DD 02-26-14 08-10am Common Viral Pathogens - Curtis Flashcards

(97 cards)

1
Q

Infection vs. Disease

A
Infection = virus has replicated in host
Disease = infection that causes symptoms
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2
Q

Lab Tests to Dx Viral Infection

A
  • Culture: can grow SOME viruses in TISSUE
  • Antigen assays
  • PCR
  • ELISA (Enzyme-Linked Immunosorbent Assay)
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3
Q

Antigen assays for viral Dx

A
  • various assays using enzymatic rxns or immunofluorescence to detect specific Ags of virus in question (ex: rapid flu test)
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4
Q

PCR for viral Dx

A
  • copying & amplifying portion of viral genome
  • very sensitive & specific
  • can be done on blood, nasal wash, CSF, biopsies

Results may be…

  • qualitative (+ or -)
  • quantitative (# of copies/mL)
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5
Q

ELISA (Enzyme-Linked Immunosorbent Assay to Dx virus

A
  • to look for host’s immune response to viral infection by looking for Abs specific for that virus

Most commonly, ELISA would…

  • Coat plate w/ viral Ag (whole virus or part)
  • Incubate host’s serum on plate to let Abs attach to Ag on bottom of wells
  • Then incubate plate w/ an antibody that detects the host antibody (i.e., a secondary antibody)
  • Then incubate plate w/ a substrate that will allow visualization of the secondary antibody
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6
Q

Herpes virus (type of virus, who they infect)

A
  • double-stranded DNA viruses

- infect most animals.

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7
Q

Hallmark of a herpes infection

A

Once a host is infected, the host is always infected.

  • establishes latency after infection
  • latent virus can become reactivated
  • reactivated infection doesn’t always cause disease
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8
Q

Antiviral medications for Herpes Viruses

A
  • work against some of the human herpes viruses

Acyclovir
= most common
= works by inhibiting the viral DNA polymerase
= indicated for HSV and VZV infections

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9
Q

Herpes Viruses that infect humans (8)

A
  • HHV-1: Herpes Simplex Virus-1 (HSV-1)
  • HHV-2: HSV-2
  • HHV-3: Varicella Zoster Virus (VZV)
  • HHV-4: Epstein Barr Virus (EBV)
  • HHV-5: Cytomegalovirus (CMV)
  • HHV-6: Roseola (HHV-6a, HHV-6b)
  • HHV-7: Roseola
  • HHV-8: HHV-8
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10
Q

Clinical Manifestations of Herpes Simplex viruses 1 & 2 (HSV-1, HSV-2)

A
  • Oral and genital herpes
  • Neonatal herpes
  • Herpes keratitis (eye)
  • Herpes encephalitis
  • Herpetic whitlow (finger lesion)
  • Herpes gladiotorum (“wrestlers”)
  • Encephalitis
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11
Q

Clincal Manifestations of Varicella zoster virus

VZV

A
  • Chickenpox,

- In immunocompromised: vasculitis, encephalitis, pneumonia

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12
Q

Clincal Manifestations of Epstein-Barr virus

EBV

A
  • Infectious mononucleosis
  • Burkitt’s lymphoma-
  • Encephalitis
  • In immunocompromised: lymphoma
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13
Q

Clincal Manifestations of Cytomegalovirus

CMV

A
  • Infectious mononucleosis-like syndrome
  • In immunocompromised: retinitis, pneumonia
  • In newborns: congenital CMV
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14
Q

Clincal Manifestations of Human herpesvirus 6 & 7

A
  • Roseola or exanthem subitum

- In immunocompromised: fever, encephalitis

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15
Q

Clincal Manifestations of Human herpesvirus 8

A
  • Kaposi’s sarcoma (only occurs in immunocompromised)
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16
Q

Signs/Symptoms of Herpes Simplex viruses 1 & 2 (HSV-1, HSV-2)

A

-painful vesicles at the site of inoculation

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17
Q

Differences between of HSV-1 & HSV-2

A

Though both can cause oral & genital herpes…

  • HSV-1 is predominantly oral lesions
  • HSV-2 is predominantly genital lesions
  • These differences are becoming less strong with time, mainly as a result of oral sex allowing the two viruses to now infect other body sites
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18
Q

Incubation Period of HSV-1 & -2

A

2-12 days

typically ~4 days

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19
Q

Transmission of HSV-1 & -2

A

Transmission occurs through inoculation from someone who is shedding virus into a mucosal surface or cut of another person.

