RESPIRATORY TRACT
INFECTIONS
Kolářová M., EPI Autumn 2019
INFLUENZA VIRUSES
Kolářová Marie, EPI, Autumn 2019
INFLUENZA
ORTHOMYXOVIRUSES - INFLUENZA VIRUSES A,B,C (D)
The body enter is the mucous membrane of respiratory tract.
The incubation time for seasonal influenza is on average two days, but ranges from one to four
days.
Source is the human from the ende of incubation period to 5. days after the onset of the
symptoms.
The replication of the viruses in the epitelial cells of the respiratory tract is very prompt after cca
4 hours with maximum the first 2 – days
The matured viruses consenquently attack a other susceptible cells; cells decay – the beginning
of fever.
On average an infectious person will infect less than two non-immune people.
Influenza spreads:
* predominantly via the droplet and contact routes when people cough and sneeze,
* and by indirect spread through respiratory secretions on hands, tissues, etc.
If the infected person doesn’t cover his or her mouth and nose people within a range of two
meters can be infected. There is also some evidence that infectious aerosols may play a role in
influenza transmission.
However, immunity to influenza viruses and vaccines wane over time and a
large part of the population is susceptible each season.
The source
of infection
Route of
transmission
Susceptibility
Etiology:
Influenza – Case definitionClinical Criteria
Any person with at least one of the following clinical forms:
Influenza-like illness (ILI) — Sudden onset of symptoms
AND: — at least one of the following four systemic symptoms: — Fever or feverishness — Malaise — Headache —
Myalgia
AND: — At least one of the following three respiratory symptoms: — Cough — Sore throat — Shortness of breath
Acute respiratory infection (ARI) — Sudden onset of symptoms
AND — At least one of the following four respiratory symptomms: — Cough — Sore throat — Shortness of breath —
Coryza
AND — A clinician's judgement that the illness is due to an infection
Laboratory Criteria
At least one the following four: — Isolation of influenza virus from a clinical specimen — Detection of
influenza virus nucleic acid in a clinical specimen — Identification of influenza virus antigen by DFA test in
a clinical specimen — Influenza specific antibody response Sub typing of the influenza isolate should be
performed, if possible
Epidemiological Criteria
An epidemiological link by human to human transmission
Case Classification
A. Possible case Any person meeting the clinical criteria (ILI or ARI)
B. Probable case Any person meeting the clinical criteria (ILI or ARI) with an epidemiological link
C. Confirmed case Any person meeting the clinical (ILI or ARI) and the laboratory criteria
INFLUENZA A/H5N1 – Case definition
Clinical Criteria
Any person with one of the following two: — Fever AND signs and symptoms of acute respiratory infection; — Death
from an unexplained acute respiratory illness.
Laboratory Criteria
At least one of the following three: — Isolation of influenza A/H5N1 from a clinical specimen; — Detection of influenza
A/H5 nucleic acid in a clinical specimen; — Influenza A/H5 specific antibody response (four-fold or greater rise or single
high titre).
Epidemiological Criteria
At least one of the following four: — Human to human transmission by having been in close contact (within 1 metre) to a
person reported as probable or confirmed case; — Laboratory exposure: where there is a potential exposure to
influenza A/H5N1; — Close contact (within 1 metre) with an animal with confirmed A/H5N1 infection other than poultry
or wild birds (for example, cat or pig); — Reside in or have visited an area where influenza A/H5N1 is currently
suspected or confirmed AND at least one of the following two: — Having been in close contact (within 1 metre) with sick
or dead domestic poultry or wild birds in the affected area; — Having been in a home or a farm where sick or dead
domestic poultry have been reported in the previous month in the affected area.
Case Classification
A. Possible case Any person meeting the clinical and the epidemiological criteria
B. Probable case Any person with a positive test for influenza A/H5 or A/H5N1 performed by a laboratory which is not
a National Reference Laboratory participating in the EU Community Network of Reference Laboratories for human
influenza (CNRL)
A. Nationally confirmed case Any person with a positive test for influenza A/H5 or A/H5N1 performed by a National
Reference Laboratory participating in the EU Community Network of Reference Laboratories for human influenza
(CNRL)
B. WHO confirmed case Any person with a laboratory confirmation by a WHO Collaborating Centre for H5
ORTHOMYXOVIRUSES - INFLUENZA VIRUSES
Influenza virus type A was first cultivated in the 1930s. Thus this
agent was first of the respiratory viruses to be cultivated in the
laboratory.
