• Dra.

Gloria Mayela Aguirre García

• Internal Medicine – Infectious Diseases Physician
• February 2024
 Assessment plan
• 1. Exam 40%
• 2. Integrative case analysis 30%
• 3. Approach of infectious syndromes activity in teams (4 teams) 30%
(flowchart)
• respiratory tract infections approach
• urinary tract infections approach
• gastrointestinal tract infections approach
• central nervous system infections approach
Respiratory Infections
Module
Dra. Gloria Mayela Aguirre García
Internal Medicine – Infectious Diseases Physician
March 2022
Introduction to the course

• We will review concepts related to the mechanisms of infectious diseases.

• It is divided by systems and by pathogens.
Theoretical
Practical Contents
Contents
Pathogenicity characteristics of viruses and Clinical and paraclinical aspects of infectious
bacteria diseases (identify serological, culture and
radiological diagnostic findings)
Mechanisms of respiratory, gastrointestinal,
urinary, and nervous system infections

Interpretation of antibiograms
Mechanisms of microbial resistance.
 The common cold
can be caused by:
• Coronavirus
Quiz: Q1 • Epstein–Barr virus
• Mycoplasma sp.
• Respiratory syncytial virus
• Rhinovirus
 • The differential diagnosis of patients who
present with the signs and symptoms of a
cold should include which of the following?
a. Sinusitis
b. Acute Bronquitis
Q2 c. Noninfectious rhinitis
d. A and B
e. All of the above
 • A yellow, green, or brown nasal discharge in
a patient with the common cold usually
indicates the presence of a secondary
Q3 bacterial infection.
True
False
 • Respiratory syncytial virus (RSV) infection
and human metapneumovirus infection
(hMVP) cause upper and sometimes lower
respiratory tract infections. Symptoms of
both viruses are similar although the viruses
are different. In which of the following ages
groups is RSV a very common cause of
Q4 respiratory tract infections?
A. Infants and young children
B. Adolescents ages 12 to 19 years
C. Adults ages 40 to 60 years
D. Adults ages 65 years and older
 • Which ONE of the following
drugs is NOT recommended by
NICE for the prophylaxis of
influenza?
a. Amantadine
Q5 b. Oseltamivir
c. Zanamivir
 • Which ONE of the following groups is
NOT considered an ‘at risk’ patient,
when influenza is circulating in the
community?

Q6 a. Age 65 years or over

b. Healthy adults
c. Children under 6 months of age
d. Morbid obesity (BMI 40 or greater)
Problem situation

• During the month of November, a 3-year-old boy is taken to the office by his
mother, because he has fever and irritability. He began his condition 4 days ago,
with symptoms of hyaline rhinorrhea, epiphora and conjunctival hyperemia. 3
days ago, the symptoms were exacerbated, and his body temperature increased
and did not improve with physical measures or antipyretics. On physical
examination, he is feverish, tachycardic and tachypneic. He does not stop crying
so the physical examination is complicated to do.

• He has a history to attend the nursery, takes a bottle at night, has a 7-year-old
brother and a neighbor with diagnosis of Influenza A.
• In this situation, it is necessary to complete the clinical history and the
relevant physical examination to generate a likely diagnosis and make
therapeutic decisions.

• The mother insists on giving him antibiotics and testing the whole
family for influenza.

• How would you explain the situation to the mother and manage the
paraclinical resources in this case?
 Class 1: Mechanisms of viral infections
• Recognize the pathogenicity characteristics of
some viruses
• Explain the clinical features of some viruses
• Analyze the diagnostic and therapeutic
mechanisms of infections caused by some
Objectives viruses

• Rhinovirus
• Adenovirus
• Coronavirus
• Influenza virus
• Parainfluenza virus
• Respiratory syncytial virus
Introduction: Viral infections

• In Mexico, as in the rest of the world, respiratory infections are a health problem that impacts
health systems.

• Globally, viral infections affect people of all ages.

