• Chapter 4

• Infection and Host Resistance

• Definition of Terms

• 1. Infection - the replication of organisms in the tissue

• 2. Carrier (colonized individual) - a person in whom organisms are

present and may be multiplying, but who shows no clinical response to
their presence.

• 3. Incubation period - the interval in the preclinical period between the

time at which the causative agent first infects the host and the onset of
clinical symptoms. During this time the agent is replicating.

• 4. Convalescent period - when the patient recovers and returns to normal

but may still continue to be a source of infection even if feeling better.
• Chain of Infection

• The chain of infection includes the three factors that lead to infection: the
etiologic agent, the method of transmission, and the host (Remington &
Klein, 1993).

• Mechanism of Bacterial Infectious Disease Processes

• We are constantly exposed to bacteria (including air, water, soil and food).
Normally due to our host defenses most of these bacteria are harmless.

• In compromised patients, whose defenses are weakened, these bacteria

often cause opportunistic infectious diseases when entering the
bloodstream (after surgery, catheterization or other treatment modalities).
• Transmission and Adhesion

• In transmission, specific bacterial species (or strains within a species) initiate

infection after being transmitted by different routes to specific sites in the human
body.

• Bacterial infections are usually initiated by adherence of the microbe to a specific

epithelial surface of the host. If not, the organism is removed by peristalsis and
defecation, ciliary action, coughing and sneezing, or urination.

• Penetration and Spread

• Some bacterial pathogens reside on Epithelial surfaces. Other species are able
to penetrate these barriers but remain locally. Others pass into the bloodstream
or from there onto other systemic sites. This often occurs in the intestine, urinary
tract and respiratory tract and much less through the skin.
• Mechanism of Viral Infectious Disease Processes

• Initiation of Infection

• To infect a cell, the virus must attach to the cell surface, penetrate into the cell, and
become sufficiently uncoated to make its genome accessible to viral or host machinery
for transcription or translation.

• Viral Pathogenesis

• Pathogenesis is the process by which an infection leads to disease. Pathogenic

mechanisms of viral disease include the following (Remington & Klein, 1993):

• 1. Implantation of virus at the portal of entry - virions implant onto living cells mainly via
the respiratory, gastrointestinal, skin-penetrating, and genital routes although other
routes can be used.
• Viral Pathogenesis

• Pathogenesis is the process by which an infection leads to disease.

Pathogenic mechanisms of viral disease include the following
(Remington & Klein, 1993):

• 1. Implantation of virus at the portal of entry - virions implant onto living

cells mainly via the respiratory, gastrointestinal, skin-penetrating, and
genital routes although other routes can be used.
• 2. Local replication - most virus types spread among cells
extracellularly, but some may also spread intracellularly.

• 3. Spread to target organs (disease sites) - viral spread can be

facilitated in one of two ways:

• a. Viremic the most common route of systemic spread from the portal of
entry through the circulation, which the virus reaches via the
lymphatics.

• b. Neural dissemination via nerves usually occurs with rabies virus and
sometimes with herpesvirus and poliovirus infections.
• 4. Spread to sites of shedding of virus into the environment - although the
respiratory tract, alimentary tract, urogenital tract and blood are the most frequent
sites of shedding, diverse viruses may be shed at virtually every site.

• Mechanism of Fungal Infectious Disease Processes

• Entry

• Fungi infect the body through several portals of entry.

• The first exposure to fungi that most humans experience occurs during birth,
when they encounter the yeast C. albicans while passing through the vaginal
canal.

• Another fungus, Malassezia furfur, is common in areas of skin rich in sebaceous

glands.
• Fungi rarely cause disease in healthy, immunocompetent hosts, even
though we are constantly exposed to infectious propagules. It is only
when fungi accidentally penetrate barriers such as intact skin and
mucous membrane linings.

• Fungi gain access to host tissues by traumatic implantation or

inhalation.

• Fungal Factors
• Most of the fungi that infect humans and cause disease are classified
by tissue or organ levels that are primary sites of colonization.

• 1. Superficial fungal infections involve only the outermost layers of the

stratum corneum of the skin or the cuticle of the hair shaft
• 2. Dermatophyte infections are caused by fungi that colonize skin, hair,
and nails on the living host.

• 3. Subcutaneous mycoses involve fungi that are abundant in the

environment and have a low degree of infectivity.

