Inpatient Viral Infections: Which Ones Should We Think About, Test For, and Treat

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1 Inpatient Viral Infections: Which Ones Should We Think About, Test For, and Treat Management of the Hospitalized Patient October 2015 Jennifer Babik, MD, PhD Assistant Clinical Professor Division of Infectious Diseases, UCSF Disclosures I have no disclosures. 1

2 Learning Objectives 1. To recognize the key clinical features of the most common viral infections encountered in hospitalized patients. 2. To develop a framework for diagnosis and management of common inpatient viral infections. Viruses Covered Herpesviruses CMV HSV VZV Respiratory viruses Influenza Other respiratory viruses 2

Case #1 47 year old M with no PMH is admitted with fever and respiratory distress. CT shows prominent GGO. HIV Ab test is positive and CD4 is 56. BAL is performed and is positive for PCP.

3 Case #1 47 year old M with no PMH is admitted with fever and respiratory distress. CT shows prominent GGO. HIV Ab test is positive and CD4 is 56. BAL is performed and is positive for PCP. BAL is also positive for CMV culture. Plasma CMV PCR is positive at 970 IU/mL. What Antibiotics Should You Start? 1. TMP SMX alone 2. TMP SMX plus ganciclovir 3. TMP SMX plus acyclovir 4. TMP SMX plus IVIG 3

4 Approach to CMV Infections: Define the Host Immunocompetent Primary infection Clinical Usually asymptomatic Heterophile ( ) mononucleosis Case reports of severe disease Diagnosis Serology > PCR Usually self limiting, no Rx Immunocompromised Primary or reactivation Clinical Asymptomatic viremia CMV syndrome End organ disease Diagnosis Serology not helpful Tissue biopsy >> culture Blood PCR Usually requires treatment Navalpotro et al, J Clin Virol 2006; 35:193. Wreghitt et al, Clin Infect Dis 2003; 37:1603. CMV Infection in Immunocompromised Patients CMV Infection Asymptomatic Viremia Asymptomatic Plasma CMV PCR (+) Decision to treat depends on viral load and host; may just follow levels CMV Syndrome Fever plus bone marrow suppression (leukopenia and/or thrombocytopenia) Plasma CMV PCR (+) Treat all patients End Organ Disease Neuro: Encephalitis, Retinitis, Polyradiculopathy Pneumonitis GI: Colitis>Esophagitis Others: hepatitis, nephritis, myocarditis, pancreatitis Plasma CMV PCR (+) (except GI disease can be compartmentalized) Treat all patients 4

CMV in HIV vs Transplant HIV Host: End organ disease in CD4<50 Most common presentations:

Pneumonitis is rare: BAL+ for CMV in ~50% of patients with other respiratory OIs Transplant

high levels of immunosuppressives or steroids (e.g. rheum patients) Most common presentations:

Deayton et al, Lancet 2004; 363: 2116. Hayner et al, Chest 1995;107;735.

CDC/NIH/HIVMA Guidelines for the prevention and treatment of OIs in HIV infected adults, 2015.

5 CMV in HIV vs Transplant HIV Host: End organ disease in CD4<50 Most common presentations: Asymptomatic viremia common (15 35% pts w/cd4<200) Retinitis GI (colitis > esophagitis) Pneumonitis is rare: BAL+ for CMV in ~50% of patients with other respiratory OIs Transplant Host: SOT and HSCT Also patients taking high levels of immunosuppressives or steroids (e.g. rheum patients) Most common presentations: Asymptomatic viremia CMV syndrome Pneumonitis Colitis Durier et al, Clin Infect Dis 2013;57:147. Deayton et al, Lancet 2004; 363: Hayner et al, Chest 1995;107;735. Miles et al, Chest 1990;97;1072. CDC/NIH/HIVMA Guidelines for the prevention and treatment of OIs in HIV infected adults, CMV End Organ Disease CMV Colitis Fever, diarrhea (+/ bloody), abd pain Dx by colonoscopy with path, IHC Blood PCR can be negative CMV Pneumonitis Fever, mild to severe resp failure CT shows diffuse bilateral GGO Dx by BAL: culture, path Blood PCR usually positive 5

