Infectious Disease Epidemiology

Lt Col A S Kushwaha

• Infectious diseases - History

• Why study Infectious diseases

• What is infectious disease epidemiology

• Concepts / definitions – IDE

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HISTORY • WORST SCOURGES OF MANKIND

• THREAT TO HUMAN SURVIVAL

• KILLED MORE MEN THAN ALL THE WARS

• CAHNGED THE COURSE OF HISTORY

• 14th century - Europe - plague kills 20-45 % of the world’s population

• 1819- - 50 million deaths due to H1N1 spanish Flu

• 1831 - Cairo – 13 % of population succumbs to cholera

• 1854-56 - Crimean war – deaths due to dysentery were 10 times higher

than deaths due to casualties• 1899-1902 - Boer War – deaths due to

dysentery were 5 times higher than deaths due to casualties

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)

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

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).

15 million deaths

DALYs INFECTIOUS DISEASES

21st Century

• Microbes are back in news

• Resistance

• Newer pathogens

• Changing environment – warming

• Bioterrorism

• 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)

SUCCESSES

Mortality due to infectious diseases

CHALLENGES• More pathogens have been identified than the

drugs developed

• Many pathogens no longer respond to drugs

• Human activity has accelerated this imbalance

• HIV

Wonder drugs to Super bugs

Global scenario

Emerging & Re-emerging infections

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

• 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

Emerging AIDS Related Infectious Diseases

1. Pneumocystis carinii pneumonia2. Tuberculosis3. Mycobacterium-avium complex4. Kaposi’s sarcoma (HHV-8)5. HSV-26. Cryptosporidium7. Microsporidium8. Cryptococcus neoformans9. Penicillium marneffei10. Disseminated salmonella11. Bacillary angiomatosis (Bartonella henselae)12. HPV

Some Emerging Non- AIDS related Infectious Diseases

1. SARS2. West Nile disease3. Variant CJD disease4. Monkey pox5. Ebola and Marburg

viruses6. Dengue7. Influenza H5/N1 (?)

8. Hanta virus9. E. Coli O157 :H7 10. Antibiotic-resistant – Pneumococci – Staph-aureus

– Gonococci – Salmonella

11. Cryptosporidium

12. Anthrax

Millions of deaths, worldwide, all ages,

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04/11/2023 272007

04/11/2023 28Charrel et al. 2007. N Engl J Med 356;8

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

Emerging Infectious Diseases Related to Animal Contact

Disease Animal1. HIV-1, LHIV-2 Primates (Africa)2. Influenza Water fowl, pigs, chickens (N5/N1)3. Ebola Primates (“bush meat”)4. Marburg Primate (“bush meat”)5. Hanta virus Deer mouse6. Arena virus Various rodents7. Variant CJD Cattle8. Cryptosporidia Cattle9. Hendra virus Fruit bats10. Nipah virus Pigs, fruit bats11. SARS Civet cats12. Monkey pox Prairie dogs

Epidemiology

• Study of distribution & determinants of disease and health related events and its application in control and prevention.

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)

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.

Two or more populationsHumansInfectious agents

Helminths, bacteria, fungi, protozoa, viruses, prions

Vectors Mosquito (protozoa-malaria), snails (helminths-schistosomiasis)Blackfly (microfilaria-onchocerciasis) – bacteria?

AnimalsDogs and sheep/goats – EchinococcusMice and ticks – Borrelia

What is infectious disease epidemiology?

(www)

A case is a risk factor …Infection in one person can be transmitted to others

What is infectious disease epidemiology?

(www)

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, non-specific immunity, clone, resistance, repeat episodes …

Infectious Disease Epidemiology

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

Epidemiologic triad

Host

Agent Environment•Biological agents•Physical agents•Chemical agents•Nutrient agents•Mechanical agents•Social agents

•Physical environment•Biological environment•Social environment

•Demographic characteristics•Biological characteristics•Socioeconomic characteristics

Infectious Disease Model

Host Pathogen

Environment

Disease

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.

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.

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

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

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.

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.

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

Contagious disease

• A contagious disease is the one that is transmitted through contact.

Examples - scabies, trachoma, STD.

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.

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)

Endemic - Epidemic - Pandemic

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

Time

Case

s

R = 1

R > 1

R < 1

(www)

Endemic EpidemicNum

ber o

f Cas

es o

f a D

isea

se

Time

Endemic vs Epidemic

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)

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

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

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.

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.

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.

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.

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.

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.

Dynamics of disease Transmission (Chain of Infection)

Source or Reservoir Modes of transmission Susceptible host

I II III

(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.”

