Viral infection in Critical Care unit

Seyed MohammadReza.Hashemian

MD.FCCMsmrhashemian@yahoo.com

Associate professor of SBMU/NRITLD

WHY IS THIS IMPORTANT?

• Most infections are caused by viruses.• Health care professionals must understand

the pathogenic mechanisms used by these pathogens.

PATTERNS OF VIRAL INFECTION

• Viral infections can be:• Acute (rapid and self limiting)• Persistent (long term)• Latent (extreme versions of persistent

infections)• Slow or transforming (complicated

types of persistent infections)

PATTERNS OF VIRAL INFECTION

• Cytopathic viruses produce virions and kill host cells rapidly (cytopathology).

• Noncytopathic viruses produce virions but do not cause cytopathology.

PATTERNS OF VIRAL INFECTION

• Incubation periods vary for different viruses.• Some are as short as days.• Some are as long as years.• During the incubation period:• The virus is replicating.• The host is beginning to respond

PATTERNS OF VIRAL INFECTION

Microbiology: A Clinical Approach © Garland Science

ACUTE INFECTIONS

VIRAL DISSEMINATION

The three main entry points are:• Respiratory system• Digestive tract• Urogenital tract

• Viruses easily disseminate from here into other areas of the body.

ICU Care is Invasive

More invasive lines and procedures including surgeries

Longer length of stay

More IV and parenteral drugs

More tube feeding and Parenteral nutrition

More ventilation

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What is MERSWhat is MERS CDC continues to work closely

with the World Health Organization (WHO) and other partners to better understand the public health risk presented by Middle East Respiratory Syndrome Coronavirus (MERS-CoV). MERS-CoV used to be called “novel coronavirus,” or “nCoV

Is this virus the same Is this virus the same as the SARS virus?as the SARS virus?

No. The novel coronavirus is not the same virus that caused severe acute respiratory syndrome (SARS) in 2003. However, like the SARS virus, the novel coronavirus is most similar to those found in bats. CDC is still learning about this new virus.

MERS Cases and MERS Cases and Deaths,Deaths,April 2012 - May 2013April 2012 - May 2013

Current as of June 11, 2013 Countries Cases (Deaths) France 2 (1) Italy 3 (0) Jordan 2 (2) Qatar 2 (0)

Saudi Arabia 40 (26) Tunisia 2 (0) United Kingdom (UK) 3 (2) United Arab Emirates (UAE) 1 (1)

Total 55 (32)

Countries Cases (Deaths)

France 2 (1)

Italy 3 (0)

Jordan 2 (2)

Qatar 2 (0)

Saudi Arabia 53 (32)

Tunisia 2 (0)

United Kingdom (UK) 3 (2)

United Arab Emirates (UAE) 1 (1)

Total 68 (38)

Australian and New Zealand Intensive Care (ANZIC)

IntroductionIntroduction

2009 H1N1 influenza (WHO, 2009/9/6) 2009 H1N1 influenza (WHO, 2009/9/6) Laboratory-confirmed cases: over 277,607 Laboratory-confirmed cases: over 277,607 Death: at least 3205 Death: at least 3205

2009/6~2009/8, Australia and New Zealand2009/6~2009/8, Australia and New Zealand Combined effect of the pandemic and Combined effect of the pandemic and winterwinter Incidence of infection was 8 times of the US Incidence of infection was 8 times of the US Population-based data Population-based data

Methods Methods Multicenter inception-cohort study Multicenter inception-cohort study

involving involving 187 ICUs187 ICUs All the ICUs (adult or pediatric) in the All the ICUs (adult or pediatric) in the two countriestwo countries 1879 beds; 1449 were equipped for 1879 beds; 1449 were equipped for ventilator ventilator

Patients admitted to the ICU with Patients admitted to the ICU with confirmedconfirmed 2009 H1N1 influenza 2009 H1N1 influenza 2009/6/1~2009/8/31 2009/6/1~2009/8/31 PCR assay PCR assay Serologic analysis Serologic analysis

Australia: 626Australia: 626 New Zealand: New Zealand: 9696

oViral pneumonitis: Viral pneumonitis: 2005: 57 2005: 57 2006: 33 2006: 33 2007: 69 2007: 69 2008: 69 2008: 69 mean: 57 patients mean: 57 patients

Incidence of ICU Incidence of ICU admission: admission: 28.7 per million 28.7 per million inhabitantsinhabitants

ResultsResults

Mechanical ventilation: Mechanical ventilation: 456/706 patients (64.6%) 456/706 patients (64.6%) median of 8 days median of 8 days total number of days of MV: 5249 days total number of days of MV: 5249 days (208 days per million inhabitants) (208 days per million inhabitants) 53/456 patients (11.6%) subsequence 53/456 patients (11.6%) subsequence with ECMO with ECMO (2.1 patients per million inhabitants) (2.1 patients per million inhabitants)

Median duration of ICU stay: 7.4 daysMedian duration of ICU stay: 7.4 days Median duration of hospital stay: 12.3 daysMedian duration of hospital stay: 12.3 days

(Exclude the 114 patients and an additional 33 for whom data (Exclude the 114 patients and an additional 33 for whom data were not available)were not available)

ICU occupied:ICU occupied:

8815 ICU bed-days 8815 ICU bed-days 350 bed-days per million 350 bed-days per million inhabitants inhabitants

Over the 3-month study period, 5.2% Over the 3-month study period, 5.2% of ICU bed-days were accounted for of ICU bed-days were accounted for by patients with 2009 H1N1 by patients with 2009 H1N1 influenza.influenza.

