people.cst.cmich.edupeople.cst.cmich.edu/alm1ew/MM Unit 3 Lecture notes.docx · Web viewDifferential lists varies depending on whether infection is acquired in the community or in

BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 1

Introduction to Solving Clinical Cases

Steps in a Clinical Encounter1.2.3.4.

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.

http://en.wikipedia.org/wiki/Human_sexual_behavior

http://en.wikipedia.org/wiki/Allergy

http://en.wikipedia.org/wiki/Alternative_medicine

http://en.wikipedia.org/wiki/List_of_childhood_diseases

http://en.wikipedia.org/wiki/Family_history_(medicine)

http://en.wikipedia.org/wiki/Organ_system

http://en.wikipedia.org/w/index.php?title=Review_of_systems&action=edit&redlink=1

http://en.wikipedia.org/w/index.php?title=History_of_past_illness&action=edit&redlink=1

http://en.wikipedia.org/w/index.php?title=History_of_present_illless&action=edit&redlink=1

http://en.wikipedia.org/wiki/Chief_complaint


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 à 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”.

http://en.wikipedia.org/wiki/Limb_(anatomy)

http://en.wikipedia.org/wiki/Head_(anatomy)


Normal Vital Signs Ranges for Children

Table 1: Normal Heart Rates (Resting)Age Normal Range (Resting)

bpmPremature 120-1700-3 months 100-1503-6 months 90-1206-12 months 80-1201-3 years 70-1103-6 years 65-1106-12 years 60-95Over age 12 55-85

Table 2: Normal Respirations (Resting)Age Normal Range (Resting)

rpmPremature 40-70 0-3 months 35-553-6 months 30-456-12 months 25-401-3 years 20-303-6 years 20-256-12 years 14-22Over age 12 12-18

Table 3: Normal Temperatures by Age and MethodAge Oral Rectal Axillary

(Armpit)Ear

0-2 years - 97.9-100.4

94.5-99.1

97.5-100.4

3-10 years 95.9 to 99.5

97.9-100.4

96.6-98.0

97.0-100.0

Over age 11 97.6-99.6 98.6-100.6

95.3-98.4

96.6-99.7

Table 4: Normal Blood PressuresAge Normal

RangeTop Number

Normal RangeBottom Number

Premature 55-75 35-450-3 months 65-85 45-553-6 months 70-90 50-65


6-12 months 80-100 55-651-3 years 90-105 55-703-6 years 95-110 60-756-12 years 100-120 60-75Over age 12 110-135 65-85

Hematology References Ranges for Children

Table 1: Complete Blood CountRBC Hgb Hct MCV MCH MCHC RDW PLTS

Age X 106/uL g/dL % fL pg g/dL % X 103/uLNewborn 4.1-6.7 15-24 44-70 102-115 33-39 32-36 13-18 150-4501-23 mos 3.8-5.4 10.5-14 32-42 72-88 24-30 32-36 11.5-16 150-4502-9 yrs 4.0-5.3 11.5-14.5 33-43 76-90 25-31 32-36 11.5-15 150-45010-17 yrsMaleFemale

4.2-5.64.1-5.3

12.5-16.112-15

36-4735-45

78-9578-95

26-3226-32

32-3632-36

11.5-1411.5-14

150-450150-450

Table 2: Differential White Cell CountWBC *Total

NeutrophilsSegs Bands Lymphs Monos Eos Basos

Age X103/uL

X103/uL

X103/uL

X103/uL

X103/uL

X103/uL

X103/uL

X103/uL

Newborn 9.1-34 6-23.5 6-20 <3.5 2.5-10.5 <3.5 <2 <0.41-23 mos 6-14 1.1-6.6 1-6 <1 1.8-9 <1 <0.7 <0.12-9 yrs 4-12 1.4-6.6 1.2-6 <1 1-5.5 <1 <0.7 <0.110-17 yrsMaleFemale

