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Respiratory Viral Ilnesses

Marshell Tendean
Department of Internal Medicine
UKRIDAJakarta
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Introduction

■ Respiratory viral ilnessess notably as most common human disease.

■ Approximately one half among human disese.

■ Adult can have 3-4 cases per year

■ Causes for drug abuse among adults

■ Among 2/3 caused by virus

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The Course of Disease:

■ Common cold
■ Pharyngitis
■ Croup
■ Tracheitis
■ Bronchiolitis
■ Bronchitis
■ Pneumonia
+ Ilness Associated with Respiratory Sydromes

aSARS-associated coronavirus (SARS-CoV) caused epidemics of pneumonia from November 2002 to July 2003 (see text).
bSerotypes 4 and 7.
cFever, cough, myalgia, malaise.
dMay or may not have a respiratory componen
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Influenza virus :

■ RNA, Othromyxoviridae
■ Affects birds and mamals,
and
■ Called
as flu or 24 h flu or
stomach flu
■ Influenza viruses can be
inactivated by sunlight,
disinfectants and detergents
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Influenza Virus:

■ InfluenzaA

■ Influenza B

■ Influenza C

CDC. Influenza virus

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Pathomechanism:

■ Antigenic shift : small gradual changes in antibody-binding sites HA,

and NA of a virus that enable the resistancy against earlier strain
■ Occurs in both type A and Bviruses

■ Antigenic shift: an abrupt major change that cause a novel influenzaA

virus that had not previously circulated
■ Occurs only in influenzaA
■ Can use wide or severe outbreaks or pandemic
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History of Pandemics :

■ Bird flu or Avian flu

■ Swine flu in 2009

■ H1N1, which caused Spanish Flu in 1918

■ H3N2, which caused Hong Kong Flu in 1968

■ H2N2, which caused Asian Flu in 1957

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■ Influenza A has 18 distinct H subtypes and 11 distinct N subtypes,of

which only Hl, H2, H3, Nl, and N2 have been associated with
epidemics of disease in humans.

■ Influenza B and C have molecular similarities but less intratypic

variation, and not occur in influenza C virus.
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Symptoms:

■ Headache, feverishness, chills, myalgia, and malaise.

■ Respiratory tract signs and symptoms, particularly cough and sore

throat.
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Target populations for treatment

■ Individuals with severe disease (requiring hospitalization or evidence

of lower respiratory tract infection) or at high risk for complications
should receive antiviral therapy. Antiviral therapy, when indicated,
should be initiated as promptly as possible.
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Laboratory Examination :

■ Virus may be detected in throat swabs, naso pharyngeal swabs or

washes, or sputum.
■ Reverse-transcriptase polymerase chain reaction (RT-PCR) is the most
sensitive and specic technique for detection of influenza viruses.
■ Rapid influenza diagnostic tests (RIDTs) detect influenza virus antigens by
immunologic or enzymatic techniques
■ Virus isolation and culture
■ Serology
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Antiviral drugs :

■ The neuraminidase inhibitors, zanavir and oseltamivir, active against

influenza A and influenzaB.

■ The adamantanes, amantadine and rimatadine, active against influenza

A.
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Complications :

■ Pulmonary :
■ Primary influenza viral pneumonia
■ Secondary pneumonia
■ Mixed viral influenza pneumonia

■ Extrapulmonary :
■ Myositis
■ Rhabdomyolisis
■ Myoglobinuria
■ CNS complications
■ Toxic shock syndrome
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Prevention:

■ Vaccination :
■ Attenuated vaccine
■ Inactivated vaccine

■ Chemoprophylaxis:
■ “considered for individu als at high risk of complications who have had
close contact with an acutely ill person with influenza”
■ Antiviral chemoprophylaxis can be administered simultaneously with
inactivated vaccine.
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Where SARS was first found!

✵ In a health care worker

✵ In Guangdong Province, China.
✵ In November, 2002.
✵SARS-CoV Urbani strain named
after Dr. Carlo Urbani (WHO)
notified WHO of unusual respiratory
disease in patient (index patient) in
Hanoi.
SARS Taxonomy
Scientific Classification
■ Group IV: Positive Sense Single

©McGraw-Hill, Inc.2005
Stranded RNA
■ Order: Nidovirales (“Nested”
viruses)
■ Family: Coronaviridae
■ Genus: Coronavirus

Courtesy of Dr. Alan Cann.

■ Species:SARS coronavirus (SAR S
–CoV, Urbani strain)
■ Hosts: Vertebrates
 Coronaviridae(s)
• 2 genus
1. Coronavirus (SARS-CoV)
* Previously Unknown
2. Torovirus(Equine torovirus)
• Pathogenesis proven by Koch’s Postulate on Monkeys
• Coronavirus
* healthy masked palm civets (paguma larvata)
* China, Hong Kong, Singapore, Hanoi, and Toronto. Courtesy of Dr. Alan Cann.

