Principles of Disease and Epidemiology Chapter 14: Principles of Disease and Epidemiology 1 1 1

Introduction Pathology is the scientific study of disease. Etiology: Cause of disease. Pathogenesis: Studies how disease develops. Virulence: A measure of pathogenicity or ability to cause disease. Infection: Invasion or colonization of the body by pathogenic organisms. Disease: Occurs when an infection results in a change from a state of health. 1 1 1

Categories of Diseasesa © 2015 Pearson Education, Inc.

Relative Virulence of Selected Pathogens

Normal Microbiota There are ~10 microorganisms/human body cell. Animals are generally free from microbes in utero. After birth, microbial populations rapidly establish themselves in the newborn’s body. Vaginal lactobacilli colonize newborn’s intestine. Feeding and breathing introduce many more microbes. E. coli and other bacteria colonize large intestine. Candida albicans colonizes mucous membranes. Normal Microbiota or Flora: Microorganisms that remain throughout an individual’s life. Transient Microbiota: Microorganisms that are present for a certain time period and then disappear. Cells in human body: 1 x 1013 Microbes associated with human body: 1 x 1014 There are ~10 microorganisms/human body cell.

Normal Microbiota of the Body Skin Bacteria Gum plaque Intestinal Flora

Location of Normal Microbiota

Some Resident Microbiota of Humansa © 2015 Pearson Education, Inc.

Relationships Between the Normal Microbiota and the Host Microbial Antagonism: Normal flora inhibits overgrowth of harmful microbes. Mechanisms include competition for nutrients and affecting environmental factors such as pH, toxic substances, and oxygen availability. Vaginal flora maintains pH of 3.5-4.5 which inhibits overgrowth of Candida albicans. In mouth streptococci produce compounds that inhibit growth of many other cocci. In intestine E. coli produce bacteriocins, which inhibit growth of closely related bacteria. C. dificile is inhibited by normal intestinal flora.

Relationships Between the Normal Microbiota and the Host SYMBIOSIS: “Living together”. Relationship between the host and its normal flora. 1. Commensalism: One organism benefits, the other is not affected (+/0). Many microbes live off secretions and dead cells and do not benefit or harm host. 2. Mutualism: Both organisms benefit from living together (+/+). E. coli synthesizes vitamin K and some B vitamins. 3. Parasitism: One organism benefits, the other is harmed (+/-). Most disease causing bacteria.

The Three Types of Symbiotic Relationships © 2015 Pearson Education, Inc.

Opportunistic Infections The nature of symbiotic relationships can change. Opportunistic Pathogens: Organisms that normally do not cause disease in their natural habitat in a healthy person. They may cause disease if the host is weakened or if they enter a different part of the body. Pneumocystis carinii pneumonia in AIDS patients. Tooth decay and gum disease caused by mouth flora. Neisseria meningitidis is usually harmless in respiratory tract, but can cause meningitis. E. coli can cause urinary tract infections, meningitis, pneumonia, and abscesses.

Cooperation Among Microbes Synergism: The effect of two microbes acting together, is greater than the effect of either acting alone. HIV and mycoplasma infection: Cells infected with mycoplasma and HIV die more readily than those infected with mycoplasma alone. HIV and Oncogenic Viruses: Women with HIV infections develop very aggressive cervical cancers which are caused by papillomavirus. Individuals with HIV and Human Herpes Virus 8 infections, are more likely to develop Kaposi’s sarcoma. Oral streptococci and pathogens that cause gingivitis and periodontal disease. Pathogens bind to streptococci instead of host tissue.

How Bacterial Cells Damage Host Cells Three mechanisms: Direct Damage Toxins* Hypersensitivity Reactions * Most bacterial damage is carried out by toxins. 1. Direct Damage Some bacteria can induce cells to engulf them (E. coli, Shigella, Salmonella, and Neisseria gonorrhoeae). Microbial metabolism and multiplication kills host cells. Other microbes enter the cell by excreting enzymes or through their own motility.

