RESPIRATORY TRACT
INFECTIONS
Kolářová M., EPI Autumn 2015
INFLUENZA VIRUSES
Kolářová Marie,ÚOPZ
INFLUENZA
ORTHOMYXOVIRUSES - INFLUENZA VIRUSES A,B,C
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
In human - a high infectivity from the onset of the disease (1st - 5th day), in infants
from the 7th day.
The animals: pigs, birds and ducks, who may, after genetic changes, be reservoirs
for new human subtypes (genetic reassortment).
A) Directly - by close contact with the sick, airborne. Most frequently in crowded,
closed rooms where a high concentration of the infectious aerosol occurs due to
sneezing, coughing and nose-blowing.
B) Indirectly - by objects contaminated with the secret of the sick.
General, the highest in children and young adults without specific antibodies.
Immunity is long-term after recovery from the disease. it is strictly type- and strainspecific
- antibodies don´t protect against the disease by a new virus variant.
The source
of infection
Route of
transmission
Etiology:
Susceptibility
Preventive measures:
Immunization against influenza is the basis of prevention.
For a vaccine to be effective it must contain the surface antigens of the circulating
influenza viruses - the topical drift variants.
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 16 types) and neuraminidase (NA 9 types)
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 coinfected
with human and animal influenza viruses is a proposed mechanism
for antigenic shifts that led to theemergence 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.
Schema
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.
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)
4 December 2015
Main conclusions and options for response
• Highly pathogenic avian influenza (HPAI) of the subtypes
A(H5N1) and A(H5N2) have been detected in birds in a backyard
and in two poultry farms in the Dordogne region of France.
• The HPAI A(H5N1) virus detected in France is not related to the
A(H5N1) viruses circulating in other parts of the world, but
appears to have evolved from a low pathogenic avian influenza
virus circulating in Europe.
• No human case has been reported related to the HPAI A(H5N1)
virus detected in France.
No human case has been reported related to any HPAI A(H5N2)
virus worldwide.
4 December 2015
• When avian influenza viruses circulate in poultry, sporadic infections or small clusters of
human cases are possible in people exposed to infected poultry or contaminated
environments, especially in households and at live bird markets in areas where the viruses
are circulating. Sustained human-to-human transmission of influenza A(H5N1) virus and its
highly pathogenic reassortants have never been observed.
• The risk of foodborne transmission, e.g. through the consumption of eggs or meat is
considered extremely low.
• People having direct contact with diseased birds or poultry, or their carcasses (e.g.
farmers, veterinarians and labourers involved in the culling and rendering) are at a potential
risk of infection. Persons at risk of exposure should therefore wear personal protective
equipment.
• People who have been exposed to the HPAI A(H5N1) or A(H5N2) virus should be
monitored for at least 10 days.
• Animal and public health authorities should be prepared for a possible introduction of
HPAI A(H5N1) or A(H5N2) virus into other European countries, although the risk is
considered low.
• Recommended composition of influenza virus vaccines
for use in the 2015-2016 northern hemisphere influenza
season
• 26 February 2015
• It is recommended that trivalent vaccines for use in the
2015-2016 influenza season (northern hemisphere winter)
contain the following:
• an A/California/7/2009 (H1N1)pdm09-like virus;
• an A/Switzerland/9715293/2013 (H3N2)-like virus;
• a B/Phuket/3073/2013-like virus.
• It is recommended that quadrivalent vaccines containing
two influenza B viruses contain the above three viruses and
a B/Brisbane/60/2008-like virus.
In the Czech Republic
Seasonal influenza vaccination guideline
In the Czech Republic, seasonal influenza vaccination is
provided on a non-compulsory, voluntary basis.
Based on the surveillance data from the Czech Republic
and policies applied by other countries, the National
Immunisation Committee (NIKO) recommends the following
vaccination strategy for the Czech Republic:
Vaccination against seasonal influenza is intended for
persons in whom it is desirable to reduce the risk of
influenza and possible complications associated with
influenza.
In the Czech Republic
Seasonal influenza vaccination guideline
Based on epidemiological analyses and discussion of the situation in Europe,
influenza vaccine is recommended to be given every year to the following two
population groups:
• 1) persons aged 65 years and over;
• 2) persons at any age (including children) with chronic conditions from any of the
categories listed below:
• chronic diseases of the respiratory tract including bronchial asthma;
• chronic cardiovascular diseases;
• chronic kidney and liver diseases;
• chronic metabolic diseases including diabetes mellitus1;
• immune system deficiency (congenital or acquired); and
• impaired bronchial and pulmonary function (including impaired respiratory
function due to brain or spinal cord injury, seizure conditions, and other
neurological or muscular disorders).
