Lecture 7: Principles of disease and epidemiology Edith Porter, M.D. 1

 Case study (Video)  Pathology, infection, and disease  Normal microbiota  Etiology of infectious diseases ▪ Koch’s postulates and exceptions  Classifying infectious diseases  Patterns of disease  Spread of infections  Nosocomial infections  Emerging infectious diseases  Epidemiology 2

 Pathology  Scientific study of disease  Etiology  Study of the cause of a disease  Pathogenesis  Development of disease  Infection  Colonization of the body by microbes that are not routinely present at this site  Disease  A change from state of health  Abnormal state in which the body is not function normally Pathos = Suffering Logos = Science HIV pos.  AIDS Tuberculin pos.  Tuberculosis

 Pathogen  Causes disease in a healthy adult  Expresses special virulence or pathogenicity factors  Is not part of normal flora  Opportunist  Does not cause disease under normal conditions  Causes disease at local or systemic breaches of host defense  Often part of normal flora  Cooperation  Different microbes together cause disease

 Body is sterile in utero  Colonized within hours after birth  Lactobacilli  Staphylococci  Outnumber body cells by at least 10– fold  Normal flora does not cause disease under normal conditions  Transient microbiota  present for a relatively short period of time (days, weeks, or months)  Resident microbiota  Normal microbiota permanently colonizing the host

6

Low numbers of Candida albicans can be found everywhere

NoseStomachIntestine

Trichomonas vaginalis is considered a pathogen  Trichomonas hominis is normal flora in large intestine

 Competes with potential pathogens for nutrients  Directly inhibits potential pathogens ▪ Lactobacilli: lactic acid, low pH ▪ Bacteriocins  Produces some vitamins (K, B) Normal microbiota

Candidiasis after antibiotic treatment Clostridium difficile diarrhea after antibiotic therapy

Pseudomembranous enterocolitis caused by C. difficile

 Administration of viable bacteria to the benefit of human health  Lactobacilli, Streptococci, Bifidobacteria  Withstand HCl, bile salts  Adhere to host intestinal mucosa  Produce useful enzymes or physiological end products  Restore normal microbiota  Prophylactic application  Lactobacilli to prevent development of antibiotic associated diarrhea  Therapeutic applications  Supplementary therapy in chronic UTI with E. coli

Robert Koch established the “Golden Rule” to positively identify a microorganism as the cause of an infectious disease 1.The same pathogen must be present in every case of disease and not in the healthy one. 2.The pathogen must be isolated from the diseased host and grown in pure culture. 3.The pathogen from the pure culture must cause same disease when it is inoculated into a healthy susceptible host. 4.The same pathogen must be isolated from the inoculated host in pure culture.

 Microorganism cannot be grown in the laboratory in/on artificial culture media  Utilization of animals or eggs for propagation  One disease can be caused by multiple microorganisms  E. g. nephritis  One microorganism can cause multiple disease conditions 15

16 AAAIs/5oG7IQ7UuHI/s1600/post+mortem+Dis+alpacas.JPG s/TB_Tuberculosis/SN_Spine/A_TB_TB_SN_02.jpg

 Microorganism cannot be grown in the laboratory in/on artificial culture media  Utilization of animals or eggs for propagation  One disease can be caused by multiple microorganisms  E. g. nephritis  One microorganism can cause multiple disease conditions  M. tuberculosis can affect skin, lungs, bones etc.  No host other than humans  E.g. HIV  More than one microorganisms cause one infection  Polymicrobial infections such as abscess caused by anaerobic bacteria 17

 Symptom  A change in body function that is felt by a patient as a result of disease  Sign  A change in a body that can be measured or observed as a result of disease  Syndrome  A specific group of signs and symptoms that accompany a disease Often used interchangeable

 Communicable disease  A disease that is spread from one host to another ▪ Example: Tuberculosis  Contagious disease  A disease that is easily spread from one host to another ▪ Example: Chicken pox  Noncommunicable disease  A disease that is not transmitted from one host to another ▪ Example: Tetanus

 Incidence  Number of people in a population who develop a disease during a particular time period  Includes new cases  Prevalence  Number of people in a population having a specific disease at a given time  Includes old a new cases  Sporadic disease  Disease that occurs occasionally in a population  Endemic disease  Disease constantly present in a population  Epidemic disease  Disease acquired by many hosts in a given area in a short time  Pandemic disease  Worldwide epidemic

21

 Acute disease  Symptoms develop rapidly  Chronic disease  Disease develops slowly  Subacute disease  Symptoms between acute and chronic  Latent disease  Disease with a period of no symptoms when the infectious agent is inactive  Herd immunity  Many immune people are present in a population preventing the spread of a disease Herd Immunity

Often contagious during incubation and prodormal period!!

