The role of the environment for the infectious process developing is the following:
v It affects the host defense
v It influences the microbial virulence
v It may be the source and reservoir of infection
v It provides the mechanisms and routs of microbial transmission
¨ Mechanisms of Transmission
Most of the infectious diseases are communicable, that is they can spread from one host to another. Direct transmission is the immediate transfer of the infectious agent from the reservoir (source of infection) to a new host with no intervening intermediary.
For diseases with human reservoirs, direct transmission may be vertical and horizontal. Vertical transmission is the spread of disease from parent to offspring by an infected sperm or egg or by passage of pathogens across the placenta during fetal development. Congenital infection is an infection that is acquired in utero and present in birth. Horizontal transmission is the spread of disease from person to person within a group (population).
Indirect transmission occurs when the infectious agent is transferred by an intermediary – a vehicle, a vector, or a contaminated (rather than infected) person.
A vehicle is a nonliving material capable of transmitting infectious agent (for example, bedding, clothing, cooking and eating utensils, surgical instruments, contaminated air, food, and water, soil, contaminated drugs, blood, discharges of infected persons, etc.). Living organisms that are intermediaries in disease transmission are called vectors. The vectors may be mechanical ( they pick up microbes on their feet or other body parts, e.g. flies often gives microbes a free ride from feces to food), or biological (they are infected, not merely contaminated. Pathogens multiply within these vectors). Biological vectors may introduce the microbe by biting, or by depositing their contaminated feces or other excretions on the skin. (For example, mosquitoes, ticks, fleas, flies, lice, etc.).
Mechanisms of infectious diseases transmission are shown in Table 11-1.
¨ Portals of Entry and Exit
‘Portals of entry’ is a site that provides access to tissues where environmental and nutritional conditions are conductive to establishing infection and where local defense mechanisms fail to subdue the pathogen.
‘Portals of exit’ is the way of microbe’s escaping from the infected person. Most pathogens escape from the infected host though the same portal they used to enter the body. Nonetheless, additional portals of exit may develop.
Table 11-1
MECHANISMS OF INFECTIOUS DISEASES TRANSMISSION
| Mechanisms (routes) of transmission | Modes of transmission | Vehicles/ vectors | Portals of entry | Infectious diseases |
| FECAL-ORAL ROUTE | Alimentary | Food | Gastro-intestinal tract | Enteric bacterial and viral infections (cholera, dysentery, typhoid fever, hepatitis A and E, etc.) |
| Via water | Water | |||
| Via contaminated objects | Dirty hands, cooking and eating utensils, mechanical vectors, etc. | |||
| TRANSMISSION VIA BLOOD | Direct (hemotransfusion, transplacentally, etc.) | Contaminated blood | Blood | AIDS, hepatitis B,C,D, malaria, plague, etc. |
| Indirect | Surgical instruments, needles, syringes, biological vectors (insects), etc. | |||
| AEROGENIC ROUTE | Via respiratory droplets (coughing, sneezing, etc.) | Respiratory droplets | Respiratory tract | Influenza, common colds, meningitis, legionelliosis, diphtheria, tuberculosis, etc. |
| Via dust particles | Contaminated dust particles | |||
| Via aerosol | Contaminated aerosols | |||
| CONTACT ROUTE | Direct contact (touching, kissing, sexual contact, etc.) | Skin and mucous surfaces, infected sperm and saliva | Skin, mucosa, hair, nails, genitourinary tract | Gonorrhea, syphilis, gas gangrene, rabies, inflammatory diseases, etc. |
| Indirect contact | Contaminated objects that contact skin/ mucosa/ wounds |
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MICROORGANISM
One of the characteristics of the pathogen that influences its clinical manifestations is whether it grows inside host cells (is an intracellular parasite) or in the hosts body fluids and tissue spaces (extracellular parasite). Many of the body's defenses are directed against extracellular invaders. Even though they do not invade the interior of cells, most extracellular parasites attach to cells when colonizing specific tissues and frequently damage the cells to which they attach.
