PRINCIPLES OF DISEASE AND EPIDEMIOLOGY Sunday, October 25, 2020 2:09 PM PATHOLOGY - Scientific study of disease ETIOLOGY -cause of disease Example : Anthrax which was first proved to be caused by Bacillus anthracis. Done by Robert Koch. PATHOGENESIS - manner of development. "How the disease developed into different stages" CHANGES - sign and symptoms that the patient experienced with the disease INFECTION - invasion or colonization of the body by pathogenic microorganisms. Pathogenic causes diseases DISEASE - abnormal state in which part or all of the body is incapable of performing normal functions. It does not rely on the presence of signs and symptoms but any abnormalities or disturbance on the homeostasis of the body. MICROBES IN OUR LIVES NON-PATHOGENIC MICROORGANISM - Greatly represented by our normal microflora or also called as microbiota • This organism are normally present inside the body without causing any harm. They begin to establish before birth. • Upon birth, from the vagina of the mother, the normal microflora there is transferred to the baby and some of these microorganisms plays a role in the protection or in the immunity of the child as it develop more • The Human Microbiome is the collection of all the normal microflora. They begin to establish themselves in an individual before birth (in utero). The placental microbiome consists of only few different bacteria, mostly Enterobacteriaceae and Propionibacterium. These bacteria are found in the newborn’s intestine. • Just before a woman gives birth, lactobacilli in her vagina multiply rapidly, and they become the predominant organisms in the newborn’s intestine. These lactobacilli also colonize the newborn’s intestine. • More microorganisms are introduced to the newborn’s body from the environment when breathing and feeding start. • An individual’s microbiome changes rapidly during the first three years as the personal microbiome becomes established. • After birth, E. coli and other bacteria acquired from foods, people, and pets begin to inhabit the large intestine. These microorganisms remain there throughout life and, in response to altered environmental conditions, may increase or decrease in number and contribute to health and disease. • When immune system gets lower, these normal microflora will decrease and cause infections that causes disease Different microorganisms that belongs to the human microbiota are distributed into the different parts of the body -this distribution and composition of the normal microbiome is affected by many factors such as: Physical & Chemical factors - They can be present in the different parts because of the optimum environment or conditions for their growth Temperature, pH, Sunlight, Oxygen, & CO2 conc. Example : S. aureus are mostly present in the nose or the nasal cavity because they like the cold temperature Lactobacilli is mainly present in the vagina and maintains the acidity - Each microorganisms present has a normal microflora in our body has a normal location Example: S.aureus doesn't cause any infection because it is their location E. coli is generally harmless as long as it remains in the large intestine; but if it gains access to other body sites, such as the urinary bladder, lungs, spinal cord, or wounds, it may cause urinary tract infections, pulmonary infections, meningitis, or abscesses, respectively Host's Defenses - when the defenses of the host weakens, our microflora could be against us or cause opportunistic infections. Or, if the host is already weakened or compromised by infection, microbes that are usually harmless can cause disease. AIDS is often accompanied by a common opportunistic infection, Pneumocystis pneumonia, caused by the MIDTERM MICROPARA LEC Page 1 AIDS is often accompanied by a common opportunistic infection, Pneumocystis pneumonia, caused by the opportunistic organism Pneumocystis jirovecii Immunocompromised patients Mechanical Factors - Includes the chewing actions of the teeth and tongue movements can dislodge microbes attached to tooth and mucosal surfaces. In the gastrointestinal tract, the flow of saliva and digestive secretions and the various muscular movements of the throat, esophagus, stomach, and intestines can remove unattached microbes. - The flushing action of urine also removes unattached microbes. This is