Epidemiology Master Level Quiz

Synthesis and Practical Applications: Populations and Measurement

Jennifer Deal, PhD Johns Hopkins University

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Motivating Example: Zika Outbreak in 2015–2016

► We will cover key concepts and material from… ► Lectures: Populations, Epidemics, Measures of Morbidity and Mortality, Validity,

Reliability, Surveillance ► Activities: Outbreak Investigation, Measuring Disease Frequency, Validity and Reliability

The material in this video is subject to the copyright of the owners of the material and is being provided for educational purposes under rules of fair use for registered students in this course only. No additional copies of the copyrighted work may be made or distributed.

Epidemics

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Patterns in Time

► 2015–2016 epidemic ► Brazil declared national public health emergency in November 11, 2015 ► WHO announced end of Zika epidemic in November 2016

Source: WHO.

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Patterns in Space (as of 21 Dec. 2017)

Source: European Centre for Disease Prevention and Control. Accessed December 18, 2018, at https://www.ecdc.europa.eu/sites/portal/files/images/ZikaMap_OutbreakClassification_World%20wide_4.png

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Epidemiologic Triad—Host, Agent, Environment

Host Agent Environment

Age Sex Race Occupation Prior exposures

Biological Chemical Physical

Temperature Humidity Water Air Food Housing Radiation

Host Agent Environment

Monkeys and humans Zika virus (genera: Flavivirus)

Tropical and subtropical regions

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Modes of Disease Transmission

► Direct transmission ► Person-to-person

● Respiratory ● Fecal-oral ● Sexual ● Blood

► Indirect transmission ► Common vehicle (e.g., food)

● Single exposure ● Multiple exposures ● Continuous exposure ● Vector

Source: CDC.

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Modes of Transmission: Zika—1

► Indirect ► Mosquito (vector-borne disease)

► Direct ► Sexual ► Maternal-fetal (intrauterine, perinatal) ► Lab exposure ► Blood transfusion, organ tissue (theoretical)

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Modes of Transmission: Zika—2

► Indirect ► Mosquito (vector-borne disease)

► Direct ► Sexual ► Maternal-fetal (intrauterine, perinatal) ► Lab exposure ► Blood transfusion, organ tissue (theoretical)

► Single exposure?

► Multiple exposure?

► Continuous exposure?

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Epidemic Curve: Zika Virus 2015–2017

Source: Pan American Health Organization. Accessed December 18, 2018.

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Incubation Period: Zika

► Incubation period: 3–14 days

► Viremia—few days to 1 week

► Virus remains in semen longer than in blood

Source: Paz-Bailey et al. (2017). Persistence of Zika virus in body fluids—preliminary report. N Engl J Med, 379(13), 1234–1243. http://dx.doi.org/10.1056/NEJMoa1613108

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Epidemic Curve and Incubation Period

► Question 8: Using the epidemic curve, calculate the estimated median incubation period for the onset of illness (defined as diarrhea without vomiting)? Assume that exposure occurred at 12 pm on 4/9.

► In a single exposure, common- vehicle epidemic, the epidemic curve = distribution of incubation periods

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Attack Rate: Zika

► Whom would you include in the denominator?

► Who is at risk? ► Sex? ► Age? ► Location?

► Attack rate

► 𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁 𝑜𝑜𝑜𝑜 𝑐𝑐𝑐𝑐𝑐𝑐𝑁𝑁𝑐𝑐 𝑐𝑐𝑁𝑁𝑜𝑜𝑎𝑎𝑎𝑎 𝑝𝑝𝑁𝑁𝑜𝑜𝑝𝑝𝑝𝑝𝑁𝑁 𝑐𝑐𝑎𝑎 𝑁𝑁𝑟𝑟𝑐𝑐𝑟𝑟

𝑇𝑇𝑜𝑜𝑎𝑎𝑐𝑐𝑝𝑝 𝑎𝑎𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁 𝑜𝑜𝑜𝑜 𝑝𝑝𝑁𝑁𝑜𝑜𝑝𝑝𝑝𝑝𝑁𝑁 𝑐𝑐𝑎𝑎 𝑁𝑁𝑟𝑟𝑐𝑐𝑟𝑟

