Epidemiology of Infectious disease 1 Symbiotic Relationships Between Microbes and Their Hosts Symbiosis means “to live together” We have symbiotic relationships with countless microorganisms Types of symbiosis Mutualism Commensalism Parasitism 2 Symbiotic Relationships Between Microbes and Their Hosts 3 Infection Mutualsim: Each one benefits Commensual: One organism benefits, the other is not harmed. Parasitism: Advantage to one, disadvantage to the other. Obligate relationship: one depends on the other for survival (parasites are obligate pathogens) Normal Flora: Organism is always on or in us; GI, GU, oral mucosa. Sterile areas of the body: Blood, CSF. Any organism here indicates something is wrong. The first indicator is decreased glucose, increased protein Opportunistic Pathogens: A normal flora organism that becomes a pathogen when the host’s immune defense decreases. Trauma, Surgery, Burns: overcomes barriers of defense Catheterization: allows increased access and decreased defense Chemotherapy: e.g. ablative (for CA) destroys bone marrow, therefore myeloid and lymphoid immunity goes down. Co-infection: e.g. haemophilic influenza is 2° to viral influenza. Tissue Tropism Tissue Tropism (organisms are selective of tissues they infect): influenza does not affect your hand; gonorrhea only effects mucosa. Tropism can also be species, organ, or non-specific. HIV integrates a provirus into our chromosome. Antibodies actually assist the HIV organisms because opsinization helps to internalize the virus. Because of almost no cell mediated immunity (T-cells are infected), AIDS patients die from TB, cytomegalovirus (CMV), Candida, pneumocystis. When a person has a second infection, it is called a CO-INFECTION. OBLIGATE PATHOGENS Will always cause infection and disease whenever and wherever they are encountered (e.g. Yersinia pestis plague, anthrax, smallpox) unless you are immune. However, they don’t want to kill their host. Virulence VIRULENCE: Ability to cause infection and disease. They have special structures that allow them to attach, invade, spread, etc. MULTIPLICITY OF INFECTION (INNOCULUM): the number of organisms needed to cause disease. There is an inverse relationship between virulence and Multiplicity of Infection. If only a few bacterial cells cause the disease, it is said to be very virulent. Obligate pathogens are virulent, even with a low inoculum, because they are effective. Most innoculum needs 103-5 organisms. Only 10 organisms can form an innoculum in a virulent organism such as anthrax. Anthrax avoids immune defenses by exploiting the very mechanisms used to fight it. It becomes activated after phagocytosis. Mycobacterium will coat the wall of vacuoles so lysozymes can’t fuse. Rickettsia is on a timer, and escapes the vacuole to invade the nucleus. PORTALS OF ENTRY (POE) CEPHALIC (7 PORTALS): Mouth, nose, eyes, ears. CORPOREAL: Mammary, Vaginal, Urethral, Rectal TRAUMA/MEDICAL: Burn, Compound Fracture, surgical/catheter, injury/IVDA, abnormal mucosa (CA chemo). MODES OF TRANSMISSION (MOT) AEROSOL: Airborne micro-particles (soil aerosol containing endospores) DROPLET NUCLEI: Mucoid micro-droplet via cough or sneeze, durable on surfaces, mainly transmitted by contact. Sneeze and cough into your elbow! DIRECT CONTACT: Direct object/tissue-to-tissue contact. o CASUAL TRANSMISSION: handshake, clothing o ASPIRATION: inhalation of oral, GI, or food-borne organisms o FECAL-ORAL: autoinoculation or contamination (poor hygiene) o SEXUAL TRANSMISSION (STD): sexual/bodily fluid contact AGENTS OF TRANSMISSION VECTOR: a living organism that spreads disease from one host to another. (mosquitoes, ticks, rats, humans) FOMITE: inanimate object that spreads disease from one host to another. (toothbrush, water glass, toys, handles, keyboard, light switch, cell phones, TV remote) HOST-PATHOGEN RELATIONSHIP (HPR) INFECTION: presence of organism DISEASE: adverse symptoms due to infection NORMAL FLORA: organism typically found on healthy individual PATHOGEN: organism causing disease (etiologic agent) IMMUNOCOMPROMISED: suppressed or deficient immunity NOSOCOMIAL: acquired in hospital setting COMMUNITY-ACQUIRED: acquired in routine, day-to-day activities OPPORTUNISTIC PATHOGEN: normal flora + compromised pathogen OBLIGATE PATHOGEN: always causes Dz if present PATHOGENESIS (Px): events leading to Dz (POEDz) MULTIPLICITY OF INFECTION (MOI): inoculum required for infxn INCUBATION (INC): time from transmission to Dz VIRULENCE: measure of Dz capability VIRULENCE FACTOR (VF): ultrastructure, exoenzyme, or exotoxin BACTERIAL SYMPTOM TERMINOLOGY BACTEREMIA: bacteria in bloodstream BACTERURIA: bacteria in urine (normal or pathogenic flora) SEPTICEMIA: Gram negative bacteremia in the bloodstream PYEMIA: Gram + bacteremia PYROGENIC: fever-producing infection or bacterial components PURULENT: pus-producing, reaches an opening to drain out. The pus is a collection of dead neutrophils, which are the 1° immune cells when there is pus. GRANULOMATOUS: infxn where macrophages are 1° immune cells (no pus) DIFFERENTIAL DIAGNOSIS (DDx): all possible causes of the disease. UROSEPSIS: Septicemia from UTI FACULTATIVE INTRACELLULAR PARASITES: are not obligate pathogens. They can survive temporarily in white cells, such as neutrophils, Monocytes/ Macrophages. EXOTOXINS: A toxin made and then secreted, e.g. pesticin, hemolysins, shigatoxins, choleragen, enterotoxins, plasminogen activating factor, coagulase, etc. ENDOTOXINS: A component of the cell wall is toxic to us, e.g. LPS and LOS. Symbiotic Relationships Between Microbes and Their Hosts Normal Microbiota in Hosts Also termed normal flora and indigenous microbiota Organisms that colonize the body’s surfaces without normally causing disease Two types Resident microbiota Transient microbiota 14 Symbiotic Relationships Between Microbes and Their Hosts Resident microbiota Are a part of the normal microbiota throughout life Are mostly commensal Transient microbiota Remain in the body for short period Found in the same regions as resident microbiota Cannot persist in the body Competition from other microorganisms Elimination by the body’s defense cells Chemical or physical changes in the body 15 Symbiotic Relationships Between Microbes and Their Hosts Acquisition of normal microbiota Development in womb free of microorganisms (axenic) Microbiota begin to develop during birthing process Much of one’s resident microbiota established during first months of life 16 Symbiotic Relationships Between Microbes and Their Hosts How Normal Microbiota Become Opportunistic 17 Pathogens Opportunistic pathogens Normal microbiota that cause disease under certain circumstances Conditions that provide opportunities for pathogens Introduction of normal microbiota into unusual site in body Immune suppression Changes in the normal microbiota Changes in relative abundance may allow opportunity for a member to thrive and cause disease Inflammation 18 Host defense summary 19 What can you catch from a toilet seat? Cell surface markers Designated as “CD” Cluster of Differentiation used to identify specific structures on a cell ~200 different designations 20 21 Reservoirs of Infectious Diseases of Humans Most pathogens cannot survive for long outside of their host Reservoirs of infection Sites where pathogens are maintained as a source of infection Three types of reservoirs Animal reservoir Human carriers Nonliving reservoir 22 Reservoirs of Infectious Diseases of Humans Animal Reservoirs Zoonoses Diseases naturally spread from animal host to humans Acquire zoonoses through various routes Direct contact with animal or its waste Eating animals Bloodsucking arthropods Humans are usually dead-end host to zoonotic pathogens 23 Reservoirs of Infectious Diseases of Humans Human Carriers Infected individuals who are asymptomatic but infective to others Some individuals eventually develop illness while others never get sick Healthy carriers may have defensive systems that protect them 24 Reservoirs of Infectious Diseases of Humans Nonliving Reservoirs Soil, water, and food can be reservoirs of infection Presence of microorganisms often due to contamination by feces or urine 25 The Movement of Microbes into Hosts: Infection Exposure to Microbes: Contamination and Infection Contamination The mere presence of microbes in or on the body Infection When organism evades body’s external defenses, multiplies, and becomes established in the body 26 The Movement of Microbes into Hosts: Infection Portals of Entry Sites through which pathogens enter the body Four major pathways Skin Mucous membranes Placenta Parenteral route (intravenous) 27 Routes by which humans acquire parasitic infections 28 Figure 23.1 Routes of entry for invading pathogens 29 Portals of exit 30 The Movement of Microbes into Hosts: Infection Portals of Entry Skin Outer layer of dead skin cells acts as a barrier to pathogens Some pathogens can enter through openings or cuts Others enter by burrowing into or digesting outer layers of skin 31 The Movement of Microbes into Hosts: Infection Portals of Entry Mucous membranes Line the body cavities that are open to the environment Provide a moist, warm environment hospitable to pathogens Respiratory tract is the most common site of entry Entry is through the nose, mouth, or eyes Gastrointestinal tract may be route of entry Must survive the acidic pH of the stomach 32 The Movement of Microbes into Hosts: Infection Portals of Entry Placenta Typically forms effective barrier to pathogens Pathogens may cross the placenta and infect the fetus Can cause spontaneous abortion, birth defects, premature birth 33 The Movement of Microbes into Hosts: Infection Portals of Entry Parenteral route Not a true portal of entry Pathogens deposited directly into tissues beneath the skin or mucous membranes (needle injection or i.v.) 34 The Movement of Microbes into Hosts: Infection The Role of Adhesion in Infection Process by which microorganisms attach 35 themselves to cells Required to successfully establish colonies within the host Adhesion factors include Specialized structures (acts like Velcro) Attachment proteins (acts like glue) The