Infection And Diseases

INFECTION AND DISEASES Infection and Disease Infection is the invasion or colonization of the body by pathogenic microorganisms. Disease occurs when an infection results in any change from a state of health. When microorganisms first associate with a host, the host is said to be contaminated. If the microbes establish themselves and grow and multiply for a period of time, the host is said to be infected and if the infection causes the damage, the host is said to have an infectious disease. Microbes capable of causing infections that result in disease are called pathogens. This characteristic is called as pathogenicity of the organism. Degree of pathogenicity of a microbe is referred to its virulence. A reservoir of microorganism is required from where the causative agent should be transmitted to a susceptible host either directly or through the agency of a vehicle or a vector. For an infectious disease to perpetuate there has to be Source and Reservoir is the person, animal, object or substance from which an infectious agent passes or disseminates to the host whereas a reservoir is defined as any person, animal, arthropod, plant, soil or substance (or combination of these) in which an infectious agent lives and multiplies. These can be Modes of Transmission The microorganisms can be transmitted to human beings directly or indirectly. Direct transmission occurs through: · Contact with man, animal or inanimate objects · Droplet infection · Breach of skin or mucous membrane · Transplacental and congenital Indirect transmission is possible by: · Vehicles (water, food etc.) · Vectors (mechanical or biological) · Air (droplet or dust) Mechanism of Infection Firstly, entry is gained into the host. The most frequent portals of entry are the respiratory tract, the gastrointestinal tract and breaks in the superficial mucous membranes and skin. From the portal of entry the parasite may spread directly through the tissues or may proceed via lymphatic channels to the blood stream, which distributes it widely and permits it to reach tissues particularly suitable for its multiplication. A satisfactory portal of exit of the parasite from the host and an effective mechanism for transmission to new hosts are paramount importance in this process. Development of Disease Once the microorganism overcomes the defences of the host, development of infectious disease follows a sequence of events. Period of Incubation: This is the time interval between the actual infection and the appearance of first clinical feature. Prodromal Period is relatively a short period follows incubation period in some diseases. It is characterised by mild early symptoms such as general aches and malaise. Period of Illness: This is the acute phase of illness characterised by typical clinical features of the infectious disease. Period of Decline: During this period the signs and symptoms subside. The fever decreases and the feeling of malaise diminishes. During this period, the person may be attacked by secondary infection. Period of Convalescence: The person regains strength during this period and body returns to prediseased state. Local or Generalised Infections An infection may be restricted to the point of entry (local) or may spread throughout the body (generalized).

MICROBIAL PATHOGENICITY

PATHOGENIC MICROORGANISMS Any microorganism that is able to infect a host and produce disease is called a pathogen. On this basis, bacteria can be organised into three major groups.

Frank Pathogens: When isolated from a patient, frank pathogens are considered to be probable agents of a disease, e.g. Salmonella typhi, Neisseria gonorrhoeae and Yersinia pestis. Opportunistic Pathogens: These are isolated from patients whose defense mechanisms have been compromised, e.g. Staph. epidermidis infection. Non-pathogens: These rarely or never cause human disease. Bacillus subtilis is an example of nonpathogenic microorganism. Whether disease ensues as a result of a host's encounter with a pathogen is dependent both upon the condition of the host and particular characteristics of the microorganism. The characteristics that contribute to the ability of a microbe to produce disease are referred to as virulence factors. VIRULENCE FACTORS OF MICROORGANISMS The virulence factors may be broadly subdivided into: · invasiveness (ability to enter host tissues, multiply there, and spread) · toxigenicity (ability to produce toxic substances)

