Title: MICROBIOLOGY - UMF - Iuliu Haţieganu

STUDY GUIDE 2009-2010
MICROBIOLOGY DEPARTMENT
III-rd YEAR COURSE
COURSE TITLE: CLINICAL MICROBIOLOGY
Introduction
Course type: compulsory
To whom is the course addressed: General Medicine students: third year
Course importance
- Revealing the bacteria, protozoa, helminthes and fungi importance as etiologic agents of
different infectious clinical entities (respiratory tract infections, CNS infections (meningitis,
encephalitis) and the diarrhea syndrome
- Learning the medical notions, concerning pathogenesis and laboratory diagnosis of bacterial,
parasitic and fungal infections, in order to understand their role in the human pathology.
Place of the discipline in the curricula: preclinical disciplines; correlation with clinic
disciplines: infectious diseases, immunopathology
Anterior knowledge and abilities: Fundamental Microbiology
Course and laboratories program: on university site:
Hours/week: Courses: 2, Practical activities: 2,
Hours/semester: Course: 28, Practical activities: 28
General goals: Medical Bacteriology, Parasitology and Mycology
Specific goals:
- Knowledge of genres and species proprieties, pathogenity factors, of pathogenesis and
laboratory diagnosis of bacterial, parasitic and fungal infections.
- Knowledge of methods and techniques used for the microorganism’s detection and
identification.
Content: Clinical Microbiology: course and laboratory
• Evaluation
Written final exam consisting of multiple choice tests and written subjects (70%)
1

Verifications tests during the year through oral/written and examination for laboratories +
practical exam (30%)
Examination mode: Written final exam consisting of 40 multiple choice questions (second year)
and 30 multiple choice questions (third year)
Marking mode:
-Written final exam 70%
-Verifications tests during the year through oral/written and examination for laboratories +
Practical exam - 30 % ( bonus will be offer for students which made presentations - see
facultative activities)
Condition for passing the exam: mark 5
Calendar of the exam: established together with the course titular, during winter session and
summer session.
Course titular: Prof. Dr. Lia Monica Junie
Consultation schedule:
Prof. Dr. Lia Monica Junie
Thursday 13 - 15
Educational objectives:
What students have to know:
1. Knowledge of methods and techniques used for the detection and identification of
microorganisms.
2. Knowledge of principles and interpretation of microbiologic diagnosis procedures results.
What students have to do?
1. Enabling students to perform some diagnostic laboratory techniques, witches are necessary for
a practitioner doctor.
2. Interpretation the microbiology laboratory data.
Facultative activities
Preparation and presentation of reviews about a subject of choice in front of colleagues
2

Course content: CLINICAL MICROBIOLOGY
Respiratory tract infection
Upper respiratory tract infections
Bacterial Angina (Pharyngitis) and laryngitis
-Corynebacterium diphteriae
-Streptococcus pyogenes group A
Bacterial Pyogenic Infections
Lower respiratory tract infections
Acute bronchitis & Pneumonia
Bacterial Pneumonia
Atypical pneumonia
Fungal Pneumonia
Fungal Infections of the CNS (meningitis)
Fungal Generalized infections
Central nervous syndrome infections
Bacterial Infections of the CNS
(meningitis); Bacterial toxins with neural
tropism
Parasitic Infections of the CNS
Encephalitis produced by parasites
Blood Protozoa
Congenital infections
Sexually transmitted infections
- Staphylococcus aureus, Genus Staphylococcus
-Streptococcus pneumoniae; Genus Streptococcus
-Bordetella pertusis
-Chlamydia, Mycoplasma pneumoniae
-Legionella pneumophila, -Coxiella burneti
- Pneumocystis jiroveci
- Aspergillus,
- Criptococcus neoformans,
- Candida,
Bacterial Infections of the CNS
-Haemophylus influenzae,
-Neisseria meningitidis
- Clostridium tetani, botulini - tetanus, botulism
-Free living amoeba: Naegleria, Acanthamoeba
-Cerebral malaria,
-Cerebral toxoplasmosis
- Plasmodium
-Toxoplasma
vaginitis: Candida and Trichomonas
- Trichomonas vaginalis
Digestive tract infections produced by
Protozoa
- Entamoeba,
- Giardia,
- Cryptosporidium,
- Microsporidium
3

Table of Contents
COURSE TITLE: CLINICAL MICROBIOLOGY.................................................................. 1
RESPIRATORY TRACT INFECTIONS................................................................................... 6
UPPER RESPIRATORY TRACT INFECTIONS................................................................. 7
BACTERIAL ANGINA ........................................................................................................ 7
Corynebacterium diphtheriae - Pharyngeal diphtheria........................................................ 7
Streptococcus pyogenes - Angina (strep throat) .................................................................. 8
LOWER RESPIRATORY TRACT INFECTIONS............................................................. 10
PNEUMONIA ....................................................................................................................... 10
Streptococcus pneumoniae - lobar pneumonia .................................................................. 10
Streptococci belonging to normal flora.............................................................................. 11
Viridans streptococci, the C, D group streptococci, the enterococci................................. 11
Bordetella pertussis, Mycoplasma pneumoniae, Chlamydia psittaci ................................ 12
Staphylococcus aureus - genre Staphylococcus................................................................. 14
CNS INFECTIONS................................................................................................................. 16
BACTERIAL MENINGITIS ............................................................................................. 16
Haemophilus influenzae..................................................................................................... 16
Neisseria meningitidis (meningococcus) ........................................................................... 17
Clostridium botulinum, Clostridium tetani........................................................................ 17
SEXUALLY TRANSMITTED DISEASES.......................................................................... 20
Neisseria gonorrhoeae - Gonorrhea .................................................................................. 20
FUNGAL INFECTIONS ........................................................................................................ 21
Pneumocistis jirovecii- (former carinii) - Pneumocystis pneumonia, pneumocistosis...... 21
Aspergillus - pulmonary aspergillosis................................................................................ 22
Cryptococcus neoformans- Pulmonary cryptococcosis..................................................... 23
4

Candida species.................................................................................................................. 24
PARASITOLOGY - PROTOZOA............................................................................................ 27
SEXUALLY TRANSMITTED DISEASES.......................................................................... 27
Trichomonas vaginalis....................................................................................................... 27
DIGESTIVE TRACT INFECTIONS.................................................................................... 28
Entamoeba hystolitica........................................................................................................ 29
Giardia lamblia intestinalis: Giardiasis............................................................................. 29
Cryptosporidium – cryptosporidiosis, cryptosporidium enteritis ...................................... 30
Microsporidia - microsporidiasis ....................................................................................... 31
INFECTIONS OF THE CNS................................................................................................. 32
Free living amoebae............................................................................................................... 33
Toxoplasma gondii............................................................................................................. 34
Plasmodium - malaria ........................................................................................................ 35
Bibliography:
1. Junie Monica, Stanila Luciana, Carmen Costache (2003),”Medical Microbiology:
Bacteriology, Virology, Infection and Immunity”, “Iuliu Hatieganu” Publishing House, Cluj-
Napoca, Romania, ISBN
2. Stanila Luciana, Junie Monica, ”General Bacteriology and Virology” (2001) “Iuliu Hatiegenu”
Publishing House, Cluj-Napoca, Romania, ISBN
3. George F. Brooks, Janet S. Butel, Stephen A. Morse, Joseph L. Melnick, Ernest Jawetz,
Edward A. Adelberg- Jawetz, Melnik Adelberg’s Medical Microbiology – 24-th edition,
McGraw-Hill Professional Ed., 2004, ISBN 0071412077, 9780071412070
4. Medical Parasitology – Markell, Voge, John, 9-th edition, 2006
5. Diagnostic Medical Parasitology - Lynne Shore Garcia, 5th Edition, ASM Press, 2006
6. www.dpd.cdc.gov/dpdx
5

RESPIRATORY TRACT INFECTIONS
Educational Objectives:
Respiratory tract infections: etiology, pathogenesis, laboratory diagnosis
I. Upper respiratory tract infections
Bacterial angina
1. Corynebacterium diphtheriae - Pharyngeal diphtheria,
2. Streptococcus pyogenes - Streptococcal angina
II. Lower respiratory tract infections
Bacterial pneumonia:
1) Streptococcus pneumoniae - lobar pneumonia
2) Bordetella pertussis - whooping cough,
4) Chlamydia psittaci, pneumoniae
5) Mycoplasma pneumoniae - atypical interstitial pneumonia
Table of Contents
1. Corynebacterium diphtheriae:
2. Streptococcus pyogenes: Streptococcal angina, other pyogenic infections
3. Staphylococcus aureus - pyogenic infections and other infections
4. Streptococcus pneumoniae; lobar pneumonia,
5. Streptococci belonging to normal flora (commensally) => opportunistic pathogen
6. Bordetella pertussis: whooping cough,
7. Chlamydia psittaci, pneumoniae,
8. Mycoplasma pneumoniae- Atypical interstitial pneumonia
Algorithm
- general properties, morphology,
- species, classification,
- transmission
- virulence factors
- pathogenesis
- immunity
- clinic: signs and symptoms
- treatment: susceptibility/ resistance to antibiotics drugs
- prevention: vaccin
6

