A microorganism is a pathogen if it is capable of causing disease; however, some organisms are highly pathogenic (i.e., they often cause disease), whereas others cause disease rarely. Opportunistic pathogens are those that rarely, if ever, cause disease in immunocompetent people but can cause serious infection in immunocompromised patients. These opportunists are frequent members of the
body’s normal flora.
Virulence is a quantitative measure of pathogenicity and is measured by the number of organisms required to cause disease. The 50% lethal dose (LD50) is the number of organisms needed to kill half the hosts, and the 50% infectious dose (ID50) is the number needed to cause infection in half the hosts. Organisms with a lower LD50 (or ID50) are said to be more virulent than those with a higher LD50 (or ID50) because fewer organisms are needed to cause death or disease.
The infectious dose of an organism required to cause disease varies greatly among the pathogenic bacteria. For example, Shigella and Salmonella both cause diarrhea by infecting the gastrointestinal tract, but the infectious dose of Shigella is less than 100 organisms, whereas the infectious dose of Salmonella is on the order of 100,000 organisms. The infectious dose of bacteria depends primarily on theirvirulence factors (e.g., whether their pili allow them to adhere well to mucous membranes, whether they produce exotoxins or endotoxins, whether they possess a capsule to protect them from phagocytosis, and whether they can survive various nonspecific host defenses such as acid in the stomach).
There are two uses of the word parasite. The term refers to the parasitic relationship of the bacteria to the host cells (i.e., the presence of the bacteria is detrimental to the host cells). Bacteria that are human pathogens can be thought of, therefore, as parasites. Some bacterial pathogens are obligate intracellular parasites (e.g., Chlamydia and Rickettsia), because they can grow only within host cells. Many bacteria are facultative parasites because they can grow within cells, outside cells, or on bacteriologic media. The other use of the termparasite refers to the protozoa and the helminthes.
WHY DO PEOPLE GET INFECTIOUS DISEASES?
People get infectious diseases when microorganisms overpower our host defenses (i.e., when the balance between the organism and the host shifts in favor of the organism). The organism or its products are then present in sufficient amount to induce various symptoms, ,the two critical determinants in overpowering the host are the number of organisms to which the host, or person, is exposed and the virulence of these organisms. Clearly, the greater the number of organisms, the greater is the likelihood of infection. It is important to realize, however, that a small number of highly virulent organisms can cause disease just as a large number of less virulent organisms can. The virulence of an organism is determined by its ability to produce various virulence factors, several of which were described previously.
The production of specific virulence factors also determines what disease the bacteria cause. For example, a strain of Escherichia coli that produces one type of exotoxin causes watery (nonbloody) diarrhea, whereas a different strain of E. coli that produces another type of exotoxin causes bloody diarrhea. A reduction in the functioning of any component of our host defenses shifts the balance in favor of the organism and increases the chance that an infectious disease will occur.
TYPES OF BACTERIAL INFECTIONS
The term infection that an organism has infected the person (i.e., it has entered the body of that person). Bacteria cause disease by two major mechanisms: (1) toxin production and (2)
invasion and inflammation. Toxins fall into two general categories: exotoxins and endotoxins. Exotoxins are polypeptides released by the cell, whereas endotoxins are lipopolysaccharides (LPS), which form an integral part of the cell wall.Endotoxins occur only in gram-negative rods and cocci, are not actively released from the cell, and cause fever, shock, and other generalized symptoms.
An infection is epidemic if it occurs much more frequently than usual; it is pandemic if it has a worldwide distribution. An endemic infection is constantly present at a low level in a specific population .Certain other infections lead to a chronic carrier state, in which the organisms continue to grow with or without producing symptoms in the host. . Members of the normal flora are permanent residents of the body and vary in type according to anatomic site . Colonizationrefers to the
STAGES OF BACTERIAL PATHOGENESIS
A generalized sequence of the stages of infection is as follows:
(1) Transmission from an external source into the portal of entry.
(2) Evasion of primary host defenses such as skin or stomach acid.
(3) Adherence to mucous membranes, usually by bacterial pili.
(4) Colonization by growth of the bacteria at the site of adherence.
(5) Disease symptoms caused by toxin production or invasion accompanied byinflammation.
(6) Host responses, both nonspecific and specific (immunity
(7) Progression or resolution of the disease.
