Principles of Infectious Disease & Epidemiology

Epidemiology

Study of the distribution and determinants of a disease in populations 

Infection

Entry and multiplication of an infectious agent in a person/animal 

Infectious Disease 

Clinically manifest disease resulting from infection 

Communicable Disease

One that can be transmitted from one human to another or from animals to humans 

Aims of Infectious Disease Epidemiology

• Identify focus of infection

• Reduce spread of illness

• Identify community risk factors

• Identify new pathogens or variants of existing pathogens 

• Evaluate efficiency of treatment, prevention, and control measures

Incidence

measure of new cases (# of instances of illness commencing) 

Incidence Rate

# of new cases of disease time/period / # persons at risk in population/time period

Prevalence 

Total number of people infected within the population at any time – old and newly diagnosed cases

measure of disease “burden”

Prevalence rate

Prevalence @ time/ Population at risk @ time

Morbidity

Disease burden

Mortality rate

# deaths/time period / population @ risk

Case fatality rate (CFR)

Severity

Number of deaths/time / Number of cases/time

Attack rate

the proportion of people who become ill with a disease in an at-risk population initially free of the disease (from beginning to end of an outbreak)

Endemic

habitual presence of disease or infectious agent within geographic region or population group

Epidemic

occurrence of cases of disease (or outbreak) with frequency clearly in excess of normal expectancy

• Something that is initially epidemic can turn endemic (ex. COVID-19)

Pandemic 

epidemic spreads worldwide – cross continents 

ex) 7 cholera pandemics; 2009 swine origin influenza; COVID-19

Sporadic

Random, isolated cases, unpredictable

ex) meningitis

Common source outbreak 

epidemic from contaminated substances (e.g., water supply, food source)

Propagated outbreak 

person to person (horizontal) transmission

Outbreak descriptive studies comprehensively characterize

Person, place, time 

Chain of Infection

Certain conditions must be met in order for infectious disease to be spread from person to person 

Can only occur all six links: disease organism (agent) - reservoir - mode of escape - mode of - transfer - mode of entry - susceptible host 

Host

Person or living animal that affords subsistence or lodgement to an infectious agent under natural conditions 

• Protists and helminths can pass successive stages in alternative hosts and different species (definitive and intermediate) 

Reservoirs of Infection

Pathogen lives and multiplies in the reservoir (person, animal, insect, plant, etc) 

Does not experience the systems of diseases when infected by pathogen 

Types of Reservoirs 

Human - carriers

Animal - zoonoses

Environmental - ex) soil and water 

Modes of disease transmission (3)

1. Direct transmission 

2. Indirect Transmission

3. Airborne transmission

Direct Transmission 

Can be horizontal or vertical

Horizontal Direct Transmission 

Direct contact - touching, biting, kissing or sexual intercourse

Direct Projections - droplet spray onto mucous membranes of conjunctiva, eye, nose or mouth during sneezing, coughing, spitting, or talking (<1 meter) 

Vertical Direct Transmission

Vertical: congenital, perinatal

• Congenital -- congenital disorders are structural and functional defects present at birth and are the result of cross-placental infection

• Perinatal – shortly before, during, and after birth 

Indirect Transmission 

Can be vehicle or vector borne 

Indirect Transmission: Vehicle-borne 

(no multiplication in or on vehicle) 

ex) Contaminated fomites, water, food, milk, biological products, injection, piercing 

Indirect Transmission: Vector-borne 

arthropods that transmit diseases to humans, e.g., ticks, flies, fleas, lice, mosquitoes

Mechanical vectors

– Transmission passively

– Disease transmission does not require replication in the vector

(e.g., flies and Vibrio cholerae)

Biological vectors 

– Active transmission

– Pathogen replicates in vector; often necessary completion of microbial life cycle in vector

– An incubation period is required before transmission of infective form

(e.g., mosquitoes and dengue virus)

Airborne Transmission (aerosols)

dissemination of microbial aerosols to a suitable portal of entry, usually by the respiratory tract

– Aerosols – small residue result from evaporation of fluid from droplets

Particles 1-5 um are easily drawn into the alveoli of lungs, remain suspended for long periods

– Dust, soil particles

The reproductive rate – Ro

The number of people that one sick person will infect (on average)

Assumes completely naive population with zero immunity 

ex) Measles has an Ro of 18!

Ro Value Meanings 

>1 : Infection is growing, outbreak expanding

= 1 : Transmission is stable, infection rate is steady (endemic level) 

< 1 : # of new infections shrinking, outbreak dying out

Re 

Reflects real-world conditions – accounting for existing immunity, vaccinations, and public health interventions

The Host-microbe Relationship 

Symbiosis association between two species

Mutualism, parasitism, commensalism, antagonism

Colonization – “normal flora“

Mutualism

• both benefit

• ex) bacteria in digestive tract, vitamin K 

Parasitism

• parasitic microbe benefits, host is harmed

• spectrum—slight harm to death

Commensalism

• one species benefits, other neither benefits nor is harmed 

• ex) skin bacteria

Antagonism

both species harm each other

Types of Pathogens

Pathogen, non-pathogen, opportunist 

Pathogen

An organism that is capable of causing disease

Non-pathogen

 An organism that is not usually capable of causing disease

Opportunist

 An organism that only causes disease when the host is compromised

– AIDS

– Immunosuppressive drugs

The Iceberg concept

• Almost all infectious diseases are like a pyramid (disease on top, asymptomatic on bottom) 

• Visible: disease detected by surveillance, usually more severe cases

• Under the surface: disease not detected by disease surveillance

• Main takeaway: for most diseases, we only detect a small portion of the disease burden

• People are infected but asymptomatic, but can still transmit the disease

Incubation period

The time interval between initial contact with an infectious agent and the first appearance of symptoms associated with the infection.

