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Viral Infections in the Immunocompetent Host. Corey Casper, M.D., M.P.H. Division of Infectious Disease, Department of Medicine The University of Washington Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center . Outline. Classification of Viruses

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viral infections in the immunocompetent host

Viral Infections in the Immunocompetent Host

Corey Casper, M.D., M.P.H.

Division of Infectious Disease, Department of Medicine

The University of Washington

Vaccine and Infectious Disease Institute,

Fred Hutchinson Cancer Research Center

outline
Outline
  • Classification of Viruses
    • Classical vs. Other Schemes
  • Diagnosis of Viral Infections
  • Common Viral Infections for the Infectious Disease Consultant
classification of viruses1
Classification of Viruses
  • Classic Taxonomy
    • Nucleic Acid Structure
      • DNA vs. RNA
      • Single vs. Double Stranded
    • Envelope
      • Presence or absence
    • Organization of genome
      • Example: Paramyxoviruses
    • Mode of transcription
      • Example: Retroviruses
  • “Functional Taxonomy”
    • Group viruses by primary organ system involved in the pathology of disease
      • Example: Respiratory Viruses
    • Group viruses with similar treatments
      • Example: Herpesviruses
your mother knows best
Your Mother Knows Best?
  • Which of the following viruses would you be most likely to acquire from touching a toilet seat? True MedCon Call!
    • HIV
    • Calicivirus
    • Herpes Simplex Virus-2
    • Parainfluenza
player or bystander
Player or Bystander?
  • A 63 y.o. man presents from an outside hospital with fever and headache for 2 weeks. Multiple blood, urine, CSF, and sputum cultures have been negative. Chest X-ray, full body CT and peripheral smear are all unremarkable. You are consulted by the medical team to assess whether the patient’s symptoms could be attributable to infection with CMV. Which of the following studies would support that diagnosis?
    • 1,000 copies of CMV DNA by PCR from the peripheral blood
    • Positive CMV IgM
    • Positive urine CMV shell-vial culture
    • None of the above
diagnostic virology culture
Diagnostic Virology: Culture
  • Clinical specimen collected and either sent directly to lab or placed in viral culture medium
  • Specimens then grown on number of different cell lines depending on type of virus suspected
    • Diagnosis either by looking for CPE, or adding fluorescently-tagged antibodies to viral antigens
      • “Shell vial” culture: Diagnosis of CMV or BK
  • Advantages: Specific, sensitivity testing?
  • Disadvantages: Slow, not as sensitive as molecular diagnostics, not possible for all viruses
diagnostic virology dfa
Diagnostic Virology: DFA

Fluorescent label

Antibody to Viral Protein

Clinical Specimen

diagnostic virology eia
Diagnostic Virology: EIA

Fluorescent label

Antibody to Human Antibodies

Sera Containing Antibodies to Viral Protein

Viral Protein

diagnostic virology pcr
Diagnostic Virology: PCR
  • Advantages:
    • Rapid
    • Sensitive
    • Quantitative
  • Disadvantages
    • Too sensitive?
    • Specificity
    • Costly

