Based on the pathology of the infections caused by these

organisms, they can be categorised as follows:

1. Primary pathogens:
These organisms adhere to the normal mucosa and establish an
infection.
 Example: Influenza virus
INTRODUCTI 2. Secondary pathogens
ON Establish infection only on a damaged mucosal cell
Example: Pneumococci
3. Respiratory pathogens in the immunocompromised:
Opportunistic infections caused by commensal bacteria
Example: Oral thrush (candidiasis in an HIV-infected
individual)
Fig. 22.1 Upper and
lower respiratory
tracts
A. UPPER
RESPIRATORY
TRACT
INFECTIONS
(URIs)
PROTECTIVE MECHANISMS OF THE UPPER
RESPIRATORY TRACT

Ciliary
movement of Hairs in the
the epithelial nostrils
cells

Natural The normal

microbiota of
secretions,
the upper
cough reflex respiratory
and saliva tract

Fig. 22.2 Common microbial agents associated

with URIs (Source: Anurupa Badrinath)
INFECTIONS OF THE UPPER RESPIRATORY
TRACT
1. Common cold
2. Sinusitis
3. Croup: Commonly of viral etiology, e.g., parainfluenza
4. Epiglottitis: Frequently caused by H. influenzae type B
5. Pharyngitis (sore throat)
6. Peritonsillar abscess (quinsy)
7. Tonsillitis: Commonly caused by group A streptococci
Table 22.1
Common
etiological agents
of acute upper
respiratory tract
infections
Pathogenesis depends on the virulence of the organism and comorbidity of the individual
URIs are usually self-limiting illnesses
Complications of URI
acute otitis media (AOM) in children
paranasal sinusitis and pneumonia in adults
Non-specific URI: Non-specific infection associated with mild or acute symptoms
Lasts about a week to 10 days and subsides spontaneously
Treatment: Non-specific, with non-steroidal anti-inflammatory agents, and decongestants
DIAGNOSIS OF Fig. 22.3 Diagnostic algorithm for upper respiratory tract
infections (ASO—antistreptolysin O; EBV—Epstein–Barr

URIs virus; HSV—herpes simplex virus; SDA—Sabouraud

dextrose agar)
 COLLECTION AND TRANSPORT OF SPECIMENS

For infections of viral etiology

Nasopharyngeal swabs, aspirates or throat washings are collected

Serum is collected when streptococcal pharyngitis or infectious mononucleosis is suspected in

order to look for antibodies
VIRAL
CAUSES OF
UPPER
RESPIRATORY
TRACT
INFECTIONS
70% of upper respiratory tract infections are caused by viruses
They are responsible for endemic, epidemic and pandemic outbreaks across the
globe affecting all age groups
Greater risk—those at the extremes of age groups and immunocompromised
individuals
ADENOVIRUSES
Capsid is an icosahedron
Appearance of a space vehicle
Classification
Over 50 serotypes
Human adenoviruses are classified into six groups
based on properties such as hemagglutination, DNA
fragment analysis and oncogenic potential
Relatively stable
Fig. 22.15 Adenovirus: (a) diagrammatic
Readily inactivated at 50°C representation of structure and morphology and (b)
microscopic view
They resist ether and bile salts
PATHOGENICITY Table 22.4 Common syndromes associated with adenovirus infection