4-10.54-10.5

1.5-6.61.5-6.6

1.3-61.3-6

<1<1

1-3.51-3.5

<1<1

<0.7<0.7

<0.1<0.1

Differential Shown as Absolute Numbers. *Total Neutrophils = SEGS + BANDS


Normal Reference Values, Adults

HematologyWBC 4.0-10.5 x 103/uLRBC – Female 3.8-5.5 x 106/uLRBC - Male 4.3-6.2 x 106/uLHemoglobin - Female 12.0-15.0 g/dLHemoglobin - Male 13.,2-16.2 g/dLHematocrit - Female 37-46 %Hematocrit - Male 40-52%Platelets 140-415 x 103/uLNeutrophils (Polymorphs, PMNs) 40-74 %Immature Polys (Bands) 0-10%Lymphocytes 14-46 %Monocytes 4-13 %Eosinophils 0-7 %Basophils 0-3 %Neutrophils, Absolute 1.8-7.8 x 103/uLMonocytes, Absolute 0.1-1.0 x 103/uLEosinophils, Absolute 0.0-0.4 x 103/uLBasophils, Absolute 0.0-0.2 x 103/uL

Blood ChemistryGlucose, Serum 65-99 mg/dLBUN 6-24 mg/dLCreatinine, Serum 0.57-1.00 mg/dLBUN/Creatinine Ratio 9-23Sodium, Serum 135-145 mmol/LPotassium, Serum 3.5-5.2 mmol/LChloride, Serum 97-108 mmol/LCarbon Dioxide, Total 20-32 mmol/LCalcium, Serum 8.7-10.2 mmol/LProtein, Total, Serum 6.0-8.5 g/dLAlbumin, Serum 3.5-5.5 g/dLGlobulin, Total 1.5-4.5 g/dLBilirubin, Total 0.0-1.2 mg/dLAlkaline Phosphatase 25-150 IUAST (SGOT) 0-40 IU/LALT (SGPT) 0-40 IU/L


Blood GasesBicarbonate 22-26 mEq/LBlood pH 7.34-7.44Partial Pressure of Carbon Dioxide (pCO2) 35-45 mmHgPartial Pressure of Oxygen (pO2) 75-100 mmHg

UrinalysisUrine Bilrubin negativeUrine Blood negativeUrine Ketone negativeUrine Leukocytes negativeUrine RBC 0-2/HPFUrine WBC 0-2/HPFUrine RBC casts 0/HPFUrine Nitrite negativeUrine Protein negative-traceSpecific Gravity 1.002-1.030Urine pH 5-7Urobilogen 0.2-1.0 hEr U/dL

Cerebral Spinal FluidCSF Glucose 50-80 ng/dLCSF Protein 15-45 mg/dLCSF RBC 0/uLCSF WBC 0-3/uL


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 High morbidity absenteeism Upper - usually mild & self-limiting Lower - can be severe & life-threatening

in children bacterial in adults

B. Clinical Syndromes

1. Upper Respiratory Tract Infectionsitis = inflammation - surface infections

Exposed to 8 microbes/min or 10,000/day

Predisposing factors decreased humidity – viral infections – antibiotic therapy -


1. Rhinitis = cold100% 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 - damage to epithelial cells 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 tonsilitisinfected 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 –.


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 à life-threatening respiratory obstruction Age – Symptoms -


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 cells4. Endotoxin

Incubation - 1-3 weeks Pathology - ciliated epithelium of trachea becomes covered w/ massive purulent exudate Presentation

early - runny nose, sneezing, fever, mild dry coughweek later - mucus & bact fill lower trachea, cough becomes paroxysmal - violent coughing fits, 5-20X w/ no breath in btwn - as air rushes back in - whoopalso 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


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 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)


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 Hospital-acquired1. E. coli (80-90%) 1. E. coli (40%)2. S. saprophyticus (5-15%) 2. Klebsiella, Enterobacter, Serratia,

Pseudomonas aeruginosa (25%)3. Proteus mirabilis 3.GPC4. Klebsiella, Enterobacter, Serratia, Pseudomonas aeruginosa

4. Proteus mirabilis

viruses - rare Predisposing FactorsAnything that: Disrupts urine flow Prevents complete emptying of bladder Promotes microbial access