► Compare risk of disease in groups with different exposures ► Assumptions

● All persons in denominator were exposed ● All persons in denominator were susceptible ● All cases were detected (for example, no subclinical cases)

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Population at Risk

► What does it mean to be at risk? ► Able to experience the endpoint of interest during the follow-up period

► Characteristics of risk ► Biologic

● Susceptibility ● Target organ

► Methodologic ● Fulfill study criteria of population ● Remain in study under observation ● If first occurrence endpoint: no prior history

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Projected Zika Virus Attack Rates—1

► Denominator: entire population of the country, including regions not exposed to vector Source: Zhang, Q., et al. (2017). Spread of Zika virus in the Americas. Proc Natl Acad Sci USA, 114(22), E4334–E4343. http://dx.doi.org/10.1073/pnas.1620161114

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Projected Zika Virus Attack Rates—What Do These Attack Rates Tell Us?

► Rates vs. Proportions ► Rates: How fast is the disease occurring?

● 𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁 𝑜𝑜𝑜𝑜 𝑁𝑁𝑒𝑒𝑁𝑁𝑎𝑎𝑎𝑎𝑐𝑐 (𝑁𝑁.𝑎𝑎.,𝑎𝑎𝑁𝑁𝑛𝑛 𝑐𝑐𝑐𝑐𝑐𝑐𝑁𝑁𝑐𝑐) 𝑃𝑃𝑜𝑜𝑝𝑝𝑁𝑁𝑝𝑝𝑐𝑐𝑎𝑎𝑟𝑟𝑜𝑜𝑎𝑎−𝑎𝑎𝑟𝑟𝑁𝑁𝑁𝑁

► Proportions: What proportion of the population is affected?

● 𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁 𝑜𝑜𝑜𝑜 𝑝𝑝𝑁𝑁𝑜𝑜𝑝𝑝𝑝𝑝𝑁𝑁 𝑐𝑐𝑜𝑜𝑜𝑜𝑁𝑁𝑐𝑐𝑎𝑎𝑁𝑁𝑎𝑎 𝑇𝑇𝑜𝑜𝑎𝑎𝑐𝑐𝑝𝑝 𝑝𝑝𝑜𝑜𝑝𝑝𝑁𝑁𝑝𝑝𝑐𝑐𝑎𝑎𝑟𝑟𝑜𝑜𝑎𝑎

Source: Zhang, Q., et al. (2017). Spread of Zika virus in the Americas. Proc Natl Acad Sci USA, 114(22), E4334–E4343. http://dx.doi.org/10.1073/pnas.1620161114

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Of What Is an Attack Rate an Example?

► An attack rate is an example of… a) Prevalence b) Cumulative incidence c) Incidence rate d) Mortality rate

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The Answer Is…

► An attack rate is an example of… b) Cumulative incidence

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Zika: Endemic, Epidemic, or Pandemic?—1

► Endemic: the habitual presence of a disease within a given geographic area

► Epidemic: the occurrence in a community or region of a group of illnesses of similar nature, clearly in excess of normal expectancy, and derived from a common or propagated source

► Pandemic: a world-wide epidemic

Endemic and epidemic disease

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Zika: Endemic, Epidemic, or Pandemic?—2

Source: New York Times article accessed December 18, 2018, at https://www.nytimes.com/2016/02/02/health/zika-virus-world-health-organization.html?mcubz=3

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Herd Immunity: Refresher

► The resistance of a group to attack by a disease to which a large portion of members are immune, thus lessening the likelihood of a patient with a disease coming into contact with a susceptible individual

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Herd Immunity: Zika

► “We expect the current epidemic to be largely over in 3 years, with seasonal oscillations in incidence caused by variation in mosquito populations and transmissibility. Herd immunity will likely then cause a delay of more than a decade until further large epidemics are possible.”

Source: Ferguson, N. M., et al. (2016). Countering the Zika epidemic in Latin America. Science, 353(6297), 353–354. http://dx.doi.org/10.1126/science.aag0219

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Other Recent Epidemics?