6 CMV Treatment IV vs PO? IV ganciclovir for severe EOD, high VL, concerns re: oral absorption PO valganciclovir okay for mild moderate disease (VICTOR trial) IVIG? Case by case basis for severe disease (pneumonitis) How long to treat? 2 3 weeks and until PCR negative Consider secondary ppx in selected patients PCR monitoring? Check 2 wks after starting rx (VL may stay the same or in 1 st wk) Then check qweek until negative Razonable et al, Am J Transplant 2013; 13:93. Asberg et al (VICTOR study group), Am J Transplant 2007; 7:2106. Case #1 Continued The patient 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. 6

7 Review question: What is the diagnosis? 1. Asymptomatic CMV viremia 2. CMV syndrome 3. CMV end organ disease CMV: Take Home Points Define your host: immunocompetent or immunocompromised (HIV vs transplant/other) Determine which type of CMV infection your patient has: Asymptomatic viremia CMV syndrome End organ disease HIV+ patients are a special category: Commonly have asymptomatic viremia Can have severe end organ disease (retinitis, GI most common) Rarely have pneumonitis despite frequent +BAL for CMV 7

8 Case #1 Continued The patient now tells you he has been having severe mouth pain. Oral exam shows significant ulcerations on his tongue and angular cheilitis. You are concerned about CMV vs HSV. The most sensitive test for HSV is this situation is: 1. Ulcer swab for HSV DFA 2. Ulcer swab for HSV culture 8

Diagnosis of Mucocutaneous HSV Lesion swab HSV Culture Vesicle 70 90% Ulcer 30 40% Crusted 20 30% More sensitive than DFA DFA Vesicle 70 90% Ulcer 30% Crusted 10% More rapid than culture PCR Overall

9 Diagnosis of Mucocutaneous HSV Lesion swab HSV Culture Vesicle 70 90% Ulcer 30 40% Crusted 20 30% More sensitive than DFA DFA Vesicle 70 90% Ulcer 30% Crusted 10% More rapid than culture PCR Overall 90% Best test if available Case #2 Continued Oral ulcer swab: HSV DFA QNS HSV culture +HSV 1 Due to concurrent CMV, he was treated with IV ganciclovir then oral valganciclovir to complete 4 weeks. After 1 week, CBC normalized and oral ulcers completely resolved. 9

Antivirals Against Herpesviruses Antiviral HSV VZV CMV EBV Acyclovir Valacyclovir Famciclovir Ganciclovir Valganciclovir ++ ++ + + ++ ++ ++ ++ Case #2 55 year old man is brought in by his neighbor

10 Antivirals Against Herpesviruses Antiviral HSV VZV CMV EBV Acyclovir Valacyclovir Famciclovir Ganciclovir Valganciclovir Case #2 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, ceftriaxone, 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 negative for HSV and VZV. 10

11 Your Next Management Step Would Be: 1. D/C acyclovir 2. Continue acyclovir 3. Add ampicillin 4. Add ganciclovir You Think The HSV PCR May Be Negative B/C: 1. He got 24 hours of acyclovir 2. It s not a sensitive test 3. It s early in the disease course 11

12 HSV Encephalitis Epidemiology: Bimodal: 1/3 of cases <20 years old, 1/3 cases >50 years old Accounts for 10 20% of encephalitis Microbiology: >90% due to HSV 1, most are due to reactivation HSV 2 rare, more common in immunocompromised patients Clinical: Frontal and temporal lobes affected Fever, personality changes, aphasia, seizures, focal weakness HSV Encephalitis: CSF Profile Classic profile: WBCs: lymphocytic pleocytosis (median 130 cells/mm 3 ) 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. 12

HSV Encephalitis: Diagnosis and Rx CSF PCR: 96% sensitive, 99% specific May have false ( ) in the first 3d if suspicion is high re tap ACV has little effect on PCR (+) within the first 5 days of

13 HSV Encephalitis: Diagnosis and Rx CSF PCR: 96% sensitive, 99% specific May have false ( ) in the first 3d if suspicion is high re tap ACV has little effect on PCR (+) within the first 5 days of therapy MRI: temporal lobe abnormalities in 90% Treatment: ACV 10mg/kg IV q8h x days Consider checking an HSV PCR at day 14 to define duration DeBiasi and Tyler, Clin Microbiol Rev 2004, 17:903. Tyler, Herpes 2004, 11 Suppl 2: 57A HSV Aseptic Meningitis 1 st episode in 1 genital HSV 2 (women>men) Recurrent aseptic meningitis: 20 30% of patients will have at least 1 recurrence Mollaret s meningitis = repeated self limiting episodes, with or without recurrent skin lesions Treatment: Role of antivirals not clearly defined: can consider ACV 10 mg/kg q8h or valacyclovir 1gm PO tid x 7 14d May be of benefit in immunocompromised patients Suppressive rx not effective to prevent recurrences Tyler, Herpes 2004, 11 Suppl 2: 57A. Aurelius et al, Clin Infect Dis 2012, 54: Berger and Houff, Arch Neurol 2008, 65:596. Sendi and Graber, CMAJ 2006, 174:1710. Noska et al, Clin Infect Dis 2015;60:

