ViralInfec,onsintheICU

Dr. Lalit Dar Professor and In-charge Virology Section Department of Microbiology AIIMS

DelhiMicrocon,12December2015,IHC

AnOutbreakofViralDisease•  In1952,anoutbreakofpoliomyeli,soccurredinDenmark

•  2722pa,entsdevelopedtheillnessover6months

•  316sufferedrespiratoryparalysis

TheIntensive-CareUnitStartedwithaVirus…

Common Viral Infections in the ICU

•  Respiratory infections

•  Gastroenteritis

•  Hemorrhagic fever

•  Neurologicalinfec,ons

•  Exogenous •  Influenza A (including H1N1, H5N1) and B •  RSV •  Parainfluenza viruses •  Adenovirus •  Metapneumovirus •  Coronaviruses (OC43, 229E/NL63, SARS, MERS)

•  Endogenous (reactivation of latent viruses) •  CMV •  HSV •  VZV

RespiratoryViralInfec,onsintheICU(1)

•  Early studies

–  Two of 39 patients with suspected VAP were “classical” respiratory virus positive in tracheal aspirates (influenza and enterovirus) (Luyt C-E et al, 2007)

–  PCR on BAL positive in 11 of 201 suspected VAP patients for several respiratory viruses, while 42 (28%) patients were positive for HSV and 28 (14%) for CMV (Daubin C et al, 2005)

–  Only < 5.5% of non-immunocompromised patients with ventilator associated pneumonia (VAP) had “classical” respiratory viruses, which may even have been acquired before ICU admission

RespiratoryViralInfec,onsintheICU(2)

RespiratoryViralInfec,onsintheICU(3)

•  Recent studies –  22.5% to 34% patients in the ICU with health-care

associated pneumonia (HCAP) had one or more respiratory virus in their lower respiratory (BAL, endotracheal aspirate) or nasopharyngeal samples (Hong H-L et al, 2015; Choi SH et al, 2012)

–  14%, in lower respiratory samples (Hong H-L et al, 2015)

–  RSV, PIV (27% each) and rhinovirus (25%) most common, followed by influenza (17%), CMV (8.5%) and coronaviruses (7%) (Hong H-L et al, 2015)

–  59.5% had bacterial infection and 8% bacterial-viral coinfection (Hong H-L et al, 2015)

Herpesviridae: HSV in Lower Respiratory Tract of ICU patients

Luyt C-E et al, 2014

Luyt C-E et al, 2014

Herpesviridae: CMV in Lower Respiratory Tract of ICU patients

HSV and CMV Infection in the ICU: Clinical Significance

•  Confirmed HSV cases with ARDS have longer periods on ventilators and hospital stay, with a higher mortality rate in some studies

•  CMV detected in blood after 12 days median ICU stay; viremia peaks at 26 days; pneumonia seen after average of 3 weeks on ventilator

•  HSV or CMV detection in BAL fluid does not necessarily mean viral VAP; may indicate only reactivation not lung parenchyma involvement and true pneumonia

•  Innocent bystanders or true pathogens? Pathogenicity of Herpesviridae in respiratory infections in the ICU not clear; decision whether to give antiviral prophylaxis, pre-emptive therapy or neither still remains open

Role of Real-time PCR on BAL (Viral Load)

•  Limited studies, but virus quantification by real-time PCR may help to decide treatment

•  HSV viral load > 100000 copies/ml in BAL fluid show poorer prognosis, more frequent ARDS, longer stay in the ICU and higher mortality

•  CMV viral load of >1000 copies/ml by real-time PCR associated with increased mortality or prolonged ICU stay

•  Randomized controlled trials needed

•  Zoster(endogenousICUinfec,on)–  Latentvaricellazostervirusreac,va,onleadingtozoster–  Zostervesicularlesionshaveinfec,ousviruswhichcanleadtoan

outbreakofchickenpox–  Earlyclinicaliden,fica,on(dermatomalvesicularrash)and

treatmentwithhighdosesofacylovirinelderlymaypreventpost-herpe,cneuralgia

•  VZVpneumonia(exogenousICUinfec,on,rarecomplica,onofchickenpox)–  Immunosuppression(malignancy,cor,costeroids,HIV,andsolid-

organtransplant)areriskfactors–  Rareinyounghealthyadults–  DevelopsinsidiouslyfewdaysaXertheonsetofchickenpoxrash;

mayprogresstorespiratoryfailureandARDSin10%to30%(upto50%,ifrespiratoryfailureensues)

Herpesviridae: VZV in ICU patients

Viral Gastroenteritis Outbreaks in the ICU

•  590 neonatal outbreaks analysed from the outbreak database (http://www.outbreak-database.com) (Civardi E et al, 2013) –  64 (11%) outbreaks due to viruses –  44 (69%) of these reported from neonatal intensive

care units (NICUs) –  Rotavirus (23%) most frequent viral agent

•  Noroviruses are emerging agents of gastroenteritis outbreaks (including adult ICU) –  Mean duration of illness of 12–60 h; vomiting in >50% ;

incubation period of 24–48 h –  Multiple modes of transmission facilitate spread

Viral Infections in the Neonatal ICU • 12-year study from a neonatal ICU in The Netherlands, based on culture and PCR (Verboon-Maciolek MA et al, 2005)

• Viral infection was confirmed in 51 of 5396 infants (<1%) • Enterovirus/ parechovirus (EV/PEV) 39%; RSV 29%; rotavirus 10%; CMV 6%; adenovirus/ PIV/ HSV 4% each; rhinovirus/ rubella 2% each

• Clinical presentation in pre-term neonates –  Sepsis like illness with seizures and gastrointestinal disease

(EV/PEV) –  Respiratory disease (RSV, PIV, rhinovirus, CMV) –  Gastrointestinal disease (adenovirus, rotavirus, EV/PEV)

• Mortality (10%) and serious sequelae (15%) were high in patients with EV/PEV

Haemorrhagic Fever

•  Viruses causing haemorrhagic fever may require ICU care, e.g., dengue (DSS/ DHF) –  Accurate and careful fluid replacement –  Monitoring haematocrit (and platelets) –  Judicious use of platelet transfusion

•  Suspected cases with exotic virus infections require special precautions in ICU care, e.g., Ebola, Crimean Congo haemorrhagic fever, hantaviruses –  Strict isolation procedures –  Adherence to guidelines for all procedures –  Dedicated equipment –  PPE (proper training and donning under observation) –  Appropriate waste disposal

Neurological Infections

•  Pa,entswithneurologicalcondi,onsmayneedtobeadmi]edtotheICU,e.g.,incomatosecondi,onorforrespiratorysupport

•  Viruses– HSV,arboviruseslikeJE,etc.

Management

•  Rapiddiagnosis•  Mainlysuppor,vetreatmentdependingonthepresenta,on

•  An,viraldrugs,whereindicated–  Acyclovir(HSV,VZV)–  Ganciclovir(CMV)–  Neuraminidaseinhibitors(influenza)–  Ribavirin/Palivizumab(RSV)

Summary•  Viralinfec,onsintheICUincluderespiratory,gastrointes,nalandneurologicalinfec,ons,aswellashaemorrhagicfevers

•  Bothexogenousandendogenous(reac,vated)infec,onscanoccurintheICU

•  Moleculartechniquesareimportantforearlydiagnosisandpreven,on

•  Preven,onofspreadrequiresclearlydefinedguidelines,whichmustbeadheredto

•  Suppor,vecareisrequired.Specifican,-viraldrugsshouldbeusedwhereindicated.

ThankYou