Types of reservoirs

Reservoir

Human reservoir

Animalreservoir

Non-livingreservoir

Human Reservoir

1. AIDS (HIV infection)2. Syphilis3. Gonorrhea4. Shigellosis5. Typhoid fever6. Hepatitis-B virus7. Herpes simplex virus

Animal Reservoir (Zoonoses)

1. Nontyphoidal salmonellosis2. Brucellosis3. Anthrax4. Listeriosis5. Viral encephalitis (SLE,WEE, CEE)6. Rabies7. Plague

Soil Reservoir

1. Histoplasmosis2. Coccidioidomycosis3. Blastomycosis4. Tetanus5. Botulism

Water Reservoir

1. Pseudomonas infectionsSepsis, UTI, “hot tub” folliculitis

2. Legionnaires’ disease

3. Melioidosis

Human Reservoir

Human reservoir

Cases Carriers

According to spectrum of disease:•Clinical cases (mild/severe-typical/atypical)•Sub-clinical cases•Latent infection cases

•Primary case•Index case•Secondary cases

Type:•Incubatory•Convalescent•Healthy

Duration:•Temporary•Chronic

Portal of exit:•Urinary•Intestinal•Respiratory•others

No infection Clinical Sub-clinical Carrier

Death Carrier Immunity No immunity

Outcome

Exposure to Infectious Agents

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”

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. The presence of the disease agent in the body.2. The absence of recognizable symptoms and signs of disease.3. The shedding of disease agent in the discharge or excretions.

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.

(II): Modes of transmission

Mode of transmission

Direct transmission

Indirecttransmission

Direct contact

Droplet infection

Contact with soil

Inoculation into skin or mucosa

Trans-placental (vertical)

Vehicle-borne

Vector-borne:MechanicalBiological

Air-borne

Fomite-borne

Unclean hands & fingers

PropagativeCyclo-propagative

Cyclo-developmental

Routes of transmission

Direct Skin-skin

Herpes type 1 Mucous-mucous

STI Across placenta

toxoplasmosis Through breast milk

HIV Sneeze-cough

Influenza

Indirect 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)

Modes of Disease Transmission

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• Propagative transmission-

(e.g. viruses, YF, WNV, EEE, etc.)

• Cyclo-developmental

(e.g. Wuchereria bancrofti-Bancroftian filariasis)

• Cyclo-propagative transmission-.

(e.g. malaria, Chagas)

(III): Susceptible host

• An infectious agent seeks a susceptible host aiming “successful parasitism”.

• Four stages are required for successful parasitism:1. Portal of entry2. Site of election inside the body3. Portal of exit4. Survival in external environment

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).

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.

• 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

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 contactsX 100

Virulence and Case Fatality Rate

• Virulence– Degree of pathogenicity; the disease evoking power of a micro-

organism 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.

Case Fatality Rate

Case fatality rate (%) Number of deaths due to disease

Number of cases of disease = x 100

Host defences• L

o

ca

l

• Sy

st

e

m

ic

• S

p

ec

ifi

c

• N

o

n

S

p

ec

ifi

c

Active Immunity•Humoral•Cellular•Combination

Passive Immunity•Normal human Ig•Specific Human Ig•Animal Antitoxins or Antisera

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.

THANK YOU

THANK YOU

Infectious Disease Process

Direct tissue invasion

Toxins

Persistent or latent infection

Altered susceptibility to drugs

Immune suppression

Immune activation (cytokine storm)

• 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

Infe

ction

Susceptible

Susceptible

Dynamics of infectiousness

Dynamics of disease

Incubation period

Symptomaticperiod

Non-diseased

Latentperiod

Infectious period

Non-infectious

Infe

ction

Time

Time

(www)

Timeline for Infection

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

P

S

S

T

Susceptible

Immune

Sub-clinical

Clinical

ST

(www)

Transmission

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

Changes to R(t), over an epidemic

0

200

400

600

800

1000

1200

0 0.05 0.1 0.15 0.2

time

nu

mb

er

Susceptible

Incident cases

Recovered

R=R0

R>1

R=1

R<1

• 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)

Reproductive Number, R0

A measure of the potential for transmissionThe 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

R0 = p • c • d

contacts per unit time

probability of transmission per contact

duration of infectiousness

(www)

Reproductive Number, R0

Infection will …..

if R < 1 --------- disappear,

if R = 1 --------- become endemic,

if R > 1 --------- become

epidemic,

• 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

Reproductive Number, R0

p condoms, acyclovir, zidovudine

c health education, negotiating skills

D case ascertainment (screening,partner notification), treatment, compliance, health seeking behaviour,

accessibility of services

R0 = p • c • d

(www)

Reproductive Number, R0

Use in STI Control

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)

What determines R0 ?

Immunity – herd immunity

If R0 is the mean number of secondary cases in a susceptible population, thenR 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 > 0.50If 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)

Vaccination coverage required for elimination

0%

20%

40%

60%

80%

100%

0 2 4 6 8 10 12 14 16 18 20

Basic reproduction number, Ro

Critic

al pro

portio

n, Pc

Pc = 1-1/Ro

rubella measles