Infection (MB 315)

The microorganism uses that person’s or animal’s body to sustain itself, reproduce,

and colonize. These infectious microscopic organisms are known as pathogens, and

they can multiply quickly. Examples of pathogens include:

A bacteria

B viruses

C fungi

D protozoa

Therefore, infection involves the interaction between the animal body (host) immune

response and the infecting microorganisms.

A) MICROORGANISMS AND HOST

Based on their relationship of the microbes to their host they can be divided into

saprophytes and parasites.

A. Saprophytes

B. Parasites

A. Saprophytes

Saprophytes (from Greek sapros decayed; and phyton plant) are free-living microbes

that live on dead or decaying organic matter. They are found in soil and water and

play an important role in the degradation of organic materials in nature. They are of

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little relevance in infectious disease because they are generally incapable of

multiplying on living tissues. However, saprophytes like Bacillus subtilis may cause

infection sometimes when host resistance is lowered.

B. Parasites

Parasites are microbes that can establish themselves and multiply in the hosts.

There are many parasitic agents or organisms among the viruses, bacteria, fungi,

plants, and animals. By convention, when the word parasite is used without

quantification, it refers specifically to a protozoan or helminthic (nematode,

trematode, cestode) organisms. Parasite mirobes may be either pathogens or

commensals:

Pathogens

Pathogens (from Greek pathos, disease, and gen, to produce) are the microorganisms

or agents, which are capable of producing disease in the host. Its ability to cause

disease is called pathogenicity.

Types of Pathogens

They are two types: Primary and opportunist pathogens.

a. Primary (frank) pathogens

Primary (frank) pathogens are the organisms, which are capable of producing disease

in previously healthy individuals with intact immunological defences. However, these

bacteria may more readily cause disease in individuals with impaired defences.

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b. Opportunist pathogens

Opportunist pathogens rarely cause disease in individuals with intact immunological

and anatomical defences. These bacteria are able to cause disease only when such

defences are impaired or compromised, as a result of congenital or acquired disease

or by the use of immunosuppressive therapy or surgical techniques. Many

opportunistic pathogens are part of the normal human flora, e.g. coagulase-negative

staphylococci and Escherichia coli.

Commensals

Commensals (organisms of normal flora) are the micro organisms that live in complete

harmony with the host without causing any damage to it. Skin and mucous membranes

are sterile at birth. The normal bacterial flora of the body consist largely of

commensals. Many commensals behave as facultative pathogens in that they can

produce disease when the host resistance is lowered.

B) INFECTION AND INFECTIOUS DISEASE

It is necessary to distinguish between the term ‘infection’ and ‘infectious disease’.

Infection

The lodgement and multiplication of a parasite in or on the tissues of a host

constitute infection. It does not invariably result in disease. In fact, disease is but

a rare consequence of infection, which is a common natural event.

Infectious disease

An infectious disease is any change from a state of health in a part or all of the

host body is not capable of carrying on its normal functions due to the presence of

an organism or its products.

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C) CLASSIFICATION OF INFECTIONS

Infections may be classified in various ways.

1. Primary infection: Initial infection with a parasite in a host is termed primary

infection.

2. Reinfections: Subsequent infections by the same parasite in the host are termed

reinfections.

3. Secondary infection: When a new parasite sets up an infection in a host whose

resistance is lowered by a preexisting infectious disease, this is termed

secondary infection.

4. Local infection: The term Local infection (more appropriately local sepsis)

indicates a condition where, due to infection or sepsis at localized sites such as

appendix or tonsils, generalized effects are produced.

5. Cross infection: When in a patient already suffering from a disease a new

infection is set up from another host or another external source, it is termed

cross infection.

6. Nosocomial infections: Cross infections occurring in hospitals are called

nosocomial infections (from Greek nosocomion hospital).

7. Iatrogenic infection: The term iatrogenic infection refers to physician induced

infections resulting from investigative, therapeutic or other procedures.

Depending on whether the source of infection is from the host’s own body or

from external sources, infections are classified as endogenous or exogenous,

respectively. Based on the clinical effects of infections, they may be classified

into different varieties.

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8. Inapparent infection: Inapparent infection is one where clinical effects are not

apparent.

9. Subclinical infection: The term subclinical infection is often used as a synonym

to inapparent infection.

10. Atypical infection: Atypical infection is one in which the typical or

characteristic clinical manifestations of the particular infectious disease are not

present.