There are three major antigenic types –A,B,C – based on antigenic
differences between their nucleocapsid and matrix proteins.
Subtypes differences are based on antigenic differences in the
hemagglutinin (HA) and neuraminidase (NA) surface proteins.
The segmented genome of influenza viruses is a key features that
alows for the genetic reassortment and creation of major antigenic
changes (antigenic drift and shift) seen with influenza A viruses.
ORTHOMYXOVIRUSES - INFLUENZA VIRUSES
Antigenic shift involving the HA protein are critical because
antibodies to this surface glycoprotein are associated with
neutralization of viral infectivity. The generation of genetic
reassortments in animals (e.g. duck) that are co-infected with
human and animal influenza viruses is a proposed mechanism for
antigenic shifts that led to the emergence of pandemic disease.
A outbreak of avian influenza A (H5N1) in Hong Kong yeilded
isolates with exclusively avian genomes. In this case as well
transmissibility of these isolates was minimal.
A recent outbreak of „pigs“ inluenza A was H1N1.
Minor antigenic changes (antigenic drift) occurs as the results of
mutation in the surface HA and NA proteins, which provide a
means for the virus to escape existing immunity.
ORTHOMYXOVIRUSES - INFLUENZA VIRUSES
Although distinct antigenic variants of inluenza B viruses cocirculate,
antigenic shift among these agents and the existence of different
subtypes has not been observed.
Inluenza A serves as the prototype strain and has organizational
similarity to inluenza B with eight RNA segments.
Gene products include:
▪ two surface glycoproteins (HA,NA);
▪ the major nucleocapsid protein (NP), which associated with tree
other proteins (PA,PB1 and PB2) to form the transcription
complex;
▪ matrix proteins (M1 and M2);
▪ nonstructural proteins (NS1 and NS2).
ORTHOMYXOVIRUSES - INFLUENZA VIRUSES
The hemagglutinins, of which three are associated with humann inluenza type A
(H1, H2,H3), are responsible for viral attachment to sialis acid-containing
cell receptors and fusion of viral and cellular membranes.
The neuraminidases, of which two are associated with human influenza type B
(N1, N2), are associated with cleavage of sialic acid residues and viral
release.
The M1 protein is the most abundant protein and underlies the viral membrane.
The M2 protein forms an ion channel that is blocked by the antiviral drug
amantadine.
Influenza C has only a single surface glycoprotein, lacks neuraminidase activity
and has one less RNA segment.
In contrast to replication of other RNA viruses, inluenza virus replication involves
the nucleus of infecte cells.
Schema
History
• From the 17. and 18. century are reports
about the epidemics in the towns and
viliges too.
• Consecutive some epidemics aflicted all
continents except Austrálie
• „archeologic sérology“ detected:
A (H2N2) in the 1889-1892 and
A (H3N8) in the 1898-1901
A (H1N1) in the 1918-1920 – „Spanish flu“
Incidence subtypes Flu A at human
population (CDC)
ORTHOMYXOVIRUSES - INFLUENZA VIRUSES
Epidemiology:
Inluenza is an a seasonal virus that infects all age groups.
Inluenza type A is the most clinicaly important, followed by types B
and C.
Influenza B infection is associated with the same disease spectrum
as influenza A but inlfuenza B infection has a lower asssociation
with severe disease and hospitalization.
Although most people appear to have experiend influenza type C
infection by early adulthood, this agentsis associated with mild
sporadic upper respiratory tract infections and is rarely associated
with lower respiratory tract disease.
• The source – is the human from the ende of
incubation period to 5. days after the onset of
the symptoms.
• The body enter is the mucous membrane of
respiratory tract
• The replication of the viruses in the epitelial
cells of the respiratory tract is very prompt after
cca 4 hours with maximum the first 2 – days
• The matured viruses consenquently attack a
other susceptible cells; cells decay – the
beginning of fever
• After 5. days is very difficult the isolation of
viruses
Epidemiologie
• The reasons of explosive spreading:
✓High infectitivity - low infectious dosis
✓Short the incubation period
✓Fast replication of the virus
✓General susceptibility of the population
Risks groups of people
• Old people - more than 65 years
• Pacients wit chronic diseases of lung
(CHOPN, bronchial astma, cystic fibrosis)
• Chronic diseases of hepar or decreased
function of kidney
• Metabolic diseases (DM)
• Neutropenie, malignit processes, defects
of immunity (HIV +, after transplantation, chronic
immunosupression)
Diagnostics
• Routine laboratory diagnostics for influenza are usually
performed by detecting the virus antigen or genome in
specimens from the respiratory tract. Sampling can e.g.
consist of swabbing the nose and nasal cavity.
