The concept that disease were infectious and caused by an unknown “something” appears in human history long period before the discovery of the microorganisms. In 1546 Fracastoro proposed a “germ theory of disease”. After opening of microorganisms by Leeuwenhoek people began to suspect that microorganisms might cause disease in human and other animals. Only Paster has proved that microbes can cause infectious disease. Robert Koch offered proof of the germ theory of disease. His approach led to the formulation of “Koch’s postulates”, which are criteria that he proposed must be satisfied to confirm the causal role of microorganisms. These criteria are as follows:
The type and severity of an infection depend on numerous factors, most of which are related to the pathogenicity of the microbe and the condition of the host. Pathogenicity describes a microorganism's potential to cause an infection or disease.
Pathogenic microbes have been traditionally divided into two categories, depending upon the nature of the microbe-host relationship. Examples include the influenza virus, plague bacillus, rabies virus, and other microorganisms with well-developed qualities of virulence
Differences in pathogenicity can be accounted for on the basis of virulence. Virulence takes into account the ability of microbes to invade a host and produce toxins (toxigenicity). These properties are called virulence factors All these factors are realized during of infectious disease and conditioned pathogenesis
Progression or resolution of the disease: 1. Death 2. Carrying formation 3. Convalescence
It is a place or organism where microorganisms can multiply and where from they are spread and infect other organisms
The ID varied widely among microbial species and depends on virulence of microorganisms.
Vector are arthropods which are carriers of disease agents. In case of biological vectors, microorganisms multiply in their organism. Yellow fever, caused by virus, is transmitted by mosquito vectors, rocky Mountain spotted fever is transmitted by ticks.
Certain bacteria have specialized structures, eg pili, or produce substance, eg. capsule or glycocalyces, that allow them to adhere to the surface of human cells, thereby enhancing their ability to cause disease. Mutants that lack these mechanisms are often nonpathogenic. For example, the pili of N.gonorrhoeae and E.coli mediate the attachment of the organisms to urinary epithelium. A lot of viruses have spikes on the calsid or supercalsid for adhesion on host cell.
A toxin molecule secreted by a living bacterial cell into the infected tissues is an exotoxin. A toxin that is not secreted but is released only after the cell is damaged or lysed is an endotoxin.
Fever due to the release by macrophages of endogenous pyrogen (interleukin-1), which acts on the hypothalamic temperature-regulatory center. Activation of the alternative pathway of the complement cascade, resulting in inflammation and tissue damage Disseminated intravascular coagulation due to action of the coagulation system through Hageman factor, resulting in thrombosis and tissue ischemia Endotoxins do not cause these effects directly. Rather, they induce synthesis of host factors such as interleudin-1 and TNF (tumor necrosis factor) by macrophages.
Several factors contribute to invasiveness by limiting the ability of the host defense mechanisms, especially phagocytosis. Phagocytosis is ineffective for several reasons. For example, some pathogens have a protective coating that makes them hard to engulf (in top) , or the phagocyte ingests them but the microbes can still multiply.
Infectious process and infectious disease are different conception.
When focal infection microorganisms spreads from local site to entire body.
The time of incubation period varies from hours to days to weeks depending on the microorganisms.
During incubation stage, the microorganisms has invaded the host and is migrating to various tissue but has not yet increased to sufficient numbers to cause discomfort or infectivity. In beginning of prodromal period the patient suffer discomfort but does not have sufficient precise symptoms to permit the clinician to make a diagnosis. When this stage patient is contagious to others. During clinical stage the disease is most severe. Communication of infection occurs from prodromal to dicline period when the human is beginning to recover.