11. Latent infection: Some parasites, following infection, may remain in the tissues

in a latent or hidden form proliferating and producing clinical disease when the

host resistance is lowered. This is termed latent infection.

D) SOURCES OF INFECTION

A. Human beings

B. Animals

C. Insects

D. Soil and water

E. Food

A. Human Beings

The commonest source of infection for human beings is human beings themselves.

The parasite may originate from a patient or carrier. Humans play a substantial role

as microbial reservoirs.

Humans serving as the microbial reservoir

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 i. Indeed, the passage of a neonate from the sterile environment of the mother’s

womb through the birth canal, which is heavily colonized with various microbial

agents, is a primary example of one human directly acquiring microorganisms from

another human serving as the reservoir.

ii. Acquisition of “strep” throat through touching.

iii. Hepatitis by blood transfusions.

iv. Gonorrhea, syphilis, and (AIDS) acquired immune deficiency syndrome by

sexual contact.

v. Tuberculosis by coughing; and the common cold through sneezing.

Carrier

A carrier is person who harbors the microorganisms without suffering from any ill

effect, because of it. There are several types of carriers.

1. Convalescent carrier: A convalescent carrier is an individual who has

recovered from the infectious disease but continues to harbor large numbers of

the pathogen.

2. Healthy carrier: A healthy carrier is an individual who harbors the pathogen

but is not ill.

3. Incubatory carrier: An incubatory carrier is an individual who is incubating

the pathogen in large numbers but is not yet ill.

4. Temporary carriers: Convalescent, healthy, and incubatory carriers may

harbor the pathogen for only a brief period (hours, days, or weeks) and lasts less

than six months and then called casual, acute, transient or temporary carriers.

Chronic carriers: They harbor the pathogen for long periods (months, years, or

life).

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 6. Contact carriers: The term contact carrier is applied to a person who

acquires the pathogen from a patient.

7. Paradoxical carrier: Paradoxical carrier refers to a carrier who acquires

the pathogens from another carrier.

Carriers may be classified according to portal of exit of the infectious agent such

as urinary carriers, intestinal carriers, respiratory carriers, nasal carriers, etc.

B. Animals

Reservoir Hosts

Many pathogens are capable of causing infections in both human beings and animals.

Therefore, animals may act as a source of infection of such organisms. These,

animals serve to maintain the parasite in nature and act as reservoir and they are,

therefore, called reservoir hosts.

Zoonosis

The diseases and infections, which are transmissible to man from animals are called

zoonosis. Humans contact the pathogens by several mechanisms.

Examples of zoonotic diseases:

Bacterial

Anthrax, brucellosis, Q fever, leptospirosis, bovine tuberculosis, bubonic plague,

Salmonella food poisoning.

Viral

Rabies, yellow fever, cowpox, monkeypox

Protozoal

Leishmaniasis, toxoplasmosis, trypanosomiasis, babesiosis.

Helminthic

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Echinococcosis, teniasis, trichinellosis

Fungal

Microsporum canis, Trichophyton verrucosum.

C. Insects

Arthropodborne Diseases

Blood-sucking insects such as mosquitoes, ticks, mites, flies, and lice may transmit

pathogens to human beings and diseases so caused are called arthropodborne

diseases.

Vectors

Insects that transmit infections are called vectors. Vector-borne transmission can

be of two types either mechanical (external) or biological (internal).

i. Mechanical vector: The disease agent is transmitted mechanically by the

arthropod. Carriage is passive, with no growth of the pathogen during trans-

mission.

Examples: Transmission of diarrhea, dysentery, typhoid, food poisoning and

trachoma by the housefly.

ii. Biological vectors: Biological vectors are those in whom the pathogens multiply

or undergo developmental changes with or without multiplication. Biological

vectors transmit infection only after the pathogen has multiplied in them

sufficiently or has undergone a developmental cycle. The interval between the

time of entry of the pathogen into the vector and the vector becoming infective

is called the extrinsic incubation period.

Examples: Aedes aegypti mosquito in yellow fever, Anopheles mosquito in malaria.

Reservoir Hosts

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Besides acting as vectors, some insects may also act as reservoir hosts (for example,

ticks in relapsing fever and spotted fever). Infection is maintained in such insects

by transovarial or transstadial passage.

D. Soil and Water

i. Soil

Some pathogens can survive in the soil for long periods.

Examples

a. Spores of tetanus and gas gangrene: Spores of tetanus and gas gangrene

remain viable in the soil for several decades and serve as source of infection.

