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Dynamics of Disease Transmission Presentation By: Ann M. Vuong, DrPH MPH History of Infectious Disease Era of Plagues “Everybody knows that pestilences have a way of recurring in the world; yet somehow we find it hard to believe in ones that crash down on our heads from a blue sky. There have been a...

Dynamics of Disease Transmission Presentation By: Ann M. Vuong, DrPH MPH History of Infectious Disease Era of Plagues “Everybody knows that pestilences have a way of recurring in the world; yet somehow we find it hard to believe in ones that crash down on our heads from a blue sky. There have been as many plagues as wars in history; yet always plagues and wars take people equally by surprise.” Bubonic Plague Smallpox Syphilis - Albert Camus 3 Agent: Yersina pestis Vector: Fleas, rats Incubation Period: 2-6 days Symptoms: Fever, headaches, vomiting, swollen and painful lymph nodes Treatment: Streptomycin, gentamicin, doxycycline Plague of Justinian – Eastern Roman Empire Bubonic Plague – 25-50 million deaths Black Death (1347-1351) – 24 million Europeans – 40 million worldwide Modern Pandemic (mid-19th century) – Originated in Eastern Asia 4 Agent: Variola major, Variola minor Transmission: Person-to-person contact via inhalation of airborne droplets of variola virus Incubation Period: 1-3 weeks Symptoms: Fever, vomiting, mouth sores, fluid filled blisters which scab over Treatment: Smallpox vaccination, supportive care, Tecovirimat 1350 BCE, Egyptian-Hittite war Epidemics in: Smallpox – Eurasia – Africa – Americas 5 Agents: Treponema pallidum Transmission: Person-to-person contact via bodily fluids, primarily during sexual intercourse Incubation Period: 3-90 days Symptoms: – Primary: Chancre – Secondary: Skin rash, swollen lymph nodes, fever – Latent: No symptoms – Tertiary: Gummatous syphilis, neurosyphilis, or cardiovascular syphilis Treatment: Intramuscular benzathine benzylpenicillin or intravenous penicillin Syphilis 1490s – Spain, Italy, and France One of the largest public health burdens during 16th-19th centuries 6 Epidemiologic Triangle Agent Epidemiologic Triangle Host: Susceptibility due to genetics, resiliency, behavioral factors, nutritional status, immune response Disease Agent: Virulence, pathogenicity, infectivity, mode of transmission Environment: Climate, building design, sanitation, social environment, access to healthcare Environment Host 8 Environment Reservoir in Nature HIV Rabies Hepatitis B Yersinia pestis Hepatitis C Leptospira Shigella Brucella Clostridium tetani Clostridium botulinum Histoplasma capsulatum Legionella Pseudomonas aeruginosa Mycobaterium marinum S. typhi 9 Agent Epidemiologic Triangle Host: Susceptibility due to genetics, resiliency, behavioral factors, nutritional status, immune response Disease Agent: Virulence, pathogenicity, infectivity, mode of transmission Environment: Climate, building design, sanitation, social environment, access to healthcare Environment Host 10 Agents of Infectious Disease Agents of Infectious Disease Bacteria Viruses Fungi Protozoa Helminths Arthropods 12 Characteristics of Infectious Agents Capacity of the agent to enter and multiply in a susceptible host and thus produce an infection Infectivity Secondary attack rate – Measure of infectivity High Infectivity Low Infectivity Tuberculosis Leprosy Pertussis Measles Ebola HPV SARS/COV Influenza 14 Capacity of the agent to cause disease in the infected host Pathogenicity Proportion of infected individuals with clinically apparent disease High Pathogenicity Low Pathogenicity Polio Tuberculosis Leprosy Measles Rabies Pertussis Ebola Smallpox Rhinovirus-URI SARS/COV Influenza 15 Severity of the disease after infection occurs Virulence Measured using case fatality rate or as the proportion of clinical cases that develop severe disease High Virulence Rabies Ebola SARS/COV Smallpox Low Virulence Rhinovirus-URI Rubella Mumps 16 Capacity of the agent to produce a toxin or poison – Endotoxins Toxigenicity Lipopolysaccharide pyrogenic substances in cell wall of gram negative bacteria Produces fever, weakly toxic – Exotoxins Proteins secreted by mostly gram positive bacteria Does not produce fever in the host, highly toxic Endotoxins Exotoxins C. botulinum C. diphtheria C. tetani S. aureus E. coli Salmonella Shigella Neisseria B. pertussis 17 Characteristics of Infectious Agents Resistance – Ability of the agent to survive adverse environmental conditions Antigenicity – Ability of the agent to induce antibody production in the host – aka immunogenicity 18 Agent Epidemiologic Triangle Host: Susceptibility due to genetics, resiliency, behavioral factors, nutritional status, immune response Disease Agent: Virulence, pathogenicity, infectivity, mode of transmission Environment: Climate, building design, sanitation, social environment, access to healthcare Environment Host 19 Mode of Transmission: Contact Direct or indirect Food- or Waterborne Ingestion of contaminated food Airborne Inhalation of contaminated air Agent to host Vector-borne Perinatal Mosquito, tick, snail, etc. In utero, at time of delivery, or during postpartum period 20 Mode of Transmission for various diseases Portal of Exit Mode of Transmission Portal of Entry Type of Disease Respiratory secretions Airborne droplets, fomites Respiratory tract Common cold, measles Feces Water, food, fomites, flies Alimentary tract Typhoid, poliomyelitis Lesions, exudate Direct contact, fomites, sexual intercourse Skin, genital membranes Carbuncles, syphilis, gonorrhea Conjunctival exudate Fomites, flies Ocular mucous membranes Trachoma Blood Bloodsucking arthropod vector Skin (broken) Malaria, yellow fever, epidemic typhus 21 Infectious Diseases Transmitted by a Collection of Modes Brucellosis Tularemia Plague Anthrax Rabies 22 Perinatal Infections Cytomegalovirus Rubella HIV 23 Varicella-zoster Parvovirus B19 First Trimester Hepatitis B Varicella-zoster Syphilis Second Trimester HIV Hepatitis B Syphilis HIV Third Trimester Hepatitis B Hepatitis B HIV Delivery Herpes Simplex Virus Parvovirus B19 Toxoplasmosis TORCH Infections Incubation Period: Interval from receipt of infection to onset of clinical illness Time needed for pathogen to replicate and cause symptoms Possible to transmit disease to other during incubation period 24 An infection does not always cause an illness Levels of infection – Infection: The entry and development or multiplication of an infectious agent in the body of man or animals Colonization (S. aureus on the skin) – Subclinical or inapparent infection (polio) – Infection documented by either an isolation by culture, demonstrated by the presence of a nucleic acid via polymerase chain reaction, or by a specific immune response in a person who is asymptomatic Latent infection (virus of herpes simplex) – Infestation - Development and reproduction of arthropods on the surface of the body or in clothing (e.g., lice) Virus is dormant and no overt symptoms are observed Manifestation or clinical infection Opportunistic infection: Infection by organisms that take the opportunity provided by a defect in the host defense to infect the host and cause disease Example: TB + AIDS 25 Clinical Subclinical Tissue Cellular Molecular Iceberg Concept of Infection 26 CELL RESPONSE HOST RESPONSE Fatal Lysis of cell Discernable effect Cell transformation or Cell dysfunction Incomplete viral maturation Below visual change Exposure without cell entry Clinical and severe disease Clinical disease Moderate severity Mild illness Iceberg Concept of Infection Infection without clinical disease Subclinical disease Exposure without infection 27 Carrier State: An asymptomatic person or organism that is infected with the pathogen who can transmit it to others, but displays no signs or symptoms Patient Zero 28 Agent Epidemiologic Triangle Host: Susceptibility due to genetics, resiliency, behavioral factors, nutritional status, immune response Disease Agent: Virulence, pathogenicity, infectivity, mode of transmission Environment: Climate, building design, sanitation, social environment, access to healthcare Environment Host 29 Immunity Innate Immunity Protect human body without prior exposure to pathogen Mechanical mechanisms Skin, mucosal surfaces, saliva, tears, gastric acid, cilia Cellular mechanisms WBCs, phagocytic cells, inflammatory cells, NK cells Natural Acquired Immunity Infection by agent Antibodies passed from mother to fetus via placenta to infant via breastmilk Artificial Vaccination Prophylaxis 30 Herd Immunity Immunity that occurs when a significant portion of the population has received a vaccination that provides a measure of protection for those who have not developed immunity Immunity Threshold* 31 Herd Immunity Threshold Disease Average number of secondary infections resulting form a single index case Herd Immunity Threshold Diphtheria 6-7 85% Measles 12-18 83-94% Mumps 4-7 75-86% Pertussis 12-17 92-94% Polio 5-7 80-86% Rubella 5-7 83-85% Smallpox 6-7 83-85% 32 Collective Action for Mandatory Vaccination Freedom of Choice versus Community Responsibility Collective Action for Mandatory Vaccination An argument for against mandatory, governmentenforced vaccination Can result in serious and sometimes fatal side effects Contains harmful ingredients Infringement on personal rights Contains “immoral” ingredients Preference for natural immunity Distrust of pharmaceutical companies, FDA, and CDC Diseases that vaccinations are targeting are essentially eradicated 34 Collective Action for Mandatory Vaccination An argument for mandatory, government-enforced vaccination Highly effective Low incidence of side effects Protects against serious illnesses Economically beneficial Protects fetuses from adverse health effects Protects those who are unable to get vaccinations (e.g., immunocompromised, children