Pathogens

A disease is a disorder or condition resulting in harm to an organism's structure or function and disturbing its homeostasis (the body's processes to physiologically regulate its internal environment). It does not result directly from external physical injury. Microbial parasites that cause disease are pathogens—any virus, microorganism, or other substance capable of causing disease. There are bacterial, viral, fungal, and other eukaryotic pathogens, in addition to pathogens called prions, which are proteinaceous infectious particles. Pathogenicity is the capacity to cause disease. The pathogenicity of an organism is dependent on context: physical location, physiological state of the pathogen, immunological state of the host, and presence of other organisms. Virulence is the relative extent or severity of disease caused by a pathogen; it refers to its ability to colonize host tissue and the severity of harm or disease it causes. As pathogenicity is context dependent, virulence is related to particular genetic elements carried by the pathogen, the number of invading pathogens, and their ability to multiply within the host.

The host-pathogen interaction is dynamic and always changing. For example, every exposure to a pathogen does not result in the host becoming ill. Assuming a normally functioning immune system, the host can fight off the pathogen. However, if the host's immune system is compromised, for example, the host is actively fighting an upper respiratory adenovirus infection, then certain resident bacteria such as Streptococcus pneumoniae begin to flourish and cause an infectious sinusitis. In this way, the resident bacterium becomes opportunistic, taking advantage of a weakened immune system to evade the body's natural defenses.

Modes of transmission refer to ways in which a pathogen gains access to a host. Direct modes of transmission include:

• touching
• kissing
• sexual intercourse
• vertical transmission from mother to fetus
• droplet transmission

Indirect modes of transmission include:

• spread of the infectious agent through an intermediate object
• airborne transmission, such as inhalation of fungal spores
• fecal-oral transmission
• vector-borne transmission

Within the host, pathogens must compete with resident microbes for food sources and space. Over 100 trillion bacteria live within the human gut. Pathogens such as Shigella dysenteriae, which can gain entry to human hosts through ingestion, are able to survive and successfully compete against resident bacteria because of their abilities to avoid host defenses. Namely, they are not killed by stomach acid like many other bacteria. Therefore, they begin to multiply in number in the stomach and small intestine. When they reach the large intestine, they invade the epithelial lining, causing inflammation, and they produce enterotoxins, which lead to severe diarrhea and bloody stool. The Shigella organism injects proteins into intestinal cells that aid in the spread of the bacterium from cell to cell. Most cases resolve without treatment in four to eight days, but severe infections can last three to six weeks. Pathogenicity and virulence interact with the host in interesting ways. Some microbes are always pathogens. An example of this is Mycobacterium tuberculosis, the causative agent of tuberculosis, which is responsible for the death of approximately two million people in sub-Saharan Africa per year. Some microbes that are typically pathogenic do not cause disease in some hosts. For example, Plasmodium malariae, the causative agent of malaria, cannot cause malaria in people with sickle-cell trait. A person with sickle-cell trait has one normal hemoglobin gene and one mutated gene resulting in the sickling of red blood cells. The Plasmodium organism infects red blood cells, relying on them for nutrients. However, a sickled red blood cell is a poor source of nutrients for Plasmodium malariae. It leaks nutrients and is selectively eliminated by the liver, thereby greatly reducing the pathogenicity of Plasmodium in these human hosts. On the contrary, some microorganisms not generally considered pathogenic do cause disease in certain hosts. Such is the case with the fungus Cryptococcus neoformans. It lives in the soil throughout the world and rarely causes problems in healthy individuals. However, in people with compromised immune systems, such as those with untreated HIV infection, infection results in a severe meningitis, or inflammation of the brain and spinal cord tissue. Damage from the disease in the host results from actions of the pathogen, the host, or both. If there is a strong immune response to the pathogen, most damage to the host results from the host's own immune response. This is seen in acute retinal necrosis, an inflammatory condition of the retina often caused by the herpes simplex virus. Treatment is geared toward suppressing the infection with antiviral medication and minimizing the inflammatory response through use of corticosteroids. Likewise, if a weaker immune response occurs, most damage to the host is caused by the pathogen. The type of pathogen (viral, bacterial, fungal, or prion) and the immune status of the host complicate or qualify the assessment of pathogenicity. Many commensal microbes live on or within hosts without causing any ill effect. However, under specific conditions, for example, in an immunocompromised host or after gaining access to a new tissue in a host through a cut, some commensal microbes will cause disease. These are opportunistic pathogens. An opportunist is a typically harmless microbe that under the right circumstances will cause infection. A common example of an opportunist is Streptococcus pneumoniae, which causes bacterial pneumonia. This bacterium is a normal resident of the upper respiratory tract. In individuals with weakened immune systems, it is able to multiply and colonize the pulmonary alveoli, triggering an immune response that causes the inflammatory symptoms of pneumonia. Pathogenicity results from the complex interactions of pathogen, host, the genetics of both, the immune system of the host, and the pathway through which the pathogen invades the host.