• 4. Systemic mycoses are fungi that have the innate ability to cause
infection and disease in humans and other animals. The primary site of
infection is the respiratory tract.
• Mechanisms of Helminthic Infectious Processes

• Transmission of Infection Helminthes are transmitted to humans in

many different ways. These can include the following:

• 1. Accidental ingestion of infective eggs or larvae (some hookworms);

• 2. Presence of larvae that actively penetrate the skin (hookworms,
schistosomes, Strongyloides);
• 3. Larvae are contained in the tissues of the intermediate host and are
taken in when a human eats that host (Clonorchis in fish, tapeworms in
meat and fish, Trichinella in meat).

• The levels of infection in humans therefore depend on standards of

hygiene (as eggs and larvae are often passed in urine or feces).
• Host Factors Influencing Susceptibility

• Human behavior is a major factor influencing susceptibility to infection.

If the infective stages of helminthes are present in the environment,
then certain ways of behaving, particularly with regard to hygiene and
food, will result in greater exposure.
• Non-Specific Host Responses

• Antigen

• An antigen is any substance that elicits an immune response (Seeley,

2003). It can be a virus, a bacteria, or a simple foreign object in a certain
body part where it is not supposed to be found.

• Innate Immunity

• The innate immunity system is what a person is born with and it is

nonspecific. It is genetically based and is passed on to children.
• Physical Barriers or Mucosal Immunity

• An intact and continuous skin is considered to be the body's first line of

defense against microbial infections. Other non-specific mechanisms that act
to provide as physical barrier or flushing mechanism include the following:

• Ciliary action in the respiratory airways;

• Coughing and sneezing:
• Flushing action of tears, saliva, and urine;
• Sloughing off of skin;
• Sticky mucus in respiratory and gastrointestinal tracts;
• Acid pH (<7.0) of skin secretions;
• Sebum secreted by hair follicles that contains lactic acid and fatty acids;
• Slightly acidic vaginal secretions (after the onset of menses)
• Inflammation

• Inflammation is nonspecific response to any trauma occurring to tissues. It is

accompanied by signs and symptoms that include heat, swelling, redness, and
pain. Inflammation mobilizes components of the immune system area sets into
motion repair mechanisms and encourages phagocytes to come to the area and
destroy any microorganisms present.

• Fever

• Fever is considered a nonspecific defense mechanism because it develops in

response to numerous traumas. Fever is initiated by circulating substances
called pyrogens, which affect the brain's hypothalamus and cause the latter to
raise the temperature. Although excessive fever can be dangerous, fever is
believed to have a beneficial role because it retards the growth of temperature-
sensitive microorganisms and it increases the metabolism of body cells while
stimulating the immune reaction.
• Vaccines in the Elimination of Disease

• Vaccines

• Vaccination is the administration of an antigenic material - known as a vaccine

- to produce immune protection against a disease.

• Active Immunization

• In active immunization, the person is given an antigen usually a part of a virus

or bacteria - to stimulate the immune system to produce antibodies against the
pathogen.

• The person is only given enough antigens to stimulate the immune system but
not enough to elicit a full clinical course of the disease.
• Passive Immunization

• Passive immunization is similar to active immunization in that the

substance is given in commercially-prepared forms. However, actual
antibodies are administered instead of antigens that stimulate the
production of antibodies.

• Types of Vaccines

• The four main types of vaccines that are currently in clinical use
presenting a foreign antigen to the immune system in order to evoke an
immune response are as follows (Remington & Klein, 1993):
• 1. Inactivated - consists of virus particles which are grown in culture
and then killed using a method such as heat or formaldehyde.

• a. The virus particles are destroyed and cannot replicate.

• b. Viral capsid proteins are intact enough to be recognized and

remembered by the immune system and evoke a response.

• c. Since the properly produced vaccine does not reproduce, booster

shots are required periodically to reinforce the immune response.

• 2. Attenuated - live virus particles with very low virulence are

administered.
• a. The virus will reproduce, but very slowly.

• b. Since they reproduce and continue to present antigen beyond the

initial vaccination, boosters are required less often.

• 3. Virus-like particle - vaccines that consist of viral protein(s) derived

from the structural proteins of a virus.

• 4. Subunit vaccine - works by presenting an antigen to the immune

system without introducing viral particles, whole or otherwise.
 • Chapter 5

• Normal Microbial Flora and Pathogenic Bacteria

• Normal Human Microbial Flora
.
• Microorganisms of the normal flora may aid the host, may harm the host, or
may exist as commensals. Even though most elements of the normal
microbial flora inhabiting the human skin, nails, eyes, oropharynx, genitalia,
and gastrointestinal tract are harmless in healthy individuals, these
organisms frequently cause disease in compromised hosts.