• In these cases, influenza vaccination including vaccine is fully covered by the
health insurance
In the Czech Republic
Seasonal influenza vaccination guideline
In addition, influenza vaccine is recommended to:
• • pregnant women at any stage of pregnancy and
women planning to become pregnant during the
influenza season;
• • persons who may increase the risk of infection to
the groups listed above, namely:
• persons providing care to high-risk individuals
(health professionals and social workers);
• persons living with high-risk individuals; and
• persons in contact with high-risk individuals
(employees of posts, shops, services, schools,
public transport, etc.).
CZECH REPUBLIC
SPAIN
UNITED KINGDOM
PORTUGAL
Specific profylaxis
• Inactivated cracked (split) vaccine
• Produced from the inactivated virions
elements, that are divided and reactive
lipides from the envelope take out
• Begrivac, Fluarix, Vaxigrip.
• Aplication: to adults 1. dosis i.m.
• For children from 3 months (under
redommendation of the producer)
Specific profylaxis
• Subdosis trivalent vaccine
• contens only external antigens H and N,
witout MATRIX and NP antigens
• = low reaktivity and good immunogenity.
• Agrippal S1, Influvac a Fluad
• For children from 6 months
Types of the vaccine
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)
The rise of the pandemic strain
Influenza and
H5N1
Interhuman transmission ?
Farm by Hanoi, 2002 (CDC)
T. Uyeki, CDC
LEGIONELOSIS
Legionella pneumophila - Gram-negative rod.
L.pneumophila - 18 serotypes, type 1 dominates. Related species: L.micdadei,
L.bozemanii, L.longbeachae, etc. These species have been isolated from
pneumonias from immunosuppressed individuals. All legionellae have a common
antigen. The phagocyted legionellae proliferate in monocytes.
The source in conception of the classical epidemiology has not been known.
As reservoir there apply various water cooling systems, cooling towers, humidifiers,
etc., from which legionellae were isolated.
The epidemiological circumstances are in favour of the inhalation transmission of
infection.
Interhuman transmission has not been proved.
It is general. The incidence increases with age. Most of cases have been observed
in persons over 50 years of age, in persons with chronic pulmonary diseases,
malignancy, immunosuppression after transplantation of the organs, and diabetes.
The prevalence is 2.5-times higher in men than in women. .
The source
of infection
Route of
transmission
Etiology:
Susceptibility
Preventive measures:
Periodical check of the air-conditioning units and distribution systems.
Periodical microbiologic control of inhalation instrument sprayers.
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 first demonstration was in 1976. The infection
occurred by infectious aerosol from cooling water of
the hotel air conditioning systém at a hotel in
Philadelphia, USA. In the course of the epidemic 34
exposed persons died.
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
Clinical features and diagnosis
• An acute bacterial disease (legionellosis) which manifests in two different
clinical forms:
as Legionnaires´ disease and
as Pontiac fever.
The disease starts with headache, anorexia, and generalized exhaustion with
an onset of fever from 39 - 40.5 C. A nonproductive cough, abdominal pains
and diarrhea is typical.
In the Legionnaires´ disease radiograph a finding of lobar pneumonia with
subsequent very slow clearing dominates. The mortality rate in hospitalized
cases reaches up to 39 %. Pneumonia is absent in Pontiac fever, which has a
benign course. Recovery occurs after a short time even without therapy. The
clinical symptomatology is attributed to a reaction of the organism to the inhaled
antigens of the legionellae..
Legionellosis
• Diagnosis is based on demonstration of the culture (detection by direct
immunofluorescence in the tissue and aspirates) and demonstration of a rise
in specific antibodies in the pair-sera.
• Diagnosis in the Czech Republic is based on a radiograph (x-ray) finding
of pneumonia with a higher fever, negative blood and sputum culture,
and detection of involvement of the liver and kidney function.
• Ag in the urine.
Rapid risk assessment on the outbreak of Legionnaires’ disease
in Portugal
14 Nov 2014
The current outbreak of Legionnaires’ disease in Vila Franca de Xira, in the
Lisbon area of Portugal is one of the largest outbreaks of the disease in the
European Union to date.
• As of 12 November, 311 cases have been identified, of which seven
have died. Despite the magnitude of the outbreak, this event can be
considered a local event and the risk is confined to people in the area or
who have travelled to the area in the past three weeks. Investigations
are ongoing to discover the source of the outbreak, and cooling towers
of major industrial installations in Vila Franca de Xira have been closed
as a precaution.
• The risk assessment also looks at the possibility of Legionnaires’
disease being transmitted through the transfusion of infected blood, and
concludes that this risk is low.
