Upper Respiratory Tract Infections

LABORATORY DIAGNOSTICS OF INFECTIOUS DISEASES

(2 lessons)

Laboratory examinations:

1) standard routine testing, usual screening

2) organ specific tests indicated on the basis of symptoms

3) inner milieu describing tests

4) type and intensity of inflammation detecting tests

5) etiology detecting tests

Ad 1) common and simple tests, e.g. ESR, blood count, urinalysis, in older persons ECG

Ad 2) tests described in internal propedeutics, examples:

cough lungs examinationchest X-ray

icterus (jaundice) liver examinationserum liver enzymes and bilirubin, urine

bilirubin and urobilinogen, liver and biliary tact USG

etc.

Ad 3) tests used in various medical specialties, will be later discussed in intensive care

It is not true that inner milieu testing = blood gases and acid-base balance (Astrup).Blood gases and acid-base tests belong to extended spectrum of tests:

Situation / Testing appropriate
general alteration;
preexisting organ disease / routine:

• blood count
• glycaemia, serum ions (Na, K, Cl)
• serum urea, creatinine
• urinalysis
• serum AST, ALT

dyspnea, disturbed pulmonary function;
hypotension, cardiovascular failure;
hemorhagic signs;
multiple organ failure / extended:

• peripheral blood oxygen saturation (pulse oxymeter)
• pH and blood gas tests (Astrup)
• coagulation tests
• serum albumin

Ad 4) hematological, biochemical and pathological testing detecting type of infection

-blood count and differential count of leukocytes

-pyogenic, suppurative infections: leukocytosis, left shift (immature neutrophilic polymorphonuclears – bands, possibly metamyelocytes), cytoplasmic granulation of neutrophils, absence of eosinophils

-intracelular pathogens: decreased number of PMNs, increased lymphocytes and monocytes

-increased eosinophils: allergy, tissue helmintoses

-CRP and other acute phase proteins

-erythrocyte sedimentation rate (ESR)

Dynamics of inflammatory parameters in the course of bacterial infection.

Ad 5) microbiology diagnostics and clinical interpretation

a) Direct methods of pathogen identification

-microscopy: light, electron, ...

-culture: aerobic vs. anaerobic, on selective media, ...

-antigen detection: clearview, latexagglutination, ....

-molecular genetic methods: PCR, genetic probes, ...

Method / Contribution / Advantages / Disadvantages
microscopy / morphology and number of microbes in sample;
microbes-leukocytes and microbes with each other interrelationship / quick, easy, cheap; low demands on equipment / inappropriate in processing of high quantity of samples;
good experience needed;
only some microorganisms can be detected on the basis of morphology
culture / features of isolated agents;
complete identification;
sensitivity testing;
storage for future testing / easy, cheap; low demands on equipment / risk of selective identification of only some microbes;
danger of laboratory infection;
prolonged testing – some pathogens grow slowly
antigen detection / detects presence of the searched agent / easy, cheap, quick; low demands on equipment / low sensitivity; with some samples also low specificity
specific genome detection / detects presence of the searched agent / quick; high sensitivity / expensive;
expensive equipment needed; easy contamination

b) Indirect methods of pathogen identification

- serology: agglutination, hemagglutination, hemagglutination inhibition,

complementfixation, enzyme-linked immunosorbent assay (ELISA), Western blot etc.

- skin tests: tuberculin test (PPD test, Mantoux II)

- detection of lymphocyte sensibilisation (TB diagnostics)

Method / Contribution / Advantages / Disadvantages
specific antibodies detection / detects antibody response / easy, cheap; appropriate for routine processing / inappropriate for identification of agents with high antigenic variability
skin tests / detects specific cell-mediated immunity / easy, very cheap / low reliability; risk of allergic reaction; may induce patient immunisation – not possible to repeat
specific cell-mediated immunity detection / detects specific cell-mediated immunity / more precise, no risk of allergy or patient immunisation / much more expensive than skin test

Serological tests interpretation:

acute infection: single sample testing (IgM vs. IgG)

paired sera testing (fourfold elevation of specific antibody titres)

chronic infection:dynamics of antibody titres in time

antibodies avidity testing (the strength of Ab-Ag bind)

