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Infectious Disease Epidemiology
Lt Col A S Kushwaha
• Infectious diseases - History
• Why study Infectious diseases
• What is infectious disease epidemiology
• Concepts / definitions – IDE
04/11/2023 3
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,
04/11/2023 262000
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
04/11/2023 78
• 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