Host-Parasite Relationships

    The concept that disease could be caused by entities too small to see with the naked eye was first proposed in the sixteenth century by the Italian scholar Girolamo Fracastoro .  Though he did not know of the existence of microorganisms, he believed that tiny "seeds" of illness could be passed from one organism to another.  This was not a wholly fantastic idea for his time, since many also believed in the concept of spontaneous generation, and that diseases were attributable to such phenomena as bad blood and gasses  in the atmosphere.  The term malaria, for example, is derived from the Latin for "bad air".  However, with the advent of the microscope and the work of others, by the Nineteenth Century it was understood that microorganisms such as bacteria were indeed the causitive agents of many illnesses.

     In the nineteenth century, Robert Koch would develop a series of steps or postulates, which he used to determine the etiologic (causitive) agent of the disease anthrax.  Koch, like Frederich Cohn, Jacob Henle, Louis Pasteur, and others, was convinced that bacteria and other microbes were responsible for illness.  This germ theory of disease was one of the great concepts to become established during the golden age of microbiology.  Koch's Postulates could be used to show cause and effect relationships between the disease and its agent:

1. The suspected pathogen must be found in all individuals suffering from the disease, but not in
    healthy individuals.

2. The suspected pathogen must be isolated and grown as a pure culture outside of its host.

3. If the suspected pathogen is introduced into the body of healthy test subjects, they should
    manifest clinical signs of the same disease as the original infected population.

4. The suspected pathogen must be re-isolated from the test subject and shown to be identical
    to the original suspected pathogen.

Colonization, Virulence, and Pathogenicity

Colonization vs. Disease
     Infection occurs when microorganisms contact the body of a host.  Colonization occurs if, after contact, the organisms establish themselves in or on the body of the host.  There are two types of colonization: (1) transient colonization, wherein the organisms only temporarily reside on the body of a host and are removed by mechanical means such as the sloughing away of dead skin cells or washing, and (2) resident colonization, wherein organisms become permanently established in or on the body, as in the case of resident microflora (often called normal flora) of the skin, oral cavity, and gastrointestinal tract.

     Disease refers to any adverse change away from the normal homeostatic balance.  Disease may be triggered by exposure to damaging physical factors such as radiation, chemical agents which trigger adverse changes in the structure or function of cells or tissues, genetic malfunctions or inherited genetic conditions which trigger damage to the individual, or infection by pathogenic microbes such as viruses, bacteria, protists, or fungi.  Disease only follows infection, however, if the presence of the microbe causes adverse host reactions which damage cells and tissues, or if the products of microbial metabolism or reproduction damage or destroy host tissues.  Infection is therefore distinct from disease.

Symbiotic Relationships
      The body of any multicellular organism serves as a host to a multitude of different microbial forms.  The microbial complement inhabiting the body are referred to as normal microflora or normal flora, terms which date to a time when bacteria were still considered part of the plant kingdom.  The relationships owing to this colonization can be considered either commensualistic, mutualistic, or parasitic, and the likelihood of the establishment of disease depends on the type of relationships which are established.  Commensals are organisms which live in or on the body of a host, do no harm in this association, but conversely do no good either, such as the Staphylococcus epidermidis and the diptheroid bacteria which live on the surface of the skin.  Mutuals form beneficial relationships with their hosts, such as many of the bacteria of the gastrointestinal tract which synthesize vitamin K, riboflavin, and biotin used by the host in return for nutrients and a warm, moist habitat.  Many of the same bacteria inhibit the growth of opportunistic pathogens (usually commensals which can trigger disease if allowed to exceed small population sizes) such as the fungal agent of yeast infections, Candida albicans, by competitive exclusion or the release of inhibitory chemical compounds.  Parasites, unlike commensals or mutuals, live in or on the body of the host and do it harm.  These organisms are usually not part of the normal microflora component, but find ways to establish themselves and either directly or indirectly cause damage to host tissues.  Some pathogenic microorganisms are parasites which have evolved along with at least one host species, and in so doing have found ways to overcome many of the host defense mechanisms.  These organisms often cause serious and persistant diseases.