presence of adhesions are considered a virulence factor. The Movement of Microbes into Hosts: Infection The Role of Adhesion in Infection Attachment proteins help in adhesion Found on viruses and many bacteria Viral or bacterial ligands (proteins) bind host cell 36 receptors Interaction can determine host cell specificity Changing/blocking a ligand or its receptor can prevent infection Inability to make attachment proteins or adhesins renders microorganisms avirulent Some bacterial pathogens attach to each other to form a biofilm The Nature of Infectious Disease Infection is the invasion of the host by a pathogen Disease results if the invading pathogen alters normal body functions Disease is also referred to as morbidity 37 The Nature of Infectious Disease Manifestations of Disease: Symptoms, Signs, and Syndromes Symptoms Subjective characteristics of disease felt only by the patient Signs Objective manifestations of disease observed or measured by others Syndrome Symptoms and signs that characterize a disease or abnormal condition Asymptomatic, or subclinical, infections lack symptoms but may still have signs of infection 38 The Nature of Infectious Disease Cause of Disease: Etiology Study of the cause of disease Germ theory of disease Disease caused by infections of pathogenic microorganisms Robert Koch developed a set of postulates one must satisfy to prove a particular pathogen causes a particular disease 39 Koch’s Postulates 40 The Nature of Infectious Disease Causation of Disease: Etiology Exceptions to Koch’s postulates Some pathogens can’t be cultured in the laboratory Diseases caused by a combination of pathogens and other cofactors Ethical considerations prevent applying Koch’s postulates to pathogens that require a human host Difficulties in satisfying Koch’s postulates Diseases can be caused by more than one pathogen Pathogens that are ignored as potential causes of disease 41 The Nature of Infectious Disease Virulence Factors of Infectious Agents Pathogenicity Ability of a microorganism to cause disease Virulence Degree of pathogenicity (how good is it at its job?) Virulence factors contribute to virulence Adhesion factors Biofilms Extracellular enzymes Toxins Antiphagocytic factors 42 The Nature of Infectious Disease Virulence Factors of Infectious Agents Extracellular enzymes Secreted by the pathogen Dissolve structural chemicals in the body Help pathogen maintain infection, invade, and avoid body defenses 43 The Nature of Infectious Disease Virulence Factors of Infectious Agents Toxins Chemicals that harm tissues or trigger host immune responses that cause damage Toxemia refers to toxins in the bloodstream that are carried beyond the site of infection Two types Exotoxins (made and secreted) Endotoxins (part of the bacterial cell wall) 44 The Nature of Infectious Disease 45 The Nature of Infectious Disease Virulence Factors of Infectious Agents Antiphagocytic factors Factors prevent phagocytosis by the host’s phagocytic 46 cells Bacterial capsule o Composed of chemicals not recognized as foreign o Slippery; difficult for phagocytes to engulf bacteria Antiphagocytic chemicals o Prevent fusion of lysosome and phagocytic vesicles o Leukocidins directly destroy phagocytic white blood cells The Nature of Infectious Disease The Stages of Infectious Disease The disease process occurs following infection Many infectious diseases have five stages following infection Incubation period Prodromal period Illness Decline Convalescence 47 The stages of infectious disease 48 The Movement of Pathogens Out of Hosts: Portals of Exit Pathogens leave host through portals of exit Many portals of exit are the same as portals of entry Pathogens often leave hosts in materials the body secretes or excretes 49 Portals of exit 50 Modes of Infectious Disease Transmission Transmission is from a reservoir or a portal of exit to another host’s portal of entry Three groups of transmission Contact transmission Direct, indirect, or droplet Vehicle transmission Airborne, waterborne, or foodborne Vector transmission Biological or mechanical 51 Classification of Infectious Diseases Diseases can be classified in number of ways The body system they affect GI system, nervous system, blood Taxonomic categories Viral disease, Gram + Their longevity and severity Chronic vs. acute; mild vs. severe How they are spread to their host STD, blood borne, food The effects they have on populations (rather than 52 on individuals): global/pandemic vs. epidemic Classification of Infectious Diseases Terms used to classify infectious disease Acute disease (rapid onset, short duration) Chronic disease (long duration) Subacute disease (slower onset, medium duration) Latent disease (present but not obvious symptoms) Communicable (Contagious) 53 Epidemiology of Infectious Diseases INFECTION: Presence of microbe DISEASE: Symptomatic consequence of infection 54 Epidemiology Epidemiology is the study of the patterns, causes, and effects of health and disease conditions in defined populations. It is the cornerstone of public health by identifying