HSV Neuro Complications: Take Home HSV encephalitis is usually caused by HSV 1 and affects the frontal/temporal lobes CSF HSV PCR is very sensitive for HSV encephalitis: There can be false ( ) within

14 HSV Neuro Complications: Take Home HSV encephalitis is usually caused by HSV 1 and affects the frontal/temporal lobes CSF HSV PCR is very sensitive for HSV encephalitis: There can be false ( ) within the first 3 days of symptoms ACV has little effect on sensitivity within the first 5 days HSV meningitis is a complication of primary genital herpes from HSV 2 and can be recurrent Case #3 64 year old man presents with a blistering painful rash on his left leg in the L4 and L5 dermatomes. He is started on acyclovir but still has new lesions on his shin after 24 hours. 14

vesicles appear for 2 4 days (antivirals new lesion formation by 1 2 days) Overlap into adjacent dermatomes in 20%

15 The Most Likely Diagnosis Is: 1. Disseminated zoster 2. Resistant zoster 3. Uncomplicated herpes zoster Zoster: Key Clinical Features 80% have prodrome preceding lesions by 2 3 days New vesicles appear for 2 4 days (antivirals new lesion formation by 1 2 days) Overlap into adjacent dermatomes in 20% (normal variation in innervation) PHN: pain lasting >3 months after zoster episode, occurs in 10 20% Dworkin et al, Clin Infect Dis 2007; 44 (Suppl1): S1. 15

16 To confirm the dx, the most sensitive test is: 1. VZV DFA 2. VZV culture Diagnosis of VZV Lesion swab VZV Culture Sensitivity 60 75% Specificity 100% Takes 1 2 weeks to grow Not usually performed DFA Sensitivity 90% Specificity 95% Rapid (hours) Test of choice in most places PCR Sensitivity 95% Best test if available 16

17 Review: Diagnosis of HSV vs VZV Lesion swab HSV VZV Culture + DFA + + PCR + + Which is the Best Choice to the Risk of PHN? 1. Prednisone 2. Valacyclovir 3. Valacyclovir and prednisone 17

18 Zoster Treatment: Antivirals Benefits of therapy duration of viral shedding and new lesion formation (by 1 2d) severity and duration of acute pain and rash Most (but not all) studies show a risk of PHN (by inhibiting viral replication and neural damage) Who to Treat? 50 years of age Moderate or severe pain or rash Nontruncal involvement Immunocompromised But consider treating EVERYONE even with mild disease as the benefit (preventing 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 initiate therapy within 72 hours Starting therapy at >72h hasn t been well studied, but it is possible there may be some benefit up to 7d If a patient presents at >72 hrs, consider treating if: Presence of new vesicles (indicating viral replication) Cutaneous, motor, ocular, neurologic complications Advanced age, severe pain (since these are RF for PHN) Immunocompromised Dworkin et al, Clin Infect Dis 2007; 44 (Suppl1): S1. 18

19 Zoster: Antiviral Regimens Drug options Acyclovir 800 mg 5 times daily for 7 10 days Famciclovir 500 mg tid daily for 7 days Valacyclovir 1000 mg tid daily for 7 days For immunocompromised patients: Treat until 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 Studies 3 RCTs: ACV+steroids vs ACV+placebo within 72 96h of onset The addition 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 Ocular VZV with significant edema No contraindications to steroid use Regimen: Prednisone 60 mg/d then taper over 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

20 Case #4 75 y/o man with HTN, CAD presents to clinic with a rash over his R eye in the V1 distribution associated with conjunctival injection. How Would You Treat Him? 1. High dose PO valacyclovir and close follow up 2. Admission and IV acyclovir 20