who are too young to receive vaccinations) New outbreaks of deadly, dangerous, or debilitating diseases (e.g., pertussis and measles) 35 36 CDC Immunization Schedule Number of Confirmed and Probable Pertussis Cases Reported, by week of onset – Washington, January 1, 2011- June 16, 2012 37 MMWR 61(28) July 20, 2012 Mycobacterium tuberculosis Low infectivity Low pathogenicity Moderate virulence Epidemiologic Triangle Tuberculosis Crowding Poor ventilation Bad sanitation Poor Nutrition Concurrent Disease Low Immunity 38 Agent Epidemiologic Triangle Interventions: Natural and public health measures to prevent and treat disease Eradicate Genetically modify Disease Environment Housing quality Sanitation, water Preventive services Remove breeding grounds Host/Reservoir Treat, isolate 39 Immunize Nutrition Educate Change activity patterns Individual Prevention Measures Hand Washing Food Safety 40 41 Individual Prevention Measures Hand Washing Food Safety Male Condoms 42 43 44 Personal Prevention Measures Against Vector-borne Diseases Avoidance and Elimination Physical Barriers Electronic Barriers Chemical Barriers Chemoprophylaxis 45 Community Prevention Measures Water Safety Sanitation Isolation Chemotherapy Environment Management Indoor Residual Spraying InsecticideTreated Bednets Larval Control 46 Disease Occurrence Classifications of Disease Occurrence Endemic – Constant presence of a disease or infectious agent within a given geographic area or population – Usual or expected frequency of disease within a population Epidemic – Unusual occurrence of a disease in a community that is considered an excess of the expected occurrence Pandemic – When epidemics occur on several continents 48 Epidemic? Outbreak? Cluster? A question of scale Epidemic – Epidemic covers a larger geographic area with more than one focal point Outbreak – Usually limited to a small focal area Cluster – An aggregation of relatively uncommon events or disease in space and/or time in amounts believed or perceived to be greater than expected by chance E.g., Cluster of acute gastroenteritis cases in a healthcare facility 49 Rates peak because we are either doing something to reduce disease or saturation occurs Epidemic Curve No official definition of when this actually occurs New endemic rate may be higher than old endemic rate Time could be measured in days, weeks, months, or years 50 Types of Epidemic Curves Point Common Source Involves a common source, with exposures occurring over a relatively brief period Characterized by a rapid increase in cases followed by a somewhat slower decline All cases tend to fall within one incubation period Hepatitis A Incubation Period: 15-50 days Average: 28-30 days 52 Continuous Common Source Cases occurring beyond the span of a single incubation period Downward slope may be sharp if common source of exposure is removed Cholera Incubation Period: 1-3 days 53 Propagated Characterized by a series of successively larger peaks, which are one incubation period apart Successive waves contain more cases until saturation occurs or control measures are implemented aka Progressive source Measles Incubation Period: 7-18 days Average: 10 days 54 Identify the Epidemic Curve Point source epidemic Salmonella Incubation Period: 1-3 days 55 Number of cases needed varies – Past historical patterns of disease Epidemic When does an increase in disease warrant a designation of an ‘epidemic?’ – Case fatality, complication rates, potential spread – Severe cases, single case = outbreak Botulism, polio, guinea worm (dracunculiasis) Triggered from an imbalance between host, agent, and environmental factors – New agent – Change in existing agent (infectivity, pathogenicity, virulence) – Change in number of susceptibles in population – Environmental changes affecting transmission of agent or growth of agent 56 Surveillance of Infectious Diseases The ongoing and systematic collection, collation, and analysis of data, and the dissemination of the results to those who need to know to avoid or prevent infections or epidemics Responsible parties: – Physicians, healthcare workers, laboratories, clinics, public health departments Local Health Department State Health Department CDC Surveillance quality – Completeness, timeliness, sensitivity, specificity, positive predictive value 57 Outbreak Investigation To control the spread of disease Determine causes, source, and mode of transmission Objectives: Determine who is at risk Determine what exposures predispose individuals to disease Know the magnitude of the problem Identify a new agent Determine effectiveness of control measures Identify methods for present and future prevention and control Research and training opportunities Public, political, legal concerns 59 Investigating an Outbreak 1. Verify the accuracy of disease reports 2. Determine the existence of an outbreak 3. Establish a case definition 4. Identify additional