Bohomolets Microbiology Lecture #8
Infection Infectious process
Genle-Koch’s postulates <ul><li>The microorganism must be present in every case of the disease and not be isolated from healthy human or from human with other disease </li></ul><ul><li>The microorganisms must be grown in pure culture from the sick host </li></ul><ul><li>The same disease must be reproduced when a pure culture of the microorganism is inoculated into a healthy, susceptible host (animal) </li></ul><ul><li>The microorganism must then be recovered from the experimentally infected host </li></ul>
Infection (infectious process) <ul><li>It is a historically formed complex of biologic events and processes that are occurred in organism when pathogenic microorganism penetrates and reproduces in it </li></ul>
Components of infectious process Organism Conditions of interaction Infectious agent
Pathogenicity <ul><li>It is a genetically conditioned possibility of microorganisms to cause infectious process </li></ul>
Categories of pathogenic microorganisms <ul><li>True pathogens (primary pathogens) are capable of causing infection and disease on healthy person with normal immune defenses </li></ul><ul><li>Opportunistic pathogens cause disease when the host’s immune system is compromised </li></ul>
Virulence <ul><li>It is a quantitative characteristic of degree of microorganism pathogenicity </li></ul>
Virulence factors <ul><li>Adhesion </li></ul><ul><li>Colonization </li></ul><ul><li>Invasion </li></ul><ul><li>Penetration </li></ul><ul><li>Toxigenicity </li></ul><ul><li>Factors of aggressive </li></ul>Virulence factors are properties of disease-causing microorganism, that enhance their pathogenicity and allow them to colonize or to invade human tissue and disrupt normal body functions
Pathogenesis <ul><li>It is a complex of reactions and mechanisms that are characterized interaction between human organism and microorganisms during infectious process </li></ul>
A generalized sequence of the stages of infection <ul><li>1. Transmission from an external source into the portal of entry </li></ul><ul><li>2. Adherence to mucous membranes </li></ul><ul><li>3. Colonization by growth of the bacteria at the site of adherence </li></ul><ul><li>4. Invasion </li></ul><ul><li>5. Forming of primary inflammatory nidus </li></ul><ul><li>6. Spread agents in the organism </li></ul><ul><li>7. Disease symptoms caused by toxin production or invasion </li></ul><ul><li>8. Host responses, both nonspecific and specific </li></ul><ul><li>9. Progression or resolution of the disease </li></ul>
Reservoir of infection <ul><li>Sick human (syphilis) </li></ul><ul><li>Sick animal (rabies) </li></ul><ul><li>Carriers (salmonellosis) </li></ul><ul><li>Soil (fungal disease, actinomycetal disease) </li></ul>It is the primary habitat in the nature world from which a pathogen originates
<ul><li>The infectious dose (ID) refers to the minimum number of microbial cell required to initiate infection in the host. </li></ul>
Sours of infectious agent <ul><li>Exogenous. When agents is originating from a source outside the body (the environment or another person or animal) </li></ul><ul><li>Endogenous . Already existing on or in the body (normal flora or latent infection) </li></ul>
Mechanisms of transmission <ul><li>Horizontal transmission is the spread of infectious disease from person to person </li></ul><ul><li>Vertical transmission is the spread of infectious disease from parent to offspring during pregnancy or delivering </li></ul>
Portal of entry <ul><li>Mucous membrane of gastrointestinal tract ( Salmonella typhi, Shigella dysenteria, Hepatitis A virus) </li></ul><ul><li>Mucous membrane of respiratory tract (Neisseria meningitidis, Mycobacterium tuberculosis, Influenza virus) </li></ul><ul><li>Mucous membrane of urinary and genital tract (Neisseria gonorrhoeae, Treponema pallidum) </li></ul><ul><li>Skin (native and hurt) (Leptospira interrogans, Clostridium tetani) </li></ul>The portal of entry is the site at which a microorganism first contacts host susceptible tissue through that microbe can penetrate into the organism
Adherence of bacteria Vibrio holerae on the surface of enterocytes Gonococci on the surface of urinary epithelium
Action of enzymes Exoenzymes dissolve extracellular barrier and make possible penetration of bacteria through or between cells to underlying tissues Collagenase and hyaluronidase , which degrade collagen and hyaluronic acid, respectively, thereby allowing the bacteria to spread through subcutaneous tissue.