• The tests performed in laboratories include RT-PCR,
enzyme-linked immunoassay, immunofluorescence, and
virus culture. Except for virus culture these results can be
available within approximately 1-2 days, and can help adjust
the treatment.
• There are also rapid point of care tests (quick test) that
require less time. However these tests generally have a low
sensitivity but high specificity, and do not allow subtype
determination.
Therapy
• Mainly symptomatic
• By the risks patients – antivirotics
• Aplication in the first two days:
– 1. generation amantadin a rimantadin 
effectivity only by the influenza types A
– 2.generation zanamivir (inhalation) and
oseltamivir (p.o.)  effectivity for types A i B.
For the best clinical benefit, treatment with antivirals
should be given early in the infection, within 48 hours, (the
earlier the better).
Therapy
• Resistance to antivirals
• Pre-exposure prophylaxis with influenza
antivirals can be prescribed for longer or
shorter time periods when an exposure is
expected, for example in healthcare settings.
• Post-exposure prophylaxis with influenza
antivirals, for example for an at-risk
unvaccinated person, is dependent on timely
prescription given that the incubation period is
1-4 days. It is usually not prescribed for more
than 10 days.
Types of the vaccine
Pandemic Preparedness and Response Plan for:
Date:
Introduction
In preparation for a potential pandemic, all individuals, government and business entities, and community organizations
and agencies should take appropriate measures to minimize the impact of a pandemic. This Pandemic Preparedness and
Response Plan recommends a series of action steps that our faith-based organization should take in response to a
potential pandemic in our community.
Steps to Developing a Pandemic Preparedness and Response Plan for Your Faith-based Organization1
• Step 1 Establish a Pandemic Planning Committee with the responsibility to develop, maintain and put into action a pandemic
preparedness and response plan.
• Step 2 Determine the potential impact of a pandemic outbreak on your organization’s usual activities and services.
• Step 3 Develop contingency plans for the performance of all critical functions of your faith-based organization during a pandemic.
• Step 4 Develop plans to extend timely and factual information about the pandemic to your staff, organizational members and people
in the communities.
• Step 5 Develop plans for crisis communications during a pandemic. Develop tools to communicate information about pandemic
status and your organization’s actions.
• Step 6 Identify people with special needs (e.g. elderly, disabled, limited English speakers), and include their needs in your response
and preparedness plan.
• Step 7 Develop plans to coordinate your pandemic preparedness and response plans with external organizations and agencies.
This includes working with public health agencies, emergency responders, local health care facilities, and other faith-based and
community organizations.
• Step 8 Share information about your pandemic preparedness and response plan with staff, organizational members
• 1 These eight steps listed are modified from:
• Flu.gov (2014). Faith-Based and Community Organizations Pandemic Influenza Preparedness Checklist.
• www.flu.gov/planning-preparedness/community/faithbaseedcommunitychecklist.pdf
Influenza and
H5N1
Fifteen subtypes of influenza virus are
known to infect birds,
thus providing an extensive reservoir of
influenza viruses potentially circulating in
bird populations.
To date, all outbreaks of the highly
pathogenic form have been caused by
influenza A viruses of subtypes H5 and
H7.
Within a country, bird flu can spread easily
from farm to farm. Large amounts of avian
flu is secreted in bird droppings, therefore
contaminating dust and soil. An airborne
virus can spread bird flu from bird to bird,
causing infection when the avian flu is
inhaled.
Bird flu viruses do not usually infect
humans, however, several cases of
human infection with bird flu viruses have
occurred since 1997.
The rise of the pandemic strain
Interhuman transmission ?
Farm by Hanoi, 2002 (CDC)
T. Uyeki, CDC
A set of 579 sentinel patients:
HRV - humann rhinovirus PIV - parainfluenza virus BOCA - bocavirus
RSV - resp. syntic. virus COV - coronaviruses
ADV - adenovirus MPV - metapneumovirus
Quadrivalent combination vaccines containing:
* two influenza A strains (H1N1 and H3N2 subtypes) and
* two influenza B strains (Victoria and Yamagata lineages)
as per WHO recommendations.
- Injected quadrivalent inactivated influenza
vaccines, available from the 2014/2015 season in
some EU/EEA countries
- In 2011, a live attenuated influenza vaccine
(LAIV) for intranasal use was approved in the
EU/EEA for children and adolescents (2-17 years of
age).