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20
Q

Clinical patterns of HSV-1 & HSV-2 depend on…

A

whether infection is primary or recurrent

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21
Q

Primary infection vs. Latent infection vs. Reactivation infection with HSV-1/HSV-2: Clinical pattern

A

Primary:

  • most are asymptomatic
  • usually worse than recurrent infection
  • If symptomatic, lesions usually develop 1-3 days after inoculation
  • Vesicular rash +/- fever
  • Usually occurs during childhood w/ HSV gingivostomatitis (historically HSV-1)

Latent:
- asymptomatic

Reactivation:

  • Contagious, though may be asymptomatic
  • If symptomatic, usually less than primary infection
  • Can be infrequent or very frequent
  • Provoked by variety of stimuli
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22
Q

HSV-1 & -2 Rash in Immunocompromised vs. Immunocompetent Hosts

A

Immune competent hosts:
- area of vesicular rash stays contained to area of inoculation
Immunocompromised host:
- Infection may involve larger areas of skin
- Can disseminate to specific/multiple organs (systemic)
- EX: encephalitis, hepatitis

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23
Q

Neonatal HSV-1 & -2 infection: Locations

A
Skin
Eye
Mucous Membrane
CNS
Disseminated
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24
Q

Latent infection with HSV-1/HSV-2: where infection occurs

A

Occurs in sensory ganglia of areas infected w/ the primary infection

  • Orofacial infection: trigeminal ganglia
  • Genital infection: sacral ganglia
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25
HSV-1/-2 Diagnosis:
Often clinical Dx If need definitive Dx: - Tzanck smear - HSV culture - Direct Fluorescent Antigen stain - PCR of lesions
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Triggers of Reactivation of HSV-1/HSV-2 Infection
- sunlight - stress - febrile illness - menstruation - immunosuppression
27
HSV Treatment
Severe HSV infections: <-- IV acyclovir = for neonatal HSV, HSV in immunocompromised hosts, encephalitis/meningoencephalitis Oral antiviral therapy (acyclovir or related antiviral) = for oral or genital outbreaks = standing Rx for ppl w/ frequent outbreaks not on suppressive therapy, so they can fill it & start treatment at very onset of reactivation / outbreak
28
Tzanck smear to Dx HSV-1/-2 infection
- direct specimen (scrape base of lesion) - put specimen on slide & stain - look for multinucleated giant cells - not specific for HSV (also VZV and CMV) - rarely used in favor of easier & more sensitive / specific testing
29
HSV-1/-2 Prevention of Reactivation Infection (& what warrants it)
Prophylactic Acyclovir - in lower doses than used for treatment - difficult to maintain Used for pts with: - frequent outbreaks of oral / genital lesions - recurrent keratitis & encephalitis
30
HSV-1/-2 Prevention of Primary Infection
- NO vaccine available - Hand hygiene - Physical barriers: gloves, condoms - Avoid contact
31
Varicella Zoster Virus (VZV) - Clinical Syndrome
VZV causes 2 clinical syndromes of importance: • Chickenpox (varicella) • Shingles (zoster)
32
Primary Varicella Zoster Virus (VZV) Infection
= Varicella, or Chicken pox
33
Clinical Pattern of Primary VZV infection (Chickenpox/Varicella)
1. Fever, malaise, headache, +/- cough 2. Rash develops, in successive waves - Typically lasts 7 days - No longer contagious when lesions all crusted over
34
Primary VZV Infection (Chickenpox / Varicella) Rash
- itchy - vesicular - “dew drop on rose petal” = clear fluid + red base - Usually starts on trunk & spreads to face & limbs - Lesions appear in successive waves, so lesions will be in various stages on physical exam
35
Pathogenesis of Primary VZV Infection (Chickenpox / Varicella)
1. Virus gains entry via respiratory tract 2. Spreads to regional lymphoid system & replicates over next 2-4 days 3. Causes primary viremia (~4-6 days after incoc.) 4. Replicates in liver, spleen & other organs causing secondary viremia. 5. Secondary viremia spreads viral particles to skin 14-16 days after initial exposure & causes typical vesicular rash.
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Primary VZV Infection - Age, Spread, Incubation, Prevention
- common childhood disease - highly contagious - incubation of 10-21 days - preventable by vaccination (introduced in 1995)
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Varicella Treatment
