40% (primarily Coxsackievirus and Echovirus)
2. Arboviruses
3. HIV
4. HSV-2
Several considerations affect differential:
Summer, fall + geographic clustering  Arboviruses
Late fall, winter + history of exposure to mice  LCMV
Late winter, early spring + male  mumps virus
With genital lesions  HSV-2
With atypical lymphocytes  EBV
With chickenpox or shingles  VZV
Diagnosis
CSF examination – ↑ lymphocytes, moderately ↑ protein, normal glucose
Prognosis - In adults, excellent
C. Fungal meningitis
Chronic presentation – symptoms develop over days to weeks
1. Coccidioides immitis
2. Cryptococcus neoformans - AIDS
IV. Infection of the Brain (Encephalon) – involvement of brain parenchyma
A. Viral encephalitis
Same viruses as for aseptic meningitis but relative frequency varies
1. Arboviruses (Arthropod-borne)
Ex. Equine encephalitis, (West Nile virus)
Bird
Mosquito
Bird
Horse
(human)
Epidemics, geographic clustering
Mosquito
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 28
2. HSV-1
no insect
sporadic, not epidemic
3. Enteroviruses, mumps
4. Rabies - Rhabodovirus
Bite
Multiplies at site
Travels to local nerves
Peripheral nerves  spinal cord  brain
Long incubation
Prodromal phase - flulike symptoms, tingling, burning, depression
Excitation phase - muscle function, speech, vision, anxiety, hydrophobia
Paralytic phase - muscles weaken, consciousness fades, death
Mortality - 100% with best treatment
Post exposure prophylaxis (PEP) - has never failed in US
B. Protozoan encephalitis
1. Primary amebic encephalitis - Naegleria fowleri
Mortality = 100%
2. African Sleeping Sickness - Trypanosoma
Misc.
1. Tetanus
Clostridium tetani – exotoxin tetanospasmin (mimics strychnine poisoning)
2. Botulism
Clostridium botulinum
Genes for toxin are carried on a bacteriophage
Exotoxin botulinum prevents release of acetylcholine
Produces a limp, flaccid, paralysis
Eyes  blurry, double vision
Throat  slurring speech, difficulty swallowing
Difficulty breathing
Cardiac problems
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 29
Infections of Skin and Wounds
Abscesses
 Abscess - a localized collection of pus
 Abscess formation localizes an infection and prevents spread
 Microorganisms in abscesses are difficult to treat with antimicrobial agents because:
1.microbes aren’t multiplying - many antimicrobial agents only work against actively
growing cells.
2.chemical nature of pus interferes with action of some antibiotics
3.antibiotics have difficulty reaching the site because of lack of vessel penetration
 Abscesses are a potential source of infection for other sites, can seed microbes into the
blood or lymph
I. Bacterial Infections of Skin, Soft Tissue, Muscle
All acute (24-48h)
A. By skin layer involved
1. infections of hair follicles – usually S. aureus
a. folliculitis - involves only the hair follicle - small red bump of inflammation
b. furuncles = boil – intense inflammation spreads to surrounding tissue – abscess w/localized
redness, swelling, tenderness, pain, pus - 1.5 mil/yr - S. aureus food poisoning
c. carbuncles - larger - several sites of draining pus - usually on neck or upper back - systemic
symptoms (fever)
2. Stratum corneum
Impetigo - a highly contagious pyoderma cau
exclusively in children - spread by contact
-streptococci (GAS)- almost
3. Epidermis
Ecthyma – untreated impetigo
4. Dermis
a. Erysipelas = St. Anthony’s fire – usually GAS - blockage of dermal lymphatics – welldefined edges. Pain and fever. 5% develop bacteremia with high mortality.
b. Lymphangitis – inflammation of the lining of lymphatic vessels
5. Subcutaneous fat layer
Cellulitis – usually S. aureus or S. pyogenes. Initial superficial skin trauma.
inflammation, enlarged lymph, malaise, chills, fever.
Diffuse
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 30
B. By specific strains of S. aureus or S. pyogenes
1. Scalded skin syndrome
 Caused by certain exotoxin producing strains of S. aureus infected by lysogenic phages
 Exotoxin is exfoliatin - carried in bloodstream to the epidermis where it causes a split in
deep layers - 40% of outer layers of skin are lost - loss of body fluid, high fever,
bacteremia.
 Rapid txt is necessary to prevent death.
 Txt with antibiotics - remove dead skin and tissue
 Most common in children under 2, esp. newborns.
 Also assoc. with w/late stages of STSS (60% mortality)
2. Necrotizing fasciitis - "flesh-eating strep" – GAS infected by phage - infection is secondary to
minor ski trauma
 Involves the subdermal tissues
 produces 2 toxins:
1. Pyrogenic toxin A - a superantigen, stimulates excessive IL-2 production
2. Exotoxin B - destroys tissues by breaking down protein, rate of 1 inch/hr.
 Similar clinical picture induced by Methacillin Resistant Staphylococcus aureus (MRSA)
II Viral diseases resulting in skin rashes = exanthems
Several childhood diseases are characterized by distinctive skin rashes caused by viruses that are
carried to the skin by the blood from sites of infection in the upper respiratory tract. All spread
by inhalation of respiratory droplets.
1 - Rubeola virus – measles
 High fever and rash that starts head & neck, then arms, upper trunk, back, finally legs
 Koplik's spots are diagnostic
 Extremely contagious – 90%
 Rash is caused by the reaction of Tc cells with virus-infected cells in the small vessels of
the skin.
