Download Laboratory Diagnosis of Infectious Diseases

YEDİTEPE
UNIVERSITY
YEDİTEPE
SCHOOL OF
MEDICINE
Laboratory Diagnosis of Infectious Diseases –I
(Basic concepts & principles)
İ. Çağatay Acuner
M.D., Clinical Microbiologist, Associate Professor
Department of Microbiology
Faculty of Medicine, Yeditepe University, Istanbul
[email protected]
Interventional opportunities to break the chain of infection by various
intervention modalities such as vaccination, sterilization, disinfection,
decontamination, antisepsis, hygiene, sanitation, biosafety precautions,
prophylaxis, treatment, etc.
Clinical Laboratory Services in Healthcare
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Service types
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Testing
Consultation
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Technical
Clinical
Surveillance
Education and Training
Research
Biobanking
Therapeutics (Theranostics)
medicine and theranostics sensu lato;
• Personalized/precision
biotherapy, gene therapy, RNA silencing, immunotherapy, phagotherapy,
stem cell therapy, tissue engineering, etc.
Clinical Decision Making Process
Clinical laboratory as a system
Laboratory types/classifications
Laboratory contribution to clinical decision making process
Four major approaches
to Infectious diseases and Clinical Microbiology fields
–Based on etiological agents
an agent may cause more than one clinical entities
–Based on clinical entities or manifestations or syndromes
a syndrome may be caused by more than one distinct agents; different agents or
mixed infections.
–Based on diagnostic methods/techniques
(=contribution of laboratory in clinical decision-making process)
a diagnostic method or technique may be used in the diagnosis of more than one
one clinical entity and etiological agent
– Based on intervention modality or therapeutic agents
an intervention modality or therapeutic agent may be used against more than one
etiological agent or clinical entity
Health states (conditions) as
“Clinical Utility Targets” of Laboratory Tests
Clinical utilities of laboratory tests:
contributions to clinical decisions
A conceptual equation of laboratory test
Test output
Laboratory test method hierarchy
Various other classification approaches to a laboratory test
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Based on multiple testing versus single testing
• Multiple testing Multiplex testing (i.e. with the same methodology, on the same run and on
the same instrumental platform)
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Serial testing (i.e. tests performed sequentially)
• Designed to make -or to assist in making- a decision related to a clinical
utility target within a group of alternatives
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Upon new test requisition
Reflex testing
Designed to make an unequivocal decision related specifically to a
clinical utility target
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Parallel testing (i.e. tests performed concurrently)
• Designed to make -or to assist in making- a decision related to a clinical utility
target within a group of alternatives
Single testing
Based on clinical utility target-group status
• Emergency testing
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Panel testing (i.e. related-group testing)
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Organ panel
System panel
Specific (i.e. to a clinical-utility-target) panel
Performance characteristics of a laboratory test
Characteristics of an ideal laboratory test
Interpretive reporting of a laboratory test
Decision limits of a laboratory test
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Reference limit: Derived from the reference distribution and used for descriptive purposes.
It is common practice to define a reference limit so that a stated fraction of the reference
values is less than or equal, or more than or equal, to the respective upper or lower limit.
The reference limit is descriptive of the reference values and may be distinguished from
various other types of decision limits.
Reference interval: The interval between, and including, two reference limits. It is
designated as the interval of values from the lower reference limit to the upper reference
limit; in some cases, only one reference limit is important, usually an upper limit, "x," and the
corresponding reference interval would be 0 to x.
Decision level/Decision point/(Cut-off level): n - A test value or statistic that marks the
upper (or lower) boundary between a negative (normal) or acceptable result and a positive
(abnormal) or unacceptable result.
Critical values/Medical decision limits: Decision limits are different from reference limits
because they are based on other scientific and medical knowledge and they may be related
to a specific medical condition.
Action limits: Action limits used in the clinical interpretation of test results depend on the
reference ranges established for the test. The specific action limit used for each clinical
decision depends on the clinical problem and the circumstances involved for that specific
patient. (e.g. Panic value)
Diagnostic Cycle in Infectious diseases
Diagnostic Test Cycle
Pre-analytic, analytic, post-analytic phases
of laboratory testing work-flow
A conceptual model of laboratory test and testing process
Diagnostic Approaches in Clinical Microbiology
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Screening approach=in healty and/or under risk population
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finding; an abnormality in laboratory or imaging tests
Differential approach=Syndromic approach=in patients with complaints,
symptoms, signs
• Syndrome= (n x symptom) + (n x sign) (etiological agent unknown)
– e.g. SARS, AIDS, etc.
– nosographical; description-based clinical entities
• complaint; most disturbing symptom that cause the patient seek medical
help
• symptom; a manifestation of pathological process that patient feels
• sign; a manifestation of pathological process that physician detects (in
physical exam)
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Definitive approach=in patients with more specific (maybe patognomonic)
complaints, symptoms, signs
• Disease= etiological agent known
– e.g. Coronavirus Infection; Pneumonia with Coronavirus, HIV Infection.
