Common Viral Pathogens Flashcards
4 ways to diagnose a viral infection
- Look for virus grown in tissue culture - distinctive patterns of CPE can be recognized
- Assay for viral antigens using enzymatic reactions or immunofluorescence (i.e. rapid flu test)
- PCR - amplifies a portion of viral genome in body tissues
- Look for host immune response to viral infection - i.e. ELISA
Herpes - Basics + 8 Types
Herpes are ds-DNA viruses that come in 8 varieites:
HHV-1: Herpes Simplex 1 (HSV1) HHV-2: Herpes Simplex 2 (HSV2) HHV-3: Varicella Zoster Virus (VZV) HHV-4: Epstein Barr Virus (EBV) HHV-5: Cytomegalovirus (CMV) HHV-6 HHV-7 HHV-8: Kaposi's Sarcoma Virus
HSV-1 / HSV-2 Primary infection
HSV-1 primary infection often occurs durig childhood and is usually asymptomatic; HSV-2 primary infection usually occurs as a result of sexual contact and is often asymptomatic
If symptomatic, painful vesicles usually develop 1-3 days after inoculation and are contained to the area of infection
Manifestations of HSV Infection (4)
Gingivostomatitis - painful mouth ulcers of lips, gums, tongue; i.e. “Cold Sores”
Herpetic whitlow - inoculation of virus from oral secretions onto fingers
Herpes gladitorum - inoculation of virus from oral secretions onto skin
Herpes keratitis - infection of cornea
Encephalitis
HSV is the most common cause of encephalitis in the US; HSV infection in the brain has a predilecton for the temporal lobe, often presenting as psychiatric illness
Neonatal HSV
Primary infection of the infant transmitted perinatally via exposure to maternal secretions containing HSV (active lesions or asymptomatic viral shedding)
Often infects the skin, eye, and CNS; may become disseminated, causing hepatitis, DIC
HSV-associated encephalitis in a newborn is associated with 30% mortality; 75% of survivors will have intellectual disability
Prevention & Treatment of neonatal HSV
Pregnant women with HSV are treated prophylactically with anti-virals; if active genital lesions are present at the time of delivery C-section is recommended
Skin vesicles in a neonate < 1 month old are assumed HSV until proven otherwise; treated with acyclovir
HSV Latency & Reactivation
Latency occurs in the sensory ganglia of the areas affected by the primary infection - trigeminal (orofacial infection) and sacral ganglion (genital infection) are most common
Reactivation is provoked by a variety of stress stimuli and may include asymptomatic shedding or symptomatic reactivation infection
HSV Treatment
Oral antiviral therapy - patients with active outbreaks often prevent too late for therapeutic benefit but may be given extra refills to start taking at first sign of next outbreak
IV Acyclovir - for severe infections such as neonatal herpes, encephalitis, or active HSV in immunocompromised hosts
Chickenpox Vaccine
Live, attenuated vaccine, consists of a 2 dose series at 12-15 months and 4-6 years; not recommended for immunocompromised patients
Varizig - VZV immune globulin given within 4 days of exposure can reduce severity of varicella in high risk individuals (passive immunization); consists of pooled antibodies from donors with high VZV titers
Shingles vaccine
Zostavax - one dose recommended for healthy individuals 60+; boosts T-cell immune response to VZV, preventing reactivation
VZV Primary Infection
Chickenpox; highly contagious with incubation period of 10-21 days; disease begins with fever, malaise, headache, and progresses to itchy vesicular rash described as “dew drops on a rose petal”; lesions appear in successive waves and typical course lasts 7 days
VZV Secondary Infection
Shingles; VZV remains dormant in the cranial, dorsal root, or trigeminal ganglia; reactivation is always symptomatic
Occurs as a result of declining T-cell mediated immunity vs. latent VZV with age
Begins as pain at the site where vesicles will erupt; lesions develop over a single dermatome and usually subside within 2 weeks
Post-herpetic neuralgia (PHN) is the most common complication; pain may last weeks to months after lesions resolve
