BIO 580 Medical Microbiology Unit 3 Clinical Manifestations 1

BIO 580 Medical Microbiology Unit 3 – Clinical Manifestations 1

Introduction to Solving Clinical Cases

Steps in a Clinical Encounter

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.

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”.

Respiratory Tract

Overview

nose to alveoli
continuous operation is essential
divided into 2 regions:
upper –
lower -

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

Clinical Syndromes

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 -

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 -
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 tonsilitis

infected mucosa or inflammation of lymphoid tissue

70% viral – symptoms often includerhinorrhea, 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
age –
onset –
symptoms –
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, Haemophilusinfluenzae, Moraxella

4. Epiglottitis

H. influenzae type B (vaccination = Hib)
Severe inflammation with edema  life-threatening respiratory obstruction
Age –
Symptoms -

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 - Bordetellapertussis (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 Mycoplasmapneumoniae
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, Chlamydiapneumoniae, Legionellapneumophila, Coxiellaburnetii
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
Aspergillusfumigatus – 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
Histoplasmacapsulatum - histoplasmosis
Coccidiodesimmitis - San Joaquin Valley Fever
Blastomycesdermititidis - blastomycosis
Pneumocystisjiroveci (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. OverviewUrinary

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-acquired
1. E. coli (80-90%) / 1. E. coli (40%)
2. S. saprophyticus (5-15%) / 2. Klebsiella, Enterobacter, Serratia, Pseudomonas aeruginosa (25%)
3. Proteus mirabilis / 3.GPC
4. Klebsiella, Enterobacter, Serratia, Pseudomonas aeruginosa / 4. Proteus mirabilis

viruses - rare

Predisposing Factors

Anything that:

Disrupts urine flow
Prevents complete emptying of bladder
Promotes microbial access

Females / Females & males / Males
Pregnancy / Renal stones / Enlarged prostate
Intercourse / Tumors
Neurological disorders
Catheters

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

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 257-259carefully, especially pay attention to how to tell what is significant bacteriuria

II. Genital/Reproductive

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 / Disease

Human Papillomavirus (HPV)

/ genital warts; associated w/ cervical cancer

*Chlamydia trachomatis D-K.

C. trachomatis L1, L2, L3 / non-specific or non-gonococcal urethritis
lymphogranuloma venereum

Candida albicans

/ vaginal thrush, balanitis

Trichomonas vaginalis

/ vaginitis, urethritis

Herpes simplex virus (HSV)

/ genital herpes

*Neisseria gonorrhoea

/ gonnorhea

/ AIDS

*Treponema pallidum

/ syphilis

*Hepatitis B virus

/ hepatitis
10. Haemophilus ducreyi / chancroid

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  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-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?

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/ 231cases 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 Syndromes

Gastritis - inflammation of the stomach - pain in the upper abdomen, sometimes bleeding
Gastroenteritis - inflammation of stomach & intestines - primarily diarrhea, sometimes nausea, vomiting, crampy abdominal pain
Colitis - intestinal syndrome that primarily involves the colon or large intestines.
Enterocolitis - inflammation of mucosa of both large & small intestine = dysentery - diarrhea often contains blood & mucus.
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:

action of toxins
adherence to & effacement of microvilli inflammation
invasion of intestinal epithelial cells

A. Toxins cause disease – microbes are not present in the body