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Infectious Disease Epidemiology

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Infectious Disease Epidemiology

  1. 1. Infectious Disease Epidemiology Lt Col A S Kushwaha
  2. 2. • Infectious diseases - History • Why study Infectious diseases • What is infectious disease epidemiology • Concepts / definitions – IDE
  4. 4. • 14th century • 1819• 1831 • 1854-56 • 1899-1902 - - Europe - plague kills 20-45 % of the world’s population - 50 million deaths due to H1N1 spanish Flu - Cairo – 13 % of population succumbs to cholera - Crimean war – deaths due to dysentery were 10 times higher than deaths due to casualties Boer War – deaths due to dysentery were 5 times higher than deaths due to casualties
  5. 5. INFECTIONS • Pre 19th Century – Era of Microbes (we didn’t know much about them) • 20th Century – Man – upper hand Vs Microbes (antibiotics, vaccines, safe water, sanitation)
  6. 6. Because infectious diseases have been largely controlled in the United States, we can now close the book on infectious diseases.” William Stewart, MD U.S. Surgeon General, 1967
  7. 7. Microbes are smarter Microbes and vectors swim in the evolutionary stream, and they swim faster than we do. Bacteria reproduce every 30 minutes. For them, a millennium is compressed into a fortnight. They are fleet afoot, and the pace of our research must keep up with them, or they will overtake us. Microbes were here on earth 2 billion years before humans arrived, learning every trick for survival, and it is likely that they will be here 2 billion years after we depart (Krause 1998).
  8. 8. 15 million deaths
  10. 10. 21st Century • Microbes are back in news • Resistance • Newer pathogens • Changing environment – warming • Bioterrorism
  11. 11. SUCCESSES • Eradication of Smallpox in 1977 • Elimination of Poliomyelitis from the Western Hemisphere in 1994 • Potential elimination of global poliomyelitis in the next 5 to 10 years • Potential elimination of measles in the next 10 to 20 years • Vaccines in development for prevention of diarrheal diseases, cervical cancer (HPV)
  12. 12. Mortality due to infectious diseases
  13. 13. CHALLENGES • More pathogens have been identified than the drugs developed • Many pathogens no longer respond to drugs • Human activity has accelerated this imbalance • HIV
  14. 14. Wonder drugs to Super bugs
  15. 15. Global scenario
  16. 16. Emerging & Re-emerging infections
  17. 17. Global Burden of infectious diseases • One death in three of the 54 million deaths worldwide is from an infectious cause • Virtually all of these deaths are in developing areas of the world – mainly India and sub-Saharan Africa • Disproportionately affect children • Many of the developing world deaths are due to preventable causes – – – – Pneumonia and Diarrhea – account for 40% of these deaths Tuberculosis Measles Malaria
  18. 18. • Of the seven biggest killers worldwide, TB, malaria, hepatitis, and, in particular, HIV/AIDS continue to surge – HIV/AIDS and TB likely to account for the overwhelming majority of deaths from infectious diseases in developing countries by 2020 – Acute lower respiratory infections, diarrheal diseases and measles appear to have peaked at high incidence levels
  19. 19. Emerging AIDS Related Infectious Diseases 1. Pneumocystis carinii pneumonia 2. Tuberculosis 3. Mycobacterium-avium complex 4. Kaposi’s sarcoma (HHV-8) 5. HSV-2 6. Cryptosporidium 7. Microsporidium 8. Cryptococcus neoformans 9. Penicillium marneffei 10. Disseminated salmonella 11. Bacillary angiomatosis (Bartonella henselae) 12. HPV
  20. 20. Some Emerging Non- AIDS related Infectious Diseases 1. SARS 2. West Nile disease 3. Variant CJD disease 4. Monkey pox 5. Ebola and Marburg viruses 6. Dengue 7. Influenza H5/N1 (?) 8. Hanta virus 9. E. Coli O157 :H7 10. Antibiotic-resistant – Pneumococci – Staph-aureus – Gonococci – Salmonella 11. Cryptosporidium 12. Anthrax
  21. 21. Millions of deaths, worldwide, all ages,
  22. 22. 2000 10/15/2013 26
  23. 23. 2007 10/15/2013 27
  24. 24. 10/15/2013 28 Charrel et al. 2007. N Engl J Med 356;8
  25. 25. Factors Leading to Emergence of Infectious Diseases • • • • • • AIDS Population growth Speed and ease of travel Dam building Global climate change Increased antibiotic use for humans and animals • Encroachment of human populations on forest • Industrial commercial agriculture • War and social disruption • Relocation of animals • Growth of daycare • Aging of the population • Human-animal contact
  26. 26. Emerging Infectious Diseases Related to Animal Contact Disease 1. HIV-1, LHIV-2 2. Influenza 3. Ebola 4. Marburg 5. Hanta virus 6. Arena virus 7. Variant CJD 8. Cryptosporidia 9. Hendra virus 10. Nipah virus 11. SARS 12. Monkey pox Animal Primates (Africa) Water fowl, pigs, chickens (N5/N1) Primates (“bush meat”) Primate (“bush meat”) Deer mouse Various rodents Cattle Cattle Fruit bats Pigs, fruit bats Civet cats Prairie dogs
  27. 27. Epidemiology • Study of distribution & determinants of disease and health related events and its application in control and prevention.
