HSCI 130: Midterm #2

Epidemiology, Tuberculosis & HIV, Social Determinants of Health

Epidemiology

The study of the distribution and determinants of health-related states in specified populations, and the application of this study to control health problems

Epidemiology Definition 2

• The study of the distribution and determinants

• Of health-related states

• In specified populations

• The application of this study to control health related problems

Epidemiology Distribution

Occurrence of cases by time, place, and person

Epidemiology Determinants

All the causes and risk factors for the occurrence of a disease, including physical, biological, social, cultural, and behavioral factors

Epidemiology Health Related States

• Diagnosis of a specified disease or cause of death

• Health-related behaviour (ex. smoking, prenatal vitamins)

Epidemiology Specified Population

A measurable group, defined by location, time, demographics, and other characteristics

Epidemiology Application

Analysis, conclusion, distribution, and timely use of epidemiologic information to protect the health of the population

Ottawa Charter for Health Promotion

• Build healthy public policy - no-smoking rules in buildings

• Create supportive environments - parks, exercise facilities

• Strengthen community action - empower communities to make healthy decisions

• Develop personal skills - life skills, coping

• Reorient health system - from treatment to prevention/upstream factors

John Snow’s Experiments

• Side of the Street experiment - which way the water flows affects who gets cholera

• Broad street pump experiment - people drinking from the Broad Street Pump gets cholera

  • Mapped cases based on where people got their water from (identified the pump as source)

• Grand experiment - source of water of everyone in London

  • Determines which company supplies the water based on sanity of the water

  • Compared cholera rates by the company

Descriptive Epidemiology

The occurrence of a disease by person, place, and time, answering "who, where, and when”

Analytic Epidemiology

Investigates the causes and risk factors by comparing groups, answering "why and how"

Person/Host Factors

What sets an individual apart from others in the context of contracting an infectious disease

Different types of host factors include:

• Personal factors people are born with

• Acquired host factors

• Transitory host factors

• Behaviours

Place/Environment

How does the prevalence of a disease vary from one place to another?

Range of factors distributed geographically:

• Climate

• Diet

• Cultural Practices

• Methods of food preparation and storage

• Population density

•  Exposure to pollutants

• Insects & bugs

Time

• How are disease changed over time?

• How are diseases cyclical? (recurring)

• How are diseases seasonal?

• Does the time of day matter?

Different agents

Factors that causes or contributes to a disease or health outcome

• Nutritive agents

• Chemical agents

• Physical agents

• Infectious agents

Triad of Distribution

Descriptive epidemiology

Includes:

• Person/Host - who is affected (age, gender, occupation)

• Place - where the disease occurs (geographical location)

• Time - when it occurs (season, year, trend)

Triad of Causation

Analytic epidemiology

Includes:

• Agents - the cause of a disease (bacteria, virus, chemical)

• Host - the person or organism susceptible to the disease

• Environment - external factors that allow the disease to occur or spread (climate, sanitation, social conditions)

Applications of Epidemiology

1. Identifying the cause of a new syndrome

2. Assessing risks of exposure

3. Determining whether treatment “x” is effective

4. Identifying heath service use and trends

5. Identifying practical convention strategies

The Epidemiologic Approach

• Counts cases or health events, and describes them in terms of time, place, and person

• Divides the number of cases by an appropriate denominator to calculate rates (morbidity and mortality)

• Compares these rates over time (trends) or for different groups of people

Endemic

Cases are continually occurring in the population

Epidemic

Outbreak of a disease in a localized group of people

Spread by:

• Vectors

• Carriers

• Sudden intro of new pathogen

Pandemic

Epidemics that have spread beyond their local region and are affecting people in various/all parts of the world

Global estimates for children (<15 years) in 2022

• Children living with HIV - 1.5 million

• New HIV infections - 130 000

• Deaths due to AIDS  - 84 000

Global estimates for adults and children in 2022

• People living with HIV - 39.0 million

• New HIV infections - 1.3 million

• Deaths due to AIDS - 630 000

3600 new HIV infections (adults and children) a day in 2022

• 50% are in sub-Saharan Africa

• 360 are among children under 15 years old

• 3200 are among adults aged 15 years and older, of whom:

  • 46% are women

  • 30% are young people (15-24)

  • 18% are young women (15-24)

People living with HIV accessing antiretroviral therapy

9.2 million people living with HIV did not have access to antiretroviral treatment in 2022

Number of children orphaned due to HIV living in sub-Saharan Africa in 2007

>10 million

Why is it hard to develop an HIV vaccine?