*single stranded RNA (+ssRNA); encodes five major proteins maybe even
more.
* responsible for the death of more than 800 patients in over 27 countries.
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Coronavirus Pathogenesis
“The envelope carries three
glycoproteins:
•S - Spike protein: receptor binding, cell
fusion, major antigen
•E - Envelope protein: small, envelope-
associated protein
• M - Membrane protein: transmembrane
- budding & envelope formation In a few
types, there is a third glycoprotein:
• HE - Haemagglutinin-esterase
The genome is associated with a basic
phosphoprotein, N.”

Courtesy of Dr. Alan Cann.

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Coronavirus Pathogenesis cont…,

•enters via endocytosis & membrane fusion

• + sense genome is translated to produce viral
polymerase
•Viral polymerase produces full length – sense
strand (poorly understood step)
•- sense strand used as a template to produce
mRNA (monocistronic), “nested set” of
transcripts
•assembled in the golgi apparatus and transport

.
Courtesy of Dr. Alan Cann
using secretory nature and released.
•REPLICATION OCCURS IN CYTOPLASM
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Symptoms and DiagnosticTests

■ Initial Symptoms:
■ fever of 100.4о F or higher, headaces, body aches, and malaise.

■ Week Later:
■ dry cough, difficulty breathing and severe diarrhea are seen in patients.

■ Recovery: starts after 5 to 6 days

• Early Diagnosis:
• patient is given antibiotics, antiviral, and steroids used for atypical pneumonia.
• Patient is are quarantined in specially ventilated rooms.

• Laboratory tests:
• RT-PCR (reverse transcription-polymerase chain reaction) assay
• Detection of SARS-CoV RNA
• EIA (enzyme immunoassay)
• Detection of serum antibody to SARS-CoV RNA
• Enzyme-linked immunosorbent assays (ELISA)
• Detects antibodies against the virus produced in response to infection
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Treatment and Prevention

• No standard treatment yet

• Patients receive combination therapy
• effective antiviral and steroid (Lopinavir/ritonavir plus ribavirin)

• Prevention
• Isolation
• Sterilization of area occupied by SARS patients
• Caution and extra precautionary measure taken by medical workers and
doctors.
• Vaccines
• According to the SAVI researchers 3 vaccines are possible to be used in
the future: Whole killed vaccine, adenovirus vector, and recombination
spike protein.( a bit more later in the presentation.)
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Epidemiology of SARS

■ Animal and environmental reservoirs

■ Farms: raising and slaughtering of infected animals like unlucky palm civets
■ Might SARS-CoV recombine with other strains of the coronavirus? NO not likely!
■ Onset of illness
■ Incubation period: 4 to 6 days
■ Infectious period is very dangerous if not treated right away leads to death of infected
person/animal
■ Transmission
■ Close contact – droplet, fomites, direct contact
■ Airborne
■ Fecal-oral
Latest on Morbidity and Mortality Reports

■ “Scientists test blood in Beijing.

China's government announced that
a vaccine for Severe Acute
Respiratory Syndrome (SARS) had
emerged from the first phase
clinical test as both safe and
effective.”2(Right)

“An infrared thermograph system at Tokyo airport.

French airport authorities are planning to experiment
with heat-detecting cameras to identify passengers with
a fever as part of efforts to combat the spread of
infectious diseases, like SARS and bird flu.(AFP/JIJI
Press)”2(Left)
Latest on Morbidity and Mortality Reports

■ “SARS Molecular Detection External

Quality assurance:
■ Commercial Test kit used to
perform tests on inactivated
severe acute respiratory
syndrome associated Coronavrius
significantly improved the
outcome. 3
■ Reference material has been
created for the fist time in this
study which can be obtained from Figure:" Probity analysis of the fractions of laboratories achieving
WHO (World Health a positive result (y-axis) in relation to the virus RNAconcentration
Organization).3 in a given positive sample (x-axis). Data points represent
individual samples in proficiency test panel. The thick line is the
regression line calculated on the basis of a probity model (dose-
response curve); the thin lines are 95% confidence intervals. Data
fit into the model with p < 0.0001.”3
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Middle East Respiratory Syndrome Coronavirus
(MERS-CoV)
■ Novel coronavirus that emerged in 2012

■ Causes severe acute respiratory illness

■ First cluster of 2 cases occurred near

Amman, Jordan April 2012
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MERS-CoVSymptoms

■ Severe acute respiratory illness:

■ Fever
■ Cough
■ Shortness of breath

■ Illness onsets were from April 2012 through June 2013

■ Some cases have had atypical presentations:

■ Initially presented with abdominal pain and diarrhea and later developed
respiratory complications
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MERS-CoVTransmission