Virulence and Pathogenicity

     Pathogenicity refers to the capability to cause disease.  To be considered a pathogen, an organism must be capable of infection, and once established, triggerring a sequence of events which result in disease.  Virulence is a measurement of the degree of pathogenicity, composed of infectivity (the ability to establish and colonize), and severity (the degree of host damage caused by the presence and activity of the infective agent).
Virulence Factors
     Those attributes an organism has which enables it to be a pathogen are called virulence factors.  These include attachment factors, spreading factors, growth and survival factors, and toxic factors.  Attachment factors enable a microorganism to adhere to the surface of cells or tissues and prevent it from becoming dislodged.  Examples of these include hemagluttinin receptor spikes on the envelope of some of the orthomyxoviruses such as influenza A, fimbriae (attachment pili), slime layers (glycocalyces) produced by various bacteria, adhesive discs produced by some protists such as Giardia lamblia, and hooks and suckers used by large multicellular parasites such as tapeworms and leeches.  Spreading factors are chemical compounds which enable microorganisms to spread between layers of cells and tissues, or to elude some nonspecific forms of host resistance.  Examples include exoenzymes such as hyaluronidase, collagenase, and lecithinase produced by Clostridium perfringens to destabilize plasma membranes and break down extracellular matrix which holds tissues together, and fibrolysins produced by clostridia, pathogenic staphylococci and streptococci to break down fibrin clots in the bloodstream.  Growth and survival factors enable a pathogen to take from the host those nutrient compounds it needs for reproduction and to prevent destruction due to host defenses and artificial agents used to limit and stop microbial growth.  These include siderophores, chemical compounds which sequester elemental iron, which is necessary for the replication of some microorganisms, capsules, which help cells clump together and form aggregates too large for phagocytosis by macrophages and other host cell types, and resistance enzymes such as the b-lactamases produced by penicillin and cephalosporin-resistant bacterial species.  Toxic factors are chemical compounds which when released from the pathogen cause host cell and tissue damage.  Examples of these include endotoxins such as the lipopolysaccharide A (lipid A) component of the outer cell membrane of some Gram negative bacteria, which can trigger vasodilation leading to shock once released by cell lysis, exotoxins such as botulin, a neurotoxin produced by Clostridium botulinum, diptheria toxin produced by Corynebacterium diptheriae, tetanus toxin produced by Clostridium tetani, hemolysins which break down red blood cells and release iron from hemoglobin, and fungal mycotoxins, such as aflatoxin produced by some Aspergillus species, ergot toxin produced by Claviceps purpurea, and a-amanitin, produced by Amanita species mushrooms.

How Diseases are Spread

Initiation of Disease
     As previously stated, virulence is associated with infectivity.  Infectivity is measured in terms of the infectious dose, i.e. the number of microbes which is necessary to initiate establishment of a growing colony.   In general, the lower the infectious dose, the more virulent a pathogenic species is.  If the potential host is compromised, meaning that its immune response has been lessened by some other factor, the normal infectious dose can be reduced and the likelihood of infection and disease can be greatly increased.

     Those outside influences which can compromise a potential host are called predisposing factors, which are either behavioral or environmental.  Behavioral predisposing factors include smoking, overeating, poor hygenic practices and food handling techniques, indiscriminant I.V. drug use, and engaging in sexual activities without taking proper precautions against direct contact with potential pathogens.  Environmental predisposing factors include air and water pollution, exposure to radiation emitted either artificially by devices such as microwaves or naturally via ultraviolet radiation from sunlight, and contact with the carriers or vectors of infectious disease such as arthropods, mammals, and contagious humans.

     Some pathogenic microbes have the ability to form pockets of infection which become chronic, leading to development of carriers who do not exhibit visible signs of disease.  Salmonella cholersesuis var. typhimurium, a pathogen responsible for food infections, can reside in the liver and gizzard of birds such as chickens and pass through the shell of the egg while it is still housed in the cloaca.  This is because the shell does not harden until after it leaves the body.  Since the bird shows no visible sign of disease, it can infect any human who consumes it if the flesh is not properly handled and thoroughly cooked.  Also, if the egg is not properly cooked, it can serve as a source of infection.  In humans, pathogens such as Salmonella typhi and Trichmonas vaginalis can be passed by carriers as well.  Trichomonas is a sexually transmitted protist which causes vaginitis (inflammation of the vaginal canal) in women.  Infection of this protist in the male, however, is asymptomatic.  This means that even if a women is given the proper medication for the infection, she can be re-infected unless both she and her sex partner are treated together.