DETERMINANTS OF BACTERIAL PATHOGENESIS
Bacteria, viruses, and other microbes can also be transmitted from mother to offspring, a process called vertical transmission. The three modes by which organisms are transmitted vertically are across the placenta, within the birth canal during birth, and via breast milk. (Horizontal transmission,by contrast, isperson-to-person transmission that is not from mother to offspring.).There are four important portals of entry: respiratory tract, gastrointestinal tract, genital tract, and skin .Animals are also an important source of organisms that infect humans. They can be either the source (reservoir) or the mode of transmission (vector) of certain organisms. Diseases for which animals are the reservoirs are called zoonoses.
2. Adherence to Cell Surfaces
Certain bacteria have specialized structures (e.g., pili) or produce substances (e.g., capsules or glycocalyces) that allow them to adhere to the surface of human cells, thereby enhancing their ability to cause disease. These adherence mechanisms are essential for organisms that attach to mucous membranes; mutants that lack thesemechanisms are often nonpathogenic. The various molecules that mediate adherence to cell surfaces are called adhesins.
After the bacteria attach, they often form a protective matrix called a biofilm consisting of various polysaccharides and proteins. Biofilms form especially on foreign bodies such as prosthetic joints, prosthetic heart valves, and intravenous catheters, but they also form on native structures such as heart valves. Biofilms protect bacteria from both antibiotics and host immune defenses such as antibodies and neutrophils. They also retard wound healing resulting in chronic wound infections, especially in diabetics. Biofilms play an important role in the persistence of Pseudomonas in the lungs of cystic fibrosis patients and in the formation of dental plaque, the precursor of dental caries.
One of the two main mechanisms by which bacteria cause disease is invasion of
tissue followed by inflammation.
Intracellular survival is an important attribute of certain bacteria that enhances their ability to cause disease. These bacteria are called “intracellular” pathogens and commonly cause granulomatous lesions. The best-known of these bacteria belong to the genera Mycobacterium, Legionella, Brucella, and Listeria.
The genes that encode many virulence factors in bacteria are clustered in pathogenicity islands on the bacterial chromosome. For example, in many bacteria, the genes encoding adhesins, invasins, and exotoxins are adjacent to each other on these islands. Nonpathogenic variants of these bacteria do not have these pathogenicity islands. Pathogenicity islands are found in many gram-negative rods, such as E. coli, Salmonella, Shigella, Pseudomonas, and Vibrio cholerae, and in gram-positive cocci, such as S. pneumoniae.
4. Toxin Production
The second major mechanism by which bacteria cause disease is the production of
BACTERIAL INFECTIONS ASSOCIATED WITH CANCER
The fact that certain viruses can cause cancer is well established, but the observation that some bacterial infections are associated with cancers is just emerging. Several documented examples include (1) the association of Helicobacter pylori infection with gastric carcinoma and gastric mucosal-associated lymphoid tissue (MALT) lymphoma, and (2) the association of Campylobacter jejuni infection with MALT lymphoma of the small intestine (also known as alpha-chain disease). Support for the idea that these cancers are caused by bacteria comes from the observation that antibiotics can cause these cancers to regress if treated during an early stage.
TYPICAL STAGES OF AN INFECTIOUS DISEASE
A typical acute infectious disease has four stages:
(1) The incubation period, which is the time between the acquisition of the organism (or toxin) and the beginning of symptoms (this time varies from hours to
days to weeks, depending on the organism).
(2) The prodrome period, during which nonspecific symptoms such as fever, malaise, and loss of appetite occur.
(3) The specific-illness period, during which the overt characteristic signs and symptoms of the disease occur.
(4) The recovery period, also known as the convalescence period, during which the illness abates and the patient returns to the healthy state.
After the recovery period, some individuals become chronic carriers of the organisms and may shed them while remaining clinically well. Others may develop a latent infection.
DID THE ORGANISM ISOLATED FROM THE PATIENT ACTUALLY CAUSE
THE DISEASE?( Koch’s postulates).
This is the problem that Robert Koch faced in 1877 when he was among the first to try to determine the cause of an infectious disease, namely, anthrax in cattle and tuberculosis in humans. 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 an organism. These criteria are as follows:
(1) The organism must be isolated from every patient with the disease.
(2) The organism must be isolated free from all other organisms and grown in pure culture in vitro.
(3) The pure organism must cause the disease in a healthy, susceptible animal.
(4) The organism must be recovered from the inoculated animal.