The human and animal intestine is the normal habitat of these organisms and they

enter the soil through their feces.

b. Fungi and parasites: Fungi (causing mycetoma, sporotrichosis, histoplasmosis)

and parasites such as roundworms and hookworms also survive in the soil and

cause human infection.

ii. Water

Water may act as the source of infection either due to contamination with

pathogenic microorganisms (Shigella, Salmonella, Vibrio cholerae, poliomyelitis virus,

hepatitis virus) or due the presence of aquatic vector (cyclops containing larvae of

guinea worm infection).

E. Food

Contaminated food may act as source of infection of organisms causing food

poisoning, gastroenteritis, diarrhea and dysentery. There are two primary types of

food-related diseases: foodborne infections and food intoxicants.

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E) MODES OF TRANSMISSION OF INFECTION

The human host may acquire microbial agents by various means referred to as the

modes of transmission. Pathogenic organisms can spread from one host to another

by a variety of mechanisms. These include:

1. Contact

2. lnhalation

3. Ingestion

4. Inoculation

5. Insects

6. Congenital

7. Iatrogenic and laboratory infections

1. Contact

Infection may be acquired by contact, which may be direct or indirect.

a. Direct contact

Direct contact implies an actual physical interaction with the infectious source.

Diseases transmitted by direct contact include STD (sexually transmitted diseases

such as syphilis, gonorrea, lymphogranuloma venereum, lymphogranuloma inguinale,

trichomoniasis, herpes simplex type 2 hepatitis B and acquired immuno deficiency

syndrome (AIDS), leprosy, leptospirosis, skin and eye infections.

The term contagious disease had been used for diseases transmitted by direct

contact and infectious disease signifying all other modes of transmission.

b. Indirect contact—fomites

Indirect contact may be through the agency of fomites, which are inanimate objects

such as clothing, pencils or toys which may be contaminated by a pathogen from one

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person and act as a vehicle for its transmission to another. Pencils shared by school

children may act as fomites in the transmission of diphtheria, and face towels in

trachoma.

Common examples of intermediary inanimate objects include thermometers, eating

utensils, drinking cups, and bedding. This embraces a variety of mechanisms including

the traditional 5 F’s - “flies, fingers, fomites, food and fluid”.

2. Inhalation

Droplet nuclei

Respiratory infections such as common cold, influenza, measles, mumps, tuberculosis

and whooping cough are acquired by inhalation. Such microbes are shed by the

patients into the environment, in secretions from the nose or throat during sneezing,

speaking , coughing and other forceful expiratory activities. Large droplets more

than 0.1 mm in diameter fly forwards and downwards from the mouth to the distance

of a few feet and they reach the floor within a few seconds or they may fall on the

eyes, face, mouth and clothes of the person standing in front of the producer of the

spray. Small droplets, under 0.1 mm in diameter, evaporate immediately to become

minute particles or droplet nuclei (usually 1-10 mm in diameter) which remain

suspended in the air for long periods, acting as sources of infection. Particles of 10

μm or greater in diameter are filtered off by nose. Particles in the 1-5 μm range are

liable to be easily drawn into the alveoli of the lungs and may be retained there.

Diseases spread by droplet nuclei: These include tuberculosis, influenza, chickenpox,

measles, Q fever and many respiratory infections.

Dust

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Some of the larger droplets which are expelled during talking, coughing or sneezing,

settle down by their sheer weight on the floor, carpets, furniture, clothes, bedding,

linen and other objects in the immediate environment and become part of the dust.

The diseases carried by infected dust: Include streptococcal and staphylococcal

infection, pneumonia, tuberculosis, Q fever and psittacosis. Airborne dust is

primarily inhaled, but may settle on uncovered food and milk. This type of

transmission is most common in hospital-acquired (nosocomial) infection.

3. Ingestion

Intestinal infections are generally acquired by the ingestion of food or drink

contaminated by pathogens. Infection transmitted by ingestion may be waterborne

(cholera), foodborne (food poisoning) or handborne (dysentery). Diseases

transmitted by water and food include chiefly infections of the alimentary tract,

e.g. acute diarrheas, typhoid fever, cholera, polio, hepatitis A, food poisoning and

intestinal parasites.

4. Inoculation

The disease agent may be inoculated directly into the skin or mucosa, e.g. rabies

virus deposited subcutaneously by dog bite, tetanus spores implanted in deep wounds,

and arboviruses injected by insect vectors.