" Airborne

" Incubation period is 10-14 days

" The following have been observed:

" Transmission between close contacts
" Transmission from infected patients to healthcare personnel

" Eight clusters of illnesses have been reported by six countries

" So far, all cases have a direct or indirect link to one of four countries:
Saudi Arabia, Qatar, Jordan, and the United Arab Emirates
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MERS-CoVCases

MERS Cases and Deaths, April 2012 - Present

Countries Cases (Deaths) Median Age = 56
France 2 (1)
All patients were
Italy 3 (0)
aged ≥ 24 yrs
Jordan 2 (2) except for a 2yo
Qatar 2 (0) and a 14yo
Saudi Arabia 49 (32)
Tunisia 2 (0)
United Kingdom (UK) 3 (2)
United Arab Emirates (UAE) 1 (1)
Total 64 (38) = 59% MR
+Number of confirmed cases of Middle East Respiratory Syndrome Coronavirus
(MERS-CoV) (N = 55) reported as of June 7, 2013, to the World Health
Organization, by month of illness onset — worldwide, 2012–2013

MMWR. June 14, 2013 / 62(23);480-483

 +Confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
=55) reported as of June 7, 2013, to the World Health Organization, and history of
travel from the Arabian Peninsula or neighboring countries within 14 days of illnes
onset — wo rldwide, 2012–2013

MMWR. June 14, 2013 / 62(23);480-483

+ Patient Under Investigation (PUI) For Avian
Inluenza, SARS, MERS COV

" Any PUI should be reported to state and local health departments
immediately

" PUI Criteria:

1. Acute respiratory infection, may include fever ≥ 100.4°F and cough
2. Suspicion of pneumonia or acute respiratory distress syndrome based
on clinical or radiological evidence
3. History of travel to the Arabian Peninsula or neighboring countries
within 14 days
4. Symptoms not already explained by any other infection or etiology
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Patient Under Investigation (PUI)

" The following persons may be considered for evaluation of MERS-

CoV:
" Persons who develop severe acute lower respiratory illness of known
etiology within 14 days after traveling from the Arabian Peninsula or
neighboring countries, but who do not respond to appropriate therapy
OR
" Persons who develop severe acute lower respiratory illness who are close
contacts of a symptomatic traveler who developed fever and acute
respiratory illness within 14 days of traveling from the Arabian Peninsula
or neighboring countries
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CloseContact

■ Any person who provided care for the patient, including a healthcare
worker or family member, or had similarly close physical contact

■ Any person who stayed at the same place (lived with, visited) as the
patient while the patient was ill
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Recommendations for PUI

" All clusters of severe acute respiratory illness (SARI) should be

investigated. If no obvious etiology is identified, local public health
officials should be notified and testing for MERS-CoV conducted if
indicated

" Local health departments should notify DPH immediately of SARI

clusters and PUIs

" Local health departments should collect data on the PUI using the
form available at: http://www.cdc.gov/coronavirus/mers/
guidance.html and fax to RDS secure fax 502-696-3803
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Probable Case Definition

" A probable case is any person who:

" Meets PUI criteria and has clinical, radiological, or histopathological evidence of
pneumonia or ARDS, but no possibility of lab confirmation exists, either because
patient or samples are unavailable or no testing available for other respiratory
infections, AND
" Is a close contact with a laboratory confirmed case, AND
" Has illness not already explained by any other infection or etiology, including all
clinically indicated tests for community-acquired pneumonia
OR any person with:
" SARI with no known etiology,AND

" An epidemiologic link to a confirmed MERS case

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Confirmed Case Definition

■ A confirmed case is any person with laboratory confirmation of

infection with MERS-CoV (PCR)
+ Infection ControlRecommendations

■ Standard, contact, and airborne precautions are recommended for

management of hospitalized patients with known or suspected MERS-
CoV infection.
■ Airborne Infection Isolation Room (AIIR)
■ If unavailable, transport to another facility

■ Place facemask on patient and isolate in a single-patient room with door

closed. Air should not recirculate without HEPAfiltration
+ Collection of LaboratorySpecimens

" Determine if patient meets PUI criteria

" Collect:
" An upper respiratory specimen:
" Nasopharyngeal AND oropharyngeal swab
" A lower respiratory specimen:
" Broncheoalveolar lavage, OR
" Tracheal aspirate, OR
" Pleural fluid, OR
" Sputum
" Serum for eventual antibody testing (tiger top tube)
" Should be collected during acute phase during first week after onset, and again
during convalescence ≥ 3 weeks later
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MERS Resources

■ MERS overview: http://www.cdc.gov/coronavirus/mers/index.html

■ Case definitions and guidance: http://www.cdc.gov/coronavirus/mers/

case-def.html

■ Additional MERS resources: http://www.cdc.gov/coronavirus/mers/

related-materials.html