Upper respiratory tract infections

18 Upper respiratory tract infections


The mucociliary system and the flushing action of saliva are defences against upper respiratory tract infection

The air we inhale contains millions of suspended particles, including microorganisms, most of which are harmless. However, the air may contain large numbers of pathogenic microorganisms if someone is near an individual with a respiratory tract infection. Efficient cleansing mechanisms (see Chs 9 and 13) are therefore vital components of the body’s defence against infection of both the upper and lower respiratory tract. Infection takes place against the background of these natural defence mechanisms, and it is then appropriate to ask why the defences have failed. For the upper respiratory tract, the flushing action of saliva is important in the oropharynx and the mucociliary system in the nasopharynx traps invaders. As on other surfaces of the body (see Ch. 8), a variety of microorganisms live harmoniously in the upper respiratory tract and oropharynx (Table 18.1); they colonize the nose, mouth, throat and teeth and are well adapted to life in these sites. Normally they are well-behaved guests, not invading tissues and not causing disease. However, as in other parts of the body, resident microorganisms can cause trouble when host resistance is weakened.

Table 18.1 The normal flora of the respiratory tract

Type of residenta Microorganism
Common residents (>    50% of normal people) Oral streptococci
Neisseria spp. Branhamella
Anaerobic cocci (Veillonella)
Fusiform bacteriab
Candida albicansb
Streptococcus mutans
Haemophilus influenzae
Occasional residents (<    10% of normal people) Streptococcus pyogenes
Streptococcus pneumoniae
Neisseria meningitidis
Uncommon residents (<    1% normal people) Corynebacterium diphtheria
Klebsiella pneumoniae
E. coli
C. albicans imageEspecially after antibiotic treatment
Residents in latent state in tissues:c
Lymph nodes, etc.
Sensory neurone/glands connected to mucosae
Pneumocystis jiroveciid
Mycobacterium tuberculosis
Cytomegalovirus (CMV)
Herpes simplex virus
Epstein–Barr virus

a All except tissue residents are present in the oronasopharynx or on teeth.

b Present in mouth; also Entamoeba gingivalis, Trichomonas tenax, micrococci, Actinomyces spp.

c All except M. tuberculosis are present in most humans.

d Formerly P. carinii.

The upper and lower respiratory tracts form a continuum for infectious agents

We distinguish between upper and lower respiratory tract infections, but the respiratory tract from the nose to the alveoli is a continuum as far as infectious agents are concerned (Fig. 18.1). There may, however, be a preferred ‘focus’ of infection (e.g. nasopharynx for coronaviruses and rhinoviruses); but parainfluenza viruses, for instance, can infect the nasopharynx to give rise to a cold, as well as the larynx and trachea resulting in laryngotracheitis (croup), and occasionally the bronchi and bronchioles (bronchitis, bronchiolitis or pneumonia).

Two useful generalizations can be made about upper and lower respiratory tract infections:

1. Although many microorganisms are restricted to the surface epithelium, some spread to other parts of the body before returning to the respiratory tract, oropharynx, salivary glands (Table 18.2).

2. Two groups of microbes can be distinguished: ‘professional’ and ‘secondary’ invaders.

Table 18.2 Two types of respiratory infection

Type Examples Consequences
Restricted to surface Common cold viruses
Streptococci in throat
Chlamydia (conjunctivitis)
Candida albicans (thrush)
Local spread
Local (mucosal) defences important
Adaptive (immune) response sometimes too late to be important in recovery
Short incubation period (days)
Spread through body Measles, mumps, rubella
Chlamydophila psittacia
Q fever
Little or no lesion at entry site
Microbe spreads through body, returns to surface for final multiplication and shedding, e.g. salivary gland (mumps, CMV, EBV), respiratory tract (measles)
Adaptive immune response important in recovery
Longer incubation period (weeks)

After entry via the respiratory tract, microbes either stay on the surface epithelium or spread through the body.

a Formerly Chlamydia psittaci; CMV, cytomegalovirus; EBV, Epstein–Barr virus.