Indirect detection methods are based on the detection of specific immune response to infection:

general advantages: can differentiate infection and colonisation

can detect infection that already passed

general limitations:cannot be used in acute and quickly progressing infections (specific immunity occurs after 1-3 weeks)

not reliable in local infections (e.g. on mucosal surface only)

fail in immunocompromised persons

UPPER RESPIRATORY TRACT INFECTIONS

(1 lesson)

Introduction, pathophysiology

- antiinfective defense of the respiratory tract

- respiratory tract as a continuum, involvement of its parts ranging from nose to trachea

- closely related structures (conjunctiva, paranasal sinuses, middle ear)

- inflammatory edema of respiratory tract mucosa and submucosal lymphatic tissue

Etiology:

- physiological bacterial colonization of the upper respiratory tract

- respiratory viruses: rhinoviruses, coronaviruses, influenza and parainfluenzaviruses, RSV

- pathogenic bacteria:

nasal mucosa: Staphylococcus aureus

nasopharynx: Streptococcus pyogenes, corynebacteria, anaerobes

epiglottis and below: H. influenzae and other gramnegative nacteria

sinuses (sinusitis, otitis): various agents – viruses, bacteria, fungi

Syndromes and etiology:

- acute rhinitis, coryza, common cold: viruses

- acute pharyngitis and tonsillitis: viruses, bacteria

- acute laryngitis: viruses

- acute epiglottitis: H.influenzae

- acute tracheitis: viruses

Complications:

- sinusitis

- otitis media, mastoiditis

- peritonsillar abscess

Separatelly discussed diaseases:

- influenza

- infectious mononucleosis

- diphtheria

Diagnostics, differentiation of viral and bacterial disease:

- inflammatory parameters

- tests for etiology detection - bacterial infection, viral infection

- complementary and syndrome-specific tests

URINARY TRACT INFECTIONS

(1 lesson)

Pathogenesis of urinary tract infections

-route of infection: ascending infection,

hematogenous infection

per continuitatem – very rare

-predisposing factors:

-anatomical factors (short uretra in females, congenital defects...)

-mechanical obstruction from inside (lithiasis, tumours, scarring and postoperative strictures) and from outside (prostatic hypertrophy, tumours, pregnancy)

-functional neuromuscular defects (paraplegia, sclerosis multiplex, spina bifida)

-metabolic factors (diabetes mellitus)

-microbial pathogenic factors:

-adherence to uroepithelium, colonisation (hemolytic E.coli)

-biofilm production (catheters, chronic infection)

-tissue invasion

Classification of UTI with regard to etiology and pathogenesis:

-community-acquired UTI

-cystitis, pyelonephritis – E.coli, Proteus mirabilis

-urethritis, prostatitis – Mycoplasma, Chlamydia, Neisseria gonorhoae

-chronic UTI in diabetic patients

-besides Gramnegative bacilli frequently Enterococcus

-hospital-acquired UTI

-commonly associated with permanent catheterisation or endoscopy (cystoscopy)

-etiology: multiresistant Gramnegative bacilli (Pseudomonas, Enterobacter, Klebsiella)

Examination procedure

-physical examination

-laboratory testing:

-inflammatory parameters (blood count + differential count of leukocytes, CRP)

-biochemical testing of urine, urine culture

-blood culture if pyelonephritis suspected

-renal function testing (urea, creatinine in serum

-imaging techniques: ultrasonography mostly sufficient

Clinical classification of UTI

Upper urinary tract infection (easy progression to sepsis)

-acute pyelonephritis and chronic pyelonephritis

-interstitial nephritis

-renal absces, pararenal absces

Lower urinary tract infection

-cystitis

-urethritis

-prostatitis

Treatment of UTI

-symptomatic therapy, fluid intake

-antibiotic therapy

CENTRAL NERVOUS SYSTEM INFECTIONS

(1 lesson)

Classification of CNS infections, terminology:

•structure most involved:meningitis, encephalitis, myelitis, radiculitis, neuritis

