MPHA 5P07 Lecture 1 FALL 2024 PDF

Lecture 1: Introduction to Medical Microbiology  Objectives 1. Define medical microbiology. 2. Understand the history of medical microbiology. 3. Identify normal flora in specific areas of the body and how organisms infect the body while evading the i...

Lecture 1: Introduction to Medical Microbiology  Objectives 1. Define medical microbiology. 2. Understand the history of medical microbiology. 3. Identify normal flora in specific areas of the body and how organisms infect the body while evading the immune system. 4. Identify characteristics of the immune system. 5. Define communicable disease and infectious disease. 6. Identify the various stages that make up the course of an infectious disease. 7. Identify characteristics of infectious disease agents. 8. Be able to explain the innate and adaptive immune response and how it maintains human health. 2  What is Medical Microbiology Microbiology may be defined as the science or study of microscopic organisms, i.e., organisms too small to be observed with the naked eye (from the Greek terms: micro = small, bio = life, and logos = discourse in or study of). Medical microbiology is also known as clinical microbiology. Medical microbiology is a subdiscipline of microbiology that focuses on the study of microorganisms such as parasites, fungi, bacteria, viruses, and prions and their relationship to human health and disease. It involves the study of the pathogenesis and epidemiology of these microorganisms. Hsu, L.Y. (2013). Medical Microbiology. In: Runehov, A.L.C., Oviedo, L. (eds) Encyclopedia of Sciences and Religions. Springer, Dordrecht. 3 https://doi.org/10.1007/978-1-4020-8265-8_672  History of Medical Microbiology The term microbe was coined in the last quarter of the 19th century. Long before microbes had been seen, observations on communicable diseases had given rise to the concept of contagion - the spread of disease by contact, direct, or indirect. 4  History of Medical Microbiology Antonie van Leeuwenhoek ~ Father of Microbiology He constructed the first microscope He was first person to observe microorganisms He first accurately described the different shapes of bacteria as cocci (spheres), bacilli (rods), and spirochetes (spiral filaments). https://www.britannica.com/biography/Antonie-van-Leeuwenhoek 5  History of Medical Microbiology Louis Pasteur ~ Father of Medical Microbiology Coined the term microbiology Proposed germ theory of fermentation Developed sterilization techniques Discovered that microorganisms cause fermentation Studies on silkworm disease Originated the process of pasteurization Developed vaccines against anthrax and rabies https://www.britannica.com/biography/Louis-Pasteur/ 6  History of Medical Microbiology Joseph Lister ~ Father of Modern Surgery He developed a system of antiseptic surgery - designed to prevent microorganism from entering wounds. He established the guiding principle of antisepsis for good surgical practice. https://www.britannica.com/biography/Joseph-Lister/ 7  History of Medical Microbiology Robert Koch ~ Father of Bacteriology He was the first to use hanging drop method by studying bacterial motility. He was the first to use an oil immersion lens and a condenser that enabled smaller objects to be seen. He was also the first to effectively use photography (microphotography) for microscopic observation. He proved that microorganisms cause disease – Koch’s postulates. Discovery of tuberculosis bacterium. https://www.britannica.com/biography/Robert-Koch/ 8 History of Medical Microbiology Because of Koch's work, the etiological agents for many important human diseases were identified in rapid succession between the years of 1876 and 1898. By 1900, the microorganisms responsible for major human diseases including cholera, diphtheria, leprosy, plague, tetanus, tuberculosis and typhoid had been identified. The period of years between 1857 and 1914 is sometimes referred to as the “Golden Age of Microbiology”, because rapid advancements and discoveries made during this period led to the establishment of microbiology as a science. During their search for disease causing agents, Koch and other microbiologists made important contributions to the techniques and materials used in the culture of microorganisms. 9 History of Medical Microbiology Richard J. Petri - developed the Petri dish in which microbial cultures could be grown and manipulated. Fanny Hesse - developed the use of agar as a solidifying agent for microbiological media. Hans Christian Gram - developed the Gram stain, a stain technique that could be used to separate two major groups of disease causing bacteria. 