Download 2-Infectious diseases

THE INFECTIOUS
DISEASES
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Infectious disease – disease caused by an infectious
agent such as a bacterium, virus, protozoan, or fungus
that can be passed on to others.
Infection is complex process of interaction between
pathogen and human body
Pathogen – an infectious agent that causes disease.
Host – an organism infected by another organism.
Virulence – the relative ability of an agent to cause
rapid and severe disease in a host.
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Most infectious agents that cause disease are microscopic in
size and thus, are called microbes or microorganisms.
Different groups of agents that cause disease are:
 Prions
 Bacteria
 Viruses
 Protozoa (Protists)
 Fungi
 Helminths (Animals
- Prions:
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Are apparently composed of abnormal forms of
a host protein, termed prion protein (PrP) .
The name derives from proteinaceous infectious
particles.
PrP is normally found in neurons. Diseases
occur when the prion protein undergoes a
conformational change that confers resistance to
proteases.
These agents cause transmissible spongiform
encephalopathies, including:
1-kuru (associated with human cannibalism)
2-Creutzfeldt-Jakob disease (CJD; associated with
corneal transplants).
3- bovine spongiform encephalopathy (BSE; better
known as mad cow disease).
4- variant Creutzfeldt-Jakob disease (vCJD; likely
transmitted to humans from BSE-infected cattle).
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2-Viruses
-Viruses are obligate intracellular parasites that
depend on the host cell's metabolic machinery
for their replication.
-Viruses are classified by their nucleic acid
genome (DNA or RNA but not both) .
Rota virus from the (Reoviridae DS RNA) cause
Childhood diarrhea.
Parvovirus from the (Parvoviridae SS DNA)
cause Erythema infectiosum, aplastic anemia
Bacteriophages, Plasmids,
Transposons
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These are mobile genetic elements that infect
bacteria and can indirectly cause human
diseases by encoding bacterial virulence
factors (e.g., adhesins, toxins, or enzymes that
confer antibiotic resistance).
Exchange of these elements between bacteria
often endows the recipient with a survival
advantage
( antibiotic resistance).
3- Bacteria
Bacterial cells are prokaryotes, meaning that
they have a cell membrane but lack
membrane-bound nuclei and other membraneenclosed organelles .
 Bacteria are classified by:
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1- Gram staining (positive or negative).
2- Shape ( spherical ones are cocci and rod-shaped ones
are bacilli).
3- Form of respiration (aerobic or anaerobic)
4- Chlamydiae, Rickettsiae,
Mycoplasmas
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These microbes are grouped together because, like other bacteria, they
divide by binary fission and are sensitive to antibiotics, but they lack
certain structures e.g.,
Mycoplasma lack a cell wall. M. pneumoniae causes an atypical
pneumonia
Chlamydia cannot synthesize ATP. Chlamydia trachomatis cause female
sterility (by scarring and narrowing of the fallopian tubes) and blindness
(by chronic inflammation of the conjunctiva .
Chlamydia and Rickettsiae are obligate intracellular organisms. Rickettsiae
causes a hemorrhagic vasculitis by injuring endothelial cells, but may also
cause a transient pneumonia or hepatitis (Q fever).
Infectious agents cause disease
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Not all pathogens have the same probability to cause
disease as a result of host variation in the general
population ( age, nutritional status, co-morbid disease,
immune status) .
Location in the body is also important in whether a
pathogens cause diseases. e.g., E. coli in colon are
normal flora but when present in lung causes pneumonia
and in urinary bladder cause cystitis.
Infectious diseases are particularly important
causes of death among:
1- the elderly people.
2-patients with acquired
immunodeficiency syndrome (AIDS).
3- patients with chronic diseases.
4-patients who receive immunosuppressive
drugs.
How microorganisms transmitted?
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Direct/Indirect contact (person to person)
Airborne
 carried in the air
Oral route
 enters body through water, food dirty hands
Insects and Pests
 picked
up on insects and pests and transferred
Classification of Infectious Disease
 By duration
Acute – develops and runs its course quickly.
 Chronic – develops more slowly and is usually less severe, but may
persist for a long, indefinite period of time.
 Latent – characterized by periods of no symptoms between outbreaks
of illness.
By location
 Local – confined to a specific area of the body.
 Systemic – a generalized illness that infects most of the body with
pathogens distributed widely in tissues.
