Host-Microbe Interactions: Principles of Disease PDF

Interaction between microbe and host: Principles of disease DR. JONATHAN ASANTE DEPARTMENT OF PHARMACEUTICAL MICROBIOLOGY U.C.C  Course content and goals Describe the Underst...

Interaction between microbe and host: Principles of disease DR. JONATHAN ASANTE DEPARTMENT OF PHARMACEUTICAL MICROBIOLOGY U.C.C  Course content and goals Describe the Understand the Appreciate At the end of relationship concept of this lecture, pathology, the role of between the students should infection and the normal normal be able to: microbiota. microbiota and disease. Classify host. Describe Establish the infectious ways of causes of diseases and acquiring infectious describe the infectious diseases (Koch’s development of agents. postulates) infectious diseases.  Microbiology-An introduction, tenth edition by Gerard J. Tortora, Berdell R. Funke and Christine L. Case. Denyer, P. S., Hodges, A. N., Gorman, P. S. & Gilmore, F. B. (2011). Hugo and Russell's Pharmaceutical Microbiology. 8th Edition, Wiley-Blackwell. ISBN: 978- Referenc 1444330632. e books Kar A. (2008). Pharmaceutical Microbiology. 1st Edition. New Age Publishers, 2008. ISBN: 978812242867- 4 Introduction Pathogen: A microorganism that is able to cause disease in a plant, animal or insect. Pathogenicity- the ability of an infectious agent to cause disease OR the ability to produce pathologic changes. Pathogenesis refers to the manner in which a disease develops. Microbes express their pathogenicity by means of their virulence. Introduction-THE BASIS OF BACTERIA PATHOGENICITY  Virulence: Extent to which an organism can inflict disease.  It is a measure of the degree of disease-producing ability of a microbe as indicated by the severity of the disease produced. Commonly assessed by measuring the dosage required to cause specific degree of pathogenicity.  The determinants of a pathogen’s virulence are any of its genetic, biochemical or structural features that enable it to produce disease in a host.  THE BASIS OF BACTERIA PATHOGENICITY Organisms of high virulence produce infection with much smaller inocula than organisms of low virulence Virulence depends on a variety of bacterial and host factors. It is defined in terms of specific bacteria factors (e.g., inoculum size , route of entry) as well as specific host factors (e.g., age, immune status, and species of host) Pathogenicity is therefore a qualitative term and virulence a quantitative one.  THE BASIS OF BACTERIA PATHOGENICITY Virulence is measured by the LD50 (the dose of an agent that kills 50% of the animals in a test group) OR ID50 (the infectious dose for 50% of a sample population).  Invasion: The process whereby organisms enter host cell or tissue and spread in the body. Introducti Infectivity: Ability to breach host defences. on Toxigenicity: Ability to produce a toxin that contributes to the development of disease.  THE BASIS OF BACTERIA PATHOGENICITY Virulence involves invasiveness and toxigenicity. Virulence is determined by invasiveness, toxicity, and other factors produced by a pathogen. Attenuation is loss of virulence. Dose: The number of pathogenic microbes entering a host.  THE BASIS OF BACTERIA PATHOGENICITY Lethal dose 50 (LD50): Number of microorganisms which kill 50% of host tissue cells ( or 50% of animals in a test group). It is a measure of virulence. The higher the LD50, the lower the virulence. True pathogen: Any microbe capable of causing disease; an infecting agent. THE BASIS OF BACTERIA PATHOGENICITY Opportunistic pathogen: A usually harmless microorganism that becomes pathogenic under favourable conditions, causing an opportunistic infection. Emerging infectious diseases are new diseases or known existing diseases with increasing incidences. Normal Microbiota Flora, Microbiota refers to microorganisms present in or characteristic of a special location. Normal microbiota, or normal flora: Refers to the microorganisms that establish more or less permanent residence (colonize) but that do not produce disease under normal conditions.  Normal Microbiota Animals, including humans, are generally free of microbes in utero. A typical human body contains 1 X 1013 body cells, yet harbours an estimated 1 X 1014 bacterial cells  Normal Microbiota In a healthy human, the internal tissues, e.g., brain, muscle, etc., are normally free of microorganisms. However, the surface tissues, i.e., skin and mucous membranes, are constantly in contact with environmental organisms and become readily colonized by various microbial species. The mixture of organisms regularly found at any anatomical site is referred to as the normal flora. Normal Microbiota The skin and mucous membranes always harbour a variety of microorganisms that can be grouped into two: 1. The resident microflora consists of relatively fixed types of microorganisms regularly found in a given area at a given age; if disturbed, it promptly reestablishes itself. 