Source of infection

1. Source of infectionSource of infection
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MU-Sofia

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Infectious disease epidemiology is a
fundamental part of the whole of
epidemiology. In fact, the subject of
epidemiology originally developed from
the study of epidemics of infectious
disease.
Infectious disease epidemiology is a
science of Public Health that studies
distribution of infectious disease.

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Selected definitions:
InfectionInfection
The entry and development or multiplication of
an infectious agent in the body of man or
animals. It also implies that the body
responds in some way to defend itself against
the invader, either in the form of an immune
response or disease. An infection does not
always cause illness.

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There are several level of infection:There are several level of infection:
Colonization /e.g.S.aureus in the skin
and normal nasopharynx/
Subclinical or inapparent infection
/e.g.polio/
Latent infection /e.g.virus of herpes
symplex/
Manifest or clinical infection

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Infectious disease
A clinically manifest disease of man or animal
resulting from an infection.
Contagious disease
A disease that is transmitted through contact.
Communicable disease
All illness due to specific infectious agent or
its toxic products capable of being directly or
indirectly transmitted from man to man,
animal to animal, or environment (through
air, dust, soil, water, food etc.) to man or
animal.

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ContaminationContamination
The presence of an infectious agent on
a body surface; also in or on clothes,
bedding, toys, surgical instruments or
dressings, or other inanimate articles or
substances including water, milk and
food. (Last's epidemiological definition)

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Epidemic processEpidemic process
The epidemic process defined as a
chain of interrelated and interconnected
infectious conditions in the population
Communicable diseases are transmitted
from the reservoir or source of infection
to susceptible host. This is the medical
model of epidemic process.

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Bacically there are 3 links in the chain
of transmission-the reservoir, mode of
transmission and the susceptible host.
Source Source
/reservoir //reservoir /
of infectionof infection
ModesModes
ofof
transmissiontransmission
SusceptibleSusceptible
hosthost

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Courses /types/ of the epidemic Courses /types/ of the epidemic
process:process:
A disease is said to be sporadicsporadic when
only a few cases occur here and there
in a given region.
OutbreakOutbreak defines as a small.usually
localised epidemic.

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Courses /types/ of the epidemic Courses /types/ of the epidemic
process:process:
Epidemic (from Greek epi- upon + demos Epidemic (from Greek epi- upon + demos
people)-people)- outbreak of disease that affects a much greater
number of people than is usual for the locality or that
spreads to regions where it is ordinarily not present. A
disease that tends to be restricted to a particular region
(endemic disease) can become epidemic if nonimmune
persons are present in large numbers (as in time of war or
during pilgrimages), if the infectious agent is more virulent
than usual, or if distribution of the disease is more easily
effected. Cholera and plague, endemic in parts of Asia, can
become epidemic under the above conditions, as can
dysentery and many other infections. Epidemics may also
be caused by new disease agents in the human population,
such as the Ebola virus

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Courses /types/ of the epidemic Courses /types/ of the epidemic
process:process:
A pandemicpandemic (from Greek pan all +
demos people) is an epidemic (an
outbreak of an infectious disease) that
spreads worldwide, or at least across a
large region.
A worldwide epidemic is known as a
pandemicpandemic, e.g., the influenza
pandemic of 1918 or the AIDS
pandemic beginning in the 1980s.

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Examples / Cholera Examples / Cholera
first pandemic 1816–1826. Previously restricted to
the Indian subcontinent, the pandemic began in
Bengal, then spread across India by 1820. It
extended as far as China and the Caspian Sea
before receding.
The second pandemic (1829–1851) reached
Europe, London in 1832, Ontario Canada and
New York in the same year, and the Pacific coast
of North America by 1834.
The third pandemic (1852–1860) mainly affected
Russia, with over a million deaths.

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Examples / Cholera Examples / Cholera
The fourth pandemic (1863–1875) spread
mostly in Europe and Africa.
In 1866 there was an outbreak in North
America.
The sixth pandemic (1899–1923) had little
effect in Europe because of advances in
public health, but Russia was badly affected
again.
The seventh pandemic began in Indonesia in
1961, called El Tor after the strain, and
reached Bangladesh in 1963, India in 1964,
and the USSR in 1966.

