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Herpesviruses
Infec3ous Diseases in Clinical Prac3ce February 2016
Jennifer Babik, MD, PhD Division of Infec3ous Diseases University of California, San Francisco
Disclosures
§ None
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Learning Objec3ves
1. To recognize the key clinical features of the most common herpes virus infec3ons encountered in inpa3ent and outpa3ent medicine.
2. To develop a framework for diagnosis and management of common herpes virus infec3ons.
Common Herpesviruses
HSV-‐1, HSV-‐2 VZV
EBV CMV
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Case #1
A 28 year old man presents with fever and severe sore throat aYer returning from his honeymoon. He has mild anterior cervical LAN and the oral exam shown. The rest of his exam is normal. Tests for Group A Strep, acute HIV, and EBV are nega3ve.
Photo courtesy of Ma\ Russell.
1. Throat swab for VZV DFA 2. Throat swab for HSV culture
3. Throat swab for CMV PCR
4. Tonsillar biopsy to r/o lymphoma
The next best test is:
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Oral HSV: Primary Infec3on
§ Children/young adults § HSV-‐1 >>> HSV-‐2
§ Symptoma3c in 10-‐30%: § Gingivostoma33s § Pharyngi3s, tonsilli3s -‐ may not have classic lesions!
§ Systemic sx (fever, LAN) – can look like mono
§ Dura3on of symptoms 10-‐14d
Ardino and Porter, J Oral Pathol Med 2008; 37:107. McMillan et al, Pediatr Infect Dis J 1993; 12:280. Ireland, Oxford Dic3onary of Den3sty 2010.
An3virals for Primary Oral HSV Infec3on
§ Oral an3vrials: ê 3me to heal by 6 days (in kids)
Cernik et al, Arch Intern Med 2008; 168:1137.
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Case #2
A 30 year old man presents to clinic complaining of “fever blisters” for the past 24 hours. He has moderate pain but mostly feels a great degree of stress and embarrassment about the lesions. This is his 5th episode in the last year.
Photo courtesy of Laura Pincus.
Oral an3virals
1. Shorten the 3me for lesions to heal
2. Are effec3ve as suppressive therapy
3. Both #1 and #2
4. Have no treatment effect
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Recurrent Oral HSV: Herpes Labialis
§ Epidemiology § 20-‐40% of HSV-‐1+ pa3ents § Average of 1.6 recurrences/year
§ Clinical § Prodrome in ~50% § 25% do not go beyond the prodrome or maculopapular stage
§ Dura3on of symptoms 1-‐10 days
Cernik et al, Arch Intern Med 2008; 1168:1137. Ardino and Porter, J Oral Pathol Med 2008; 37:107.
Episodic Therapy for Recurrent Oral HSV
§ ê 3me to heal by 0.5-‐2.5 days § Not effec3ve in abor3ng lesions
Cernik et al, Arch Intern Med 2008; 168:1137.
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Suppressive Regimens for Oral HSV
§ ê recurrences by 40-‐50% (in pts with ≥4-‐6 recurrences/year) § Not known if can ê oral HSV-‐1 shedding or transmission
Cernik et al, Arch Intern Med 2008; 168:1137.
Oral HSV: Take Home Points
§ Primary HSV-‐1 can be a cause of pharyngi3s in young adults (and may not present with vesicles)
§ Oral an3virals have a modest treatment effect: they can shorten healing 3me and be used as suppressive therapy to prevent recurrences
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Case #3
A 22 year old man has fever, lymphadenopathy, and painful blisters at the base of his penis.
He is diagnosed with primary genital herpes. HSV-‐2 is detected on culture of one of the lesions.
He wants to know how likely this is to recur in the next 12 months.
Photo courtesy of Laura Pincus.