UPPER RESPIRATORY TRACT INFECTIONS
BACTERIAL ANGINA
Corynebacterium diphtheriae - Pharyngeal diphtheria
Corynebacterium Genre: species, infections C. diphtheriae is a pathogenic bacterium that causes
diphtheria. It is also known as the Klebs-Löffler bacillus,
Essential: C. diphtheriae: general properties, morphology, classification, subspecies: C.
diphtheriae mitischodis, C. diphtheriae intermedius, C. diphtheriae gravis, C. diphtheriae
belfanti, transmission (infected persons, carriers), toxigenic and non-toxigenic strains.
Diphtheria toxin (exotoxin): general properties, molecular mechanism of action: stages,
consequences on eukaryotic cells. Structure correlated with the functions of fragments: B, A, T;
The toxin in the bloodstream, the effect on different cells and on different organs: cardiotoxic
and neurotoxic effects. Toxin production: strains, lysogenic conversion, non- lysogenised
strains: significance. Factors influencing the secretion of toxin: the iron concentration.
Diphtheria Antitoxin: definition, effect on toxin, practical application. Toxoid and
immunization: DTaP (diphtheria-tetanus-pertussis), Td (tetanus-diphtheria toxoid):
definition, properties, application and results.
Important: Diphtheria: Pathogenesis: adherence, penetration and multiplication, consequences
on pharyngeal mucosa: the throat membrane. The effect of diphtheria toxin in human body:
local (mucosal damage) and general phenomena of infection. Immunity: antibodies, antitoxic
serum and protective level: definition, effect on the toxin in blood and in cells, practical
application. Serum therapy: definition, application, result. Diphtheria immunity testing: The
Schick test: purpose, procedure type, aspect of the skin around the injection, interpretation,
Positive, Negative reaction. Laryngeal diphtheria (diphtheritic croup): pathogenesis
(inflammation of the larynx, and respiratory obstruction), risk groups, consequences,
supportive care. Cutaneous diphtheria. Sensitivity to antibiotics of C. diphtheriae
Laboratory diagnosis of diphtheria: at practical activity.
Useful: The signs and symptoms of diphtheria.
Genus Corynebacterium: general properties, species, habitat, risk factors for infections,
infections, practical applications.
Optional: differential diagnosis with other types of angina (e.g. strep throat).
Questions and reviewing
1. Diphtheria toxin is produced only by those strains of C. diphtheriae that are:
a. Glucose fermenters
b. Sucrose fermenters
7

c. Lysogenized with - β tox. prophage
d. of the Mitis strain
e. Encapsulated strain
2. Which of the following diseases can be prevented by vaccination?
a. whooping cough
b. tetanus
c. diphtheria
d. erysipelas
e. gas gangrene
Essential:
Streptococcus pyogenes - Angina (strep throat)
Streptococcus pyogenes: Group A β-hemolytic streptococcus (abbreviated GAS or GABHS):
general properties, classification, group, serotypes.
Virulence factors: Streptococcal Surface factors (M protein, fibronectin-binding protein
(Protein F) and lipoteichoic acid for; hyaluronic acid capsule), non-toxic extracellular factors,
hemolysins, streptolysine S and O, streptokinase, hyaluronidase, streptodornase, C5a peptidase,
chemokine protease), Exotoxins, Streptococcal pyrogenic exotoxin A: properties, target of
action, mechanism of action, effect on cells (leukocytes, red blood cells) and tissues of the
human body; role in producing infection (e.g. adherence, dissemination factors), immunogenicity
(antigen, superantigen, induced specific antibodies, neutralizing antibodies, protective
immunity), importance in diagnostic.
Angina-Pharyngitis ("strep throat"): transmission, carriers, pathogenesis, streptococcal
serotypes involved, immunity and specific antibodies: anti-streptococcal antibodies, antistreptolysine
O antibodies-AS(L)O: effect on human structures, method: importance and
interpretation. Complications: Suppurative (pyogenic) and non-suppurative (non-pyogenic).
Scarlet fever: strains, streptococcal serotypes involved, pathogenesis: Erythrogenic toxin - Dick
toxin: production, antigenic types, role. Immunity in scarlet fever: Dick test: local reaction,
interpretation.
Poststreptococcal "non-pyogenic" syndromes, that occur after infection with Group A
streptococci: rheumatic fever; acute glomerulonephritis: streptococcal serotypes involved,
pathogenesis, prevention.
Laboratory diagnosis of strep throat: at practical activity.
Important: Other infections caused by Streptococcus pyogenes: Pyogenic infections: Skin
diseases: Impetigo, Ecthyma, Cellulitis, Erysipelas, Necrotising fasciitis, Invasive streptococcal
infections: Puerperal Fever, streptococcal toxic shock syndrome.
8

Useful: Streptococcal pharyngitis: geographical, seasonal, age group distribution, clinical
evolution and treatment.
Optional: Other hemolytic streptococci, group B streptococci: habitat and human infections
(neonatal infections, postpartum septicemia, bacteriemia, pneumonia, and urinary infections),
treatment and prevention.
Questions and reviewing
1. Pharyngitis can be produce by:
a. Clostridium tetani
b. Klebsiella pneumoniae
c. Herpes simplex virus 1 (HSV-1)
d. Streptococcus pyogenes
e. Corynebacterium diphteriae
2. Scarlet fever is produce by the exotoxin of:
a. Staphylococcus aureus
b. Corynebacterium diphteriae
c. Haemophilus influenzae
d. Streptococcus pneumoniae
e. Streptococcus pyogenes
3. Group A β-hemolytic streptococcus:
a. is also known as GAS
b. is also known as Streptococcus pyogenes
c. produces rheumatic fever
d. produces acute glomerulonephritis
e. produces diphtheria.
9

LOWER RESPIRATORY TRACT INFECTIONS
PNEUMONIA
Algorithm
- general properties, morphology,
- species, classification,
- transmission
- virulence factors
- pathogenesis
- immunity
- clinic: signs and symptoms
- treatment: susceptibility/ resistance to antibiotics drugs
- prevention: vaccine
Streptococcus pneumoniae - lobar pneumonia
Essential: Streptococcus pneumoniae -Pneumococci: properties, habitat, transmission, access to
the lung, location, infections. Virulence factors: on pneumococci surface (polysaccharide
capsule, pili, pneumococcal surface proteins: pneumococcal surface adhesin A (PsaA), protective
antigen (PspA), choline binding protein A-CbpA, M protein, cell wall components), intracellular
toxins (autolysins (LytA, LytB, LytC), pneumolysin-Ply, hydrogen peroxide, nitric oxide),
extracellular non-toxic compounds (IgA1 protease, neuraminidase, hemolysins, hyaluronidase,
serine protease): production, chemical composition, mechanism of action, role in the
pathogenesis of pneumococcal infection, effect on bacterial cells, red blood cells, lymphocytes,
phagocytes (anti-phagocytic, opsonization, antiopsonizing), on bronchial epithelium on secretory
IgA and inflammatory cascades (cytokines, complement system); inflammatory effect (purulent
or suppurative exudate), type-specific pneumococcal antigens, immunogenicity: effect of
induced antibodies (induction of neutralizing, protective, and opsonizing antibodies, typespecific
protective antibodies), immunological memory, immunological immaturity in children ≤
2 year.
The pathogenesis of pneumococcal infection: in the lung (attachment to respiratory mucosa, to
the epithelium, colonization of pharyngeal and bronchial mucosa, penetration of pneumococci to
the alveoli) and extra pulmonary (systemic invasion, bacteriemia, meningitis).
Laboratory diagnosis of pneumococcal infections, Laboratory diagnosis of pneumonia: at
practical activity.
Important: Pathogenesis of pneumonia: is a complex interplay between pneumococcal
virulence determinants and the host immune response. Pneumococcal adherence to human
epithelial oropharyngeal cells, colonization of the nasopharynx mucosal epithelium, penetration
of endothelial mucosa, bacteria in the alveolar space, adherence on alveolar cells type II,
10

multiplication in the alveolar space, cytotoxic effects on pulmonary cells and pulmonary
inflammation. The molecular events in pneumococcal inflammation; the mechanism of the
inflammatory response in the lung (inflammatory exudate): serous exudate and purulent exudate
in alveoli. Pathogenesis of meningitis: pneumococcus adherence to brain capillaries (choline,
CbpA, cell receptors), inflammatory response.
Useful: Pneumococcal Pneumonia (Lobar Pneumonia): incidence, pneumococcal types,
transmission, contributing factors, risk groups, complications, mortality.
Hospital-acquired infections: Antibiotic resistant strains and antibiotic susceptibility testing.
Antibiotic therapy recommended for infections caused by resistant strains.
Pneumococcal meningitis: particularities.
Optional: Pneumococcal capsular polysaccharides, serotypes; vaccine: composition, type of
vaccine, immunogenicity and protection.
Streptococci belonging to normal flora
Viridans streptococci, the C, D group streptococci, the enterococci
Essential: habitat, species, human infections, pathogenesis.
a) Viridans streptococci: habitat (commensally bacteria, opportunistic pathogen bacteria),
properties (lack either the polysaccharide-based capsule typical of S. pneumoniae or the
Lancefield antigens of the pyogenic members of the genus, optochin resistant), human infections:
Subacute bacterial endocarditis: mechanism of production: dental extractions, bacteria into the
bloodstream, multiplication of the streptococci on damaged heart valves by rheumatic lesions,
congenital heart disease; S. mutans: Role in tooth decay (adhesion to the surface of teeth, dental
plaque, dental caries).
b) Enterococci: habitat (normal flora of the bowel, mouth), human infections: hospital
opportunistic infections, urinary infections, subacute bacterial endocarditis.
c) Group C, D streptococci: human infections.
Important: Streptococcus Genre: General properties, Classification. Peptostreptococcus -
anaerobic streptococci. Laboratory diagnosis of infections produced by: viridans streptococci,
group B streptococci, enterococci (at practical activity)
Useful: Streptococcaceae family: general properties, pathogenic genera for humans
(Streptococcus, Enterococcus), commensal species of upper respiratory tract, rarely pathogenic
species for humans.
Optional: non-pathogenic species for humans: bacteria present in the air, on fruits, vegetables
(saprophytes of plants), bacteria present in milk and cheese (Lactococcus), Lactobacillus,
Leuconostoc, Pediococcus, nutritional "deficiencies"variants (Abiotrophia) .
11

