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1. Clinical case Management
Of Severe Acute Respiratory
Infection
SARI
By
Dr. Ashraf El-Adawy
Consultant Chest Physcian
TB TEAM Expert - WHO

2. Clinical case Management of
Severe Acute Respiratory Infection (SARI )
Introduction:
 Emerging respiratory infectious diseases pose a substantial risk for humans due to
their extremely high potential to spread from person-to-person. These diseases
can produce high morbidity and in serious forms, show high rates of
hospitalization and high case-fatality rates.
 There have been several incidents of emerging respiratory infectious diseases in
the last hundred years, including the influenza pandemic of 1918 known as the
“Spanish flu”, the 1957 “Asian flu” pandemic, the 1968 “Hong Kong flu”pandemic,
the 2003 Severe Acute Respiratory Syndrome (SARS) , and the influenza A (H1N1)
pandemic of April 2009.
 One important lesson learned from the 2009 influenza pandemic was the
importance of obtaining information about severe cases. To that end, resources
should be focused on expanding Severe acute respiratory infections (SARI)
surveillance.
 Severe acute respiratory infections (SARI) have been a key presenting feature of
two recent novel respiratory pathogens , Avian Influenza A (H7N9) virus in China
and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV),that have
caused severe human illness and the need for intensive care unit (ICU) admission
for many of the infected persons.
 In the event that human cases of these novel viruses emerge , clinicians will
require guidance on the management of patients presenting with SARI in the ICU
setting , since most severe cases require ICU admission, mechanical ventilation
and frequently multisystem organ support.
 All of these events demonstrate the importance of having a respiratory disease
surveillance system that can detect new viruses rapidly and provide information
to assess impact on the population and having operational preparedness plans.

3. The World Health Organisation (WHO) definition of SARI is an acute
respiratory infection with:
 History of fever or measured fever of ≥ 38 C°
 Cough
 Onset within the last 10 days
 Requires hospitalization
o Shortness of breath is not typical of uncomplicated influenza virus infection, and
is suggestive of severe disease.
o Respiratory rate is a very useful parameter in evaluating dyspnea or difficulty
breathing .
Upper limits of respiratory rate by age AGE Increased respiratory
rate (tachypnea)
< 2 months > 60 breaths/minute
2-11 months > 50 breaths/minute
12 months to 5 years > 40 breaths/minute
Adults > 26 breaths/minute
o Another parameter which can be used to evaluate difficulty breathing is oxygen
saturation while breathing ambient air.
o Measured by digital pulse oximetry, saturation should be 95% or greater.
Saturation < 90% is an indication of severe disease, while in pregnant women,
<95% can indicate severe disease.
o The clinical manifestations Of SARI are not specific, Rather, they are shared by
many different infectious diseases.
o The case definition for severe acute respiratory infection (SARI) is provided for
use in the in-patient hospital settings.

4. The principal etiologic agents
o The case definition for Severe Acute Respiratory Infection (SARI) is provided as a
standard to enumerate severe respiratory infections (including those caused by
influenza) leading to hospitalization.
o SARI can be caused not only by the influenza virus but also by other viruses, such
as respiratory syncytial virus (RSV), Parainfluenza subtypes 1, 2 and 3 and
Adenovirus, SARI can also be of bacterial origin.
o Also, when considering the possible causative agent, clinicians should maintain an
awareness of currently circulating respiratory pathogens including novel
respiratory viruses circulating elsewhere in the world .
o Recognition of a cluster or similar cases within a family or in the community is a
very important clue.
o It may be difficult for clinicians at the hospital level to recognize this since patients
may present to other hospitals. For these reasons, clinicians should consult with
local medical officer of health/public health officials, as well as their local
infectious disease specialist.
Recent Novel Pathogens Causing SARI
o Clearly many different respiratory infections may present with these features, but
there are cases where additional infection prevention and control precautions
and specialist diagnostic testing are required, Specifically this is when infection is
suspected or proven to be due to :
 Avian influenza A (e.g. H7N9 or H5N1)
 MERS-CoV (Middle East Respiratory Syndrome Coronavirus
o The only way of knowing with certainty the etiology of a case of SARI is by
means of laboratory diagnosis.
o Ideally, every patient meeting the SARI case definition, should be sampled.