The likelihood of recurrence in the next 12 mo:
1. 10%
2. 30%
3. 50%
4. >70%
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Genital Herpes: Changing Epidemiology
§ Historically, HSV-‐2 had accounted for 75% of all GH
§ But HSV-‐1 now accounts for >50% of primary GH § Increase in HSV-‐1 because:
§ ê HSV-‐1 seroprevalence in childhood § é rates of oral sex in young adults
§ HSV-‐1 and HSV-‐2 are clinically iden3cal but HSV-‐1 recurrence rate is êê c/w HSV-‐2
Bernstein et al, Clin Infect Dis 2013;56:344. Gupta et al, Lancet 2007; 370:2127. Horowitz et al, J Amer Coll Health 2010; 59:69.
§ Only 10-‐25% of those with GH are aware they have it § Asymptoma3c shedding occurs on 20-‐25% of all days
§ Most transmission occurs from persons unaware they have herpes or who are asymptoma3c
Genital Herpes: Transmission
Gupta et al, Lancet 2007; 370:2127. Mark et al, J Infect Dis 2008; 198:1. Sacks et al, An3viral Res 2004; 63S1:S19.
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Primary Genital Herpes: Clinical
§ Incuba3on 4-‐7 days
§ Most are asymptoma3c
§ Can have systemic symptoms: § Fever, HA, myalgias, dysuria, LAN
§ Can get new lesions for up to 3 wks
Photo courtesy of Laura Pincus.
Classic “scalloped” border
*Another strong predictor of recurrence risk is severity of primary infec3on
Benedeq et al, Annals Int Med 1994; 121:847. Benedeq et al, Annals Int Med 1999; 131:14.
Recurrent Genital Herpes
HSV primary infec/on
% with a recurrence within 1 year
# recurrences in 1st year
HSV-‐1 20-‐50% 1
HSV-‐2 70-‐90% 4-‐5
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Test Sensi/vity Specifcity Take home points
HSV: Diagnos3cs
Mosely et al, J Clin Microbiol 1981; 13:913. Wald et al, J Infect Dis 2003; 188:1345. Van Wagoner and Hook, Curr Infect Dis Rep 2012; 14:175. Lafferty et al, J Clin Microbiol 1987; 25:323.
PCR ~90% overall
99% Most sensi3ve test Not always available
DFA Vesicle 70-‐90% Ulcer 30% Crusted 10%
99% Rapid (hours) Slightly ê sensi3vity c/w culture
Culture
Vesicle 70-‐90% Ulcer 30-‐40% Crusted 20-‐30%
100% Moderate sensi3vity Takes 1-‐2 days
When to Order HSV-‐2 Serology
§ CDC guidelines: 1. Recurrent genital symptoms and (-‐) HSV cultures 2. Partner has genital herpes (to assess risk for acquisi3on) 3. Consider for pa3ents presen3ng for an STD evalua3on or
MSM at increased risk for HIV acquisi3on
§ Can IgM be used to determine primary vs recurrence? § Limited window in primary infec3on (from ~ day 10-‐24) § Limited specificity: found in up to 70% of recurrences § But IgM+ IgG-‐ should indicate primary infec3on
CDC, STD Treatment Guidelines 2010, MMWR 59 (No. RR-‐12). Page et al, Sex Transm Infect 2003.
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Treatment Regimens: First episode
§ Efficacy § ê dura3on of symptoms by 2-‐4 days § No impact on recurrence rate
§ Regimens
CDC, STD Treatment Guidelines 2010, MMWR 59 (No. RR-‐12). Mertz et al, JAMA 1984; 252:1147.
Efficacy: § Start in prodrome or <1
day of symptoms
§ Can abort lesions in 20-‐30% or ê symptoms by 1-‐2 days
§ Does not reduce rate of transmission to uninfected partners
Episodic Therapy: Recurrent Episodes
CDC, STD Treatment Guidelines 2010, MMWR 59 (No. RR-‐12). Strand et al, Sex Transm Infect 2002; 78:435.