Bordetella pertussis, Mycoplasma pneumoniae, Chlamydia psittaci
Essential: Bordetella pertussis: the causative agent of pertussis or whooping cough; general
properties, pathogenic factors (adhesion factors, toxins: filamentous hemagglutinin, pertussis
toxin (PTx), adenylate cyclase (CyaA)), mechanism of action, pathogenesis of whooping cough
(colonization stage = upper respiratory disease, toxemic stage), immunization: Pertussis vaccine,
DTaP.
-Mycoplasma pneumoniae: major pathogen, general properties, transmission (by respiratory
droplets), distribution: worldwide, group risk (young adults), pathogen only for humans, the
causative agent of human primary atypical pneumonia (PAP) or walking pneumonia:
outbreaks in groups with close contacts: families, college students, increase incidence in winter.
Treatment: Tetracycline, Erythromycin.
-Chlamydia pneumonia: human upper respiratory infections, atypical pneumonia: general
properties, transmission.
-Chlamydia psittaci: general properties, reservoir normal hosts (birds, parrots and pigeons,),
human contamination (avian excreta, respiratory way, and respiratory secretions), psittacosis
(ornithosis or parrot fever), pathogenesis of human lung infection: primary atypical
pneumonia. (C psittaci attaches to the respiratory epithelial cells, spreads via the blood stream
(bacteremia) to the reticuloendothelial system (systemic disease), lung infection. Prophylaxis:
restricting the contact with birds (parrots), adding tetracycline to bird feed, flocks of turkeys and
ducks surveyed. Treatment: Tetracycline, Doxycicline, Azytromycin.
Important: Genus Bordetella: species, infections. Genus Mycoplasma: species, infections,
Genus Chlamydia: Chlamydia trachomatis: the most common human agent of STD.
Laboratory diagnosis of infections produced by species of: Bordetella Genus, Chlamydia Genus,
and Mycoplasma Genus; at practical activity.
Useful: Legionella: The genus is named after the outbreak of pneumonia among people
attending the American Legion convention in Philadelphia in 1976. Legionella pneumophila:
source: environmental water (water taps, sinks and showers, water cooling systems); portal of
entry = respiratory system, transmission (person-to-person transmission does not occur),
serotypes, disease: mild influenza-like syndrome to a severe atypical pneumonia (Legionaires'
disease). Treatment: erythromycin (or erythromycin plus rifampin). Prophylaxis: eliminating
aerosols from water sources, hiperclorination and high temperature in water supplies, diagnosis.
Optional: Symptoms of whooping cough. Symptoms, treatment, prevention of atypical
pneumonia.
Questions and reviewing
1. Lower respiratory tract infections can be produce by:
12

a. Streptococcus pneumoniae
b. herpes simplex virus 1 (HSV-1)
c. Pneumocistis jirovecii
d. rabies virus
e. Klebsiella pneumoniae.
2. Pneumolysin of pneumococci:
a. stimulates the production of inflammatory cytokines
b. stimulates lymphocyte proliferation
c. inhibits beating of the epithelial cell cilia
d. increases the bactericidal activity of neutrophils
e. inactivates the complement
3. Which of the following bacteria: A. Streptococcus pyogenes; B. Neisseria gonorrhea; C.
Staphylococcus aureus; D. Mycobacterium tuberculosis; E. Streptococcus pneumoniae; F.
Neisseria meningitidis, G. Corynebacterium diphteriae, are responsible for the following
diseases: l. scarlet fever, 2. diphtheria, 3. tuberculosis; 4. Pneumonia, 5. Meningitis, 6.
gonococcal urethritis; 7. Furuncles; Make pairs!
5. Bacterial pneumonia
a. is always an atypical pneumonia
b. is an interstitial pneumonia produced by Streptococcus pneumonie
c. may be produced by Mycoplasma pneumonie
d. produced by Streptococcus pneumonie is the typical type of pneumonia
e. may be produced by Pneumocistis jiroveci
6. Pertussis toxin:
a. produces cutaneous edema due to its adenylate cyclase function.
b. causes muscle spasm by blocking the release of inhibitory neurotransmitter
c. enhances adenylate cyclase activity, increases the secretion of mucus, by stimulating
production of cAMP.
d. inactivates EF2 (elongation factor 2) by ADP-ribosylation (inhibits cellular protein synthesis).
e. blocks the release of acetylcholine.
13

Staphylococcus aureus - genre Staphylococcus
Staphylococcus can cause pyogenic infections and a wide variety of infections in humans and
animals through either toxin production or invasion.
Essential: Staphylococcus aureus: general properties, classification, grape-like clustering
common to Staphylococcus species, habitat and reservoir of infection: healthy carriers, pharynx
(80-90% of the hospital staff); transmission, portal of entry in the human body, strains. Acquired
resistance to antibiotics: antibiotics resistant strains in hospitals. Virulence factors of S. aureus:
chemical composition, structure, biological properties, genetic determinism, mechanism of
action, effects. Role in the pathogenesis of Staphylococcus aureus infections: resistance to
phagocytosis (coagulase, capsule, protein A, leukocidin, biofilm), resistance to immune
responses (coagulase, leukocidin), adherence and colonization (cell-bound adhesins: protein A);
of the pharyngeal mucosa (asymptomatic healthy carriers), of the skin (localized infection),
invasion (invasins: staphylokinase, hyaluronidase, extracellular enzymes: proteases, lipases,
nucleases, collagenase), tissue damage, pus formation, practical applicability (e.g. identification
of streptococci - Streptic test); Immunogenicity: antigen, specific antibodies (protection,
opsonization). Staphylococcal toxins: hemolysins (,,,), leukocidin, toxic shock syndrome
toxin (TSST), enterotoxins (A-G), exfoliatin toxin: mechanism of action, types, genetic
determinism, phage group, resistance to digestive enzymes and temperature, antigenic properties.
Effect on human and animal cells (leukocytes, neutrophils and macrophages, lymphocytes, blood
platelets, enterocytes, red blood cells - erythrocytes: α, β haemolysis. Effect on the skin, tissues,
CNS, invasion: pyrogenic, cytotoxic, anti-phagocytic, necrotic, lethal effect. Antigens;
superantigen; toxoid, specific antibodies.
The diversity of staphylococcal infections: Staphylococcal infections are the result of bacterial
multiplication, of dissemination by invasion factors, and toxins. Staphylococci (S. aureus)
present numerous pathogenic factors, with chromosomal and extrachromosomal determinism
(plasmids, phages).
Important: Staphylococcal infections: risk groups, favoring factors, and pathogenesis.
-Suppurative (pyogenic) infections (with pus): boils (furuncles and carbuncles), and pimples
(folliculitis), abscesses, impetigo, surgical wounds infection, axillary hydrosadenitis, mastitis,
osteomyelitis, sinusitis, otitis, pneumonia: pus formation
-Invasive infection (invasion of the bloodstream): bacteriemia, septicemia, meningitis,
endocarditis.
-Infections caused by staphylococcal toxins: staphylococcal scalded skin syndrome (SSSS), toxic
shock syndrome (TSST-1), food poisoning, postantibiotic enterocolitis.
-Hospital-acquired infections: risk groups, resistance to penicillin and other -lactam drugs: -
lactamases (penicillinase), methicillin resistant strains of Staphylococcus.
-Other infections caused by S. aureus: urinary infections (cystitis, pyelites), peritonitis.
14

Laboratory diagnosis of staphylococcal infections: at practical activity.
Useful: Staphylococcal infections: clinical evolution and prognosis. Treatment of staphylococcal
infections: AB therapy, antibiotics susceptibility testing. Prophylaxis: control and sterilization of
"healthy carriers". Vaccine: No vaccine is generally available. Autovaccine.
Genus Staphylococcus: other species: Staphylococcus epidermidis, Staphylococcus
saprophyticus: habitat, commensally bacteria (nasal and skin), opportunistic infections.
Optional: Micrococcaceae family: genus Micrococcus
Questions and reviewing
1. A box of ham sandwiches with mayonnaise prepared by a person with a boil on his neck was
left out of the refrigerator for the on-call interns. Three doctors became violently ill
approximately 2 h after eating the sandwiches. The most likely cause is:
a. S. aureus enterotoxin
b. Coagulase from S. aureus in the ham
c. S. aureus leukocidin
d. C. perfringens toxin
e. Penicillinase given to inactivate penicillin in the pork
2. Staphylococcus aureus causes a wide variety of infections, ranging from wound infection to
pneumonia. Treatment of S. aureus infection with penicillin is often complicated by the:
a. Inability of penicillin to penetrate the membrane of S. aureus
b. Production of penicillinase by S. aureus
c. Production of penicillin acetylase by S. aureus
d. Lack of penicillin binding sites on S. aureus
e. Allergic reaction caused by staphylococcal protein
15