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Examples / InfluenzaExamples / Influenza
The "Spanish fluSpanish flu", 1918–1919.
An estimated 17 million died in India, 500,000 in the
United States and 200,000 in the UK. The virus was
recently reconstructed by scientists at the CDC studying
remains preserved by the Alaskan permafrost. They
identified it as a type of H1N1 virus.

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Courses /types/ of the epidemic Courses /types/ of the epidemic
process:process:
In epidemiology, an infection is said to be
endemic endemic (from Greek en- in or within +
demos people) in a population when that
infection is maintained in the population
without the need for external inputs. For
example, chickenpox is endemic in the UK,
but malaria is not. Every year, there are a few
cases of malaria acquired in the UK, but these
do not lead to sustained transmission in the
population due to the lack of a suitable vector
(mosquitoes of the genus Anopheles).

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SOURCE AND RESERVOIR
The source of infection is defined as the person, animal,
object or substance from which an infectious agent
passes or disseminated to the host.
A reservoir is defined as “any person, animal, arthropod,
plant, soil or substance in which an infectious agent
lives and multiplies, on which it depends primarily for
survival, and where it reproduced itself in such
manner that it can be transmitted to a susceptible
host”. In short the reservoir is the natural habitual in
which the organism metabolized and replicates.

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In Bulgaria the source of infection is
defined only as the person or animal in
which an infectious agent live and
multiplies and from which an infectious
agent passes to the host, inanimate
things and arthropods are defined as a
vehicles of transmission.

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HUMAN RESERVOIR
By far the most important source or
reservoir of infection for humans is man
himself. He my be a case or carrier.
Man is often described as him own
enemy because most of the
communicable disease of which man is
heir to a contacted from human
sources.

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HUMAN RESERVOIR - CASE
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. A variety of
criteria ( clinical, biochemical, laboratory )
may be used to identify cases. Broadly, the
presence of infection in the host may be
clinical, subclinical or latent.

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A case is a risk factor …
Infection in one person can be transmitted
to others
What is infectious disease
epidemiology?

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The clinical illness.
The clinical illness maybe mild or
moderate, typical or atypical,
severe or fatal.
Epidemiologically, mild cases may be
more important sources of infection
than severe cases because they are
ambulant and spread the infection
wherever they go, whereas severe
cases usually confined to bed.

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2.The subclinical cases are variously referred
to as inapparent, covert, missed or abortive cases.
They are equally important sources of infection.
The disease agent may multiply in the host but
does not manifest itself by sign and symptoms.
The disease agent is, eliminated and contaminates
the environment in the same way as clinical
cases.person who are thus sick contribute more
than symptomatic patient to the transmission of
infection to others and what is more, they do not
appear in any of statistics
Subclinical cases play a dominant role in maintaining
the chain of infection in the community. The
latent infection must be distinguished from
subclinical infection. In latent infection, the host
does not shed the infectious agent.

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The subclinical cases
Subclinical infection can be detected only
by laboratory tests.
Barring a few(mesles, varicella),
subclinical infection occurs in most
infectious disease. In some
disease(rubella, mumps, polio, hepatitis
A and B, influenza, diphteria) a great
deal of subclinical infection occurs.

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Latent infection
The term latent infection must be
distinguished from subclinical infection.
In latent infection, the host does not
shed the infectious agent which lies
dormant within the host without
symptoms (and often without
demonstrable presence in blood, tissues
or bodily secretions of the host). For
examples, latent infection occurs in
herpes symplex, Brill-Zincer disease.

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CARRIERS
In some disease, either due to inadequate
treatment or immune response, the disease
agent is not completely eliminated, leading to
a carrier state. A carrier is defined as an
infected person or animal that harbors a
specific infectious agent in the absence of
discernible clinical disease and serves as a
potential source of infection for others.

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CARRIERS
As a rule carriers are less infectious than
cases, but epidemiologically, they are
more dangerous than cases because
they escape recognition and continuing
as they do live a normal life among
population or community, they readily
infect the susceptible individuals over a
wider area and longer period of time
under favorable conditions.the “Typhoid
Mary” is a classic example of a carrier-
cooker Mary who gave rise to more than
1300 cases in her life time.