By timing
 Primary – initial infection in a previously healthy person.
 Secondary – infection that occurs in a person weakened by a primary
infection
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Host Barriers to Infection
Skin
The defense properties are :
1-The dense, keratinized outer layer of skin is a
natural barrier to infection .
2-the low pH of the skin (about 5.5) .
3-the presence of fatty acids inhibit growth of
microorganisms other than residents of the
normal flora
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Break down properties in the skin barrier
1-Most M.O penetrate through breaks in the skin,
including :
 superficial pricks (fungal infections).
 wounds (staphylococci).
 burns (Pseudomonas aeruginosa).
2-certain types of fungi (dermatophytes) can infect the
stratum corneum, hair, and nails .
3-few M.O are able to traverse the unbroken skin,ex:
Schistosoma larvae penetrate swimmers' skin by
releasing collagenase, elastase, and other enzymes
that dissolve the extracellular matrix.
4-Needle sticks can expose the recipient to
potentially infected blood and may transmit
HBV, HCV, or HIV.
5- Some pathogens penetrate the skin via an
insect or animal bite ,ex:
- mosquitoes (malaria, leishmaniasis)
-lice break the skin and transmit arboviruses
(causes of yellow fever and encephalitis)
- Dog bite can lead to infections with rabies
virus.
Gastrointestinal Tract
The defense properties are:
1-Acidic gastric secretions .
2-the viscous mucous layer covering the gut .
3-lytic pancreatic enzymes and bile detergents .
4-mucosal antimicrobial peptides called
defensins .
5-normal flora .
6-secreted IgA antibodies
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Break down properties of
gastrointistinal tract
1-Low gastric acidity .
2-Antibiotics that unbalance the normal bacterial
flora(pseudomembranous colitis).
3- mechanical obstruction.
4-Most enveloped viruses are killed by the bile
and digestive enzymes, but nonenveloped
viruses may be resistant
( hepatitis A virus, rotaviruses, reoviruses).
Respiratory Tract
Defense properties:
1-Large microbes are trapped in the mucociliary
that lines the nose and the upper respiratory tract.
2-Microorganisms are trapped in the mucus
secreted by goblet cells and are then transported
by ciliary action to the back of the throat, where
they are swallowed and cleared.
3- Organisms smaller than 5 µm travel directly to
the alveoli, where they are phagocytosed by
alveolar macrophages or by neutrophils recruited
to the lung by cytokines.
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Breakdown properties
1-Damage to the mucociliary defense results from repeated
insults in smokers and patients with cystic fibrosis.
2-influenza viruses possess hemagglutinin proteins bind to
sialic acid on the surface of epithelial cells lead to engulf
the virus then entry and replication within the host cell.
3-influenza viruses possess Neuraminidase that lowers the
viscosity of mucus and facilitates viral transit within the
respiratory tract.
4-Certain respiratory bacterial pathogens can impair ciliary
activity,ex: Haemophilus influenza and Bordetella
pertussis elaborate toxins that paralyze mucosal cilia .
Spread of microorganism
Some microorganisms proliferate locally, at the site of infection, whereas
others penetrate the epithelial barrier and spread to other sites via the
lymphatic, blood, or nerves.
1- Locally proliferate in site of infection e.g.,(cholera can stay superficial
and confined to the lumen of hollow viscera, papillomaviruses,
dermatophytes pathogens can adhere to epithelial cells.
2- Many of pathogens (bacteria, fungi and helminthes) are invasive using
their ability to motile and secrete lytic enzymes (staphylococci secrete
hyaluronidase, which degrades the extracellular matrix between host
cells).
4- Some pathogens may be transported free in blood e.g.,( bacteria
and fungi, some protozoa (African trypanosomes), and all helminthes
are transported free in the plasma.
5- M. tubercolosis foci can disseminate from lung by blood and lymph
system and form secondary foci in other organ . They can be:
A-single and large (a solitary abscess or tuberculoma)
B- multiple and tiny ( miliary tuberculosis).
(A)
Pulmonary TB will create a hole in the lungs.
(B)
Miliary tuberculosis of the spleen
6- Some viruses and protozoa are infect leukocytes and able to
carry by which ex. (herpesviruses, HIV, mycobacteria, Leishmania
and Toxoplasma).
7- Certain viruses (Colorado tick fever virus) and parasites
(Plasmodium) are carried by red blood cells.