Infection by inoculation may be iatrogenic when unsterile syringes and surgical

equipment are employed. Hepatitis B and the human immunodeficiency virus (HIV)

may be transmitted through transfusion of infected blood, or the use of

contaminated syringes and needles, particularly among addicts of injectable drugs.

5. Insects

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Vectorborne

In infectious disease epidemiology, vector is defined as an arthropod or any living

carrier (e.g. snail) that transports an infectious agent to a susceptible individual. In

some diseases, blood-sucking insects play an important role in the spread of infection

from one individual to another. Table 1 shows common arthropods and diseases

transmitted by them. Transmission by a vector may be mechanical or biological.

6. Congenital

Vertical Transmission

Some pathogens are able to cross the placental barrier and reach the fetus in utero.

This is known as vertical transmission. This is another form of direct transmission.

Vertical transmission may result in abortion, miscarriage or stillbirth. Live infants

may be born with manifestations of a disease, as in congenital syphilis. Intrauterine

infection with the rubella virus, especially in the first trimester of pregnancy, may

interfere with oncogenesis and lead to congenital malformation. Such infections are

known as teratogenic infections.

Examples: So-called TORCH agents (Toxoplasma gondii, rubella virus,

cytomegalovirus and herpes virus), varicella virus, syphilis, hepatitis B, coxsackie B

and AIDS.

7. Iatrogenic and Laboratory Infections

If meticulous care in asepsis is not taken, infections like AIDS and hepatitis B may

sometimes be transmitted during administration of injections, lumber puncture and

catheterization. Modern methods of treatment

Diseases Transmitted

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1. Mosquito Malaria, filaria, viral encephalitis (e.g.

Japanese encephalitis), viral fevers (e.g.

dengue, West Nile, viral hemorrhagic

fevers (e.g. yellow fever, dengue

hemorrhagic fever)

2. Housefly Typhoid and paratyphoid fever, diarrhea,

dysentery, cholera, gastroenteritis,

amebiasis, helminthic infestations,

poliomyelitis, conjunctivitis, trachoma,

anthrax, yaws, etc.

3. Sand fly Kala-azar, oriental sore, sand fly fever,

oraya fever

4. Tsetse fly Sleeping sickness

5. Louse Epidemic typhus, relapsing fever, trench

fever, pediculosis

6. Rat flea Bubonic plague, endemic typhus,

chiggerosis, Hymenolepis diminuta

7. Blackfly Onchocerciasis

8. Reduviid bug Chagas disease

9. Hard tick Tick typhus, viral encephalitis, viral fevers,

viral hemorrhagic fever, (e.g. Kyasanur

forest disease), tularemia, tick paralysis,

human babesiosis

10. Soft tick Q fever, relapsing fever

11. Trombiculid mite Scrub typhus, Rickettsialpox

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 12. Itch-mite Scabies

13. Cyclops Guinea worm disease, fish tapeworm (D.

latum)

14. Cockroaches Enteric pathogens

such as exchange transfusion, dialysis, and heart and transplant surgery have

increased the possibilities for iatrogenic infections. These are known as iatrogenic

or physician-induced infections. Laboratory personnel handling infectious material

and doing mouth-pipetting are particularly at risk.

F) FACTORS PREDISPOSING TO MICROBIAL PATHOGENICITY

Pathogenicity and Virulence

Pathogenicity

Denotes the ability of a microbial species to cause disease. The term virulence (Latin

virulentia, from virus, poison) denotes the ability of a strain of a species to produce

disease.

Virulence

Virulence provides a quantitative measure of pathogenicity, or the likelihood of

causing disease. For example, encapsulated pneumococci are more virulent than

nonencapsulated pneumococci, and Escherichia coli that express Shiga-like toxins

are more virulent than those that do not express these toxins. The virulence of a

strain is not constant and may undergo spontaneous or induced variation.

Exaltation

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Enhancement of virulence is known as exaltation. This can be induced by serial

passage of a strain in an experimental animal.

Attenuation

Reduction of virulence is known as attenuation and can be induced by passage through

unfavorable hosts, repeated culture in artificial media, growth under high

temperature or in the presence of weak antiseptics, desiccation, or prolonged

storage in culture.

Virulence Factors

Virulence factors refer to the properties (i.e. gene products) that enable a

microorganism to establish itself on or within a host of a particular species and

enhance its potential to cause disease. Virulence is determined by three

characteristics of the pathogens: invasiveness, infectivity, and pathogenic potential.

A major aspect of pathogenic potential is toxigenicity.