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The elements in a carrier state are:
The presence in the body of disease
agent
The absence of recognizable
symptoms and signs of disease
The shedding of disease agent in the
discharges or excretion.

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incubatory carriers: are those who shed
the infectious agent during the incubation
period. This usually occurs during the the
last few days of incubation period. As for
example:
Measles-the period of communicability is 4 days
before the rush.
Mumps-usually 4-6 days before onset of
symptoms
Polio-7-10 days before onset of symptoms
Hepatitis B-for a month before jaundice,about 6
weeks after exposure
Carrier may be classified :
BY TYPE

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Carrier may be classified :
BY TYPE
convalescent carriers: that is those who
continue to shed the disease agent during
the period of convalescence(typhoid fever,
cholera, diphteria, bacillary disentery). In
the disease, clinical recovery does not
coincide with bacteriological recovery.

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Carrier may be classified :
BY TYPE
healthy carriers: they are victims of
subclinical infection who have developed
carrier state without suffering from overt
disease, but are nevertheless shedding
the disease agent, e.g. poliomyelitis,
cholera, meningococcal meningitis,
salmonellosis, diphtheria.

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BY DURATION
Temporary carriers are those who shed
the infectious agent for short period of
time.
Chronic carriers are those who excretes
the infectious agent for indefinite periods
e.g. typhoid fever, hepatitis B, dysentery,
etc.They are known to reintroduce disease
into areas which are otherwise free of
infection.

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Chronic carriers
Chronic carriers are far more important sources of
infection than cases. The longer the carrier state,
the greater the risk of community. The duration
of the carrier state varies with the disease. In
typhoid fever and hepatitis B, the chronic carrier
state may last for several years.In chronic
dysentery it may last for year or longer. In
diphtheria, the carrier state is associated with
infected tonsils, in typhoid fever with gall
bladder disease.

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BY PORTAL OF EXIT OF THE IFECTIOUS
AGENT
Urinary
Intestinal
Respiratory
Others
In typhoid fever, the urinary carrier is more
dangerous than an intestinal carrier.

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EARLY DIAGNOSIS IS NEEDED FOR:
The treatment of patient
For epidemiological investigation
To study the time, place and
person distribution
For the institution of prevention
and control measures
The first step in the control of a communicable
disease is its rapid identification.

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Gastro Intestinal / Fecal Oral Route
Transmission by the fecal-oral route is the second
most important mode of transmission after the
respiratory tract
r

excreted by the feces
e

transmitted to the oral
portal of entry through
p

contaminated food
c

contaminated
water, milk, drinks
w

hands
h

flies
Viruses with envelopes do not
survive exposure to hydrochloric
acid in the stomach, bile acids
in the duodenum, salts and
enzymes of the gut. Small
enterovirus without envelope
(Norwalk agent, rotavirus, polio
and coxsackie are able to
resist. HepatitisA and E are
also transmitted by the
fecal oral route.

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Transmission by gastrointestinal route
Fecal oral route
F

Typhoid fever
T

Shigella
S

Cholera
C

Polio
P

Coxsackie, Echo, Reo
C

Norwalk agent
N

Rotavirus
R

Hepatitis A, Hepatitis E

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Intestinal diseases
Human Pathogens
Enterobacteriaceae as a group were
originally divided into pathogens and
nonpathogens based on their ability to
cause diarrheal disease of humans. The
pathogenic genera were Salmonella and
Shigella. However, it is now known that
E. coli causes at least five types of
gastrointestinal disease in humans.
Pathogenicity in E. coli strains is due to
the presence of one or more virulence
factors, including invasiveness factors
(invasins), heat-labile and heat-stable
enterotoxins, verotoxins, and
colonization factors or adhesins.

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Intestinal diseases
Yersinia enterocolitica causes diarrhea,
probably by a combination of invasiveness
and the presence of a heat-stable
enterotoxin. Strains of Klebsiella
pneumoniae and Enterobacter cloacae
isolated from patients with tropical sprue
contained a heat-stable enterotoxin.

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Cholera (frequently called
Asiatic cholera or epidemic
cholera) is a severe
diarrhoeal disease caused by
the bacterium Vibrio
cholerae. Transmission to
humans is by water or food.
The natural reservoir of the
organism is not known. It
was long assumed to be
humans, but some evidence
suggests that it is the aquatic
environment.