10  History of Medical Microbiology During the 20th century, microbiology experienced significant growth, with the emergence of key subfields such as immunology, virology, and molecular genetics, particularly through advances in recombinant DNA technology. These disciplines have not only deepened our understanding of microbial life but also transformed medicine, agriculture, and biotechnology. Future discoveries in microbiology hold the potential to revolutionize areas like food and fuel production, and environmental remediation - innovations that are becoming increasingly essential as the global population expands. Microbes may ultimately play a role in guiding humanity toward a more sustainable and balanced coexistence with the natural world. 11  Organisms In The Body Normal flora (microbiota) is an extensive array of organisms that live symbiotically in and on the host, particularly on the skin and mucous membranes. Altering the balance of the microbiota can lead to disease. For example, antibiotic use can disrupt the normal flora in the gut. Wil learn about normal flora in specific areas of body and how organisms infect the body while evading immune system Will also learn about how pathogens spread 12  Location of Normal Flora There are 7 major anatomical sites that are colonized by organisms (called their flora). Each site has its own distinctive flora. Genitourinary Tract GI Tract Respiratory Tract Eyes Mouth Female Genital Tract Skin 13  Location of Normal Flora Genitourinary Tract The organisms residing in the urethra are similar to those on the skin in the same anatomical site; however, urination washes off all organisms. The bladder, ureters, and kidneys are considered not to have any normal flora. Facultative Anaerobe: organism that makes ATP by aerobic respiration if GI Tract oxygen is present, but is capable of The flora present in the GI tract is dependent on location. switching absent to fermentation if oxygen is The upper GI tract has fewer organisms that are mainly facultative anaerobes, whereas the lower GI tract has more organisms present that are mainly anaerobes. Stomach acids, peristalsis, and digestive enzymes limit the growth of these organisms. There are some bile-resistant organisms that can survive in the GI tract. Examples of normal flora of the GI tract include Enterobacteriaceae, anaerobic bacteria, and Enterococci. 14  Location of Normal Flora Respiratory Tract The respiratory tract is typically sterile and is maintained by physical mechanisms such as the mucociliary elevator and coughing. Chemical mechanisms of this system include: Lysozyme: enzyme present in respiratory secretions that breaks down the cell wall of organisms. Lactoferrin: binds free iron required by bacteria, limiting their growth. Secretory Ig A: antibody found in secretions that prevent colonization of organisms in the upper respiratory tract. Alveolar Macrophages: immune cells that can engulf organisms that reach the lungs. Eyes The conjunctiva does not have normal flora as tears, blinking, and lysozyme control the presence of organisms. Mechanical deposition is the primary way that one can get conjunctival infections i.e. rubbing your eyes with your fingers or towels. Examples of normal flora of the eyes include transient organisms from the skin such as: Corynebacteria Staphylococci Streptococci Propionibacterium 15  Location of Normal Flora Skin The normal flora of the skin varies depending on the conditions of the skin. Only certain organisms can live on dry skin. PH differences throughout the skin limit the survival of some organisms. Shedding of skin removes organisms located on those cells. Sebaceous glands are an important component of the skin and secrete complex lipids which serve as substrate for bacteria that are part of the normal flora. These bacteria, in turn, create end products that are inhibitory for potentially pathogenic organisms, hence protecting the skin from infection. Normal flora on the skin include: § Staphylococcus aureus § Staphylococcus epidermidis § Propionibacterium acnes § Corynebacterium species 16  Location of Normal Flora Mouth The flora in the oral cavity depends on the dental hygiene of the individual, with swallowing and the presence of saliva controlling the overgrowth of the normal flora. Examples