2. Transient microbiota refers to those that may be present for several days, weeks, or months and then disappear.  Normal Microbiota Members of the transient microbiota are derived from the environment, do not produce disease, and do not establish themselves permanently on the surface. Members of the transient flora are generally of little significance so long as the normal resident flora remains intact. However, if the resident flora is disturbed, transient microorganisms may colonize, proliferate, and produce disease.  The skin is a generally dry, acidic environment that does not support the growth of most microorganisms. But moist areas, especially around sweat Normal glands, are colonized by gram-positive bacteria. Microbiot a Skin is continually being inoculated with transient microorganisms non-pathogenic or potentially pathogenic microorganisms Resident microorganisms are able to multiply , not merely survive on the skin.  Normal microbiota  Microorganisms are not found throughout the entire human body but are localized in certain regions.  Microbes can colonize only those body sites that can supply the appropriate nutrients.  The relationship between the normal microbiota and the host is called symbiosis (Revise symbiosis).  Normal microbiota  Many of the microbes that make up our normal microbiota are commensals.  Such as corynebacteria that inhabit the surface of the eye and certain saprophytic mycobacteria that inhabit the ear and external genitals.  These bacteria live on secretions and sloughed-off cells, and they bring no apparent benefit or harm to the host.  Normal microbiota  The normal flora of humans consists of a few eucaryotic fungi and protists.  Bacteria are however the most numerous and obvious microbial components of the normal flora.  A healthy foetus in utero is free from microorganisms.  During birth the infant in exposed to vaginal flora.  Within a few hours of birth oral and nasopharyngeal flora develops and, in a day, or two resident flora of the lower intestine appears  Relationships between the Normal Microbiota and the Host  The normal microbiota can benefit the host by preventing the overgrowth of harmful microorganisms.  This phenomenon is called microbial antagonism, or competitive exclusion.  Consequently, normal microbiota protect the host against colonization by potentially pathogenic microbes by: Competing for nutrients Producing substances harmful to the invading microbes Affecting conditions such as pH and available oxygen Relationships between the Normal Microbiota and the Host  Disease may result when this balance between normal microbiota and pathogenic microbes is disturbed.  E.g. The normal bacterial microbiota of the adult human vagina maintains a local pH of about 4. Normal vaginal microbiota inhibits the overgrowth of the yeast Candida albicans. C. albicans can grow when the balance between normal microbiota and pathogens is upset and when pH is altered. Relationships between the Normal Microbiota and the Host  Dysbiosis occurs if bacterial population is eliminated by: Antibiotics, excessive douching, or deodorants.  Consequently, vaginal pH reverts to nearly neutral, and C. albicans can flourish and become the dominant microorganism there.  This may lead to vaginal infection. Relationships between the Normal Microbiota and the Host Dysbiosis-imbalance of microbial species due to a reduction the microbial diversity within certain bodily microbiota. Beneficial bacteria are usually minimized, whereas harmful bacteria increase in number Factors influencing the composition of the microbiota: Medications Dietary changes Psychological & physical stress  Relationships between the Normal Microbiota and the Host Probiotics are live microbial cultures applied to or ingested that are intended to exert a beneficial effect. Probiotics may be administered with prebiotics. Prebiotics are chemicals that selectively promote the growth of beneficial bacteria. Example is ingesting certain lactic acid bacteria (LAB) to alleviate diarrhoea and prevent colonization by Salmonella enterica.  The normal flora of the oral cavity Bacteria can grow on tooth surfaces in thick layers called dental plaque. Plaque microorganisms produce adherent substances. Acid produced by microorganisms in plaque damages tooth surfaces, and dental caries result. A variety of microorganisms contribute to caries and periodontal disease.  Normal flora of the GI tract  The stomach is very acidic and is a barrier to most microbial growth.  The intestinal tract is slightly acidic to neutral and supports a diverse population of microorganisms in a variety of nutritional and environmental conditions.  