Determinants of Virulence

1. Transmissibility

2. Adhesion

3. Invasiveness

4. Toxigenicity

5. Avoidance of host defence mechanisms

6. Enzymes

7. Plasmids

8. Bacteriophages

9. Communicability

10. Infecting dose

11. Route of infection

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1. Transmissibility

The first step of the infectious process is the entry of the microorganism into the

host by one of several ports: the respiratory tract, gastrointestinal tract, urogenital

tract, or through skin that has been cut, punctured, or burned. Once entry is

achieved, the pathogen must overcome a diversity of host defenses before it can

establish itself. These include phagocytosis, the acidic environments of the stomach

and urogenital tract, and various hydrolytic and proteolytic enzymes found in saliva,

in stomach, and in the small intestine.

2. Adhesion

Adhesins

The initial event in the pathogenesis is the attachment of the bacteria to body

surfaces. This attachment is not a chance event but a specific reaction between

surface receptors on host cells and adhesive structures (ligands) on the surface of

bacteria. These adhesive structures are called adhesins.

Adhesions may occur as organized structures, such as fimbriae or fibrillae and pili,

or as colonization factors. Nonspecific surface properties of the bacterium,

including surface charge and hydrophobicity, also contribute to the initial stages

of the adhesion process.

Some bacteria (for example, Escherichia coli) use their pili to adhere to the surface

of host cells. Group A streptococci have similar structures (fimbriae). A striking

example of the importance of adhesion is that of Neisseria gonorrhoeae in which

strains that lack pili are not pathogenic. If bacterium is invasive in nature, adherence

helps in penetrating host cells.

Adhesins as Virulence Factors

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Adhesins serve as virulence factors, and loss of adhesins often renders the strain

avirulent. Adhesins are usually made of protein and are antigenic in nature. Specific

immunization with adhesins has been attempted as a method of prophylaxis in some

infections, as for instance against E. coli diarrhea in calves and piglets, and gonorrhea

in human beings.

3. Invasiveness

Invasiveness signifies the ability of a pathogen to spread in the host tissues after

establishing infection. For many disease-producing bacteria, invasion of the host’s

epithelium is central to the infectious process. Highly invasive pathogens

characteristically produce spreading or generalized lesions (e.g. streptococcal

septicemia following wound infection), while less invasive pathogens cause more

localized lesions (e.g. staphylococcal abscess). Some pathogens though capable of

causing serious or even fatal diseases lack invasiveness (e.g. the tetanus bacillus

which remains confined to the site of entry and produces the disease by elaborating

a potent toxin).

4. Toxigenicity

Some bacteria cause disease by producing toxins, of which there are two general

types: the exotoxins and the endotoxins. Both gram-positive and gram-negative

bacteria secrete the exotoxins, which are proteins. In contrast, the endotoxins,

which are lipopolysaccharides, are not secreted, but instead are integral components

of the cell walls of gram-negative bacteria (Table .2).

Exotoxins

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Exotoxins are soluble, heat-labile proteins inactivated at 60 to 80°C which are

secreted by certain species of bacteria and diffuse readily into the surrounding

medium.

These are highly potent in minute amounts and include some of the most poisonous

substances known. It is estimated that as little as one microgram of tetanus

exotoxin can kill an adult human, One mg of tetanus or botulinum toxin is sufficient

to kill more than one million guinea pigs and 3 kg of botulinum toxin can kill all the

inhabitants of the world.

Treatment with dilute formaldehyde destroys the toxic activity of most exotoxins,

but does not affect their antigenicity. Formaldehyde—inactivated toxins, called

toxoids, are thus useful in preparing vaccines.

Exotoxin proteins are in many cases encoded by genes carried on plasmids or

temperate bacteriophage.

They exhibit specific tissue affinity and pharmacological activities, each toxin

producing a typical effect which can be made out by characteristic clinical mani-

festations or autopsy appearances.

They are associated with specific diseases and have specific mechanisms of action.

They are easily inactivated by formaldehyde, iodine, and other chemicals to form

immunogenic toxoids.

They are unable to produce a fever in the host directly and often given the name of

the disease they produce (e.g. the diphtheria toxin).

Exotoxins are generally formed by gram-positive bacteria but may also be produced

by some gram-negative organisms such as Shiga’s dysentery bacillus, cholera vibrio

and enterotoxigenic E. coli.