VZV Pathogenesis
Virus gains entry through the respiratory tract then spreads to the lymphatic system; primary viral replication takes place in regional lymph nodes and is followed by primary viremia; secondary replication occurs in the liver, spleen, and other organs and spreads through secondary viremia to the skin
VZV treatment
Chickenpox is usually self-limited and requires no treatment; immunocompromised patients should receive anti-viral treatment
Shingles may be treated with Acyclovir within 48-72 hours of symptoms to decrease number and duration of lesions as well as pain
EBV Primary Infection
Transmitted via saliva - 95% of individuals are infected by 40 years
Primary infection in young children is often asymptomatic; primary infection in teens/adults causes infectious mononucleiosis in 40% characterized by fever, sore throat, lymphadenopathy, fatigue, exudative tonsillitis, and splenomegaly; symptoms resolve in 4-8 weeks
EBV Pathophysiology
EBV infects the nasopharyngeal epithelium, resulting in cell lysis and viral spread to adjacent oropharyngeal lymphoid tissue; viremia occurs with distribution to the liver, spleen, and B lymphocytes
EBV remains latent in nasopharyngeal epithelium and B cells; may contribute to some B cell cancers (Burkitt’s and Hodgkin Lymphoma)
EBV Diagnosis
Many patients display >10% atypical lymphocytes in peripheral blood smear
Monospot/heterophile test - detects presence of antibodies that agglutinate horse/sheep/cattle RBCs via cross-reaction with EBV
EBV serology - presence of IgM indicates recent infection (4-6 weeks); IgG indicates past infection
CMV Epidemiology
Transmitted via infected body fluids (saliva, breast milk, sexual contact, blood, tears, urine) or from mother to fetus (in utero, perinatal)
40-80% of people in the US infected by 40 years old
CMV Primary Infection
CMV infects the epithelia of the salivary gland or genital tract; primary infection in healthy persons is almsot always asymptomatic but may be serious in immunocompromised patients and cause retinitis, colinitis, etc.
CMV Secondary Infection
CMV remains latent in monocytes and lymphocytes; reactivation infection is asymptomatic in normal patients but virus is being shed in bodily secretions
Reactivation may be serious in immunocomrpomised patients; often non-focal viral syndrome or organ-specific infection (hepatitis, pneumonitis, etc.)
Diagnosis of CMV
Serology:
IgM alone is seen in primary CMV infection
IgG alone is seen in previous CMV infection
IgM and IgG together are seen in recent reactivation infection
Tissue histology - infected cells have “owel’s eye” appearance (densely staining body surrounded by a halo) due to intranuclear inclusion bodies (viral proteins or particles)
CMV treatment
Gancyclovir
Passive immunization for pregnant women positive for CMV - pooled CMV antibodies
Risk of CMV transmission during pregnancy
CMV is the most common in-utero infection in the US; risk of transmission is 3-5% for a mother with primary CMV and <1% for a mother with reactivated CMV
10-15% of infected infants will have symptoms at birth
Congenital CMV Syndrome
Low birth weight Microcephaly Hearing loss - leading cause of congenital hearing loss in the US Mental Impairment Hepatosplenomegaly Skin rash (blueberry muffin spots) Jaundice
Treated with oral valganciclovir or gancyclovir
RSV Pathogenesis
RSV is an enveloped virus with a ssRNA genome transmitted by contact with respiratory droplets at mucus membranes; localized infection of respiratory tract with cell-cell transfer of virus leads to spread from upper to lower respiratory tract
2 important surface proteins:
G protein mediates viral attachment to host cells; F (fusion) protein mediates fusion of infected cells to neighboring cells to form syncytia, multi-nucleated giant cells
RSV Primary Infection
Usually symptomatic and causes acute respiratory disease in patients of all ages: most often bronchiolitis (children < 1), viral pneumonia (children and the elderly) and URI (children and adults)