21 VZV Ophthalmicus Defined as zoster in the V1 distribution Without treatment, 50% will develop ocular complications Conjunctivitis Anterior uveitis Necrotizing retinitis Keratitis Corneal ulcer Orbital apex syndrome Harding et al, Br J Ophthalmol VZV Ophthalmicus: Management Ophtho consult For all patients with eye symptoms, with lesions on the tip or side of the nose, or who are immunocompromised Antivirals: All patients should be treated irrespective of the duration of symptoms Treat with intravenous ACV in immunocompromised patients or with eye involvement Consider systemic steroids if there is significant edema, which can cause orbital apex syndrome via pressure on nerves entering the orbit Dworkin et al, Clin Infect Dis 2007; 44 (Suppl1): S1 21

22 Case #5 A 59 year old man with SLE on cellcept and prednisone (10 mg/day) presents with diffuse vesciular rash. VZV DFA is positive. How Would You Treat Him? 1. High dose PO valacyclovir and close follow up 2. Admission and IV acyclovir 22

Complicated Zoster Disseminated Zoster Neurologic Complications Aseptic Meningitis Encephalitis (small vessel vasculopathy) Stroke (large vessel vasculopathy) Transverse Myelitis Ocular involvement

23 Complicated Zoster Disseminated Zoster Neurologic Complications Aseptic Meningitis Encephalitis (small vessel vasculopathy) Stroke (large vessel vasculopathy) Transverse Myelitis Ocular involvement Disseminated VZV = lesions outside the the primary or adjacent dermatomes Usually in immunocompromised, occurs via viremic spread to the skin Patients may have new lesions for up to 2 weeks Patients are at high risk for pneumonitis, hepatitis, DIC Cohen, NEJM 2013, 369:

24 VZV Encephalitis Usually occurs in immunocompromised patients Clinical: HA, fever, AMS, seizures Rash can be absent (in up to 1/3) CSF profile: Lymphocytic pleocytosis (median 110 cells/mm 3 ) Elevated protein (median 260 mg/dl) Glucose normal to slightly low (median 55 mg/dl) Positive VZV PCR (sensitivity %, specificity 98%) Positive VZV IgG (more sensitive than PCR for chronic cases) Gilden et al, NEJM Pahud et al, J Infect Dis 2011, 203:316. Treatment of Complicated Zoster When to admit patients for IV acyclovir? Disseminated disease or CNS complications Severely immunocompromised patients with localized disease (to prevent dissemination) Strongly consider in VZV Ophthalmicus How long to treat and when can you switch to PO? Total duration 2 3 weeks Use IV for at least 7 days (and until all lesions are crusted) Can switch to PO valacyclovir on a case by case basis Pergam et al, Am J Transplantation Dworkin et al, Clin Infect Dis 2007; 44 (Suppl1): S1 24

VZV: Take Home Points DFA (or PCR) is the diagnostic method of choice for cutaneous zoster Antivirals decrease symptom severity and duration, and may have some benefit in risk of PHN Steroids provide

25 VZV: Take Home Points DFA (or PCR) is the diagnostic method of choice for cutaneous zoster Antivirals decrease symptom severity and duration, and may have some benefit in risk of PHN Steroids provide no additional benefit in risk of PHN Admit patients for IV acyclovir if they have disseminated disease, CNS complications, or are severely immunocompromised Case #6 A 35 year old man is admitted in January with 5 days of fever, cough and progressive respiratory distress. He rapidly deteriorates and is intubated. Rapid influenza antigen test in the ED is negative. 25

26 What is the Sensitivity of the Rapid Antigen Tests? % % 3. >90% Diagnostic Tests for Influenza Rapid Antigen Testing Point of care tests Widely available in clinics and ERs ~50 70% sensitive >90% specific Cannot be used to exclude influenza during flu season Molecular Assays ~95% sensitive and specific Test of choice Some assays can determine: Influenza A vs B Influenza A subtypes (seasonal H1N1, seasonal H3N2, pandemic H1N1) Harper et al, Clin Infect Dis 2009, 48:1003. CDC, Influenza Symptoms and the Role of Laboratory Diagnostics,

27 Diagnosis: Samples Upper tract samples: NP swabs or aspirates Collect samples preferably within 5 days (as shedding is after 5d) In critically ill patients: collect both upper and lower tract specimens Lower tract samples can be positive even if viral shedding is no longer detectable in the upper tract If suspicion is high, do not stop empiric therapy until lower tract sample is negative Harper et al, Clin Infect Dis 2009, 48:1003. CDC, Influenza Symptoms and the Role of Laboratory Diagnostics, Case #6 Continued He gets an NP swab influenza PCR assay and the sample is positive for influenza A. 27