Most influenza vaccines, both inactivated and
live attenuated, are based on production of
influenza viruses/antigens in fertilised hens'
eggs. These vaccines can therefore not be
given to egg-allergic individuals developing
severe symptoms upon exposure to egg
proteins.
Hence, a few manufacturers have developed
cell-based influenza vaccines which can be
given to severely egg-allergic individuals.
Risk groups for severe influenza
Older adults - cca 65 yers
All persons (over six months of age) with chronic medical conditions:
• respiratory system e.g. asthma
• cardiovascular system e.g. coronary artery disease
• endocrine system e.g. diabetes
• hepatic system e.g. liver cirrhosis
• renal system e.g. chronic renal failure
• neurological/neuromuscular conditions e.g. parkinsonism
In addition to the above:
• any condition compromising respiratory functions e.g. morbid obesity (BMI > 40), physical
handicap in children and adults
• immunosuppression due to disease or treatment including due to haematological
conditions and HIV infection
From 2012 --- new group - pregnant women
- health care workers with patient contact.
Česká republika - závažné případy chřipky s prokázanou nákazou virem chřipky vč.
úmrtí – stav hlášení od 1.9.2015 do 15.1.2016:
V ČR bylo v uvedeném období hlášeno celkem 16 klinicky závažných případů chřipky,
• z nichž ve 3 případech došlo k úmrtí.
Jako etiologické agens byl ve 3 případech prokázán virus chřipky typu B,
ve 3 případech se jednalo o virus chřipky A,
v 8 případech se jednalo o subtyp A/H1N1 a
ve 2 případech se jednalo o subtyp viru chřipky A/H3N2.
U všech pacientů bylo v anamnéze některé ze základních chronických onemocnění a nebyli
• očkováni proti chřipce popř. záznam o tomto očkování chybí. Věk pacientů se pohyboval
• v rozmezí 35 let – 82 let..
Z uvedeného počtu pacientů se jednalo v 5 případech o ženy a v 11 případech o muže. V 9
případech byla do 48 hodin podána antivirotika.
• MUDr Martina Havlíčková, CSc, NRL pro chřipku a nechřipková virová respirační onemocnění
ECDC
In the course of the 2012–13 season,
A(H1N1)pdm09, A(H3N2) and B/Victoria- and
B/Yamagata-lineage influenza viruses have co
circulated in ECDC-affiliated countries over what was an
extended influenza season.
• The relative prevalences of each virus
type/subtype/lineage has varied between
countries.
• Type A (~60%) and type B (~40%) viruses have
been detected in similar proportions but with type A
peaking and declining slightly before type B.
• A(H1N1)pdm09 viruses have been detected at
approximately twice the level of A(H3N2) viruses.
• • The vast majority of A(H1N1)pdm09 viruses have remained
antigenically similar to the vaccine virus, A/California/07/2009,
but continued to show genetic drift with an increasing
prevalence of genetic group 6 viruses, predominant in the 6C
subgroup.
• • The vast majority of A(H3N2) viruses have been
antigenically and genetically similar to cell-propagated
A/Victoria/361/2011, a genetic subgroup 3C virus and
the prototype vaccine virus for the 2012–13 influenza
season; subgroup 3C viruses have circulated
exclusively in recent months, and the recommended
vaccine virus for the 2013–14 season,
A/Texas/50/2012, is in this genetic group.
Viruses of the B/Yamagata-lineage have predominated
over those of the B/Victoria-lineage.
• B/Victoria-lineage viruses have remained
antigenically similar to cell-propagated reference
viruses of the B/Brisbane/60/2008 genetic clade.
• B/Yamagata-lineage viruses formed two antigenically
distinguishable genetic clades: clade 3 represented by
B/Wisconsin/1/2010 (the recommended vaccine
component for the 2012–13 influenza season) and, in
increasing numbers, clade 2 (75% of B/Yamagata
detections recently) represented by
B/Massachusetts/2/2012 (the recommended vaccine
component for the 2013–14 influenza season).
Zpráva NRL pro chřipku a nechřipkové
respirační viry
14.10.2013 -- Souhrn epidem. situace v ČR a v Evropě:
Situace v ČR je ohledně incidence chřipky stále zcela klidná,
není zatím evidován ani sporadický výskyt.