6. SARI Clinical Presentation:
o SARI represents and increasingly common consideration for critical care clinicians
assessing and treating patients with respiratory insufficiency and critical illness.
o SARI presentation can vary depending on the etiologic agent & is defined
primarily by a clinical presentation of (Public Health Agency of Canada,2013) :
I. Respiratory symptoms
 Fever (≥ 38.0 degrees Celsius) AND
 New onset of (or exacerbation of chronic) cough or breathing difficulty
Note: fever may not be prominent in patients under 5 or over 65 years of age, or as
well as immunosuppressed individuals receiving anti-pyretic medications .
Self-reported symptoms of elevated body temperature should be considered as
evidence of fever.
AND
II. Evidence of illness progression
 Either radiographic evidence of infiltrates consistent with pneumonia, or a
diagnosis of acute respiratory distress syndrome (ARDS) or severe influenza-
like illness (in addition to the symptoms of ILI, severe ILI may include complications
such as encephalitis, myocarditis, acute coronary syndrome, sudden death or other
severe and life-threatening complications)
AND
III. ICU/ mechanical ventilation
 Either admission to the ICU/other area of the hospital where critically ill
patients are cared for OR mechanical ventilation.
NOTE:
SARI is not equivalent to classic pneumonia and would not always present as
pneumonia.

7. Early recognition of patients with SARI
 Recognize suspect cases with severe manifestations of acute respiratory
infection (ARI)
 Life-threatening manifestations include severe pneumonia, ARDS, sepsis and
septic shock.
 Early recognition of these clinical syndromes allows for timely initiation of
IPC as well as therapeutics.
Diagnostic Considerations
 Clinicians should consider the patient clinical presentation & epidemiological
links (exposures) when investigating SARI.

8. Assessing Exposure History
 All patients with signs and symptoms of possible SARI , presenting to the
Emergency Department or admitted to Hospital ,should be questioned about
recent travel to, residence in or contact with sources for SARI-related novel
and emerging infections.
 Severe acute respiratory illness (SARI) has been documented as a common
feature of recent emerging respiratory pathogens e.g avian influenza A (H7N9)
and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).
 Human cases of H7N9 virus have occurred only in China, with travel-related
cases in Taiwan and Hong Kong.
 MERS CoV cases have been reported in several Middle Eastern countries as
well as a number of exported cases to European countries. To date there has
been no sustained human to human transmission.
 Exposure criteria : Clinicians should assess for epidemiological risk factors
by obtaining an exposure history including recent links to affected areas ( in
countries where emerging respiratory illnesses such as MERS-CoV1 or variant
influenza strains such as H7N9 have been reported) OR close contact with an
ill person (with a confirmed or probable case within the 10-14 days prior to
symptom onset) ..
 A close contact is defined as a person who provided care for the patient,
including health care workers, family members or other caregivers, who had
other similarly close physical contact to the patient or a possible cluster
member OR who stayed at the same place.
 Clinicians should be aware of possible clusters in their region through
communication with local experts and public health offices.
Note:
 Routine surveillance for SARI will not only help to achieve the traditional
virologic objectives of seasonal influenza surveillance but will also provide
epidemiologic and virologic data on more severe influenza infections.

9.  In addition, sentinel surveillance for SARI may ultimately be used as a
surveillance platform from which to assess the contribution of multiple viral
respiratory pathogens to hospitalized respiratory disease burden.
Take home message:
o SARI may be caused by respiratory pathogens of known or unknown origin
including novel respiratory viruses (Avian Influenza H7N9, H5N1, MERS-CoV ,
etc.)
o The primary objective of SARI surveillance system is early detection &
containment of cases of emerging/re-emerging respiratory infectious
diseases.
Policy/ Guideline/ Protocol
Initial Assessment
 In patients with no epidemiological risk factors for avian influenza A (H7N9 or
H5N1) and MERS-CoV, clinicians should rule out the most common pathogens
(e.g. conventional bacteria and respiratory viruses including seasonal influenza)
before considering an unusual or more highly virulent pathogen.
Laboratory Testing& active finding of suspect cases of SARI
To aid clinicians in the diagnosis of severe respiratory infections due to unknown and
known respiratory pathogens that have the potential for large-scale epidemics
Pathogens that should be excluded on preliminary testing include:
1) Conventional bacteria (including Mycoplasma pneumoniae, Legionella
pneumophila) should be investigated:
 Specimen : Sputum and urine specimens
 Testing : (gram stain and routine culture ± Legionella antigen detection)
• Legionella urinary antigen
• Mycoplasma pneumoniae for Polymerase Chain Reaction (PCR) .
Collect blood cultures for potential bacterial pathogens that can also
cause pneumonia and sepsis, ideally before antimicrobial therapy,this
must NOT significantly delay the start of antimicrobial therapy.

