Systemic Viral Infection
Epstein Bar Virus pathogens
"kissing disease": it takes two, on the li(m)ps (lmp1and2) Viral LMP-1 and LMP-2 prtns drive naive B cels to proliferate and become resting memory cells (which is where latent virus resides)
EBV infections: intervention
**Treat symptoms only: supportive treatment (antipyretics, analgesics, fluids, nutrition) -steroids help reduce tonsillar swelling in cases of severe tonsillitis or respiratory compromise
CMV disease in pts with AIDS
*CMV retinitis (30-85% of HIV+ pts) -cutaneous lesions (10-25%) -esophagitis (sever esphogeal ulcers) -encephalitis
Diagnosing VHF diseases
*Serology: -IgM anti-virus -ELISA for viral antigen **Travel history
Fever with hemorrhaging: Consider these agents if large numbers of patients suddenly present with symptoms of serious and uncommon infectious disease, esp. with ** NO TRAVEL HISTORY
*Yersenia pestis: dissemination from lung or skin--communicable among humans *HF viruses: athropods,penetration through abraded skin, unknown inhalation(potential bioterrorist scenario); some agents are communicable among humans
Filoviruses
*both from Africa -Ebola -Marburg *zoonotic transmission but can be spread person-person (via body fluid contact) *fever, dysentery, severe headache, vomiting, thrombocytopenia, rash, bleeding/bruising (25-90% mortality rates)
VHF: intervention
*supportive care: -supplemental O2 -alleviate hypotension -fluid replacement *Lassa fever: treated with Ribavirin (viral RNA polymerase inhibitor) *Patient isolation and barrier precautions!!!!!!!!!
EBV infection-differentials
-CMV infection (esp if monospot negative) -Group A Streptococcal, especially strep throat
Epstein-Barr Virus Infection and presentation
-Causative agent of infections mononucleosis "mono" -highest incidence 15-24 years with symptoms -sxs: fever, night sweats, malaise, pharyngitis, tonsillitis, lympadenopathy, splenatomegaly
(bioterrorism) Patient presents with Hemorrhagic fevers (HFs). What could it be?
-Ebola virus -Lassa fever
Viral hemorrhagic fever (VHF)
-Flaviviruses -Filoviruses -Arenaviruses *The hemorrhagic fever (HF) viruses are all enveloped RNA viruses
EBV sero profile: Past infection
-VCA-IgG -EBNA: EBV nuclear antigen
EBV sero profile: Reactivation Infection**
-VCA-IgG -EBNA: nuclear antigen -EA: early antigen *Reactivation ~occurs without symptoms of illness (like children); the virus is infectious in this stage!!
VHF transmission
-Vector: Arthropod (arboviruses) -Mosquitoes: *Flaviviruses (Dengue fever)
VHF presentation/symptoms
-abrupt onset of high-grade fever and non-specific sxs: anorexia, headache, prostration and sever myalgia -bleeding disorders: conjuctival injection, purpura (easily bruising), edema
EBV sero profile: Acute
-heterophile antibodies (anti-sheep RBC Abs yielding a positive monospot test- may only be present later in infection) -VCA-IgM (viral capsid antigen) -can have VCA-IgG -EA: early antigens
Cytomegalovirus infections
-infects monocytes -mainly causes disease in immunosupressed pts and neonates
CMV disease in Cancer/TPX pts
-interstitial pneumonitis (30-70% of tax pts) -gastroenteritis
CMV infection
-latent infection -inhibition of host cellular immune responses: helps hide from Immune system -transplacental passage to fetus
Typical lab findings in VHF
-leukopenia is suggestive -thrombocytopenia is typical -hematocrit normal or increased early (hemoconcentration) -AST (SGOT) typically elevated and has prognasic value
Dengue
-mosquito-borne illnesses caused by dengue virus -especially found in SE Asia -virus has four distinct serotypes: DEN1-4
Why are exotic viral diseases important health problems?