Females Females & males MalesPregnancy Renal stones Enlarged prostateIntercourse Tumors

Neurological disordersCatheters


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 SyndromesLower UTI1. urethritis (urethra)Symptoms - dysuria

2. cystitis (bladder)Symptoms - rapid onset of dysuria; increased urgency/frequencyUrine - cloudy - pyuria (inflammation) or bacteriuria (bacteria); blood (hematuria)

3. prostatitis (prostate)Symptoms - dysuria, increased frequency, low back pain, systemic indications (fever)

Upper UIT1. 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


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 Disease1. Human Papillomavirus (HPV) genital warts; associated w/ cervical cancer2. *Chlamydia trachomatis D-K.

C. trachomatis L1, L2, L3non-specific or non-gonococcal urethritislymphogranuloma venereum

3. Candida albicans vaginal thrush, balanitis4. Trichomonas vaginalis vaginitis, urethritis5. Herpes simplex virus (HSV) genital herpes6. *Neisseria gonorrhoea gonnorhea7. HIV AIDS8. *Treponema pallidum syphilis9. *Hepatitis B virus hepatitis10. Haemophilus ducreyi 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


#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


#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 à 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.

Complications (in addition to reactivation) – aspetic meningitis or encephalitis in adults. Neonatal disseminated herpes or encephalitis.

Txt – acyclovir (Zovirax), famciclovir, valacyclovir (Valtrex)


#6. Gonorrhea - Neisseria gonorrhoea – 260,530 U.S. in 2009/ 14,471 cases MI Transmission – direct, usually sexual, person-personIf 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?


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.


#8. Syphilis ((#3 bacterial STI in U.S.) - Treponema pallidum – 12,833 U.S. in 2009/ 231 cases MI

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.


Infections of the GI and Diarrheal Illness

Clinical Syndromes1. Gastritis - inflammation of the stomach - pain in the upper abdomen, sometimes bleeding2. Gastroenteritis - inflammation of stomach & intestines - primarily diarrhea, sometimes nausea,

vomiting, crampy abdominal pain3. 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.

PathogensCause disease by 3 mechanisms:a. action of toxinsb. adherence to & effacement of microvilli à inflammationc. invasion of intestinal epithelial cells

A. Toxins cause disease – microbes are not present in the bodyToxin types Action on intestine/intestinal cellsEnterotoxin results in net secretion w/out intestinal damageCytoskeleton-altering toxin alters cell shape, may injure cells but is not lethalCytotoxin causes cell damage and ultimately cell deathNeural 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) à nausea & vomiting 1-5 hrs after ingestion of toxin - lasts ~1-6 hrs. can be difficult to distinguish from S. aureus food poisoning.


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 -

Pathology1. Ingestion of large numbers (> 108); only 0.001% survive passage through stomach2. Flagella & mucinase allow Vibrio to reach epithelial cells3. Attachment by way of fimbriae to receptors on brush border & crypt cells of small intestine4. 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 à increase in cGMP à increased fluid secretion.

B. cereus – ingested àdiarrheal toxin produced in the small intestine (cytotoxin targets villi à villus necrosis) à diarrhea 8-16.5 hrs after ingestion (note, this is the other presentation for B. cereus, not the food poisoning)



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 colon1. Ingestion - only 10-100 organisms required, 55% survive passage through stomach - most effective of

bacterial pathogens of GI2. Secrete enterotoxins during passage through small intestine à profuse, watery diarrhea3. 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 epithelium5. Phagocytized by macrophages but escape from phagolysosome into cytoplasm6. Trigger macs to produce IL-1, also triggers apoptosis7. 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 à ulcerations

à blood in stoolS. 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 à enteritis + diarrheaYersinia enterocolitisEntamoeba histolytica à amoebic dysenteryHuman diarrhoeal viruses (rotavirus, Norwalk virus) - gastroenteritisVirus 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.