8- Viruses also may propagate from cell to cell by fusion or
transport within nerves (rabies virus).
9 - Chickenpox and measles viruses can arise at sites distant from
those of pathogens entry, they enter through the airways but cause
rashes for chickenpox and lesion for measles in the skin.
10- Poliovirus enters through the intestine but kills
motor neurons.
11- Schistosoma mansoni penetrate the skin but localize
in portal and mesenteric blood vessels.
12 - Rubella virus can transported by vertical transmission
by placenta.
13- Infection also can occur during passage through the
birth canal ( gonoccocal and chlamydial infections)
Release of Microbes from the Body
For transmission of disease to occur, exit of a
microorganism from the host's body is as important as
the original entry .
 Release route of microbes can occur by skin
shedding, coughing, sneezing, urination or defecation,
or through insect vectors.
 Some enteric pathogens are shed for long periods by
asymptomatic carrier hosts (Salmonella typhi).
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Transmission from person to person can occur by
respiratory (Influenza, TB ), fecal-oral (Hepatitis A virus)
or sexual routes (HIV).
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Viruses infecting the salivary glands (EBV, CMV,
mumps viruses) are transmitted principally by talking.
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M.O can transmitted from animals to humans by
invertebrate vectors such as insects or directly from
animals to humans (zoonotic infections) e.g., listeriosis
Mechanisms of Host – mediated
Immune injury
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Host immune response to microbes can be sometimes
the cause of tissue injury.
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The best example for injurious effect mediated by the
cell mediated immunity, is the immune response to
mycobacteria.
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The granulomatous inflammatory reaction to TB is a
delayed hypersensitivity response that sequesters the
bacilli and prevents spread, but also can produce tissue
damage and fibrosis.
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Other example :the liver damage following hepatitis B
virus infection of hepatocytes is mainly due to the
immune response to the infected liver cells and not to
cytopathic effects of the virus.
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The humoral immune response to microbes also can have
pathologic consequences. e.g., following infection with βhemolytic streptococci, antibodies produced to the
streptococcal M protein can cross-react with cardiac
proteins and become deposited in the heart, and lead to
rheumatic fever.
IMMUNE EVASION BY
MICROBES
(1) Remaining inaccessible to the host immune system.
- Microbes that propagate in the lumen of the intestine (e.g.,
Clostridium difficile) or gallbladder ( Salmonella typhi) are
concealed from many host immune defenses.
-Some larger parasites ( the larvae
- of tapeworms)
form cysts in host tissues that are
covered by a dense fibrous capsule
and are thus inaccessible to host
immune cells and antibodies.
(2) resisting innate immune defenses (inactivating antibodies or
complement), resist phagocytosis, growing within phagocytes after
ingestion.
Some M.O secrete proteases that degrade antibodies such as
Neisseria, Haemophilus, and Streptococcus. Other M.O escape
from killing by phagocytic cells and complement. e.g., the capsule
of all the major bacteria that cause pneumonia or meningitis
(pneumococcus, meningococcus and Haemophilus influenzae)
makes them more virulent by shielding bacterial antigens and by
preventing phagocytosis of the organisms by neutrophils.
(3) varying or shedding antigens.
 Microbes can evade immune responses either by varying antigens
or by shedding antigens.
- Streptococcus pneumonia exhibit antigenic variation ,their are at
least 80 different serotypes of these microbes, each with different
capsular polysaccharides.
-Cercariae of Schistosoma mansoni shed their antigens within
minutes of penetrating the skin, preventing recognition by host
antibodies.
(4) suppressing the host adaptive immune response, ex: by
inhibiting MHC expression and antigen presentation.
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some microbes use a strategy of reducing the ability of CD4
helper T cells and CD8 cytotoxic T cells to recognize infected
cells.
CMV, EBV inhibit production of MHC class I protein or alter
their intracellular trafficking, impairing peptide to CD8 T cells
and preventing killing of infected cells.
Patterns of inflammatory responses to infection
There are five major histologic patterns of tissue reaction
in infections
1- Suppurative Inflammation.
2- Mononuclear and Granulomatous Inflammation.
3- Cytopathic-Cytoproliferative response.
4- Necrotizing response.
5- Chronic Inflammation and Scarring.
Suppurative inflammation
It is the reaction to acute tissue damage. Characterized
by increased vascular permeability and leukocyte
exudates, predominantly of neutrophils.