Microbial antagonism occurs in the large intestine where E. coli cells produce bacteriocins. Normal flora of the GI tract Bacteriocins are proteins that inhibit the growth of other bacteria of the same or closely related species, such as pathogenic Salmonella and Shigella. Bacteriocins are used in medical microbiology to help identify different strains of bacteria. Similarly, the normal microbiota of the large intestine effectively inhibit Clostridium difficile, possibly by making host receptors unavailable, competing for available nutrients, or producing bacteriocins. Normal flora of the GI tract C. difficile can become a problem after disruption of the normal intestinal microflora. This microbe is responsible for nearly all gastrointestinal infections after antibiotic therapy, from mild diarrhoea to severe or even fatal colitis (inflammation of the colon).  Normal flora of the respiratory tract In the upper respiratory tract (nasopharynx, oral cavity, and throat), microorganisms live in areas bathed with the secretions of the mucous membranes. The normal lower respiratory tract (trachea, bronchi, and lungs) Respiratory microbiota essential for the normal organ function prevents the colonization of pathogens.  Acquiring infectious agents: Portals of entry Skin Infection can occur through the skin following trauma such as burns, cuts and abrasions. In some instances, through insect or animal bites or the injection of contaminated medicines.  Mucous Respiratory tract membranes Acquirin Air contains a large number of g suspended microorganisms. infectiou Almost all of these airborne s organisms are non-pathogenic agents: bacteria and fungi. Portals Averagely, a person inhales of entry approximately 10 000/day. A mucociliary blanket covers the upper respiratory tract and nasal cavity, providing protection.  Mucous membranes Respiratory tract A successful pathogen must avoid: Acquiring  Being trapped in mucous and infectious swallowed. agents:  Phagocytosis by macrophages if deposited in the alveolar sac. Portals of  Digestion if phagocytosed. entry  The possession of surface adhesins, specific for epithelial receptors, aids attachment of the invading microorganism  This prevents removal by the mucociliary blanket.  Acquiring infectious agents: Portals of entry Mucous membranes Respiratory tract Some pathogens export of ciliostatic toxins (i.e. Corynebacterium diphtheriae ) that paralyse the cilial bed. Certain respiratory viruses (e.g. influenza virus) destroy respiratory epithelia. The decrease in ciliated epithelial cells makes the individual susceptible to infection.  Acquiring infectious agents: Portals of entry Mucous membranes Intestinal tract  The extreme acidity and presence of digestive enzymes in the stomach deleterious to many microorganisms.  GIT carries its own commensal flora of yeast and lactobacilli that afford protection by, for example, competing with potential pathogens like Helicobacter pylori.  Bile salts solubilize the outer membrane of many Gram- negative bacteria  Acquiring infectious agents: Portals of entry Mucous membranes Intestinal tract The small intestine is normally colonized by lower numbers of bacteria than the colon. The lower gut is, however, highly populated by commensal microorganisms Acquiring infectious agents: Portals of entry  Mucous membranes Intestinal tract The pathogenicity of incoming bacteria and viruses depends on:  Their ability to survive passage through the stomach and duodenum.  Their capacity for attachment to, or penetration of, the gut wall, despite competition from the commensal flora and the presence of secretory antibodies  Acquiring infectious agents: Portals of entry Mucous membranes Urinogenital tract  The bladder, ureters and urethra are sterile in healthy individuals.  Organisms invading the urinary tract must avoid being detached from the epithelial surfaces and washed out during urination.  Acquiring infectious agents: Portals of entry Mucous membranes Urinogenital tract The female urethra is much shorter ( c. 5 cm) and is more readily traversed by microorganisms that are normally resident within the vaginal vault. Thus, bladder infections are therefore much more common in female.  Acquiring infectious agents: Portals of entry Mucous membranes Urinogenital tract Lactic acid in the vagina gives it an acidic pH (4.0) Together with other products of metabolism, the low pH inhibits colonization by most bacteria Some lactobacilli survive within the vaginal environment. Bacteria able to establish themselves in the vagina are associated with STIs.  Acquiring infectious agents: Portals of entry Mucous membranes Conjunctiva  The conjunctiva is usually free of microorganisms.  It is protected by the continuous flow of secretions from lachrymal and other glands.  Lachrymal fluids contain a number of inhibitory compounds, together with lysozyme.  