Expression and Progress of Disease
     The way a disease expresses itself may be directly obvious or may be invisible to the individual attempting to make a diagnosis.  Any outwardly visible aspects like development of lesions, visible pyogenic activity such as in strep throat infections by Streptococcus pyogenes, copious diarrhea, sneezing and coughing, and others, which present themselves as  consequences of the disease process are called signs.  Invisible aspects of the disease which are related by the infected individual to the health care professional such as nausea, headache, and body pains are called symptoms.  The combination of both signs and symptoms is called the disease syndrome.

     Some diseases leave behind cell and tissue damage as they subside.  These residual products of the disease process are called sequelae, and they may inhibit the proper functioning of tissues or organs even long after the pathogen has been eliminated from the body.  Sequale can have a direct and sometimes permanent impact on the health of the individual, and can make the individual more prone to infection by microbes in the future.

     Diseases begin with a period of incubation, which represents the time from initial infection and subsequent colonization, to the first appearance of the disease syndrome.  This period may be relatively brief, two to three days as with some food and waterbourne infections, or as long as several weeks, months, or sometimes years depending on the type of microbe involved, the site of entry, since some microbes infect more quickly closer to the area of the body they most readily colonize, and the level of immune resistance carried by the host.  However, once colonization is established, the host enters the prodromal phase, which is generally a period of dissimated, general symptoms such as headache, fever, and nausea.  This is soon followed by the acme period, which is the most acute stage of the disease.  During this period, visible signs of disease appear, such as rashes, skin and mucus membrane lesion, mucus or fluid discharge, jaundice, and/or high fever.  If the body of the host is sufficiently immunocompetent, the acme period will eventually begin to subside, and the individual will enter convalescence, where the body begins to return to its normal level of homeostasis.

Types of Infections
     Infections occur as either primary or secondary forms.  A primary infection occurs the first time a previously healthy host is exposed to a pathogen, if the microbe colonizes and stimulates disease.  Secondary infections are caused by opportunistic pathogens which are either already part of the normal microflora of the host, or can only infect once bodily defenses have been compromised.  An example of the secondary type which represents a major concern for the health care industry is called the nosocomial infection.  This is hospital-aquired, and is usually transmitted by the health care workers themselves.  Opportunistic pathogens such as enterococci, Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis, and Pseudomonas aeruginosa are carried from place to place on the hands of staff who fail to follow proper sanitary procedures when traveling from one patient to another.  The most serious of the secondary infections is called a superinfection, which can sometimes occur when an opportunistic pathogen establishes itself so firmly that it overwealms and eliminates normal commensal and mutual microflora. Superinfections are extremely difficult ot treat, since they usually are caused by microbes which are resistant to most forms of antibiotic therapy.
Routes of Transmission
     Before infection and disease can occur, a potential pathogen must find some way to enter the body of the host.  Commonly this is via direct contact, wherein the individual becomes exposed to the pathogen which is present either in air as aerosol droplets spread through the coughing and sneezing of infected individuals, or by sexual intercourse, or indirectly, through food which was handled improperly, or contact with contaminated fomites.  Sexual, contact, and food borne transmission could also be considered behavioral, in that these routes could be blocked by simple prevention techniques such as handwashing, abstinence, and prophylaxis.  The parenteral route allows invasion through the protective outer layers of the skin, such as in bites, cuts, invasive surgical procedures, burns, and intravenous drug use.