Virus is genetically diverse - has a rapid genetic mutation rate which makes HIV unique for everyone

Measures of Disease Occurance

Useful for:

• Finding which diseases people suffer from

• Determining the extent to which the disease causes death/disability

• Carrying out disease surveillance

To perform these functions, it is important to use a consistent set of indicators in order to make comparisons

Prevalence

The proportion of individuals in a population with the disease at a given point in time

• Must report the time period at which people are counted

• Can be reported as proportion or percentage

Prevalence Formula

= # of existing cases/# of people in a population at given point in time

Point Prevalence vs. Period Prevalence

• Point Prevalence - the proportion of individuals in a population with the disease at a given point in time (ex. on June 30, 2015)

• Period Prevalence - the proportion of individuals in a population with the disease at any time during a specified time period (ex. during the year 2015)

Uses of Prevalence

• Quantify the proportion of people with a disease (how many people are affected?)

• Estimated the probability that an individual will have the disease during a point in time

• Project heath care and other policy needs or issues

• Estimate the costs associated with a particular disease

Cannot tell us:

• Duration of disease

• Cause of disease

Cumulative Incidence

Proportion of people who become diseased during a specific time period

• Must report the time period of interest with a cumulative incidence

• Reported as a proportion

• Assume the entire population of interest is at risk at the beginning of the time period and should exclude…

  • People who already have the disease (cases)

  • People who cannot develop the disease (age, sex, immune, organ removed)

Cumulative Incidence Formula

= # of new cases/# of people in the population at risk of developing the disease at the beginning of the period

Uses of Cumulative Incidence

• Estimate the probability (average risk) that a person will develop the disease during a specific time period

• Research on causes, prevention, and treatment of diseases

Incidence Rate

Measure of the rate of development of a disease in a population

• Rates can go up or down

• Denominator represents window of time people are at risk of disease - not number of people at risk at the beginning

• reported in units of time per 1000 person years

Incidence Rate Formula

= # of new cases/# of person time when people were at risk of developing the disease

Uses of Incidence Rates

Research on causes, prevention, and treatment of disease

Attack Rate

The proportion of a population that becomes ill with a disease during a specific time period

Crude Mortality Rate

Overall incidence of death in a population

• all cause mortality - deaths from all causes

• disease specific mortality - deaths from specific disease

Crude Mortality Rate Formula

= number of deaths/average population during year x 10^5

Standardized Mortality Rates

Age-standardized rate: a procedure where weighted averages of age-specific rates are used to modify rates to a standard population in order to minimize the effects of differences in age composition of different populations

Standardized Mortality Rates - The How…

To use DIRECT standardization, you need to have:

1. Age-specific disease/death rates in a population of interest

2. Age distribution of a standard population

Steps:

1. Calculate morality rate for each age group in population

2. Multiply age specific rate X standard population

3. Add up total expected deaths in a standard population

4. Expected deaths/standard population

Standardized Incidence/Morality Ratios

Compares the observed number of deaths in a population to the number of deaths that would be expected if the population had the same age-specific death rates as a standard population

Standardized incidence/Mortality Ratios Formula

= Observed # of cases (deaths)/# expected for standard

Proportional Mortality Ratio

Proportional Mortality Ratio: Compares the proportion of deaths with a standard population

Proportional Mortality Ratio Formula

= proportion of deaths from specific cause/proportion expected for standard population

Case Fatality Rate

Proportion of people with a given disease who will die from thay disease during a specific time period

• Often used as a measure of the short term severity of acute disease

• expressed per 100 cases (ex. %age)

Case Fatality Rate Formula

= # of deaths from disease in a specified time period/total number with disease 

Infant Mortality Rate Formula

= # of deaths in children up to 1 year in specific year/# of births the same year

• Usually expressed per 1000 births

Why do we use standardized mortality rates?

To account for differences in the age structure of populations

How do you establish causation?

Bradford Hill Criteria of Causality

• Temporality - exposure/effect has to occur before the cause

• Strength of Association - is there a strong connection between the variables

• Consistency - association should be consistently observed in different studies, populations, and settings

• Specificity - The exposure is associated with a specific outcome

• Dose Response - level of duration and exposure

Absolute proof is not needed to justify action

Sufficient Cause

Factor (or more usually a combination of several factors) that will inevitably produce disease 

• Contribution of necessary and contribution causes that makes disease inevitable in an individual

Component Cause

Factor that contributes towards disease causation but is not sufficient to cause disease on it’s own

• Needed in some cases

Necessary Cause

Any agent (or component cause) that is required for the development of given disease