All notified cases
For 2013, 5 851 cases of LD were reported by 28 EU Member States and Norway.
The number of notifications per million inhabitants was 11.4, well within the 2005–
2012 range.
Six countries (France, Italy, Spain, Germany, the Netherlands and the United
Kingdom) accounted for 83% of all notified cases.
The number of notifications ranged from below 0.1 per million inhabitants in
Bulgaria to 39.4 per million in Slovenia.
Most cases were communityacquired (73%), 19% were travel-associated, and 8%
were linked to healthcare facilities.
People over 50 years of age accounted for 81% of all cases.
The male-to-female ratio was 2.4:1.
The case-fatality ratio was 10% in 2013, similar to previous years.
Most cases (88%) were confirmed by urinary antigen test, but an increasing
proportion of cases are reported to have been diagnosed by PCR.
L. pneumophila serogroup 1 was the most commonly identified pathogen,
accounting for 83% of culture-confirmed cases.
EU case definition of Legionnaires’ disease
Clinical criteria
• Any person with pneumonia
Laboratory criteria for case confirmation
• At least one of the following three:
• • Isolation of Legionella spp. from respiratory secretions or any normally sterile site
• • Detection of Legionella pneumophila antigen in urine
• • Significant rise in specific antibody level to Legionella pneumophila serogroup 1 in paired serum samples.
Laboratory criteria for a probable case
• At least one of the following four:
• • Detection of Legionella pneumophila antigen in respiratory secretions or lung tissue, e.g. by DFA staining
• using monoclonal-antibody-derived reagents
• • Detection of Legionella spp. nucleic acid in respiratory secretions, lung tissue or any normally sterile site;
• • Significant rise in specific antibody level to Legionella pneumophila other than serogroup 1 or other
• Legionella spp. in paired serum samples
• • Single high level of specific antibody to Legionella pneumophila serogroup 1 in serum.
Case classification
• Probable case: Any person meeting the clinical criteria AND at least one positive laboratory test for a
probable
• case.
• Confirmed case: Any person meeting the clinical AND the laboratory criteria for case confirmation.
Figure 5. Reported cases and notifications of Legionnaires’ disease per million, by reporting
country,
EU/EEA, 2013
Coronavirus infections
Middle East respiratory syndrome
coronavirus
The Middle East respiratory syndrome coronavirus (MERSCoV)
is a new beta virus strain of an animal coronavirus
that was first identified in Saudi Arabia in September 2012.
•This novel coronavirus differs from the previously identified
coronaviruses such as the SARS coronavirus (SARSCoV),
which caused the 2003 SARS outbreaks.
•There is still much to be investigated, but it is considered
likely that this virus originated from an animal source.
Coronavirus infections
Middle East respiratory syndrome
coronavirus
•Coronaviruses are enveloped RNA viruses from the
Coronaviridae family and part of the Coronavirinae
subfamily. With its characteristic surface, the virions
appear as a crown like image under the electron
microscope and so the viruses are named after the
Latin word corona, meaning 'crown' or 'halo'.
•In animals the viruses infect the respiratory and
gastrointestinal systems as well as occasionally
affecting the liver and the neurological systems.
Coronavirus infections
Middle East respiratory syndrome
coronavirus
•The human coronaviruses mainly infect the upper respiratory and
gastrointestinal tract. They often result in upper respiratory tract
infections (simple colds) in humans, causing mild illnesses usually
of short lasting nature with a rhinitis, cough, sore throat, as well as
fever.
•Occasionally, the viruses are able to cause more significant lower
respiratory tract infections in human with pneumonia; this is more
likely in immunocompromised individuals, people with
cardiopulmonary illnesses, as well as the elderly and young
children. Only very rarely do the humans viruses cause severe
disease, like sever acute respiratory syndrome.
Coronavirus infections
Middle East respiratory syndrome
coronavirus
• The five coronaviruses types which affect humans are alpha (229E and NL63), beta
(OC43), HKUI1 and SARS-CoV - although the latter is best considered an animal virus that
has only rarely infected humans.
• In humans, the transmission of coronaviruses between an infected individual and others
can occur via respiratory secretions. This can happen either directly through droplets from
coughing or sneezing, or indirectly through touching contaminated objects or surfaces as
well as close contact, such as touching or shaking hands.
• There are currently no vaccines or specific treatments for the coronaviruses. Hence, in
order to reduce the risk and prevent the spread of infections, simple preventative measure
are: good respiratory hygiene, including washing hands; avoiding touching one's eyes,
mouth and nose; sanitary disposal of oral and nasal discharges as well as avoiding contact
with sick people.