- Typically self-limited & requires no treatment - Treatment accelerates resolution of chickenpox & decreases symptoms - Immunocompromised patients should always receive treatment
38
Varicella Prevention/Prophylaxis
Varicella vaccine: is a live-attenuated vaccine - Beware in immunocompromised hosts - 2-dose series at 12-15 mo & 4-6 yo - Can be used post-exposure in certain situations Varicella-zoster immune globulin (Varizig) - for reducing severity of varicella in high-risk individuals if given w/in 4 days of exposure = pooled Abs from ppl w/ high VZV Ab titers
39
Pathogenesis of Latency and Reactivation of VZV
- Latent in cranial, dorsal root and/or trigeminal ganglia = Only herpes virus w/out asymptomatic viral shedding in normal hosts - Reactivation is ALWAYS SYMPTOMATIC - Reactivates in ganglion & tracks down sensory nerve to skin innervated by the nerve - Causes dermatomal rash that is pathognomonic for Zoster
40
Zoster (Shingles) Infection = Reactivation of Primary VZV
- in up to 30% of population - 1st symptom is pain at site where vesicles will erupt in a few days. Lesions - develop in single dermatome. - itchy, but main symptom is pain - usually crust over within 2 weeks
41
Complications of Zoster (Shingles):
- Similar to Varicella - Secondary skin infections - VZV ophthalmicus - Encephalitis - CNS vasculitis - Myelitis (spinal cord inflammation) - Cranial-nerve palsies: Ramsay-Hunt syndrome, Bell’s palsy - Peripheral nerve palsies - Post-herpetic neuralgia (PHN): can be very debilitating & last weeks to months after lesions resolve
42
Immune response to VZV reactivation
- Cell-mediated immunity is crucial to maintaining latency & preventing reactivation of VZV - Cell-mediated immunity decreases w/ age & is often affected by immunosuppression and HIV
43
Complications of Varicella (Primary VZV)
Secondary infection: - Group A Strep - Necrotizing fasciitis - Pneumonia (bacterial or viral) - Encephalitis or encephalomyelitis - Hepatitis - Congenital varicella (TORCH infection, severe) Adolescents & adults have more severe disease Pregnant / immunocompromised ppl have higher morbidity / mortality from primary VZV
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Zoster treatment
Acyclovir - decreases number & duration of lesions - decreases pain PAIN = often worst part of shingles - can be treated w/ NSAIDS & opiates, occasionally with steroids
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Zoster Prevention/Prophylaxis:
- Live-attenuated vaccine, Zostavax (ZOS) - One dose age 60+ recommended by ACIP - Boosts immune response to VZV, thereby preventing reactivation - Can also use acyclovir for people w/recurrent shingles (usually the immunocompromised)
46
Epstein Barr Virus - Primary Infection
- very common (almost all ppl infected by age 40) - primary infections often occur in early childhood - either asymptomatic or are a mild febrile illness - incubation period is 4-6 weeks - Transmission via saliva: kissing, sharing utensils/food/drink
47
Infectious mononucleosis
= clinical syndrome that occurs when older child, adolescent or adult gets primary EBV infection (or less commonly CMV) = in ~40-50% of primary infections in this age group = “kissing disease” Symptoms include: - fever - sore throat - swollen lymph nodes - fatigue Physical exam: - Exudative tonsillitis - Enlarged cervical nodes - Splenomegaly, occasionally hepatomegaly Symptoms usually resolve in 4-8 weeks
48
Pathogenesis of EBV infection
1. Infects nasopharyngeal epithelium 2. Results in cell lysis & viral spread to adjacent structures (salivary glands, oropharyngeal lymphoid tissue, etc.) 3. Viremia occurs w/ distribution to liver, spleen, & infection of B lymphocytes 4. Remains dormant/latent in nasopharyngeal epithelium & B cells 5. Periodically, can reactivate (normally asymptomatic) & is commonly found intermittently in saliva of infected persons
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Diagnosis of EBV (Infectious Mono)
- Often clinical diagnosis - Atypical lymphocytes on peripheral blood smear & often are >10% on the differential - Monospot/heterophile tests - If definitive Dx needed, can do EBV serology
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Monospot/heterophile tests for EBC/Infectious mononucleosis
- Detects presence of Abs that agglutinate horse / sheep / cattle RBCs - After acute infection w/EBV, 75-90% of pts develop Abs that cross-react & agglutinate RBCs - Heterophile Abs highest during 1st four weeks of infection