 More than 15% of children infected with measles die of measles complications pneumonia, encephalitis - major ww killer
 In U.S. in children less than 15 months because of vaccination program
(2 – Scarlet fever – phage infected S. pyogenes – produces an erythrogenic toxin that is
distributed systemically  scarlet fever rash)
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 31
3 - Rubella virus - German measles = 3 day measles - one of the mildest of the viral diseases that
cause rashes
 Low grade fever, eye pain - rash first on face then spreads downward
 Seriousness - maternal infection in 1st trimester  serious fetal damage
4 – Scarlatina - ??
5 - Fifth Disease = Erythema infectiosum - Parvovirus B19
6 - Sixth Disease = Roseola infantum - Human Herpesvirus 6 (HHV-6)
Others un-numbered
Varicella-Zoster - chickenpox and shingles
 Chickenpox - highly contagious
 Spread by coughing, sneezing, direct contact, aerosolization
 Highest incidence in March and April
 Generally mild in 5-9 year olds, 1in 10 experience complications
 Fatal in infants, adolescents, adults, immunocompromised of any age (10-30% mortality)
due to __________________________________________
 Deaths every year in unvaccinated individuals
 Dorsal root ganglion near spine - Shingles, reactivation, over 45.
Kawasaki Disease
III. Fungal Skin Diseases - Read in your text
BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 32
IV. Infections of Wounds
A. Infections of Trauma Induced Wounds
Many type wounds result in anaerobic conditions in the tissues:
1. Dirty
2. Crushed
3. Puncture wounds (including little puncture wounds from nails, tacks, thorns, splinters)
4. Projectile (bullets, fireworks) - battlefields, especially cavalry - tetanus
EX. Gas gangrene - Clostridium perfringens and C. septicum - many trauma wounds
 Onset 12-48 hrs after injury - tissues become anoxic spores germinate  bacteria grow
& ferment carbohydrates of muscles  prod gases (carbon dioxide & hydrogen), gas
bubbles destroy tissue.
 Foul odor, high fever, shock, massive tissue destruction, blackening of the skin, rapidly
spreading
 Txt - Debridement, amputation, hyperbaric chamber - pressurized oxygen-rich
atmosphere - oxygen saturates the infected tissue, prevents growth of clostridia.
EX. Pasteurella multocida - GNR, ox +, grows on MAC. - animal bite wounds
B. Infections of Surgical Wounds
 5-12% of all surgical patients develop post-operative infections.
 Role of sutures - usually 10,000 S. aureus needed to establish infection but sutures down
to 100.
 Also IV catheters, artificial valves & joints.
 The pathogens:
S. aureus - highest single agent, about 20% all surgical wounds
BUT
Infections caused by coagulase (-) staphylococci, Enterobacteriaceae, and Pseudomonas
together cause 60% of surgical wound infections.
They are less invasive than S. aureus but more antibiotic resistant.
C. Infections of Burn Damaged Skin
 Burned areas with damaged skin are ideal sites for infection by bacteria from the
environment or normal flora. Almost any opportunistic pathogen can infect wounds but
the most serious is Pseudomonas aeruginosa - very antibiotic resistant - major cause of
death in burn patients.
 GNR, oxidase +, characteristic blue-green pigment called pyocyanin- can color tissues
green as well.
Staphylococcus aureus virulence factors
Factor
1. Leukocidin
2. Coagulase
Effect
Kills WBC by producing holes in their cytoplasmic membranes
(also kill RBC).
May impede the progress of WBC into the infected area by causing
plasma to clot in the surrounding capillaries. Also disguises staph
antigens with self material (antigenic mimicry).
Separates the layers of epidermis, aids in invasion.
3. Exfoliative toxin
(exotoxin)
4. Toxic Shock Syndrome Superantigen - stimulates TH to over produce IL-2. Causes rash,
toxin (exotoxin)
diarrhea, falling blood pressure resulting in shock
5. Protein A secreted
Binds to Fc portion of antibody so antibody can’t bind to Fc
receptors on phagocytes (anti-opsonic).
6. Capsule
Inhibits phagocytosis of nonopsonized bacteria.
7. Lipase
Breaks down lipids, aids in colonization of oily hair follicles.
8. Protease
Degrades collagenase, aids in spread.
9. Hyaluronidase
Breaks down hyaluronic acid in connective tissue, aids in spread.
10. Penicillinase
Destroys the beta-lactam ring of penicillin.
Streptococcus pyogenes virulence factors
Factor
1. Hemolysins =
streptolysins
2. Streptokinase
3. DNase
4. Hyaluronidase
5. Erythrogenic toxin
6. Proteases
7. Hyaluronic acid capsule
8. M-protein
Effect
Kill WBC by producing holes in their cytoplasmic membranes
(also kill RBC).
Converts plasminogen to plasmin, promotes lysis of fibrin clots,
aids in spread.
Breaks down the viscous DNA in pus to facilitate spread.
Breaks down hyaluronic acid (the cement that holds cells together)
in connective tissue, allows rapid spread (also eventually breaks
down their own capsule).
Produced by lysogenic strains (virus infected), responsible for rash.
Break down proteins.
Same as hyaluronate of connective tissue. Inhibits phagocytosis of
nonopsonized bacteria, also disguises strep antigens.
Interferes with phagocytosis and blocks complement action. The
major virulence factor.