There is a gap between the incubation period and latent period: can easily infect people without knowing since you don’t have the symptoms yet but you are infected 

Latent period

time between exposure and period of communicability

The epidemiologic triad

host, microbe, environment

Pathogenesis

The method by which an infectious agent produces disease in the host. The study concerns itself with the mechanisms by which microbial agents injure discrete populations of cells in different organs to produce the signs and symptoms of disease in a particular host.

Virulence

The capacity of an infectious agent, compared to other closely related infectious agents, to produce disease in a host. Virulence depends on a variety of microbes and host factors.

Disease

The sum of the effects on the host of microbial replication and of the immune response.

Co-evolution of host and microbe

Pathogens evolve to maximize their transmission and survival

1. If virulence aids transmission -> more virulent pathogens will out-compete

2. If severity decreases the likelihood of transmission -> less virulent pathogens favored

Attenuation 

Weakening of the pathogen by sub- culturing on/in laboratory media, laboratory animals

Infectivity – “dose”

• Entry – Adherence

– Specific molecules for adherence to host cells (e.g., virus receptor)

• Colonization and Infection

– Nutrient availability – e.g., the battle for iron

• Host: transferrin, lactoferrin

• Bacterial pathogens: siderophores

Invasion

• Ability to invade host cells and tissues, cause disease and reach secondary sites

– Can be through direct extension into tissues

– Or via the blood and lymph systems

• Microorganisms in blood

– Bacteremia, Viremia, Parasitemia, Fungemia

Two main types of toxins

Exotoxins (proteins) and endotoxins (lipopolysaccharide; LPS)

Endotoxins

– Gram negative bacteria – LPS

– Cell-bound, released when cell lyses

Exotoxins

– Toxic proteins released from growing cells; generally heat labile

– Travel from site of infection and cause damage at distant site

Enterotoxins

Subset of exotoxins – exotoxins affecting the gastrointestinal tract, usually small intestine

Types of exotoxins

Cytolytic, AB, superantigen

Cytolytic toxins

• Secreted, soluble, extracellular proteins

• Damage host cell membrane, cell lysis (e.g., hemolysins, leukocidins)

AB toxins

• B component binds to host cell receptor—facilitates transfer of A

which damages cell

• Diphtheria, cholera, tetanus, botulism

Superantigen toxins

• Toxic shock syndrome

Host factors in infectious diseases

Genetics

– cell receptors

– genetic traits (sickle cell trait and malaria)

– HLA type (MHC)

• Age: old and young usually more susceptible

• Gender – e.g., structure of urinary tract (UTI)

• Pregnancy

• Nutritional status

• Co-morbidities: obesity, diabetes, hypertension

- Hormonal balance

– Glucocorticoids can depress immune system (stress, lack of

sleep)

• Integrity of organ system

– Abnormal urinary tract predisposes to urinary tract infections

– Smoking can predispose to respiratory tract infections

• Integrity of immune system – immunocompromised

• Immune status: previous exposure or vaccination

• Behavior: smoking, diet, drinking, sexual practices, exercise

COVID-19 examples of susceptibility

• Males more susceptible  

• Infection in young people, deaths in old people 

Environmental factors of susceptibility 

Physical

– Weather, climate, geology

– Ecological zone

• Biological

– Sources of food, water, and air

– Presence of vectors, flora and fauna

• Social and cultural

– Density, crowding, adequate housing, war, sanitation,

availability of health care

• Agricultural practices

• Development, urbanization, suburbanization

• Interrupting the chain of infection (mitigation; flatten curve)

Primary Prevention 

Methods to avoid occurrence of disease.

ex) population-based health promotion efforts

Secondary Prevention 

Methods to diagnose and treat existent disease in early stages before it causes significant morbidity

Quarantine

restriction of activities for well persons or animals who have been exposed  to

prevent disease transmission during the incubation period

Isolation

separation for a period at least equal to the period of communicability of infected persons to prevent or limit the transmission of an infectious agent

Monitoring

examination of inanimate objects for the presence of pathogens (air, food, water – threshold level)

Surveillance

systematic collection, analysis and use of epidemiologic data for planning, implementation and assessment of disease control

Information for Action: Passive

public health authorities; central collection of data – Notifiable disease reporting (physicians, laboratory)

Information for Action: Active 

proactive, focused (e.g., CDPH UNEX [unexplained deaths])

• Search for cases

• Syndromic surveillance – e.g., for diarrheal diseases

• Surveys

• Sentinel Surveillance

• Field investigations of epidemics, cases

• Collection of data from affected populations

CDC Surveillance System (maybe include?) 

Foodborne diseases active surveillance network: (FoodNET)

Waterborne Disease and Outbreak Surveillance System: (WBDOSS)

ArboNET: National surveillance system for arboviral diseases in the United States

National Antimicrobial Resistance Monitoring Systems: (NARMS)

Cholera & other Vibrio illness surveillance system: (COVISS) – Gulf coast

National Health & Nutrition Examination Surveillance: (NHANES)

California West Nile Surveillance Program

• Human case surveillance

• Mosquito testing

• Sentinel chicken testing

• Dead bird/tree squirrel surveillance

• Animal case surveillance