     In general, the spread of many infectious diseases can be attributed to the four Fs of infection: fingers, fomites, flies, and feces.  Improper sanitary measures such as the washing of hands provides a pathway for microorganisms to be spread from human to human quickly.  Fomites are any nonliving objects an individual might touch, including books, counter surfaces, appliances, and surgical implements which have not been properly disinfected or sterilized prior to contact.  Flies, roaches, and other arthropods which commonly associate themselves with areas inhabited by humans carry diseases either on the hairy surface of their bodies or in their gastrointestinal tracts.  Human feces contaminated with disease-causing microorganisms can be spread through the anal-to-oral route or serve as a source of contamination for improperly sanitized water supplies. Zoonoses are outbreaks of disease carried by animal reserviors, usually mammals associated with arthropod vectors including fleas, lice, biting flies, and ticks.

     The study of the sources and spread of disease is called epidemiology.  The earliest example of this was in 1849, when a English physician named John Snow was asked to determine the source of an outbreak of cholera in London.  He systematically traced the spread of the disease by linking the infected individuals to specific parts of the city, and was suprised to find that almost all of the patients had at one time or the other taken water from a single well.  After he removed the handle from the pump, the incidence of cholera subsided.  He was thus able to establish a cause-and-effect relationship between the occurrence of a disease and its reservior.

     Today, epidemiologists apply demographic and statistical techniques to determine the precise point of origin of a disease and to track its spread.  With luck, a specific index (first) case can be found, which gives the scientist what they need to establish where a disease first appeared.  This can be extremely difficult since geographic barriers which once existed between populations of individuals have been removed by modern modes of mass transportation.  Data gathered is divided into two major categories, morbidity, or the rate of incidence, and mortality, the death rate due to a particular disease.  This data is gathered primarily by the World Health Organization (WHO), and in the United States by the Centers for Disease Control (CDC).  The CDC issues a constantly updated publication called the Morbitity and Mortality Weekly Report (MMWR), both as a magazine and electronically on the World Wide Web to keep epidemiologists, health care workers, and scientists apprised of any new data concerning any cause of disease and death on a constant basis.

How Diseases Spread across Populations
     Diseases which have established themselves in a specific area due to environmental factors such as climate, but which are present with a regular or constant pattern, are said to be endemic.  One example of an endemic disease is African trypanosomaisis, also called African sleeping sickness.  The etiologic (causal) agents of this disease are protists such as Trypanosoma gambiense and T. rhodesiense, which are carried by an arthropod vector, the tse tse fly.  These flies are very sensitive to environmental changes, thus they remain within relatively strict boundaries, keeping the disease local to the area.  Epidemic diseases, however, begin at one site and quickly spread over larger areas.  The black plague, caused by Yersinia pestis, a gram negative member of the Enterobacteriaceae, was carried by the Norwegian rat from the Middle East throughout Europe in the fourteenth century and was responsible for over 25 million deaths.  Pandemic diseases spread worldwide.  In the nineteenth century, the influenza A virus rapidly travelled around the world, killing countless millions.  Currently, the human immunodeficiency virus (HIV) is responsible for a pandemic of acquired immunodeficiency syndrome (AIDS).  With no currently known effective treatment for this viral disease, it is highly likely that it will continue to sweep the globe for some time to come.
Control of Disease
     One can control disease either through prevention or containment.  It is preferable to prevent the spread of disease by keeping it from occurring at all.  This can be accomplished by avoiding contact with infected individuals or reservoirs of infection, proper water and sewage treatment, proper food handling and preparation, and the control of pathogen vectors.  If infection does or has already occurred, the first step in prevention of spread is isolation and quarantine of diseased animals or humans.  Next, the suspected pathogen must be isolated and identified, so treatment options can be considered.  Finally, proper aseptic and antiseptic techniques must be maintained to prevent the nosocomial spread of the agents of infection to others.

Critical Thinking Exercises

1.  It has been hypothesized that the best type of parasite is one which forms a mutualistic
     symbiotic relationship with its host.  Yet, many severe pathogens, such as the ebola virus
     replicate in tissues so rapidly that they almost always kill the host.  Do agree with the idea
     that pathogens eventually must evolve into symbiotic partners?  Defend your answer.

2.  During the disease cycle, which of the periods (incubation, prodromal, acme, convalescence)
     are most likely to be associated with the spread of a contagious pathogen.  Why?

3.  Why is it that contagious diseases such as influenza and AIDS are able to spread so rapidly?
Test Yourself- Use this to quiz yourself about host-parasite relationships.
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