  28. 28. What is infectious disease epidemiology? • • • • Epidemiology Deals with one population Risk  case Identifies causes Infectious disease epidemiology  Two or more populations  A case is a risk factor  The cause often known (www)
  29. 29. Importance of Studying Communicable Diseases Epidemiology • Changes of the pattern of infectious diseases • Discovery of new infections • The possibility that some chronic diseases have an infective origin.
  30. 30. What is infectious disease epidemiology? Two or more populations Humans Infectious agents Helminths, bacteria, fungi, protozoa, viruses, prions Vectors Mosquito (protozoa-malaria), snails (helminths-schistosomiasis) Blackfly (microfilaria-onchocerciasis) – bacteria? Animals Dogs and sheep/goats – Echinococcus Mice and ticks – Borrelia (www)
  31. 31. What is infectious disease epidemiology? A case is a risk factor … Infection in one person can be transmitted to others (www)
  32. 32. Concepts Specific to Infectious Disease Epidemiology Attack rate, immunity, vector, transmission, carrier, subclinical disease, serial interval, index case, source, exposure, reservoir, incubation period, colonization, generations, susceptible, nonspecific immunity, clone, resistance, repeat episodes …
  33. 33. Infectious Disease Epidemiology
  34. 34. Objectives • The epidemiologic triad • Definition of communicable diseases • Importance of studying communicable diseases epidemiology • Terminology • Dynamics of disease transmission (chain of infection): – Human reservoir or source – Modes of transmission – Susceptible host
  35. 35. Epidemiologic triad •Demographic characteristics •Biological characteristics •Socioeconomic characteristics Host Agent •Biological agents •Physical agents •Chemical agents •Nutrient agents •Mechanical agents •Social agents Environment •Physical environment •Biological environment •Social environment
  36. 36. Infectious Disease Model Pathogen Host Disease Environment
  37. 37. Definition of communicable diseases • A communicable disease is an illness due to a specific infectious (biological) agent or its toxic products capable of being directly or indirectly transmitted from man to man, from animal to man, from animal to animal, or from the environment (through air, water, food, etc..) to man.
  38. 38. Importance of Studying Communicable Diseases Epidemiology • Changes of the pattern of infectious diseases • Discovery of new infections • The possibility that some chronic diseases have an infective origin.
  39. 39. Terminology and Definitions • • • • • • • • • • Infection Contamination Infestation Host Contagious disease Epidemic Endemic Hyperendemic Holoendemic Pandemic • Exotic • Sporadic • Zoonosis, epizootic and enzootic • Nosocomial infection • Opportunistic infection • Eradication • Elimination
  40. 40. Infection • Infection is the entry and development or multiplication of an infectious agent in the body of man or animals. • An infection does not always cause illness. • There are several levels of infection (Gradients of infection): – – – – Colonization (S. aureus in skin and normal nasopharynx) Subclinical or inapparent infection (polio) Latent infection (virus of herpes simplex) Manifest or clinical infection
  41. 41. Contamination • The presence of an infectious agent on a body surface, on or in clothes, beddings, toys, surgical instruments or dressings, or other articles or substances including water and food.
  42. 42. Infestation • It is the lodgment, development and reproduction of arthropods on the surface of the body or in the clothing, e.g. lice, itch mite. This term could be also used to describe the invasion of the gut by parasitic worms, e.g. ascariasis.
  43. 43. Host • A person or an animal that affords subsistence or lodgement to an infectious agent under natural conditions. • Types include: – an obligate host- the only host – definitive (primary) host-attains maturity or passes sexual stages – intermediate host-passes asexual stage – transport host-does not undergo development
  44. 44. Contagious disease • A contagious disease is the one that is transmitted through contact. Examples - scabies, trachoma, STD.
  45. 45. Epidemic • “The unusual occurrence in a community of disease, specific health related behavior, or other health related events clearly in excess of expected occurrence” • (epi= upon; demos= people) • Epidemics can occur upon endemic states too.