10. 2) Conventional respiratory viruses ( including human influenza, parainfluenza,
respiratory syncytial virus, adenovirus, human metapneumovirus, coronavirus
rhinovirus/enterovirus,) should be investigated with :
 Specimen : Nasopharyngeal swab(NPS), endotracheal secretions, ±
bronchoalveolar lavage(BAL), ± throat swab for PCR testing and sputum .
o In cases of ILI or SARI, nasopharyngeal and oropharyngeal swabs are collected
from adults and children five and older .
o For pediatric patients under five, a nasopharyngeal aspirate is a suitable
replacement to a Nasopharyngeal swab(NPS).
o NPS is the primary specimen type for respiratory viruses including seasonal
influenza. However, deeper specimens such as endotracheal secretions or BAL
must be collected in cases of severe respiratory infection with negative NPS.
 Testing:
o Influenza A and B by RT-PCR with subtyping (H3N2 or H1N1) should be the
primary method for detection of influenza (24 hour turnaround time (TAT).
o Respiratory multiplex RT-PCR for parainfluenza, human metapneumovirus,
coronavirus, rhinovirus/enterovirus, adenovirus should be done on negative
influenza specimens (48 hour TAT) when there is a clinical indication to detect
noninfluenza viruses.
o Rapid Influenza Diagnostic Tests (RIDTs ) should not be used to rule out
influenza A. The sensitivity of currently available RIDT for human influenza
strains is suboptimal.
o The most appropriate specimens for MERS-CoV testing are LRT specimens
( LRT samples are more likely to be positive than URT specimens and virus can
be detected in LRT specimens for longer periods than in URT specimens)

11.  Collect upper respiratory tract specimens, preferably both nasopharyngeal
and throat swabs, for viral testing.
 Viral testing should be done by reverse-transcriptase polymerase chain
reaction (RT-PCR)
 Collect lower respiratory tract specimens, i.e., sputum (not saliva),
endotracheal aspirate, bronchoalveolar lavage, for both bacterial and viral
testing
 If more invasive samples are collected they should be processed for a wide range
of pathogens:
 Bronchial-alveolar wash for all cultures (bacteria, viruses, mycobacteria,
fungi).
 Open lung biopsy – for all cultures, RT-PCR and histology (ensure specimen is
not put in formalin for microbiology testing).
3) If MERS-CoV/Avian Influenza is a considered a possible diagnosis
before continuing with the initial assessment:
o Isolate patient in a side room to minimise contact/exposure to staff and
other patients.
o Ask the patient to wear a surgical mask.
o Wear personal protective equipment –this should be a correctly fitted
FFP3 respirator, gown, gloves and eye protection.
 A number of Avian Influenza A viruses, including H7N9, have been detected in
throat swabs. Recently, H7N9 was only detectable in sputum specimen in 1 of 4
patients.
 While sputum and throat swabs are not ideal for most influenza viruses, until the
ideal specimen for H7N9 can be identified, multiple specimens types should be
considered in patients suspected of having Avian Influenza A viruses.

12.  As was the case with pH1N1, lower respiratory tract secretions are likely more
sensitive for detection of both Influenza A, including H7N9, and MERS-CoV.
 At this time the probability that a severe acute respiratory illness is due to MERS-
CoV or influenza A (H7N9) is extremely low.

13. Initial SARI treatment
 Initial treatment decisions should be based on clinical presentation and
epidemiological data and should not be delayed pending laboratory
confirmation.
 Initial management should include appropriate infection prevention and
control procedures, evidence-based supportive critical care and empiric
antibiotic and antiviral therapy while awaiting diagnostic testing.
 Antiviral therapy with neuraminidase inhibitor, specific for treatment of
influenza, when there is local circulation or possible risk factors for
exposure to animal influenza viruses (e.g., avian H5N1 or H7N9) .
 Oseltamivir is the recommended first- line antiviral agent for
neuraminidase-sensitive influenza virus infection, ideally initiated within
48 hours of symptom onset.
 Intubated patients with influenza illness should receive oseltamivir
through a nasogastric tube.