2. Toxin Production Toxins: Poisonous substances produced by microbes. Frequently toxins are the main pathogenic factor. Toxigenicity: Ability of a microbe to produce toxins. Toxemia: Presence of toxins in the blood. Toxin effects: May include fever, cardiovascular problems, diarrhea, shock, destruction of red blood cells and blood vessels, and nervous system disruptions. Of 220 known bacterial toxins, 40% damage eukaryotic cell membranes. Two types of toxins: Exotoxins Endotoxins

Exotoxins versus Endotoxins

A. Exotoxins Proteins: Enzymes that carry out specific reactions. Soluble in body fluids, rapidly transported throughout body in blood or lymph. Produced mainly by Gram-positive bacteria, but also some Gram negative bacteria. Most genes for toxins are carried on plasmids or phages. Produced inside bacteria and released into host tissue. Responsible for disease symptoms and/or death. Cytotoxins: Kill or damage host cells. Neurotoxins: Interfere with nerve impulses. Enterotoxins: Affect lining of gastrointestinal tract. Antibodies called antitoxins provide immunity. Toxoids: Toxins that have been altered by heat or chemicals. Used as vaccines for diphtheria and tetanus.

Important Exotoxins Diphtheria Toxin: Corynebacterium diphtheriae when infected by a phage carrying tox gene. Cytotoxin inhibits protein synthesis in eucaryotic cells. Two polypeptides: A (active) and B (binding). Erythrogenic Toxins: Streptococcus pyogenes produces three cytotoxins which damage blood capillaries, causing a red rash. Botulinum Toxins: Produced by Clostridium botulinum. Neurotoxin that inhibits release of neurotransmitter acetylcholine and prevents transmission of nerve impulses to muscles, causing flaccid paralysis. Extremely potent toxins. Tetanus Toxin: Produced by Clostridium tetani. A neurotoxin that blocks relaxation of skeletal muscles, causing uncontrollable muscle spasms (lockjaw) and convulsions. Vibrio Enterotoxin: Produced by Vibrio cholerae. Two polypeptides: A (active) and B (binding). The A subunit of enterotoxin causes epithelial cells to discharge large amounts of fluids and electrolytes. Staphylococcal Enterotoxin: Staphylococcus aureus produces an enterotoxin similar to cholera toxin. Other enterotoxins cause toxic shock syndrome.

Rash of Scarlet Fever Caused by Erythrogenic Toxins of Streptococcus pyogenes

Muscle Spasms of Tetanus are Caused by Neurotoxin of Clostridium tetani Neonatal Tetanus (Wrinkled brow and risus sardonicus) Source: Color Guide to Infectious Diseases, 1992

Vibrio Enterotoxin Causes Profuse Watery Diarrhea Rice-water stool of cholera. The A subunit of enterotoxin causes epithelial cells to discharge large amounts of fluids and electrolytes. Source: Tropical Medicine and Parasitology, 1995

Diseases Caused by Staphylococcal Toxins Scalded Skin Syndrome Toxic Shock Syndrome

Endotoxins Part of outer membrane surrounding Gram-negative bacteria. Endotoxin is lipid portion of lipopolysaccharides (LPS), called lipid A. Effect exerted when gram-negative cells die and cell walls undergo lysis, liberating endotoxin. All produce similar signs and symptoms which may include: Chills, fever, weakness, general aches, blood clotting and tissue death, shock, diarrhea, bleeding, inflammation, and even death. Can also induce miscarriage. Fever: Pyrogenic response is caused by endotoxins.

Endotoxins (Continued) Endotoxins do not promote the formation of effective antibodies. Organisms that produce endotoxins include: Salmonella typhi Proteus spp. Pseudomonas spp. Neisseria spp. Medical equipment that has been sterilized may still contain endotoxins. Limulus amoebocyte assay (LAL) is a test used to detect tiny amounts of endotoxin.