CNS INFECTIONS
BACTERIAL MENINGITIS
Educational Objectives: CNS infections Meningitis: etiology, pathogenesis, laboratory
diagnosis
Table of Contents
1. Haemophilus influenzae, Genus Haemophylus
2. Neisseria meningitidis, Genus Neisseria
3. Clostridium tetani, botulinum: infections, pathogenesis
Haemophilus influenzae
Essential: Haemophylus influenzae or Pfeiffer's bacillus: General properties (capsulated human
bacterium, 6 serotypes), habitat, reservoir, transmission (respiratory).
Pathogenicity factors: surface compounds (capsule, pili, membrane proteins: P2, P6,
endotoxin), extracellular products (protease, bacteriocins,): chemical structure (polysaccharide,
protein, lipopolysaccharide- LPS); structural particularities, structural variability correlated with
the pathogenicity, biological proprieties, functions, role in the pathogenicity (resistance to
phagocytes, destroying secretory IgA, adherence and colonization of the pharyngeal mucosa,),
consequences (asymptomatic healthy carriers or respiratory infections), invasion, practical
application (preparation of a vaccine from the P2 and P6 proteins), antigenicity, immunogenicity:
the effect of the specific induced antibodies (protector, opsonizing, bactericidal) and of the
maternal antibodies. Particularities of the natural immunity according with bacterium, age, the
development of immune system (increased susceptibility in children from 6 months to 1 year).
Bacteriocins: mechanism of action, role in producing infection. Encapsulated serotypes b (Hib),
other encapsulated types): particularities, infections. Unencapsulated strains termed nontypable
(NTHi): particularities, infections.
Important: Diseases produced by H.influenzae:
-Meningitis: pathogenesis, major virulence factors of disseminated infection, serotype, risk
groups, complications, clinical evolution, prognosis, sequella. Prophylaxis: vaccines available
against Hib.
-Pneumonia: type of H. influenzae, pathogenesis.
-Obstructive Laryngitis (Epiglottitis): pathogenesis.
-Laboratory diagnosis of H.influenzae infections (at practical activity).
Useful: Haemophylus Genus: general properties, classification, species: Haemophylus ducreyi,
H. parainfluenzae, H. aegyptius (H. influenzae biogroup aegyptius): transmission, infections. H.
influenzae biogroup aegyptius (Hae) is a causative agent of conjunctivitis.
16

Optional: Pasteurellaceae family, Haemophylus Genus, Pasteurella and Actinobacillus Genus.
Non-pathogenic strains, commensally strains: Haemophylus aphrophylus, H.paraprophylus, H.
haemolyticus, H. parahaemolyticus: habitat, favoring factors, infections.
Neisseria meningitidis (meningococcus)
Essential: Neisseria meningitidis - strict human pathogens with worldwide distribution. General
properties, transmission, classification: serogroups and serotypes involved in human pathology,
in the production of outbreak of epidemic meningitis, in different geographical areas, in children.
Virulence factors: Meningococcal Surface structures (Polysaccharide capsule, endotoxin (LPS),
Protease IgA, pili): chemical composition, antigenic specificity, mechanism of action, role in
pathogenicity; practical applicability, efficiency. Effect on: secretory IgA, bacteria and
phagocytes. Immunogenicity - acquired immunity (passing through infection or vaccination),
antibodies (anti-capsule antibodies, group, and maternal antibodies): effect (neutralizing,
protection from invasion, reinfection, and diagnostic values). Consequences on human body: the
consequences of mucosal colonization, meningococcal carriage, "healthy carriers", epidemic
strains of the meningococcus and dissemination. Pathogenesis of meningococcal infection.
Sensitivity/ Resistance to antibiotics: Penicillin G, Sulphonamides.
Laboratory diagnosis of meningococcal meningitis: at practical activity.
Important: Sporadic or epidemic meningococcal meningitis: pathogenesis, clinical forms, risk
groups, favoring factors, meningococcal group, complications, prognosis, and sequela. Invasive
meningococcal infection, Invasive meningococcal disease (IMD): evolution, risk groups.
Treatment and Prophylaxis of meningococcal meningitis: chemoprophylaxis: AB, route of
elimination, duration, action on pharyngeal mucosa and on carriers. Immunizations, Vaccine:
composition and efficiency.
Useful: Genus Neisseria: Classification. Pathogenic species, commensal species, and
nonpathogenic species: species (Neisseria catarrhalis Subgenus Branhamella (Moraxella genus),
Neisseria lactamica, subflava, sicca, flavescens): habitat, favoring factors, infections: respiratory
tract infections (upper and lower), meningitis, endocarditis, arthritis, eye infections, urinary
infections.
Optional: Family Neisseriaceae: Genres: Genus Neisseria Moraxella, Kingella, Acinetobacter,
subgenres (Branhamella).
Summary
- Species
- Infections
Clostridium botulinum, Clostridium tetani
Genus Clostridium
- General characteristics: obligate anaerobes, toxin, toxoid, antitoxin (definitions)
17

1. Clostridium botulinum - botulism
Essential: food-poisoning paralytic disease, wound botulism (rarely), ubiquitous (soil, marine
sediment). Botulism: Pathogenesis: toxin = botulin with 8 antigenic forms (A=>G), human
strains: toxins A, B or E, mechanism of action (neurotoxin, flaccid paralysis)
Important: Treatment: Penicillin + Antitoxin: trivalent antitoxin (A,B and E) or a specific
antitoxin. Prophylaxis.
Diagnosis: is primarily by clinical presentation because culture and identification take a few
days. Laboratory diagnosis: at practical activity.
Useful: Symptoms of food poisoning and wound botulism.
2. Clostridium tetani - tetanus
Essential: Clostridium tetani: habitat, mode of infection, tetanus (local, generalized tetanus),
Tetanus: pathogenesis: toxin = tetanospasmin, mechanism of action (neurotoxin, spastic
paralysis), Generalized tetanus, Local tetanus, Cephalic tetanus, Neonatal tetanus.
Prophylaxis: immunization with tetanus toxoid (DTaP, TT), In children under the age of seven,
the tetanus vaccine is often administered as a combined vaccine, DPT/DTaP vaccine, which also
includes vaccines against diphtheria and pertussis. Calendar of immunization: For adults and
children over seven, the Td vaccine (tetanus and diphtheria) or Tdap (tetanus, diphtheria, and
acellular pertussis) is commonly used.
Important: Treatment: must be initiated on a clinical diagnosis: Penicillin + antitoxin (serum
with antibodies - antitoxin, tetanus Ig) + tetanus toxoid.
Diagnosis: is primarily by clinical presentation because culture and identification take a few
days. Laboratory diagnosis: at practical activity.
Useful: Tetanus: sign and symptoms
3. Clostridium perfringens and gas gangrene
Essential: Pathogenesis: exotoxins, mechanism of action. Diseases: gas gangrene (myonecrosis),
localized cellulites, necrotising enteritis.
Species: Clostridium septicum, Clostridium histolyticum Clostridium sporogenes Clostridium
aedematiens
Important: Treatment - as soon as the clinical diagnosis is made. High dosages of penicillins +
polyvalent serum.
Laboratory diagnosis (at practical activity)
18

Useful: Symptoms of gas gangrene
4. Clostridium difficile
Essential: Diseases: Antibiotic-associated diarrhoea, Pseudo membranous (necrotizing) colitis.
Pathogenesis: cytotoxins A and B, mechanism of action.
Important: Treatment, Laboratory diagnosis (at practical activity)
Useful: Symptoms of colitis
Questions and reviewing
1. Bacterial meningitis can be produced by:
a) Streptococcus pneumoniae
b) Neisseria meningitidis
c) Mycobacterium tuberculosis
d) Haemophilus influenzae
e) Mycoplasma pneumoniae
2. Meningococcal toxin: a. is an exotoxin, b. is an endotoxin, c. is used for vaccine preparation,
d. produces fever, e. produces toxic shock
3. Clostridium tetani pathogenesis factor is an:
a) exotoxin that blocks release of acetylcholine
b) exotoxin that inactivates EF2 (elongation factor 2) by ADP-ribosylation (inhibits
cellular protein synthesis)
c) causes muscle spasm by blocking the release of the inhibitory neurotransmitter glycine
d) produces cutaneous edema due to its adenylate cyclase function
e) endotoxin
4. Symptoms of C. botulinum food poisoning include double vision, inability to speak, and
respiratory paralysis. These symptoms are consistent with:
a. Invasion of the gut epithelium by C. botulinum
b. Secretion of an enterotoxin
c. Endotoxin shock
d. Ingestion of a neurotoxin
e. Activation of cyclic AMP.
19