► Not all epidemics are infectious!

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Epidemics: Summary

► Defined the epidemic ► Person ► Place ► Time

► Described modes of transmission

► Identified epidemic curve

► Reviewed attack rates

► Discussed impact of herd immunity

The material in this video is subject to the copyright of the owners of the material and is being provided for educational purposes under rules of fair use for registered students in this course only. No additional copies of the copyrighted work may be made or distributed.

Populations

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Disease Burden

► How many people are affected? ► Helps to determine how important the

problem is to individuals within a population and to society

► Allows determination of whether the problem merits the risks and benefits of intervention

► Principal functions of public health ► Assess the burden of disease ► Assess risk factors for disease

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Disease Burden: Zika in the United States

► As of August 2017… ► 5,381 symptomatic Zika virus disease cases in US states ► 37,007 symptomatic Zika virus cases in US territories ► 91 liveborn infants with birth defects in US states ► 128 liveborn infants with birth defects in US territories

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Disease Burden: Worldwide

► >85 countries with reported cases of Zika virus disease

► 565,753 suspected cases

► 217,271 confirmed cases

► 3,408 confirmed congenital syndromes associated with Zika virus

► How do we know who is a case?

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Zika Symptoms ► In adults, mild illness with: ► Fever ► Skin rash ► Joint or muscle pain ► Headache ► Conjunctivitis

► No symptoms

► Neurological symptoms

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Zika & Guillian-Barré

Source: Musso, Nilles, & Cao-Lormeau. (2014). Rapid spread of emerging Zika virus in the Pacific area. Clin Microbiol Infect, 20(10), O595-6. http://dx.doi.org/10.1111/1469-0691.12707

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Zika and Microcephaly— 1

► In pregnant women, miscarriage or microcephaly in the fetus

► October 2015: Brazil reports increase in cases of microcephaly

Source: CDC. Accessed December 19, 2018.

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Zika and Microcephaly— 2 Hopkins scientists help find a possible link between Zika and

birth defect, by Meredith Cohn – Contact Reporter “When scientists in Brazil suspected a link between a troubling upswing in the birth defect microcephaly and the mosquito-borne Zika virus last fall, the hunt began for proof. Johns Hopkins neuroscientists and their partners in Florida and Atlanta now say they’ve discovered a big clue. In lab dishes full of stem cells, they may have seen how the virus becomes the disease. Zika damaged and destroyed cells that are the building blocks of the brain.”

Sourcer: Cohn, M. (2016, March 4). Baltimore Sun. Accessed December 19, 2018, at https://www.baltimoresun.com/health/bs-hs-zika-and-microcephaly-20160229-story.html

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Zika and Microcephaly— 3

Source: Tang, H., et al. (2016). Cell Stem Cell, 18(5), 587–90. http://dx.doi.org/10.1016/j.stem.2016.02.016

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Zika Causality Statement

Zika causality statement 7 September 2016

Zika virus infection: update on the evidence for a causal link to congenital brain abnormalities and Guillain-Barré syndrome Update of WHO Statement published on 31 March 2016

Source: WHO. Accessed December 19, 2018, at http://www.who.int/emergencies/zika-virus/causality/en/

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Congenital Zika Syndrome

► Severe microcephaly in which the skull has partially collapsed

► Decreased brain tissue with a specific pattern of brain damage, including subcortical calcifications

► Damage to the back of the eye, including macular scarring and focal pigmentary retinal mottling

► Congenital contractures, such as clubfoot or arthrogryposis

► Hypertonia restricting body movement soon after birth

Source: CDC.

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Zika: Case Definition

► Subtype(s) ► Zika virus, congenital ► Zika virus, non-congenital

► Types of case definitions ► Ideal case definitions are clear,

unambiguous, and easy to use

► Classification system for cases and disease outcomes ► Confirmed ► Probable ► Suspected

Source: CDC. National Notifiable Diseases Surveillance System. Accessed December 20, 2018, at https://wwwn.cdc.gov/nndss/conditions/zika/case-definition/2016/06/

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Per CDC—Case Definition for Outbreak Investigation—1

► “Purpose of a case definition: ► Development of a clear case definition is critical to effective investigation of an

outbreak. Use of a common case definition allows for standardization of the cases of interest both within an ongoing outbreak investigation and possibly between outbreak investigations that differ over time or geographic location.”