Evropa: hlásí pouze ojedinělé záchyty. Zpráva WISO (Weekly
Influenza Surveillance System) za 40. KT uvádí 132
vyšetřených sentinelových vzorků, z nich:
3 byly pozitivní – 1x H1 (Španělsko) a 2x B (Belgie, Irsko).
Z nesentinelových zdrojů bylo prokázáno 15 případů chřipky,
přičemž u 11 pacientů se jednalo o typ A u 4 pacientů o typ B.
U skupiny chřipek A byl 3x dourčen subtyp H3, 1x H1.
Dále je hlášen jeden případ těžkého průběhu chřipky B typu z
Irska ( 31letá těhotná pacientka).
MUDr Martina Havlíčková
Legionellosis
• People over the age of 50 are more at risk than younger people, and males
are more at risk than females. Effective antibiotic treatment is available if the
diagnosis is made early in the illness. Deaths occur in about 5-15% of
travellers who get the disease, depending on their age and individual health
status. Smokers are more at risk than non-smokers.
• People become infected when they breathe in air that contains tiny droplets
of water known as aerosols, inside of which are the Legionella bacteria. If
the bacteria get inhaled into the lungs they can cause infection.
Legionellosis cannot be got from water you drink that enters your stomach in
the normal way – the bacterium has to get into the lungs through breathing it
in. The illness is not spread from person to person.
•
Legionellosis
• The bacterium responsible for Legionnaires' disease
was identified in 1976, after a large outbreak at a hotel
in Philadelphia, USA. The disease got its name from
the group of people affected in this outbreak. They
were retired American service personnel who were
attending a legion convention. Since the outbreak in
1976, cases and outbreaks have been reported from
all countries in Europe, many of them linked to hotels
and other types of holiday accommodation.
Legionellosis
• What is legionellosis?
• Legionellosis is an uncommon form of pneumonia. The disease has no
particular clinical features that clearly distinguish it from other types of
pneumonia, and laboratory investigations must be carried out to confirm the
diagnosis. It normally takes between two to ten days to develop symptoms
(typically five to six days) but very rarely some cases may take two to three
weeks to develop symptoms. Patients usually start with a dry cough, fever,
headache and sometimes diarrhoea and many people go on to get
pneumonia. People over the age of 50 are more at risk than younger people,
and males are more at risk than females. Effective antibiotic treatment is
available if the diagnosis is made early in the illness. Deaths occur in about
5-15% of travellers who get the disease, depending on their age and
individual health status. Smokers are more at risk than non-smokers.
Legionellosis
• People become infected when they breathe in air that contains tiny droplets
of water known as aerosols, inside of which are the Legionella bacteria. If
the bacteria get inhaled into the lungs they can cause infection.
• Legionellosis cannot be got from water you drink that enters your stomach in
the normal way – the bacterium has to get into the lungs through breathing it
in.
• The illness is not spread from person to person.
• Where do the Legionella bacteria come from?
• Legionella bacteria are common and can be found naturally in environmental
water sources such as rivers, lakes and reservoirs, usually in low numbers.
The bacteria are able to survive in the nature at a wide range of
temperatures. The bacteria can multiply in man-made aquatic systems like
cooling towers, evaporative condensers, humidifiers, decorative fountains,
hot water systems and similar systems.
Legionellosis
• How do outbreaks occur?
• Experience shows that outbreaks in hotels are mostly associated with hot or cold water
distribution systems. If the bacteria is in the water in quantities that can cause infection,
someone taking a shower would inhale the bacteria trapped inside the tiny aerosols that are
created when the shower water hits the hard surfaces of the shower unit or bath. They may also
be affected by other water systems that cause aerosols, for example whirlpool spas and
fountains.
• In contrast, large explosive outbreaks in the community are mostly associated with cooling
towers. Cooling towers are devices used to cool buildings. They are also called “wet air
conditioning systems” because the process of cooling air involves extensive contact between
water and air, thereby creating aerosols. When the Legionella bacteria are present in these
systems they can cause Legionnaires' disease. Air conditioning units that use water to cool the
air can also pose a risk in hotels.
• However, many air conditioning systems are “dry” and these pose no risk for legionellosis.
• When an outbreak of legionellosis occurs, the source may be found through two types of
investigation. One collects information on the activities and whereabouts of the patients with
legionellosis to look for links between cases such as staying at or visiting the same places
before they became ill. The other involves looking for the Legionella bacteria in the suspected
water sources and in clinical specimens from the patients. If the bacteria are found in both,
specialised laboratory methods are used to see if they are of the same type.
•
.