why it is advice to urinate every after sexual intercourse to flash all the possibly introduced microorganism that would cause urinary tract infection. - The flushing action of urine also removes unattached microbes. In the respiratory system, mucus traps microbes, which cilia then propel toward the throat for elimination. Chewing RELATIONSHIP BETWEEN HOST AND BACTERIA - Once established, the normal microbiota can benefit the host by preventing the overgrowth of harmful microorganisms. This phenomenon is called microbial antagonism, or competitive exclusion. Your normal microbiota will compete with the introduced bacteria which could be pathogenic. thereby preventing the growth of the pathogenic bacteria. - For example, the normal bacterial microbiota of the adult human vagina maintains a local pH of about 4. The presence of normal microbiota inhibits the over- growth of the yeast Candida albicans, which can grow when the pH is altered. If the bacterial population is eliminated by antibiotics, excessive douching, or deodorants, the pH of the vagina reverts to nearly neutral, and C. albicans can flourish and become the dominant microorganism there. This condition can lead to a form of vaginitis (vaginal infection). - Another example of microbial antagonism occurs in the large intestine. E. coli (being normal microflora) cells produce bacteriocins, proteins that inhibit the growth of other bacteria of the same or closely related species, such as pathogenic Salmonella and Shigella. - A final example involves another bacterium, Clostridium difficile, also in the large intestine. The normal microbiota of the large intestine effectively inhibit C. difficile, possibly by making host receptors unavailable, competing for available nutrients, or producing bacteriocins. However, if the normal microbiota are eliminated (for example, by antibiotics), C. difficile can become a problem. This microbe is responsible for nearly all gastrointestinal infections that follow antibiotic therapy, from mild diarrhea to severe or even fatal colitis (inflammation of the colon). Symbiosis - At least 1 is dependent to another Commensalism - S. epidermidis in the skin; Corynem bacterium in the eye These bacteria live on secretions and sloughedoff cells, and they bring no apparent benefit or harm to the host. Mutualism - is a type of symbiosis that benefits both organisms. For example, the large intestine contains bacteria, such as E. coli, that synthesize vitamin K and some B vitamins. Parasitism - One benefits at the expense of the other. For example is the pathogenic bacteria, they thrive to the expense of the host Microorganism can cause different types of infection. ETIOLOGY OF DISEASE Demonstration of Koch's postulate • POSTULATE 1 ○ The same microorganisms are present in every case of the disease. ▪ Example: Anthrax- present is bacillus anthracic • POSTULATE 2 ○ Explains to us the idea of culture. ○ The microorganism are isolated from the tissues a dead animal in a pure culture. • POSTULATE 3 ○ Inoculation of pure culture into a healthy susceptible animal reproduced the disease. MIDTERM MICROPARA LEC Page 2 ○ Inoculation of pure culture into a healthy susceptible animal reproduced the disease. • POSTULATE 4 ○ The identical microorganisms are isolated in pure culture from lesions of the experimental animal In general, most microorganisms seek to follow Koch postulate but we have some exemptions. Some of them cannot be cultured in an artificial media EXEMPTIONS • • • • T. PALLIDUM M. LEPRAE RICKETTSIA SSP. VIRUSES – Intracellular parasites. There could be a problem in postulate number 2 OTHER ISSUES ON KOCH POSTULATES • COMMON SIGNS & SYMPTOMS • 1 BACTERIA= >1 DISEASES • ETHICAL CONSIDERATIONS - issue in usage of different animal subjects wherein we intentionally infect them or kill them to get the pure isolates. - In other cases, 2 or more organisms could work in synergy to cause disease. - 1 organism can cause several diseases. - Symptoms could also be similar across diseases, this can be an issue to postulate 3 and 4. DEVELOPMENT OF DISEASE Microbes overcomes the host's defenses • INCUBATION PERIOD ○ No signs or symptoms. ○ Interval between the initial infection and the first appearance of signs and symptoms. ○ Could range from days • PRODROMAL PERIOD ○ Mild signs or symptoms ○ Relatively short period wherein it is characterized by the currently mild symptoms of the disease. This could include weakness of the body, body pains etc. • PERIOD OF ILLNESS ○ Most severe signs and symptoms ○ Fever, chills, sore throat, muscle pain, gastrointestinal disturbances, etc. ○ During this period the white blood cells may increase or decrease. • PERIOD OF DECLINE ○ Signs and symptoms subside ○ Fever decreases ○ Patient is vulnerable to secondary infections->susceptible of another infection • PERIOD OF CONVALESCENCE ○ Regains strength ○ Recovery has occurred Which stage do you think people can surpass reservoir of disease or can easily spread the infection to other people? PERIOD OF ILLNESS THE SPREAD OF INFECTION Reservoir –> mode of transmission (droplet, direct contract, vector, vehicle, airborne) -> Susceptible host CHAIN OF INFECTION • GERMS (AGENT) ○ Bacteria ○ Viruses MIDTERM MICROPARA LEC Page 3 ○ Parasites • WHERE GERMS LIVE (RESERVOIR) For a disease to perpetuate itself it must have a continual source of disease organism. This source can be living or non-living. It can be considered a reservoir if it provides a pathogen with additive condition for survival and multiplication and opportunity for transmission. ○ People - directly or indirectly ▪ Human carriers plays an important role in the spread of such diseases such as typhoid fever, hepatitis, streptococcal infection, etc. ○ Animals/pets, Wild animals -> direct contact, bites, wastes ▪ ex: rabies- dogs,cats, etc ○ Food, soil, water -> nonliving reservoir ▪ Food- meat, vegetables if not properly cleaned ▪ Soil ▪ Water- can be contaminated by feces or urine ○ Fomites -> example is bacteria/pathogens that is present in doorknob • HOW GERMS GET OUT (PORTAL EXIT) ○ Mouth- vomit, saliva ○ Cuts in the skin ( blood) ○ During diapering and toileting (stool) • GERMS GET AROUND (MODE OF TRANSMISSION) ○ Contact (hands, toys, sand) ○ Droplets – when you speak, sneeze or cough • HOW GERMS GET IN (PORTAL ENTRY) Reservoir to susceptible host ○ Skin- relatively thick ▪ natural openings such as sweat glands, hair follicles, abrasions, scratch, wounds, scrapes, stabs open the skin to infection by many contaminants. Some microorganisms like parasitic worm are also capable in penetrating your skin example hook worms, fungi ○ Mucus Membranes (mouth, eyes) ▪ relatively thin, moist, and warm ▪ pathogens find mucus membrane hospitable and easier to penetrate as a portal entry ▪ Some bacteria enters in the respiratory tract via the eyes by contaminated hands or fingers ○ Placenta ▪ there are some pathogens that are able to cross your placenta infect the embryo or the fetus, sometimes causing spontaneous abortion. Example is your toxoplasma gondii. ▪ Some infection can cause birth defects and premature birth. Example: aids, German measles, etc. • NEXT SICK PERSON (SUSCEPTIBLE HOST) ○ Babies ○ Children ○ Elderly ○ People with weak immune system ○ Unimmunized people ○ Anyone Adherence MIDTERM MICROPARA LEC Page 4 Adhesins – Surface projection on pathogen, mostly made of glycoproteins or lipoproteins. Adhere to complementary receptors on the host cells. Adhere can be part of • Glycocalyx: e.g. Streptococcus mutans • Fimbriae (also pili and flagella) ex. E. coli Enables them to better pernitrate Host cell receptors are commonly sugars ( mannose for E. coli ) Since it bind the manos to the cells Biofilms – Provide attachments capacity and resistance to antimicrobial agents. Overcoming Host Defenses • Capsule: Inhibits or prevention of phagocytosis • Cell Wall Proteins: e.g. M protein of S. pyogenes • Antigenic Variation: Avoidance of IS, >IS produces antibodies which are specific for identified antigens e.g. Trypanosoma, Neisseria • Penetration into the Host of the Cell Cytoskeleton: Salmonella and E. coli produce invasins, proteins that cause the actin of the host cell's cytoskeleton to form a basket that carries the bacteria into the cell. ○ Invasins – Salmonella alters host actin to enter a host cell ○ Use actin to move from one cell to the next – Listeria >Can better spread from one cell to another Enzymes Coagulase: Blood clot formation. Protection from phagocytosis (Virulent S. aureus) - coagulase positive meaning more virulent (capacity to cause diseases) Kinase: Blood clot dissolve (e.g. Streptokinase), > produce by