Source: http://www.nupedia.com/newsystem/upload_file/678/pcr.png

case 1 hpi
Case 1: HPI
  • 18 y.o. woman from Sitka, Alaska who presents with fevers and abdominal pain for 2 weeks
  • Initially presented to ED in AK 2 weeks PTA with dysuria and mild abdominal pain
    • Treated with TMP-SMX without improvement
  • Re-presented 3 days later with severe abdominal pain, headache and temperature to 102F. Had diffuse vesicular rash
  • Admitted to hospital where she had the following labs/studies:
    • Normal CBC, SMA-7, negative UA, negative CXR and KUB
    • AST 110, ALT 124, nml INR, GGT, Amylase, Alk Phos
  • Hospital Course:
    • Subsequent multiple blood and urine cultures negative
    • CT of chest, abdomen and pelvis negative
    • Exploratory laparotomy found lesions on the liver as on the following slide
    • Persistent fevers and abdominal pain despite Cefotetan, Doxycycline and Metronidazole
    • Transferred to UWMC
case 1 physical exam on transfer to uwmc
Case 1: Physical Exam on Transfer to UWMC
  • T 38.9, HR 110, RR 22, BP 118/72
  • Abd: Diffuse TTP, no rebound or guarding
  • Skin: Adjacent rash
  • GU: Nml genitalia
the herpesvirus family
The Herpesvirus Family
  • HHV-1 : Herpes Simplex 1 (HSV-1)
    • Clinical: Oral Herpes
  • HHV-2 : Herpes Simplex 2 (HSV-2)
    • Clinical: Genital Herpes
  • HHV-3 : Varicella Zoster Virus (VZV)
    • Clinical: Chickenpox, Zoster
  • HHV-4 : Epstein Barr Virus (EBV)
    • Clinical: Mono, lymphoma
  • HHV-5: Cytomegalovirus (CMV)
    • Clinical: Retinitis, Pneumonitis, etc
  • HHV-6/7: Roseolavirus
    • Clinical: Exanthem subitum
  • HHV-8: Kaposi’s Sarcoma-Associated Herpesvirus (KSHV)
    • Clinical: KS, multicentric Castleman’s disease, primary effusion lymphoma
herpesvirus family characteristics
Herpesvirus Family Characteristics
  • Large, Enveloped DNA-viruses
    • Envelope:
      • Transmission via mucosal surfaces
      • Fomite acquisition is uncommon
    • Large
      • Smart!
        • Evolved many complex mechanisms for immune evasion and pathogenesis
    • DNA
      • Use similar cellular machinery to human DNA, so therapy must find novel areas of difference (in contrast to HIV)
  • Ubiquitous
    • Except for HSV-2 and HHV-8, all infect more than 50% of most populations worldwide
  • Latency allows for life-long infection
    • Intermittent reactivation and lifelong shedding can make understanding clinical symptoms and diagnostic tests challenging
    • Long term infection with some herpesvirus can lead to cancer
herpesvirus therapy dna synthesis inhibitors
Herpesvirus Therapy: DNA Synthesis Inhibitors
  • Aciclovir and ganciclovir require viral TK to make dGMP, then cellular kinases make dGTP which terminates DNA synthesis
  • Cidofovir and foscarnet do not require TK
  • Ribavirin depletes intracelluar GTP

Source: Naesens and de Clercq Herpes 2001

case 2
Case 2
  • 34 y.o. nurse presents with 3 weeks of coughing, post-tussive emesis, sinus congestion and malaise in January
respiratory viruses clinical
Respiratory Viruses: Clinical
  • Heterogeneous group of viruses
    • DNA and RNA, enveloped and “naked”
  • Similar clinical presentations
  • Seasonality is important
what goes around comes around
What goes around comes around…
  • http://depts.washington.edu/rspvirus/respiratory.htm
influenza virus strains
Influenza: Virus Strains
  • Type A - moderate to severe illness - all age groups - humans and other animals

- Subtypes of type A determined by hemagglutinin and neuraminidase

  • Type B - milder epidemics - humans only - primarily affects children
  • Type C - rarely reported in humans - no epidemics
influenza virus
Influenza Virus
  • Neuraminidase
  • Antigenic Determinant
  • Confer virulence
  • Allow viral mobility through
  • Respiratory tract
  • Hemagglutinin
  • Binds virus to cell
  • Confers target specificity