  46. 46. Endemic • It refers to the constant presence of a disease or infectious agent within a given geographic area or population group. It is the usual or expected frequency of disease within a population. • (En = in; demos = people)
  47. 47. Endemic - Epidemic - Pandemic R>1 R=1 R<1 Time  Endemic  Transmission occur, but the number of cases remains constant  Epidemic  The number of cases increases  Pandemic  When epidemics occur at several continents – global epidemic (www)
  48. 48. Number of Cases of a Disease Endemic vs Epidemic Endemic Time Epidemic
  49. 49. Hyperendemic and holoendemic • The term “hyperendemic” expresses that the disease is constantly present at high incidence and/or prevalence rate and affects all age groups equally. • The term “holoendemic” expresses a high level of infection beginning early in life and affecting most of the child population, leading to a state of equilibrium such that the adult population shows evidence of the disease much less commonly than do the children (e.g. malaria)
  50. 50. Sporadic • The word sporadic means “scattered about”. • Cases - irregularly, haphazardly and generally infrequently. • Cases - few and separated widely in time and place e.g. polio, meningococcal meningitis, tetanus…. • May be starting point of an epidemic
  51. 51. Pandemic and Exotic • An epidemic usually affecting a large proportion of the population, occuring over a wide geographic area such as a section of a nation, the entire nation, a continent or the world, e.g. Influenza pandemics(1918,1957 & 2009). • Exotic diseases are those which are imported into a country in which they do not otherwise occur, as for e.g., rabies in the UK, Yellow fever in India, CCHF
  52. 52. Zoonosis, Epizootic and Enzootic • Zoonosis is an infection that is transmissible under natural conditions from vertebrate animals to man, e.g. rabies, plague, bovine tuberculosis – Anthropozoonoses e.g., Rabies – Zooanthroponoses e.g., Human TB in cattle – Amphixenosis e.g., T.cruzi • An Epizootic is an outbreak (epidemic) of disease in an animal population, e.g. Rift valley fever, Anthrax. • An Enzootic is an endemic occurring in animals, e.g. Bovine TB.
  53. 53. Nosocomial infections • Nosocomial (hospital acquired) infection is an infection originating in a patient while in a hospital or another health care facility. It has to be a new disorder unrelated to the patient’s primary condition. E.g., infection of surgical wounds, hepatitis B and urinary tract infections.
  54. 54. Opportunistic infection • This is infection by organisms that take the opportunity provided by a defect in host defense (e.g. immunity) to infect the host and thus cause disease. • E.g., opportunistic infections are very common in AIDS. Organisms include Herpes simplex, cytomegalovirus, M. tuberculosis etc.
  55. 55. Iatrogenic (Physician induced) Disease • Any untoward or adverse consequence of a preventive, diagnostic or therapeutic regimen or procedure that causes impairment, handicap, disability or death resulting from a physician’s professional activity or from professional activity of other health professionals. • E.g., reaction to penicillin, hepatitis B infection following blood transfusion.
  56. 56. Eradication • Termination of all transmission of infection by the extermination of the infectious agent through surveillance and containment. Eradication is an absolute process, an “all or none” phenomenon, restricted to termination of infection from the whole world.
  57. 57. Elimination • The term elimination is sometimes used to describe eradication of a disease from a large geographic region. Disease which are amenable to elimination in the meantime are polio, measles, leprosy and diphtheria.
  58. 58. Dynamics of disease Transmission (Chain of Infection) I Source or Reservoir II Modes of transmission III Susceptible host
  59. 59. (I): Source or Reservoir • The source of infection is defined as “the person, animal, object or substance from which an infectious agent passes or is disseminated to the host. • The reservoir is “any person, animal, arthropod, plant, soil, or substance, or a combination of these, in which an infectious agent normally lives and multiplies, on which it depends primarily for survival, and where it reproduces itself in such a manner that it can be transmitted to a susceptible host. • It is the natural habitat of the infectious agent.”