• In pediatric age, they occur frequently below the age of five and especially in children under
two years of age. 
• The etiology of respiratory infections has been studied, in greater detail, in hospitalized
patients with moderate to severe diseases.
Introduction: Viral infections

• In children under two years of age the most frequent virus is RSV (50%), followed by
the group of rhinoviruses (30%), adenovirus, and other viruses associated with
common cold, or influenza appear in children with mild respiratory infections.
• In infants, the most frequently involved viruses are, above all, rhinoviruses, followed
by respiratory syncytial viruses, and to a lesser extent, coronaviruses.
• Clinical features in outpatients are catarrhal symptoms of the upper tract,
bronchiolitis, recurrent wheezing, and laryngitis. (Bayonne, 2015)
Viral infections
• Viral infections commonly affect the
upper or lower respiratory tract.
 Although the
Particles small
entire respiratory
enough to reach Antimicrobial
tract is constantly
The epiglottis, its the trachea and factors present in
exposed to air,
closure reflex bronchi stick to respiratory
the majority of
and the cough the respiratory secretions
particles are
reflex all reduce mucus lining further disable
filtered out in
the risk of their walls and inhaled
the nasal hairs
microorganisms are propelled microorganisms.
and by inertial
reaching the towards the They include
impaction with
lower respiratory oropharynx by lysozyme,
mucus covered
tract. the action of cilia lactoferrin and
surfaces in the
(the ‘mucociliary secretory IgA.
posterior
escalator’).
nasopharynx
Acquisition of microbial pathogens

• It’s primarily by inhalation, but aspiration and mucosal and haematogenous

spread also occur.
• Respiratory pathogens have developed a range of strategies to overcome host
defences.
• Influenza: has specific surface antigens that adhere tomucosal epithelial cells.

• In some lower respiratory tract infections, the host response is the principal
cause of damage.
Acute Respiratory Infections
 • Although respiratory infections can be classified by the causative virus
(eg, influenza), they are generally classified clinically according to
syndrome (eg, the common cold, bronchiolitis, croup, pneumonia).

• Although specific pathogens commonly cause characteristic clinical

manifestations (eg, rhinovirus typically causes the common

Facts cold, respiratory syncytial virus [RSV] typically causes bronchiolitis),

each can cause many of the viral respiratory syndromes

• Severity of viral respiratory illness varies widely; severe disease is

more likely in older patients and infants.

• Morbidity may result directly from viral infection or may be indirect,

due to exacerbation of underlying cardiopulmonary conditions or
bacterial superinfection of the lung, paranasal sinuses, or middle ear.
Viral respiratory syndromes
 •Smoking – active and passive
•Air pollution – indoor and outdoor
•Crowding e.g family size, day care centers,
refugee camps, poor housing
•Malnutrition
Risk factors •Low birth weight
•Acute lower respiratory infections @ < 2
years
•Socioeconomic status
Influenza
• Influenza virus has been
causing recurrent epidemics
every 1–3 years for the past
400 years.

Diagram of influenza virus structure. Eight segments of viral RNA are contained
within the lipid envelope and matrix (M1) shell. Each codes for one or more
proteins that form the virus or regulate its intracellular replication.
• A unique feature of influenza is its ability to alter
the antigenic properties of the envelope glycoproteins, the
hemagglutinin (HA), and neuraminidase (NA).
• Hemagglutinin: attaches virions to cells by binding to terminal sialic acid
residues on glycoproteins/glycolipids to initiate the infectious cycle
• Neuroaminidase: cleaves terminal sialic acids, releasing virions to complete
the infectious cycle

• Antigenic drift refers to minor modifications (point

mutations) within HA, NA, or both leading to localized
outbreaks.

• Antigenic shift refers to more radical changes in the antigenicity

of HA, NA, or both (segment reassortment) leading to
widespread disease or pandemics.

• The greatest pandemic was in 1918–1919, when 21 million

deaths were recorded worldwide.

• In 2009 the H1N1 influenza pandemic demonstrated the risk of

severe influenza associated with pregnancy.
• In general, excess mortality
has been associated with
influenza A/H3N2 and to a
lesser extent with
influenza A/H1N1.