of normal flora of the mouth include: § Streptococcus § Staphylococcus § Corynebacterium Female Genital Tract The vaginal flora alters with age. In prepubescent and postmenopausal women, vaginal flora is equivalent to that of the skin. In women of childbearing age there are several microorganisms present; however, there is a predominance of Lactobacillus species, which have low pathogenic potential. Lactobacillus species play a central role in determining vaginal health, producing lactic acid, and creating an acidic pH in the vagina, which limits growth of potentially harmful bacteria. Normal flora of the female genital tract include: § Steptococcus species § Lactobacillius species § Cornebacterium species 17  The Immune System The immune system has many nonspecific host defense mechanisms that help maintain the balance in the normal flora. If these nonspecific defenses are disturbed or altered, there is an imbalance in the normal flora, which can lead to infection or disease. The inflammatory response is the next line of defense, primarily against bacteria. If the inflammatory responses can be avoided, the organism can go on to cause disease. 18  The Inflammatory Response An acute inflammatory response acts as a barrier to infection. Signs of inflammation include: Tissue redness (erythema) Tissue swelling (edema) Heat Pain Kegel, M. (2016, September 29). Potential Scleroderma Therapy Seen to Stop Inflammation in Phase 1 Trial. Retrieved December 10, 2024, from https://sclerodermanews.com/2016/09/29/corbus-scleroderma- treatment-resunab-shows-promise-in-phase-1-study 19  PHAGOCYTOSIS Phagocytosis Phagocytosis is an important method of eliminating invading pathogens. This process is activated by the recognition of Pathogen-associated molecular patterns (PAMPs). PAMPs: are small molecule motifs conserved within a group of pathogens that are recognized by phagocytes of the innate immune system. The process of phagocytosis involves five major steps: 1. Attachment 2. Ingestion 3. Fusion with vesicles containing digestive enzymes 4. Digestion 5. Release Kegel, M. (2016, September 29). Potential Scleroderma Therapy Seen to Stop Inflammation in Phase 1 Trial. Retrieved January 06, 2024, from https://sclerodermanews.com/2016/09/29/corbus-scleroderma- treatment-resunab-shows-promise-in-phase-1-study 20  Potential Pathogens vs. Strict Pathogens Bacteria that are part of the normal flora are either non-pathogens or potential pathogens. Potential pathogens are capable of causing disease when there is an imbalance in the host. The presence and expression of one or more virulence factors determines whether an organism is a potential pathogen (e.g. Staphylococcus aureus) or a strict pathogen (e.g. Vibrio cholera). In contrast, strict pathogens are not considered to be part of the normal flora, such that when they colonize a host, they will cause disease. If an individual is not protected via previous exposure or vaccination, it is very likely that they will become infected once exposed to a strict pathogen. Examples of strict pathogens include: Ebola Virus Influenza Virus Corynebacterium diphtheriae (causes diphtheria) Salmonella enterica Plasmodium species (parasite that causes Malaria) Vibrio cholera 21  Pathogenicity Potential Pathogens which can be part of the normal flora can become pathogenic via 2 main mechanisms: ORGANISM TRANSLOCATION Organisms translocate into a sterile space. The most obvious example of this is the seeding of normal flora into otherwise sterile sites that include blood, cerebrospinal fluid, or bone marrow. In this case, the translocation of the organisms to a normally sterile body site results in clinical disease. For example, Staphylococcus aureus is normally present on the skin, but if it translocates into blood, it can lead to clinical disease and is the leading cause of bacteremia, sepsis, and endocarditis - all of which are associated with significant morbidity and mortality. COMPROMISED DEFENSES Potential pathogens can also be pathogenic when the host’s natural defenses are compromised. These immunocompromised patients can include those that take immunosuppressive drugs following a transplant and those with inherited immune diseases. In this case, colonization with a potential pathogen that would not normally cause infection can become pathogenic as the host defenses cannot control infection. For example, reactivation of Cytomegalovirus in organ transplant patients. 