Source: CDC. Accessed December 20, 2018, at https://www.cdc.gov/urdo/downloads/casedefinitions.pdf

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Per CDC—Case Definition for Outbreak Investigation—2

► “Developing outbreak case definitions: ► A case definition includes criteria for person, place, time, and clinical features. These should be

specific to the outbreak under investigation. ► ‘Person’ describes key characteristics the patients share in common. For example, this description

may include: age, sex, race, occupation and exclusion criteria (e.g., ‘persons with no history of X disease’).

► ‘Place’ typically describes a specific geographic location (state, county) or facility associated with the outbreak (X nursing home, Y high school).

► ‘Time’ is used to delineate a period of time associated with illness onset for the cases under investigation. Limiting the time period enables exclusion of similar illnesses which are unrelated to the outbreak of interest.

► Initially, ‘clinical features’ should be simple and objective (e.g., sudden onset of fever and cough). The clinical criteria may later be characterized by the presence of specific laboratory findings.”

Source: CDC. Accessed December 20, 2018, at https://www.cdc.gov/urdo/downloads/casedefinitions.pdf

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From CDC Outbreak Investigation Materials

► “Examples of a case definition: ► ‘Student attending X High School who has onset of fever and cough between January 4

and 24, 2007.’ ► ‘A resident of, or visitor to, Rapid City, South Dakota who was diagnosed by a physician,

either clinically or radiographically, with community-acquired pneumonia (CAP) with symptom onset after May 1, 2005 and who had laboratory confirmation of Legionnaires’ disease by culture of Legionella, by urinary antigen test for Legionella pneumophila serogroup 1 (Lp1), by a four-fold or greater rise in serum antibody titer to Lp1, or detection of specific Legionella antigen by direct fluorescent antibody staining.’”

Source: CDC. Accessed December 20, 2018, at https://www.cdc.gov/urdo/downloads/casedefinitions.pdf

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Case Definitions: Zika Virus, Congenital

“Clinical Criteria Liveborn infant with congenital microcephaly, or intracranial calcifications, or structural brain or eye abnormalities, or other congenital central nervous system-related abnormalities not explained by another etiology. (As part of the complete evaluation of congenital microcephaly or other central nervous system [CNS] birth defects, testing for other congenital infections such as syphilis, toxoplasmosis, rubella, cytomegalovirus infection, lymphocytic choriomeningitis virus infection, and herpes simplex virus infections should be considered. An assessment of potential genetic and other teratogenic causes of the congenital anomalies should also be performed.) Case Classification

Probable A neonate meets clinical criteria for congenital disease; AND The neonate’s mother has an epidemiologic linkage or meets laboratory criteria for recent ZIKV or flavivirus infection; AND The neonate has laboratory evidence of ZIKV or flavivirus infection by: ► Positive ZIKV IgM antibody test of serum or CSF collected within 2 days of birth; AND

● positive neutralizing antibody titers against ZIKV and dengue or other flaviviruses endemic to the region where exposure occurred; OR ● negative dengue virus IgM antibody test and no neutralizing antibody testing performed.

Confirmed A neonate meets the clinical criteria for congenital disease AND meets one of the following laboratory criteria:

● ZIKV detection by culture, viral antigen, or viral RNA in fetal tissue, umbilical cord blood, or amniotic fluid; or neonatal serum, CSF, or urine collected within 2 days of birth; OR

● Positive ZIKV IgM antibody test of umbilical cord blood, neonatal serum or CSF collected within 2 days of birth with positive ZIKV neutralizing antibody titers and negative neutralizing antibody titers against dengue or other flaviviruses endemic to the region where exposure occurred.”