• Influenza should be
suspected in any patient
who presents with acute
onset of fever, cough, and
systemic symptoms, such
as myalgias, between fall
and spring.

• Fever and cough during a

local epidemic are the
most predictive findings of
influenza infection.
 IL-6, tumor necrosis
factor–α (TNF-α),
interferon-α (IFN-α),
iral replication and the
Viral replication is possible in host cells due to IL-8, and IL-1β
intensity of the main
activation of nuclear factor kappa B (NF-κB) and increase significantly
influenza symptoms
the Raf/MEK/ERK cascade, and then in response to the
are correlated with
proinflammatory cytokines are produced with viral invasion resulting
the level of cytokines,
interleukin 6 (IL-6) being the most important of in the development of
particularly with IL-6
them fever, nasopharyngeal
and TNF-α
mucous production,
and respiratory and
systemic symptoms.
Clinical manifestations
• The typical incubation period is one to four days (average two days) 
• Abrupt onset of fever, nonproductive cough, and myalgia.
• In some cases, the onset is so abrupt that patients can recall the precise time at which
symptoms began.
• Fever usually ranges from 37.8 to 40.0°C (100 to 104°F) but can be as high as 41.1°C (106°F) 

• Other symptoms, including malaise, sore throat, nausea, nasal congestion, and headache,
are common

• The spectrum of clinical manifestations and the severity of infection can vary with different
types of influenza
Diagnosis

• Diagnostic testing should only be used when the results will influence clinical decision-making or
infection control measures.

• Rapid influenza diagnostic tests (RIDTs) are available and work by detecting parts of the virus that
stimulate an immune response (i.e., influenza A and B viral nucleoprotein antigens).

• RIDTs provide results within 10–15 minutes but can be variable (i.e., more likely to be a true
positive during an influenza outbreak) in sensitivity.

• RT-PCR is the preferred confirmatory test and detects the genetic material of the virus (i.e., viral
RNA) providing better accuracy than other rapid tests.
Treatment

• Empirical treatment is recommended in patients who present after the onset of fever
and cough during influenza season who are at high risk for complications (e.g., young
children, adults 65 years of age and older, pregnant women, presence of asthma, heart
disease, diabetes, and other comorbidities).
• Empirical treatment is also recommended for severely ill patients who are hospitalized
and at high risk for complications of influenza.

• Treatment: Neuraminidase inhibitors (e.g., oseltamivir, zanamivir) are recommended for

treatment when initiated in the first 48 hours after symptom onset.
• Peramivir is a new neuraminidase inhibitor approved for intravenous administration for
influenza infection.
• Secondary bacterial pneumonia with Staphylococcus aureus or Streptococcus pneumoniae is a
complication of influenza infection.

• Annual influenza vaccination is recommended for everyone older than 6 months of age in the United
States.

• Inactivated and recombinant influenza vaccines are recommended while the intranasal vaccine is not.

• Chemoprophylaxis is recommended in patients

• Who present within 48 hours of exposure to an infected person.
• Who are at high risk of developing complications from influenza and have not been vaccinated.
• Who have been vaccinated within the past 2 weeks.
• Who are severely immunosuppressed.
Respiratory syncytial virus

• RSV is a well-recognized cause of morbidity and

mortality in immunocompromised individuals.

• Disease can range from a bronchiolitis or mild URI

to a more fulminant lower respiratory tract infection
(LRTI).

• RSV is a leading cause of viral LRTI in

immunocompromised children and adults.