51
EBV serology
- used if definitive Dx of EBV is needed - measures development of Abs to EBV antigens: EBNA and VCA (viral capsid antigen) IgM response to VCA indicates recent infection: - appears early in infection & disappears in 4-6 wks - seen by the time symptoms appear IgG response to VCA indicates prior infection: - appears at 2-4 weeks after symptoms begin & persists for life EBNA (IgG) indicates past infection: - infection at least a few months back - NEVER positive in an acute infection
52
EBV Prevention/Prophylaxis
- NO vaccine available | - Prevention of primary infection through preventing contact w/ infectious saliva
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Cancers associated with EBV
- Not part of a primary infection, but occur later Burkitt’s Lymphoma: - endemic in Africa & sporadic elsewhere - B cell tumor often affecting the jaw Hodgkin’s lymphoma Nasopharyngeal carcinoma: esp. in Chinese Lymphoproliferative disease: - in immunocompromised patients <-- uncontrolled proliferation of EBV-infected B cells
54
EBV Treatment
In normal hosts - treated supportively (fluids, antipyretics) Steroids - for pts w/impending tonsillar enlargement threatening to occlude airway - for pts w/ severe hepatitis In immunocompromised hosts - very difficult to treat - mainstay is restoring immune function (reducing immunosuppression) if possible
55
Cytomegalovirus (CMV) Transmission
Transmission through contact w/ infected body fluids - Saliva, milk, sexual contact, blood, tears, urine - Blood transfusions & organ transplantation Infected pregnant women can pass the virus to their unborn babies (in utero or perinatally)
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Zoster/Shingles diagnosis
- Usually diagnosed clinically | - can use Direct IFA, PCR, or culture
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Pathogenesis of CMV:
1. Infects epithelial cells of salivary gland or genital tract 2. Persistent infection & intermittent viral shedding * All cells where CMV becomes latent UNKNOWN 3. Likely viremia causing wide distribution of virus to other organs & tissues * Infection of GU system leads to shedding in urine
58
Primary Infection with CMV in normal, healthy people
In most healthy persons acquiring CMV after birth: - Almost always asymptomatic - Sometime mild febrile illness - Sometimes mono-like syndrome (similar to EBV) w/ fever, swollen lymph nodes, & mild hepatitis - no longterm consequences Incubation period 2 weeks to 2 months
59
Primary Infection with CMV in Immunocompromised
- serious & can infect most organs - severity parallels degree of impairment of cell-mediated immunity - severe disease most common in pts with organ / marrow transplants or HIV (w/very low CD4 counts) - -> CMV pneumonia, colitis, retinitis, hepatitis, encephalitis - -> CMV retinitis & colitis in HIV patients
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Pregnancy & CMV
- Most common in utero infection in US - When pregnant woman develops primary CMV infection, 3-5% chance that child will be born w/ congenital CMV infection. - Infection of fetus can also occur if pregnant women reactivates CMV, but much lower risk (<1% infected & even fewer symptomatic)
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Congenital CMV Syndrome
- Most congenitally infected infants asymptomatic - Only 10-15% have symptoms at birth (this is 3-5% of infants born to mothers w/ primary infections) Syndrome: - Low birth weight - Microcephaly - Hearing loss - Mental impairment - Hepatosplenomegaly & Jaundice - Skin rash (blueberry muffin spots) - Chorioretinitis
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Latency and Reactivation of CMV:
- Latent in monocytes & lymphocytes | - May reactivate from time to time, during which infectious virions appear in urine & saliva
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Reactivation of CMV in Pregnant Women
- can lead to vertical transmission (mom to fetus) | - more common in mothers w/ primary infection
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Epidemiology of CMV Infection
- In developed countries w/ high standard of hygiene, 50-80% of entire population is infected by 40 yo - In developing countries, over 90% are infected
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Reactivation of CMV in immunocompromised individuals