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 à salmonellosis 44,468 U.S. / 911 MI

Salmonella typhi, paratyphi – invasive species à typhoid fever

SourcesS. enteritidis - S. typhi -

Pathology1. Ingestion of large numbers (105-1010); 0.001% survive passage through stomach2. Attach specifically to fibronectin of epithelial cells of small intestine3. Transported by M cells of GALT4. Invade gut wall ulcerations & hemorrhage. Also spread to intestinal lymphatics & are phagocytized

by macs but escape from phagolysosome into cytoplasm5. 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 GI7. 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

SalmonellosisIncubation –

Symptoms –

Txt -

Complications –

Other pathogens that cause disease by similar mechanism: Hepatitis A virus - 1,849 cases U.S. / 70 MIReovirusesEnteroviruses (includes poliovirus)



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:

bonesinusesmiddle ear

4. trauma

II. Clinical Syndromes

A. meningitis - of meningesCharacterized by high fever, headache, stiff neck (classic triad)

Pathology due to acute inflammation:Vascular permeability à ↑WBC, ↑fluidsFluids à swellingSwelling à ↑pressure à headacheInflammation affects muscles à stiff neckInflammation à fever

Causes:clogging of blood vessels (DIC) à necrosis of tissue↓ CSF flowimpaired 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 brainCharacterized by acute febrile illness + changes in mental state, consciousness, behavior

C. myelitis - of spinal cordSymptoms vary depending on where damage to cord occurs


III. Infections of the Meninges

A. Bacterial meningitisAcute - nearly always fatal

Strong correlation of microbe with age of patient – influences the top R/O:Neonates – E. coli, Group B streptococci1 month to 5 yrs - Haemophilus influenzae type B (Hib)5 to 40 - Neisseria meningitidis30 and over - Streptococcus pneumoniae

Pathogenesis1. colonization and invasion of nasopharynx 2. nasopharynx à bloodstream à BBB to subarachnoid3. replicate and induce inflammation in subarachnoid space à increased permeability of

BBB, cerebral edema, increased intracranial pressure, decreased cerebral blood flow.

PathologySubarachnoid space purulent exudates, vein distension, focal necrosis

DiagnosisCSF examination – elevated opening pressure, very ↑neutrophils, very ↑ protein, ↓glucose

PrognosisSerious to grave

Mortality ratesHib without txt = near 100% with txt = 5%N. meningitides without txt = near 100% with txt = 7-10%S. pneumoniae without txt = near 100% with txt = 20-30%

All can be present in humans in an asymptomatic carrier state


1. Haemophilus influenzae type B (Hib) (1 month – 5)GNRNormal upper RT microbiotaInactivate IgA using IgA proteaseColonize the nasopharynx using common piliPenetrate submucosa (invasive)à bloodstream (capsule to avoid phagocytosis)Incubation - 5-6 daysSymptoms develop over 1-2 daysEndotoxin:

1. inflammation2. DIC

Complications – hearing loss, delayed language development, mental retardationPrevention – Vaccination

2. Neisseria meningitidis (5-40) GNdCPerson-person in respiratory droplets; 20% carriers (as high as 60-80%)Inactivate IgA using IgA proteaseColonize the nasopharynx using pili à sore throatEndocytized à bloodstream (capsule to avoid phagocytosis)Incubation 1-3 daysSymptoms develop over 6-24 hoursEndotoxin:

1. affects blood vessel permeability à cross BBB (attach to dura mater w/ pili)2. drop in blood pressure à shock3. clotting of blood à hemorrhage (rash = petichiae and purpura), also DIC

Complications – amputations, permanent hearing lossPrevention - Vaccination

3. Streptococcus pneumoniae (30+) GPCNormal upper RT microbiota

sinuses or middle ear à brainorpneumonia in lungs à bloodstream à brain

CapsuleTeichoic acid à inflammationPrevention - Vaccination


B. Viral meningitis = aseptic meningitisMost commonSelf-limiting, non-fatal

Many different viruses:1. Enteroviruses - 40% (primarily Coxsackievirus and Echovirus)2. Arboviruses3. HIV4. HSV-2