Exotoxins versus Endotoxins

Etiology of Infectious Diseases Diseases can be caused by many factors: infection, genetics, degeneration, and others. Koch’s Postulates Developed by Robert Koch in 1877 to establish cause of infectious diseases: anthrax and TB. 1. Same pathogen must be present in every case of the disease. 2. Pathogen must be isolated from diseased host and grown in pure culture. 3. Pathogen from pure culture must cause disease when inoculated in healthy, susceptible laboratory animal. 4. Pathogen must be isolated from inoculated animal and shown to be the original organism.

Koch’s Postulates for Infectious Diseases

Exceptions to Koch’s Postulates Koch’s principles do not apply to all diseases. 1. Some microbes cannot be cultured in artificial media. Treponema pallidum (syphillis) Mycobacterium leprae (leprosy) Ricketsias, chlamydias, and viruses only multiply within cells. 2. One disease may involve several different pathogens. Diarrhea Pneumonia Meningitis Peritonitis Nephritis 3. Some pathogens may cause several different diseases. Streptococcus pyogenes: Scarlet fever, sore throat, skin infections, bone infections, etc. Mycobacterium tuberculosis: Causes disease of lungs, skin, bones, and internal organs. 4 6

Effects of Infectious Diseases Diseases alter normal body function and/or structure. Symptoms: Subjective feelings not obvious to an observer. Example: Pain and malaise. Signs: Objective changes that can be measured. Example: Fever, redness, swelling, paralysis. Syndrome: A group of signs and symptoms that are associated with a disease. Example: AIDS (Acquired Immune Deficiency Syndrome) is a syndrome that varies from one individual to another.

Signs Versus Symptoms © 2015 Pearson Education, Inc.

Classifying Infectious Diseases Communicable Diseases: Spread from one host to another, directly or indirectly. Example: Tuberculosis, herpes, flu, AIDS, chickenpox, mumps, polio, and hepatitis. Contagious Diseases: Spread easily from one person to another. Example: Chickenpox and measles. Noncommunicable Diseases: Not spread from one host to another. Caused by microbes that live outside the body or by opportunistic pathogens that live inside the body. Example: Tetanus, botulism, and yeast infections. 7 8

Disease Occurrence Disease Incidence: New cases of a disease. Percentage of population that contracts a disease in a given time period. Incidence = Number of New Cases No. of People at Risk Disease Prevalence: Total number of cases. Percentage of population that has the disease during given time period. Prevalence = Number of New + Old Cases

Incidence and Prevalence of AIDS in US Adults

Reported AIDS Cases in the United States

Frequency and Distribution of Disease Occurrence Sporadic Disease: Occurs only occasionally. Example: Polio in U.S. Endemic Disease: Constantly present in the population. Example: Common cold or ear infections. Epidemic Disease: Many more people than expected acquire disease in a given time period. Example: Influenza, gonorrhea, chlamydia, and AIDS. Pandemic Disease: Worldwide epidemics occuring on more than one continent. Example: Influenza and AIDS.

Disease Occurrence

Epidemics: Higher Numbers of Cases Than Expected

Disease Duration Acute Disease: Develops rapidly, but lasts a short time. Examples: Flu and common cold. Chronic Disease: Develops more slowly, and reactions are less severe. Tend to recur for long periods or to be continual. Examples: Tuberculosis, hepatitis B, and infectious mononucleosis. Subacute Disease: Intermediate between acute and chronic. Examples: Subacute bacterial endocarditis (streptococci). Latent Disease: Causative agent remains inactive for a time, but then becomes active and produces disease symptoms. Examples: Shingles, genital and oral herpes, AIDS.

Host Involvement Local Infection: Microbes are limited to small area of body. Examples: Boils, abscesses, and acne. Systemic (Generalized) Infection: Microbes are spread throughout body by blood or lymph. Examples: Measles, AIDS. Bacteremia: Presence of bacteria in the blood. Septicemia: Bacteria multiply in blood. Toxemia: Presence of toxins in blood. Viremia: Presence of viruses in blood. Focal Infection: Starts as a local infection and spread to other parts of body. Examples: From teeth, tonsils, and appendix.