22  Pathogenesis The host immune system has several defenses in place to prevent pathogen from invading the body, however, pathogens have developed novel methods to evade the immune system and establish infection. The three mechanisms by which organisms evade the immune response to establish infection are: 1. Avoiding ingestion by phagocytosis 2. Avoiding being killed by phagocytosis 3. Antigenic variation 23  MECHANISMS TO EVADE THE IMMUNE SYSTEM: 1 Avoid Ingestion by Phagocytes There are two ways in which an organism may avoid ingestion by a phagocyte. Opsonization Prevented (capsule) Organisms that have a capsule can avoid phagocytosis. Opsonization by the host immune cells is required to phagocytose these organisms. However, developing antibodies for the capsule takes 7-10 days (adaptive immune system lag time). This lag time permits these organisms to initiate disease. Examples of organisms that have capsules include Neisseria meningitidis, Haemophilus influenzae, and, Streptococcus pneumoniae. Opsonization: Immune process where pathogens are marked for destruction by an immune cell. Biofilm If an organism has the capacity to develop a slime layer (biofilm), it is protected from antibodies, antibiotics, and inflammatory cells. An example of these organisms is Staphylococcus epidermidis, which is part of the normal flora. Some strains have the ability to form a hydrophobic biofilm that can stick to foreign objects such as medical devices. 24  MECHANISMS TO EVADE THE IMMUNE SYSTEM: 2 Some pathogens may not be able to avoid being opsonized by phagocytes, but they can avoid being killed once engulfed in 3 main ways : Avoid Being Killed by Phagocytes Once pathogens are in phagocyte, pathogen can remain and survive in cytoplasm Phagolysosome fusion inhibited Fusion of phagosome and lysosome inhibited by organism (e.g. Mycobacterium tuberculosis, Chlamydia). Survival within this requires pathogen to prevent fusion of phagosome and lysosome (Forms phagolysosome) Escape into cytoplasm Organism escapes from the phagolysosome into the cytoplasm and replicates within phagocytes (i.e. Francisella tularensis). Resistance to Killing Organism resists being killed by producing enzymes (e.g. by catalase in Staphylococci). enzyme capable to breakdown chemicals produced by phagocytes to kill pathogen Survival in phagocytic cell can be beneficial for some pathogens, providing means of long term survival, transfer to other sites and spread of infection 25  Another example of how some pathogen avoid post defenses: an Antigenic Variationtigenic Some pathogens have the ability to alter the expression of specific proteins on their surface (antigens). When this happens, any antibodies previously developed for that pathogen will be ineffective in targeting that pathogen. This is known as antigenic variation. A common example of a pathogen that makes use of antigenic variation to evade the immune system is the influenza A virus. This virus undergoes minor antigenic variation yearly (antigenic drift) and major antigenic variation (antigenic shift) every several decades. 26  The Course of Infectious Disease CONVALESCENCE INCUBATION PHASE ACTIVE PHASE PHASE DEFINITION This is the time interval During this phase, the infecting Recovery period between the introduction organisms are actively following illness. of an organism and the multiplying and causing onset of illness. damage to the host. SYMPTOMS This stage is asymptomatic, This phase is always During this phase the but the patient may be symptomatic, and patients are patient may still be contagious. highly contagious. contagious LENGTH OF Length varies from days Length varies from days (e.g. Length varies from PHASE (e.g. influenza virus, Norovirus: 1 to 3 days) to weeks (e.g. Norovirus: Norovirus) to weeks (e.g. weeks (e.g. Chickenpox: 1 to 2 weeks) to years Chickenpox, Syphilis). typically, 1-2 weeks), to months (e.g. Syphilis: 5-20 (e.g. Syphilis: up to 3 months years without for the primary infection). treatment). 27  Duration of Symptom Diseases can be classified as acute, chronic, or latent based on time to symptom onset and duration of the active phase. Acute: rapid onset and has a short duration (e.g. Streptococcus pyogenes - causative agent of Strep throat). DURATION Chronic: disease develops slowly and has a long duration (e.g. H I V). OFLatent: the infection is never completely eliminated, although symptoms might disappear over time (e.g. Tuberculosis). SYMPTOMS Both bacteria and viruses can cause latent infections. BACTERIA § Bacterial latency is not nearly as common as viral latency. § The original bacteria remain alive in the host and can therefore reactivate and multiply at a later time (e.g. latent T B and syphilis). VIRUS The genetic information of the virus incorporates into either the host's genome (HIV) or associated with the host's cells to be expressed later. 