Several considerations affect differential:Summer, fall + geographic clustering à ArbovirusesLate fall, winter + history of exposure to mice à LCMVLate winter, early spring + male à mumps virusWith genital lesions à HSV-2With atypical lymphocytes à EBVWith chickenpox or shingles à VZV

DiagnosisCSF examination – ↑ lymphocytes, moderately ↑ protein, normal glucose

Prognosis - In adults, excellent

C. Fungal meningitisChronic presentation – symptoms develop over days to weeks1. Coccidioides immitis 2. Cryptococcus neoformans - AIDS

IV. Infection of the Brain (Encephalon) – involvement of brain parenchyma

A. Viral encephalitisSame viruses as for aseptic meningitis but relative frequency varies1. Arboviruses (Arthropod-borne)

Ex. Equine encephalitis, (West Nile virus) Bird

Mosquito Mosquito

BirdHorse

(human)Epidemics, geographic clustering


2. HSV-1no insectsporadic, not epidemic

3. Enteroviruses, mumps

4. Rabies - Rhabodovirus BiteMultiplies at siteTravels to local nervesPeripheral nerves à spinal cord à brainLong incubationProdromal phase - flulike symptoms, tingling, burning, depressionExcitation phase - muscle function, speech, vision, anxiety, hydrophobiaParalytic phase - muscles weaken, consciousness fades, deathMortality - 100% with best treatmentPost exposure prophylaxis (PEP) - has never failed in US

B. Protozoan encephalitis1. 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 bacteriophageExotoxin botulinum prevents release of acetylcholineProduces a limp, flaccid, paralysisEyes à blurry, double visionThroat à slurring speech, difficulty swallowingDifficulty breathingCardiac problems


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 antibiotics3. 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. aureusa. 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 corneumImpetigo - a highly contagious pyoderma caused by group A -streptococci (GAS)- almost exclusively in children - spread by contact

3. EpidermisEcthyma – untreated impetigo

4. Dermisa. Erysipelas = St. Anthony’s fire – usually GAS - blockage of dermal lymphatics – well-defined edges. Pain and fever. 5% develop bacteremia with high mortality.

b. Lymphangitis – inflammation of the lining of lymphatic vessels

5. Subcutaneous fat layerCellulitis – usually S. aureus or S. pyogenes. Initial superficial skin trauma. Diffuse inflammation, enlarged lymph, malaise, chills, fever.


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 skin 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 à scarlet fever rash)


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 à 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


IV. Infections of Wounds

A. Infections of Trauma Induced WoundsMany type wounds result in anaerobic conditions in the tissues:

1. Dirty2. 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 àspores germinate à bacteria grow

& ferment carbohydrates of muscles à 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 woundsBUTInfections 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 Effect1. Leukocidin Kills WBC by producing holes in their cytoplasmic membranes

(also kill RBC).2. Coagulase 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).

3. Exfoliative toxin (exotoxin)

Separates the layers of epidermis, aids in invasion.

4. Toxic Shock Syndrome toxin (exotoxin)

Superantigen - stimulates TH to over produce IL-2. Causes rash, 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 Effect1. Hemolysins = streptolysins

Kill WBC by producing holes in their cytoplasmic membranes (also kill RBC).

2. Streptokinase Converts plasminogen to plasmin, promotes lysis of fibrin clots, aids in spread.

3. DNase Breaks down the viscous DNA in pus to facilitate spread.4. Hyaluronidase Breaks down hyaluronic acid (the cement that holds cells together)

in connective tissue, allows rapid spread (also eventually breaks down their own capsule).

5. Erythrogenic toxin Produced by lysogenic strains (virus infected), responsible for rash.6. Proteases Break down proteins.7. Hyaluronic acid capsule Same as hyaluronate of connective tissue. Inhibits phagocytosis of

nonopsonized bacteria, also disguises strep antigens.8. M-protein Interferes with phagocytosis and blocks complement action. The

major virulence factor.

Documents

people.cst.cmich.edupeople.cst.cmich.edu/alm1ew/MM Unit 3 Lecture notes.docx · Web viewDifferential lists varies depending on whether infection is acquired in the community or in