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Suppressive Therapy for Genital Herpes
§ Effects: § ê recurrences by 70-‐80% § êê shedding § ê transmission to nega3ve partner by ~50% (but absolute RR of ~2%)
§ When to use? § CDC: consider if “frequent” episodes (? ≥ 6) or discordant couples § SF City Clinic: offers to most with a new diagnosis of HSV-‐2
§ An3virals: § Acyclovir 400mg bid, famciclovir 250mg bid, valacyclovir 500-‐1000mg daily § Trial off therapy qyear
CDC, STD Treatment Guidelines 2010, MMWR 59 (No. RR-‐12). Corey et al, N Engl J Med 2004; 350:11.
Genital Herpes: Take Home Points
§ HSV-‐1 accounts for >50% of cases of primary genital herpes
§ HSV-‐1 and HSV-‐2 are clinically iden3cal, but HSV-‐2 is much more likely to recur
§ Most transmission occurs in pa3ents who are asymptoma3c or are unaware they have genital herpes
§ HSV culture, DFA, and PCR are the diagnos3c methods of choice
§ Oral an3virals can shorten symptom dura3on, abort lesions en3rely, and can be used as suppressive therapy to decrease the number of recurrences as well as transmission
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Case #3
55 year old man is brought in by his neighbor for bizarre behavior for 12 hours. He is found to be febrile and has a witnessed seizure in the ED. MRI is shown. He is started on vancomycin, ceYriaxone, and acyclovir and is tapped 24 h later. Lumbar puncture:
§ 50 WBC (89% lymphs), 50 RBC, protein 80, glucose 78.
§ CSF culture is NGTD § PCR is nega3ve for HSV and VZV.
The HSV PCR May Be Nega3ve Because:
1. He got 24 hours of acyclovir
2. It’s not a sensi3ve test
3. It’s early in the disease course
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HSV Encephali3s
§ Epidemiology: § Accounts for 10-‐20% of encephali3s
§ Microbiology: § >90% due to HSV-‐1, most are due to reac3va3on § HSV-‐2 rare, more common in immunocompromised pa3ents
§ Clinical: § Frontal and temporal lobes affected § Fever, personality changes, aphasia, seizures, focal weakness
HSV Encephali3s: CSF Profile
§ Classic profile: § WBCs: lymphocy3c pleocytosis (median 130 cells/mm3) § RBCs: elevated (usually <500) § Protein: elevated (median 80 mg/dl) § Glucose: normal
§ CSF does not always have RBCs or WBCs: § RBCs normal in 15% § WBC normal in 4-‐15%
Whitley et al, JAMA 1982, 247:312. Whitley et al, JAMA 1989, 262:234. Tang et al, Clin Infect Dis 1999, 29:803. Domingues et al, Clin Infect Dis 1997, 25:86.
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HSV Encephali3s: Diagnosis and Rx
§ CSF PCR: § 96% sensi3ve, 99% specific § May have false (-‐) in the first 3d à if suspicion is high re-‐tap § ACV has li\le effect on PCR (+) within the first 5 days of therapy
§ MRI: temporal lobe abnormali3es in 90%
§ Treatment: § ACV 10mg/kg IV q8h x 14-‐21 days § Consider checking an HSV PCR at day 14 to define dura3on
DeBiasi and Tyler, Clin Microbiol Rev 2004, 17:903. Tyler, Herpes 2004, 11 Suppl 2: 57A
HSV Asep3c Meningi3s
§ 1st episode in 1˚ genital HSV-‐2 (women>men)
§ Recurrent asep3c meningi3s: § 20-‐30% of pa3ents will have at least 1 recurrence § Mollaret’s meningi3s = repeated self-‐limi3ng
episodes, with or without recurrent skin lesions
§ Treatment: § Role of an3virals not clearly defined: can consider
ACV 10 mg/kg q8h or valacyclovir 1gm PO 3d x 7-‐14d § May be of benefit in immunocompromised pa3ents § Suppressive rx not effec3ve to prevent recurrences
Tyler, Herpes 2004, 11 Suppl 2: 57A. Aurelius et al, Clin Infect Dis 2012, 54: 1304. Berger and Houff, Arch Neurol 2008, 65:596. Sendi and Graber, CMAJ 2006, 174:1710. Noska et al, Clin Infect Dis 2015;60:237.