28  Carriers of Infection Convalescent Carrier A convalescent carrier is a person who has recovered from the disease and still carries the pathogen. A famous example is Typhoid Mary - an Irish-American cook who was the carrier of Salmonella Typhi and presumed to have infected 51 people, three of whom died. Asymptomatic Carrier An asymptomatic carrier is a person who has contracted the pathogen but is free from disease symptoms. Two common examples are Chlamydia trachomatis and Neisseria gonorrhoeae, with a large percentage of infected individuals never developing any symptoms. 29  Reservoirs Reservoirs are sites where infectious pathogens can persist for long periods of time. Reservoirs can be broadly classified as biological (human or non-human) or environmental. Human Humans are the natural reservoirs for a vast majority of communicable diseases. Carriers can be either asymptomatic or can host antibiotic-resistant bacteria, such as Methicillin Resistant Staphylococcus aureus (MRSA). Non-human Animals are a common source of human pathogens. GI pathogens often spread due to poor animal and food handling practices. An example is poultry meat which may carry Campylobacter and Salmonella. 30  Reservoirs Environmental A typical example is a doorknob that can harbor the influenza virus after someone with a cold has sneezed into their hand and then opened the door. Tetanus (Clostridium tetani) can be contracted from stepping on a contaminated rusty nail. 31  What Happens if a Host is Exposed to an Infectious Agent? The host may have No infection Infection If infected, the host may have No disease Present with disease van Seventer, J. M., & Hochberg, N. S. (2017). Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control. International Encyclopedia of Public Health, 22–39. https://doi.org/10.1016/B978-0-12-803678-5.00516-6 32  Characteristics of Infectious Disease Agents Agent factors (Pathogen factors) Host Factors (example, Human host) Infectivity Individual susceptibility to the infection Pathogenicity Virulence Toxigenicity Resistance Antigenicity van Seventer, J. M., & Hochberg, N. S. (2017). Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control. International Encyclopedia of Public Health, 22–39. https://doi.org/10.1016/B978-0-12-803678-5.00516-6 Robert H. Friis and Thomas A. Sellers. Epidemiology for public health practice, Fifth edition (2014) 33  Infectivity Infectivity Infectivity is the likelihood that an infectious agent will infect a host, given that the host is exposed to the agent. Refers to the capacity of the infectious agent to enter and multiply in a host and produce infection or disease. Polio and Measles have high infectivity. Measured by secondary attack rate. !"#$%& '( )*+%+ *#',- )',.*).+ '( /&0#*&1 )*+%+ 𝑆𝑒𝑐𝑜𝑛𝑑𝑎𝑟𝑦 𝐴𝑡𝑡𝑎𝑐𝑘 𝑅𝑎𝑡𝑒 % = x100% !"#$%& '( +"+)%/.0$2% /%&+',+ 0,.3% -&'"/40,0.0*2 )*+%(+) van Seventer, J. M., & Hochberg, N. S. (2017). Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control. International Encyclopedia of Public Health, 22–39. https://doi.org/10.1016/B978-0-12-803678-5.00516-6 Robert H. Friis and Thomas A. Sellers. Epidemiology for public health practice, Fifth edition (2014) 34  Pathogenicity Pathogenicity refers to the ability of an agent to cause disease in an infected host. Measles is a disease of high pathogenicity [few subclinical cases (no recognizable clinical signs and symptoms)] Polio is a disease of low pathogenicity (most cases of polio are subclinical) Measured by the ratio of the number of individuals with clinically apparent disease to the number exposed to an infection. 35 van Seventer, J. M., & Hochberg, N. S. (2017). Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control. International Encyclopedia of Public Health, 22–39. https://doi.org/10.1016/B978-0-12-803678-5.00516-6 Robert H. Friis and Thomas A. Sellers. Epidemiology for public health practice, Fifth edition (2014)  Virulence Virulence Is the likelihood of causing severe disease among those with disease. !"# $%&'#( )* !)!+, -+.#. /0!" )1#(! 0$*#-!0)$ Virulence is measured = !)!+, $%&'#( )* 0$*#-!#2 -+.