 Suppurative inflammation is a response to certain types
of bacteria that are “pyogenic” (pus producing), e.g.,
S. aureus, S. pneumoniae, etc.
 The neutrophils are recruited to the site of infection by
release of chemoattractants from the "pyogenic"
organisms and from host cells.
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Collections of neutrophils may give rise to localized
liquefactive necrosis, forming abscesses.
The necrotic tissue and inflammatory cells constitute
pus.
The sizes of exudative lesions vary from tiny
microabscesses formed in multiple organs during
bacterial sepsis secondary to a colonized heart valve
to diffuse involvement of entire lobes of the lung
during pneumonia.
Suppurative inflammation. polymorphonuclear exudate.
Mononuclear and Granulomatous
Inflammation
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Diffuse mononuclear interstitial infiltrates are a common
feature of all chronic inflammatory processes, but when they
develop acutely, they often are a response to viruses,
intracellular bacteria or intracellular parasites, spirochetes and
helminths provoke chronic inflammatory responses.
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Mononuclear cell predominates within the inflammatory
lesion depends on the host immune response to the organism.
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For example, mostly plasma cells are seen in the primary and
secondary lesions of syphilis, whereas lymphocytes
predominate in HBV infection or viral infections of the brain.
Granulomatous Inflammation
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is a distinctive form of mononuclear inflammation usually
evoked by infectious agents that resist eradication (e.g., M.
tuberculosis, Histoplasma capsulatum, schistosome eggs) and
are capable of stimulating strong T cell-mediated immunity.
Granulomatous inflammation is characterized by
accumulation of activated macrophages called "epithelioid"
cells, which may fuse to form giant cells. In some cases, there
is a central area of caseous necrosis .
Chronic inflammation
Mononuclear inflammation
The morphologic spectrum of tuberculosis. A characteristic tubercle at
low magnification (A) and in detail (B) illustrates central caseation
surrounded by epithelioid and multinucleated giant cells. This is the
usual response seen in patients who have developed cell mediated
immunity to the organism.
Cytopathic- Cytoproliferative response
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It is usually produced by viruses.
The lesions are characterized by cell necrosis or cellular
proliferation, usually with sparse inflammatory cells.
Some viruses replicate within cells and make viral aggregates
that are visible as inclusion bodies (e.g., herpesviruses or
adenovirus).
Other viruses induce cells to fuse and form multinucleated
cells called polykaryons (e.g., measles virus or herpesviruses).
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Focal cell damage in the skin may cause epithelial cells to
become detached, forming blisters.
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Some viruses can cause epithelial cells to proliferate (e.g.,
venereal warts caused by human papillomavirus or the
umbilicated papules of molluscum contagiosum caused by
poxviruses).
viruses can cause dysplastic changes and contribute to the
development of malignant neoplasms (HBV, HCV, EBV, HIV,
HPV).
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Necrotizing response
Clostridium perfringens and other organisms
that secrete powerful toxins can cause
such rapid and severe necrosis that tissue
damage is the dominant feature.
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Entamoeba histolytica causes colonic
ulcers and liver abscesses characterized by
Extensive tissue destruction with liquefactive
necrosis.
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Chronic Inflammation and Scarring
The final common pathway of many
infections is chronic inflammation,
which can lead to extensive scarring.
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For example, chronic HBV
infection may cause cirrhosis of
the liver, in which dense fibrous
septae surround nodules of
regenerating hepatocytes.
Sometimes the exuberant scarring response is the major cause of
dysfunction (ex: the fibrosis of the urinary bladder wall caused
by schistosomal eggs or the constrictive fibrous pericarditis
caused by tuberculosis).
Schistosoma haematobium infection of the bladder with numerous calcified
eggs and extensive scarring
Diagnosis of infectious diseases
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Epidemiological dates
Clinical features
Symptoms and signs
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Laboratory findings
Routine examination of blood, urine, feces
Bio-chemical examinations
Etiological examinations
Direct exam
Isolation of pathogen
Molecular biological examinations
Immunological examinations
Endoscope examinations
Image examinations
Prevention of infectious disease
Management of source of infection
 Cut off of route
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Personal hygiene, public hygiene,
insecticide, disinfection
Protect susceptible population
 Vaccines
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Active immunization
Passive immunization