• Normal Flora of Skin

• 1. Staphylococcus epidermidis - the major inhabitant of the skin, and in some

areas it makes up more than 90 percent of the resident aerobic flora.
• 2. Staphylococcus aureus - present in the nose and perineum.
• 3. Micrococci not as common as staphylococci and diphtheroids; however,
they are frequently present on normal skin.
• Respiratory Tract Flora

• The normal flora of the oral cavity and the upper respiratory tract
include the following:

• 1. General distribution - Bordetella parapertussis, Eikenella corrodens.

2. Nose - Cardiobacterium species and Staphylococcus aureus.
• 3. Nasopharynx - Acinetobacter species, Campylobacter sputorum,
Hemophilus species,.
• 4. Pharynx - Candida albicans, Hemophilus parainfluenzae,
Hemophilus paraphrophilus,.
• 5. Upper respiratory tract - Kingella species, Peptococcus species, and
Streptococcus pyogenes.
• Gastrointestinal Tract Flora

• The normal flora of the gastrointestinal tract includes the following:

• 1. General distribution - Bacteroides fragilis, Campylobacter coli.

• 2. Mouth - Actinomyces species, Aggregatibacter actinomycetemcomitans.

• 3. Gingiva - Bacterionema matruchotii.

• 4. Saliva- Lactobacillus species

5. Sputum - Lactobaciliter freundi, Gordonia bacterium, Mycobacterium

chelonae, and Neisseria sicca.
• Gram Positive Bacteria Pathogenic to Man

• Bacteria Gram positive bacteria stain blue or violet by Gram staining because
they are able to retain the crystal violet stain because of their peptidoglycan cell
wall.

• Actinomyces

• Actinomyces are characterized by contigious spread, suppurative and

granulomatous inflammation, and the formation of multiple abscesses and sinus
tracts that often discharge sulfur granules.

• Clostridium
• Clostridia are rod-shaped obligate anaerobes that produce endospores. They
are involved in a variety of human diseases, the most important of which are gas
gangrene tetanus, botulism, pseudomembranous colitis and food poisoning.
• 2 Clostridial species that produce tetanus include C tetani.

• a. Tetanus is a severe disease caused by the toxin of C tetani.

• i. This organism grows in a wound and secretes a toxin that invades

systemically and causes muscle spasms.

• ii. Cramping and twitching of muscles around a wound symptom -

initial symptom

• iii. No fever but sweats profusely and begins to experience pain,

especially in the area of the wound and around the neck and jaw
muscles (trismus).
• iv. Portions of the body may become extremely rigid, and opisthotonus
(a spasm in which the head and heels are bent backward and the body
bowed forward) is common.

• v. Complications include fractures, bowel impaction, intramuscular

hematoma, muscle ruptures, and pulmonary, renal, and cardiac
problems.

• Prevention and control include the following:

• - Meticulous wound care using aseptic technique

• - Prophylactic injections of tetanus toxoid
• - Local debridement, after the patient's spasms are controlled by
benzodiazepines.
• - Penicillin or metronidazole is usually administered to kill the bacteria, but may
not be a necessary adjunct in therapy.

• - Human tetanus immunoglobulin (HTIG) injected intramuscularly: dosage

recommendations vary from 500 IU in a single intramuscular injection to 3000-
6000 IU injected intramuscularly in several sites.

• - Supportive measures, such as respiratory assistance and intravenous fluids.

• Corynebacterium

• Corynebacteria are rod-shaped, aerobic or facultative anaerobic, non-spore-

forming and non-motile bacteria that are straight or slightly curved. Its most
important specie, C diphtheriae, causes diptheria. Diphtheria is most
commonly an infection of the upper respiratory tract and causes fever, sore
throat, and malaise.
• 3. Prevention and control include the following:

• a. Adequate immunization with diphtheria toxoid: formaldehyde-inactivated

diphtheria toxin that remains antigenically intact.

• b. Penicillin and erythromycin

• Enterococcus

• Enterococci are a common commensal of the intestines. These are facultative

anaerobic bacteria that occur in pairs (diplococci) or short chains.

• It is often the cause of urinary tract infections, bacteremia, bacterial

endocarditis, diverticulitis, and meningitis. Enterococci exhibit a high level of
antibiotic resistance even to Beta-lactam and aminoglycoside antibiotics.
• Staphylococcus

• Staphylococci are facultative anaerobic commensals of the skin and the

nares. They appear round and form in grape-like cluster. Most of the
species are harmless and reside normally on the skin and mucus
membranes. Pathogenic species produce toxins or penetrate and invade
tissues to cause disease in humans.

• 1. S. aureus - major cause of nosocomial and community-acquired

infections.

• a. Superficial skin infections - boils, furuncles, styes, impetigo

• b. Serious infections in immunocompromised or immunosuppressed

patients - pneumonia, deep abscesses, meningitis.
• Streptoccocus

• Streptococci are non-motile and non-spore-producing spherical bacteria

that causes scarlet fever, rheumatic heart disease, glomerulonephritis,
and pneumococcal pneumonia.