Endotoxins

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 These are heat-stable, lipopolysaccharide (LPS) components of the outer membranes

of gram-negative bacteria but not gram-positive bacteria. Their toxicity depends

upon the the component (lipid A).

They are released into the host’s circulation following bacterial cell lysis.

They are toxic only at high doses (milligram per kilogram amounts).

They cannot be toxoided.

They are poor antigens and weakly immunogenic and their toxicity is not completely

neutralized by the homologous antibodies.

They do not exhibit specific pharmacological activities. They are generally similar,

despite source.

All endotoxins, produce similar effects whether isolated from pathogenic or

nonpathogenic bacteria.

Administration of small quantities of endotoxin in susceptible animals causes an

elevation of body temperature manifested within 15 minutes and lasting for several

hours. The pyrogenic effect of fluids used for intravenous administration is usually

due to the presence of endotoxins from contaminant bacteria. They are usually

capable of producing general systematic effects. Intravenous injections of large

doses of endotoxin and massive gram-negative septicemias cause endotoxic shock

marked by fever, leukopenia, thrombocytopenia, significant fall in blood pressure,

circulatory collapse and bloody diarrhea leading to death (Table 2).

Table 2: Differences between exotoxins and endotoxins

Exotoxins Endotoxins

1. Proteins 1. Lipopolysaccharide on outer membrane.

Lipid A portion is toxic

2. Heat-labile (inactivated at 60º-80ºC) 2. Heat-stable

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3. Actively secreted by the cells; diffuse into3. Form integral part of the cell wall; do not

the surrounding medium diffuse into surrounding medium

4. Readily separable from cultures by physical4. Obtained only by cell lysis

means such as filtration

5. Action often enzymic 5. No enzymic action

6. Specific pharmacological effect for each6. Nonspecific action of all endotoxins

exotoxin

7. Specific tissue affinities 7. No Specific tissue affinities

8. Highly toxic and fatal in microgram8. Moderate toxicity. Active only in very large

quantities doses

9. Highly antigenic 9. Weakly antigenic

10. Action specifically neutralized by antibody10. Neutralization by antibody ineffective

11. Usually do not produce fever 11. Usually produce fever by release of

interlukin-1

12. Produced by both gram-positive bacteria

and gram-negative bacteria

13. Frequently controlled by extrachromosomal

genes (e.g. plasmids)

14. Disease, e.g. Botulism, diphtheria, tetanus14. Gram-negative infections, meningococcemia

5. Avoidance of Host Defence Mechanisms

Bacteria also have evolved many mechanisms to evade host defenses. Several of

these evasive mechanisms are now discussed.

a. Capsules

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Some bacteria such as Streptococcus pneumoniae, Neisseria meningitidis, and

Haemophilus influenzae can produce a slippery mucoid capsule that prevents the

phagocyte from effectively contacting the bacterium, and noncapsulate variants

usually exhibit much reduced virulence.

b. Streptococcal M protein

Other bacteria evade phagocytosis by producing specialized surface proteins such

as the M protein on Streptococcus pyogenes.

c. Resistance to killing by phagocytic cells

Some bacteria have evolved the ability to survive inside neutrophils, monocytes, and

macrophages. These pathogens not only survive within macrophages and other

phagocytes, but may actually multiply intracellulary.

Different organisms use different strategies for survival:

i. To escape from the phagosome before it merges with the lysosome, as seen with

Listeria monocytogenes, Shigella, and Rickettsia.

ii. To prevent phagolysosome fusion, e.g. in Mycobacterium tuberculosis, probably at

least partly because of its waxy external layer.

iii. Production of catalase by Staph. aureus and N. gonorrhoeae is thought to protect

these organisms from such toxic products.

d. Antigenic variation

Variation in surface antigen composition during the course of infection provides a

mechanism of avoidance of specific immune responses directed at those antigens.

Examples

i. Pathogenic Neisseria.

ii. The borrelia generate antigenic variation.

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 iii. Other bacteria show strain-specific antigenic variability such as group A

streptococci 75 antigenically distinct serotypes of M proteins.

e. Serum resistance

To survive in the blood, bacteria must be able to resist lysis as a result of deposition

of complement on the bacterial surface. Some gram-negative bacteria can lengthen

the 0 chains in their lipopolysaccharide to prevent complement activation.

f. Siderophore and iron acquisition

Many bacteria produce these low molecular weight compounds called siderophores

that can acquire iron from the host’s iron binding proteins. This property enhances

the virulence.