SEXUALLY TRANSMITTED DISEASES
Neisseria gonorrhoeae - Gonorrhea
Gonococci: Heterogeneity of surface antigens, variability of gonococcal pilli and of external
membrane proteins and production of IgA protease, allowing gonococci to withstand the action
of the body's defense factors and produce chronic infection.
Essential: Neisseria gonorrhoeae: Gonococcus: general properties, structure and its importance
for the gonococcus pathogenicity; habitat, serotypes. Transmission: sexual contact, mother's
genital tract to the newborn during birth. Virulence and pathogenicity factors: surface structures
(common pili, endotoxin and external membrane proteins OMP (PorP, OpaP): structure,
chemical composition, functions, genetic determinism, and role in the pathogenesis of
gonococcal infections. Effect on bacterial cells, phagocytes, complement system (C') and
secretory IgA. Antigen, immunogenicity, variability (transformation): mechanism of action,
consequences. Immune response: effect of specific antibody, cross-reactivity, practical
applicability (identification of gonococcal serotypes by serological reactions). Inflammatory
response, Invasive strains: properties. Defence mechanisms of human body: protective role
against gonococci: phagocytes, the mucous membrane, invasion with neutrophils, followed by
epithelial sloughing, formation of submucosal microabscesses, and purulent discharge.
Laboratory diagnosis of gonococcal infections; Laboratory diagnosis in gonorrhea - (at practical
activity).
Important: gonococcal infections: localized infections: urethritis in men, cervicitis, vaginitis in
women, pelvic inflammatory diseases (PID), neonatal ophthalmia (ophthalmia neonatorum),
rectal gonorrhea, pharyngeal gonorrhea (gonorrhea of the throat): frequency, risk groups.
Pathogenesis: primary infection: attachment of gonococci to mucosal surfaces, colonization of
urethral and vaginal mucosa, multiplication. Complications: local inflammation (in men,
inflammation of the epididymis (epididymitis); prostate gland (prostatitis), pelvic inflammatory
diseases (PID) in women, chronic and disseminated gonococcal infections. Antibiotics
resistance: resistance to penicillin, tetracycline, molecular mechanism (penicillinase producing
strains (PPNG), multiple-resistant strains to antibiotics);
Useful: Gonorrhea: Signs and symptoms: urethral pus discharge, vaginal discharge,
complications. Neonatal ophthalmia: contamination, incidence, symptoms, prevention (1% silver
nitrate, 1% tetracycline, and 0.5% erythromycin ophthalmic ointments to all infants shortly after
birth). Disseminated gonococcal infection (DGI): risk groups, pathogenesis. Rectal infections:
risk groups.
Treatment and Prevention of gonorrhea: sexual hygiene, treatment of the patients and their
contacts; co-infection with Chlamydia.
Optional: Complications of gonorrhea: infertility, arthritis, skin lesions, endocarditis,
pericarditis, meningitis. Differencial diagnosis: Vaginitis: T. vaginalis. Genitourinary tract
infection: C. trachomatis, syphilis, and T. vaginalis.
20

Questions and reviewing
-Should the sexual partner be alerted so that they can be tested?
-Has the gonorrhea progressed into Pelvic Inflammatory Disease (PID)?
-Can the gonorrhea come back without additional exposure?
FUNGAL INFECTIONS
Summary
1. Pneumocystis jirovecii- Pneumocystis pneumonia, pneumocistosis
2. Aspergillus sp.
3. Cryptococcocus neoformans
4. Candida sp.
Algorithm
- Generalities
- morphology
- transmission
- risk factors**
- pathogenesis
- diseases*
- susceptibility to antifungal drugs
- treatment,
- clinic
- diagnosis
- prevention
*opportunistic infections: in immunocompetent patients (rarely), **in immunocompromised
patients, immunosuppression (frequent): immunosuppressive drugs: chemotherapy, steroid
therapy (high-dose, long-term), cancer, hematological malignancies or lymphoma, acute
leukemia and neutropenia, transplants (bone marrow, lung, heart), advanced AIDS, congenital
immunodeficiency.
Essential:
Pneumocistis jirovecii- (former carinii) - pneumocistosis,
Pneumocystis: Generalities: properties, habitat, geographical distribution, transmission (by
respiratory route, inhalation and probably person-to-person transmission), location (human lung
tissue), stages, forms (cysts, spores/sporozoites)
Pneumocystis pneumonia: lung infection, diffuse bilateral alveolar disease. Pathogenesis: in
healthy people: latent infection, induction of humoral immunity (antibody). In
immunocompromised patients: attachment of Pneumocystis to the alveolar epithelium, massive
21

multiplication in the alveolar spaces, inflammation, lung injury, the airspace obliteration, and
impaired gas exchange, reduced gas exchange, significant hypoxia. Hypoxia, along with high
arterial carbon dioxide (CO2) levels, stimulates ventilation, thereby causing dyspnea. Oxygen is
less able to diffuse into the blood. The alveolar exudate: pinkish substance, an amphophilic,
foamy, amorphous material, composed of proliferating fungi & cell debris; changes in noninvolved
alveoli and in the interstitial tissue of the lungs.
Risk groups: AIDS: the most commonly opportunistic infection*, immunosuppression**,
premature or severely malnourished children, 3 to 6 months old infants.
Important: Pneumocystis: taxonomy (fungus or protozoa), currently designation; species:
Pneumocystis carinii (animal), jirovecii (human),
Susceptibility to antifungal drugs: anti-pneumocystis medication, drugs currently available:
Pentamidine isothionate (high frequency of side effects), Sulfamethoxazole/trimethoprim (cotrimoxazole
or Bactrim): low toxicity and greater efficacy, Atovaquone, Trimetrevate.
Course of the disease: fatal if not treated;
Prophylaxis: Preventive treatment: pentamidine inhalations or oral co-trimoxazole:
Useful: Characteristic signs & symptoms: healthy people (sub clinical infection, only
antibodies); pneumocistosis: immunocompromised patients (fever, dry cough, non-productive
cough, difficulty in breathing, dyspnea, tachypnea); infants 3 to 6 months old (usually no fever,
but gradually begins to breathe faster than normal. The child's lips, fingernails, and skin: blue or
gray).
Diagnosis of pneumocystis pneumonia: X-ray, Bronchoscopy. Laboratory diagnosis of
pneumocistosis: Identification of Pneumocystis jirovecii in pulmonary tissue or in lung fluids.
Laboratory diagnosis: at practical activity.
Optional: Pneumocystis Morphology: Trophozoit: ovoid, 2- 4μ, single nucleus. Cysts: contain
up to 8 ovoid-to-fusiform spores or sporozoites (also called intracystic bodies), 7-10μm in
diameter, globular, a thick wall. Free trophic forms: 1.5-5μ and have small nuclei (0.5-1μ)
Aspergillus - pulmonary aspergillosis
Essential: Aspergillus: Generalities: is a spore-forming fungus (mold). Distribution: worldwide.
Habitat: spores in the air, soil, on many plants and trees. Transmission: The most common
portal of entry is the respiratory system, spores - colonization with aspergillus of the airways
mucous membranes, ingestion of contaminated foods: bread, potatoes, and nuts. Aspergillus
fumigatum is the most prevalent fungal pathogen responsible for fatal invasive aspergillosis.
Toxins released by the fungi (mycotoxicosis).
Aspergillosis: a group of lung diseases. Aspergilloma, Allergic bronchopulmonary aspergillosis
(ABPA); Chronic necrotizing pulmonary aspergillosis (CNPA), Invasive aspergillosis (IA),
Disseminated invasive aspergillosis: (DIA)
22

Pathogenesis: Aspergilloma (a "fungus ball"): a clump of fungus in the lung parenchyma; a ball
(dead lung tissue, mucus, and other debris). Asymptomatic radiographic abnormality or cases
complicated by severe hemoptysis (occasionally).
ABPA (eosinophilic pneumonia): hypersensitivity response to aspergillus antigens type I and a
type III, mast cell degranulation, inflammation (inflammatory cells, cytokines), bronchoconstriction,
increased mucus production, eosinophilic infiltrate, necrosis; progressive
pulmonary fibrosis. CNPA: subacute pneumonia, a progressive infiltrate in lung cavities. IA:
invasion of blood vessels, multiple location and cavities infiltrates, progressive, often fatal.
Dissemination to other organs, particularly the central nervous system, may occur. DIA: an
infection spread widely through the body.
Risk factors: Aspergilloma: the cavities caused by tuberculosis, other necrotizing pulmonary
processes or sacs of the airways (bronchial enlargement); ABPA: patients who are allergic to
Aspergillus, with asthma and/or cystic fibrosis. CNPA: underlying pulmonary disease (COPD,
interstitial lung disease, previous thoracic surgery), some degree of immunosuppression,
alcoholism, collagen-vascular disease or chronic granulomatous disease. Invasive aspergillosis:
*opportunistic infections, severely immunosuppression**, central venous catheters;
Important: Species: Important medically species: Aspergillus fumigatus, flavus, niger, terreus,
nidulans, the most common specie: Aspergillus fumigatus.
Susceptibility to antifungal drugs (antifungal medications): Fungizone (Amphotericin B),
Itraconazole (Sporanox), Fungizone (Amphotericin B), + Itraconazole. Antifungal drugs
(Itraconazole) can not to eradicate aspergillus. Antifungal drugs (Itraconazole), in combination
with steroid therapy (oral corticosteroids) - ABPA.
Diagnosis: Chest X-rays, or computed tomography.
Laboratory diagnosis of aspergillosis (at practical activity): serum IgE and eosinophilia,
immunological tests (the antibody levels) for Aspergillus, sputum staining and cultures.
Useful: Treatment & Prevention
Aspergilloma: do not require treatment (most cases), or surgery; Mucus plugs may be removed
by bronchoscope aspiration.
Optional: Morphology: spores: small (2 to 3 micrometer),
Signs & Symptoms of Pulmonary Aspergillosis: fever, cough, shortness of breath, chronic
sputum production, coughing up brownish mucous plugs, dyspnea, pleurisy chest pain,
hemoptysis and recurrent infections.
Cryptococcus neoformans- Pulmonary cryptococcosis,
Essential: Cryptococcus neoformans: Morphology: encapsulated yeast. Naturally, often found
in soil contaminated by bird excrement. Cryptococcosis occurs in both animals and humans.
Contamination: via the respiratory route (inhalation, pigeon droppings). No transmission:
animal-to-human or person-to-person. Cryptococcosis: Pulmonary cryptococcosis, Wound or
cutaneous cryptococcosis, Cryptococcal meningitis.
23