MortalityMortality In-hospital mortality: exceed 16% In-hospital mortality: exceed 16%

no higher than patients with seasonal influenza A no higher than patients with seasonal influenza A who were admitted to an ICU who were admitted to an ICU

Poor prognostic factor:Poor prognostic factor: Older age Older age A requirement for invasive ventilation A requirement for invasive ventilation Presence of coexisting conditions Presence of coexisting conditions > 16 y/o: higher APACHE III scores > 16 y/o: higher APACHE III scores < 16 y/o: prematurity, immunodeficiency, cystic < 16 y/o: prematurity, immunodeficiency, cystic fibrosis, congenital heart disease, fibrosis, congenital heart disease, neuromuscular disorder, or chronic neuromuscular disorder, or chronic neurological impairment; neurological impairment; asthma, chronic pulmonary disease, chronic asthma, chronic pulmonary disease, chronic heart heart failure, DM failure, DM

2010from 23 June

2009 through 11 February 2010

220 admitted to anintensive care unit (ICU)

with completed outcome data were analyzed.

Invasive mechanical ventilation was

used in 155 (70.5%). Sixty-seven (30.5%) of the

patients died in ICU and

Survival graph

Cox regression analysis

adjusted for severity and potential confounding factors identified that early use of corticosteroids was not significantly

VIRAL INFECTIONS OF THE RESPIRATORY TRACT

Influenza virus Rhinovirus Coronavirus

Parainfluenza viruses

Respiratory Syncytial viruses

Adenovirus Coxsackievirus

Viral infections in the ICU

Nosocomial viral disease

Herpesviridae HSV CMV

Respiratory viruses Influenza, Rhinovirus, RSV,

Adenovirus, etc.

Herpes Simplex

General population (saliva): 1-5% ICU patients: 22% In a recent study on 201 non

immunocompromised patients ventilated for at least 5 days, HSV was detected in the throat of 109 patients (54%) 44% symptomatic

Herpes simplex virus often produces sharply demarcated ulcerations in oral, esophageal, or perianal regions. Here is the edge of an

ulcer seen microscopically.

Herpes simplex virus, seen here in the esophagus, infects the squamous epithelium and manifests with

multinucleated cells and inclusions

Herpes Simplex

HSV can be detected in the lower respiratory tract of 5– 64% of ICU patients.

HSV detection in the lower respiratory tract does not necessarily mean herpetic pulmonary disease. Contamination Local tracheobronchial excretion Real HSV bronchopneumonitis

Herpes Simplex

The exact role of HSV in ICU patients, that is, as a marker of disease severity or true pathogen with its own morbidity or mortality or both, remains unclear.

Oropharyngeal and tracheobronchial HSV carriage has been associated with prolonged hospital stay and higher mortality.

Herpes Simplex

Only a randomized trial evaluating

a specific antiviral treatment could

answer such a question.

CMV infection

• CMV infection occurs in 0 to 36% (median

25%) of critically ill patients between 4 and

12 days after ICU admission, especially

those with sepsis, requiring mechanical

ventilation, and receiving transfusion.

Critical Care 2009, 13:R68 (doi:10.1186/cc7875)

Molecular diagnosis of respiratory viruses and its impact on clinical management

Cell Culture Widely used Result in 7-14

days or longer

Respiratory Viruses: Diagnosis Pre 1990’s.Advantages Disadvantage

sTissue Culture

“Open” TechniqueSensitiveFurther characterisationEvidence of active infection

Not applicable to allTime consumingviable virus onlyContamination/toxins

Serology Detects current and past infection (immunity)Important for fastidious viruses

Prolonged testing time

Antigen detection

RapidDetects non-viable virusCan test large numbers of samples

Not applicable to allinterference

DEAFF test for CMV

(Virology Laboratory, Yale-New Haven Hospital)

Laboratory Diagnosis (2)

1. CMV antigenaemia test - widely used in many European countries. CMV antigens at the surface of polymorphonuclear leukocytes are detected by immunoperoxidase or immunofluorescence techniques. A result can be obtained within 4 to 6 hours but the technique is very tricky.

2. Polymerase chain reaction - becoming the method of choice in a few laboratories, had been reported to carry a higher prognostic value for CMV disease than the DEAFF test. Potential problems with sensitivity.

3. Serology - not reliable in general but occasionally, rises in IgG titre and the presence of IgM may be seen.

Antigen detection by Immunofluorescence

Rapid Relatively

insensitive Not suitable for all

speciemn types Subjective

Serology

Technically demanding

InsensitiveAcute and

convalescent serum sample

Polymerase Chain Reaction (PCR)-Xeroxing DNA! Kary Mullis Won the

NobelPrize in 1993 for describing the methodology in 1985 to replicate DNA in a test tube.

PCR

Viral pneumonia Gives a pattern of

acute injury similar to adult respiratory distress syndrome (ARDS)

Acute inflammatory infiltration less obvious

Viral inclusions sometimes seen in epithelial cells

LIVER

IMMUNOPEROXIDASE IN LUNG

CMV

Management (1)

Ganciclovir - is the drug of choice. However, it is associated with neutropenia and thrombocytopenia.

Forscarnet - can be used as the 2nd line drug. Again it is very toxic and is associated with renal toxicity.

Cifofovir (HPMCC) - approved for the treatment of CMV retinitis. It is also associated with renal toxicity.

Fomivirsen - intravitreal fomivirsen is approved for the treatment of CMV retinitis.

CMV hyperimmune globulin - found to be effective against CMV pneumonitis.

Management (2)

Transplant Recipients - once clinical disease is established, the patient should be treated vigorously with antiviral agents. Ganciclovir is the drug of choice. CMV hyperimmune globulin had been found to be useful in the treatment of CMV retinitis.

AIDS patient with retinitis - vigorous antiviral therapy should be given. Both systemic and local (intravitreal implants) may be used.

2011 California San Diego presentation