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Infectious Disease

D. Blicq dblicq@rrc.mb.ca  June 2006  (update 01/04/2010) DIRECTORY I BIO I NOTICE BOARD

Under normal conditions, a healthy individual will have a considerable microbial population living on (and inside) their person. This natural balance is essential to good health - the microbial population of the gastrointestinal tract (G.I.) produce enzymes which facilitate digestion of many compounds. Other naturally "resident flora"  serve to displace pathogenic organisms and protect healthy individuals from infection and disease. In healthy individuals, the resident flora are largely comprised of bacteria (and possibly a few fungi). This relationship is symbiotic - the human and microbial population both benefiting from the circumstance.

 In good health (i.e. a properly functioning immune system) the indigenous microbial population is of significant benefit. In the ill or immuno-compromised, even the formerly symbiotic relationship may change - micro-organisms will adapt to take advantage of any food source or environmental niche. To a certain extent, the healthy human organism is in equilibrium with it's indigenous microflora until such time as this normal symbiotic relationship is disturbed, resulting opportunistic infection.

Other infectious diseases are caused by micro-organisms that the immune system either fails to recognize or is incapable of responding to in an effective manner. Depending on factors such as virulence and mortality there can be severe consequences.

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The Infection

An infection is a pathological condition which results from the invasion of the body by pathogenic microorganisms. The colonization by pathogenic micro-organisms can have a number of negative consequences:

  1. Production of Toxins - many different toxins may be produced with a number of negative effects. The toxins may be cyto-toxic, causing inflammation or other damage to local tissues, or may release toxins in general circulation resulting in systemic damage (botulism, tetanus)

  2. Virulence - virulence describes the extent of pathogenicity of a microorganism as indicated by the severity of the disease produced and its ability to invade the tissues of a host. Virulence factors may negate the effectiveness of the host's immune response by suppressing immune function while others employ enzymes which enhance tissue infiltration or actively destroy immunoglobulins. Other virulence factors slow or partially block the digestive / lytic capacity of the host, thus limiting the effectiveness of phagocytosis.

  3. Adhesion - the ability of a microbial population to adhere to tissues is directly linked to pathogenicity. Adhesion provides an epicenter from which the invading population can reproduce, spread toxins and virulence factors and extend the infection to other tissues.

  4. Resistance to Antibiotics - although antibiotics have been massively successful in aiding the recovery of countless patients, their excessive use has resulted in surviving pathogenic populations with significant resistance to these agents. Furthermore, many microbes can transfer antibiotic resistance as part of small, circular, non-chromosomal rings of DNA termed plasmids imparting resistance to other cells. Obviously, the ability to resist treatment by standard antibiotics is a significant factor affecting pathogenicity.

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Natural Defense Mechanisms

Healthy humans have a broad range of immunological and biochemical defense mechanisms which serve to protect against infection by pathogens. This is essential since every moment of our lives we will breathe, eat, touch and otherwise be exposed to potentially pathogenic organisms. In general, there are two categories of defense - the first is the  "envelope" of skin, membranes and other physical barriers which limit access to the interior. The second level of defense is the wide range of immune responses, cells, antibodies and mechanisms to identify and eliminate pathogenic organisms and molecules inside a potential host. These defense mechanisms include

  1. Dermis / Skin - the simplest means of keeping pathogenic organisms from causing infection is to simply keep them out. The dermis is remarkably capable of performing this task - repairing damage, calling for biochemical and immunological support when breached and continuously growing to maintain an intact surface. In areas where there is internal / external interaction (nose / mouth) there are mucous membranes which secrete a remarkable array of anti-microbial compounds. 

  2. Lungs - the lungs are continuously responding to inhaled micro-organisms. Although most air-borne pathogens do not survive the passage through the nasal and bronchial airways a few will make it through. In the lung macrophages may engulf pathogens directly, while coughing can eliminate contaminants quite well. The immunological and physical defense mechanisms are finite, however, and can be overwhelmed by excessive numbers of pathogens.

  3. Gastrointestinal Tract (GI) - the environmental conditions of the stomach and GI tract are inhospitable to many micro-organisms. The acidic pH is simply below the operational range of many bacterial species. Enzymes in the bile and pancreas are also antibacterial. On top of all this, the indigenous symbiotic population of the GI tract represents severe competition for invading pathogens as these co-existing populations are not easily displaced.  Elimination of the normal GI flora through antibiotics used to treat other conditions may decrease this effectiveness.

Deaths due to Infectious Disease

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Immunological Defense

Immune responses fall into two categories: specific and non-specific responses.