14. For undifferentiated SARI in which the causative agent is unknown and there
is concern about a novel influenza strain or influenza is circulating in the
community, empiric treatment with neuraminidase inhibitors should not be
delayed while awaiting the results of diagnostic testing.
 Give empiric, effective antimicrobials to treat all likely pathogens,
including community-acquired pneumonia or health care-associated
pneumonia (if infection was acquired in health care setting) and sepsis.
Give within one hour.
 Antibiotic treatment should be selected based on local epidemiology,
susceptibility data and guidance until the diagnosis is confirmed.
 Empiric therapy can then be adjusted on the basis of laboratory results.
Early supportive therapy and monitoring
 Give supplemental oxygen therapy to patients with SARI with signs of
respiratory distress, hypoxaemia (SpO2 < 90%) or shock immediately.
 Initiate oxygen therapy at 5 L/min and titrate flow rates to reach target
SpO2 ≥ 90% in non-pregnant adults and children and SpO2 ≥ 92-95 % in
pregnant patients .
 All areas where patients with SARI are cared for should be equipped with
pulse oximeters, functioning oxygen systems and disposable, single-use,
oxygen-delivering interfaces (nasal cannula, simple face mask, and mask
with reservoir bag) .
 Recognize severe hypoxemic respiratory failure when a patient with
severe respiratory distress is failing standard oxygen therapy as:
Patients may continue to have increased work of breathing or hypoxemia
even when standard oxygen therapy is delivered via a face mask with
reservoir bag (flow rates of 10 -15 L/min delivers oxygen concentration,
FiO2, between 0.60 and 0.95).

15.  Wherever available, and when staff members are trained, institute
mechanical ventilation early in patients with increased work of breathing
or hypoxemia that persists despite standard high flow oxygen therapy.
 NIV is the delivery of bi-level positive airway pressure through a tight-
fitting mask. It reduces the need for endotracheal intubation in patients
with severe exacerbations of chronic obstructive pulmonary disease and
cardiogenic pulmonary oedema.
 There is, however, insufficient evidence to promote its use in patients
with severe pneumonia or ARDS, unless immunosuppression is also
present or disease is mild without impaired consciousness or
cardiovascular insufficiency
 When NIV used, it should be used as a short trial, Monitor the patient
closely in an ICU. Because NIV has potential to generate aerosols, use with
AIRBORNE precautions. If NIV is unsuccessful, do not delay endotracheal
intubation.
NOTES:
 Patients with SARI should be treated cautiously with intravenous fluids,
because aggressive fluid resuscitation may worsen oxygenation especially
in settings where there is limited availability of mechanical ventilation
 Closely monitor patients with SARI for signs of clinical deterioration, such
as rapidly progressive respiratory failure and sepsis syndrome and apply
supportive care interventions immediately.
 Understand the patient’s co-morbid condition(s) as this will impact the
management of their critical illness and their prognosis.
 Clinicians will require guidance on the management of patients presenting
with SARI in the ICU setting, since most severe cases require ICU
admission, mechanical ventilation and frequently multisystem organ
support.

16. Implementation of Infection prevention & Control (IPC) measures
 Infection control precautions are important to protect HCW and other patients
and visitors.
 Prior to any patient interaction, all healthcare workers (HCWs) have a
responsibility to assess the infectious risk posed to themselves and to other
patients, visitors.
In Triage Settings
 At triage, recognize patient with ARI, give the patient a surgical mask and
place the patient in separate area.
 If possible, immediately place patient in an adequately ventilated single room
away from other patient care areas.
 If single rooms are insufficient for the number of individuals, then apply
cohorting (placement of patients with the same etiological diagnosis in the
same designated unit or ward) to reduce transmission to other patients or
health care workers.
 Organize the space and process to permit spatial separation , Keep at least 1-2
meter between each patient with ARI and other individuals not wearing PPE.
 Limit the number of people entering the assigned area to the minimum
number required for patient care.
 Encourage respiratory Etiquette (i.e. covering the mouth and nose during
coughing or sneezing with a tissue, sleeve or flexed elbow), followed by hand
hygiene and disposing tissue immediately.
o Recommendations for infection prevention and control measures for patients
presenting with suspected or confirmed infection or co-infection with SARI in all
health care settings include:
A. Standard Precautions:
Routinely, For all patients, at all times, in all healthcare settings (including

17. when performing a point-of-care risk assessment), and adherence to
respiratory hygiene and hand hygiene.
B. Contact and Droplet Precautions (should be implemented empirically):
o Wear gloves and a long-sleeved gown upon entering the patient's room,
cubicle or bedspace.
o Wear facial protection (surgical or procedure mask and eye protection, or
face shield, or mask with visor attachment) when within 2 metres of a
patient suspected or confirmed to have SARI infection.
C. Airborne Precautions:
 When performing an aerosol generating procedures (AGMPs) , e.g aspiration
or open suctioning of respiratory tract specimen, intubation, bronchoscopy,
cardiopulmonary resuscitation) also apply AIRBORNE precautions.
 Use PPE including gloves , long-sleeved gowns ,a particulate respirator (N95 or
equivalent) and face/eye protection should be used by all HCWs present in a
room where an AGMP is being performed on a patient suspected or confirmed
to have SARI infection.
 Whenever possible, AGMPs should be performed in an airborne infection
isolation room(Negative pressure room).
o In general, Advise visitors and family members about risk of transmission.
Instruct them on personal protection equipment (PPE) use and hand hygiene.
Evaluate for symptoms of ARI before visit.
o Limit visitors to those essential for support. Advise that anyone who is at
increased risk of severe disease does not care for the ill person.

