Common Viral Pathogens

Question 1

4 ways to diagnose a viral infection

Answer 1

1. Look for virus grown in tissue culture - distinctive patterns of CPE can be recognized
2. Assay for viral antigens using enzymatic reactions or immunofluorescence (i.e. rapid flu test)
3. PCR - amplifies a portion of viral genome in body tissues
4. Look for host immune response to viral infection - i.e. ELISA

Question 2

Herpes - Basics + 8 Types

Answer 2

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

Question 3

HSV-1 / HSV-2 Primary infection

Answer 3

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

Question 4

Manifestations of HSV Infection (4)

Answer 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

Question 5

Encephalitis

Answer 5

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

Question 6

Neonatal HSV

Answer 6

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

Question 7

Prevention & Treatment of neonatal HSV

Answer 7

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

Question 8

HSV Latency & Reactivation

Answer 8

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

Question 9

HSV Treatment

Answer 9

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

Question 10

Chickenpox Vaccine

Answer 10

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

Question 11

Shingles vaccine

Answer 11

Zostavax - one dose recommended for healthy individuals 60+; boosts T-cell immune response to VZV, preventing reactivation

Question 12

VZV Primary Infection

Answer 12

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

Question 13

VZV Secondary Infection

Answer 13

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

Question 14

VZV Pathogenesis

Answer 14

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

Question 15

VZV treatment

Answer 15

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

Question 16

EBV Primary Infection

Answer 16

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

Question 17

EBV Pathophysiology

Answer 17

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)

Question 18

EBV Diagnosis

Answer 18

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

Question 19

CMV Epidemiology

Answer 19

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

Question 20

CMV Primary Infection

Answer 20

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.

Question 21

CMV Secondary Infection

Answer 21

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.)

Question 22

Diagnosis of CMV

Answer 22

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)

Question 23

CMV treatment

Answer 23

Gancyclovir

Passive immunization for pregnant women positive for CMV - pooled CMV antibodies

Question 24

Risk of CMV transmission during pregnancy

Answer 24

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

Question 25

Congenital CMV Syndrome

Answer 25

``` 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

Question 26

RSV Pathogenesis

Answer 26

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

Question 27

RSV Primary Infection

Answer 27

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

Question 28

RSV Reinfection

Answer 28

Presents in older children and adults as a severe cold / URI

Question 29

RSV Diagnosis & Treatment

Answer 29

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

Question 30

Rotavirus - Epidemiology

Answer 30

Leading single cause of severe diarrhea and gastroenteritis in infants and young children worldwide

Question 31

Rotavirus - Disease

Answer 31

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

Question 32

Rotavirus Pathogenesis

Answer 32

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

Question 33

Rotavirus - Prevention, Diagnosis, Treatment

Answer 33

2 oral, live-attenuated vaccines available for use in infants Diagnosis - ELISA on stool sample Treatment - supportive, with attention to fluids

Question 34

Influenza Structure

Answer 34

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)

Question 35

Type A Influenza

Answer 35

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

Question 36

Type B Influenza

Answer 36

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

Question 37

Pathophysiology of Influenza

Answer 37

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

Question 38

Signs and Symptoms of influenza

Answer 38

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

Question 39

Matrix Protein Inhibitors

Answer 39

Effective for susceptible type A viruses Ex: Amantadine, Rimantadine

Question 40

Neuraminidase Inhibitors

Answer 40

Effective for susceptible both type A and B viruses Ex: Osteltamivir (Tamiflu), Zanamivir (Relenza)

Question 41

Pandemic H1N1

Answer 41

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

Question 42

Inactivated Influenza Vaccine (TIIV)

Answer 42

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

Question 43

Live attenuated influenza vaccine (LAIV)

Answer 43

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