#. If the disease is fatal, virulence is measured by case fatality rate (CFR) 3%&'#( )* 2#+!". 2%# !) + 20.#+.# “5” CFR= x 100% during a time period 3%&'#( )* 7+.#. )* 20.#+.# “5” The rabies virus is almost always fatal in humans and an extremely virulent agent with a high CFR 36 van Seventer, J. M., & Hochberg, N. S. (2017). Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control. International Encyclopedia of Public Health, 22–39. https://doi.org/10.1016/B978-0-12-803678-5.00516-6 Robert H. Friis and Thomas A. Sellers. Epidemiology for public health practice, Fifth edition (2014)  Toxigenicity Is the capacity of the agent to produce toxins or poisons. Botulism and shellfish poisoning results from the toxin produced by the Microorganism. Robert H. Friis and Thomas A. Sellers. Epidemiology for public health practice, Fifth edition (2014) 37  Resistance Of The Microbial Agent The ability of the agent to survive adverse environmental conditions. Microbial agents such as coccidioidomycosis (causes Valley fever) and hepatitis, are very resistant. Gonococcus and influenza viruses are extremely fragile. 38 Robert H. Friis and Thomas A. Sellers. Epidemiology for public health practice, Fifth edition (2014)  Antigenicity (Immunogenicity) Antigenicity (Immunogenicity) Refers to the ability of the microbial agent to induce antibody production in the host. Infectious agents may or may not induce long-term immunity against infections. Repeated reinfection is common with gonococci Repeated reinfection with measles is thought to be rare. 39 Robert H. Friis and Thomas A. Sellers. Epidemiology for public health practice, Fifth edition (2014)  Individual Susceptibility to Infection and Disease Susceptibility refers to the ability of an exposed individual (or group of individuals) to resist infection or limit disease as a result of their biological makeup. Factors influencing susceptibility include both innate, genetic factors and acquired factors such as the specific immunity that develops following exposure or vaccination. Susceptibility can also be affected by extremes of age, stress, pregnancy, nutritional status, and underlying diseases. These latter factors can impact immunity to infection, as illustrated by immunologically naïve infant populations, aging populations experiencing immune senescence, and immunocompromised HIV/AIDS patients. 40 Taken directly from: van Seventer, J. M., & Hochberg, N. S. (2017). Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control. International Encyclopedia of Public Health, 22–39. https://doi.org/10.1016/B978-0-12-803678-5.00516-6  Mechanisms of Immunity The human body has a variety of mechanisms that provide protection against infectious agents There are two systems of immunity that work together to provide protection: Innate immune system Adaptive (acquired or specific) immune system 41 Battle C. Essentials of public health biology: A guide for the study of pathophysiology. Jones & Bartlett Publishers; 2009 Oct 6.  Innate vs. Acquired Immunity Innate Immunity Acquired Immunity Present from birth and is the first line of Involves that activation of immune cells and development of defense against infectious agents substances that will aid in the elimination of the pathogen and facilitate immunological memory. The response is nonspecific, that is, it does Specific response (humoral and cell mediated) not differentiate between different Humoral immunity (B cells - involved in Antibody challenges and reacts in the same manner no production and memory cells) matter what the pathogen is. Cell mediated immunity(T cells - involved in memory cells, cytotoxic cells, helper cells and suppressor cells) A wide range of anatomical and physiological barriers create an environment that is inhospitable to the pathogen. No memory cells (if second exposure with the pathogen takes place innate immunity will not remember the first encounter) Battle C. Essentials of public health biology: A guide for the study of pathophysiology. Jones & Bartlett Publishers; 2009 Oct 6. 42  Comparison of Active and Passive Immunity Active Passive Natural infection- exposure to infectious agent and Natural- Maternal antibodies production of antibodies and memory cells by natural means Acquired- Immunity could be artificially obtained by Acquired- Artificially through injection of means of vaccination immunoglobulin Battle C. Essentials of public health biology: A guide for the study of pathophysiology. Jones & Bartlett Publishers; 2009 Oct 6. 43