Host Resistance Determines Extent of Infection Primary Infection: Acute infection that causes initial illness. Example: Common cold Secondary Infection: Caused by opportunistic pathogen after primary infection has weakened host immune system. Example: Pneumonia or bronchitis may develop after the common cold. Subclinical Infection: Does not cause any noticeable illness in host. Example: Over 90% of polio infections are asymptomatic.

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Spread of Infection Reservoirs of Infection Human Reservoirs: Infected individuals who may or may not present disease. Carriers are infected individuals without any signs or symptoms of disease (AIDS, polio, gonorrhea). Animal Reservoirs: Zoonoses are diseases that occur primarily in wild and domestic animals. About 150 different zoonoses are known (rabies, anthrax, and Lyme disease). Nonliving Reservoirs: Two major sources are soil and water. Soil: Clostridium tetani and botulinum. Water: Vibrio cholerae and Salmonella typhi.

Transmission of Disease I. Contact Transmission: Spread by direct contact, indirect contact, or droplet transmission. A. Direct Contact Transmission: Person-to-person transmission. No intermediate object is involved. Examples: Touching, kissing, sexual intercourse. B. Indirect Contact Transmission: Agent is transferred via a nonliving object (fomite). Examples: Towels, eating utensils, thermometers, stethoscopes, bedding, clothes, money, and syringes. C. Droplet Transmission: Microbes are spread in mucus droplets that travel short distances (less than 1 meter). Examples: Sneezing, coughing, talking, and laughing.

Transmission of Microbial Disease Direct Contact Droplet Transmission Vehicle Transmission Vector Transmission

Transmission of Disease (Continued) II. Vehicle Transmission: Transmission of disease via medium such as water, food, air, blood, body fluids, and intravenous fluids. Waterborne Transmission: Usually caused by water contaminated with sewage. Airborne Transmission: Spread of agents by droplets in dust that travel more than 1 m to host. III. Vectors: Animals that carry disease from one host to another. Arthropods (insects) are most important animal vectors. Mechanical Transmission: Passive transport of pathogens on insect’s body. Biological Transmission: Pathogen spends part of its life cycle in the vector.

Microbial Portals of Entry

Portals of Exit Site at which microbes leave body. Most common exit portals are respiratory and gastrointestinal tracts. Respiratory Tract: Exit in discharges (mucus droplets) from nose and mouth. Transmission by coughing, sneezing, spitting, etc. Examples: Tuberculosis, influenza, pneumonia, common cold, measles, mumps, scarlet fever, and meningococcal meningitis. Gastrointestinal Tract: Exit in feces or saliva. Feces: Amoebas, poliovirus, cholera, typhoid fever, salmonella, shigella, and many helminths. Saliva: Rabies virus, herpes simplex 1.

Microbial Exit Portals

Portals of Exit (Continued) Urogenital Tract: Exit in secretions or urine. Penis and vagina: Sexually transmitted diseases. Chlamydia, herpes simplex 2, HIV, gonorrhea, and syphilis. Urine: Brucellosis and typhoid fever. Skin and Wound Infections: Spread through direct contact or through fomites. Example: S. aureus, P. aeruginosa, scabies, ringworm. Blood: Transmission through insects, needles, and syringes. Insects: Malaria, yellow fever, and Lyme disease. Needles: AIDS and hepatitis B.

Nosocomial (Hospital Acquired) Infections “Nosocomial” Greek word for hospital. Infections acquired at a health care facility. According to Center for Disease Control (CDC), 5-15% of all hospital patients acquire N.I.s. At least 100,000 deaths in US from N.I.s every year. Predisposing Factors: Wide variety of microbes in hospital environment Weakened or immunocompromised patients Chain of transmission: Mainly through direct or indirect contact. From health care workers to patient From patient to patient Fomites: Catheters, needles, dressings, beds, wheelchairs Airborne transmission