· plasmid mediated phenotypic expressions Toxins and Enzymes Endotoxin has been identified as a component of Gram-negative bacterial cell wall envelope and is composed of a complex of lipopolysaccharide with outer membrane proteins. Most of the toxic effects of endotoxins are due to the lipid- A, component of the lipopolysaccharide. Table 12-1. Enzymes Some bacteria also have the ability to produce enzymes that can directly damage host tissue. Few important enzymes produced by bacteria are: · Proteases · Kinases · Hyaluronidase · Collagenase · Coagulase Proteases specifically cleave IgA which is the most important immunoglobulin for protection at mucosal surface thus diminishing the protective function of the IgA molecule. Both virulent streptococci and staphylococci produce kinase that enhance the spread of microbe by dissolving fibrin clots and inhibiting the clotting of plasma. These organisms also produce hyaluronidase that enhances dissemination of the infecting microorganism by breaking down the intercellular mucopolysaccharide hyaluronic acid that 'cements' cells together. Virulent strains of staphylococci produce coagulase ;: which causes deposition of fibrin around the invading cocci and thus protects them from the phagocytes. Collagenase produced by Clostridium perfringens produces breakdown of collagen in connective tissue. This results in destruction of the muscle tissue and enhances the spread of the bacteria. Exotoxins Exotoxins are proteins which are secreted by certain viable bacteria. These are the most potent poisons known. Most of these are composed of two subunits: Fragment A is the toxic or enzymatic unit that exerts pathologic action. Fragment B is the carrier, binds to the host cell receptor and enables fragment A to enter the cell. Differences between exotoxins and endotoxins Exotoxins 1. Protein polypeptides with mol. wt ranging between 10000-900000 2. Secreted by living cells into medium from cell cytoplasm. Found in high concentration in fluid medium 3. Heat labile. Toxicity is destroyed rapidly on exposure to temperature above 60°C 4. Highly antigenic 5. Stimulates immune system to produce specific antitoxin which can neutralize toxin 6. Can be converted into antigenic but nontoxic, toxoid by formalin, acid, heat etc. 7. Do not produce fever in host 8. Specific for particular tissue (e.g. tetanus toxin for nervous system) 9. Produced mainly by Gram +ve bacteria and some gram-negative Frequently controlled by extra chromosomal genes

Endotoxins 1. Lipopolysaccharide complex. Lipid A portion is probably responsible for toxicity 2. Present in cell wall as a constituent. Released only on disruption of cells 3. Relatively heat stable and can withstand heat over 60°C for hours without loosing toxicity 4. Poorly antigenic 5. No antitoxin is formed. Only antibodies against polysaccharide 6. Cannot be converted into toxoids 7. Usually produce fever in host 8. Nonspecific in action 9. Produced mainly by Gram -ve bacteria 10. Synthesis directed by chromosomal genes

Exotoxins can be converted into toxoids which are often used as immunogens for prophylactic immunization. Many organisms produce exotoxins which exert their activity in gastrointestinal tract. These are called as enterotoxins. Enterotoxin production may take place in contaminated food.

Genetic Mechanism (R-factors) Plasmids are extrachromosomal DNA segments that carry genes for antibiotic resistance known as Rfactors. These factors are readily transferrable by conjugation to bacterial cells of the same species as well as to cells of different species and even genera, and can confer resistance to many antibiotics. Plasmids also code for pathogenic mechanisms such as colonization factors, enterotoxin production and siderophore synthesis. Some of these plasmids may get integrated with bacterial chromosome. Bacteriophages may also contribute to the virulence of bacteria. Toxin production by C. diphtheriae occurs as a result of lysogenic infection of the bacterium by a specific phage. Microbes Escape Mechanisms To survive the powerful forces of natural and adaptive host immunity against it, a parasite must have one or several survival strategies. These include: Avoiding Phagocytosis . A voiding Death in the Phagocyte · A voiding Complement . Antigenic Variation Immunosuppression: The power of HIV to suppress T cell immunity is all too familiar, but similar effects are seen with many protozoa (trypanosomes, malaria), bacteria (TB) and, more transiently, other viruses (measles). Immunosuppression by microbes often involves: · T cells (HIV, measles) . B cells (Epstein-Barr Virus) . Macrophages (HIV, Leishmania) . Dendritic cells (HIV).