They can enzymically degrade the peptidoglycan of Gram-positive bacteria such as staphylococci. Acquiring infectious agents: Portals of entry Mucous membranes Conjunctiva Mechanical abrasion or reductions in tear flow can damage the conjunctiva. This increases microbial adhesion and allow colonization by opportunist pathogens. Increased likelihood of infection by physical damage, exposure to chemicals, use of hard & soft contact lenses, damage & infection of the eyelid border  Acquiring infectious agents  Direct penetration  Trauma or surgical procedure  Needlestick  Arthropod bite  Sexual transmission  Transplacental  OBLIGATORY STEPS FOR INFECTIOUS MICROORGANISMS STEP REQUIREMENT PHENOMENON Attachment +/- entry into Evade natural protective Entry (infection) body and cleansing mechanisms Local or general spread in Evade immediate local Spread the body defenses Multiplication Increase numbers Multiplication Evasion of host defenses Evade immune and other Microbial answer to host defenses long enough for defenses the full cycle in the host to be completed Shedding from body Leave body at a site and Transmission (exit) on a scale that ensures spread to fresh hosts Cause damage in host Not strictly necessary but Pathology, disease often occurs Infection vs disease Infection: The Disease: An abnormal colonization and/or condition of body invasion and functions or structure that multiplication of is considered to be pathogenic harmful to the affected microorganisms in the individual (host) host. Any deviation from or interruption of the normal structure or function of any part, organ, or system of the body. Infection vs Disease (definitions) Benign: A non-life or non-health threatening condition. Malignant: a disease tending to become progressively worse and potentially result in death. Contagious: capable of being transmitted from one host to another; communicable, infectious. Infectious dose: number of pathogenic organisms required to cause disease in a given host. Opportunistic microorganisms Symbiotic associations can change under certain conditions. E.g., given the proper circumstances, a mutualistic organism, such as E. coli, can become harmful. Such microbes are called opportunistic pathogens They ordinarily do not cause disease in their normal habitat in a healthy person but may do so in a different environment. Opportunistic microorganisms E. coli is generally harmless as long as it remains in the large intestine; but if it gains access to other body sites, can cause these corresponding diseases: Urinary bladder - urinary tract infections Lungs- pulmonary infections Spinal cord- meningitis Wounds-abscesses.  AIDS is often accompanied by a common opportunistic infection, Pneumocystis pneumonia, Opportuni caused by the opportunistic stic organism Pneumocystis microorga jirovecii. nisms This secondary infection can develop in AIDS patients because their immune systems are suppressed.  In addition, microbes generally considered pathogenic may be haboured but may not Opportunis cause diseases in those tic people. microorgan E.g., Streptococcus isms pneumoniae, a normal resident of the nose and throat, can cause a type of pneumonia. Establishing cause of infectious disease-Koch’s postulates Four criteria were established by Robert Koch to identify the causative agent of a particular disease:  The microbe must be present in every case of the disease.  The microbe must be isolated from the diseased host and grown in a pure culture.  The disease must be reproduced when a pure culture of the pathogen is introduced into a non-diseased susceptible host (laboratory animal).  The microbe must be recoverable from an experimentally infected host. Koch’s postulates  Exceptions to Koch's Postulates Virulent strains of Treponema pallidum (causative pathogen for syphilis),have never been cultivated on artificial media. The causative agent of leprosy, Mycobacterium leprae, has also never been grown on artificial media. Many rickettsial and viral pathogens cannot be cultured on artificial media because they multiply only within cells.  Some pathogens can cause several disease conditions. Mycobacterium tuberculosis, for example, is implicated in diseases of the lungs, skin, bones, and internal organs. Exceptions Streptococcus pyogenes can cause to Koch's sore throat, scarlet fever, skin infections (such as erysipelas), and Postulates osteomyelitis (inflammation of bone), among other diseases. Pneumonia, meningitis, and peritonitis are infectious diseases with poor aetiologies.  Classifying infectious diseases Often classified in terms of how they behave within a host and within a given population:  Communicable disease: any disease that spreads from one host to another, either directly or indirectly. Examples are chickenpox, measles, genital herpes, typhoid fever and tuberculosis.  Contagious disease: one that easily spreads from one person to another. E.g. Chickenpox and measles Noncommunicable disease: one that is not spread from one host to another. E.g. tetanus: Clostridium tetani produces disease only when it is introduced into the body via abrasions or wounds  Classifying infectious diseases Non-communicable diseases are caused by microorganisms that normally inhabit the body and only occasionally produce disease OR By microorganisms that reside outside the body and produce disease only when introduced into the body.  