  1. Non-specific Immunological Defenses - specific biomolecules such as cytokines (interleukins, interferons) can initiate a powerful non-antibody based response. This acute response is often indicated by fever with large numbers of neutrophils being released into circulation to enhance general resistance.  Other non-specifc responses include inflammation - the enhancement of circulation (and tissue permeability) at the site of injury or infection which serves to greatly enhance the delivery of immunological agents and cellular repair systems. Inflammation also serves to enhanced localized phagocytosis to further eliminate infectious agents both physically and enzymatically.

  2. Specific Immunological Defenses - infected organisms have a range of intensive immunological defenses which can exceptionally specific and effective. Immunoglobulins (also known as antibodies) identify and bind to infectious pathogens with a molecular-level specificity. Once antibodies bind to an invading cell they biochemically signal for assistance from a number of  immunological systems. The complement system initiates the production of cells and enzyme systems which digest or disrupt the cell walls of pathogenic cells. The opsonization system "tags" invading cells to further identify them for removal (particularly important in the case of encapsulated micro-organisms which may be resistant to other forms of immunological response).

 

Consequences of Infection

There are many different consequences of uncontrolled infection. The general conditions are summarized below per general areas of infection.

  1. Fever  - a body temperature measurement (oral) of > 38 ºC indicates fever.  Fever elevates the thermoregulatory controls to cause constriction of blood vessels to reduce the heat loss through external limbs and tissues. Increased heat production is caused by the muscle contractions produced by shivering. The high temperatures are maintained until the elevated temperatures trigger a decrease in the thermal control centre in hypothalamus. 

  2. Blood -  pathogenic infections infecting the blood are described as hematological conditions. The outcomes can include anemia (destruction of red blood cells), coagulation issues, leukocytosis and a number other severs problems. Indicators are increased levels of neutrophils in circulation. With severe blood-based infections the immune system may be overwhelmed leading to a poor prognosis.

  3. Heart - cardiac infections are serious. Consequences range from dangerous alterations in cardiac capacity including myocardial functioning.  A number of researchers are investigating the possibility of resident microbial populations having a role in cardiac disease and heart attacks.

  4. Lungs - coughing, congestion, hyperventilation and (in severs cases) respiratory failure can be consequences of pathogenic infection in these tissues.

  5. Liver - the liver and hepatic tissues can be damaged directly or indirectly. Since the liver processes significant volumes of blood jaundice may be a clinical indicator of severity.

  6. Kidney - the kidney can be at significant risk with some types of infection. Damage may be mild protein accumulation or may range to complete renal failure.

 

Geography of Infectious Disease

When the geographic distribution of deaths by infectious disease is examined it becomes immediately apparent that financial and social stability have an impact on mortality. The following chart illustrates this point quite clearly:

Infectious Disease Deaths as a Proportion of all Deaths Chart

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Example Bacterial Infectious Diseases

bulletAnthrax
bulletBacterial Meningitis
bulletBrucellosis
bulletCampylobacteriosis
bulletCholera
bulletDiphtheria
bulletGonorrhea
bulletLegionellosis
bulletLeprosy
bulletListeriosis
bulletLyme Disease
bulletMRSA infection
bulletPertussis
bulletPlague
bulletPneumonia
bulletQ fever
bulletSalmonellosis
bulletScarlet Fever
bulletShigellosis
bulletSyphilis
bulletTetanus
bulletTuberculosis
bulletTyphoid

Example Viral Infectious Diseases

bulletAIDS
bulletChickenpox
bulletCommon Cold
bulletCytomegalovirus
bulletDengue Fever
bulletEpidemic parotitis
bulletHand, foot and mouth disease
bulletHepatitis
bulletHerpes simplex / zoster
bulletInfuenza
bulletLassa Fever
bulletMeasles
bulletMarburg Fever
bulletMononucleosis
bulletMumps
bulletPolio
bulletRabies
bulletRubella
bulletSARS
bulletSmallpox
bulletViral encephalitis
bulletViral meningitis
bulletViral pneumonia
bulletWest Nile Virus
bulletYellow Fever

Example Parasitic Infectious Diseases

bulletAmebiasis
bulletChagas Disease
bulletEnterobiasis
bulletGiardiasis
bulletMalaria
bulletPinworms
bulletScabies
bulletSchistosomiasis
bulletTrichinosis
bulletTrypanosomiasis

Example Fungal Infectious Diseases

bulletAspergillosis
bulletBlastomycosis
bulletCryptococcosis
bulletHistoplasmosis

Example Prion / Viroid Infectious Diseases

bulletCreutzfeldt-Jakob disease  (BSE)
bulletKuru Leprosy

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Infectious Disease

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