Download INFECTIOUS DISEASES

INFECTIOUS DISEASES
1
BY:
DR (MRS) B.J.THANENTHIRAN (MBBS)
INFECTION
The presence and growth of a microorganism
that produces tissue damage. The extent of the
infection depends on the number and virulence of
the organisms and the ability of the body to
contain or destroy them.
2
Improved living conditions
 Appropriate vaccination
 Effective antibiotics

Then why infectious diseases continue?
3
Because of
 Chronic diseases
 Treatment with immunosuppressive drugs
 AIDS
But in developing countries due to
 Malnutrition
 Unsanitary living conditions
4
CATEGORIES OF INFECTIOUS AGENTS
Prions – modified host proteins
 Viruses – obligate intracellular agents8
 Bacteriophages, plasmids & transposan – mobile
genetic elements
 Bacteria
 Chlamydiae, rickettsiae & mycoplasma
 Fungi
 Protozoa
 Helminths
 Ectoparasites

5
FACTORS INFLUENCING THE
ESTABLISHMENT OF INFECTION
A.
In the host
In addition to a good state of general health
& nutrition the following mechanisms operate in
preventing & limiting infection.
1.
Skin – dense keratinized outer layer
low pH
presence of fatty acids
2.
Urogenital tract – flushed many times/day
long length of urethra in males
3.
Respiratory tract – mucociliary blanket
6
4.
Intestinal tract –
acid gastric juice
viscous mucus layer covering gut
lytic pancreatic enzymes
bile detergent
secreted IgA
commensal flora
7
A.
B.
In the microorganisms – factors potentiating
invasive capacity
1.
2.
Quantity of dose
Virulence
8
EXAMPLES OF FAILURE OF PROTECTIVE
1.
AND DEFENSE MECHANISM
In skin
1.
2.
3.
4.
5.
2.
Direct breach by wounding & burns
Softening of the surface by exposure to water &
sweat
IV cannulation
Needle prick
Bites by arthropods / animals
In respiratory tract
1.
2.
3.
4.
Repeated smoking
Patients with cystic fibrosis
Intubated patients
Aspiration of gastric acid
damage to mucociliary
defense
9
3.
In intestinal tract
1.
2.
3.
Low gastric acidity
Antibiotics that unbalance normal bacterial flora
Mechanical obstruction
4.
Deficiency of the immunological system
5.
Debilitating diseases
10
ROUTES OF ENTRY OF INFECTIOUS AGENTS
1.
Through the skin or mucous membranes
1.
2.
3.
2.
By ingestion
1.
3.
By direct close contact
By contamination of abrasions & wounds
By inoculation
Contaminated food & water
By inhalation
1.
By dust & droplets
11
SPREAD OF MICROBES THROUGHOUT THE
BODY
Microbes spread rapidly along the wet epithelial
surfaces of intestine, lungs, genitourinary tract
Many microbes don’t travel beyond epithelium, but
others spread
Tissue planes of least resistance
Regional lymphatics
Vascular system
12

In blood they spread

Free in plasma

By leucocytes – mycobacterium, HIV, CMV

By RBC – plasmodium
13
RELEASE OF MICROBES FROM THE BODY

Skin shedding

Coughing & sneezing

Urination & defecation

Talking & singing

Spitting

Kissing
14
HOW INFECTIOUS AGENTS CAUSE DISEASE
1.
Infectious agents can contact or enter host cells
& directly cause cell death.
2.
Pathogens can release endotoxins / exotoxins



3.
That kill host cells at a distance
Release enzymes that degrade tissue component
Damage blood vessels & cause ischemic injury
Pathogens can induce host cell responses that
may cause additional tissue damage, usually by
immune mediated mechanisms.
15
IMMUNE EVASION BY MICROBES


Remaining inaccessible
Cleaving
antibody,
resisting
complement
mediated lysis or surviving in phagocytic cells

Varying / shedding antigens

Causing specific/ nonspecific immunosuppression
16
DIAGNOSIS OF INFECTIOUS AGENTS

Staining
Gram stain
 Acid fast stain
 Silver stain
 PAS

Culture
 PCR
 Antibody probes

17
INFLAMMATORY RESPONSE TO INFECTIOUS
AGENTS

Histologic patterns of host reaction induced by
infectious agents are
Suppurative polymorphonuclear inflammation
1.