RNA

  • M2 protein
  • only on type A
  • Allows H+ ions to enter virus to lower
  • pH for viral uncoating
influenza antigenic changes
Influenza Antigenic Changes
  • Hemagglutinin and neuraminidase antigens change with time
  • Changes occur as a result of point mutations in the virus gene (“antigenic drift”), or due to exchange of a gene segment with another subtype of influenza virus (“antigenic shift”)
  • Impact of antigenic changes depend on extent of change (more change usually means larger impact)
influenza clinical features
Influenza Clinical Features
  • Incubation period 2 days (range 1-4 days)
  • Severity of illness depends on prior experience with related variants
  • Abrupt onset of fever, myalgia, sore throat, nonproductive cough, headache
influenza complications
Influenza Complications
  • Pneumonia
    • primary influenza
    • secondary bacterial
  • Reye syndrome
  • Myocarditis
  • Death 0.5-1 per 1,000 cases
influenza treatment prophylaxis
Influenza: Treatment & Prophylaxis
  • M2 Inhibitors
    • Amantadine and rimantidine
    • “Effective” against Influenza A
      • 2007, >97% of influenza was resistant
      • SWINE FLU IS RESISTANT
    • Inhibit viral replication
    • Single mutation confers resistance, occurs with every 1,000-10,000 replications
  • Neuraminidase inhibitors
    • Oseltamivir (oral pill) and Zanamivir (inhaled)
    • Effective against Influenza A and B
    • 98% of H1N1 strains (except SWINE FLU) were resistant in 2008-9!
  • Combination therapy?
    • Oseltamavir, rimantidine and ribavirin have been shown to have combined efficacy
respiratory viruses adenovirus
Respiratory Viruses: Adenovirus
  • Common cause of URI and keratoconjuntivitis. Has been occasionally associated with pneumonia in community outbreaks, diarrhea in children, and hepatitis.
  • May cause cystitis or nephritis in transplant patients
  • Treatment: Supportive. IV cidofovir may be effective in the immunocompromised
respiratory viruses parainfluenza
Respiratory Viruses: Parainfluenza
  • Four subtypes
    • PIV3 seen most commonly in severe infections
  • In children, leading cause of croup. Can be a cause of severe lower respiratory tract illness in some children or transplant patients
  • Treatment is supportive, but aerosolized ribavirin may be used in life-threatening cases
respiratory viruses metapneumovirus
Respiratory Viruses: Metapneumovirus
  • Recently identified from retrospective series of unidentified respiratory illnesses.
  • Serologic studies suggest most are infected by 5 years of age, peak 6-12 months
  • Mild URI in most, with rare progression to severe LRTI
  • Wheezing is a common initial presentation
  • Treatment is supportive
respiratory viruses coronaviruses
Respiratory Viruses: Coronaviruses
  • Large family of viruses with multiple animal hosts
  • Generally cause non-specific symptoms such as fevers, myalgias, fatigue. May progresses to non-productive cough and dyspnea.
  • Diagnosis is by PCR, and treatment is supportive
  • SARS
    • Newly identified virus associated with severe LRTI in Asia in 2003. Thought to be transmitted by contact with small mammals (civets) in Asia, spread between humans through respiratory droplets and feces
    • Development of respiratory failure occurs in minority of cases, but may be more common in Asian persons
pcr for respiratory virus detection
PCR for Respiratory Virus Detection
  • Problem of inadequate specimens for immunoblot or DFA
  • PCR is more sensitive and perhaps equally as specific
  • Molecular Virology Lab now offers multiplex PCR for detection of 12 viruses