Source: CDC. Accessed December 20, 2018, at https://wwwn.cdc.gov/nndss/conditions/zika/case-definition/2016/06/

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Case Definitions: Zika Virus, Non-congenital

“Probable

Meets clinical criteria for non-congenital disease; AND Has an epidemiologic linkage; AND Has laboratory evidence of recent ZIKV or flavivirus infection by:

► Positive ZIKV IgM antibody test of serum or CSF with: ● positive neutralizing antibody titers against ZIKV and dengue or other flaviviruses endemic to the region where

exposure occurred; OR ● negative dengue virus IgM antibody test and no neutralizing antibody testing performed.

Confirmed

Meets clinical criteria for non-congenital disease; AND Has laboratory evidence of recent ZIKV infection by:

► Detection of ZIKV by culture, viral antigen or viral RNA in serum, CSF, tissue, or other specimen (e.g. amniotic fluid, urine, semen, saliva); OR

► Positive ZIKV IgM antibody test of serum or CSF with positive ZIKV neutralizing antibody titers and negative neutralizing antibody titers against dengue or other flaviviruses endemic to the region where exposure occurred.”

Source: CDC. Accessed December 20, 2018, at https://wwwn.cdc.gov/nndss/conditions/zika/case-definition/2016/06/

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Populations at Risk: Test Your Knowledge—1

► Given what we know, who is at greater risk for Zika Virus infection? 1. Scenario 1

a) Male, 30, competing in 2016 Rio Olympics

b) Male, 30, competing in 2014 World Cup Series in Brazil

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Populations at Risk: Test Your Knowledge—2

► Given what we know, who is at greater risk for Zika Virus infection? 1. Scenario 1

a) Male, 30, competing in 2016 Rio Olympics

b) Male, 30, competing in 2014 World Cup Series in Brazil

Person, place, time!

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Populations at Risk: Test Your Knowledge—3

► Given what we know, who is at greater risk for Zika Virus infection? 1. Scenario 1

a) Male, 30, competing in 2016 Rio Olympics

b) Male, 30, competing in 2014 World Cup Series in Brazil

2. Scenario 2 a) Female, 27, residing in Colombia

(6,500 feet above sea level) in 2015 b) Female, 27, pregnant, visiting

family in Puerto Rico in 2015

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Populations at Risk: Test Your Knowledge—4

► Given what we know, who is at greater risk for Zika Virus infection? 1. Scenario 1

a) Male, 30, competing in 2016 Rio Olympics

b) Male, 30, competing in 2014 World Cup Series in Brazil

2. Scenario 2 a) Female, 27, residing in Colombia

(6,500 feet above sea level) in 2015 b) Female, 27, pregnant, visiting

family in Puerto Rico in 2015

The material in this video is subject to the copyright of the owners of the material and is being provided for educational purposes under rules of fair use for registered students in this course only. No additional copies of the copyrighted work may be made or distributed.

Measures of Disease Frequency

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Measures of Disease Frequency: Reminder

► Measures of disease frequency quantify the occurrence of the endpoint with respect to time ► New endpoints

● Incidence rate ● Cumulative incidence (risk)

► Existing endpoints ● Prevalence

► Measures of disease occurrence ► Rates: How fast is the disease

occurring?

● 𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁 𝑜𝑜𝑜𝑜 𝑁𝑁𝑒𝑒𝑁𝑁𝑒𝑒𝑒𝑒𝑒𝑒 (𝑁𝑁.𝑔𝑔.,𝑒𝑒𝑁𝑁𝑛𝑛 𝑐𝑐𝑐𝑐𝑒𝑒𝑁𝑁𝑒𝑒) 𝑃𝑃𝑜𝑜𝑃𝑃𝑁𝑁𝑃𝑃𝑐𝑐𝑒𝑒𝑃𝑃𝑜𝑜𝑒𝑒−𝑒𝑒𝑃𝑃𝑁𝑁𝑁𝑁

► Proportions: What proportion of the population is affected?