Intracellular parasites face a different series of challenges for survival. They must adhere to the host cells in which they will reproduce before they can invade them. Some pathogens are engulfed by phagocytic cells, survive destruction, and make themselves at home in the otherwise hostile phagocyte (incomplete phagocytosis).
The interior of a host cell protects the intracellular parasites against destruction by the body's defense mechanisms. Intracellular infections are poorly controlled by chemotherapeutic agents that either fail to penetrate the infected host cells or are ineffective in its cytoplasm. Because they are difficult to eradicate, intracellular parasites often produce chronic diseases with less rapid onsets, much longer recovery times (even with chemotherapy), and a greater likelihood of clinical relapse.
To initiate infection, pathogens must enter the body through a portal of entry that allows them access to tissues displaying the appropriated surface receptors.
The affinity most pathogens exhibit for a limited number of preferential tissues is called tissue tropism. Tissue tropism determines not only the location of the primarysite ofcolonization (the first habitat infected, sometimes with little or no damage to the area), but also the predilection for specific secondarysites of infection once the initial lines of defense have been breached.
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NOTE: Tissues that lack surface receptors complementary to the microbes attachment sites usually remain uninfected, although they may still be damaged by extracellular toxins or cytocidal substances released either from the microbe or from neighboring injured tissues.
Based on their relationship to hosts, microbes can be classified as:
v Saprophytes (sapros = decayed, phyton = plant). They are free-living microbes that subsist on dead or decaying organic matter. They are found in soil and water and play an important role in the degradation of organic materials in nature. They usually produce no disease in the healthy host, but occasionally can be harmful for immunocompromized host.
v Pathogenic microbes (pathos = suffering, gen = produce). These are disease producing microbes, usually parasites, which can establish themselves and multiply in the living hosts.
v Facultative pathogens, or opportunistic microbes. They are usually commensals that can live in complete harmony with the host without causing any damage to it (for example, microbes of the normal flora). In case of lowering the host defense, these microbes can produce the infectious process.
The term “ pathogenicity ” refers to as the potentialability of a microbial species to produce disease or tissue injury.
The term “ virulence ” is applied to the same property in a strain of the microbe and characterizes the degree of pathogenicity. The virulence of a strain is not constant and may undergo spontaneous or induced variation. Reduction of virulence is known as attenuation and can be achieved by passage through unfavorable conditions. These avirulent attenuated strains of pathogenic microbes are applied as vaccine strains. (See LESSON 15).
Virulence is quantified by determining the pathogens lethaldose, the number of microorganisms required to cause the death of infected animals. The greater the pathogens virulence, the fewer microbes are required to cause disease symptoms. The result is expressed as LD50, the number of microbes required to cause disease and death in 50 percent of the laboratory animals experimentally infected with the pathogen.
For virulence tests, the commonly used laboratory animals are guinea pigs, rabbits, rats, and mice. The routes used for animal infecting may be subcutaneous, intramuscular, intraperitoneal, intracerebral, or intravenous. The oral route and nasal spray can also be used.
¨ Virulence Factors
Any property of a microbe that enhances its ability to establish infection, survive the host's defenses, or injure the infected host increases the microbes virulence. These properties, collectively called virulence factors, tend to shift the balance in favor of the offending microorganism.
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Virulence is a sum total of several determinants, as detailed below.
· Adhesive surface structures (viruience factors that favor establishment of infection).
Most pathogens establish infection by attaching to host tissues, anchoring themselves to target cells. Bacteria attach to their target cells using molecules, collectively termed adhesins, on their surfaces. Adhesin is any molecule on a microbe that mediates its attachment to another cell or to an inanimate surface. The pili of some gram-negative bacteria attach to mucous surfaces of the intestinal, urinary, or genital tracts. Attachment protects the microbe from being flushed out by the flow of fluids or intestinal contents. Some bacteria adhere to their target host tissues by the surface of their capsules or glycocalyxes or by other adhesive surface structures. A few bacteria "coat" themselves in host proteins (such as fibronectin and collagen), which then attach to host cells.