Pathogenesis: Pulmonary cryptococcosis: pulmonary nodules (cryptococom) or an
asymptomatic pulmonary infection followed later by the development of meningitis,
Cryptococcal meningitis: result of dissemination of the fungus from a pulmonary infection, is
often the first indication of disease. Central nervous system involvement often causes death or
leads to permanent damage.
Risk factors: *opportunistic infection (one of the most common life-threatening fungal infection
in patients with AIDS), other immunocompromised patients**,
Important: Species, variants, serotypes: C neoformans v. gattii, C. neoformans v. neoformans,
A and D. with C. neoformans (most infections): lung infection, meningitis.
Prevalence: has been increasing over the past 20 years (the increase in incidence of AIDS).
Susceptibility to antifungal drugs:
Pulmonary cryptococcosis: the majority of cases resolved without antifungal therapy.
Fluconazole (Trifulcan). Cryptococcal meningitis: Amphotericin B (Fungizone), 5- Flucytosine
(Ancotil), followed by Fluconazole.
Laboratory diagnosis of Cryptococcosis: at practical activity.
Useful: Distribution: worldwide, C. gattii is found mostly in the tropics. Prevention and
treatment: long time: oral (ten weeks) intravenous (two weeks). Mortality: 100% without
treatment, 20% with treatment
Optional: Signs & Symptoms
Pulmonary Cryptococcosis: In people with a normal immune system, Pulmonary infection:
“silent” or few symptoms (chest pain, dry cough). Cryptococcal meningitis: Neurological
symptoms.
Candida species
Essential: Candida: General properties: morphology, commensally yeast; some Candida species
have the potential to cause disease. Habitat: oral mucosa, vaginal mucosa, healthy vagina, skin,
gastrointestinal tract. Transmission: from one person to another (sexually, mother to newborn).
Diseases produced by Candida spp.: Superficial infections of the mouth, of the respiratory tract,
of the gastrointestinal tract (esophageal, gastric, intestinal mucosa), of the urogenital tract.
Infections of the nails (onychomycosis), Skin infections: Cutaneous candidiasis, Systemic
infections: Septicemia, Visceral candidiasis,
Candidiasis: oral candidiasis (oral thrush), bronchitis, bronchopulmonary candidiasis,
esophagitis, laryngitis, epiglottis, gastritis, enteritis, peritonitis, vaginal candidiasis, balanoprostatitis,
urethritis. Pathogenesis: colonization, biofilm, the starting point: endogenous
(digestive, pulmonary), exogenous (iatrogenic), dissemination, visceral location: lung, eye, heart,
CNS, etc. Risk factors: endogenous, exogenous infections: extended antibiotic therapy, oral
contraception, decrease body's resistance (in newborns, pregnancy, diabetes, old persons),
24

profession, immunosuppression** medical/therapeutic devices/vascular injury (intravenous
catheter, injections, parenteral nutrition, prostheses, (e.g. laryngeal prosthesis, valve) and surgery
(abdominal, cardiac surgery), peritoneal dialysis.
Important:
Pulmonary candidiasis: pathogenesis, types (bronchopneumonia, interstitial pneumonia),
complications (dissemination through blood), differential diagnosis.
Gastrointestinal tract infections: Esophagitis, Gastritis, Enteritis, Peritonitis: favoring factors,
pathogenesis, lesions, complications; forms, incidence, risk group, pathogenesis complications
(intestinal mucosa perforation, disseminated candidiasis) (infants, children) (diarrhea,
dehydration),
Urogenital tract infections in women and men: Vaginitis, Balano-prostatitis, Urethritis:
transmission (sexually transmitted disease), incidence, pathogenesis, Candida specie, favoring
factors, recurrent vaginal candidiasis, signs and symptoms (creamy white discharge).
Septicemia: generalized candidiasis, candidemia: risk groups, risk factors, pathogenesis,
Visceral candidiasis: pneumonia, endophthalmitis, cardiac candidiasis (endocarditis,
myocarditis, pericarditis), vasculitis; meningitis, arthritis, osteomyelitis, pyelonephritis,
hydronephrosis.
Cerebral Candidiasis: Meningitis: risk factors, Candida species, mortality, complications.
Cutaneous candidiasis: involved skin areas, Candida species, Risk groups, risk factors,
spreading, contagiously.
Useful: Susceptibility to antifungal drugs, Class of antifungal drugs: Azoles (Clotrimazole,
Ketaconazole, Econazole, Ravuconazole Voriconazole, Posaconazole, Fluconazole,
Itraconazole); Echinocandins (caspofungin, micafungin, anidulafungin), Amphotericin B,
Flucytosine. Echinocandins (should be used as the first-line treatment of candidemia).
The sensitivity testing of isolated strain is necessary due to the emergence of resistant strains to
antifungal drugs.
Laboratory diagnosis of Candidiasis: at practical activity.
Species: Over 200 species of Candida exist in nature; only few species have been associated
with disease in humans: Candida albicans (important),
Optional: Candida species: Candida krusei, C. quilliermondii, C. parapsilosis, C. tropicalis, C.
glabrata, C. pseudotropicalis, C. lusitaniae. Treatment: topical or oral (systemic) therapy,
Prevention
25

BIBLIOGRAPHY
1. Monica Junie, Luciana Stănilă, Carmen Costache, Medical Microbiology, “Iuliu Haţieganu”
University Publishing House, Cluj-Napoca 2003
2. Medical Microbiology – Jawetz, Melnick & Adelberg’s, 22 - nd autori: Brooks G. F., Butel J.S.
and Ornston L.N.
QUESTIONS AND REVIEWING
Pneumocistis jirovecii (former carinii)
Aspergillus:
a. produces a human disease called ........................................
b. is a protozoan with double symmetry.
c. is transmitted via respiratory airways
d. is localized in the pulmonary alveolus
e. can be identified in the following pathological products: .........................................
a) produces aspergilloma (fungus ball)
b) produces ascaridosis
c) is a mould (filamentous fungi)
d) is a protozoan
e) is transmitted to humans throughout meat consumption.
Which one of the following may cause pneumonia?
a. Pneumocistis jirovecii (carinii)
b. Aspergillus.
c. Candida.
d. Criptosporidium.
e. Cryptococcus.
Candida albicans may produce:
a. skin infections
b. pneumonia
c. systemic infections
26

d. cysts inside the brain
e. endocarditis
PARASITOLOGY - PROTOZOA
EDUCATIONAL OBJECTIVES
Definition of: parasites, parasitism, definitive host, intermediary host, vector (active, passive),
life cycle. Parasites classification: Transmission/ human contamination;
Parasites action on human body: Nutritional lost, Mechanic (macroscopic => compression,
microscopic => e.g. red cell break), Favoring bacterial implantation & development, Irritation
(tissue => isolation through membrane => cyst formation, Sensitive => modification of
peristaltic movements).
Human body reaction to the presence of parasite: Hypereosinophilia, Immunity (cellular,
humoral), definitive (e.g. toxoplasmosis), temporary/partial (e.g. malaria in endemic areas).
Algorithm
- Generalities
- morphology
- life cycle
- transmission
- clinic
- diagnosis,
- treatment,
- prevention
SEXUALLY TRANSMITTED DISEASES
Trichomonas vaginalis
Essential: Properties: parasite, Protozoa: trophozoit does NOT have a cyst form, strictly human
parasite; infect the genital and urinary tract both in males and females, widespread prevalence in
populations, important public health concern.
Transmission: Sexually Transmitted disease (STD); rarely: contaminated towels, douche
equipment, examination instruments, and other objects
Pathogenesis: Trichomoniasis: "trich" or "trick": Acute infection in females, Evolution,
Chronic infection. Factors affecting pathogenesis: intensity of infection, pH and physiologic
status, the hormonal changes. Infection normally limited to vagina, cervix and vulva, urinary
tract involvement (cystitis); vaginal mucosal surface: tender, inflamed, eroded, vaginal
discharge. Complications: sterility, bacterial infection, cervical carcinoma.
27

Important: Laboratory diagnosis: at practical activity.
Useful: Clinical findings: Asymptomatic: healthy carriers (men, women), Acute infection: in
females and in male. Symptoms & signs in women. Treatment, Prevention,
Optional: Morphology: Trophozoit: 5-15 μm long - up to 30 μm, four anterior flagella plus a
recurrent flagellum, undulating membrane, costa, single nucleus, axostyl
Questions and reviewing
1. Trichomonas vaginalis
a. is a helminthes
b. is a protozoan living inside erythrocytes
c. is a protozoan living inside duodenum
d. is a protozoan present at the level of vagina and cervix
e. exists only as a vegetative form (trophozoit)
2. Which of the following symptoms are specific for urogenital trichomoniasis?
a. it is asymptomatic in males
b. symptoms of bladder infection can occur
c. in time, infection becomes chronic
d. reactivations during pregnancy are possible
e. parasites produce ulcerations of the vaginal mucosa
Summary
1. Entamoeba hystolitica
2. Giardia lamblia intestinalis
3. Cryptosporidium
4. Microsporidium
Algorithm
- Generalities
- Morphology
- life cycle
28
DIGESTIVE TRACT INFECTIONS