● 𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁 𝑜𝑜𝑜𝑜 𝑃𝑃𝑁𝑁𝑜𝑜𝑃𝑃𝑃𝑃𝑁𝑁 𝑐𝑐𝑜𝑜𝑜𝑜𝑁𝑁𝑐𝑐𝑒𝑒𝑁𝑁𝑎𝑎 𝑇𝑇𝑜𝑜𝑒𝑒𝑐𝑐𝑃𝑃 𝑃𝑃𝑜𝑜𝑃𝑃𝑁𝑁𝑃𝑃𝑐𝑐𝑒𝑒𝑃𝑃𝑜𝑜𝑒𝑒

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Incidence of Zika Virus: Brazil

Autochthonous cases— suspected

Autochthonous cases— Confirmed

Imported cases Incidence rate

218,931 135,740 0 169.25

► Population of Brazil: 209,553 × 1000

► Suspected + Confirmed / Population of Brazil

► = 218,931 + 135,740 / 209,553 × 1000

► = 169.25

Source: Pan American Health Organization. Accessed December 20, 2018, at https://www.paho.org/hq/index.php?option=com_content&view=article&id=12390:zika-cumulative-cases&Itemid=42090&lang=en

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Incidence: USA

Autochthonous cases— suspected

Autochthonous cases— Confirmed

Imported cases Incidence rate

0 225 5,076 0.07

► Population of USA: 325,296 × 1000

► Suspected + Confirmed / Population of USA

► = 0 + 225 / 325,296

► = 0.07

Source: Pan American Health Organization. Accessed December 20, 2018, at https://www.paho.org/hq/index.php?option=com_content&view=article&id=12390:zika-cumulative-cases&Itemid=42090&lang=en

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Comparing Incidence: Ratios

► Brazil vs. USA ► 169.25 / 0.07 = 2,418

► Brazil vs. All countries in the Americas ► 169.25 / 78.03 = 2.2

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Zika: Mortality Rates

Country/territory Deaths among

Zika cases Confirmed congenital syndrome

associated with Zika virus infection Population × 1000

Bermuda 0 0 71

Canada 0 1 36,284

United States of America 0 91 325,296

Subtotal 0 92 361,651

Brazil 11 2,775 209,553

Total 20 3,408 1,003,509

Note: Deaths from Zika do not include deaths from Guillain-Barré syndrome. Source: Pan American Health Organization. Accessed December 21, 2018.

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Zika: Calculate Mortality Rates

► Calculate the mortality rate for: ► USA ► Brazil ► Total

► Mortality rates are low!

► Cause-specific mortality rates

► Annual mortality rate from lung cancer (per 1,000 population) = 𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇𝑇 𝑇𝑇𝑙𝑙𝑙𝑙𝑙𝑙 𝑐𝑐𝑇𝑇𝑙𝑙𝑐𝑐𝑐𝑐𝑐𝑐 𝑑𝑑𝑐𝑐𝑇𝑇𝑇𝑇𝑑𝑑𝑑 𝑖𝑖𝑙𝑙 𝑇𝑇𝑙𝑙𝑐𝑐 𝑦𝑦𝑐𝑐𝑇𝑇𝑐𝑐 𝑃𝑃𝑐𝑐𝑐𝑐𝑑𝑑𝑇𝑇𝑙𝑙𝑑𝑑 𝑖𝑖𝑙𝑙 𝑇𝑇𝑑𝑐𝑐 𝑝𝑝𝑇𝑇𝑝𝑝𝑙𝑙𝑇𝑇𝑇𝑇𝑇𝑇𝑖𝑖𝑇𝑇𝑙𝑙 𝑇𝑇𝑇𝑇 𝑚𝑚𝑖𝑖𝑑𝑑𝑦𝑦𝑐𝑐𝑇𝑇𝑐𝑐

× 1,000

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Measures of Disease Frequency: Numerators

► Measures of disease frequency ► Quantify the occurrence of the

endpoint with respect to time ● New endpoints  Incidence rate  Cumulative incidence (risk)

● Existing endpoints  Prevalence

► Measures of disease occurrence ► Rates: How fast is the disease

occurring?

