RESPIRATORY TRACT
INFECTIONS
Kolářová M., EPI Spring 2018
RESPIRATORY TRACT
INFECTIONS
Kolářová M., EPI Spring 2016
Upper Respiratory Infections: Common Cold, Sinusitis, Pharyngitis,
Epiglottitis and Laryngotracheitis, Otitis externa, Otitis media
Pathogenesis: Organisms gain entry to the respiratory tract by inhalation of
droplets and invade the mucosa. Epithelial destruction may ensue, along
with redness, edema, hemorrhage and sometimes an exudate.
Etiologic agents include viruses :
Rhinoviruses with more than 100 serotypes - causing at least 25% of colds
in adults. Coronaviruses may be responsible for more than 10% of cases.
Parainfluenza viruses, respiratory syncytial virus, adenoviruses and
influenza viruses.
Type A coxsackieviruses can cause a severe ulcerative pharyngitis in
children (herpangina), and adenovirus and herpes simplex virus, although
less common, also can cause severe pharyngitis. Pharyngitis is a common
symptom of Epstein-Barr virus and cytomegalovirus infections.
Upper Respiratory Infections: Common Cold, Sinusitis, Pharyngitis,
Epiglottitis and Laryngotracheitis, Otitis externa, Otitis media
Etiologic agents include bacteria :
The most common bacterial agents responsible for acute sinusitis are
Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella
catarrhalis. Other organisms including Staphylococcus aureus,
Streptococcus pyogenes, gram-negative organisms and anaerobes have
also been recovered.
For otitis externa, the skin flora such as Staphylococcus epidermidis,
Staphylococcus aureus, diphtheroids and occasionally an anaerobic
organism, Propionibacterium acnes are major etiologic agents. In a moist
and warm environment, a diffuse acute otitis externa (Swimmer's ear) may
be caused by Pseudomonas aeruginosa.
For otitis media, the commonest causative bacteria are Streptococcus
pneumoniae, Hemophilus influenzae and beta-lactamase producing
Moraxella catarrhalis.
Upper Respiratory Infections: Common Cold, Sinusitis, Pharyngitis, Epiglottitis and
Laryngotracheitis, Otitis externa, Otitis media
Group A beta-hemolytic streptococcus or Streptococcus pyogenes is the most important
bacterial agent associated with acute pharyngitis and tonsillitis. Corynebacterium
diphtheriae causes occasional cases of acute pharyngitis, as do mixed anaerobic
infections (Vincent's angina), Corynebacterium haemolyticum, Neisseria gonorrhoeae, and
Chlamydia trachomatis. Outbreaks of Chlamydia pneumoniae (TWAR agent) causing
pharyngitis or pneumonitis have occurred in military recruits.
Mycoplasma pneumoniae and Mycoplasma hominis have been associated with acute
pharyngitis. Candida albicans, which causes oral candidiasis or thrush, can involve the
pharynx, leading to inflammation and pain.
Haemophilus influenzae type b is the most common cause of epiglottitis, particularly in
children age 2 to 5 years. Epiglottitis is less common in adults.,
2. Lower Respiratory Infections: Bronchitis, Bronchiolitis and Pneumonia
Pathogenesis: Organisms enter the distal airway by inhalation, aspiration or by
hematogenous seeding.The pathogen multiplies in or on the epithelium, causing
inflammation, increased mucus secretion, and impaired mucociliary function; other lung
functions may also be affected. In severe bronchiolitis, inflammation and necrosis of the
epithelium may block small airways leading to airway obstruction.
Etiology: Causative agents of lower respiratory infections are viral or bacterial.Viruses
cause most cases of bronchitis and bronchiolitis.
In community-acquired pneumonias, the most common bacterial agent is Streptococcus
pneumoniae. Atypical pneumonias are cause by such agents as Mycoplasma pneumoniae,
Chlamydia spp, Legionella, Coxiella burnetti and viruses. Infections due to Haemophilus
influenzae (usually nontypable) and Klebsiella pneumoniae are more common among
patients over 50 years old who have chronic obstructive lung disease or alcoholism.
The most common agents of nosocomial pneumonias are aerobic gram-negative bacilli
that rarely cause pneumonia in healthy individuals. Pseudomonas aeruginosa, Escherichia
coli, Enterobacter, Proteus, and Klebsiella species are often identified. Less common
agents causing pneumonias include Francisella tularensis, the agent of tularemia; Yersinia
pestis, the agent of plague; and Neisseria meningitidis, which usually causes meningitis
but can be associated with pneumonia, especially among military recruits. Xanthomonas
pseudomallei causes melioidosis, a chronic pneumonia in Southeast Asia.