risk factors for disease and provides information for preventive healthcare. Major areas of epidemiological study include disease etiology, outbreak investigation, disease surveillance and screening, biomonitoring, and comparisons of treatment effects such as in clinical trials. John Snow Dr. John Snow is known as the father of modern epidemiology. He showed that cholera was water-borne, and debunked the Miasma theory, which stated that cholera came from bad air. John Snow John Snow was a British physician in London in 1854, where a major cholera outbreak struck the nearby city of Soho. In three days, 127 people who lived near Broad Street died of Cholera. Within a week, 500 people had died and one in seven people who developed cholera eventually died from it. John Snow suspected contamination of the water, but couldn’t find any organic matter in it. Almost all the cases of cholera occurred close to the Broad Street Water Pump. Snow mapped out the cases of cholera in relation to the water pump. The evidence Snow presented convinced the local council to remove the pump handle, halting the spread of the disease. It wasn’t until 1885, when Robert Koch identified V. cholerae as the bacillus causing the disease that he had proof of his theory. He was right, but wasn’t around to see this discovery himself. John Snow died four years later, at the age of 45. Epidemiology of Infectious Diseases Frequency of Disease Track occurrence of diseases using two measures Incidence Number of new cases of a disease in a given area during a given period of time Prevalence Number of total cases of a disease in a given area during a given period of time Occurrence also evaluated in terms of frequency and geographic distribution 61 The incidence and estimated prevalence of AIDS 62 Epidemiologists report data in a number of ways 63 Different terms for the occurrence of disease 64 Epidemics Defined Relative to Expected Number of Cases 65 Epidemiology of Infectious Diseases Epidemiological Studies Descriptive epidemiology Careful tabulation of data concerning a disease Record location and time of the cases of disease Collect patient information Try to identify the index case (or first case) of the disease 66 Epidemiology of Infectious Diseases Epidemiological Studies Analytical epidemiology Seeks to determine the probable cause 67 (etiology), mode of transmission, and methods of prevention Useful in situations when Koch’s postulates can’t be applied Often retrospective Investigation occurs after an outbreak has occurred Epidemiology of Infectious Diseases Epidemiological Studies Experimental epidemiology Involves testing a hypothesis concerning the cause of a disease Application of Koch’s postulates is experimental epidemiology 68 Endemic 1: characteristic of or prevalent in a particular field, area, or environment 2: restricted or peculiar to a locality or region “Endemic" means "in the population." "Endemic" is often used to characterize diseases that are generally found in a particular area; malaria, for example, is said to be endemic to tropical and subtropical regions. This use differs from that of the related word "epidemic" in that it indicates a more or less constant presence in a particular population or area rather than a sudden, severe outbreak within that region or group. The word is also used by biologists to characterize the plant and animal species that are only found in a given area. Epidemic Affecting or tending to affect a DISPROPORTIONATELY large number of individuals within a population, community, or region at the same time Demographics The changes (such as the number of births, deaths, marriages, and illnesses) that occur over a period of time in human populations; also : a set of such changes. The demographics of a particular disease would include the ratio of males to females that have the disease, the average age, the geographical distribution, and the incidence (the likelihood of a person getting the disease) in a particular Country. Epidemiology of Infectious Diseases Hospital Epidemiology: Nosocomial Infections Types of nosocomial infections Exogenous Pathogen acquired from the health care environment Endogenous Pathogen arises from normal microbiota due to factors within the health care setting Iatrogenic Results from modern medical procedures 72 The interplay of factors that result in nosocomial infections 73 Epidemiology of Infectious Diseases Hospital Epidemiology: Nosocomial Infections Control of nosocomial infections Precautions designed to reduce factors that result in disease Hand washing is the most effective way to reduce nosocomial infections 74 Epidemiology of Infectious Diseases Epidemiology and Public Health Agencies at the local, state, national, and global level share information concerning disease The United States Public Health Service World Health Organization (WHO) Public health agencies work to limit disease transmission Monitor water and food safety Public health agencies campaign to educate the public on healthful choices to limit disease 75 Basic Principles of Microbial Control