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HSV Neuro Complica3ons: Take-‐Home
§ HSV encephali3s is usually caused by HSV-‐1 and affects the frontal/temporal lobes
§ CSF HSV PCR is very sensi3ve for HSV encephali3s: § There can be false (-‐) within the first 3 days of symptoms § ACV has li\le effect on sensi3vity within the first 5 days
§ HSV meningi3s is a complica3on of primary genital herpes from HSV-‐2 and can be recurrent
Case #4
64 year old man presents with a blistering painful rash on his leY leg in the L4 and L5 dermatomes. He is started on acyclovir but s3ll has new lesions on his shin aYer 24 hours.
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The Most Likely Diagnosis Is:
1. Disseminated zoster
2. Resistant zoster
3. Uncomplicated herpes zoster
Zoster: Key Clinical Features
§ 80% have prodrome (lasts 2-‐3 days)
§ New vesicles appear for 2-‐4 days (an3virals ê new lesion forma3on by 1-‐2 days)
§ Overlap into adjacent dermatomes in 20% (normal varia3on in innerva3on)
§ PHN: pain las3ng >3 months aYer zoster episode, occurs in 10-‐20%
Dworkin et al, Clin Infect Dis 2007; 44 (Suppl1): S1.
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To confirm the dx, the most sensi.ve test is:
1. VZV DFA
2. VZV culture
Test Sensi/vity Specifcity Take home points
VZV: Diagnos3cs
Dworkin et al, Clin Infect Dis 2007; 44 (Suppl1): S1.
PCR 95%
99% Most sensi3ve test Not always available
DFA 90% 95% Rapid (hours) Test of choice in most places
Culture
60-‐75%
100% Takes 1-‐2 weeks to grow Usually not done
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Review: Diagnosis of HSV vs VZV
Lesion swab HSV VZV
Culture + -‐-‐
DFA + +
PCR + +
Which is the Best Choice to ê the Risk of PHN?
1. Prednisone
2. Valacyclovir
3. Valacyclovir and prednisone
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Zoster Treatment: An3virals
§ Benefits of therapy § ê dura3on of viral shedding and new lesion forma3on (by 1-‐2d) § ê severity and dura3on of acute pain and rash § ê risk of PHN (by inhibi3ng viral replica3on and neural damage)
§ Who to Treat? § ≥50 years old § Moderate or severe pain or rash § Immunocompromised § Consider trea3ng EVERYONE even with mild disease as the
benefit (preven3ng PHN) likely outweighs risk (drugs are safe)
Dworkin et al, Clin Infect Dis 2007; 44 (Suppl1): S1. Chen et al, Cochrane Database Syst Rev 2010; Issue 12.
Timing of Therapy
§ Timing: § All RCTs ini3ate therapy within 72 hours § Star3ng therapy at >72h hasn’t been well studied, but it is possible there may be some benefit up to 7d
§ If a pa3ent presents at >72 hrs, consider trea3ng if:
§ Presence of new vesicles (indica3ng viral replica3on) § Cutaneous, motor, ocular, neurologic complica3ons § Advanced age, severe pain (since these are RF for PHN) § Immunocompromised
Dworkin et al, Clin Infect Dis 2007; 44 (Suppl1): S1.
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Zoster: An3virals
§ Drug op3ons § Acyclovir 800 mg 5 3mes daily for 7–10 days § Famciclovir 500 mg 3d daily for 7 days § Valacyclovir 1000 mg 3d daily for 7 days
§ For immunocompromised pa3ents:
§ Treat un3l all lesions have crusted given the risk of relapse (this may take longer than 7-‐10 days)
Dworkin et al, Clin Infect Dis 2007; 44 (Suppl1): S1.