Viruses attach to host cells to begin the infection process. Attachment of certain viruses is aided by surface proteins that are integral parts of the virus particle. For example, the influenza virus envelope contains neuraminidase, an enzyme that dissolves neuraminic acid, an important component of mucus that normally covers the respiratory cells and protects them from viral attachment. Neuraminidase exposes receptor sites on these underlying cells to virus.
NOTE: The infectivity of most pathogens can be neutralized by preventing their attachment to the host cells. Many successful vaccines stimulate the host to produce antibodies that block the attachment sites on the pathogens surface.
· Factors for colonization, spreading, and invasion (virulence factors that promote pathogen survival and host injury).
Once infection has been established, the development of disease depends on the microbe's ability to evade host defenses. Several virulence factors protect the microbe from host resistance mechanisms. Many also increase the pathogens ability to multiply in host tissues and spread from the original site of infection. The pathogen often damages host tissues as it gains access to nutrients and portals of exit from the host. These virulence factors are discussed according to their effects.
Spreading Factors. Pathogenic bacteria may discharge enzymes that dissolve host tissue, thereby destroying physical barriers that impede the microbes' spread throughout the infected body. These spreading factors may cause alarming injury to the patient.
The tissue destruction associated with gas gangrene, for example, is largely due to the production of collagenase by the pathogen. Collagenase is an enzyme that hydrolyzes collagen and it destroys protein of skin, bone, and cartilage, literally liquefying tissues in the process.
The pathogen also produces lecithinase (also called alpha-toxin), an enzyme that depolymerizes host cell membranes, destroying additional physical barriers.
Another spreading factor, hyaluromdase, dissolves hyaluronic acid, which forms the matrix of connective tissue. Hyaluronidase is believed to facilitate the spread of Streptococus pyogenes and Staphylococcus aureus from their initial sites of infection.
S. pyogenes also produces fibrinolysin, an enzyme that dissolves the fibrin clots that wall off an infection site and prevent the dissemination of the pathogen.
NOTE: This protein, also known as streptokinase, has been produced through genetic engineering for injection as an anticoagulant to dissolve blood clots that block the flow of blood, causing strokes or heart attack.
Coagulase is an enzyme produced by staphylococci that causes the clotting of blood plasma fibrin. There are some other enzymes and toxic compounds that contribute to the microbe virulence.
· Toxic Factors. Some pathogens damage the host and reduce host defenses by producing exotoxins, endotoxins, or both.
Exotoxins are soluble proteins produced by microorganisms and secreted into their surroundings. Exotoxins may be carried by the bloodstream to any part of the body. In this way, a localized infection can have fatal consequences. For example, Clostridium tetani infections are restricted to the site of the wound into which the organism was introduced. The organism itself destroys local tissue only, but it produces a powerful exotoxin that dissolves in the blood and is dispersed throughout the body. The toxin attacks motor nerves, triggering involuntary muscle contractions that may be strong enough to break the patients spine. Death is usually due to paralysis of the patients respiratory muscles.
Some exotoxins clearly benefit the microbe by facilitating invasion of tissues, protecting against host defenses, or promoting transmission to a new host. For example, enterotoxins, exotoxins that affect the intestinal mucosa, produce an explosive diarrhea or vomiting that encourages the shedding of intestinal pathogens and increases the likelihood of their transmission to new hosts.
Exotoxins are major virulence factors in the pathogenesis of diseases such as diphtheria, scarlet fever, botulism, tetanus, gas gangrene, bacterial dysentery, cholera, and whooping cough (pertussis). They are among the most lethal substances known. The major symptoms of many diseases are caused primarily by the specificexotoxin produced by the bacteria. Exotoxins usually elicit an immune response, and people who survive an infection are often protected against further bouts with disease caused by the same pathogen.