cases 5. Conduct descriptive epidemiology 6. Generate and test hypotheses Note: Sequence is not important and not all steps are involved in every investigation. Several steps can be implemented simultaneously and may be ongoing 7. Monitor course of the outbreak and reassess strategies 8. Carry out lab and environmental investigations 9. Implement disease control measures 10. Communicate findings 60 Outbreak Investigation Issues Pressure and urgency to complete investigations quickly Publicity Incomplete, inaccurate data sources Analysis of small numbers 61 62 Difficulty of Investigating Cancer Clusters Cancer Cluster Difficulties Time between exposure to cancer-causing agent Existence of other risk factors Development of cancer can be decades Cancer cases are more likely to represent a cancer cluster if they involve – One type of cancer – A rare type of cancer – A type of cancer in a group not usually affected by that cancer (e.g., cancer in children that is normally seen in adults) Cases of common cancers are those most often perceived and reported by the public as being part of a cancer cluster 63 Measures of Disease Outbreaks Measures of Disease Outbreaks # of deaths from during period of time to a specific disease Total persons with specified disease Attack Rate = Ill Ill + Well × 100 = × 100 = Number of new cases in group – Initial cases Number of susceptible people – Initial cases × 100 = Case Fatality Rate Attack Rate Secondary Attack Rate 65 Number of new cases in group – Initial cases Secondary Attack Rate Number of susceptible people – Initial cases × 100 = Secondary Attack Rate The number of cases of an infection that occur among contacts within the incubation period following exposure to a primary case in relation to the total number of exposed contacts Purpose – Assessing infectivity of an infectious disease agent – Evaluating control measures – Evaluating efficacy of a prophylactic agent – Trace secondary spread of a disease of unknown etiology to determine whether there is a transmissible agent 66 Secondary Attack Rate Calculation 67 Spread of Measles in a Military Barracks Housing Reserve Officers’ Training Corps Summer Cadets Number of Cadets in Barracks Number of Initial Cases Number of Secondary Cases Unimmunized Immunized Unimmunized Immunized Unimmunized Immunized 14 6 2 0 8 0 Number of new cases in group – Initial cases Number of susceptible people – Initial cases 10 – 2 14 – 2 × 100 = × 100 = 66.7% Secondary Attack Rate Study Design Epidemiologic Studies of Infectious Diseases To evaluate the contributions of various factors in the transmission and acquisition of infectious pathogens, as well as those factors favoring endemic transmission and epidemics 69 Case Reports: Thorough description and evaluation of a single case of disease and may describe the transmission, natural clinical history, and/or response to treatment 70 Constantine DG. (1962) Public Health Rep 77(4) Case Reports: Thorough description and evaluation of a single case of disease and may describe the transmission, natural clinical history, and/or response to treatment 71 Bryson YJ, et al. (1995). N Engl J Med 332(13) Case Series: Data from a cluster or series of cases are reported with the purpose of inferring mode of transmission and risk factors for infection 72 Auerbach DM, et al. (1984). Am J Med 76(3) Ecological Studies: Utilize populations with different levels of exposure and examine the correlation of exposure levels with population-level disease frequency Ecological Fallacy* Moses S, et al. (1990). Int J Epi 19(3) 73 Case Control Studies: To compare the exposure characteristics of cases with a representative sample of the target population within which the cases occurred May be important in outbreaks of acute infectious diseases Purpose: – To define the relationship of an infectious agent to a clinical syndrome – To define important risk factors in relation to infectious disease outbreaks Often must be completed quickly during an acute infectious disease to control the epidemic 74 Wisconsin CaseControl Study of Toxic Shock Syndrome (TSS) 75 Adapted from: KE Nelson, John Hopkins University Photo by: Jennifer Rovero/ Camaraface Toxic Shock Syndrome (TSS) Agent: Streptococcus pyogenes or Staphylococcus aureus Symptoms: Fever Rash Skin peeling Low blood pressure Malaise Confusion Treatment: Antibiotics, incision and drainage of any abscesses, intravenous immunoglobulin 76 Wisconsin Case-Control Study of Toxic Shock Syndrome A total of 38 cases of TSS was reported to the Wisconsin State Health Department before June 30, 1980 – 37 women – 35 cases during menses Symptoms included: shock, multisystem illness, and a rash during menstrual period, with unknown cause Background 77 Wisconsin Case-Control Study of Toxic Shock Syndrome Fever ≥102ºF Rash diffuse, macular, erythema Desquamation Hypotension (BP

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