Factors Contributing to Nosocomial Infections

Important Nosocomial Pathogens Normal microbiota: Many are opportunistic pathogens Antibiotic resistance: Very high due to the use of antimicrobials in health care facilities. Principle microorganisms: Used to be gram-positive microbes. Today most are gram-negative bacteria. Enterobacteria: Over 40% of all infections. E. coli, Klebsiella spp., Proteus spp., Enterobacter spp., and Serratia marcescens. Staphylococcus aureus (11%) Fungi: (10%) C. albicans and others Enterococcus (10%) Pseudomonas aeruginosa (9%)

Principal Kinds of Nosocomial Infections Percentage

Control of Nosocomial Infections Aseptic techniques to avoid contamination Careful handling and disposal of contaminated material Frequent and adequate hand washing Proper infection control training of staff Isolation wards and rooms Avoid unnecessary antibiotic prescriptions Avoid unnecessary invasive procedures Regular disinfection of respirators and humidifiers and maintenance of autoclaves Use disposable and/or sterile supplies Infection control committee

Control of Nosocomial Infections

Predisposing Factors for Disease Factors that make an individual more susceptible to a given disease. Gender Genetic factors Climate and weather Nutrition Fatigue/Stress Occupation Environment Lifestyle Age Other illness

Development of an Infectious Disease 1. Incubation Period: Time between initial infection and appearance of signs and symptoms.

Development of an Infectious Disease 2. Prodromal Period: Early, mild symptoms of disease. 3. Illness Period: Disease is most acute. Overt signs and symptoms. Patient immune system actively fights off infection. If not successful may die at this stage. 4. Decline Period: Signs and symptoms subside. Patient is vulnerable to secondary infections because of weakened defenses. 5. Convalescence Period: Recovery. Body returns to predisease state.

The Stages of an Infectious Disease

Epidemiology Science that studies when and where diseases occur and how they are transmitted in a population. Modern epidemiology began in 1854 during a cholera epidemic in London. Epidemiologists collect information to determine: Etiology: Cause of disease (pathogen). Predisposing factors: Age, sex, lifestyle, etc. Incidence: Number of individuals acquiring disease in a given time period. Prevalence: Number of individuals with disease in a given time period. Transmission Public Health Policy and Prevention

Epidemiological Data from 1854 London Cholera Epidemic

Epidemiological Data

Epidemiological Data

Types of Epidemiological Investigation Descriptive Epidemiology: Retrospective studies that collect data on diseases occurrence. Collect data on location and time of disease and on patients (age, gender, occupation, health history, socioeconomic groups, etc). Try to identify the “index case’ or first case for a disease in a given area or population. Examples: Initial studies on cholera and toxic shock syndrome outbreaks. Analytical Epidemiology: Analyzes a disease to determine its probable cause, means of transmission, and prevention. May be used when Koch’s postulates cannot be applied. Case control method: Look for factors that precede disease. Compare sick individuals to healthy individuals. Cohort method: Study two populations, one that has been exposed to a certain risk factor (e.g.: blood transfusion or sexual contact) . Control group is not exposed to risk factor. Experimental Epidemiology: Test hypotheses on disease causes. Can also test drugs or vaccines on susceptible populations.

Case Reporting Procedure that requires health workers to report specified diseases to government agencies. 60+ reportable diseases in the U.S. (2015): AIDS Anthrax Botulism Brucellosis Chlamydia (genital) Cholera Dengue Diphtheria Gonorrhea Hansen’s Disease (Leprosy) Hepatitis A, B, and C HIV infection Lyme Disease Malaria Measles Mumps Plague Rabies (animal and human) Rubella Syphilis Tetanus Tuberculosis Viral hemorrhagic fever Yellow fever

Table 14.13 Nationally Notifiable Infectious Diseasesa © 2015 Pearson Education, Inc.

CDC Reporting

Center for Disease Prevention and Control (CDC) Central source of epidemiological information in U.S. Branch of U.S. Public Health Service Located in Atlanta, Georgia Weekly publication “Morbidity and Mortality Report” (MMWR) Morbidity: Number of specific notifiable diseases. Mortality: Number of deaths from diseases. Reports on disease outbreaks Special interest case histories Summaries on status of diseases Recommendations for diagnosis, immunization, and treatment.