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S. aureus causes food poisoning by releasing
enterotoxins into food, and toxic shock
syndrome by release of superantigens into
the blood stream.

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Staphylococcal food poisoning (staphyloenterotoxicosis;
staphyloenterotoxemia) is the name of the condition caused
by the enterotoxins which some strains of S. aureus produce.
The onset of symptoms in staphylococcal food poisoning is
usually rapid and in many cases acute, depending on
individual susceptibility to the toxin, the amount of
contaminated food eaten, the amount of toxin in the food
ingested, and the general health of the victim. The most
common symptoms are nausea, vomiting, retching,
abdominal cramping, and prostration. Some individuals may
not always demonstrate all the symptoms associated with the
illness.
Recovery generally takes two days, However, it us not
unusual for complete recovery to take three days and
sometimes longer in severe cases.

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Normal flora/ FECES ANALYSIS
Staphylococcus aureus /only the
predominance of S. aureus and Candida/
Candida albicans
E.coli
Proteus
Klebsiella
Enterobacter
Serratia
Citrobacter
Pseudomonas aeruginosa /exceptionally
enteropathogenic, and in this case in a pure
culture /

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Intestinal diseases
FECES ANALYSIS
Collection of stools-A fresh specimen of
stool should be collected for laboratory
examination. Sample should be collected
before the person is treated with
antibiotics. After the stools been collected,
there occurs within a few hours an
acidification which is noxious for some
bacteria species.The feces analysis should
begin within 2 to 3 hours after the samples
have been taken.

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MICROSCOPIC EXAMINATION
Before diluting a fragment of the stools in
distilled water, observe:
There consistency: liquid, soft,
molden;
The possible presence of blood,
mucus or glairs.

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DIRECT EXAMINATION
Observe the possible presence of
leucocytes/ suspicion of invading
bacteria/;
Investigate the presence of bacilli with
monotrichous motility /suspicion of
Campylobacter or Vibrio/

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After Gram strain:
Note the percentage of Gram/+/ and
Gram/-/ bacteria, the flora is normally
polymorphous and composed of
about 20% Gram/+/ and 80% Gram/-/;
Investigate the possible presence of
curved Gram/-/ rods;

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The following flora are abnormal:
Predominance of Gram /+/ cocci:
suspicion of staphylococcal
enterocolitis;
Abundant yeast
Monomorphous aspect, presence of
Gram/-/ bacilli only;

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Laboratory
diagnosis
of shigellosis
and
salmonellas
salmonella

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Diagnosis of staphylococcal foodborne
illness.
Incriminated foods should be collected
and examined for staphylococci. The
presence of relatively large numbers of
enterotoxigenic staphylococci is good
circumstantial evidence that the food
contains toxin.

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LABORATORY DIAGNOSIS OF CHOLERA
If a microscope with dark field illumination is
available , it may be possible to diagnose
about 80% of the cases within a few minutes ,
and more cases after 5-6 hours of incubation
in alkaline peptone water . In the dark field ,
the vibrios evoke the image of many shooting
stars in a dark sky. In motility cases on mixing
with polyvalent anti-cholera serum , the
organism are presumed to be cholera vibrios.
Culture method: Bile Salt Agar medium;
In liquid choleric stools , V. cholerae is a pure
culture. In stools from healthy carriers, V.
cholerae is found small quantities mixed with
the commensal flora.

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LABORATORY DIAGNOSIS OF CHOLERA

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LABORATORY DIAGNOSIS

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Diagnostic studies
The diagnosis of pertussis is based on a
characteristic history and physical
examination. If a child presents with a
history of paroxysmal cough for greater than
1 week associated with vomiting, whoops, or
cyanosis, the child is suspected of having
pertussis.
The best method for making the diagnosis of
pertussis is culture the organism from the
nasopharynx.
For culture and/or PCR tests, it is still
recommended to take nasopharyngeal
secretion with a bent charcoal swab.