6. Enzymes

Many species of bacteria produce tissue-degrading enzymes that play important

roles in the infection process.

i. Coagulase: Coagulase is produced by S. aureus. This thrombin-like enzyme

prevents phagocytosis by forming a fibrin barrier around the bacteria and walling

off the lesion.

ii. Lecithinase-C and collagenase: C. perfringens produces lecithinase-C and

collagenase. Lecithinase

C damages cell membranes by splitting lecithin to phosphorylcholine and diglyceride

while collagenase degrades collagen, the major protein of fibrous connective

tissue thus promoting spread of infection in tissue.

iii. Hyaluronidases: Hyaluronidases split hyaluronic acid which is a component of

intercellular connective tissue and thus facilitate the spread of infection along

tissue spaces.

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iv. Streptokinase (fibrinolysin): Many hemolytic streptococci produce streptokinase

(fibrinolysin). Fibrinolysins promote the spread of infections by breaking down

the fibrin barrier in tissues.

v. Cytolysins: These include, hemolysins capable of destroying erythrocytes and

leukocidins damage polymorphonuclear leukocytes.

a. Streptolysin O and streptolysin S are produced by group A streptococci.

b. Most strains of Staphylococcus aureus produce hemolysins.

c. Escherichia coli strains that cause urinary tract infections produce hemolysins

whereas those strains that are part of normal gastrointestinal flora may or

may not produce hemolysins.

vi. IgA 1 proteases: These enzymes specifically cleave immunoglobulin IgA which

protects at mucosal surfaces. It is an important virulence factor of N.

gonorrhoeae, N. meningitidis, H. influenzae, S. pneumoniae, some strains of

Prevotella melaninogenica and some streptococci associated with dental caries.

7. Plasmids

Plasmids are extrachromosomal DNA segments that carry genes for antibiotic

resistance known as R-factors. Multiple drug resistance (R) plasmids increase the

severity of clinical disease by their resistance to antibiotic therapy.

Genes coding for some virulence characteristics may be plasmidborne. Surface

antigens responsible for the colonization of intestinal mucosa by E. coli and entero-

toxin production by E. coli and Staph. aureus are examples of plasmidborne virulence

factors.

8. Bacteriophages

The classical example of phage directed virulence is seen in diphtheria. All the

strains of C. diphtheriae produce exotoxin only when they are lysogenized with a

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bacteriophage called betaphage. In diphtheria bacilli, the gene for toxin production

is present in beta or other tox+ corynephages. The elimination of this phage abol-

ishes the toxigenicity of the bacillus.

9. Communicability

The ability of a microbe to spread from one host to another is known as

communicability. This property determines the survival and distribution of a parasite

in a community but does not influence the production of disease in an individual host.

A correlation need not exist between virulence and communicability. In fact, a high

degree of communicability may not be exhibited by a highly virulent parasite due to

its rapidly lethal effect on the host.

In general, infections in which the pathogen is shed in secretions, as in respiratory

or intestinal-diseases, are highly communicable. In some instances, infection

represents a dead end, as in hydrophobia, there being an interruption in the spread

of the pathogen to other hosts.

Occurrence of epidemic and pandemic diseases requires that the pathogen should

possess high degree of virulence and communicability.

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10. Infecting Dose

Adequate number of bacteria is required for successful infections. The dosage may

be estimated as the minimum infecting dose (MID) or minimum lethal dose (MLD).

Minimum Infecting Dose (MID)

Minimum number of bacteria required to produce clinical evidence of infection in a

susceptible animal under standard conditions is called minimum infective dose (MID).

Minimum Lethal Dose (MLD)

MLD is a minimum number of bacteria that produce death in the animal under

standard conditions.

As animals exhibit considerable individual variation in susceptibility, these doses are

more correctly estimated as statistical expressions, ID50 and LD50 as the dose

required to infect or kill 50 percent of the animals tested under standard conditions.

11. Route of Infection

Some bacteria can initiate infection whatever be the mode of entry such as

streptococci. Certain bacteria are infective when introduced through optimal route,

for example, cholera vibrios can produce lesion only when administered by oral route,

but unable to cause infection when introduced subcutaneously. However,

Staphylococcus aureus can cause lesion whatever may be the portal of entry.

Probably this difference is related to modes by which different bacteria are able to

initiate tissue damage and establish themselves.