• 1. Group A streptococcus include S pyogenes which is a beta-hemolytic

streptococci, meaning it completely destroys blood cells.

• a. Leading cause of streptococcal pharyngitis or "strep throat", acute

rheumatic fever, scarlet fever, acute glomerulonephritis, and necrotizing
fasciitis.

• b. May also produce sinusitis, otitis, joint or bone infections, meningitis.

• Gram Negative Bacteria Pathogenic to Man

• Overview of Gram Negative Bacteria

• Gram negative bacteria do not retain the crystal violet stain such that
the final stain is characterized by a pink or pale red stain.

• Bordetella

• Bordetella pertussis belongs to the genus Bordetella in the family

Alcaligenaceae, which contains several species of closely related
bacteria with similar morphology. В pertussis and B parapertussis cause
whooping cough (pertussis) in humans.
• 1. Clinical manifestations:

• a. Incubation period of 1 to 2 weeks

• b. Catarrhal phase-1-2 weeks

• i. Whooping cough begins
• ii. Low-grade fever, rhinorrhea, and progressive cough; the patient is highly infectious

• Prevention and control include the following:

• a. Tetracycline, erythromycin, and chloramphenicol

• b. Human hyperimmune pertussis globulin is still used occasionally.

• c. Susceptible children (unimmunized children without a history of whooping cough) should

have no contact with pertussis patients during the first 4 weeks of illness, although such
isolation is often difficult.
• Chlamydia

• Chlamydia is a group of obligate intracellular parasitic bacteria that are the most common
cause of bacterial sexually transmitted infectious blindness. Chlamydial species of
medical interest include C trachomatis, C pneumoniae, and C psittaci.

• - Tetracycline and erythromycin are the antibiotics commonly used to treat chlamydial
infections in humans.

• Escherichia
• Escherichia are non-spore-forming, facultatively anaerobic and rod-shaped bacteria which
are normal inhabitants of the gastrointestinal tract. As long as these bacteria do not
acquire genetic elements encoding for virulence factors, they remain benign commensals.

• 1. There are three groups of E coli are associated with diarrheal diseases.

• a. ETEC (enterotoxigenic) - E coli strains that produce enterotoxins.

• b. EIEC ( enteroinvasive) – E coli strains have invasion factors and cause tissue
destruction and inflammation resembling the effects of Shigella.

• c. EPEC (enteropathogenic) – E coli associated with outbreaks of diarrhea in

newborn nurseries, but produce no recognizable toxins or invasion factors.

• Helicobacter

• Helicobacter is a group of microaerophilic bacteria that lives in the lining

of the upper Gl tract and has been implicated in the development of
peptic ulcers, chronic gastritis duodenitis, and gastric cancer.
Helicobacter pylori is the type specie of the genus.
• Neisseria

• The Neisseria family of bacteria includes Neisseria, Moraxella, Kingella,

and Acinetobacter with Neisseria as the only significant contributor of
human pathogens. Neisseria gonorrhea and N meningitidis are the
agents of gonorrhea and acute bacterial meningitis, respectively.

• Most common symptom of uncomplicated gonorrhea:

• i. Discharge that may range from a scanty, clear, or cloudy fluid to one
that is copious and purulent

• ii. Very often with dysuria

Prevention and control include:

• a. Use of condoms in preventing N gonorrhea transmission

• b. N gonorrhea antibiotic therapy with penicillin, tetracycline,
erythromycin, cephalosphorins, and quinolones
• c. N meningitidis antibiotic therapy with sulfonamides, rifampin

• Pseudomonas

• Most pseudomonads known to cause disease in humans are associated

with opportunistic infections.
• 1. Species include the following:

• a. P. aeruginosa produces localized infection following surgery or burns results

in a generalized and frequently fatal bacteremia.

• i. Urinary tract infections following introduction of P aeruginosa on

• catheters or in irrigating solutions. .

• ii. Cystic fibrosis patients are chronically colonized with P aeruginosa.

•
• iii. Necrotizing pneumonia may occur in other patients following the use of
contaminated respirators.

• iv. Pseudomonas aeruginosa can cause severe corneal infections following

eye surgery or injury.
• 3. Prevention and control include the following:

• a. Proper isolation procedures, aseptic technique, and careful cleaning

and monitoring of respirators, catheters, and other instruments.

• b. Topical therapy of burn wounds with antibacterial agents such as

mafenide or silver sulfadiazine, coupled with surgical debridement.

• c. Gentamicin, tobramycin