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Isolation requires special media (chocolate
agar or Bordet-Gengou medium). The
organism requires both the X and V factors
for growth especially for initial isolation.
B.pertussis Bordet-Gengou medium

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MENINGOCOCCAL DISEASE
Bacterial meningitis most commonly
result from the dissemination of
microorganisms from a distant site
of infection, the most common
pathogenic agents in approximately
95% of bacterial meningitis cases
are H. influenzae, Streptococcus
pneumoniae, and N. meningitidis.

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At least 16 serogroups, characterized
by differences in the polyside
capsule, have been identified.
Groups A, B and C account about
90% of meningococcal disease.
Nasopharyngeal carriage of
meningococci is relatively common
among healthy young children /
5~15%/, whereas the correspond
ding figure in adult population is
about 1%.

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N. meningitidis.

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Diphtheria (Greek for “leather,” (διφθερα, dipthera)
Clinical Features Respiratory diphtheria presents as a sore
throat with low-grade fever and an adherent membrane of the
tonsils, pharynx, or nose. Neck swelling is usually present in
severe disease. Cutaneous diphtheria presents as infected skin
lesions which lack a characteristic appearance.
Etiologic Agent Toxin-producing strains of
Corynebacterium diphtheriae.
TransmissionDirect person- to-person transmission by intimate
respiratory and physical contact. Cutaneous lesions are
important in transmission.

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Diphtheria
Pharyngeal diphtheria with membranes
covering the tonsils and uvula
C. diphtheriae

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A throat swab should be cultured on
Loffler’s medium, a tellurite plate, and a
blood agar plate. Specimens should be
transported to the laboratory immediately.
The laboratory should be notified ahead of
time of a suspected diagnosis of diphtheria.
If the specimen cannot be transported
immediately to the laboratory, a transport
medium such as Amies may be used. If
more than 24 hours will elapse before
receipt in the laboratory, specimens should
be shipped at 4o C by courier to the
receiving laboratory. The typical gray-color
of tellurium in the colony is a telltale
diagnostic criterion.
Diphtheria-laboratory diagnosis

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Viral hepatitis
The term hepatitis refer to any condition in which the liver
becomes inflamed and its cells degenerate and die.
4.Viral causes of hepatitis
•Hepatitis A virus
•Hepatitis B virus
•Hepatitis C virus
•Hepatitis D virus
•Hepatitis E virus
•Others :Ebstein-barr
•virus, rubella, cytomegalovirus, herpes virus, varicella zoster
and coxackie B;
12.Bacterial causes of hepatitis include: many organisms that
cause septicaemia, among them E. coli
13.Chemical cause of hepatitis include

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Source of
virus
feces blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
feces
Route of
transmission
fecal-oralpercutaneous
permucosal
percutaneous
permucosal
percutaneous
permucosal
fecal-oral
Chronic
infection
no yes yes yes no
Prevention pre/post-
exposure
immunization
pre/post-
exposure
immunization
blood donor
screening;
risk behavior
modification
pre/post-
exposure
immunization;
risk behavior
modification
ensure safe
drinking
water
Type of
Hepatitis
A B C D E

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Laboratory Diagnosis
Acute infection is diagnosed by the
detection of HAV-IgM in serum by EIA.
Past Infection i.e. immunity is
determined by the detection of HAV-IgG
by EIA.

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High Moderate
Low/Not
Detectable
blood semen urine
serum vaginal fluid feces
wound exudates saliva sweat
tears
breastmilk
Concentration of Hepatitis B
Virus in Various Body Fluids

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Diagnosis
A battery of serological tests are used for the diagnosis of acute
and chronic hepatitis B infection.
HBsAg - used as a general marker of infection.
HBsAb - used to document recovery and/or immunity to HBV
infection.
anti-HBc IgM - marker of acute infection.
anti-HBcIgG - past or chronic infection.
HBeAg - indicates active replication of virus and therefore
infectiveness.
Anti-Hbe - virus no longer replicating. However, the patient can
still be positive for HBsAg which is made by integrated HBV.
HBV-DNA - indicates active replication of virus, more accurate
than HBeAg especially in cases of escape mutants. Used mainly
for monitoring response to therapy.