Mononuclear inflammation
2.

Chronic inflammation, response to viruses, intracellular
bacterias / intracellular parasites
Cytopathic – cytoproliferative inflammation
3.

Viruses
Necrotizing inflammation
4.

5.
Pyogenic bacterias
C.perfringens
Chronic inflammation & scarring
18
NOSOCOMIAL INFECTION / HOSPITAL
INFECTION


Infection acquired in a hospital.
They can be exogenous in origin or endogenous in
origin

Exogenous in origin – source may be another person
in hospital (cross infection) or a contaminated item of
equipment / building service (environmental
infection)

Endogenous in origin – infecting organisms being
derived from the patient’s own skin, GI / upper
respiratory flora (self infection)
19
INANIMATE RESERVOIRS OF INFECTION

Equipment & materials in use in hospital

Organisms in air, dust & on surfaces

Fluids
20
ROLE OF ANTIBIOTIC TREATMENT


Use of antibiotics affect microbial flora in GIT
which leads to antibiotic associated diarrhoea.
Sensitive strains of microorganisms which
normally maintain a protective function on the
skin & other mucosal surfaces tend to be
eliminated whereas those that are resistant
survive.
21
SUSCEPTIBILITY TO NOSOCOMIAL
INFECTION

Low natural resistance – in infants & elderly

Preexisting disease – Eg-DM


Medical / surgical treatment –
immunosuppressive drugs, radiotherapy,
splenectomy
Bypass of body’s natural resistance – injury /
procedures ( indwelling catheter, tracheostomy)
22
MICROORGANISMS CAUSING HOSPITAL
INFECTION
Urinary tract infections
Escherichia coli
Klebsiella
Pseudomonos aeruginosa
Respiratory infections
Haemophilus influenzae
Streptococcus pneumonia
Staphylococcus aureus
Wounds & skin sepsis
Staphylococcus aureus
Streptococcus pyogenes
Escherichia coli
Gastrointestinal infections
Salmonella serotypes
Clostridium difficile
Viruses
23
ROUTES OF TRANSMISSION
Route
Source
Examples of diseases
1. Aerial (from persons)
droplets
skin scales
Mouth
Nose
Skin exudates
Measles, TB, Pneumonia
Staphylococcus sepsis
Stap & strep sepsis
2. Aerial (from inanimate source)
particles
Respiratory equipment
Air conditioning plant
Gram – negative respiatoy
infection
Legionnaires disease
3. Contact (from person)
direct spread
indirect via
equipment
Respiratory secretions
Faeces ,urine, skin &
wound exudates
Stap & strep sepsis
Enterococcal
&
viral
diarrhoea
Pseudomonas
aeruginosa
sepsis
4. Contact (environmental source)
Equipment, food, fluids
Enterobacterial sepsis
Pseudomonas aeruginosa
5. Inoculation
Sharp injury, blood
products
Hepatitis B, HIV, malaria
24
PREVENTION & CONTROL OF NOSOCOMIAL
INFECTION

Infection control policy
Infection control committee
 Infection control team


Sterilization

Aseptic techniques

Cleaning & disinfection
25

Skin disinfection & antiseptics

Prophylactic antibiotics

Protective clothing

Isolation


Source isolation
Protective isolation

Hospital building & design

Personnel – screening of staff & immunization
26
HUMAN IMMUNODEFICIENCY VIRUS


HIV is a lentivirus (a member of the retrovirus
family)
Acquired immunodeficiency syndrome is a
collection of symptoms & infections resulting
from the specific damage to the immune system
caused by HIV.
27
28


Spherical & contains dense, cone – shaped core
surrounded by a lipid envelope derived from the
host cell membrane.
The virus core contains
The major capsid protein p24
 Nucleocapsid protein
 2 copies of genomic RNA
 3 Viral enzymes