Steroids in Acute Zoster
§ 3 RCTs all show that addi3on of steroids to ACV: § Accelerated healing and reduced acute pain (by ~1.5-‐3 fold) § Improved quality of life § But no decrease in PHN
§ So when to consider steroids? § Moderate to severe pain § Facial nerve paralysis § No contraindica3ons to steroid use § Regimen: Prednisone 60 mg/d then taper over 10-‐21 d
Wood et al, N Eng J Med 1994; 330:896. Whitley et al, Annals Int Med 1996; 125:376. Esmann et al, Lancet 1987; 330:126. Chen et al, Cochrane Database Syst Rev 2010; Issue 12.
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Case #5
75 y/o man with HTN, CAD presents to clinic with a rash over his R eye in the V1 distribu3on associated with conjunc3val injec3on.
How Would You Treat Him?
1. High dose PO valacyclovir and close follow-‐up
2. Admission and IV acyclovir
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VZV Ophthalmicus
§ Defined as zoster in the V1 distribu3on
§ Without treatment, 50% will develop complica3ons § Conjunc3vi3s § Anterior uvei3s § Necro3zing re3ni3s § Kera33s § Corneal ulcer § Orbital apex syndrome
Harding et al, Br J Ophthalmol 1987.
VZV Ophthalmicus: Management
§ Ophtho consult § For all pa3ents with eye symptoms, with lesions on the 3p or side of the nose, or who are immunocompromised
§ An3virals: § All pa3ents should be treated irrespec3ve of the dura3on of symptoms
§ Treat with intravenous ACV in immunocompromised pa3ents or with eye involvement
Dworkin et al, Clin Infect Dis 2007; 44 (Suppl1): S1
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Case #6
A 59 year old man with SLE on cellcept and prednisone (10 mg/day) presents with diffuse vesciular rash. VZV DFA is posi3ve.
How Would You Treat Him?
1. High dose PO valacyclovir and close follow-‐up
2. Admission and IV acyclovir
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Complicated Zoster
§ Disseminated Zoster
§ Neurologic Complica3ons § Asep3c Meningi3s § Encephali3s (small vessel vasculopathy) § Stroke (large vessel vasculopathy) § Transverse Myeli3s § Ocular involvement
Disseminated VZV
§ = lesions outside the the primary or adjacent dermatomes
§ Usually in immunocompromised, occurs via viremic spread to the skin
§ Pa3ents may have new lesions for up to 2 weeks
§ Pa3ents are at high risk for pneumoni3s, hepa33s, DIC
Cohen, NEJM 2013, 369:255.
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VZV Encephali3s
§ Usually occurs in immunocompromised pa3ents
§ Clinical: § HA, fever, AMS, seizures § Rash can be absent (in up to 1/3)
§ CSF profile:
§ Lymphocy3c pleocytosis (median 110 cells/mm3) § Elevated protein (median 260 mg/dL) § Glucose normal to slightly low (median 55 mg/dL) § Posi3ve VZV PCR (sensi3vity 80-‐100%, specificity 98%) § Posi3ve VZV IgG (more sensi3ve than PCR for chronic cases)
Gilden et al, NEJM 2000. Pahud et al, J Infect Dis 2011, 203:316.
Treatment of Complicated Zoster
§ When to admit pa3ents for IV acyclovir? § Disseminated disease or CNS complica3ons § Severely immunocompromised pa3ents with localized disease (to prevent dissemina3on)
§ Strongly consider in VZV Ophthalmicus
§ How long to treat and when can you switch to PO? § Total dura3on 2-‐3 weeks § Use IV for at least 7 days (and un3l all lesions are crusted) § Can switch to PO valacyclovir on a case by case basis
Pergam et al, Am J Transplanta3on 2013. Dworkin et al, Clin Infect Dis 2007; 44 (Suppl1): S1
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VZV: Take Home Points
§ DFA or PCR are the diagnos3c method of choice for cutaneous zoster
§ An3virals decrease symptom severity and dura3on, and may have some benefit in ê risk of PHN
§ Steroids provide no addi3onal benefit in ê risk of PHN
§ Admit pa3ents for IV acyclovir if they have disseminated disease, CNS complica3ons, or are severely immunocompromised
Case #7
47 year old M with no PMH is admi\ed with fever and respiratory distress. CT shows prominent GGO. HIV Ab test is posi3ve and CD4 is 56. BAL is performed and is posi3ve for PCP. BAL is also posi3ve for CMV culture. Plasma CMV PCR is posi3ve at 970 IU/mL.