Zanamavir 10mg inhaled bid x 5 days Antivirals Matrix proteins (M1 and M2) X M2 Inhibitors Amantadine,

28 Would You Give Him Antivirals? 1. No antivirals (he is out of the treatment window) 2. Oseltamivir 75mg PO bid x 5 days 3. Oseltamivir 150mg PO bid x 10 days 4. Zanamavir 10mg inhaled bid x 5 days Antivirals Matrix proteins (M1 and M2) X M2 Inhibitors Amantadine, rimantidine Influenza A only Widespread resistance Neuraminidase Inhibitors Oseltamivir, Zanamivir, Peramivir Influenza A and B Drugs of choice 28

29 Neurominidase Inhibitors Drug Adult dosage Can use if intubated? Contraindications Adverse Effects Oseltamivir 75mg PO bid x 5 d Yes None Nausea/vomiting Zanamivir 10mg INH bid x 5 d No Underlying resp disease (asthma, COPD) Bronchospasm, cough Peramivir 600mg IV x 1 Yes None Diarrhea Timing of Oseltamivir in Inpatients Treatment of inpatients within 48hrs of symptom onset: mortality by 50 65% But >40% of patients hospitalized with influenza present at >48 h Multiple studies have shown a mortality benefit for treating inpatients at >48hrs: Treatment seems to be effective even out to 5 days Earlier is better: each day in delay risk of death by 20% So if influenza is suspected, start treatment empirically while awaiting test results Lee and Ison, Clin Infect Dis 2012, 55:1205. Viasus et al, Chest 2011, 140:1025. Muthuri et al, J Infect Dis 2013, 207:

Timing of Rx: Better Late than Never % patients who survived Rx No Rx Days after symptom onset 0 1 2 3 4 5 Treatment mortality, even up to 5 days after symptom onset Louie et al, Clin Infect Dis

30 Timing of Rx: Better Late than Never % patients who survived Rx No Rx Days after symptom onset Treatment mortality, even up to 5 days after symptom onset Louie et al, Clin Infect Dis 2012, 55:1198. Treatment: High Dose Oseltamivir? Is there a benefit of high dose (150mg PO bid)? 2 RCTs in 2013 of high vs regular dose oseltamivir x 5d: Hospitalized kids or adults, immunocompetent, non ICU Results: No difference in viral clearance, mortality, duration of fever, use of O2, ICU admission or intubation, LOS High dose oseltamivir was well tolerated Conclusion: there is no benefit in hospitalized patients who are immunocompetent, non ICU patients What about critically ill or immunocompromised? Controversial, some experts still recommend South East Asia ID Clinical Research Network, BMJ 2013, 346:f3039. Lee et al, Clin Infect Dis 2013, 57:1511. WHO Guidelines for Pharmacological Management of Pandemic Influenza A(H1N1) 2009 and other Influenza Viruses,

31 Duration of Therapy 5 days in uncomplicated cases Consider 10 days in critically ill and immunocompromised because of longer shedding Can consider prolonging the treatment duration beyond this depending on clinical response and follow up testing (although no data for this) Peramivir (IV) FDA approved 12/2014 for adults with uncomplicated influenza and symptoms <48hrs When to use? Any concerns for GI absorption of oseltamivir (note: limited data shows that oseltamivir is well absorbed in obese and critically ill patients icluding those on CRRT and ECMO) Patients not responding to oseltamivir? Critically ill patients? How to dose? FDA approved for a single dose in uncomplicated influenza Under the EUA in 2009: was given as a daily dose for 5 10 days UCSF guidelines: 5 days Whitley et al, Antivir Ther 2014, Oct 15 Epub. Kohno et al, Antimicrob Agents Chemother 2010, 54:4568. de Jong et al, Clin Infect Dis 2014, 59:e

32 Case #6 Continued After 10 days his influenza PCR is still positive. You decide to treat him for an additional 7 days since he is critically ill. However, he remains critically ill and his PCR continues to be positive. What is Your Next Step? 1. Change to IV oseltamivir 2. Start vancomycin and cefepime 3. Change to inhaled zanamavir 4. Send to the DPH for resistance testing 32