Kuypers, et al 2006

gastrointestinal viruses
Gastrointestinal Viruses
  • Most common viruses to cause gastrointestinal illnesses are Norovirus, calicivirus, rotavirus, astrovirus, and adenovirus
  • Present with diarrhea, fever and/or abdominal pain. Children more often affected, although incidence high in institutional or “closed” settings (i.e. cruise ships)
  • Transmission via fecal-oral route
  • Diagnosis:
    • PCR of stool, or plasma PCR if disseminated disease suspected (adenovirus)
case 3
Case 3
  • 21 year old UW student presents with fever to 39, headache, stiff neck and photophobia shortly after returning for Fall Quarter
  • Student health service concerned about risk of meningitis epidemic
case 3 continued
Case 3: Continued
  • Physical examination revealed the following:
enteroviruses
Enteroviruses
  • Large group of viruses including the subgroups: poliovirus, echovirus, and coxsackieviruses
  • Worldwide pathogens with most infections in summer and fall
  • Chronic meningoencephalitis among persons with agammaglobulinemia
  • Diagnosis
    • PCR of stool, oropharynx or CSF
enteroviruses coxsackievirus
Enteroviruses: Coxsackievirus
  • Common causes of aseptic meningitis
  • Heterogeneous and non-distinct exanthems (skin rashes). Exception: Hand-Foot-Mouth (Coxsackievirus A16) with oral vesicles and papules/vesicles on palms and soles.
  • Complications:
    • Group A
      • herpangina (dysphagia with lesions on soft palate)
    • Group B
      • Myopericarditis
case 4
Case 4
  • 62 y.o. man taken to HMC from cruise ship docked at Pier 66 with fevers, altered mental status, and weakness in the left leg
flaviviruses
FLAVIVIRUSES
  • Heterogeneous group of zoonotic / arthropod transmitted viruses
    • West Nile Virus
    • Dengue
    • Yellow Fever
    • Japanese Encephalitis
    • St. Louis Encephalitis
    • Tick-Borne Encephalitis
  • Diagnosis
    • Serology
      • IgM during acute illness or IgG in convalescence
        • Serum should be collected 8-10 days after illness onset.
        • Follow up with a convalescent serum specimen obtained at least 2 weeks after the first specimen.
        • CSF should be collected within 8 days of illness onset. IgM may appear in CSF earlier than in serum.
        • IgM does not cross the blood brain barrier: its presence in CSF indicates neuroinvasive disease.
        • IgM antibody can persist for more than
      • Non-specific (but this may be a good thing!)
    • PCR
      • Less sensitive, but useful in immunocompromised hosts
flaviviruses west nile virus
Flaviviruses: West Nile Virus
  • Rapidly emerging virus across U.S. since 1999
    • WA one of the few states without any documented infections
  • Transmitted from reservoirs in birds to human via mosquitoes
  • Majority of infections are without symptoms or only with fever and malaise, but most severe complication is neurological (encephalitis and muscle weakness)
flaviviruses dengue
Flaviviruses: Dengue
  • Tropical virus transmitted by Aedes aegypti (day biting) mosquito
  • Illness characterized by high fever, headache (often retro-orbital), myalgias/arthralgias and rash
  • Hemorrhagic fever or shock may occur shortly after resolution of fever. May be more common in persons previously exposed.
flaviviruses yellow fever
Flaviviruses: Yellow Fever
  • Endemic to sub-Saharan Africa and South America
  • Transmitted by mosquito bites
  • Symptoms range from constitutional to severe. Symptomatic patients likely to experience headache, altered mental status, icterus, and many have diffuse hemorrhage
  • Preventable by vaccine, which may cause vaccine-induced encephalitis among young infants or the elderly
other flaviviruses
Other Flaviviruses
  • Japanese Encephalitis
    • High fevers and altered mental status
    • Endemic to regions in Asia where mosquitoes interact with pigs and birds
  • St. Louis Encephalitis
    • Fevers and altered mental status, especially among the elderly.