Infections of the respiratory tract

Eye
Bladder
Intestine
LABORATORY DIAGNOSIS
Tissue culture
Tissue cultures of human origin such as human embryonic kidney, HeLa or HEp-2
Cytopathic changes: Cell rounding and aggregation into grape-like clusters
Intranuclear inclusions may be seen in stained preparations
Shell vial technique
Serodiagnosis: Rising antibody titre in paired sera
Electron microscopy: For fecal virus detection
Immunofluorescence: Viral antigen detection
PCR-based tests: Detection of viral DNA
MYXOVIRUSES
A group of enveloped RNA viruses characterized by their ability to adsorb onto
mucoprotein receptors on erythrocytes, causing hemagglutination
Two separate families:
i) Orthomyxoviridae, consisting of the influenza viruses,
ii) Paramyxoviridae, consisting of the parainfluenza viruses, Newcastle disease
virus, mumps virus, measles virus and respiratory syncytial viruses
Table 22.5 Distinguishing features of orthomyxoviruses and
paramyxoviruses
INFLUENZA VIRUS
Sporadic, epidemic and pandemic forms of respiratory
infections
Birds, particularly aquatic: Primary reservoir of influenza
viruses
Type A influenza virus comprises animal and human strains
Type B consists of exclusively human viruses
Influenza C contains human and swine viruses
Non-human influenza viruses emergence of pandemic
influenza
MORPHOLOGY
Usually spherical
Core consists of ribonucleoprotein in helical symmetry
The negative-sense single-stranded RNA genome is segmented into eight
pieces
Has viral RNA-dependent RNA polymerase
Nucleocapsid is surrounded by an envelope
Surface membrane protein (matrix or ‘M protein’)—M1 and M2
Projecting from the lipid envelope are two types of spikes—hemagglutinin
(HA) spikes and neuraminidase (NA) spikes
CLASSIFICATION
 Three serotypes—A, B and C—is based on
the antigenic nature of the ‘internal’ or
ribonucleoprotein (RNP) and the matrix (M)
protein antigens
 The influenza virus type A virus is further
divided into subtypes based on the HA and
NA glycoproteins
 15 HA subtypes: H1–H15
 9 NA subtypes: N1–N9
 Human isolates belong to H1–H3, H5 and
N1, N2 subtypes
Fig. 22.16 Influenza virus showing surface protein
hemagglutinin (HA), neuraminidase (NA) and the
segments of ribonucleoprotein and M2 ion channels
(Source: CDC, PHIL, Image ID 17346)
 NOMENCLATURE
SYSTEMS
The standard nomenclature systems include:
Serotype, host of origin (except for human isolates), geographic origin, strain
number & year of isolation, followed by HA and NA subtypes in parenthesis
 For a human isolate: A/Hong Kong/01/68 (H3N2)
 For other host origin: A/swine/Iowa/15/30 (H1N1)
ANTIGENIC
STRUCTURES
RNP antigen
Ribonucleoprotein antigen
Demonstrated by complement fixation & immunoprecipitation tests
Hemagglutinin
Neuraminidase
  Composed of two polypeptides, HA 1 & HA 2
 Responsible for hemagglutination & hemadsorption
 Helps in viral adsorption to mucoprotein receptors on
HEMAGGLUT respiratory epithelial cells
ININ  Strain-specific antigen & capable of great variation
 Fifteen HA subtypes, H1–H15, have been identified
 Strains found in humans are H1, H2, H3 and H5
  Glycoprotein enzyme which destroys cell receptors by
hydrolytic cleavage

NEURAMINID  Inhibit the release and spread of progeny virions

ASE  Strain-specific antigen & exhibits variation

 Nine different subtypes have been identified (N1–N9)
 Only N1 and N2 have been recovered from humans
 Antigenic shift
 An abrupt, drastic & discontinuous variation in the antigenic
structure
 Produces a novel strain, unrelated antigenically to previous
strains
 May involve hemagglutinin, neuraminidase or both
ANTIGENIC  Results in major epidemics or pandemics
VARIATION
Antigenic drift
 The gradual sequential change in antigenic structure
 New antigens, still related to previous strain
 Occurs due to mutation and selection
 Accounts for the periodic epidemics of influenza
 IMMUNITY
An episode of influenza confers effective protection for one or
two years

EPIDEMIOLOGY
Influenza occurs sporadically as epidemics or in pandemic form
The source of infection is an infected individual
Influenza virus type C: Endemic throughout the world
Type B strains: Sporadic as well as epidemic influenza
Type A strains can cause pandemics as well
Ability to cause epidemics and pandemics: After antigenic shift
pandemic strains originate from some animal or avian reservoir