Most common cause of bronchiolitis and viral pneumonia in young children; almost all children infected at least once by 2 years
Infection more commonly leads to severe respiratory disease in premature infants <32 weeks
RSV Reinfection
Presents in older children and adults as a severe cold / URI
RSV Diagnosis & Treatment
Diagnosis is usually clinical; rapid test exists but is not very sensitive (false negatives are common)
Treatment is mostly supportive - some children may benefit from a bronchodilator; Ribavirin can be used in high risk patients
Rotavirus - Epidemiology
Leading single cause of severe diarrhea and gastroenteritis in infants and young children worldwide
Rotavirus - Disease
Transmitted via the oral-fecal route with low infectious dose (10-100 particles)
Disease course lasts 3-8 days and is characterized by vomiting, watery diarrhea, fever, and abdominal pain
Rotavirus Pathogenesis
dsRNA virus with a segmented genome; allows for reassortment and generation of multiple serotypes / strains
Rotavirus infects mature absorptive epithelial cells or enterocytes located at the tip of villi in the proximal 2/3 of the ileum; cell death leads to reduced absorptive surface area of small intestine, loss of enzymes that break down complex sugars, increased fluid and osmotic load in gut, and severe diarrhea
Rotavirus - Prevention, Diagnosis, Treatment
2 oral, live-attenuated vaccines available for use in infants
Diagnosis - ELISA on stool sample
Treatment - supportive, with attention to fluids
Influenza Structure
RNA virus with a segmented genome; made up of 8 different pieces of ss-RNA which encode different viral proteins; core is surrounded by a lipid envelope with a lining of matrix protein (M protein) on the inner side and cell surface proteins on the outside, including:
Hemagluttinin (H)
Neuraminidase (N)
Type A Influenza
Infects horses, seals, swine, birds, humans; causes pandemics and epidemics of potentially severe illness
Nomenclature:
Virus Type / Geographic origin / Strain/ Year of Isolation / Virus Subtype
Type B Influenza
Only infects humans, causing less severe disease; does not cause pandemics
From 1 of 2 lineages (Victoria or Yamagata); different strains exist
Nomenclature:
Virus Type / Geographic origin / Strain / Year of Isolation / Lineage
Pathophysiology of Influenza
Transmitted by respiratory droplets and small particle aerosols that make contact with host mucous membranes; transmission may also occur via contact with infected fomites
Incubation period is 1-3 days
Signs and Symptoms of influenza
Neonates: Lethargy, decreased eating, mottling, apnea
Infants and tolddlers: Nausea, vomiting, diarrhea, fever, anorexia, various respiratory syndromes (croup, bronchiolitis, etc.)
Older children and adults: Acute onset of fever, chills, myalgias, headache, and cough
Matrix Protein Inhibitors
Effective for susceptible type A viruses
Ex: Amantadine, Rimantadine
Neuraminidase Inhibitors
Effective for susceptible both type A and B viruses
Ex: Osteltamivir (Tamiflu), Zanamivir (Relenza)
Pandemic H1N1
i.e. “Swine Flu,” or A/California/7/2009 (H1N1)-like virus; first detected human cases occurred in Mexico; rate of infection was highest among children and young adults 65, likely due to pre-existing immunity against an antigenically similar strain that circulated prior to 1957
Inactivated Influenza Vaccine (TIIV)
Injectable, killed virus approved for all individuals 6 months and older, including pregnat and immunocompromised
Trivalent (2A and 1B strains) widely available
Available in standard dose and high dose (for adults >65)
Typically 50-70% effective among healthy persons <65 in well-matched years; 30-40% effective among elderly
Live attenuated influenza vaccine (LAIV)
i.e. FluMist
Delivered intranasally via a fine mist applicator; approved for healthy persons 2 - 49 years old except for pregnant and/or immunocompromised
Quadrivalent (2A + 2B) formulation recently approved