-most of world population at risk -pathogens are potential biological warfare/bioterror agents
How CMV differed from EBV mono
-no heterophile (anti-sheep RBC) antibodies -cervical lymphadentitis and pharanygitisis are rare -age of onsets is later ~28 yrs **milder liver invovlment (less elevation of liver enzymes)
EBV infection-sequelae
-rashes are common in mono patients treated with amoxicillin or ampicillin (~95% of pts with exposure to drug) -hematologic complications -80% of pts will have elevated liver enzymes
Dengue Fever
-severe febrile disease, a non-specific febrile illness
Dengue Fever
-severe pain behind eyes -"breakbone fever" -rapid onset of high fever, headache, retro-orbital pain, diffuse body pain (muscle and bone), prostration, maculopapular rash, capillary friability *luekopenia and thrombocytopenia *1/3 of pts have mild hemorrhagic sxs
(bioterrorism) A single case of uncommon organism.... What is the source?
-smallpox -pulmonary anthrax -ebola virus
Lassa fever
-spread primarily by inhalation of dried rodent excreta/urine -contagious!! -mortality rate is 5-30% in hospitalized -gradual onset.....facial edema -mortality is highest in pregnant women, and pts with bleeding
Chikungunya Virus characteristics
Alphaviridae of Togavirus family RNA virus Mosquito-borne Sudden, acute illness
Lassa fever
Arenovirus in West Africa
Junin virus
Argentine hemorraghic fever
What is the most common viral cause of birth defects?
CMV also causes still births
Mild Dengue Serotypes
DENV1 and 4
Severe Dengue Serotypes
DENV2 and 3
EBV oncogenesis
EBV can IMMORTALIZE human B cells in vitro: LMP1 induces cellular transformation, promotes cell motility and invasion. -LMP1 engages multiple signaling cascades -EBV nuclear antigen 1 (EBNA1)
EBV nuclear antigen 1
EBV nuclear antigen 1 (EBNA1) is expressed in all EBV-associated malignancies, also contributes to cell growth and transformation
(bioterrorism) Clue: An unusual geographic distribution Potential source or cirumcstance???
Ebola virus in the US
Two members of the Herpes virus
Epstein Barr Virus and CytoMegaly Virus -enveloped DNA viruses -causes persistent infections by latently infecting different cell types
treatment of life-threatening CMV infection
Ganciclovir valganciclovir cidofovir foscarnet
CMV infection in IMMUNOCOMPETENT adults
In adults, CMV can cause a mild mononucleosis, with fever, malaise and atypical lymphocytosis.
Death by VHF!!
Mortality: -hypovolemic shock -specific organ dysfunction may contribute
Arenaviruses?
Rodent contact
VHF transmission
Rodent contact: infected via direct contact with infected rodents: bites or inhalation of rodent feces/urine *Arenaviruses
CMV infection
Typical CMV infected cell: *haloed nuclear inclusion "owl's eye" inclusion
(bioterrorism) A large number of unexplained deaths, especially in young healthy adults What is going on?!?!
Various agents could be causing this.
(bioterrorism) Clue: clusters of a similar illness in noncontiguous areas, domestic or foreign
Various agents could cause this
Is EBV a carcinogen?
YES! Induces three neoplastic diseases -Burkitt's lymphoma -Nasopharyngeal carcinoma -B cell lymphoma: occurs in immunocompromised pts, esp. post-transplant lymphoproliferative diseases and AIDS
VHF pathogenesis
combination of endothelial dysfunction causing: -capillary leak syndrome with edema -bleeding diathesis (bleeding form injection sites) -thrombocytopenia -toxic effects on endothelial cells -diffuse intravascular coagulation
Chikungunya Virus symptoms
high fever headache fatigue back pain rash incapacitating polyarthralgias
Dengue fever: secondary infection
higher risk of plasma leakage that *NEED fluid management or could lead to shock
VHF: differentials
malaria
Dengue fever and secondary infection
mediated by binding of cross-reactive, neutralizing antibodies at sub-neutralizing concentration that *enhances* infection of monocytes and dendritic cells via FcR-mediated binding of antibodies
Flavoviruses?
mosquitos
EBV dx: EBV is a _______clonal B cell activator.
poly (polyclonal) -elevated serum Ig, -presence of heterophile antibodies -IgM antibodies to viral capsid antigens (VCA) -marked lymphocytosis with atypical lymphocytes (activated T lymphocytes)
Severe dengue
presence of dengue fever with: --plasma leakage resulting in shock or respiratory distress --severe bleeding --severe organ involvement (elevation in liver enzymes) --impaired consciousness --myocardial dysfunction