Bacteria after introduction into tissues also differ in their sites of election in the

host body. They also differ in the ability to produce damage of different organs in

different species of animals. Lesions are caused mainly in the kidney and infrequently

in the liver and spleen when tubercle bacilli injected into rabbits but in guinea pigs

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the lesions are mainly in the liver and spleen, the kidneys being spared. The reasons

are largely obscure for such selective multiplication in tissues, though they may be

related to the presence in tissues of substances that may selectively hinder or favor

their multiplication.

G) TYPES OF INFECTIOUS DISEASES

Infectious diseases may be localized or generalized.

A. Localized

Localized infections may be superficial or deep-seated.

B. Generalized

Generalized infection involves the spread of the infecting agent from the site of

entry by contiguity, through tissue spaces or channels, along the lymphatics or

through the bloodstream (bacteremia) which leads to dissemination of organisms.

1. Bacteremia

Circulation of bacteria in the blood is known as bacteremia. Transient bacteremia is

a frequent event even in healthy individuals and may occur during chewing, brushing

of teeth or straining at stools. The bacteria are immediately mopped up by

phagocytic cells and are unable to initiate infection. Bacteremia of greater severity

and longer duration is seen during generalized infections as in typhoid fever.

2. Septicemia

It is the condition where bacteria circulate and multiply in the blood, form toxic

products and cause high, swinging type of fever.

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3. Pyemia

It is condition where pyogenic bacteria produce septicemia with multiple abscesses

in internal organs such as the spleen, liver and kidney.

H) EPIDEMIOLOGICAL TERMINOLOGY

Depending on the spread of infectious diseases in community, they may be classified

as endemic, epidemic, and pandemic.

1. Endemic

The disease which is constantly present in a particular area, e.g. typhoid fever is

endemic in some parts of Zambia.

2. Epidemic

The disease that spreads rapidly, involving many persons in a particular area at the

same time, is called epidemic disease, e.g. meningococcal meningitis. In the cold

countries influenza causes annual winter epidemics.

3. Pandemic

It is an epidemic that spreads through many areas of the world involving very large

number of persons within a short period, e.g. cholera, influenza and enteroviral con-

junctivitis.

Epidemics vary in the rapidity of spread. Waterborne diseases such as cholera and

hepatitis may cause explosive outbreaks, while diseases which spread by person-to-

person contact evolve more slowly. Such creeping or smouldering epidemics, as that

of cerebrospinal fever, are termed prosodemic diseases.

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KNOW MORE

Infection

Humans and microorganisms inhabit the same planet, and their paths cross in many

and varied ways so that interactions are inevitable.

Serum Resistance

In the enterobacteriaceae, resistance is primarily due to the composition of the

lipopolysaccharide (LPS) present in the bacterial outer membrane. Others such as

Neisseria gonorrhoeae generate serum resistance.

) KEY POINTS

• Infection and immunity involve interaction between the animal body (host) and

the infecting microorganisms.

• Parasites are microbes that can establish themselves and multiply in the hosts.

Parasite mirobes may be either pathogens or commensals:

Infection

Infections may be classified in various ways:

Sources of Infection: 1. Human beings—from a patient or carrier; 2. Animals; 3.

Insects; 4. Soil and water; 5. Water. 6. Food

Modes of Transmission of Infection

1. Contact; 2. Inhalation; 3. Ingestion; 4. Inoculation; 5. Insects; 6. Congenital; 7.

Iatrogenic and laboratory infections.

Determinants of Virulence

1. Transmissibility; 2. Adhesion; 3. Invasiveness; 4. Toxigenicity; 5. Enzymes; 6.

Plasmids; 7. Bacteriophages; 8. Communicability; 9. Infecting dose; 10. Route of

infection.
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Types of Infectious Diseases

A. Localized infections may be superficial or deepseated.

B. Generalized infection

1. Bacteremia; 2. Septicemia; 3. Pyemia

FURTHER READING

Mims CA. The Pathogenesis of Infectious Disease, 3rd edn. London: Academic Press

1987.

Poxton IR, Arbuthnot JP. Determinants of bacterial virulence, Chap. 13 In: Topley

and Wilson’s Principles of Bacteriology Virology and Immunity, 8th edn. Vol. 1.

London: Edward Arnold 1990.

Relman DA, Falkow S: A molecular perspective of microbial pathogenicity. In:

Mandell, Donglas and practice of intertious diseases, 5th ed. Mandell GL, Bennett

JE, Dolan R (Editos) Churchill Livingstone 2000.

Salyers AA, Whitt DD. Bacterial Pathogenesis: A Molecular Approach. American

Society for Microbiology Press, 1994.

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