steptbacteria Hyaluronidase: (Spreading factor) Digestion of "intercellular" • Destroys hyaluronic acid -> tissue penetrations > keep together the cells, allows the cell to better penetrations. It allows the pathogens to spread the better tissues and better penetrations Collagenase: Collagen hydrolysis > Destroys your collagen IgA protease: IgA destruction > primarily associated with diff. Secretions ( inhibit the growth of bacteria ) ▪ Sweats ▪ Surface of the skin How Pathogens Damage Host Cells 1. Use Host nutrients; e.g. Iron > used up by hookworms, causes higher deficiency 2. Cause Direct damage 3. Produce toxins > common gram (+)(-), which make them more intense in causing diseases 4. Induce Hypersensitivity reactions > e.g. hydatid parasite - the cysts of the hydatid burst and release triggers to cause hypersensitivity in action, MIDTERM MICROPARA LEC Page 5 > e.g. hydatid parasite - the cysts of the hydatid burst and release triggers to cause hypersensitivity in action, which could be fatal to host causing anaphylactic shock Examples of toxins • Exotoxins: Proteins (gram – and + bacteria can produce) • Endotoxins: Gram (-) bacteria only. LPS, Lipid S part -> released upon cell death. Symptoms due to vigorous inflammation. Massive release -> endotoxic shock Exotoxins Summary Source: Gram + and Gram - Relation to microbe: By-products of growing cell Chemistry: Protein Fever? No Neutralized by antitoxins? Yes LD50 Small Circulate to site of activity. Affect body before immune response possible. Exotoxins with special action sites: Neuro-, and enterotoxins Membrane-Disrupting Toxins Lyse host's cells by 1. Making protein channels into plasma membrane, e.g. S. aureus 2. Disrupting phospholipid bilayer, e.g. C. perfringens > positive agent of gas gangrene Examples: Leukocidin: PMN destructions Hemolysin (e.g. Streptolysin): RBCs lysis Superantigens Special type of exotoxin Nonspecifically stimulate T-cells. Cause intense immune response due to release of cytokines from host cells Symptoms: Fever, nausea, vomiting, diarrhea, shock, and death Examples Exotoxin A - produce by s. aurous. Because of the exotoxin A, simple infection could be toxic shock syndrome, because of extreme toxic lobe has a lot of exotoxin produce, it causes intense immune respond due to the release of cytokines from host cells. • Immune system ovary acts to the presence of exotoxins leading to unfavorable sequences > ex. Tampons, who do not change regularly. Endotoxins • Bacterial cell death, antibiotics, and antibodies may cause the release of endotoxins. • Cause fever (by inducing the release of interleukin-1) and shock (because of a TNF-induced decrease in blood pressure). • TNF release also allows bacteria to cross BBB. • The LAL assay (Limulus amoebocyte lysate) is used to detect endotoxins in drug and on medicinal devices. Endotoxin Summary Source Gram ( - ) Relation to microbe Present in LPS of outer membrane MIDTERM MICROPARA LEC Page 6 Relation to microbe Present in LPS of outer membrane Chemistry Lipid A components of LPS Fever? Yes Neutralized by antitoxins? No LD50 Relatively large ENDOTOXIN SUMMARY Gram (-) • main source of endotoxin • "N" for gram neg • Not produce by bacteria but part of lypopolysaccharide • It is lipid (mahirap mamatay) and can only cause fever • Relatively large LD50 -> To produce lethal effect we need plenty of endotoxin however not neutralize by any other antitoxin -> It is screened thru lal (?) acid test Antitoxin: Antibodies against a specific toxin. Vocabulary related to Toxin Production 1. Toxin ○ Improve or contribute disease causing capability of organism ○ Substances that contribute to pathogenicity 2. Toxigenicity ○ Ability to produce toxin 3. Toxemia ○ "Emia" - blood ○ Toxin is already present in the blood circulation 4. Toxoid ○ "Toxoid" - Part of vaccine ○ Are toxins from pathogenic organism that are attenuated or weakened to help us produce antitoxin (pang counter sa toxin) but we do not experience the disease causes by the toxin ○ Ex. Tetanus toxoid – a toxin that can trigger immune response 5. Antitoxin ○ Can only be applied to exotoxin ○ Antibodies against a specific toxin. Pathogenic Properties of Viruses Evasion of Immune system by ▪Growing inside cells -enter cell in disguised Examples: ▪Rabies virus spikes - mimic Ach ▪HIV - hides