    • Seen in North, Central and South America as well as the Caribbean.
  • Tick-Borne Encephalitis
    • Infection via Ixodes species ticks
    • Europe and Asia
    • History: persons with outdoor exposure.
    • Presents with fever, but may progress to altered mental status and paralysis.
case 5
Case 5
  • 28 year old latina sheep-sheerer from Oregon presents to UWMC with increasing lesion on hand
poxviruses orthopox
Poxviruses: Orthopox
  • Monkeypox: recently spread by prairie dogs
  • Cowpox: cause “milkers nodules” on hands of dairy workers
  • ORF: nodule on hands, arms or face after exposure to ruminants
  • Smallpox
  • Diagnosis
    • Electron Microscopy
poxviruses smallpox
Poxviruses: Smallpox
  • Smallpox is the only infectious disease eradicated with vaccination, now threatening to return in the setting of bioterrorism
  • Infection via respiratory droplets or contact with infected lesions. Acquisition is largely asymptomatic for first 7-10 days, followed by a non-specific prodrome consisting of fevers and malaise.
  • Patient becomes infectious upon development of rash. Typically, rash is maculopapular, starts in the oropoharynx/head/neck/upper extremities, and moves caudally. Lesions are usually in the same stage (i.e. vesicular, pustular, crusted), which differentiates the lesion from varicella.
  • Diagnosis is by PCR or electron microscopy of vesicular fluid
  • Treatment is supportive, although cidofovir may be effective if given early after infection. Vaccination within 4 days of exposure may mitigate course of infection
poxviruses parapox
Poxviruses: Parapox
  • Molluscum contagiousum
    • Umbilicated firm cutaneous
    • May be more persistent in immunocompromised adults
    • Typically is treated with curettage or cryotherapy.
case 6
Case 6
  • 26 year old medical student wanders on to general medical ward with conjunctival hemorrhages, fever, and confusion
hemorrhagic viruses
HEMORRHAGIC VIRUSES
  • Filoviridae
    • Ebola
    • Marburg
  • Bunyaviridae
    • Hantavirus
    • Rift Valley Fever
    • Crimean-Congo Hemorrhagic Fever
  • Arenaviridae
    • Lassa virus
  • Diagnosis
    • Serology from CDC or PCR
filoviridae
Filoviridae
  • Ebola and Marburg
  • Acquired through contact with non-human primates in Africa
  • Fevers and myalgias are followed by maculopapular rash, after which between 10 and 50% will develop disseminated intravascular coagulation
bunyaviridae
Bunyaviridae
  • Rift Valley Fever
    • Transmitted by Aedes mosquitos in sub-Saharan Africa
    • Three clinical syndromes
      • Non-specific febrile illness (~90%)
      • Macular Retinitis / Vasculitis (10%)
      • Fulminant disease: hepatic failure / hemorrhage
  • Crimean-Congo Hemorrhagic Fever
    • Transmitted by ticks in Southwest Asia, Middle East and Africa
      • Hemorrhagic fever / DIC in 20-50%
  • Hantavirus
    • Transmitted by wild rodents
    • Two types
      • Asian strains: fever and renal failure
      • North American strains: fever and pulmonary edema
arenaviruses
Arenaviruses
  • Transmitted to humans via contact with rodents
  • Endemic to Africa and South America
  • Lassa fever
    • Severe systemic illness with shock
    • ~20% mortality
  • Lymphocytic Choriormeningitis Virus (LCMV)
    • Aseptic meningitis with low mortality
case 7
Case 7
  • You are called in the middle of the night because sibling’s child has high fevers and an unusual rash
parvovirus
PARVOVIRUS
  • Smallest DNA virus
  • Epidemiology
    • Widespread infection
      • 50% of adolescents and nearly all elderly persons have serum antibodies to Parvovirus B19
    • Spread among close contacts by respiratory droplets or blood
  • Clinical
    • Cause of erhythema infectiousum (“slapped cheek” or 5th disease), arthritis, red cell aplasia or aplastic crisis, and hemophagocytic syndrome
    • Fetal infection may lead to hydrops fetalis or miscarriage
      • 10% fetal loss in 1st trimester pregnancies
      • Risk of hydrops greatest in 3rd trimester