33 What If My Patient Doesn t Get Better? Consider oseltamivir resistance Especially critically ill or immunocompromised pts who may shed for weeks Send to DPH or CDC Rare (<2% of isolates over last 2 years) If concerned for resistance IV zanamivir available via urgent EIND approval from GSK and the FDA Consider whether PO absorption is adequate if not, use IV peramivir Influenza Treatment: Take Home Points Who to treat? All inpatients irrespective of duration of symptoms Which drug? Oseltamivir (high dose if critically ill, immunocompromised?) Zanamivir (only if no COPD/asthma and not intubated) Peramivir if need an IV option How long? 5 days Consider 10 d if critically ill, immunocompromised? Peramivir: 1 day or 5 days? 33

Rapid Fire Respiratory Viruses RSV Parainfluenza Human metapneumonvirus Adenovirus RSV in Adults Epidemiology Winter seasonality Affects up to 10% of adults/year Common cause of CAP Clinical:

34 Rapid Fire Respiratory Viruses RSV Parainfluenza Human metapneumonvirus Adenovirus RSV in Adults Epidemiology Winter seasonality Affects up to 10% of adults/year Common cause of CAP Clinical: Wheezing and dyspnea more common than flu Bacterial co infection in 12% Mortality rate 10% in elderly, >50% in HSCT patients CXR findings: Normal in 50% Unilateral 82%, Consolidation 24%, GGO 20% Treatment only in ICH: ribavirin + immunomodulator (IVIG) Cesario, Clin Infect Dis 2012, 55:107. Lee et al, Clin Infect Dis 2013, 57:1069. Lee et al, Clin Infect Dis 2013, 57:1069. Cesario, Clin Infect Dis 2012, 55:107. Lee et al, Clin Infect Dis 2013, 57:

Parainfluenza PIV 3 is most common type in adults (PIV 1 and PIV 2 cause croup in kids) Seasonality is spring summer Clinical: Fever, cough, SOB, wheeze Causes URI,

Human Metapneumovirus Epidemiology: ~4% of CAP Seasonality: winter spring Clinical: 40 70% of infections are asymptomatic URI symptoms, cough, wheeze Usually afebrile CXR

35 Parainfluenza PIV 3 is most common type in adults (PIV 1 and PIV 2 cause croup in kids) Seasonality is spring summer Clinical: Fever, cough, SOB, wheeze Causes URI, bronchiolitis, bronchitis, PNA Can be severe in immunocompromised No treatment clearly effective (ribavirin, DAS 181) Marx et al, Clin Infect Dis 1999, 29:134. Human Metapneumovirus Epidemiology: ~4% of CAP Seasonality: winter spring Clinical: 40 70% of infections are asymptomatic URI symptoms, cough, wheeze Usually afebrile CXR infiltrate in 27% Can be severe, especially in high risk populations Treatment: case reports of using ribavirin + IVIG (like RSV) in transplant patients Walsh et al, Arch Intern Med 2008, 168:

Adenovirus Can cause severe PNA in ICH host, rarely in immunocompetent The classical features of adenoviral infection (pharyngitis, conjunctivitis, rash, diarrhea) may be absent Diagnosis: Some

36 Adenovirus Can cause severe PNA in ICH host, rarely in immunocompetent The classical features of adenoviral infection (pharyngitis, conjunctivitis, rash, diarrhea) may be absent Diagnosis: Some respiratory viral panel PCR assays are only ~60% sensitive for adenovirus If high suspicion, also send the serum PCR (has sensitivity) Treatment: can consider cidofovir Louie et al, Clin Infect Dis 2008, 46:421. Clark et al, J Med Case Rep 2011, 5:259. Pabbaraju et al, J Clin Microbiol 2008, 46:3056. Thank You! Questions: jennifer.babik@ucsf.edu 36

3/15/2017. Herpesviruses. Disclosures. Learning Objectives. Common Herpesviruses in Clinical Practice. I have no disclosures.

3/15/2017. Herpesviruses. Disclosures. Learning Objectives. Common Herpesviruses in Clinical Practice. I have no disclosures. Disclosures I have no disclosures. Herpesviruses 38 th Annual Advances in Infectious Diseases March 2017 Jennifer Babik, MD, PhD Assistant Clinical Professor Division of Infectious Diseases, UCSF Learning