NOTE: The ability to neutralize exotoxins such as the ones that cause diphtheria and tetanus can be acquired in humans by vaccination with toxoids, inactivated forms of the protein toxin. (see LESSON 15)
Endotoxin is the lipid A component of lipopolysaccharide found in the cell walls of gram-negative bacteria Endotoxin, released when bacterial cells disintegrate, triggers white blood cells to discharge chemicals into the blood and surrounding tissues. These released host substances induce fever and pain at the site of infection. Rash may develop as the result of capillary hemorrhage. In large doses, endotoxin prevents normal capillary constriction, resulting in a severe drop in blood pressure, sometimes leading to fatal endotoxic shock. Because these physiological effects are produced by host factors released in response to endotoxin, many gram-negative bacterial infections are similar in their symptoms. Endotoxin does not stimulate the formation of protective antibodies during natural infections. Several pharmaceutical companies are testing commercially prepared antibodies to endotoxin in people with gram-negative infections.
· Antiphagocytic Factors
Capsules are some pathogens' most important virulence factors, protecting the bacteria from being engulfed and destroyed by the hosts phagocytic cells.
Capsules cover the bacterial surface components to which phagocytes attach, preventing engulfment and destruction of the target cell. Some capsules allow attachment of the phagocyte but prevent the binding of a chemical that promotes ingestion of the microbe. They may also create a hydrophilic surface that resists ingestion. The antiphagocytic activity of capsules is responsible for the infectivity of many important pathogens. For example, encapsulated strains of Streptococcus pneumoniae avoid destruction by phagocytosis and cause dangerous disease of the lower respiratory tract. Nonencapsulated strains of the same organism are nonpathogenic).
Some bacteria produce soluble antiphagocytic substances. Leukocidin, for example, is one of several virulence factors that poison phagocytic leukocytes (white blood cells). Coagulase is an enzyme that triggers the clotting of plasma around the site of infection. In this way some strains of Staphylococcus aureus may protect themselves from phagocytic cells, which cannot penetrate the wall of clotted fibrin. Some pathogens produce antichemotactic factors that hinder chemotaxis, the movement of phagocytes toward the site of infection. Still other pathogenic bacteria secrete hemolysins, extracellular proteins that destroy red blood cells. The significance of hemolysins to virulence, however, is likely due to their additional ability to destroy phagocytic cells. Hemolysins can cause different types of erythrocyte lysis: alpha hemolysis is a greenish zone of partial clearing around colonies of certain microbes on blood agar.(This occurs because of methemoglobin production). Beta hemolysis - is a zone of complete clearing around the colonies of certain microbes growing on blood agar.
Some intracellular parasites "outwit" phagocytes by surviving after being engulfed, often using the phagocytes to spread the infection throughout the body. Neisseria gonorrhoeae has adapted particularly well to its existence within phagocytes. It produces enzymes that help it escape from the phagocytic vesicle into the cytoplasm of the phagocyte, where the bacterium reproduces (this is termed uncompleted phagocytosis). Some of the progeny migrate to the host cell membrane and induce the formation of pseudopod-like projections. Neighboring phagocytes engulf these projections as if they were foreign particles. Thus bacterial spread is accomplished without exposure to extracellular host defenses.
Intracellular pathogens of epithelial, endothelial, and other normally nonphagocytic cells produce factors that promote phagocytic uptake. (For example, Yersinia species that invade the intestinal tract, for example, synthesize a protein called invasin that is incorporated into their outer membrane. Invasin binds to mammalian cell receptors and stimulates the cells to engulf the bacteria).
· Additional Virulence Factors
Other virulence factors include enzymes that destroyhost antibodies, Neisseria gonorrhoeae and Streptococcus pnenmoniae are among the bacteria that produce proteases that specifically cleave antibodies designed to protect the mucous membrane surfaces of the body. One factor that limits the survival of many pathogens is the low concentrations of free iron within host tissues. Many microbes, including E. coli and M. tuberculosis, produce iron-binding substances called siderophores that withdraw iron from the host and make it available to the bacteria. The genes for siderophore production are often plasmid-encoded and can be transferred among the organisms.