    • Immunocompromised patients may have chronic low-level viremia which is not associated with disease
  • Consider IVIG in non-immune, exposed pregnant women
  • Diagnosis
    • Plasma PCR
    • Low reticulocyte count in presence of anemia could be an early diagnostic clue
case 8
Case 8
  • 7 year old boy presents with fever and rash after visiting Hunan Province of China
  • Also traveled to Hong Kong and San Francisco
  • 11 other children had fever and similar rash
measles rubeola
Measles (Rubeola)
  • Virology
    • Extremely infectious paramyxovirus spread through contact with respiratory droplets
    • Nearly 2 week incubation period followed by
  • Symptoms
    • Constitutional symptoms
    • “Classic”: cough, coryza and Koplik’s spots (small, bluish granules on erythematous buccal mucosa)
    • Erythematous maculopapular rash spread cranio-caudally and may desquamate and involve palms / soles.
  • Complications
    • Pneumonia with secondary bacterial superinfection
    • Encephalitis (may be chronic in subacute sclerosing panencephalitis)
  • Diagnosis
    • Serology
mumps
Mumps
  • Paramyxovirus acquired through nasopharyngeal contact with respiratory droplets or fomites
  • Extended (2-4 week) incubation period
  • Clinical illness heralded by otalgia and parotid hypertrophy and sialadenitis, and may be followed by meningitis, encephalitis or orchitis
  • Diagnosis:
    • Serology
rubella german measles
Rubella (German Measles)
  • Benign viral infection characterized by fever and maculopapular non-confluent craniocaudal rash.
  • May occasionally be complicated by arthralgia
  • Congenital infection
    • May lead to fetal death and congenital abnormalities, including hearing loss, heart disease, cognitive delay
hsv 1 epidemiology
HSV-1: Epidemiology
  • Prevalence
    • Worldwide, 90% of people seropositive for HSV-1 by age 40
    • In US, approximately 50% and declining, but closer to 90% in groups with low SES
  • Transmission
    • Via saliva
    • Vesicles>Ulcers>Asymptomatic
      • Culture positivity: 80%, 33% and <25% respectively
hsv 1 primary infection
HSV-1: Primary Infection
  • Asymptomatic
    • 47% of people with positive HSV-1 serology do not recall history of oral / genital ulcers
  • Oral or Genital Ulcers
    • Fever / pharyngitis in first 12-24 hours (oral)
    • Vesicles by median of 7 days
    • Resolved by 14 days
  • Skin Infections
    • Herpetic Whitlow
  • Ocular Disease
    • Leading cause of blindness worldwide is Herpes Keratitis!
  • Encephalitis
    • Neonates or immunocompromised
  • Pneumonitis
    • Neonates or immunocompromised
  • Hepatitis
    • Fulminant and fatal in 80%
hsv 1 recurrences
HSV-1: Recurrences
  • Oral / Genital Ulcer Disease
    • Recurrence rates vary greatly by individual
    • 85% with prodrome 24h prior to lesion, then lesion x 8d
    • HSV-1 recurs infrequently at genital sites (average once per year)
  • Encephalitis
    • Recurrences after primary encephalitis not uncommon (in contrast to HSV-2)
    • First episode of encephalitis may result from reactivation of HSV-1 from oral primary in trigeminal ganglion
  • Pneumonitis
    • First episode of pneumonitis may result from aspirating reactivated oral HSV-1 during intubation or AMS
hsv 1 diagnosis
HSV-1: Diagnosis
  • Serologic
    • Detect IgG antibodies to HSV-1 and 2 gG (envelope glycoprotein)
    • Develop within 7-21 days
      • May be delayed by use of antivirals
    • Some antibody assays have difficulty differentiating between HSV-1 and 2
    • IgM testing is unreliable
  • Virologic
    • “Looking” for the virus
      • Tzanck
        • Insensitive and not specific
      • DFA
        • Rapid, specific and pretty sensitive for persons with active lesions
    • Growing the virus
      • Culture
        • Sensitive, specific, time consuming (3-7 days)
    • Amplifying viral DNA
      • PCR
        • Sensitive, specific, rapid
        • Prone to contamination
        • Not widely available
vzv natural history
VZV – Natural History