● 𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁 𝑜𝑜𝑜𝑜 𝑁𝑁𝑒𝑒𝑁𝑁𝑒𝑒𝑒𝑒𝑒𝑒 (𝑁𝑁.𝑔𝑔.,𝑒𝑒𝑁𝑁𝑛𝑛 𝑐𝑐𝑐𝑐𝑒𝑒𝑁𝑁𝑒𝑒) 𝑃𝑃𝑜𝑜𝑃𝑃𝑁𝑁𝑃𝑃𝑐𝑐𝑒𝑒𝑃𝑃𝑜𝑜𝑒𝑒−𝑒𝑒𝑃𝑃𝑁𝑁𝑁𝑁

► Proportions: What proportion of the population is affected?

● 𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁 𝑜𝑜𝑜𝑜 𝑃𝑃𝑁𝑁𝑜𝑜𝑃𝑃𝑃𝑃𝑁𝑁 𝑐𝑐𝑜𝑜𝑜𝑜𝑁𝑁𝑐𝑐𝑒𝑒𝑁𝑁𝑎𝑎 𝑇𝑇𝑜𝑜𝑒𝑒𝑐𝑐𝑃𝑃 𝑃𝑃𝑜𝑜𝑃𝑃𝑁𝑁𝑃𝑃𝑐𝑐𝑒𝑒𝑃𝑃𝑜𝑜𝑒𝑒

Note: For all measures, the case definition is the numerator.

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Measures of Disease Frequency: Denominators

► People at risk for the disease ► Person ► Place ► Time

► Rates: How fast is the disease occurring?

► 𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁 𝑜𝑜𝑜𝑜 𝑁𝑁𝑒𝑒𝑁𝑁𝑒𝑒𝑒𝑒𝑒𝑒 (𝑁𝑁.𝑔𝑔.,𝑒𝑒𝑁𝑁𝑛𝑛 𝑐𝑐𝑐𝑐𝑒𝑒𝑁𝑁𝑒𝑒)

𝑃𝑃𝑜𝑜𝑃𝑃𝑁𝑁𝑃𝑃𝑐𝑐𝑒𝑒𝑃𝑃𝑜𝑜𝑒𝑒−𝑒𝑒𝑃𝑃𝑁𝑁𝑁𝑁

► Proportions: What proportion of the population is affected?

► 𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁 𝑜𝑜𝑜𝑜 𝑃𝑃𝑁𝑁𝑜𝑜𝑃𝑃𝑃𝑃𝑁𝑁 𝑐𝑐𝑜𝑜𝑜𝑜𝑁𝑁𝑐𝑐𝑒𝑒𝑁𝑁𝑎𝑎

𝑇𝑇𝑜𝑜𝑒𝑒𝑐𝑐𝑃𝑃 𝑃𝑃𝑜𝑜𝑃𝑃𝑁𝑁𝑃𝑃𝑐𝑐𝑒𝑒𝑃𝑃𝑜𝑜𝑒𝑒

Note: Time may be explicit or implicit in the denominator.

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Measures of Morbidity and Mortality: Summary

► Reviewed measures of morbidity and mortality

► Factors that affect incidence include: ► Time (e.g., 2014 vs. 2016) ► Place (e.g., Brazil vs. USA) ► Population at risk → denominator ► Population affected (e.g., suspected vs. confirmed cases)* → numerator

*Laboratory testing → Correct identification depends on characteristics of the test.

The material in this video is subject to the copyright of the owners of the material and is being provided for educational purposes under rules of fair use for registered students in this course only. No additional copies of the copyrighted work may be made or distributed.

Validity and Reliability

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Validity: Definitions

► Validity: the ability of a test to distinguish between individuals who have a disease and individuals who do not have the disease 1. Sensitivity: ability of a test to correctly identify individuals who have the disease 2. Specificity: ability of a test to correctly identify individuals who do not have the

disease

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Reliability: Definitions

► Reliability: the degree to which the results from a test can be replicated

► Validity ► Are the test results correct? ► Analogous to accuracy

► Reliability ► Are the test results the same when the

same test is repeated in the same individual under similar conditions?

► Analogous to precision

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Validity vs. Reliability

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Zika: Diagnostic Testing

► Testing is complex ► Depends on case definition ► Multiple tests required ► Sensitivity/specificity still being explored

► Would you want higher sensitivity or specificity?