  60. 60. Types of reservoirs Reservoir Human reservoir Animal reservoir Non-living reservoir
  61. 61. Human Reservoir 1. AIDS (HIV infection) 2. Syphilis 3. Gonorrhea 4. Shigellosis 5. Typhoid fever 6. Hepatitis-B virus 7. Herpes simplex virus
  62. 62. Animal Reservoir (Zoonoses) 1. Nontyphoidal salmonellosis 2. Brucellosis 3. Anthrax 4. Listeriosis 5. Viral encephalitis (SLE,WEE, CEE) 6. Rabies 7. Plague
  63. 63. Soil Reservoir 1. Histoplasmosis 2. Coccidioidomycosis 3. Blastomycosis 4. Tetanus 5. Botulism
  64. 64. Water Reservoir 1. Pseudomonas infections Sepsis, UTI, “hot tub” folliculitis 2. Legionnaires’ disease 3. Melioidosis
  65. 65. Human Reservoir Human reservoir Cases •Primary case •Index case •Secondary cases According to spectrum of disease: •Clinical cases (mild/severe-typical/atypical) •Sub-clinical cases •Latent infection cases Type: •Incubatory •Convalescent •Healthy Duration: •Temporary •Chronic Carriers Portal of exit: •Urinary •Intestinal •Respiratory •others
  66. 66. Exposure to Infectious Agents No infection Death Clinical Carrier Sub-clinical Immunity Outcome Carrier No immunity
  67. 67. Cases • A case is defined as “a person in the population or study group identified as having the particular disease, health disorder, or condition under investigation”
  68. 68. Carriers • • • It occurs either due to inadequate treatment or immune response, the disease agent is not completely eliminated, leading to a carrier state. It is “an infected person or animal that harbors a specific infectious agent in the absence of discernible (visible) clinical disease and serves as a potential source of infection to others. Three elements have to occur to form a carrier state: 1. 2. 3. The presence of the disease agent in the body. The absence of recognizable symptoms and signs of disease. The shedding of disease agent in the discharge or excretions.
  69. 69. Animal reservoirs • Zoonosis is an infection that is transmissible under natural conditions from vertebrate animals to man, e.g. rabies, plague, bovine tuberculosis. • There are over a 100 zoonotic diseases that can be conveyed from animal to man.
  70. 70. (II): Modes of transmission Mode of transmission Direct transmission Direct contact Droplet infection Contact with soil Inoculation into skin or mucosa Trans-placental (vertical) Indirect transmission Vehicle-borne Vector-borne: Mechanical Biological Air-borne Propagative Cyclo-propagative Cyclo-developmental Fomite-borne Unclean hands & fingers
  71. 71. Routes of transmission Direct Indirect  Skin-skin  Herpes type 1  Mucous-mucous  STI  Across placenta  toxoplasmosis  Through breast milk  HIV  Sneeze-cough  Influenza  Food-borne  Salmonella  Water-borne  Hepatitis A  Vector-borne  Malaria  Air-borne  Chickenpox  Ting-borne  Scarlatina Exposure  A relevant contact – depends on the agent Skin, sexual intercourse, water contact, etc (www)
  72. 72. Modes of Disease Transmission
  73. 73. • Propagative transmission(e.g. viruses, YF, WNV, EEE, etc.) • Cyclo-developmental (e.g. Wuchereria bancrofti-Bancroftian filariasis) • Cyclo-propagative transmission-. (e.g. malaria, Chagas) 10/15/2013 78
  74. 74. (III): Susceptible host • • An infectious agent seeks a susceptible host aiming “successful parasitism”. Four stages are required for successful parasitism: 1. 2. 3. 4. Portal of entry Site of election inside the body Portal of exit Survival in external environment
  75. 75. Incubation and Latent periods • Incubation period: time from exposure to development of disease. In other words, the time interval between invasion by an infectious agent and the appearance of the first sign or symptom of the disease in question. • Latent period: the period between exposure and the onset of infectiousness (this may be shorter or longer than the incubation period).
  76. 76. Serial interval, Generation time and Infectious period • Serial interval: Gap in time between the onset of the primary and the secondary cases • Generation time : Interval between receipt of infection and maximal infectivity of the host • Infectious (communicable) period: length of time an infectious agent can be transmitted directly or indirectly from an infected person to another person, from an infected animal to man or from an infected person to animal.
  77. 77. • Index Case – Person that comes to the attention of public health authorities • Primary Case – Person who acquires the disease from an exposure • Secondary Case – Person who acquires the disease from an exposure to the primary case – Secondary attack rate
  78. 78. Secondary attack rate • The number of exposed persons developing the disease within the range of the incubation period, following exposure to the primary case. • SAR = No. of exposed persons developing the disease within the range of incubation period Total no. of exposed / susceptible contacts X 100
  79. 79. Virulence and Case Fatality Rate • Virulence – Degree of pathogenicity; the disease evoking power of a microorganism in a given host. – Numerically expressed as the ratio of the number of cases of overt infection to the total number infected. – When death is the only criterion of severity, this is the case fatality rate. • Case fatality rate – Proportion of infected individuals who die of the infection. This is a function of the severity of the infection.