Classifying infectious diseases- Occurrence of a disease (frequency)  Sporadic disease: A disease occurs only occasionally. E.g. typhoid fever in the United States.  Endemic disease: A disease constantly present in a population, it has a constant rate of infection in a community. e.g. the common cold.  Epidemic disease: A disease in which the rate of infection suddenly increases in a community, it affects a large number of people within a community, population, or region.  Pandemic: an epidemic that occurs worldwide  Classifying infectious diseases Severity or duration of disease  An acute disease is one that develops rapidly but lasts only a short time. E.g. influenza.  A chronic disease develops more slowly, and the body’s reactions may be less severe, but the disease is likely to continue or recur for long periods. E.g. tuberculosis and hepatitis B. Classifying infectious diseases- Severity or duration of disease  Subacute disease: intermediate between acute and chronic e.g. subacute sclerosing panencephalitis  A latent disease: The causative agent remains inactive for a time but then becomes active to produce symptoms of the disease. E.g. shingles (caused by varicella virus).  Classifying infectious diseases- Extent of host involvement A local infection is one in which the invading microorganisms are limited to a relatively small area of the body. E.g. boils and abscesses. Systemic (generalized) infection-one in which the microorganisms or their products are spread throughout the body by the blood or lymph. E.g., Measles Focal infection: Here the agents of a local infection enter a blood or lymphatic vessel and spread to other specific parts of the body, where they are confined to Classifying infectious diseases Extent of host involvement Focal infections can arise from infections in areas such as the teeth, tonsils, or sinuses. Sepsis is a toxic inflammatory condition arising from the spread of microbes, especially bacteria or their toxins, from a focus of infection. Classifying infectious diseases- Extent of host involvement Septicaemia (blood poisoning), is a systemic infection arising from the multiplication of pathogens in the blood. Bacteraemia refers to the presence of bacteria in the blood  Classifying infectious diseases- Extent of host involvement  Toxemia-presence of toxins in the blood (as occurs in tetanus).  Viremia-refers to the presence of viruses in blood.  A primary infection-an acute infection that causes the initial illness.  Classifying infectious diseases Extent of host involvement A secondary infection - one caused by an opportunistic pathogen after the primary infection has weakened the body's defenses. E.g., Pneumocystis pneumonia A subclinical (inapparent) infection does not cause any noticeable illness. Poliovirus and hepatitis A virus, for example, can be carried by people who never develop the illness. Classifying infectious diseases Nosocomial infections: an infection acquired in a hospital setting that was not present in the host prior to admission, generally occurring within 72 hours of admission. Nosocomial infections represent the eighth leading cause of death in the United States. Classifying infectious diseases A nosocomial infection does not show any evidence of being present or incubating at the time of admission to a hospital. It is acquired as a result of a hospital stay.  Classifying infectious diseases Factors that facilitate the acquisition of nosocomial infections are: Microorganisms in the hospital environment The compromised immune status of the host The chain of transmission in the hospital.  Nosocomial infections in acute care institutions Infection site % of all nosocomial Common causative agents infections Urinary tract 40% Escherichia coli, Enterococcus, Proteus, Klebsiella, Pseudomonas aeruginosa Surgical wound 20% Staphylococcus aureus, Staphylococcus epidermidis, E. coli Pulmonary 10% Klebsiella, Pseudomonas, E. coli, S. aureus Classifying infectious diseases Iatrogenic diseases are diseases induced by a Diagnostic medical treatment or Therapeutic procedures investigation Occurs when deleterious effects of the therapeutic or diagnostic regimen causes pathology independent of the condition for which the regimen is advised. Patterns of disease Development of disease Once a microorganism overcomes the defenses of the host, development of the disease follows a certain sequence that tends to be similar whether the disease is acute or chronic.  