Source: CDC. Accessed December 21, 2018, at https://www.cdc.gov/zika/pdfs/testing-symptomatic-pregnant.pdf

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Diagnostic Testing Algorithm for Zika Virus

Source: CDC. Accessed December 21, 2018, at https://www.cdc.gov/zika/hc-providers/types-of-tests.html

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Factors Affecting Sensitivity and Specificity

► Use of different cutpoints (cutoff) can affect the sensitivity and specificity of the test

► Zika example: “For symptomatic pregnant women with possible exposure to Zika virus, NAT should be performed concurrently with IgM serology.” —CDC

► Sensitivity and specificity are measures of validity and are fixed characteristics of a test

► Cutpoints to define a positive test affect the number of false positives and false negatives that result from the test (Important to maximize sensitivity or specificity?)

► In sequential testing, net sensitivity is decreased, but net specificity is increased. We see the opposite pattern with simultaneous testing.

► Predictive value is important to patients. Positive predictive value increases with increasing disease prevalence and with increasing specificity.

Source: CDC. Accessed December 21, 2018, at https://www.cdc.gov/zika/hc-providers/types-of-tests.html

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Diagnostic Testing for Microcephaly—Case Definition

Source: Clinical Laboratory International. Accessed December 21, 2018, at http://www.clinlabint.com/fileadmin/pdf/Sponsored_Links/Euroimmun_spons_link_CLI_June_2017.pdf

These data were used to draw a receiver operating characteristic curve (appendix p 12) showing the sensitivity (based on definite or probable cases) and specificity (based on the normal distribution of head circumferences among non-affected newborns) of different cutoffs for head circumference. The cutoff of −2 SD has a sensitivity of 83% and specificity of 98%.

Among 319 definite or probable cases with full information, 161 (50%) of 319 had both microcephaly (<−2 Z scores) and a history of a rash, and 277 (87%) of 319 had at least one of the two symptoms. For the 266 suspected cases with a report of a rash, 77 (29%) of 266 were discarded, indicating a positive predictive value of 71.1% (189/266).

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Summary

► Cutpoints can affect sensitivity/specificity

► Positive predictive value more important for expecting mothers infected with Zika

► Different case definitions have different sensitivity/specificity

The material in this video is subject to the copyright of the owners of the material and is being provided for educational purposes under rules of fair use for registered students in this course only. No additional copies of the copyrighted work may be made or distributed.

Surveillance

2

Surveillance: Definition

► “Public health surveillance is the continuous, systematic collection, analysis and interpretation of health-related data needed for the planning, implementation, and evaluation of public health practice.” — WHO

Source: WHO. Accessed December 21, 2018, at https://www.who.int/topics/public_health_surveillance/en/

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Types of Surveillance: Active vs. Passive Surveillance

► Active surveillance ► Advantages

● Can be highly sensitive ● Can collect more detailed

information ● May be more representative

► Disadvantages ● Costly/resource intensive ● Labor intensive ● Difficult to sustain over time

► Passive surveillance ► Advantages

● Less costly ● Easier to design and carry out (can

cover large areas) ● Useful to monitor trends over time

► Disadvantages ● Low sensitivity ● Amount of data available is limited ● May not be representative

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Recall… Where Did These Numbers Come From?

► As of August 2017 ► 5,381 symptomatic Zika virus disease cases in US states ► 37,007 symptomatic Zika virus cases in US territories ► 91 liveborn infants with birth defects in US states ► 128 liveborn infants with birth defects, US territories

Source: CDC.

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Zika Active Surveillance

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Importance of Populations at Risk

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Surveillance: Summary

► Introduction to different methods for identifying Zika cases

► Identify types of surveillance (passive vs. active)

► Use knowledge to prevent future outbreaks

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Lessons Learned

► Described the Zika epidemic

► Calculated and interpreted measures of morbidity and mortality for Zika

► Discussed the importance of validity in testing for Zika

► Introduced surveillance systems for Zika

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Resources of Interest

► CDC ► https://www.cdc.gov/zika/index.html

► Zika podcast ► http://www.who.int/mediacentre/multimedia/podcasts/2017/en/

► New England Journal of Medicine Series ► http://www.nejm.org/page/zika-virus