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What An3bio3cs Should You Start?
1. TMP-‐SMX alone
2. TMP-‐SMX plus ganciclovir
3. TMP-‐SMX plus acyclovir
4. TMP-‐SMX plus IVIG
Approach to CMV Infec3ons: Define the Host
Immunocompetent
§ Primary infec3on § Clinical
• Usually asymptoma3c • Heterophile (-‐) mononucleosis
§ Usually self-‐limi3ng, no Rx
Immunocompromised
§ Primary or reac3va3on
§ Clinical • Asymptoma3c viremia • CMV syndrome • End-‐organ disease
§ Usually requires treatment
Navalpotro et al, J Clin Virol 2006; 35:193. Wreghi\ et al, Clin Infect Dis 2003; 37:1603.
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CMV Infec3on in Immunocompromised Pa3ents
Asymptoma/c Viremia
Asymptoma3c
Plasma CMV PCR (+)
Treatment depends on host
CMV Syndrome
Fever plus bone marrow suppression (leukopenia and/or thrombocytopenia)
Plasma CMV PCR (+)
Treat all pa3ents
End-‐Organ Disease
• Neuro: Encephali3s, Re3ni3s • Pneumoni3s • GI: Coli3s>Esophagi3s • Others: hepa33s, nephri3s, myocardi3s, pancrea33s
Plasma CMV PCR (+) (GI can be compartmentalized)
Treat all pa3ents
CMV Infec3on
CMV in HIV+ Pa3ents
§ Asymptoma3c viremia in up to 35% pts w/CD4<200 § Most common end-‐organ disease:
§ Re3ni3s § GI (coli3s > esophagi3s)
§ Pneumoni3s is rare: BAL+ for CMV in ~50% of pa3ents (without CMV pneumoni3s)
Durier et al, Clin Infect Dis 2013;57:147. Deayton et al, Lancet 2004; 363: 2116. Hayner et al, Chest 1995;107;735. Miles et al, Chest 1990;97;1072. CDC/NIH/HIVMA Guidelines for the preven3on and treatment of OIs in HIV-‐infected adults, 2015.
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CMV End-‐Organ Disease
CMV Coli3s • Fever, diarrhea (+/-‐ bloody), abd pain • Dx by colonoscopy with path, IHC • Blood PCR can be nega3ve
CMV Pneumoni3s • Fever, mild to severe resp failure • CT shows diffuse bilateral GGO • Dx by BAL: culture, path • Blood PCR usually posi3ve
CMV Treatment
§ IV vs PO? § IV ganciclovir for severe disease, high VL, concerns re: oral absorp3on § PO valganciclovir okay for mild-‐moderate disease
§ IVIG? à Case-‐by-‐case basis for severe disease (pneumoni3s)
§ How long to treat? § 2-‐3 weeks and un3l PCR nega3ve § Consider secondary ppx in selected pa3ents
§ PCR monitoring? § Check 2 wks aYer star3ng rx (VL may stay the same or ñ in 1st wk) § Then check qweek un3l nega3ve
Razonable et al, Am J Transplant 2013; 13:93. Asberg et al (VICTOR study group), Am J Transplant 2007; 7:2106.
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Case #7 Con3nued
The pa3ent was treated for PCP and started on ARVs. He was not treated for CMV. 3 weeks later he represents with fever but no other localizing signs or symptoms. Labs:
§ WBC 1.0, platelets 81 (both previously normal) § CMV viral load in the plasma is now 226,091 IU/mL.