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Transfusion or transplant from infected donor
Injecting drug use
Hemodialysis (yrs on treatment)
Accidental injuries with needles/sharps
Sexual/household exposure to anti-HCV-
positive contact
Multiple sex partners
Birth to HCV-infected mother
Risk Factors
Associated with
Transmission of
HCV

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Laboratory Diagnosis
HCV antibody - generally used to diagnose hepatitis C
infection. Not useful in the acute phase as it takes at
least 4 weeks after infection before antibody appears.
HCV-RNA - various techniques are available e.g. PCR
and branched DNA. May be used to diagnose HCV
infection in the acute phase. However, its main use is in
monitoring the response to antiviral therapy.
HCV-antigen - an EIA for HCV antigen is available. It
is used in the same capacity as HCV-RNA tests but is
much easier to carry out.

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Coinfection
–severe acute disease.
–low risk of chronic infection.
Superinfection
–usually develop chronic HDV infection.
–high risk of severe chronic liver disease.
–may present as an acute hepatitis.

Hepatitis D -
Clinical Features

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Incubation period:Average 40 days
Range 15-60 days
Case-fatality rate:Overall, 1%-3%
Pregnant women,
15%-25%
Illness severity:Increased with age
Chronic sequelae:None identified
Hepatitis E - Clinical
Features

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Diagnostic Methods in Virology
1. Direct Examination
2. Indirect Examination (Virus Isolation)
3. Serology

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Direct Examination
1. Antigen Detection immunofluorescence, ELISA etc.
2. Electron Microscopy morphology of virus particles
immune electron microscopy
3. Light Microscopy histological appearance
inclusion bodies
4. Viral Genome Detection hybridization with specific
nucleic acid probes
polymerase chain reaction
(PCR)

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Indirect Examination
1.Cell Culture cytopathic effect (CPE)
haemabsorption
immunofluorescence
2. Eggs pocks on CAM
haemagglutination
inclusion bodies
3. Animals disease or death

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Serology
Detection of rising titres of antibody between acute and
convalescent stages of infection, or the detection of IgM in
primary infection.

Classical Techniques Newer Techniques
1. Complement fixation tests (CFT)1. Radioimmunoassay (RIA)
2. Haemagglutination inhibition tests2. Enzyme linked immunosorbent assay (EIA)
3. Immunofluorescence techniques (IF)3. Particle agglutination
4. Neutralization tests 4. Western Blot (WB)
5. Counter-immunoelectrophoresis5. RIBA, Line immunoassay

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ELISA for HIV antibody
Microplate ELISA for HIV antibody: coloured wells indicate reactivity

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Western Blot
HIV-1 Western Blot
Lane1: Positive Control
Lane 2: Negative
Control
Sample A: Negative
Sample B:
Indeterminate
Sample C: Positive

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Polymerase Chain Reaction
(1)
PCR allows the in vitro amplification of specific target DNA sequences by
a factor of 10
6
and is thus an extremely sensitive technique.
It is based on an enzymatic reaction involving the use of synthetic
oligonucleotides flanking the target nucleic sequence of interest.
These oligonucleotides act as primers for the thermostable Taq
polymerase. Repeated cycles (usually 25 to 40) of denaturation of the
template DNA (at 94
o
C), annealing of primers to their complementary
sequences (50
o
C), and primer extension (72
o
C) result in the exponential
production of the specific target fragment.
Further sensitivity and specificity may be obtained by the nested PCR.
Detection and identification of the PCR product is usually carried out by
agarose gel electrophoresis, hybridization with a specific oligonucleotide
probe, restriction enzyme analysis, or DNA sequencing.

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Polymerase Chain Reaction
(2)
Advantages of PCR:
Extremely high sensitivity, may detect down to one viral genome per sample
volume
Easy to set up
Fast turnaround time
Disadvantages of PCR
Extremely liable to contamination
High degree of operator skill required
Not easy to set up a quantitative assay.
A positive result may be difficult to interpret, especially with latent viruses such
as CMV, where any seropositive person will have virus present in their blood
irrespective whether they have disease or not.
These problems are being addressed by the arrival of commercial closed systems
such as the Roche Cobas Amplicor which requires minimum handling. The use of
synthetic internal competitive targets in these commercial assays has facilitated the
accurate quantification of results. However, these assays are very expensive.

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Schematic of PCR
Each cycle doubles the copy number of the target

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Some Pathogens that Cross the Placenta