Viral core is surrounded by a matrix protein p17
beneath viral envelope
Viral envelope itself is studded by 2 viral
proteins.
29
ROUTE OF INFECTION
1.
Sexual transmission
2.
Parenteral transmission (IV drug abusers,
hemophilics receiving blood concentrate)
3.
Mother to infant transmission (transplacental
spread, during delivery, ingestion of HIV
contaminated breast milk)
30
Attachment of HIV to cells by the interaction of the
external envelope glycoprotein gp120 with part of
the CD4 molecule of T helper cells
Attachment is followed by interaction of the HIV
envelope with a second receptor(CCR5,CXCR4)
Entry of virus with the fusion of the viral envelope
with the cellular membrane
Viral RNA released into cytoplasm
Reverse transcriptase act to form dsDNA
31
DNA copy circularized, enters the nucleus & is
spliced into the host DNA
Viral mRNA production by host RNA polymerase
RNA & protein synthesis
Virion formation
Virions are assembled at the membrane
32
33
34

Numerous organ systems are infected by HIV







Brain: macrophages and glial cells
Lymph nodes and thymus: lymphocytes and dendritic
cells
Blood, semen, vaginal fluids: macrophages
Bone marrow: lymphocytes
Skin: langerhans cells
Colon, duodenum, rectum: chromaffin cells
Lung: alveolar macriphages
35
GENERAL MECHANISMS OF HIV
PATHOGENESIS

Direct injury






Nervous (encephalopathy and peripheral neuropathy)
Kidney (HIVAN = HIV-Associated Nephropathy)
Cardiac (HIV cardiomyopathy)
Endocrine (hypogonadism in both sexes)
GI tract (dysmotility and malabsorption)
Indirect injury

Opportunistic infections and tumors
consequence of immunosuppression
as
a
36
STAGES OF INFECTION
1.
Early acute phase



2.
Short flu like illness
No symptoms
Infected persons can infect others
Middle chronic phase





Last for an average of 10yrs
Free from symptoms
There may be swollen glands
Level of HIV in blood drops to very low levels
HIV antibodies are detectable in the blood
37
3.
Final crisis





Symptoms are mild
Immune system deteriorates
Emergence of opportunistic infections
Immune system weakens
Illness become more severe leading to AIDS
diagnosis
38
39
EXAMPLES OF AIDS INDICATOR DISEASES

Candidiasis

Coccidioidomycosis

Pneumosystis carinii pneumonia

Toxoplasmosis of brain

Kaposi’s sarcoma
40
HIV RISK REDUCTION

Avoid unprotected sex

Use barriers such as condum

Avoid multiple partners


Don’t share needles used by others for drugs,
tattoos, body piercing
In pregnancy – antivirals in late pregnancy &
consider on breast milk
41
Morphological features
Anatomic changes in tissues (with exception of lesions
in brain) are neither specific nor diagnostic.

Changes in lymph nodes
In early stages
 Marked follicular hyperplasia
 Intense plasmacytosis in medulla
 Increased cellularity in sinuses ( macrophages plasma
cells, B cell lymphoblasts)
 HIV particles can be seen in germinal centers
With disease progression
 Follicular involution & generalized lymphocyte depletion ,
organized net work of follicular dendritic cell is disrupted,
follicle becomes hyalinized.
42

Changes in brain
Bain is often atrophic.
 Morphological features are more pronounced within
white matter & basal ganglia.
 Myelin pallor associated with the presence of
macrophages, scanty perivascular mononuclear
inflammatory infiltrates, microglial nodules &
multinucleated giant cells.
 HIV encephalopathy often associated with vacuolar
myelopathy, a condition characteized by vacuolation
& myelin breakdown in dorsal & lateral columns of
the spinal cord.

43
CLOSTRIDIUM INFECTIONS




Gram positive, spore bearing, anaerobic bacilli.
Most are saphrophytes normally occur in soil,
decomposing plants & animal matters.
Clostridium perfringens & Clostridium sporogens are
commensals of animal & human gut.
Pathogenic species of clostidia
Clostridium perfringens
 Clostridium tetani
 Clostridium bolulinum
 Clostridium difficil

44
CLOSTRIDIUM PERFRINGENS

Causing
Gas gangrene
 Food poisoning
 Colitis
 Enteirtis necroticum

45
Gas gangrene


Clostridium perfringens is the commonest cause
of gas gangrene.
Gas gangrene is almost always a polymicrobial
infection involving anaerobes & facultative
organisms.

Main source of infection – animal & human
excreta and spores.

Infection usually derived from contamination of a
wound with soil.