• RSV usually begins with signs and symptoms of a

URI, which can progress to bronchiolitis,
pneumonitis, and pneumonia.
 - Necrosis of epithelial cells
- Infiltration with T cells and monocytes around arterioles
- Infiltration with neutrophils between the vascular structures and small airways

Airway obstruction

Pathophysi
Air trapping
Increased airway resistance
Neutrophilia in bronchoalveolar lavage

ology
The cytokines interleukin (IL)-8, IL-6, tumor necrosis factor (TNF)-alpha, and IL-1 beta
can be detected in airway secretions of infected children

IL-6 levels correlate with severe disease

Chemokines:
chemokine ligand (CCL)3 (macrophage inflammatory protein-1 [MIP-1 alpha]), CCL2
(monocyte chemoattractant protein-1 [MCP-1]), CCL11 (eotaxin), and CCL5 (RANTES
[regulated on activation, normal T cell expressed and secreted])
Clinical manifestations
• RSV can cause severe lower respiratory tract
disease, including bronchiolitis, bronchospasm,
pneumonia, and acute respiratory failure in
children
• Bronchiolitis is a clinical syndrome of
respiratory distress that occurs primarily in
children younger than two years of age and
generally presents with fever (usually
≤38.3°C [101°F]), cough, and respiratory
distress (eg, increased respiratory rate,
retractions, wheezing, crackles).

• 20 percent of infants develop RSV-associated

wheezing during the first year of life; 2 to 3
percent require hospitalization 

• RSV can also cause apnea in infants

Diagnosis
• Clinical suspicion
• Epidemiologic features (eg, age <12 months, lower respiratory tract disease, winter season, known
circulation of RSV)
• Serology testing
• Not widely used
• Acude and convalescent phase serology paired with PCR increases the diagnostic yield
• Point-of-care tests
• Antigen detection
• Variable sensitivity –second generation POC tests improved their sensitivity
• Molecular tests
• high sensitivity
• Viral culture
• The standard for definitive diagnosis is isolation of RSV in human epithelial type 2 (HEp-2) cells.
RSV treatment
• Both standard and contact precautions are needed for
hospitalized patients with RSV.

• Treatment of RSV must take into consideration the

patient’s risk of developing more serious disease.

• Ribavirin is a potential treatment option with limited

efficacy data.

• Palivizumab is another option on the market that is a

humanized monoclonal antibody designed to reduce
RSV infections
 Parainfluenza Virus (PIV)
• PIV are the major causes of croup or laryngotracheobronchitis in young
children.
• PIVs are single-stranded, enveloped RNA viruses belonging to the
genus Paramyxovirus.
• Serotype PIV-1 usually causes outbreaks biennially during the fall of odd-
numbered years. In contrast, PIV-2 and PIV-3 occur in annual epidemics in the
fall and spring, respectively.

• PIV has also been identified as causing disease in adult

immunocompromised patients.
• PIVS are transmitted from person to person, primarily via inhalation of large
droplets or fomites

• There is no proven treatment for PIV infection.

• PIV infection has been demonstrated to be a risk factor for airflow
decline and a cause of long-term pulmonary complications in
hematopoietic stem cell transplant (HSCT) recipients.
 Viral antigen can be detected in the apical
initially infect epithelial cells of the nose Viral replication rises significantly in the
portion of respiratory epithelial cells from
and oropharynx and can spread distally to first 24 hours following initial infection,
days 1 to 6 of infection with a decrease on
the large and small airways peaking at approximately two to five days 
day 7

PIV-1 and PIV-2 replicate efficiently in the The host immune response is likely to play
upper airway epithelium and are typically an important role in the pathogenesis of
PIV-3 replicates in the lower respiratory
associated with upper respiratory PIV
tract, and infection can lead to
infections (URIs) and croup (which results
bronchiolitis and pneumonia Minimal cellular damage results from
from laryngeal and upper tracheal
inflammation)  direct viral effects

The increase in airway responsiveness (eg,

bronchospasm) that is often associated
with PIV-3 infection (and other respiratory
viruses such as respiratory syncytial virus)
may result from increased stromal
interleukin-11 production, enhanced
acetylcholine release, and increased
release of leukotrienes
Clinical manifestations
• Vary based on the patient's age and immune status as well as the
infecting PIV serotype.
• Upper respiratory infections (URIs) and acute bronchitis are the most
common clinical manifestation of PIV infection in adults. 
• fever, rhinorrhea, cough, and/or sore throat
• Croup, occur more commonly in children.
• Prolonged cough is typically a dominant symptom of PIV-associated acute
bronchitis. Wheezing and mild dyspnea may accompany the cough.
• Infection progresses to involve the lower respiratory tract, particularly
in older and immunocompromised adults
Diagnosis
• For most immunocompetent outpatients with mild respiratory tract infections
TESTING IS NOT NECESSARY