Pathogenic enzymes Dissolves blood clots Fibrinolysin Destroys red blood cells and other tissue cells Lecithinase Breaks down DNA Deoxyribonuclease Breaks down fat Lipase Breaks down hyaluronic acid, a tissue component Hyaluronidase (spreading factor) Breaks down collagen (connective tissue fiber) Collagenase Coagulates plasma; blood clots Coagulase Breaks down lecithin, a lipid component of mammalian cell membrane Phospholipase Function Enzyme
Definition <ul><li>Bacteremia. Indicating the presence of bacteria in the blood, usually transient </li></ul><ul><li>Viremia. Indicating the presence of viruses in the blood . </li></ul><ul><li>Toxemia . Indicating the presence of bacterial toxins in the blood </li></ul><ul><li>Sepsis. Stage of infectious process when agent is not only present in the blood, but can multiply there </li></ul><ul><li>Septicopyemia. When agent is not only multiply in the blood, but and can form purulent nidus in organs and tissues of sick human . </li></ul>
Action of toxins Exotoxins diffuse to target cells, which are poisoned and disrupted
Differential characteristics of bacterial exotoxins and endotoxins (1) Stable at 100 0 C for 1 hour Destroyed rapidly at 60 0 C Heat stability Bacterial chromosome Bacterial chromosome, plasmid or bacteriophage Location of genes Lipopilysaccharide (LPS) Polypeptide Chemical Released by cell during lysis Secreted from live cell Manner of release Most of gram-negative bacteria A few gram-positive and gram-negative bacteria Source Endotoxin Exotoxin Property
Differential characteristics of bacterial exotoxins and endotoxins (2) Low (toxic in high dose) High (toxic in minute amounts) Toxicity Systemic: fever, inflammation Specific to a cell type Clinical effects Do not convert to toxoid Convert to toxoid that used as vaccines Toxoid formation Low. Poorly antigenic High. Induces high titer antibodies called antitoxins Antigenicity Yes Usually not Fever stimulation Endotoxin Exotoxin Property
Classification of exotoxins based on mechanism of action Staphylococcus aureus Cytotoxin that causes the lysis of human erythrocytes and some other cells. Hemolysin Corynebacte-rium diphtheriae Causes cell death, often by lysis and/or interference with protein synthesis Cytotoxin Vibrio cholerae Inflammation of the gastrointestinal tract; typically causes excessive secretions of fluid and electrolytes from the lining of the gastrointestinal tract Enterotoxin Clostridium botulinum Interference with nerve transmission Neurotoxin Bacterium-producer General site and mode of action Type of toxin
Effects of endotoxin Activation of Hageman factor Coagulation Alternative pathway of complement (C3a,C5a) Inflammation Bradykinin, nitric oxide Hypotension (shock) Interleukin-1 Fever Mediator or mechanism Clinical findings
Factors of aggressive <ul><li>Capsule. Prevents phagocyte from adhering to the bacterium </li></ul><ul><li>Cell wall protein of gram-positive cocci, such as the M protein of Streptococcus pyogenes and protein A of St. aureus. </li></ul>
Infectious disease <ul><li>It is an extreme extent of infectious process when precise clinical sings occur and pathologic changes in an organism are present </li></ul>
Types of infection <ul><li>Localized. Restricted to a confined area in the body </li></ul><ul><li>Systemic. An infection in which the microorganisms spread throughout the body </li></ul><ul><li>Primary. Caused by one type of microorganisms </li></ul><ul><li>Secondary. Caused by a microorganism following a primary infection </li></ul><ul><li>Mixed. An infection caused by two or more microorganisms </li></ul><ul><li>Subclinical. An infection that does not display any symptoms </li></ul><ul><li>Acute. An infection that appears suddenly, has a short course, is relatively severe </li></ul><ul><li>Chronic. An infection that persist over a long period of time with or without symptoms </li></ul>
Type of infection caused by one species of microorganisms <ul><li>Reinfection occurs when the human was infected by microorganism of same species after recovery </li></ul><ul><li>Superinfection occurs when the human was infected by microorganism of same species during infectious process </li></ul><ul><li>Relapce occurs when symptoms of disease are appeared without exogenous infecting </li></ul>Recovered Reinfection Sick Superinfection Relapce Asymptomatic
Typical stages of an infectious disease <ul><li>The incubation period , which is the time between the acquisition of the microorganisms (or toxin) and beginning of symptoms </li></ul><ul><li>The prodromal period , during which nonspecific symptoms such as fever, malaise, and loss of appetite occur </li></ul><ul><li>The specific-illness (clinical) period , during which the overt characteristic signs and symptoms of the particular disease occur </li></ul><ul><li>The recovery period , during which the illness abates and the patient returns to the healthy state </li></ul>