A predisposing factor makes the body more susceptible to a disease and may alter the course of the disease. E.g. gender in (UTI) and pneumonia, genetics (in sickle cell anaemia)  Other predisposing factors include inadequate nutrition, age, lifestyle, occupation, preexisting illness, chemotherapy  Development of disease  The incubation period is the interval between the initial infection and the first appearance of any signs or symptoms. The incubation period depends on: Specific microorganism involved. Virulence The number of infecting microorganisms The resistance of the host.  Development of disease The prodromal period: a relatively short period that follows the period of incubation in some diseases. It is characterized by early, mild symptoms of disease, such as general aches and malaise. Period of illness-the disease is most severe in this period. Exhibition of overt signs and symptoms of disease (fever, chills, photophobia etc) Development of disease Period of decline: Signs and symptoms subside. During this phase, which may take from less than 24 hours to several days, the patient is vulnerable to secondary infections. Period of convalescence: strength is regained and the body returns to its prediseased state. Recovery has occurred. People can serve as reservoirs of disease and can easily spread infections to other people during this period (typhoid fever and cholera). However, spread of infection can also occur during the Stages of disease Spread of infection What are the sources of pathogens and how are diseases transmitted?  Reservoir of infection: refers to either a living organism or an inanimate object that provides a pathogen with adequate conditions for survival and multiplication, and an opportunity for transmission.  Reservoirs ensure a continual source of the disease organism.  Read about human, animal and non-living reservoirs. Spread of infection Carrier (carrier state): An asymptomatic individual who is host to a pathogenic microorganism with the potential to pass the pathogen to others (Typhoid Mary). Human carriers play an important role in the spread of such diseases as AIDS, diphtheria, typhoid fever, hepatitis, gonorrhoea, amoebic dysentery, and streptococcal infections.  Spread of infection Major non-living reservoirs of importance are soil and water. Soil: important reservoirs for pathogens such as fungi, Clostridium botulinum and C. tetani. Both species of clostridia are part of the normal intestinal microbiota of horses and cattle. Thus, the bacteria are found especially in soil where animal faeces are used as fertilizer. Spread of infection Water: contaminated (faeces) water habour several pathogens such as Vibrio cholerae and Salmonella typhi. Other non-living reservoirs include foods that are improperly prepared or stored. They may be sources of diseases such as trichinellosis and salmonellosis.  Transmission of disease The causative agents of disease can be transmitted from the reservoir of infection to a susceptible host by three principal routes: Contact Vehicles Vectors Contact transmission-spread of an agent of disease by direct contact, indirect contact, or droplet transmission.  Transmission of disease  Direct contact transmission (person-to -person transmission):  direct transmission of an agent by physical contact between its source and a susceptible host. No intermediate object is involved.  Touching, kissing, and sexual intercourse-most common forms of direct contact. Examples of diseases spread by direct contact are: Viral respiratory tract diseases such as common cold and influenza Staphylococcal infections, hepatitis A, measles, scarlet fever, STIs Transmission of disease Indirect contact transmission: causative agent is transmitted from its reservoir to a susceptible host by means of a non-living object. Fomite refers to any non-living object involved in the spread of an infection. E.g., tissues, handkerchiefs, towels, bedding, eating utensils, and money. Droplet transmission is a third type of contact transmission in which microbes are spread in droplet nuclei (mucus droplets) that travel only short distances.  Transmission of disease Droplets are discharged into the air by coughing, sneezing, laughing, or talking and travel less than a meter from the reservoir to the host. Disease agents that travel such short distances are not regarded as airborne. Influenza, pneumonia, and pertussis (whooping cough) are spread by droplet transmission. Vehicle transmission is the transmission of disease agents by a medium, such as water, food, or air. Further distinguished as:  Transmission of disease Vehicle transmission further distinguished as: waterborne transmission-usually spread by water contaminated with untreated or poorly treated sewage. e.g., cholera, waterborne shigellosis, and leptospirosis Airborne transmission: spread of agents of infection by droplet nuclei in dust that travel more than 1 meter from the reservoir to the host (tuberculosis). Foodborne pathogens are generally transmitted in foods that are incompletely cooked, poorly refrigerated, or prepared under unsanitary conditions. Foodborne pathogens cause diseases such as food poisoning and tapeworm infestation. THANK YOU