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OUTBREAK INVESTIGATION 1 OUTBREAK INVESTIGATION 1

Outbreak Investigation Composition of Field Investigation Team: --- Requires team of people with skills Outbreak Investigation Composition of Field Investigation Team: --- Requires team of people with skills in: • Epidemiology • Questionnaire design • Interview techniques • Biostatistics • Data management • Microbiology (including access to lab) 2

Outbreak Investigation Major components of an outbreak investigation: • Confirm diagnosis and develop a Outbreak Investigation Major components of an outbreak investigation: • Confirm diagnosis and develop a case definition • Ascertain cases • Construct an epidemic curve • Formulate a hypothesis • Assess risk factors • Conduct laboratory investigation • Establish control measures • Prepare report 3

Outbreak Investigation Confirm diagnosis and develop a case definition: • Preliminary case definition is Outbreak Investigation Confirm diagnosis and develop a case definition: • Preliminary case definition is based on signs and symptoms of infection, the etiologic agent, or both • In the definition, include period under investigation and geographic area or population in which the problem occurred. • If the causal agent is known, it can be included in the case definition. • As investigation proceeds, refine the case definition to increase its specificity (can classify cases as “definite”, “probable”, or “possible”. ) 4

Outbreak Investigation Confirm diagnosis and develop a case definition: • Example of a typical Outbreak Investigation Confirm diagnosis and develop a case definition: • Example of a typical case definition: “All children in classroom 3 of the local school who took part in the field trip on November 20, and who fell ill with vomiting and/or diarrhea between the evening of the 20 th and the evening of the 21 st. ” • Usually, the case definition which start out broader than this, and become progressively more specific. 5

Outbreak Investigation Ascertain cases: • Conduct active surveillance to ascertain any additional cases. --- Outbreak Investigation Ascertain cases: • Conduct active surveillance to ascertain any additional cases. --- In “closed” populations (e. g. day care center), may be able to identify and interview all persons potentially exposed. --- In “dynamic” situations (e. g. restaurants), may need to canvass local physicians, emergency rooms, and other sources. • Collect demographic information and means to contact each case. 6

Outbreak Investigation Ascertain cases and collect risk factor information: • Collect potential risk factor Outbreak Investigation Ascertain cases and collect risk factor information: • Collect potential risk factor information including person, place, and time of illness --- Person (age, gender, underlying illnesses) --- Place (closed environment locations such as schools, sites of routine activities such as pools, and location where the person lives). --- Time (onset of symptoms, activities during potential exposure period, and dates of any medical evaluations). 7

Outbreak Investigation Construct an epidemic curve: • Plots number of cases by the onset Outbreak Investigation Construct an epidemic curve: • Plots number of cases by the onset of illness. • Provides information on: --- probable time of exposure of the cases to the source(s) of infection --- probable incubation period --- whether outbreak was due to common point source (e. g. contaminated food), propagated source (e. g. person-to-person contact), or both. --- whether outbreak was time limited or ongoing. 8

Outbreak Patterns: Classification of Epidemics l Common Source Epidemics – all susceptible individuals have Outbreak Patterns: Classification of Epidemics l Common Source Epidemics – all susceptible individuals have a common exposure – indirect transmission most likely – shape of epidemic curve l fewest number of cases before the minimum incubation period l midline of the curve defines the usual incubation period l uni-modal shape typical l prolonged exposure to source of outbreak widens the apex of the common source curve 9

Outbreak Patterns: Classification of Epidemics l Point Source Epidemics – type of common source Outbreak Patterns: Classification of Epidemics l Point Source Epidemics – type of common source epidemic in which all susceptible individuals are exposed at one point in time l usually brief period – Shape of curve l typically sharp peak - only one incubation period l decline in curve is more rapid 10

Example of Epidemic Curve # of cases Clinic Propagated source, single exposure, no secondary Example of Epidemic Curve # of cases Clinic Propagated source, single exposure, no secondary cases (e. g. measles) 11

Example of Epidemic Curve # of cases Propagated source, secondary and tertiary cases (e. Example of Epidemic Curve # of cases Propagated source, secondary and tertiary cases (e. g. hepatitis A) 12

Example of Epidemic Curve # of cases x am pm am pm X = Example of Epidemic Curve # of cases x am pm am pm X = food handler Days Common source, point exposure (e. g. salmonellosis following a company picnic) 13