- may produce serious disease w/ high morbidity & mortality Disease can be... - non-focal viral syndrome - organ-specific infection (ex:hepatitis, pneumonitis)
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Diagnosis of CMV infection
- Serology (CMV IgM & IgG) - Viral culture (easy to grow, takes several days) - PCR - Direct fluorescence test - Tissue histology
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Reactivation of CMV in persons with normal immune systems
- asymptomatic | - BUT virus is being shed in bodily secretions
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Tissue histology in CMV infection
"Owl's Eye" appearance of infected cells = densely staining body surrounded by a halo - due to intranuclear inclusion bodies (viral proteins or particles) Intracytoplasmic inclusions (multiple smaller inclusions) are also seen in CMV infection
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Treatment of CMV in Immunocompetent hosts
No treatment indicated
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Treatment of CMV in Pregnant woman
- Some protection offered by immunoglobulin preparation w/ high titer of CMV Abs (CMV-IG)
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Treatment of CMV in Infants w/ Congenital CMV
- Gancyclovir in infants w/congenital CMV is currently being studied - NEW standard of practice will likely be treatment of symptomatic congenital CMV infection for first 6 mos of life w/ oral valganciclovir
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Prevention of CMV
- NO vaccines available In Immunocompromised pts at very high risk for severe CMV disease: - IV CMV-IG once a month as prophylaxis - Ganciclovir or valganciclovir as prophylaxis in some circumstances (ex: post-transplant)
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Respiratory Syncytial Virus (RSV) -- Family & Structure
- Paramyxoviridae family - Enveloped - ssRNA genome - 2 important surface proteins: G-protein & F-protein
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2 Important Surface Proteins in RSV
G-protein - for viral attachment to host cells F-protein (Fusion protein) - fusion of infected cells to neighboring cells to form syncytia (multinucleated giant cells)
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Primary Infection w/ RSV (w/ ages)
- Usually Symptomatic - lasts 7-21 days - Acute respiratory disease in patients of all ages - Bronchiolitis: children <1 yr of age - Viral pneumonia: young children & elderly - Upper respiratory tract infection: children & adults
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Transmission of RSV & Incubation period
- By contact w/ droplets (respiratory secretions) on fomites, with subsequent contact w/eye, nose, or mouth - By aerosol droplets also possible - Incubation period is 5 days
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Clinical patterns of RSV in premature infants & young children
Most frequent cause of bronchiolitis & viral pneumonia Almost all children infected at least once by 2yo Symptoms include: - fever - runny nose - cough - wheezing w/ involvement of lower respiratory tract
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Clinical patterns of RSV infection (seasonality, hospitalizations)
- Seasonal illness, peaking in Winter | - Up to 125,000 hospitalizations annually
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Reinfection w/ RSV
- In adults and older children - Rarely Asymptomatic - Generally resembles severe cold - Usually confined to upper respiratory tract
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Bronchiolitis w/ RSV
1. URI w/ congestion, sore throat, fever 2. Cough deepens & becomes more prominent 3. Lower respiratory tract involvement develops w/ - increased respiratory rate - intercostal muscle retraction - wheezing Wheezing in child <2 yr of age is most likely bronchiolitis
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Pathogenesis of RSV infection
1. Entry through mucosa of eye & nose 2. Infects respiratory tract locally 3. Cell-to-cell transfer of virus leads to spread from upper to lower respiratory tract 4. Syncytia formed through fusion of adjacent cell membranes
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Pathogenesis of Bronchiolitis in RSV infections
Bronchiolitis results from: - Mucosal edema - Cell necrosis & sloughing - Increased mucous secretion & plugging of bronchiolar lumina w/ epithelial debris & mucous Airway hyper-reactivity & bronchoconstriction also occur as a result of inflammation --> wheezing