Mycobacterium tuberculosis can cause pneumonia. Atypical Mycobacterium species can
cause lung disease indistinguishable from tuberculosis.
Air-borne diseases
Climatic factors such as absolute humidity have been associated with risk of lower
respiratory tract infection.
Respiratory syncytial virus (RSV) is one of the most important viral respiratory pathogens especially
for infants. The epidemic activity of RSV infection is related to meteorological conditions and thus to
latitude: persistently high temperature and humidity results in epidemic peaks in summer and
early autumn, while in temperate climates RSV infection peaks in the winter. A causal link with
temperature seems inconsistent based on these climatic data, but the RSV infection season in
England and Wales has ended earlier and its duration has shortened as the climate has become
warmer.
Seasonality has been documented for a number of other respiratory infections including
tuberculosis, and seasonal fluctuations of El Niño-southern oscillation in California are
associated with the impact of influenza epidemics (hospital admissions or mortality profiles;) but a
direct link to climate change has not been established.
Furthermore, increased use of cooling towers during heat waves might increase the risk
for exposure to Legionella spp, although appropriate public health measures should be able to
contain this risk.
INFLUENZA VIRUSES
Case definition
Influenza
Clinical 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 symptoms:
• — 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) and with an
epidemiological link
• C. Confirmed case
• Any person meeting the clinical (ILI or ARI) and the laboratory
criteria
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.
Seasonal influenza
Seasonal influenza is a vaccine-preventable disease that
each year infects approximately ten to thirty per cent of
Europe's population,
and causes hundreds of thousands of hospitalisations
across Europe.
Older people, younger children and those with chronic
conditions suffer the most, but everyone is at risk of
developing serious complications—which include
pneumonia, myocarditis and encephalitis—that may result in
death.
Schema
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.
The rise of the pandemic strain
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)
Types of the vaccine
Influenza and
H5N1
Interhuman transmission ?
Farm by Hanoi, 2002 (CDC)
T. Uyeki, CDC
Bird flu viruses do not usually infect
humans, however, several cases of
human infection with bird flu viruses have
occurred since 1997.
Coronavirus infections
Middle East respiratory syndrome coronavirus
The Middle East respiratory syndrome
coronavirus (MERS-CoV) is a new beta
virus strain of an animal coronavirus that
was first identified in Saudi Arabia in
September 2012.
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.
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.
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.
Legionellosis
The Genus Legionella is
a pathogenic group of Gram-negative bacteria which include
Legionella pneumophila, the cause of Legionellosis (from 40
types around 20 types are patogenic).
Legionella organisms are aerobic, motile, pleomorphic rods.
It may be visulized in a silver stain, or cultured in cysteine rich
media such as BCYE(Buffered charcoal yeast extract)
• The organism is found mainly in aquatic
medium.
• Freshwater amoebae appear to be the
natural reservoir for the organisms
– Natural aquatic habitats
• Freshwater streams
• Lakes
• Water reservoirs
– artificial sources
• Cooling towers
• Potable water distribution systems
• Air conditioning devices
Legionella survive and multiplay in water:
 at temperatures between 20°- 50°C (shower, taps,
spa)
 in pipes with little or no water flow (this include
unoccupied rooms
 in slime (biofilm) and dirt on the inner surfaces of pipes
and tanks.
Legionella was discovered after an outbreak in 1976 amongst
people who attended a Philadelphia convention of the American
Legion. Those who were affected suffered from an atypical
pneumonia that eventually became known as
Legionnaires’ disease.
The bacteria was found in the Colling tower of the AC system.
The total number of cases reported were 211.
A total of 34 deaths were reported.
• The first identified cases of Pontiac fever occurred in
1968 in Pontiac, Michigan, in people who worked at
and visited the city’s health department.
• It was only when Legionella was discovered in 1976
that public health officials were able to show that the
same bacterium causes both diseases.
• The incubation period is up to two weeks.
• Pontiac fever
– acute, non fatal respiratory disease that resembles
influeza, it resolves spontaneously.
– Named after Pontiac city, where the first case was
recognized in 1968.
• Legionnaires´s disease
– Form of atypical pneumonia, more severe then Pontiac
fever.
– Legionares´s afects mainly immunocompromised and
elderly.
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.
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.
Graph 1. Notification rate of legionnaires´s disease in EU by year of
reporting, 1995-2013
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.