It may derived from dirty clothing, street dust &
air of an OT if ventilating system is poorly
designed.
46

Characters of gas gangrene
Rapidly spreading edema
 Myositis
 Necrosis of tissue
 Gas production & profound toxemia

47
Pathogenesis of gas gangrene

Impairment of normal blood supply of tissue with a
consequent reduction in oxygen tension may allow an
anaerobic focus to develop
Circumstances & events that may lead to gas
gangrene
Tissue damage & contamination with clostridial
spores & pyogenic organisms.
1.
2.
Presence of foreign bodies, including soil with
damaging salts
3.
Inflammatory reaction
48
4.
5.
Extravasation of fluid, oedema
Impaired tissue perfusion; stasis
6.
Impaired phagocytosis & intraleucocytic
bactericidal mechanisms
7.
8.
9.
10.
Poor oxygenation
Multiplication of facultative bacteria
Further reduction in oxygen & pH
Germination & outgrowth of clostridial spores
49
Multiplication of obligate anaerobes with
production of toxins, aggressins (hyaluronidase,
collagenase, alpha toxin) & gas in affected
tissues
11.
12.
Further impairment in local blood supply &
extension of area of tissue damage.
13.
Profound toxemia & shock
50
Food poisoning
Meat is often contaminated with heat resistance
spores.
 Disease is mediated by enterotoxin production.
 Clinical
features – abdominal cramps &
diarrhoea

51
CLOSTRIDIUM TETANI




The germination of spores & their outgrowth depend
on reduced oxygen tension in devitalized tissue & non
viable materials in a wound.
Simultaneous
present.
growth
of
anaerobic
organism
is
Tetanus bacilli remains strictly localized but tetanus
toxin (tetanoplasmin – neurotoxin) is elaborated &
diffuse.
Toxin diffuses to affect the relevant level of spinal
cord (local tetanus) & then to affect the entire system
(generalized tetanus)
52
Toxins attach to gangliosides & the toxin is
internalized
Moved from the peripheral to the central nervous
system by retrograde axonal transport & transsynaptic spread
Once the entire toxin is internalized into
presynaptic cells, they affect the membrane of
synaptic vessicles
Prevent the release of neurotransmitter gama
aminobutric acid
Motor neurones are left under no inhibitory control
& undergo sustained excitatory discharge
53

Sites of infection





Infection in superficial abrasion, thron prick,
contaminated splinter.
Otogenic tetanus
Cryptogenic tetanus
Tetanus neonatorum
Postoperative tetanus
54

Clinical features

IP – 10-14 days but there is a considerable range

Stiffness & pain in or near a recent wound

Stiffness of jaw – lock jaw

Pain & stiffness in neck & back

Stiffness spread to involve all muscle groups

Sympathetic stimulation – sweating, tachycardia,
arrythmias & swings in BP
55
56

Prevention & control
Prompt & adequate wound toilet & proper surgical
debridement of wounds.
 Immunization (active &passive)

57
CLOSTRIDIUM BOTULINUM

Factors make it as a formidable pathogen
Wide spread occurrence in nature
 Ability to produce potent neurotoxin in food
 Resistance of its spores to inactivation

58
Food poisoning





Botulism is a severe often fatal form of food poisoning.
The preformed toxin in the food is absorbed from the
intestinal tract.
Although it is a protein, it is not inactivated by the
intestinal proteolytic enzymes.
After absorption into the blood stream, botulinum
toxin binds irreversibly to the presynaptic nerve
endings of the peripheral nervous system & cranial
nerves.
Inhibits acetylcholine release.
59

Clinical features

IP – 1-2days, but it may be much long.

Nausea & vomiting.

Diplopia & drooping eyelids with squint

Vertigo & blurred vision.

Progressive descending motor loss with flaccid paralysis.

Weakness.

Sleepiness.

Thirsty with dry mouth & tongue.

Difficulty in speech & swallowing.

Difficulty in breathing.
60

Control & prevention
Great care in canning factories.
 Immunization (active & passive)

61
CLOSTRIDIUM DIFFICILE

Commonly occurs in faeces of neonates & babies
until the age of weaning.

Not generally found in adults.

Produce an enterotoxin & cytotoxin.

Causea antibiotic associaded
pseudomembranous colitis.
diarrhoea
&
62
THANK YOU
63