Review ques3on: What is the diagnosis?
1. Asymptoma3c CMV viremia
2. CMV syndrome
3. CMV end-‐organ disease
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CMV: Take-‐Home Points
§ Define your host: immunocompetent or immunocompromised (HIV vs transplant/other)
§ Determine which type of CMV infec3on your pa3ent has: § Asymptoma3c viremia § CMV syndrome § End-‐organ disease
§ HIV+ pa3ents are a special category: § Commonly have asymptoma3c viremia § Can have severe end-‐organ disease (re3ni3s, GI most common) § Rarely have pneumoni3s despite frequent +BAL for CMV
Case #8
22 y/o woman admi\ed with fever, sore throat, and petechial rash.
3.5 13
19
Diff: 40% lymphs
Blood cultures nega3ve
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The Best Treatment Is:
1. Acyclovir
2. Valacyclovir
3. Ganciclovir
4. No an3virals
EBV
§ 75% of US is seroposi3ve by age 18
§ Clinical: § Incuba3on period 4-‐6 weeks § <18 y/o: Most are asymptoma3c or nonspecific illness § >18 y/o: Most are symptoma3c § Infec3ous mononucleosis = classic triad of sore throat, cervical lymphadenopathy, fever
Balfour et al, J Infect Dis 2013; 207:80.
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Diagnosis of IM: Monospot
Pa3ent’s blood: IgM against viral an3gens
+
Sheep or horse RBCs Agglu3na3on
X-‐reac3vity
§ Sensi3vity: 90-‐95% aYer the 1st week, but only 75% in the 1st week § Specificity: 94%
Luzuriaga and Sullivan, N Engl J Med 2010; 362:21.
Diagnosis of IM: Atypical Lymphocytes
Atypical lymphs >10% § Sensi3vity 75% § Specificity 92%
Luzuriaga and Sullivan, N Engl J Med 2010; 362:21. Vouloumanou et al, Curr Opin Hematol 2012; 19:14.
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Diagnosis of IM: EBV Serologies
Luzuriaga and Sullivan, N Engl J Med 2010; 362:21.
IgM VCA
IgG VCA
IgG EBNA
Acute Infec3on + +/− −
Prior Infec3on − + +
• Sensi3vity 85-‐90% • Specificity >95%
Diagnosis of IM: EBV PCR
§ Not a lot of data § ~100% posi3ve early, undetectable by week 3 § Can be useful if serologies are inconclusive
Berth et al, J Clin Virol 2011; 50:184.
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Mononucleosis: Treatment
§ Steroids? à Not for all, maybe in some cases § Cochrane review 2006: “insufficient evidence to recommend” for symptom control, lack of research into side effects
§ Consider short course to treat severe complica3ons (e.g., upper-‐airway obstruc3on)
§ An3virals? à NO, mul3ple RCTs show no benefit
Luzuriaga and Sullivan, N Engl J Med 2010; 362:21. Candy and Hotopf, Cochrane Database Syst Rev 2006; Issue 3. Balfour et al, J Clin Virol 2007; 39:16.
EBV and Shedding
§ 20% shed virus into saliva before symptoms § Most shed into the oral cavity for at least 6 months aYer acute infec3on
§ Reac3va3on is common and shedding occurs in healthy adults ~25-‐75% of the 3me – likely the main reservoir for transmission
Balfour et al, J Infect Dis 2013; 207:80. Ling et al, J Infect Dis 2003; 187:1571. Fafi-‐Kremer et al, J Infect Dis 2005; 191:985.
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EBV Take Home Points
§ Diagnosis of IM: § Monospot tes3ng is only 75% sensi3ve in the 1st week § Serology is 85-‐90% sensi3ve § Test characteris3cs of PCR unknown § Atypical lymphs can be an important clue to diagnosis
§ Treatment is suppor3ve in most cases
§ Shedding occurs before symptoms and in healthy adults 25-‐75% of the 3me
Thank You!
§ Ques3ons: [email protected]