Professional invaders are those that successfully infect the normally healthy respiratory tract (Table 18.3). They generally possess specific properties that enable them to evade local host defences, such as the attachment mechanisms of respiratory viruses (Table 18.4). Secondary invaders only cause disease when host defences are already impaired (Table 18.3).

Table 18.3 The two types of respiratory invader – professional or secondary

Type Requirement Examples
Professional invaders (infect healthy respiratory tract) Adhesion to normal mucosa (in spite of mucociliary system) Respiratory viruses (influenza, rhinoviruses)
Streptococcus pyogenes (throat)
Strep. pneumoniae
Chlamydia (psittacosis, chlamydial conjunctivitis and pneumonia, trachoma)
  Ability to interfere with cilia Bordetella pertussis, M. pneumoniae, Strep. pneumoniae (pneumolysin)
  Ability to resist destruction in alveolar macrophage Legionella, Mycobacterium tuberculosis
  Ability to damage local (mucosal, submucosal) tissues Corynebacterium diphtheriae (toxin), Strep. pneumoniae (pneumolysin)
Secondary invaders (infect when host defences impaired) Initial infection and damage by respiratory virus (e.g. influenza virus) Staphylococcus aureus; Strep. pneumoniae, pneumonia complicating influenza
  Local defences impaired (e.g. cystic fibrosis) Staph. aureus, Pseudomonas
  Chronic bronchitis, local foreign body or tumour Haemophilus influenzae, Strep. pneumoniae
  Depressed immune responses (e.g. AIDS, neoplastic disease) Pneumocystis jirovecii, cytomegalovirus, M. tuberculosis
  Depressed resistance (e.g. elderly, alcoholism, renal or hepatic disease) Strep. pneumoniae, Staph. aureus, H. influenzae


Rhinoviruses and coronaviruses together cause more than 50% of colds

Viruses are the most common invaders of the nasopharynx, and a great variety of types (Table 18.4) are responsible for the symptoms referred to as the common cold. They induce a flow of virus-rich fluid which is called rhinorrhoea from the nasopharynx, and when the sneezing reflex is triggered, large numbers of virus particles are discharged into the air. Transmission is therefore by aerosol and also by virus-contaminated hands (see Ch. 13). Most of these viruses possess surface molecules that bind them firmly to host cells or to cilia or microvilli protruding from these cells. As a result, they are not washed away in secretions and are able to initiate infection in the normally healthy individual. Virus progeny from the first-infected cell then spread to neighbouring cells and via surface secretions to new sites on the mucosal surface. After a few days, damage to epithelial cells and the secretion of fluid containing inflammatory mediators such as bradykinin lead to common cold-type symptoms (Fig. 18.2).

Pharyngitis and tonsillitis

About 70% of acute sore throats are caused by viruses

Microorganisms that cause sore throats (acute pharyngitis) are listed in Table 18.5. Those viruses that infect the upper respiratory tract inevitably encounter the submucosal lymphoid tissues that form a defensive ring around the oropharynx (see Fig. 18.1). The throat becomes sore either because the overlying mucosa is infected or because of inflammatory and immune responses in the lymphoid tissues themselves. Adenoviruses are common causes, often infecting the conjunctiva as well as the pharynx to cause pharyngoconjunctival fever. Epstein–Barr virus (EBV) and cytomegalovirus (CMV) multiply locally in the pharynx (Fig. 18.3), and herpes simplex virus (HSV) and certain coxsackie A viruses multiply in the oral mucosa to produce a painful local lesion or ulcer. Certain enteroviruses (e.g. coxsackie A16) can cause additional vesicles on the hands and feet and in the mouth (hand, foot and mouth disease; Fig. 18.4).