This Photo by Unknown Author is licensed under CC BY-NC-ND

HIGH-RISK GROUPS
Elderly individuals
Diabetics
Persons who have kidney, liver or cardiac disease
Pregnant women
Immunocompromised individuals
Cancer patients

Avian influenza
Highly pathogenic
H5N1 strain
 TRANSMISSION OF
NOVEL STRAINS
 Wild aquatic birds carry genes of all influenza strains
 The viruses do not cause any disease in them or undergo any
mutational changes
 Birds shed the viruses abundantly in feces, which in turn
contaminate lakes and ponds
 Recombination may take place in pigs
 These strains has the potential to reach pandemic proportions

Swine influenza I
 March 2009
 New H1N1 virus
Fig. 22.17 Transmission cycle of avian influenza
 Influenza A, seasonal influenza
virus—human → pig → aquatic bird (waterfowl)
PATHOGENE
SIS
 The route of entry: Respiratory
tract
 Site of viral replication: Ciliated
cells of the respiratory tract
 The viral neuraminidase
facilitates infection

Fig. 22.18 Sequence of events involved in the pathogenesis of influenza

  Incubation period is 1–3 days
 Severity varies from mild coryza to fatal pneumonia
 Most infections are subclinical

CLINICAL Complications
FEATURES Pneumonia: Due to bacterial superinfection
Cardiac complications: Congestive failure or myocarditis
Neurological involvement: Encephalitis
Reye’s syndrome
LABORATORY
DIAGNOSIS
Specimen collection
 Gargling samples, nasal wash or throat swabs (alginate swabs) are collected using virus
transport media

Demonstration of the virus antigen

 Immunofluorescence

Isolation of the virus

 Primary monkey kidney cell cultures
 Amniotic cavity of chick embryos
LABORATORY
DIAGNOSIS
Serology
 Demonstration of a rise in titre of antibodies in paired sera by HAI test

PCR-based diagnosis
 Reverse transcriptase PCR (RT-PCR)
 Highly sensitive & rapid
IMMUNOPROPHYL
AXIS
Inactivated influenza vaccines (IIV)
Subunit vaccine
Recombinant vaccine
Killed vaccine
Indications for IIV: Individuals of six months of age and older, including pregnant women and
persons with chronic medical conditions and other high-risk groups
 Live attenuated (cold-adapted) influenza vaccine (LAIV)
 Indications for live influenza vaccine: persons aged 2–49 years who do not have underlying
medical conditions; the vaccine should not be administered to pregnant women
TREATME
NT
 Approved drugs: Oseltamivir, zanamivir, peramivir & baloxavir
 Zanamivir and oseltamivir, block viral neuraminidase
 Rimantadine or amantadine
 Important pathogens of infants and children
Respiratory syncytial virus
Parainfluenza viruses
Measles virus
Mumps virus
PARAMYXOVI
RUS  Larger and more pleomorphic than orthomyxoviruses
 100 nm to 300 nm in size
 The helical nucleocapsid
 The genome: (-) sense ss RNA (unsegmented)
 Antigenically stable
 ANTIGENIC
STRUCTURE
Hemagglutinin (H)
 Causes adsorption of the virus to the host cell surface
 may also possess neuraminidase (NA) activity;
 Also known HN protein

 F (fusion) protein
 Causes cell-to-cell fusion, forming syncytia

Matrix M protein

Fig. 22.19 Antigenic components of

paramyxoviruses
CLASSIFICATION OF
PARAMYXOVIRUSES
Subfamily Paramyxovirinae
• Respirovirus: Parainfluenza 1 and 3
• Rubulavirus: Parainfluenza 2, 4a, 4b, mumps
• Morbillivirus: Measles
• Henipavirus: Nipah and Hendra

