clearance mechanisms protect the respiratory tract. Air is humidified and warmed as it is drawn in by passing over the turbinate bones and through the nasal sinuses. Any particles settle on the sticky mucus of the respiratory epithelium and are transported by the cilial ‘conveyor belt’ to the oropharynx where they are swallowed. As a result, only particles with a diameter of less than 5 μm reach the alveoli, so the respiratory tract is dynamically sterile below the carina.
In chronic obstructive pulmonary disease and bronchiectasis, excessive mucus or anatomical derangement means that bacteria are not cleared and patients suffer recurrent respiratory infections with organisms such as Haemophilus or Pseudomonas. The thickened mucus associated with cystic fibrosis creates a similar problem.
Intubation in intensive care bypasses this barrier and allows a direct path to the lungs, facilitating ventilator associated pneumonia. Tobacco smoking, air pollution and cooking on open fires can paralyse the cilia, making those individuals exposed, especially children, to be at increased risk of both infection and severe disease.
Secreted antibacterial compounds include mucus, which contains polysaccharides of similar antigenic structure to the underlying mucosal surface; organisms bind to the mucus and are removed. Other antibacterial compounds secreted by the body include lysozyme in tears, which degrades Gram‐positive bacterial peptidoglycan; lactoferrin in breast milk, which binds iron and inhibits bacterial growth; and lactoperoxidase, a leucocyte enzyme, which produces superoxide radicals that are toxic to microorganisms.
Gastric acid kills ingested organisms and acid suppression increases the risk of intestinal infection. This is a particular risk in intensive care units and is compounded by the use of antibiotics.
Urinary flushing protects the urinary tract, with the flushing action of urinary flow keeping the tract sterile, except near the urethral meatus. Obstruction by stones, tumours, benign prostatic hypertrophy or scarring of the urethra or bladder may cause a reduction of urinary flow and stasis, increasing the risk of subsequent bacterial urinary infection. Urinary catheterization results in chronic colonization of the bladder, which may be followed by sepsis (see Chapter 60). The chronic colonization can make confirming the diagnosis of infection challenging.
Antibiotic treatment Antibiotic administration can change the bacterial flora, especially mucosal anaerobes making the patient more vulnerable to colonization with potentially pathogenic or antibiotic resistant organisms. Once established these replace the normal flora and may go on to cause infection at a later time.
4 Pathogenicity and pathogenesis of infectious disease
Definitions
Humans encounter bacteria, viruses and parasites that do not cause disease. An infection occurs when an organism invades the body and causes ill‐health.
| Term | Definition |
|---|---|
| Pathogen | An organism capable of causing disease |
| Commensal | An organism that is part of the normal flora |
| Pathogenicity | The capacity to cause disease |
| Virulence | The capacity to cause severe disease |
The capsule of Streptococcus pneumoniae is a pathogenicity determinant because acapsulate strains do not usually cause disease, but some capsular types cause more serious disease, i.e. they are more virulent (Chapter 19). The term parasite is often used to describe protozoan and metazoan organisms (see Chapters 49–52), but this is confusing as these organisms may be either pathogens or commensals.
Types of pathogen
Obligate pathogens are always associated with disease (e.g. Treponema pallidum and HIV) i.e., their presence is diagnostic and usually requires action. Some pathogens may cause disease if the conditions are right. For example, Bacteroides fragilis is a gut commensal, but if it accesses the peritoneal cavity through perforation of the viscus it causes severe infection and peritonitis. Opportunistic pathogens usually cause infection when the host defences are compromised. For example, Pneumocystis jiroveci usually causes lung infection only in a host who has severely compromised T‐cell immunity.
Mechanisms of pathogenicity
The process of infection has several stages.
Access to the host: transmission
Organisms are transmitted by various means, but most are adapted to a particular route such as respiratory pathogens. Strains may develop epidemic potential by developing adaptation to an environment that either favours transmission or better survival, for example, most respiratory pathogens induce coughing that facilitates their spread, expelling aerosols of organisms in respiratory droplets. Vomiting and diarrhoea associated with organisms that are spread by the faecal–oral route increases environmental contamination and increases the risk of transmission.
Attachment to the host
Microorganisms attach themselves to host tissues to colonize them, and each species employs a different strategy. The distribution of the receptors to which a particular organism can bind will define the organs that it will infect (its tissue tropism) as in the following examples.
Neisseria gonorrhoeae adheres to the genital mucosa using fimbriae.
Influenza virus attaches to the respiratory mucosa by its haemagglutinin antigen accounting for its species‐specific pathogenesis (the ability of certain strains to cause disease in a particular species, such as avian or porcine strains) and intraspecies variation in affinity and susceptibility (Chapter 40).
Bacterial biofilms aid colonization of indwelling prosthetic devices, such as catheters and the respiratory tract. Some strains of staphylococci have genes that mediate attachment to plastics and to the biological molecules that coat intravascular devices.
Mucosal destruction by viruses may expose a variety of host molecules such as fibronectin, vibronectin and collagen to which invading organisms can bind.
Invasion
Some bacteria have mechanisms that help them get close to the mammalian epithelium. For example, Vibrio cholerae excretes a mucinase to help it reach the enterocyte. Microorganisms have a variety of strategies that allow them to cross mucosal barriers or different types of cell membrane.
Motility
The ability to move in order to locate new sources of food or in response to chemotactic signals enhances pathogenicity. V. cholerae is motile by virtue of its flagellum, and is more virulent than non‐motile strains.
Immune evasion
To survive in the human host, pathogens must overcome the host immune defences.
Respiratory