attachment site -> CD4 long and slender so it cannot be easily targeted by the immune system Visible effects of viral infection = Cytopathic Effects (disease causing or seen on the cellular level) MIDTERM MICROPARA LEC Page 7 Visible effects of viral infection = Cytopathic Effects (disease causing or seen on the cellular level) 1.cytocidal (cell death) ▪ Viruses can propagate or multiply inside the cell and to release out in the open it causes cell death by lysis of the cell ▪ Cell death – cause by the lysis of the cell 2.noncytocidal effects (damage but not death). ▪ Can cause damge but not death Pathogenic Properties of Fungi Fungi • Are generally chronic infection (long duration disease compared to other organisms) •Fungal waste products may cause symptoms •Chronic infections (long duration of disease compared to other organisms) provoke allergic responses Some fungal organisms are also capable of having different virulence EXAMPLE •Proteases (production of different enzymes) –Candida -Trichophyton (causative agent for tinea infections: athletes foot) •Capsule prevents phagocytosis –Cryptococcus – causes fungal meningitis - NOTABLE CAPSULATED FUNGI Fungal Toxins - produce further aggravate diseases •Ergot toxin –from Claviceps purpurea -produce ergot alkaloid - capable of producing ergotism or ergotosicosis or St. Anthony's fire (redness of the skin) •Aflatoxin –Aspergillus flavus –fungi that commonly affects crops Ex. Corn, peanuts which can lead to liver cancer Pathogenic Properties of Protozoa & Helminths -The waste product can cause symptoms •Presence of protozoa •Protozoan waste products may cause symptoms •Avoid host defenses by –Growing in phagocytes (phagocytes by WBC but it grows in there) –Antigenic variation (evades IS by varying antigens) •Presence of helminths interferes with host function -hookworm –causes iodine dificiency -Diphylobotrium latum (from fishes) fishtape worm – B12 dificiency •Helminths metabolic waste can cause symptoms -ex. Filariasis cause by " Wuchereria bancrofti" it gets bigger because of the presence of multiplication of helminths or parasites blocks the lymphatic drainage which causes enlargement of body parts Virulence Factors of Infectious Agents • All of capabilities, structures and features are called virulence factors MIDTERM MICROPARA LEC Page 8 Virulent- it is the degree of diseases causing capability of organism -the more virulent the more "malala or mas maka cause" ng disease More virulent (more intense of causing disease) 1. Francisella tularensis (rabbit Fever) - this infection is requires higher antibiotic (mahirap puksain lol) 2. Yersinia Pestis (plague) 3. Bordetella pertussis (whooping cough) 4. Pseudomonas aeruginosa (infections burns) 5. Clostridium difficile (antibiotic – induced colitis) 6. Candida albicans (vaginitis, thrush) - can cause disease when there is opportunity, produces proteases which could contribute disease causing capability 7. Lactobacili, diptheroids - normally microbiota, very rare cause disease, very not virulent Less virulent Portals of Exit – from the infected person how does the microorganism get out to other suspectable host Ex. Vomit, saliva, blood, stool Mode of transmission – the causative agents of disease can be transmitted from the reservoir of the infection to susceptible host by 3 principal routes 1. Contact transmission ▪ Direct contact transmission - "person to person transmission" it is by physical contact between its source and the host and there is no intermediate object is involved and can also apply through animals ex. Rabies , animal bites ▪ Ex. Touching, kissing, and sexual intercourse ( syphilis, herpes, aids) ▪ Congenital – transmission of disease from mother to baby occurs when the pathogen present in the mothers blood ▪ Indirect contact transmission - there is intermediate object involved in between ▪ Ex. Doorknob, stethoscope, syringe, ▪ Droplet transmission – microbes are spread in droplet nuclei or mucus droplets and travels short distances. Discharge to the air by coughing, talking and laughing. The droplet cannot travel less than 1 meter. Ex. Influenza, pneumonia and whooping cough ○ Airborne transmission – it is capable of staying longer in the air also travels more than 1 meter from the reservoir Ex. Histoplasmosis(butt), staphylococci and streptococci ○ Waterborne transmission – water contaminated ex. Cholera, leptospirosis ○ Foodborne transmission - improperly or incompletely cooked ex. Kinilaw, tapeworm infestation ○ Cross contamination – ex. Utensils that are used is contaminated by bacteria or unsanitary of cook ○ Vector borne – arthropods or animals carries the pathogens from one host to another ex. Insects, Lice, mosquito either mechanical or biological transmission Mechanical transmission – passive transport of the pathogens of the insects feet or other body parts if the insect makes contact with the host food pathogens and transfer through the food and later swallowed by the host ex. Mosquito transport from the person with typhoid to the food Biological transmission – more on active transport. The vector has a rule of lifecycle of pathogen 2. vehicle transmission 3. Through the use of vectors GERMS GET AROUND Biological transmission - more on active transport ; the vector has a role in the lifecycle of pathogens Ex. mosquito in malaria, the plasmodium sporozoites are present in the salivary glands in mosquitos NEXT SICK PERSON MIDTERM MICROPARA LEC Page 9 Susceptibility of hosts depends on the immune system • Babies • Children • Elderly • People with weakened immune system – ex. Patients taking immunosuppression drugs ; Immune system – fights/ destroys anything foreign • Unimmunized people • Anyone Diagnosis- evaluation of signs and symptoms and lab results - cross analyzing different laboratory results CLASSIFICATION OF DISEASES 1. Ease of spreading • Communicable disease - "contagious disease" -infected person transmits the agent to another person Ex. COVID 19 • Non-communicable disease – not spread easily -acquired only when introduced to the body Ex. Rabies 2. Occurrence of disease • Incidence – rate of no. Of new cases -could be a good indicator of spread of the disease -part only of prevalence • Prevalence - no. Of old and new cases -indicateshoe long and seriously a disease affects a population • Recurrence • Mortality – ex. Cardiovascular diseases = high mortality rate 3. Frequency of Disease • Sporadic – only occurs occasionally; ex polio • Endemic – constantly present in a given area of population; ex malaria in palawan • Epidemic- after many people in an area in a relatively short period of time; AIDS 4. Severity or Duration of disease • Chronic – develop more slowly but continues to recur for long; ex hepatitis • Acute – develop rapidly but lasts only a short period of time • Latent disease – causative agent remains active for a time but the becomes active to produce signs and symptoms; ex chickenpox 5. Extent of host involvement • Local - "focal infection" -limited to a relatively small part of the body • Systemic infection - "generalized infection" -spread throughout the body by the blood or lymph nodes SEPSIS – more of a clinical term wherein test and vital signs or symptoms are considered SEPTICEMIA – the mere presence of pathogens in the bloodstream ○ Toxemia ○ Bacteremia ○ Viremia 6. State of host's resistance Primary Infection - Acute infection that cause the initial illness MIDTERM MICROPARA LEC Page 10 Primary Infection - Acute infection that cause the initial illness Secondary Infection - Result after primary infections has weakened the immune system Subclinical infection - "inapparent infection" ; does not cause any noticeable illness ;ex TB infection Predisposing factors – increase susceptibility to a disease ○ ○ ○ ○ Gender – in females, predisposed to UTI than males Genetic factors Climate and weather – influenza virus Other specific factors – ex. Vaccination, lifestyle HealthCare-Associated Infections - "nosocomial infections" -acquired while receiving treatment for other conditions at a health care facility -1940s & 1950s : S.aureus as Primary Cause of HAIs – happens after 2 days exposure Control of Infections ○ Universal precautions □ employed to decrease transmission of microbes – started during HIV pandemic □ all blood and/or bloody fluids should be considered infectious ○ Standard Precautions – definition of infections was changed to ALL body fluids except sweat with or without bloody fluids ○ Transmission-Based precautions – droplet respiratory transmission ○ Handwashing = single most important means of prevention ○ Infection control committee MIDTERM MICROPARA LEC Page 11