 Subfamily Pneumovirinae
• Pneumovirus: Respiratory syncytial virus
• Metapneumovirus: Human metapneumovirus
PARAINFLUENZA
VIRUS
 Respiratory infections in children & adults
 PI types 1 and 2: Croup, a serious clinical disease
 PI type 3: Bronchitis, bronchiolitis & pneumonia in infants & young children
 Type 4: Minor respiratory illnesses
 LABORATORY DIAGNOSIS
 Specimen
• Throat and nasal swabs
 Virus isolation
• Primary monkey kidney cell cultures or monkey kidney cell lines (LLC–MK2)
 Serology
• Paired sera can be tested by neutralisation, ELISA, HAI or CF for rise in the titre of antibodies
 Molecular diagnosis
• Reverse transcriptase PCR
 MUMPS VIRUS
Epidemiology

 Causative agent of mumps

 Humans are the only natural hosts
 The source of infection: Humans who are infected
 No human carriers or animal reservoirs exist

Route of transmission: Direct or indirect contact, airborne droplets,

fomites contaminated with saliva, and also possibly, urine
CLINICAL
FEATURES
 Incubation period
• 12–25 days
 Inapparent infection:
• Almost 1/3rd of infections are subclinical
 Parotid swelling
• First sign of illness
• Parotid swelling (U/L or B/L)
• Fever, local pain and tenderness
• Fig. 22.20 Parotid gland swelling in a
Resolves within a week
child with mumps (Source: CDC,
PHIL, Image ID 3186)
  Epididymo-orchitis
 Orchitis

COMPLICATI  Meningitis

ONS 
Aseptic meningitis
Meningoencephalitis
 Others: Arthritis, oophoritis, nephritis, pancreatitis, thyroiditis
& myocarditis
LABORATORY
DIAGNOSIS
 Specimen: Saliva, urine, CSF
 Virus isolation: Primary monkey kidney, human amnion and HeLa cells
 Antigen detection: Direct antigen detection by IFA
 Serology:
Demonstration of a rise in the titre in paired serum
IgM-ELISA
 Molecular diagnosis: Reverse transcriptase PCR
 PROPHYLA
XIS
Vaccination
 An effective live virus vaccine is available
 The Jeryl–Lynn strain of the mumps
virus
 Subcutaneous route
 Given alone or in combination with
measles & rubella vaccine
 A quadrivalent MMRV (measles-
mumps-rubella-varicella) combination
vaccine has recently been launched
PNEUMOVIRUS
Respiratory syncytial virus
Metapneumovirus
Respiratory syncytial virus
(RSV)
 RSV is pleomorphic, 150– 300 nm in size
 The viral envelope has glycoproteins: G protein & fusion
(F) protein
 No hemagglutinin, neuraminidase, hemolytic properties
 Propagated on human cell cultures, HeLa & HEp-2
 causes cell fusion and the formation of multinucleated
syncytia in cell cultures
 Highly labile & is inactivated rapidly at room temperature
 Antigenically stable with one serotype

This Photo by Unknown Author is licensed under CC BY-SA

CLINICAL
FEATURES
 The incubation period is 4–6 days
 In infants, infection begins as febrile rhinorrhea, cough, progressing to
tracheobronchitis, bronchiolitis and pneumonia
 Causes otitis media in young children
 May present as febrile common cold in adults
 EPIDEMIOL
OGY
 Outbreaks are common in children’s wards, nurseries & daycare centres
 Most common in children between 6 weeks & 6 months of age
 Transmission: Among close contacts & through contaminated fingers and
fomites
  Specimen: Nasopharyngeal swabs or nasal
washings
 Virus isolation
• HeLa or HEp-2

LABORATORY • In cultured cells, characteristic giant cell and

syncytial formation
DIAGNOSIS  Serology: Demonstration of rising antibody
titres in paired serum samples by ELISA, CF,
neutralisation tests
 PCR
PROPHYLAXIS &
TREATMENT
 No effective vaccine is available

 Management is primarily by supportive care

 Administration of ribavirin by continuous aerosol