• Found in all cases

Odds Ratio

(A/C)/(B/D) = AD/BC

• Used in control studies

• What is the odds of exposure among cases and controls

• OR> 1.0 positive, OR<1.0 protective factor

If OR = 2.0 odds of disease two times higher than among exposed

Absolute Risk & Relative Risk 

If you are exposed to a risk factor, what is the risk you will get the disease (outcome)

• A/A+B (outcome is exposed/all exposed)

• C/C+D (outcome is unexposed/all unexposed)

CI is exposed/CI is unexposed

Observational Studies

Researcher does not intervene in any way;

• Measurement of occurrence of disease or health outcome

• Comparing patterns of exposure and disease outcomes

• Identifying risk factors associated with health/disease

Both descriptive and analytical can fit here!

Experimental Studies

Investigator tries to change something and measure the effect on disease outcome - clinical trials, preventative trials

Descriptive Studies

Research that described the occurrence of disease and/or exposure

• Explains what is happening by observing data

• Remember: person, place, time

• Ask: who, what, where, when?

Case Reports: Detailed descriptions usually by a doctor(s) identifying diseases that are unusual/interesting; may be related to unusual exposure

• Routine data - mortality, life expectancy

• Prevalence surveys

• Migrant studies

Analytic Studies

Primary purpose is to evaluate the ASSOCIATION between an EXPOSURE or CHARACTERISTIC and the development of a particular disease

• why and how it is happening by analyzing relationships between variables

Exposure

Includes:

• Infectious Agents

• Behaviours

• Intrinsic Characteristic of Individuals

• Social or Environmental Factors

Ecological Studies

Compares the prevalence of exposure and disease occurrence in populations

• Observations collected/displayed at the group level may not apply at the individual level

Cross-Sectional Studies

Study group chosen to represent a subgroup of society/cross-section of the population

Case Control Study

• Involves chosen individuals with disease or outcome of interest (cases) and a comparison group without the disease (controls)

• Multiple ways of selecting the control group

• Compares the odds of exposure

Prospective Cohort Studies

• Follow-Up Studies: Follows people over time to see what happens

• Compares the rates of occurrence of disease in people with or without a particular exposure

Important findings from Smyth ET.AL.

• Current drinking associated with a reduced risk of MI (heart attack)

• Current drinking associated with an increased risk of alcohol related cancers and injury

• High alcohol intake associated with increased mortality

• There are different associations between alcohol and these outcomes, depending on the level of income in the region

Example: Rationale & Research Question

Rationale: Cocoa consumption may improve CVD outcomes

Small Studies had documented improvements in:

• Blood pressure

• Endothelial function

• Insulin sensitivity

Research Question: What about habitual consumption in a group of the population at high risk for heart disease

TB Infection vs. TB Disease

• Begins with latent infection = exposure to TB bacillus (latent infection is asymptomatic)

• Usually affects the lungs and respiratory tract; TB can affect other organ systems in the body

  • Pulmonary disease (primarily)

  • Extra-pulmonary disease

  • Systemic infection when lymphatic dissemination spreads TB bacilli throughout the body

Symptoms of Pulmonary Disease

• Bad cough (>2 weeks)

• Chest pain

• Coughing up blood or sputum (phlegm)

• Weakness or feeling tired

• Weight loss

• Loss of appetite

• Chills

• Fever

• Night sweats

Koch, 1882

Discovered Tubercle bacilli

• Group of five closely related mycobacteria

• Slender, slightly curved rod-shaped bacteria

• Slow growing; generation time (~24 hours)

• High molecular weight of lipids in their cell walls

The Organism

• Genetic mapping indicated that the bacteria is not a mutation of M.bovis

• Million years ago in soil and water in Paleolithic period

• Traces identified in Egyptian mummies from 3500-400 BC

• Initial sporadic becoming endemic

• AD100 in Mediterranean states and Europe

• Increased incidence during Industrial Revolution

• Established in North America by the early 1700s

• Largely unknown in Africa at the beginning of 1900s spread with European colonization 

Overarching findings of world TB report 2023

1. Major global recovery in the number of people being newly diagnosed with TB in 2022, after 2 years of COVID-related disruptions

2. This has started to reverse or moderate the damaging impact of the pandemic on the number of people dying from TB and falling ill with TB

BUT

3. In 2022, TB remained the second leading cause of death from an infectious disease after COVID-19

4. Global TB targets set for 2018-2022 at the first UN high-level meeting on TB were mostly missed and End TB Strategy targets are off track

TB Diagnostic Tests

1. TB skin test

2. Sputum smear microscopy

3. Xpert MTB/RIF

Accuracy of Testing

Measuring Accuracy - do the test results correspond to the true state of the phenomenon?

