Viral infection in Critical Care unit
Seyed MohammadReza.Hashemian
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