- Human contamination
- pathogenesis
- clinic
- diagnosis, treatment, prevention
Entamoeba hystolitica
Essential: Generalities: cause amebiasis called also amebic dysentery and liver abcess,
worldwide, most frequently in tropical countries, areas with poor sanitation, homosexuals.
Human contamination: by the fecal-oral route (by cysts).
Amoebiasis, sometimes spelt amebiasis: asymptotic carriers (90% of infected person), acute
intestinal amebiasis, evolution, chronic amebiasis (amebom), visceral amebiasis.
Pathogenesis: Acute intestinal amebiasis (amoebic dysentery or amoebic colitis). The
trophozoites invade the colic epithelium: secrete enzymes => localized necrosis, lesions reaches
the muscular layer, form ulcers (a typical teardrop ulcer), progression into the submucosa, leads
abscesses’ formation, progression into capillaries => invasion of the portal circulation: visceral
amebiasis: the most frequent site of systemic disease is the liver, where abscess form.
Important: Morphology: Trophozoit; (the motile amoebae- pseudopod), Cyst in feces. Life
cycle: cysts, trophozoites, cysts in feces.
Diagnosis: finding either trophozoites in diarrhea stools or cysts in formatted stool; cysts are
passed intermittently, at least 3 specimens should be examined. Serologic testing - diagnosis of
invasive amebiasis Complete examination for cysts includes a wet mount in saline, an iodinestained
wet mount and a fixed, trichrome-stained preparation.
Useful: Clinic: Symptoms & signs
Acute intestinal amebiasis: mild diarrhea to dysentery with blood and mucus in the stool, lower
abdominal discomfort, flatulence, tenesmus.
Chronic amebiasis: low grade symptoms: occasional diarrhea, weight loss and fatigue.
Amoebic liver abscesses: right, upper, quadran pain, weight loss, fever tender, enlarged liver.
Prevention: signs good sanitary practices, avoiding fecal contamination of food and water.
Treatment: Metronidazole (Flagyl) plus iodoquinol, Hepatic amebiasis is treated with
Dyhidroemetine. Asymptomatic cyst carriers should be treated with iodoquinol.
Optional: Morphology details: Trophozoites; Cyst: usually spherical, but may be ovoid, 4
nuclei.
Giardia lamblia intestinalis: Giardiasis
Essential: Generalities: worldwide distribution, most easily recognized intestinal parasite, main
cause of diarrheal outbreaks from contaminated water supplies, considered in differential
diagnosis of any “traveler’s diarrhea”.
29

Transmission: fecal - oral routes: food and water (water - borne outbreaks of diarrhea), person
to person transmission, by the ingestion of infective cysts. Giardiasis: a major diarrheal disease.
Pathogenesis: enteric protozoan parasite. Trophozoites colonize the small intestine mucosa, the
gallbladder or cholecyst: attachment, on mucosa, inflammation, watery diarrhea, malabsorbtion
syndrome.
Important: Morphology: Trophozoites: bilaterally symmetrical, roughly pear shaped, two
nuclei, four pairs of flagella, median body, sucking disk. Cysts: ovoid, four prominent nuclei, 4
pair of flagella.
Life cycle: cysts, excystation, trophozoites, cysts in feces.
Laboratory diagnosis: at practical activity.
Useful: Clinic: asymptomatic or clinical symptoms: in adults and children: anorexia, abdominal
pains, nausea and epigastric pain or tendress.
Treatment: Metronidazole (Flagyl).
Prevention: boiling, filtering, and adding iodine to unreliable water sources (cysts resist chlorine
treatment). Treatment of human carriers, periodic screening of the staff working in daycare
centers and food handlers
Optional: Morphology details: Trophozoites: length: 10 to 15 μm, and width: 5 to 7 μm,
anterior portion of the ventral surface form a sucking disk, round or ovoid central nucleolus.
Cysts: ovoid, 8 -12 μm by 6-10 μm in width, four prominent nuclei, flagella dispersed in a
seemingly helter-skelter fashion, cyst wall: smooth and bright, median bodies
Cryptosporidium – cryptosporidiosis,
Essential: Generalities: worldwide distribution, twenty species from a variety of vertebrates,
including mammals, birds and fish. Species that infects humans and most mammals is C.
parvum, recently recognized as a cause of diarrheal disease in humans. Risk groups: immunecompromised
individuals-AIDS, immunocompetent persons: animal handlers, travelers, children
in day-care centers.
Transmission: by oocysts (containing sporozoites) via: fecal-oral route, food and water.
Pathogenesis: enteritis: Development of Cryptosporidium occurs in the brush border of the
epithelial cells of the small intestine (great numbers of parasites under the mucosal epithelium of
the intestine), enter epithelial cells: damage to the microvilli, inflammation, enterotoxin
production, watery diarrhea, malabsorbtion. In immunocompromised persons: chronic evolution,
severe and prolonged watery diarrhea associated with marked fluid loss (up to 15L- 25 liters
/day), dehydration and 10% weight loss; particularly severe and often fatal. In AIDS patients:
pulmonary cryptosporidiosis in addition to intestinal cryptosporidiosis.
Important: Morphology and Live Cycle: Oocysts, Sporozoites, Trophozoites, and Merozoites.
Cryptosporidium in the epithelial cells of small intestine: sexual and asexual cycle. Asexual
cycle: Sporozoites, trophozoites, meront (containing 8 arc-shaped merozoites), merozoites -
30

infect other enterocytes. Sexual cycle: (gametogony): macrogamonts, microgamonts, micro and
macrogametes, the formation of oocysts (containing sporozoites).
Laboratory diagnosis: at practical activity.
Useful: Clinic: immunocompetent persons: transient diarrhea with watery stools and abdominal
cramps.
Treatment: drugs: Pyrimetamine + Sulfadiazine, paromomycin, atovaquone, azithromycin:
unnecessary for patients with normal immunity, temporarily effective for immunocompromised
patients: supportive therapy (fluid rehydration, electrolyte correction).
Prevention: Careful hand washing, boiling water. Cryptosporidium oocysts: hardy and resistant
to numerous disinfectants, highly resistant to chlorine disinfection.
Optional: Morphology details: Oocysts: round or spherical ( 5µ), contain 4 sporozoites each,
Trophozoites: 2-5 µ, intracellular spheres.
Microsporidia - microsporidiasis
Essential: Generalities: is more fungal than protozoa, spore-forming unicellular microorganism,
opportunistic infectious agents, worldwide, more than 1,200 species, at least 14 microsporidia
identified as human pathogens: e.g. Encephalitozoon intestinalis, Enterocytozoon bieneusi.
Reservoirs: animals, birds, (especially parrot), Transmission: spores. The spores are inhaled or
consumed by humans.
Pathogenesis: immunocompromised patients, AIDS. Intestinal microsporidiosis - enteritis: in
AIDS patients, chronic severely diarrhea, malabsorption, and gallbladder disease, significant
mortality risk. Lung infection.
Important: Morphology & life cycle: The infective form: the resistant spore (survive for a long
time in the environment). Inside the cell, the sporoplasm undergoes extensive multiplication
either by merogony (binary fission) or schizogony (multiple fission), free mature spores (can
infect new cells). Laboratory diagnosis: at practical activity.
Useful: Microsporidiosis - microsporidiasis: in immunocompetent patients (rare cases), in
immunocompromised patients (the most common), clinical forms: very diverse, varying
according to the causal species: keratoconjunctivitis, skin and deep muscle infection, urinary
tract infections, etc. Treatment: Fumagillin, Albendazole, Prevention.
Optional: Species of Microscoporidia infecting humans, genera Encephalitozoon,
Enterocytozoon, Microsporidium, Nosema, Pleistophora, symptoms
Questions and reviewing
1. Entamoeba hystolytica:
a. produces cholera-like enteritis
b. produces dysentery-like enteritis
31

c. evolves with feces with mucous and blood
d. evolves with watery diarrhea
e. can produces serious surgical complications
2. Which of the following properties correspond to Giardia intestinalis?
a. It exists as trophozoite and cyst
b. Contamination occurs by eating viable cysts from feces-contaminated water or
vegetables
c. It is a human parasite
d. the main route of contamination is by sexual contact
e. the main location of the parasite is the genital tract
3. Which one of the following parasites may be a cause of diarrhea in immune compromised
persons?
a. Pneumocistis jiroveci
b. Aspergillus.
c. Microsporidium
d. Criptosporidium.
e. Criptococcus.
4. A diarrhea syndrome with the following characteristics (bloody, mucus containing diarrhea) in
a patient returning from Togo is more likely produced by:
a. Vibrio cholere
Summary
b. Trichomonas
c. Entamoeba hystolitica
d. Entamoeba coli
e. Plasmodium ovale
INFECTIONS OF THE CNS
1. Free living amoeba: Naegleria, Acanthamoeba
2. Toxoplasma gondii
3. Blood Flagelates: Plasmodium
4. Encephalitis produced by parasites: cerebral toxoplasmosis, cerebral malaria,
32