• Polymerase chain reaction (PCR) is the preferred testing method, it has

higher sensitivity than culture or antigen detection assays
• Most PCR assays detect serotypes 1, 2, and 3 reliably.

• Culture and serology are not widely available and have long turnaround times.
• Rapid antigen testing kits are also not routinely available and have only
moderate sensitivity 
Treatment
• Supportive care: supplemental oxygen, bronchodilators
• Reduction of immunosuppression (if immunocompromised)
• Close monitoring and prompt treatment for secondary infections 

• Vaccine development — There is no licensed vaccine to prevent

infection with PIVs, although vaccine development is underway
Adenovirus

• Adenoviruses are DNA viruses that usually cause self-limited

disease in normal hosts.
• AdV has been described with respiratory, gastrointestinal, and
conjunctival infections.
• AdV can cause end-organ disease and disseminated infections in
patients who are recipients of stem cell and solid organ
transplants.
• In HSCT recipients, AdV infections have been specifically
associated with the following:
• T-cell depleted graft recipients.
• Acute graft versus host disease.
• Transmission can occur via aerosol droplets, the fecal-oral route,
and by contact with contaminated fomites. 
• Real-time PCR has been useful for monitoring patients with
disseminated AdV infection
• Cidofovir has been shown to be active against all strains of AdV
during in vitro testing and has been used to treat AdV infections.
 Pathogenesis

Serotype-specific clinical
Fatal adenovirus infections occur
manifestations may be partially
Adenoviruses are immunogenic most commonly in
determined by differences in cell
and elicit strong innate and immunocompromised patients,
tropism, manifested by their
adaptive immune responses. especially those with defects in
binding to different cellular
cell-mediated immunity
receptors.

Adenoviruses express early

Viral DNA replication takes
regulatory proteins under the Virions are then assembled in
place after expression of the
control of the early region 1A the nucleus and released when
early proteins, followed by
(E1A). E1A is a trans-activating the cell dies. This process of
synthesis of late structural viral
region that controls expression virus release is facilitated by the
proteins and inhibition of host
from the other early regions E1B, E3 region 11.6K protein
protein synthesis
E2, E3, and E4.
Clinical
manifestations
• Vary according to the age and
immunocompetence of the host
• Adenoviruses are among the most
common viruses isolated from young
children with febrile respiratory illnesses.
The usual duration of illness is five to
seven days, although symptoms may
persist for up to two weeks. Bacterial
superinfections can occur.
• A number of adenovirus serotypes (1, 2, 3,
4, 5, 7, 14, 21, and 35) have been reported
to cause pneumonia
• Pharyngoconjunctival fever is a classic
adenoviral syndrome that consists of a
benign follicular conjunctivitis often
accompanied by a febrile pharyngitis and
cervical adenitis. 
Diagnosis
• Viral culture, adenovirus-specific viral antigen assays, and polymerase
chain reaction (PCR) assays are used most frequently.
Diagnosis
Treatment
• Most adenovirus infections are self-limited and treatment is supportive.
• However, adenovirus infections can be fatal in neonates and
immunocompromised hosts and rarely in healthy children and adults.
• Antiviral therapy is generally reserved for patients with severe
adenovirus disease, the majority of whom are immunocompromised.
• Cidofovir has been the antiviral agent most frequently used to treat adenovirus
infections, but severe nephrotoxicity is a major dose-limiting toxicity. 
• Brincidofovir, an experimental lipid ester of cidofovir that has lower potential for
nephrotoxicity than cidofovir, is being studied for adenovirus but is no longer
available for use through an expanded access protocol
• Prevention of adenovirus transmission requires decontamination of
environmental surfaces and instruments with agents such as
chlorine, formaldehyde, or heat; adenoviruses are not susceptible to
alcohol, ether, or many other commonly used disinfectants.