• Sensitive Tests - ideal case; your tests will identity all people with disease (most people with disease identified)

• Specific Tests - ideal case; your tests will identify only people with disease (most identified actually have disease)

Sensitivity 

How well does the test classify people with disease as diseased?

• Decreasing false negatives will increase proportion of true positives

• Number with disease → A/(A+C) 

Specificity

How well does the test classify people without disease as non-diseased?

• Decreasing false positives will increase proportions of true negatives

• Number without the disease → D/(B+D)

Increasing the sensitivity for TB tests

Why is this important to TB prevention? (decrease # of false negatives)

• TB can spread to other people and they can die without treatment

Improving the specificity of TB tests

Why is this important for TB prevention? (decrease # of false positives)

• Waste of resources

• Stigma

• Antibiotic resistance; won’t work effectively if they contract TB in the future

Factors that influence false positives

• Non-tuberculosis mycobacteria (tropical/subtropical climates)

• BCG vaccination

  • Received before 2 years of age - not likely to be the case

  • Received in childhood/adolescence - 15%-25% have positive reactions up to 20 years later

Factors that influence false negatives

• Immuno-suppression: HIV patients - 20% with CD4>500 and 80%-100% with CD4<200

• Malnutrition

• Corticosteroid use

• Concurrent viral illness

• Recent TB infections (2-10 weeks for reaction)

• Very young age (immune system not developed)

TB Skin Test

• Errors in technique can lead to false positives and negatives

• Canada - TB test positive if reaction > 10mm therefore further diagnostics

• Anergy - non-responsiveness of immune system

Sputum Smear Microscopy 

• Test developed over 100 years ago

• Being phased out in most countries

• Still the most commonly used for of testing for TB

Xpert MTB/RIF

• Rapid molecular test have been developed

• Diagnosis within 100 minutes

• Price of tests reportedly decreased in August 2012 from $16.86 USD to $9.98 USD

Xpert MTB/RIF Pros and Cons

Pros:

• Better sensitivity and specificity than smear microscopy

• Rapid - 2 hours

• Operators don’t need laboratory training/biosafety equipment

  • Can test HIV viral load and test for resistant bacteria

Cons:

• Expensive

• Sophisticated hardware/computer facilities and computer training needed

• Needs continuous electrical supply and conditioning

• Cannot differentiate between live and dead M. tuberculosis

Why is treatment for TB difficult?

• Duration of treatment

• Asymptomatic early

• Regimen of pills

DOTS

Directly Observed Treatment Short-course

• $10 per patient/6-8 months; total treatment costs estimated $100-$1000 for non-drug resistant TB

• Helps in the delivery of ARV treatment for people with HIV/AIDS

• Decreases incidence/prevalence of TB

• Important for reducing drug resistant TB

Prevention

Types of prevention:

• Prevent new cases of infection 

• Prevent activation and reactivation of disease 

Preventing transmission:

• Suspected cases in respiratory isolation; ideally in hospital

• Quasi-isolation at home (no work, school, indoor public places)

• Non contact with people susceptible to TB

• Compliance with therapy

BCG Vaccination

• Part of standard vaccines in WHO Expanded Programme on Immunization; implemented in 100 countries

• Administered at birth

Smallpox Eradication Challenges

Ring Vaccination

• There wasn’t enough vaccines for everyone -  a “ring” is created around a confirmed case and those who had close contact with the infected person were vaccinated

• Difficulty reaching remote places

Polio Campaign Challenges

Had to vaccinate everyone under 5 years old

• Disease wasn’t as visible in comparison to smallpox

• Massive population

• Vaccine was heat sensitive - had to be kept in low temperatures

• Conflicts with religion

Podcast on Indigenous TB

Talks about the history of Indian hospitals

• Mixed TB patients with general patients 

• Isolated/kept people for decades because they assumed they wouldn’t comply with treatment

• Affects how Indigenous people today see the healthcare system - lack of compliance, mistrust, feat

Public health/upstream/downstream (prevention)

• Public health approach - improving the health of the entire populations rather than just an individual

• Responsibilities of the public health system - health emergencies, disease prevention, chronic diseases (protecting and promoting heath of the population)

• Differences between public health and clinical medicine - focus on prevention and promoting health in populations vs. focus on diagnosis and treatment of disease in individual patients

• Features of public health - preventing disease and injury; focuses on protecting the entire population rather than solely on individual treatment