– nosological; definition-based clinical entities
Major Clinical Syndromes in Infectious Diseases
(Based on System/Organ Manifestations)
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Fever
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– Fever of Unknown Origin
– The Acutely İll Patient with Fever and Rash
Upper Respiratory Tract Infections
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– The Common Cold
– Pharyngitis
– Acute Laryngitis
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– Acute Laryngotracheobrochitis
– Otitis Externa, Otitis Media, and Mastoiditis
– Sinusitis
– Epiglottitis
– Infections of Oral Cavity, Neck, and Head
Pleuropulmonary and Bronchial Infections
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(Lower Respiratory Tract Infections)
– Acute Bronchitis
– Chronic Obstructive Pulmonary Disease,
Chronic Bronchitis, and Acute
Exacerbations
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– Brochiolitis
– Acute Pneumonia
– Pleural Effusion and Empyema
– Lung Abscess
– Chronic Pneumonia
– Cystic Fibrosis
Urinary Tract Infections
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Asymptomatic/Symptomatic, Acute/Chronic
Upper/Lower
Complicated/Uncomplicated
Sepsis, Severe Sepsis, and Septic Shock (Bloodstream
Infections)
Intra-abdominal Infection
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Peritonitis and Intraperitoneal Abscesses
Infections of the Liver and Biliary System
Pancreatic Infections
Splenic Abscess
Appendicitis
Diverticulitis and Typhlitis
Cardiovascular Infections
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Endocarditis and Intravascular Infections
Infections of Prostetic Valves and Other Cardiovascular Devices
Myocarditis and Pericarditis
Mediastinitis
Central Nervous System Infections
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Acute Meningitis
Cerebrospinal Fluid Shunt Infections
Chronic Meningitis
Encephalitis, Myelitis and Neuritis
Brain Abscess
Subdural Empyema, Epidural Abscess, and Suppurative Intracranial
Thrombophlebitis
Major Clinical Syndromes in Infectious Diseases
(Based on System/Organ Manifestations)
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Skin and Soft Tissue Infections
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Bone and Joint Infections
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Cellulitis and Subcutaneous Tissue Infections
Myositis
Lymphadenitis and Lymphangitis
Esophagitis
Nausea, Vomiting, and Noninflammatory
Diarrhea
Antibiotic-Assocaited Colitis
Inflammatory Enteritides
Enteric Fever and Other Causes of Abdominal
Symptoms with Fever
Foodborne Disease
Tropical Sprue/Enteropathy
Whipple’s Disease
Infectious Arthritis of Native Joints
Osteomyelitis
Infections with Prostheses in Bones and Joints
Diseases of Reproductive Organs and
Sexually Transmitted Diseases
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Genital Skin and Mucous Membrane Lesions
Urethritis
Vulvovaginitis and Cervicitis
Infections of the Female Pelvis
Prostatitis, Epididymis, and Orchitis
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Eye Infections
– Microbial Conjunctivitis
– Microbial Keratitis
– Endophthalmitis
– Infectious Causes of Uveitis
– Periocular Infections
Hepatitis
– Acute Viral Hepatitis
– Chronic Viral Hepatitis
Acquired Immunodeficiency Syndrome
Miscellaneous Syndromes
– Chronic Fatigue Syndrome
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Approximately 100 (>87) major clinical
syndromes in infectious diseases
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Approximately 100 infectious (etiological)
agents
– Bacterial
– Viral
– Fungal
– Parasitic
Laboratory test method modalities in medical microbiology
Conventional and current molecular test methods
A classification of molecular test methods (NATs; including NAATs.)
Classification schemes for laboratory technologies
Evidence based laboratory medicine
(with unsolved problems!)
Acuner İ.Ç. Unpublished manuscript-1.
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Evidence based laboratory medicine
(with unsolved problems!)
Reliability Measures
Practicality Measures
Can it work? (Efficacy)
Evidence
Generation
Does it work? (Effectiveness)
PCT
RCT
Decision
Making
Is it worth it? (Value)
Evidence
Evaluation
Bugdet
Impact
CED
SRE
SRT
Evidence
Synthesis
Observational
Studies
Outcome Measures
Clinical
Guidelines
Product
Approval
Physician
and patient
decision
Coverage &
reimbursement
decision
Acuner İ.Ç. Unpublished manuscript-1.
Luce BR, et al. EBM, HTA, and CER: Clearing the Confusion.
Milbank Q. 2010 Jun;88(2):256-76.
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Assessment of the efficacy (or effectiveness)
of a laboratory diagnostic test/method/technology
Defining normality by the predictive value method:
The positivity criterion
Diagnostic Value of a Test Result: Predictive value theory
Truth Table (2x2)
Positivity in sick people
Negativity in healty people
Predictive value of a positive test result
Predictive value of a negative test result
Diagnostic Value of a Test Result: Predictive value theory
Truth Table (2x2) (High prevalence example)
Positivity in sick people
Negativity in healty people
Predictive value
of a positive test result
Predictive value
of a negative test result
Diagnostic Value of a Test Result: Predictive value theory
Truth Table (2x2) (Low prevalence example)
Predictive value
of a positive test result
Predictive value
of a negative test result
Diagnostic Value of a Test Result: Predictive value theory
Truth Table (2x2) (Effects of prevalence and accuracy; example)
Diagnostic Value of a Test Result: Predictive value theory, Bayes’ theorem, LR
Fagan Nomogram (Pre-test versus Post-test Probability; example)
Analytical Value of a Test Result:
Analyical sensitivity & specifity,
Accuracy versus Precision
(measurement uncertainty, random error, systematic error)