• type of inflammation:purulent x nonpurulent, aseptic
• pathogen: bacterial, viral, fungal, parasitic
• extent of inflammation:

difusse - meningitis, meningoencephalitis, encephalitis

focal – necrotising encephalitis (HSV), cerebritis, abscess

• course of disease: acute x chronic

Pathogenesis:

- invasion of CNS- via blood (blood-brain, blood-cerebrospinal fluid barrier)

- via direct spreading from adjacent structures

- via peripheral nerves

- response of CNS to bacterial and viral invasion

- brain edema

Clinical manifestations and etiology of CNS infections:

- meningeal syndrome (headache, vomitus, meningeal signs), fever, coma

- examination of meningeal signs

- symptoms of encephalitis

- purulent meningitis

- clinical presentation

- etiology (pneumococcus, meningococcus, listeria, other agents)

- aseptic meningitis, meningoencephalitis

- clinical presentation

- etiology (tick-borne encephalitis, respiratory viruses, borrelia, leptospira)

Diagnostics:

- diagnosis of CNS inflammation and type of inflammation

lumbar puncture, cerebrospinal fluid testing and findings

- detection of etiology – dirrect and indirrect methods

Basic principles of treatment:

- causative therapy

- symptomatic therapy (including brain edema therapy)

- risk of delayed diagnosis (meningococcal invasive disease, purulent meningitis,

necrotising encephalitis)

IMPORTED INFECTIONS

(1 lesson)

Basic features of imported diseases

-infections of cosmopolitan occurrence

-infections limited to tropical and subtropical climate

Danger: delayed diagnosis

risk of spreading

Diseases obligatory reported to WHO: variola, cholera, plague, haemorhagic fevers, SARS

The most important syndromes in imported diseases:

fever:malaria, typhoid fever, dengue fever, haemorrhagic fevers, amebiasis

diarhea:food-poisoning

bacterial etiology (except pathogens common in middle Europe):

enterotoxigenic E. coli (ETEC), shigellae, V. cholerae

parasitic etiology: Entamoeba histolytica, Giardia intestinalis, Trichuris

trichuria, Ancylostoma duodenale

icterus:viral hepatitis (A,E,B), yellow fever

leptospirosis

amebic liver abscess, echinococcosis, schistosomosis

exanthema:disesases eliminated by vaccination in developed countries (measles, rubella)

diseases limited to tropical and subtropical climate (dengue, rickettsiosis, haemorrhagic fevers, larva migrans cutanea)

Examination of traveller:

history including detailed travell history

physical examination, „dominant symptom“

laboratory tests: basic screening + special tests with respect to the suspected diagnosis

Malaria

endemic area

malaric plasmodia: Plasmodium vivax, ovale, malariae, falciparum

life cycle of plasmodium, insect vector (Anopheles mosquito)

clinical manifestation: attack of fever

fever patterns – tertian, quartan, tropical (falciparum) malaria

danger of falciparum malaria

diagnostics: microscopy - thick smear, thin smear of blood

treatment and prevention, increasing resistance to antimalarial drugs

EXANTHEM OF INFECTIOUS ORIGIN

(2 lessons, slide show)

Introduction, terminology:

exanthem (skin), enanthem (mucosal surfaces)

infectious diseases with exanthem as an obligatory symptom and facultative symptom

pathogenesis of exanthem

Examination of patient with rash:

morphological classification of the rash, distribution, pattern of progression, timing

history: vaccination, travelling abroad, known allergy

morphologic types of skin lesions: macula, papula, nodule, vesicle, bulla, pustula

Morphologic classification of exanthems, representative diseases:

1. macular and/or papular exanthem:

scarlet fever (scarlatina)

measles (rubeola, morbilli)

German measles (rubella, rubeola)

Fifth disease (erythema infectiosum)

Sixth disease (exanthema subitum, roseola infantum)

dif. dg. allergic reaction

2. vesicular and pustular exanthem:

generalized: chickenpox (varicella)

smallpox (variola)

localized: herpes zoster

herpes simplex

impetigo

3. petechial purpuric eruptions:

rickettsiosis – purpuric fever

infections associated with disseminated intravascular coagulopathy:

meningococcal invasive disease

viral hemorrhagic fevers

severe sepsis

Falciparum malaria