• Hospitalized patients with gastrointestinal, conjunctival, and

respiratory adenovirus infection should be placed on contact
precautions
Coronavirus

• Coronaviruses normally cause mild

respiratory infections in humans but can
occasionally lead to more severe infections.
• Coronaviruses also infect many animals and
have crossed over to humans (e.g., severe
acute respiratory syndrome [SARS] and
Middle East respiratory syndrome [MERS]).
Coronavirus
• SARS was originally identified in Guangdong Province of the
People’s Republic of China, spread to Hong Kong, and then to
the rest of the world.
• A rapid public health effort was coordinated by the WHO and
transmission ceased throughout the world.
• Infection control work dedicated to contact and droplet
spread was used successfully to control the outbreak.
• MERS coronavirus was discovered when a man was admitted
in 2012 to a hospital in Saudi Arabia with the presentation of
acute pneumonia and renal failure.
• More cases were subsequently discovered in individuals living
in or traveling in the Middle East.
• SARS-CoV-2 was originally described in Wuhan, China, causes
COVID-19.
Coronaviruses
• The coronavirus subfamily is further classified into four genera: alpha,
beta, gamma, and delta coronaviruses.
• The human coronaviruses (HCoVs) are in two of these genera: alpha
coronaviruses (HCoV-229E and HCoV-NL63) and beta coronaviruses
(HCoV-HKU1, HCoV-OC43, Middle East respiratory syndrome
coronavirus [MERS-CoV], the severe acute respiratory syndrome
coronavirus [SARS-CoV]), and SARS-CoV-2
• They are medium-sized enveloped positive-
stranded RNA viruses whose name derives from
their characteristic crown-like appearance in
electron micrographs 
• The spike (S) protein projects through the viral
envelope and forms the characteristic spikes in the
coronavirus "crown: mediates receptor binding and
fusion with the host cell membrane.
• The membrane (M) protein has a short N-terminal
domain that projects on the external surface of the
envelope 
• The nucleocapsid protein (N) associates with the
RNA genome to form the nucleocapsid. 
Binding receptors

• The alphacoronavirus genus includes two human virus species, HCoV-

229E and HCoV-NL63. HCoV-229E, like several animal
alphacoronaviruses, utilizes aminopeptidase N (APN) as its major
receptor 

• SARS-CoV and SARS-CoV-2 (betacoronaviruses), uses angiotensin-

converting enzyme-2 (ACE-2)
Clinical manifestations
• Respiratory syndromes
• URTI
• LRTI: pneumonia
• Gastrointestinal syndromes

• Possible associations:
• Neurologic disease:
• clear involvement of several animal coronaviruses in acute and chronic neurologic
disease has stimulated a search for similar pathogenicity of human coronaviruses. 
• Kawasaki disease
Diagnosis • Clinical
• Respiratory PCR panel
•Bacteria
• Bordetella
(mostly RNA) pertussis
• Virus • Mycoplasma
• Adenovirus pneumoniae
• Coronavirus • Chlamydophila
pneumoniae
• Metapneumovirus
• Influenza
• Parainfluenza
• Coronavirus
• Rhinovirus
• Respiratory
syncytial virus
Treatment
• Supportive mostly
• Some antivirals

• Antibacterial drugs are ineffective

against viral pathogens, and
prophylaxis against secondary
bacterial infections is not
recommended. 
Antivirals: specific
viral illnesses
• Oseltamivir and zanamivir are effective
for influenza.
• Ribavirin, a guanosine analog that
inhibits replication of many RNA and
DNA viruses, may be considered for
severely immunocompromised
patients with lower respiratory tract
infection due to RSV.
• Palivizumab, a monoclonal antibody to
RSV fusion protein, is being used
to prevent RSV infection in certain
high-risk infants