 Local infection  Pathogens limited to a small area of the body  Systemic infection  An infection spread through the body (via blood or lymphatic system)  Focal infection  Systemic infection that began as a local infection

 Bacteremia  Bacteria in the blood  Septicemia  Spread of bacteria through the blood with organ manifestation  Toxemia  Toxins in the blood  Fungemia  Fungi in the blood  Viremia  Viruses in the blood Common cause for bacteremia: Coagulase negative staphylococci colonizing i.v. catheter

 Factors that make the body more susceptible to disease  Primary and secondary infection ▪ Acute infection that causes the initial illness and predisposes to a secondary, often opportunistic infection  Male versus female  Genetic background  Climate and weather  Nutrition  Lifestyle  Occupation  Pre-existing illness Example: Influenza and Haemophilus influenzae

 Continual sources of the disease organisms  Humans — AIDS, gonorrhea  Carriers may have inapparent infections or latent diseases  Animals — Rabies, Lyme disease  Some zoonoses may be transmitted to humans  Nonliving — Botulism, tetanus  Soil Tick Borrelia burgdorferi Lyme Disease: Skin manifestation

28

 Direct  Requires close association between infected and susceptible host  Includes fecal-oral  Indirect  Spread by fomites  Droplets  Transmission via airborne droplets

 Inanimate reservoir  Food  Water  Vectors  Arthropods ▪ Fleas : plague ▪ Ticks: Lyme disease ▪ Mosquitoes: malaria  Mechanical  Biological : some part of the development of the microbe takes place in the vector

 Acquired during a hospital stay  Source is hospital  5-15 % of all hospital patients affected

 Diseases that are new, increasing in incidence, or showing a potential to increase in the near future

 Appearance of new strains by genetic recombination  E. coli O157:H7  Avian influenzavirus H5N1  Evolution of new serovars  V. cholerae O139  Inappropriate use of antibiotics and pesticides  Antibiotic resistant strains  Multidrug resistant M. tuberculosis  Global warming and weather changes  Hantavirus pulmonary syndrome  Spread of known diseases by modern transportation  Cholera  Ecological Disaster  Coccidioidomycosis after Northridge earthquake  Failures in public health  Missed immunizations

 As told by CDC …  It seems that one of their scientists, on first arriving at CDC from a clinical practice, found himself somewhat unsure of what epidemiology was all about, so he sought an answer down the street at Emory University.  The first person he asked was a medical student, who told him that epidemiology was "the worst taught course in medical school."  The second, a clinical faculty member, told him epidemiology was "the science of making the obvious obscure."  Finally, knowing that statistics are important to epidemiology, he asked a statistician, who told him that epidemiology is "the science of long division" and provided him with a summary equation. Giving up on finding a real answer, he returned to CDC.  On the way, however, he decided to try one more time. He stopped a native Atlantan who told him that epidemiology was "the study of skin diseases.”

 Discipline that find answers to When? Where? How transmitted?  Study—Epidemiology is the basic science of public health. It's a highly quantitative discipline based on principles of statistics and research methodologies.  Distribution—Epidemiologists study the distribution of frequencies and patterns of health events within groups in a population. To do this, they use descriptive epidemiology, which characterizes health events in terms of time, place, and person.  Determinants—Epidemiologists also attempt to search for causes or factors that are associated with increased risk or probability of disease. This type of epidemiology, where we move from questions of "who," "what," "where," and "when" and start trying to answer "how" and "why," is referred to as analytical epidemiology.

 Health-related states—Epidemiology as it is practiced today is applied to the whole spectrum of health-related events, which includes chronic disease, environmental problems, behavioral problems, and injuries in addition to infectious disease.  Populations—One of the most important distinguishing characteristics of epidemiology is that it deals with groups of people rather than with individual patients.  Control—Epidemiological data steers public health decision making and aids in developing and evaluating interventions to control and prevent health problems. This is the primary function of applied, or field, epidemiology.

 John Snow  Cholera outbreaks in London  Ignaz Semmelweis  Childbed fever (puerperal sepsis)  Florence Nightingale  Epidemic typhus 1858

 Cholera epidemics in London 1846 – 1849  Snow analyzed the death records and interviewed survivors  Created map  Most individuals who died of cholera used water from Broad street pump  Survivors did not drink water but beer instead or used another pump  Identified the Broad street water pump as likely source  After closing this pump number of cholera cases dropped significantly

Mandatory hand washing introduced

 Recorded statistics on epidemic typhus in English civilian and military populations  Published a 1000 page report in 1858  Statistically linked disease and death with poor food and unsanitary conditions  Novel graph: coxcomb chart or polar area diagram chart ▪ Fixed angle and variable radii  Resulted in reforms in the British Army  Nightingale became the first female member of the Statistical Society

 Experimental  Epidemiologist is in control of the circumstances at the beginning of the study  Begins with a hypothesis  Prospective study that usually involves controls  Example: Semmelweis’ study; vaccine efficacy trials  Observational (or descriptive)  Epidemiologist is not in control of the circumstances at the beginning of the study  Descriptive ▪ Collect data about affected individuals, the places and the periods in which disease occurred (Who? Where? When?) ▪ Typically retrospective ▪ E.g. Snow’s study  Analytical ▪ Analyzes a particular disease to determine its probable cause (How? Why?) ▪ Case control method – look for factors that might have preceded the disease ▪ Cohort method – study of two populations, one having had contact with the disease agent and the other that has not ▪ E.g., Nightingale’s study