Example of Epidemic Curve # of cases Days Common source, intermittent exposure (e. g. Example of Epidemic Curve # of cases Days Common source, intermittent exposure (e. g. bacteremia associated with contaminated blood product) 14

Outbreak Investigation Formulate a hypothesis: • Review signs/symptoms of disease exhibited by cases --- Outbreak Investigation Formulate a hypothesis: • Review signs/symptoms of disease exhibited by cases --- GI Sx: probable ingested toxin or pathogen --- Pulmonary Sx: probable inhaled toxin or pathogen • Evaluate epidemic curve to calculate probable incubation period. • Develop list of all potential risk factors associated with infection. • Generate hypothesis(es) and select appropriate 15 study design to assess potential risk factors.

Outbreak Investigation Assess risk factors (select study design): • In a “closed” population (e. Outbreak Investigation Assess risk factors (select study design): • In a “closed” population (e. g. hospital, school), retrospective cohort study may be used. • In general, the case-control study is especially suited to investigating outbreaks because: --- multiple etiologic hypotheses (exposures) can be tested concurrently --- analysis does not require full enumeration of the whole cohort --- makes efficient use of time and resources 16

Outbreak Investigation Assess risk factors (select study design): • In a “closed” population (e. Outbreak Investigation Assess risk factors (select study design): • In a “closed” population (e. g. hospital, school), retrospective cohort study may be used. • In general, the case-control study is especially suited to investigating outbreaks because: --- multiple etiologic hypotheses (exposures) can be tested concurrently --- analysis does not require full enumeration of the whole cohort --- makes efficient use of time and resources 17

Outbreak Investigation Retrospective cohort study design: • Classify persons on the basis of exposure Outbreak Investigation Retrospective cohort study design: • Classify persons on the basis of exposure to the suspected source of infection • Compare “attack rate” (AR) between exposed and non-exposed persons Number of cases of a disease AR = ------------------Total population at risk for a limited period of observation 18

Outbreak Investigation Retrospective cohort study design (example): Of 75 persons who attended a church Outbreak Investigation Retrospective cohort study design (example): Of 75 persons who attended a church supper, 46 became ill within several hours (AR = 46 / 75): AR = 61. 3% Hypothesis: Contaminated vanilla ice cream was the source of the GI infection. Exposure status Did not eat ice cream Ate ice cream N 18 54 Became ill Attack rate Relative risk 3 16. 7% 1. 0 43 79. 6% 4. 77 19

Outbreak Investigation • Note: The “ secondary attack rate” (SAR) is an index of Outbreak Investigation • Note: The “ secondary attack rate” (SAR) is an index of the spread of disease within a household or other circumscribed unit (all persons are exposed to primary case) Number of cases in group – initial case(s) SAR = --------------------------Number of susceptible persons in group – initial cases • SAR is conditional on being exposed to infection • Used to assess infectivity of infectious disease agent • May be used to evaluate efficacy of prophylactic 20 agent

Outbreak Investigation • Note: The “ case fatality rate” (CFR) reflects the fatal outcome Outbreak Investigation • Note: The “ case fatality rate” (CFR) reflects the fatal outcome of disease, which is affected by the efficacy of available treatment CFR = Number of deaths due to disease X ----------------------Number of cases of disease X • For example, mortality from human rabies is very uncommon in the U. S. (hence low overall “mortality rate”), however, the CFR may be relatively high due to frequent failure to receive post-exposure prophylaxis. 21

Outbreak Investigation Case control study design: • Classify persons on the basis of infection Outbreak Investigation Case control study design: • Classify persons on the basis of infection status • Compare odds of exposure to suspected causal agent between case and control subjects • When outbreak occurs in a “closed” population (e. g. hospital), controls are usually selected from persons within who were potentially exposed. • Recall bias is especially likely if the outbreak investigation is conducted after a prolonged period of time. 22

Outbreak Investigation Case control study design (example): Several college students presented with GI-related symptoms Outbreak Investigation Case control study design (example): Several college students presented with GI-related symptoms thought to have been associated with food served in the cafeteria Hypothesis: Contaminated macaroni salad was source of the GI infection. Exposure status Cases Controls Ate salad 12 4 Did not eat salad 6 14 12 / 6 OR = ------4 / 14 OR = 7. 0 23