  80. 80. Case Fatality Rate Case fatality rate (%) = Number of deaths due to disease x 100 Number of cases of disease
  81. 81. Host defences • Local • Systemic Active Immunity •Humoral •Cellular •Combination • Specific Passive Immunity • Non Specific •Normal human Ig •Specific Human Ig •Animal Antitoxins or Antisera
  82. 82. Herd Immunity • The level of resistance of a community or group of people to a particular disease. • Provides an immunological barrier to spread of disease in the human herd. • If herd immunity sufficiently high, the occurrence of epidemic is unlikely. • If high level of immunity is achieved and maintained to a point where the susceptible persons are reduced to a small proportion, it may even lead to elimination of a disease e.g., Polio. • Herd immunity does not protect against Tetanus.
  84. 84. Infectious Disease Process Direct tissue invasion Toxins Persistent or latent infection Altered susceptibility to drugs Immune suppression Immune activation (cytokine storm)
  85. 85. • Microbial pathogenesis- process of causing disease • Colonization - presence of microbes at site of body – Does not imply tissue damage or disease symptoms – Does imply invasion of site and multiplication
  86. 86. Timeline for Infection Dynamics of infectiousness Latent period Infectious period Non-infectious Susceptible Time Dynamics of disease Incubation period Symptomatic period Non-diseased Susceptible Time (www)
  87. 87. Transmission Cases  Index – the first case identified  Primary – the case that brings the infection into a population  Secondary – infected by a primary case  Tertiary – infected by a secondary case T S P Susceptible Immune Sub-clinical S S T Clinical (www)
  88. 88. After invasion: the effective reproduction number, R(t) • As pathogen invades, the number of susceptibles declines through recovery (or death) • Eventually, insufficient susceptibles to maintain chains of transmission • On average each infectious person infects < 1 other, epidemic dies out Initial invasion, R(t) = R0 Peak of epidemic R(t) = 1
  89. 89. Changes to R(t), over an epidemic 1200 number 1000 800 Susceptible Incident cases Recovered R=1 600 R<1 R>1 400 R=R0 200 0 0 0.05 0.1 time 0.15 0.2
  90. 90. Reproductive Number, R0 • Useful summary statistic • Definition: the average number of secondary cases a typical infectious individual will cause in a completely susceptible population • Measure of the intrinsic potential for an infectious agent to spread (www)
  91. 91. Reproductive Number, R0 A measure of the potential for transmission The basic reproductive number, R0, the mean number of individuals directly infected by an infectious case through the total infectious period, when introduced to a susceptible population probability of transmission per contact R0 = p • c • d duration of infectiousness contacts per unit time (www)
  92. 92. Infection will ….. if R < 1 --------- disappear, if R = 1 --------- become endemic, if R > 1 --------- become epidemic,
  93. 93. Reproductive Number, R0 • If R0 < 1 then infection cannot invade a population – implications: infection control mechanisms unnecessary (therefore not cost-effective) • If R0 > 1 then (on average) the pathogen will invade that population – implications: control measure necessary to prevent (delay) an epidemic
  94. 94. Reproductive Number, R0 Use in STI Control R0 = p • c • d p c condoms, acyclovir, zidovudine health education, negotiating skills D case ascertainment (screening, partner notification), treatment, compliance, health seeking behaviour, accessibility of services (www)
  95. 95. What determines R0 ? p, transmission probability per exposure – depends on the infection  HIV, p(hand shake)=0, p(transfusion)=1, p(sex)=0.001  interventions often aim at reducing p  use gloves, screene blood, condoms c, number of contacts per time unit – relevant contact depends on infection  same room, within sneezing distance, skin contact,  interventions often aim at reducing c  Isolation, sexual abstinence d, duration of infectious period  may be reduced by medical interventions (TB, but not salmonella) (www)
  96. 96. Immunity – herd immunity If R0 is the mean number of secondary cases in a susceptible population, then R is the mean number of secondary cases in a population where a proportion, p, are immune R = R0 – (p • R0) What proportion needs to be immune to prevent epidemics? If R0 is 2, then R < 1 if the proportion of immune, p, is > 0.50 If R0 is 4, then R < 1 if the proportion of immune, p, is > 0.75 If the mean number of secondary cases should be < 1, then R0 – (p • R0) < 1 p > (R0 – 1)/ R0 = 1 – 1/ R0  If R0 =15, how large will p need to be to avoid an epidemic? p > 1-1/15 = 0.94 The higher R0, the higher proportion of immune required for herd immunity (www)
  97. 97. Vaccination coverage required for elimination Critical proportion, Pc 100% Pc = 1-1/Ro 80% 60% 40% 20% rubella 0% 0 2 4 6 measles 8 10 12 14 16 18 20 Basic reproduction number, Ro
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