Algorithm
- Generalities
- Morphology
- life cycle
- Human contamination
- pathogenesis
- clinic
- diagnosis, treatment, prevention
Free living amoebae
- Naegleria fowleri: primary amoebic meningoencephalitis
- Acanthamoeba: encephalitis: granulomatous encephalitis, in patients with an
immunodeficiency, cutaneous amoebiasis and keratitis.
These species are often described as "opportunistic free-living amoebas" as human infection is
not an obligate part of their life cycle.
Essential: Naegleria fowleri: Generalities: Morphology: trophozoite, cysts, habitat (fresh water).
Human contamination: bathing in contaminated water. Meningo-encephalitis: pathogenesis:
penetration of the cysts into the nasal cavities, the lamina cribriforma of the ethmoid bone,
progression via the first cranial nerve to the brain, amoebae multiplication in the brain
(haemorrhagic necrosis), multiplication in the cerebrospinal fluid. Important: Evolution:
fulminant (fatally in less than 3 days).
Useful: Clinic: rhinopharyngitis, meningeal signs and symptoms (fever, headache, vomiting and
disturbances of smell and taste). Treatment: early treatment Amphotericin B (Fungizone), rare
cases survive. Prevention: avoiding bathing in suspect water.
Optional: Morphology: trophozoite 10-35 m, with pseudopodia, flagella. The cysts are
spherical. The cerebrospinal fluid: cloudy or haemorrhagic, pleiocytosis, red blood cells, low
glycorrhachia.
Questions and reviewing
1. Naegleria fowleri:
a. produces a human disease called fasciolosis
b. is transmitted to humans through meat consumption
c. is transmitted to humans through the eye (swimming in contaminated pools)
d. is transmitted to humans by sexual contact
e. is an amoeba causing acute meningo- encephalitis
33

2. Encephalitis can be produce by:
a. rabies virus
b. Mycobacterium tuberculosis
c. Toxoplasma gondii
d. Naegleria fowleri
e. Plasmodium falciparum
Toxoplasma gondii
Essential: Toxoplasma gondii: Generalities: coccidian protozoan, worldwide distribution infects
a wide range of animals and birds. The natural reservoir of Toxoplasma: domestic cat, other
felines; Intermediary host: almost all animal species and birds. Morphology: trophozoite, tissue
cyst, oocyst. Human contamination: with tissue cysts (contaminated raw or undercooked beef,
lamb, or pork, oocysts (soil, milk, water, or vegetables), Contaminated blood transfusions, organ
transplants, and accidental inoculation acquired in the laboratory. Risk groups: Exposure to cats,
workers in animal farms, meat holders, AIDS, pregnant woman
Pathogenesis: Acquired toxoplasmosis: acute toxoplasmosis (most frequently a mild condition,
swollen lymph nodes); latent toxoplasmosis (cysts in nervous and muscle tissue); chronic
toxoplasmosis: cysts in the brain; reactivation, and damage to the brain - cerebral toxoplasmosis
(encephalitis), with a severe evolution, in immunocompromised patients (e.g. AIDS patients).
Congenital toxoplasmosis: acute infection during the pregnancy: severity, percentage of
transplacental infection, fetus age; pregnancy evolution, forms of congenital toxoplasmosis:
stillbirth or severe forms; intracerebral calcification or chorioretinitis, latent forms.
Important: Life cycle: Sexual cycle: definitive host, sexual multiplication, oocysts. Asexual
cycle: intermediary hosts, asexual reproduction, cysts.
Laboratory diagnosis: at practical activity. Diagnosis of acute toxoplasmosis, in pregnant
women, new born and other patients: serology: detection of Ig.M or of Ig.A antibodies against
Toxoplasma. Fetus infection: fetal blood, amniotic liquid analysis.
Useful: Clinical presentations: Signs & symptom of acquired toxoplasmosis and congenital
toxoplasmosis.
Treatment: Rovamicine, Spiramicine. Prevention: deep freezing and cooking of meat. Pregnant
women should avoid close contact with cats and their litter boxes.
Optional: Serologic assays: tests, Ig G high avidity test, PCR, Isolation of Toxoplasma from
blood, amniotic liquid.
Bibliography
1. Medical Parasitology, Markell, Voge, John, 9-th edition, 2006
2. Diagnostic Medical Parasitology, Lynne Shore Garcia, 5th Edition, ASM Press, 2006
34

3. www.dpd.cdc.gov/dpdx
Questions and reviewing
1. Acute Toxoplasma gondii infection acquired in the first semester of the pregnancy;
a. is always (100%) transmitted to fetus
b. is responsible for severe forms of congenital toxoplasmosis.
c. is the cause of the latent forms of congenital toxoplasmosis. ?
d. diagnosis of mother is made by the detection of specific Ig G antibodies in blood
e. diagnosis is made by the detection of T. gondii oocysts in mother’s feces
2. Acute Toxoplasma gondii infection acquired
A) in the first semester of the pregnancy;
B) in the second semester of the pregnancy;
C) in the 3 rd semester of pregnancy:
1) is always (100%) transmitted to fetus, 2). is responsible for severe forms of congenital
toxoplasmosis. 3). is the cause of the latent forms of congenital toxoplasmosis, 4).
diagnosis is made by the detection of specific Ig M antibodies, 5). may be responsible for
cranial malformations, cranial calcification, etc.
1 2 3 4 5
A …………………………………………………………………..........
B ………………………………………………………………………..
C ………………………………………………………………………..
Plasmodium - malaria
Essential
Plasmodium: Generalities, Morphology and Life cycle: intracellular parasites (sporozoites,
trophozoites, schizont, merozoites). Transmission to human: by bloodsucking bite of Anopheles
mosquitoes. Species: vivax, ovale, falciparum, malariae. Plasmodium falciparum is the most
serious (pernicious abscess). Plasmodium vivax is the most common.
Malaria: Pathogenesis: passage of sporozoites from the salivary glands of the mosquito into
human blood. The hepatic cycle: sporozoites, hepatocytes, latent or dormant form of
Plasmodium (hypnozoite), merozoites. The erythrocytic cycle: changes in erythrocytes: anemia,
splenomegaly, and hepatomegaly. Each species has distinct morphologic characteristics during
erythrocytic cycle. Pernicious abscess, cerebral malaria: in falciparum malaria, modified
infected erythrocytes are more adhesive to the vascular endothelium, adhere to the interior lining
of blood vessels and block blood flow through these vessels in the brain, liver, and kidneys (clots
formation) cerebral anoxia.
Important
Clinic: The signs and symptoms of malaria: Early symptoms: could mistake for influenza or
gastrointestinal infection, recurrent attacks: tertian malaria (benign: Plasmodium vivax,
Plasmodium ovale, malign: Plasmodium falciparum, quatrain malaria (Plasmodium malariae).
35

Laboratory diagnosis: at practical activity: demonstration of the parasites in thin and thick
blood smears: Giemsa-stained blood smears.
Useful: Life cycle: Sexual cycle in Anopheles mosquitoes (gametocytes, gametes fertilization,
zygote, ookinete, oocyst, sporozoites in saliva); Asexual cycle in humans: the hepatic cycle:
(sporozoites, trophozoites, schizont, merozoites), the erythrocytic cycle (ring stage, trophozoite,
schizont, merozoites)
Treatment: chloroquine for the erythrocyte stage, primaquine for the hepatic stage of vivax and
ovale malaria, quinine, pyrimethamine and sulfadiazine for therapy of P. falciparum malaria.
Prevention: No efficient vaccin, experimental malaria vaccine, Chemoprophylaxis Insecticide
Optional: Merozoites, schizonts or gametocytes can be seen within erythrocytes and may
displace the host nucleus. Merozoites have a “signet-ring” appearance due to a large vacuole that
forces the parasite’s nucleus to one pole. Schizonts are round to oval inclusions that contain the
deeply staining merozoites. Gamonts, Gametocytes.
Plasmodium species particularities: in peripheral blood, in visceral blood, mature schizont,
gametocytes
Bibliography
1. Medical Parasitology – Markell, Voge, John, 9-th edition, 2006
2. Diagnostic Medical Parasitology - Lynne Shore Garcia, 5th Edition, ASM Press, 2006
3. www.dpd.cdc.gov/dpdx
Questions and reviewing:
1. Plasmodium falciparum:
a. produces a mild form of malaria
b. is responsible for severe cases of malaria
c. has a particular shape (banana or sausage-like) of the gametocyte
d. is responsible for quatrain fever
e. all evolutionary forms are usually found in capillary blood
2. Rapid diagnosis and determination of the causal species are essential because of the
immediately life-threatening nature of which one of the following parasitic infections:
a. malaria
b. chronic amebiasis
c. ascaridosis
d. trichomoniasis
36

e. giardiasis
3. The seriousness of Plasmodium falciparum infection compared with the other 3 forms of
malaria is due to one of the following:
a. destruction of white blood cells
b. stem cells in the marrow are largely destroyed
c. extensive damage to the liver can occur during the erythrocytic phase
d. blood stream parasites reinvade the liver and induce a more severe disease state
e. misshapen infected red cells adhere to the interior lining of blood vessels and block
blood flow through these vessel => pernicious abscess
37