18. Severe acute respiratory illness (SARI) Screening Tool
Place surgical mask on all patients presenting with severe acute respiratory
symptoms (unless the patient’s clinical condition will be compromised by
wearing the mask).
Ensure that it remains in place during any transportation of the patient for
medical investigations/examinations, including Chest X-ray .
Complete the following sceening questions - Indicating Yes or No for each of the criteria:
PATIENT presents with ALL SARI-defining features:
Yes No Fever (≥38˚ C), and
Yes No Cough or breathing difficulty, and
Yes No
Radiographic evidence of infiltrates consistent with pneumonia or Respiratory
Distress Syndrome(ARDS)
Yes No
Severe influenza-like illness ,Other severe life threatening illness suggestive
of infectious process.
Yes No Admission to a Critical Care Unit or mechanical ventilation
IN the 14 DAYS before the onset of symptoms, were any of the following present:
Yes No
1.a) Close contact with a suspect or probable case of SARI
[Close contact means having cared for, lived with, or had face to face (within
2 meters) contact with, or having had direct contact with respiratory
secretions and/or body fluids of a person with SARI]
Yes No 1.b) Travel to a country where there is a Public health notice of respiratory
illness in effect e.g., novel influenza (H5N1&H7N9) or emerging pathogens
Yes No
1.c) Recent exposure/close contact to a potential source of a SARI which may
include reports of illness or die offs in domestic poultry flocks or illness in
other animal vectors such as camels or swine.
1.d) Occupational exposure ( specify: □ Healthcare □ Lab □ Animal)

19. TEST - Collect specimens and clearly mark specimens “URGENT: for SARI Screen”
Collect the specimens when clinically indicated
 Nasopharyngeal Swab or aspirate
 Oropharyngeal swab
 Endotracheal secretions, Broncoalveolar lavage
 Mycoplasma pneumoniae and Chlamydia
pneumoniae PCR.
 Sputum (gram stain and routine culture
±Legionella )
 Legionella urinary antigen
 Blood culture
 Acute serology
 Lung tissue (not in formaline if done)
 Initial emperical treatment decisions should be
based on clinical presentation & epidemiological
data , including evidence-based supportive
critical care and empiric antibiotic and antiviral
therapy while awaiting diagnostic testing
 Appropriate infection prevention and control
procedures

20. References:
1. Operational guideline for ARI, ILI & SARI surveillance- Public Health
Laboratory Department of Public Health -Ministry of Health Thimphu:
Bhutan 2012
2. Severe Acute Respiratory Infection(SARI) Jan 2015 NHS
3. Malaysia Influenza Surveillance Protocol -2015
4. Guidance for the Management of Severe Acute Respiratory Infection in the
Intensive Care ( Prepared on behalf of the Canadian Critical Care Society -
2013)
5. Protocol for Microbiological Investigations of Severe Acute Respiratory
Infections (SARI) 2013
6. Severe acute respiratory illness (SARI)* Screening tool- Public Health Agency
of Canada
7. Operational Guidelines for Sentinel Severe Acute Respiratory Infection (SARI)
Surveillance - September 2014
8. Health Establishments Preparation for Unusual or Unexpected Cases or
Clusters of Severe Acute Respiratory Infection SARI-Version APRIL 2009 Pan
American health orginization
9. Severe Acute Respiratory Infection (SARI) Guidelines-Canada 2013
10. ILI & SARI Surveillance Second Edition 2014
11. IMAI District Clinician Manual: Hospital Care for Adolescents and Adults.
Geneva: WHO 2012.
12. Clinical management of severe acute respiratory infection when Middle East
respiratory syndrome coronavirus (MERS-CoV) infection is suspected- Interim
guidance - July 2015
13. Global epidemiological surveillance standards for influenza-who 2013
14. WHO Regional Office for Europe guidance for sentinel influenza surveillance
in humans- May 2011
15. WHO Interim Global Epidemiological Surveillance Standards for Influenza
(July 2012)