2. Etiology, Diagnosis, and Prevention of Infectious Diseases

• the cause of a disease in general - cause of all cases of a disease in a population
• can be singular or mixed

identification of a disease in a single case

• microorganism may be present but difficult to detect, may need better techniques for detection
• does not mean that disease must be present in every infection with the microorganism - iceberg concept, many people can carry an organism but not be sick

• pure culture means on an agar plate, where a single colony can be selected
• not possible with viruses and some bacteria - obligate intracellular parasites, must be grown in cells so not pure

may be difficult to find an animal model - must be susceptible and exhibit same disease, not ethical to use humans

may be more difficult to recover from animal

• there is an increase in either the cell-mediated or humoral immune response to the organism after onset of the disease
• persons with no antibody or cell-mediated immune responses are susceptible to the disease, and persons with a high antibody level or strong cell-mediated response to the organism are resistant
• the disease can be prevented by vaccination with a preparation of the organism or one with similar antigenic specificity

• first two immunological postulates showed EBV is the cause of infectious mononucleosis
• - tested Yale students
• - those developed IM were EBV antibody negative whne they entered and became EBV antibody positive after developing disease
• - students who entered EBV antibody postive never developed disease

• 3rd immunological postulate showed that Mareck's disease is caused by Gallid herpesvirus 2
• unsure of cause so created a vaccine that was antigenically similar to the virus
• inoculated chickens were protected from disease

• subjective evidence of a disease stated by the patient, but which cannot be verified by another person
• malaise - a general feeling of discomfort
• chill - a sensation of cold, usually occurs at initial stage of an infectious disease
• nausea - an unpleasant sensation in the stomach, often leading to vomiting

• objective evidence of disease recognizable by another person
• lymphadenopathy - enlargement of the lymph nodes
• rigor - visible shivering
• vomiting - forcible expulsion of stomach contents through the mouth
• diarrhea - increased frequency and liquidity of fecal discharges
• cutaneous manifestations - abnormal appearance of the skin

• record of a patient's medical experiences and characteristics throughout life
• age, race, diseases, medications, family history
• occupation - may expose patient to a certain reservoir
• exposure to pets - can result in zoonoses
• underlying diseases
• geographic areas of residence and travel
• exposure to others known to have an infectious disease

• clinical
• physical
• differential
• etiological

• symptoms
• signs
• medical history

• made on the basis of objective physical measurements
• palpation - examination by touching with hands
• fever - body temperature
• imaging techniques

distinguishes a disease from others with which it might be confused

• identification of a disease in terms of its cause
• - for ID, means lab identification of the microorganism

• proper treatment
• clue about an underlying disease
• controlling epidemics
• required for reportable diseases

• almost all are infectious
• reasonably severe
• most are diseases which have promise of being controlled by public health measures

• on the basis of morphology and structure
• on the basis of biochemical properties
• immunologic and molecular identification
• host's immune response
• DNA sequencing
• strain typing
• animal models

• primary method for infections with protozoa, helminths and arthropods
• used for fungal infections after growing fungus on agar
• important for bacteria
• morphology of host cells used for some viruses

• intracellular reactions
• - metabolic pathways - ability to use a particular carbon and end products, cell walls (gram stain)
• extracellular products (bacterial enzymes)
• - hemolysins - enzymes that lyse erythrocytes, detected by growing bacteria on agar media with sheep erythrocytes

alpha - partial lysis, greenish tint

beta - complete lysis, clear

gamma - no lysis

• a reagent antibody made in lab reacts specifically with a microorganism
• antibody is labeled with a marker substance for detection
• adheres tightly to microorganism and is not removed during washing
• antibody from lab, antigen from patient

molecular probe: nucleic acid sequence complementary to sequence of microorganism, labeled with marker for detection, probe will hybridize and adhere if microorganism is present

polymerase chain reaction: DNA extracted from specimen, nucleic acid primers specific for the suspected microorganism are reacted with the DNA, will amplify even a few copies

DNA sequencing of 16S ribosomal RNA gene to determine genus/species

• main use is on direct smear - taken directly from the patient
• useful for difficult to culture organisms
• useful for slow growing organisms

• use host serum, react it with known laboratory antigen from a microorganism
• measure a humoral immune response (antibodies)
• patient provides antibody, lab provides antigen

• measure the reaction of the host to antigens
• injected between layers of skin
• usually measures cell-mediated immunity

• antigen attached to well
• patient serum added (with antibody)
• secondary antibody with enzyme added - binds patient antibody
• substrate added, causes color producing reaction

• causative agent cannot be cultured
• causative agent is expensive to culture
• causative agent is dangerous to culture
• causative agent is slow growing

antibiotic sensitivity - can indicate strains and be used to trace epidemics, help guide proper therapy

phage sensitivity (lytic phages) - which phages a bacteria is sensitive to is strain specific, can use to trace epidemics

• PCR and restriction based methods - organism specific
• Pulsed-field gel electrophoresis - whole genome restriction
• multilocus sequence typing - DNA sequencing of 7 housekeeping gene loci
• gold standard - full genome sequencing

• important to distinguish to the strain level to =
• determine vehicle of spread for an epidemic
• determine whether there is a common source for an epidemic
• determine whether new cases of disease are part of same epidemic or new one
• evaluate the effectiveness of control measures

• used primarily to test virulence
• animal injected, watched for morbidity and mortality
• most animal tests are no longer used - more human methods

prevention of the infection from ever occurring in the first place

in a person already infected, prevention of disease or sequelae (pathological condition resulting from disease)

• quarantine
• isolation
• body hygiene
• lifestyle
• source-reduction in reservoir
• vaccination