Outbreak Investigation Conduct laboratory investigation: • Used to isolate or otherwise identify the specific Outbreak Investigation Conduct laboratory investigation: • Used to isolate or otherwise identify the specific toxin or pathogen (very important for subsequent control measures) • May be indicated when an environmental source is possible • Molecular analyses of isolates from cases, and if available from the environment, may conclusively demonstrate presence of an outbreak and linkage to an environmental source. 24

Outbreak Investigation Establish control measures: • Initial control measures --- Interrupt transmission from suspected Outbreak Investigation Establish control measures: • Initial control measures --- Interrupt transmission from suspected reservoir • When multiple control measures are possible, select those most effective for interrupting the epidemic, ease of implementation, expense, and safety. --- Engineering changes (e. g. recall of contaminated food) are usually easier to implement than behavioral changes (e. g. alter food practices). • Conduct follow-up studies to assess whether the 25 incidence of illness has been reduced.

Outbreak Investigation Prepare report: • Prepared after control measures have been instituted and effectiveness Outbreak Investigation Prepare report: • Prepared after control measures have been instituted and effectiveness has been evaluated. • Report typically describes: --- Extent of outbreak --- Results of investigation --- Control measures implemented --- Effectiveness of control measures 26

Real Life Example of an Outbreak Hepatitis B Outbreak: • Observation: During 10 -month Real Life Example of an Outbreak Hepatitis B Outbreak: • Observation: During 10 -month period in 198990, 20 cases of acute hepatitis B were diagnosed among patients in a hospital – compared to 4 cases during the previous year. • Potential Risk Factors: Of the 20 cases: --- 18 had diabetes --- 19 were male --- All 20 admitted to one single medical ward at some time in 6 -months preceding illness. Improbable that these 3 factors arose by chance. 27

Real Life Example of an Outbreak Hepatitis B Outbreak: • Additional Cases: Of the Real Life Example of an Outbreak Hepatitis B Outbreak: • Additional Cases: Of the 500+ cases admitted to the ward in 1989, blood samples taken and additional 7 cases were identified. Note: Most cases overall were asymptomatic and identified through routine testing. • Construct Epidemic Curve: The typical incubation period of hepatitis B is 2 to 6 months. 28

# of cases D = Diabetic; N = Non-diabetic N D D 1989 D # of cases D = Diabetic; N = Non-diabetic N D D 1989 D D D D Month of the Year D D N D D D 1990 The above epidemic curve could describe: --Person-to-person spread --primary case diagnosed in March 1989 --secondary case diagnosed in June 1989 --25 tertiary and higher-order cases thereafter 29

Real Life Example of an Outbreak Hepatitis B Outbreak: • Additional Risk Factors Explored: Real Life Example of an Outbreak Hepatitis B Outbreak: • Additional Risk Factors Explored: In addition to presence of diabetes: --- Age, sex, race, date of hospitalization, location of beds in the ward, other behavioral risks, etc. --- All factors explored by use of retrospective cohort study. This included all patients with diabetes admitted to the ward AFTER the primary case had been discharged (n=23 of the 27 original cases), and 37 additional patients still susceptible to hepatitis B infection. 30

Real Life Example of an Outbreak • The only factor that showed a strong Real Life Example of an Outbreak • The only factor that showed a strong association with infection was the use of a spring-loaded device for taking capillary blood samples (e. g. blood glucose levels). Spring Device not device used Infected 23 0 23 Susceptible 32 55 5 5 37 60 Incidence. DEVICE Incidence. NO DEVICE = = 23 / 55 = 0. 42 0/5 = 0. 0 31

Real Life Example of an Outbreak • Subsequent case-control analysis conducted on 3 non-diabetic Real Life Example of an Outbreak • Subsequent case-control analysis conducted on 3 non-diabetic pts with hepatitis B and random sample of non-diabetic susceptible patients. Spring Device not device used Infected 3 0 3 Susceptible 0 3 20 20 20 23 Note: The odds ratio cannot be calculated due to the cells, but the data strongly indicate spring device use is associated with infection (p = 0. 006). 32

Real Life Example of an Outbreak • The investigators concluded: ---Minute amounts of infected Real Life Example of an Outbreak • The investigators concluded: ---Minute amounts of infected blood probably remained on the spring device; this was the probable source of infection. ---The first case was a hepatitis B carrier. ---The second case was a long-term patient of the ward who was routinely tested for capillary blood glucose; he acted as a “reservoir” for the spread to other patients. 33