Source: Gilden DH, et. al. N Engl J Med 2000 342: 635-645

varicella zoster virus clinical syndromes
Varicella Zoster Virus – Clinical Syndromes
  • Varicella (Primary Infection)
    • 90-95% of persons by the age of 18 have had chickenpox
  • Zoster (Recurrent)
    • Common: 30-50 cases per 1000 person years
    • 20-30% of patients with HIV will develop Zoster
      • More likely to be multi-dermatomal
      • Associated with Immune Reconstitution
        • 8% in one study
          • Domingo P, Am J Med 2001; 110:605-9
  • Chronic encephalitis
    • Seen rarely outside immunocompromised persons
    • Subacute headache, fever, altered mental status
  • Acute Retinal Necrosis
    • Weeks to months after varicella or zoster
    • Likely due to hematogenous spread, so initial lesion at site distant to eye does not rule out ARN
    • 75-85% chance of detachment leading to blindness, with little benefit from antivirals
      • May prevent spread to contralateral eye

Source: http://www.dermis.net/bilder/CD18/img0054.jpg

ebv primary infection
EBV: Primary Infection
  • Asymptomatic
    • Common in kids under 2
    • May have negative Monospot
  • Infectious Mono
    • Fever, malaise, pharyngitis, lymphadenopathy, atypical lymphocytosis, splenomegaly without jaundice or hepatomegaly
  • Hemophagocytic syndrome
ebv malignancies after chronic infection
EBV: Malignancies after Chronic Infection
  • Mechanism
    • Persistent infection / activation of B cells coupled with viral immune evasion and control of cell cycle
  • Burkitt’s
    • Most common malignancy in childhood in Africa, along malaria belt
  • HIV Associated Lymphomas
    • Primary CNS
    • NHL
  • Nasopharyngeal Carcinoma
  • Post-Transplant Lymphoproliferative Disorder
    • Associated with degree of immunosuppression after SOT
    • Lung (up to 9%)>Heart>Kidney>Liver (1-2%)
    • Risk Factors: Lymphocyte depletion (OKT3 or ATG), D+/R-
ebv diagnostic tools and cautions
EBV: Diagnostic Tools and Cautions
  • Serologic
    • Heterophile Test (MonoSpot)
      • Antibodies to sheep erythrocytes
      • Develop in up to 70% of patients and may persist for > 1 year
    • Antibodies to EBV Proteins
      • Viral Capsid Antigen (VCA)
        • IgM develop immediately and rapidly fall, but laboratory test is difficult and prone to inaccuracy
        • IgG develop rapidly and persist (not useful for diagnosis)
      • Epstein Barr Nuclear Antigen (EBNA)
        • Appears at the end of course of IM and persists for life
        • Allows for viral latency
      • Early Antigen (EA)
        • Develop within 2-4 weeks and disappear
  • Virologic (PCR)
    • PCR for EBV from blood should be interpreted with caution
      • May be found in blood from asymptomatic individuals
        • Possibly due to B-cell stimulation
      • Quantity does NOT predict development of malignancy
    • Helpful from CSF to predict CNS lymphoma
hhv 8
HHV-8
  • Diseases
    • Kaposi Sarcoma
    • Primary Effusion Lymphoma
    • Multicentric Castleman Disease
    • Prostate Cancer?
    • Multiple Myeloma – NO
    • Pulmonary Hypertension - NO
  • Prevalence
    • General Population
      • Random Blood Donors: US 5%, Italy 20-30%, Middle East 20-30%, Africa 20-100%, South America 3-70%, Asia 5-30%
    • High Risk Groups
      • MSM: 20-30% HIV-negative in US, 30-50% HIV-pos
      • Recent study suggests that women in the United States may also have high rates of infection (16%)