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High-risk patients for RSV infections
Infants at high risk for severe RSV bronchiolitis - Premature infants (< 32 weeks gestation) - Pts w/ Chronic lung disease - Pts w/Complicated congenital heart disease Adults & older children at high risk for severe RSV disease are those w/significant immunosuppression (bone marrow or solid organ transplant)
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High risk infants vs. Non-high risk infants with RSV infection
High risk (premature) infants: - 8-10 x higher hospitalization rates - Higher need for ICU care & mechanical ventilation - 2-6 x higher Mortality rates
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Treatment of CMV in Immunocompromised hosts:
- Treat with gancyclovir or valganciclovir | - Choice of med & duration of treatment depends on the disease
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Treatment of RSV
-Mostly supportive Can use inhaled bronchodilators (albuterol) Ribavirin = only antiviral available for Tx of RSV - Currently limited use (only in dire circumstances -- bone marrow transplant, complicated congenital heart disease, etc.) - Controversial efficacy / safety - Modest effects in studies - Given as an aerosol - VERY Expensive
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RSV Prevention
- Humoral immunity (antibodies) - NO licensed vaccine available - Primary prevention via avoiding infected secretions
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Humoral immunity (antibodies) in Prevention of RSV infection
Infants w/ high levels of maternal Abs to RSV are less likely to be infected RSV F-protein mAb prep - can be given IM to high risk infants - -> ~50% reduction in hospitalizations due to RSV - Administered monthly during RSV season - Very expensive
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Rotavirus (Family, Structure, etc.)
Reoviridae family Double stranded RNA virus w/ segmented genome --> Allows for reassortment & genetic diversity ``` Several serotypes (strains) of rotavirus - 5 strains responsible for >90% of rotavirus disease in the U.S. ```
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Diagnosis of RSV:
- usually clinical - Viral culture - Serology - Direct fluorescent antibody
91
Transmission of Rotovirus
- Fecal oral transmission most common - Kids excrete 100 billion rotavirus particles per mL of feces - Infectious dose is 10-100 virus particles - 43% of rotavirus virions survive on human fingers for 60 minutes - Rotavirus in feces may survive for days to weeks on environmental surfaces
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Pathogenesis of Rotavirus & Recovery
1. Infects mature absorptive epithelial cells or enterocytes (at tips of villi) in proximal 2/3 of ileum 2. Cell death leads to: - Reduced absorptive surface area of sm. intestine - Loss of enzymes that break down complex sugars - Increased fluid & osmotic load --> diarrhea Regeneration of villi takes 7-10 days (recovery period)
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Natural Immunity to Rotovirus
- 1st infections --> severe gastroenteritis - Subsequent infections --> milder or asymptomatic - Protective immunity develops after each infection which protects against symptomatic disease
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Epidemiology of Rotovirus infection
- Leading single cause of severe diarrhea and/or gastroenteritis in infants & young children - Prior to vaccine, nearly every child had been infected at least once w/ rotavirus by age 5
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Rotovirus Treatment
- No antivirals available - Supportive management = Attention to fluids (Pedialyte, 50/50 Gatorade / water, IV fluids for severe dehydration)
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Rotovirus Prevention/Prophylaxis
2 oral, live-attenuated rotavirus vaccines licensed for use in infants: - RotaRix (2 doses): monovalent human - RotaTeq (3 doses): pentavalent human-bovine reassortment Both vaccines roughly equivalent in safety & efficacy Both highly protective in prevention of moderate & severe rotavirus disease - ~90% reduction in all types of health care visits
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Diagnosis of rotavirus
ELISA on stool samples