Stages and Patterns of Infectious Disease

• Candelaria Gonzalez Moreno, DVM, PhD is the Locum.

Stages of Infectious Disease

• Infection occurs and starts the clock for the different periods of disease progression.
• The latent period is the time between infection and when the host is infectious.
• The incubation period is the interval between exposure to the virus and the onset of clinical signs.
• The subclinical infectious period is when an infection occurs without symptoms or only mild symptoms
• The infectious period is the time during which the host can shed the virus and transmit it.
• The clinical period is when the virus reaches peak replication, and clinical signs become evident.

Patterns of Infection

• Acute Infections: Rhinovirus, Rotavirus, and Influenza virus.
• Latent Infections: Herpes simplex virus 1 and 2, and Bovine herpesvirus 1.
• Persistent Asymptomatic Infections: Lymphocytic choriomeningitis virus, and Bovine viral diarrhea virus.
• Persistent Pathogenic Infections: Human immunodeficiency virus type 1, and Canine distemper virus.

Acute Viral Infection Course

• Induction of adaptive response occurs after innate defenses have begun
• The adaptive response causes virus reproduction to decrease
• Memory cells remain after the virus has been cleared or controlled

Pathogenicity and Virulence

• Pathogenesis refers to the processes that follow a host infection that leads to disease.
• Pathogenicity refers to the potential to produce disease in a host; a virus is either pathogenic or not (apathogenic).
• Virulence is the measure of a pathogenic virus's ability to produce severe disease in a host, and is a quantitative measure.

Tissue Tropism

• The capacity of a virus to infect cells selectively in particular organs is referred to as tropism.
• Enterotropic, neurotropic and hepatotropic are examples of tissue tropism
• Tissue tropism ranges from limited to pantropic.

Determinants of Tissue Tropism

• Susceptibility is the presence of appropriate virus receptors on the host cell, such as Canine parvovirus.
• Permissivity is the ability of a cell to support viral replication and can reflect a virus's ability to inhibit innate antiviral defense mechanisms.
• Accessibility is the ability of the virus to physically reach the target.
• Immune defenses

Avian Influenza Strains: Tissue Tropism

• In mammals, influenza virus reproduction is restricted to epithelial cells of the respiratory tract because of local production of tryptase.
• In birds, highly virulent influenza virus strains reproduce in the intestinal and respiratory tracts and have wide tissue tropism.
• This is because of mutations in the HA that permits it to be cleaved by ubiquitous proteases like furins

Mechanisms of Host Cell Damage

• Loss of cellular function includes immune suppression and neuronal dysfunction.

Mechanisms of Host Cell Damage: Cytopathic Effects

• Cytopathic effects include cell fusion, host cell death, metabolic alterations, induction of host immune cell damage, oncogenesis (development of cancer) etc

Laboratory Diagnosis of Viral Infections

• Diagnostic methods include collecting specimens

Specimen Collection

• Respiratory specimens include Nasal or throat swab, nasopharyngeal aspirate, tracheal wash fluid
• Enteric specimens include Feces
• Genital specimens include Genital swab
• Eye specimens include Conjunctival swab
• Skin specimens include Vesicle swab or scraping; biopsy of solid lesion
• Central nervous system specimens include Cerebrospinal fluid
• Generalized specimens include Nasal swab, feces, blood leukocytes, serum, urine
• Biopsy specimens include Relevant organ
• Any disease specimens include Blood for serology

Diagnostic Methods

• Diagnostic methods include electron microscopy, virus culture and identification, viral nucleic acids, viral antigens and antiviral antibodies

Electron Microscopy

• Electron microscopy can be used to examine characteristic morphology of virus families.
• Electron microscopy has the advantage of being rapid and specific.
• Electron microscopy disadvantages are low sensitivity, expensive equipment and technically demanding.

Culture and Identification

• Samples are placed in appropriate cell cultures and the presence of a virus is detected by various methods.
• 3 main kinds of cell cultures are primary cell cultures, diploid cell strains and continuous cell lines.
• Primary cell cultures are derived from tissues but die after a few generations.
• Diploid cell strains are single cell type that grow for up to 100 generations.
• Continuous cell lines are transformed (cancerous) immortal cell lines like HeLa and Vero cells.

Detection Methods

• Cytopathic effects
• Noncytopathic infected cells: immunoassays or molecular assays

Tissue Culture Infectious Dose (TCID50)

• TCID50 = Tissue culture infectious dose: the number of viruses required to cause infection in 50% of the cell culture.
• A lower TCID50 is more virulent

Identification of Viral Nucleic Acids

• With any laboratory test, positive results need to be interpreted in light of the clinical history, clinical signs, and the pathogenesis of the disease in question

Identification of Viral Antigens

• Lateral flow immunochromatographic assay,
• Immunohistochemistry,
• Immunofluorescence

Detection of Antiviral Antibodies (Serology)

• IgM indicates recent illness and uses a single serum specimen.
• IgG stays elevated for long, paired serum specimens needed to confirm recent infection if there is a ≥4-fold rise in titer.
• No rise in titer is indicative of no recent infection