Table 18.5 Microorganisms that cause acute pharyngitis

Organisms Examples Comments
Viruses Rhinoviruses, coronaviruses A mild symptom in the common cold
  Adenoviruses (types 3,4,7,14,21) Pharyngoconjunctival fever
  Parainfluenza viruses More severe than common cold
  Influenza viruses, cytomegalovirus Not always present
  Coxsackie A and other enteroviruses Small vesicles (herpangina)
  Epstein–Barr virus Occurs in 70–90% of glandular fever patients
  Herpes simplex virus type 1 Can be severe, with palatal vesicles or ulcers
Bacteria Streptococcus pyogenes Causes 10–20% of cases of acute pharyngitis; sudden onset; mostly in 5–10-year-old children
  Neisseria gonorrhoeae Often asymptomatic; usually via orogenital contact
  Corynebacterium diphtheriae Pharyngitis often mild, but toxic illness can be severe
  Haemophilus influenzae Epiglottis
  Borrelia vincentii plus fusiform bacilli Vincent’s angina; commonest in adolescents and adults

Cytomegalovirus infection

Cytomegalovirus can be transmitted by saliva, urine, blood, semen and cervical secretions

Cytomegalovirus is the largest human herpesvirus (Fig. 18.5) and is species specific; humans are the natural hosts. Cytomegalovirus refers to the multinucleated cells, which together with the intranuclear inclusions, are characteristic responses to infection with this virus. CMV was originally called ‘salivary gland’ virus and is transmitted by saliva and other secretions. In addition, CMV can be transmitted by sexual contact, as semen and cervical secretions may also contain this virus, and by blood transfusions (although leukodepletion reduces the risk significantly) and organ transplants from CMV antibody-positive donors. The CMV load will be high in the urine from babies with congenital CMV infection and careful hand washing and disposal of nappies will reduce the risk of transmission to susceptible individuals. CMV can be detected in breast milk, but this is of doubtful significance in transmission.

Cytomegalovirus infection is often asymptomatic, but can reactivate and cause disease when cell-mediated immunity (CMI) defences are impaired

After clinically silent infection in the upper respiratory tract, CMV spreads locally to lymphoid tissues and then systemically in circulating lymphocytes and monocytes to involve lymph nodes and the spleen. The infection then localizes in epithelial cells in salivary glands and kidney tubules, and in cervix, testes and epididymis, from where the virus is shed to the outside world (Table 18.6).

Table 18.6 The effects of cytomegalovirus (CMV) infection

Site of infection Result Comment
Salivary glands Salivary transmission Via kissing and contaminated hands
Tubular epithelium of kidney Virus in urine Probable role in transmission by contaminating environment
Cervix, testis/epididymis Sexual transmission Up to 107 infectious doses/ml of semen in an acutely infected male
Lymphocytes, macrophages Virus spread through body via infected cells
Mononucleosis may occur
Immunosuppressive effect
imageProbable site of persistent infection
Placenta, fetus Congenital abnormalities Greatest damage in fetus after primary maternal infection rather than reactivation

CMV is a ‘well-behaved parasite’, causing little or no damage to the host unless it infects the fetus or placenta to cause congenital abnormalities or it reactivates following depressed cell-mediated immunity (post-transplant, immunosuppression) to cause viraemia, fever, hepatitis or pneumonia.

Infected cells may be multinucleated or bear intranuclear inclusions, but pathologic changes are minor. The virus inhibits T-cell responses, and there is a temporary reduction in their immune reactivity to other antigens.

Although specific antibodies and CMI responses are generated, these fail to clear the virus (see Ch. 16), which often continues to be shed in saliva and urine for many months. The infection is, however, eventually controlled by CMI mechanisms, although infected cells remain in the body throughout life and can be a source of reactivation and disease when CMI defences are impaired.

CMV owes its success in our species to its ability to evade immune defences. For instance, it presents a poor target for cytotoxic T (Tc) cells by interfering with the transport of major histocompatibility complex (MHC) class I molecules to the cell surface (see Ch. 10), and it induces Fc receptors on infected cells (see Ch. 16).

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Jul 9, 2017 | Posted by in MICROBIOLOGY | Comments Off on Upper respiratory tract infections

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