Chapter 113. Introduction to Infectious Diseases: Host–Pathogen Interactions (Part 2) docx

Chapter 113. Introduction to Infectious Diseases:
Host–Pathogen Interactions
(Part 2)

Host Factors in Infection

For any infectious process to occur, the pathogen and the host must first
encounter each other. Factors such as geography, environment, and behavior thus
influence the likelihood of infection. Although the initial encounter between a
susceptible host and a virulent organism frequently results in disease, some
organisms can be harbored in the host for years before disease becomes clinically
evident. For a complete view, individual patients must be considered in the context
of the population to which they belong. Infectious diseases do not often occur in
isolation; rather, they spread through a group exposed from a point source (e.g., a
contaminated water supply) or from one individual to another (e.g., via respiratory
droplets). Thus, the clinician must be alert to infections prevalent in the
community as a whole. A detailed history, including information on travel,
behavioral

factors,

exposures

to

animals

or

potentially

contaminated

environments, and living and occupational conditions, must be elicited. For


example, the likelihood of infection by Plasmodium falciparum can be
significantly affected by altitude, climate, terrain, season, and even time of day.
Antibiotic-resistant strains of P. falciparum are localized to specific geographic
regions, and a seemingly minor alteration in a travel itinerary can dramatically
influence the likelihood of acquiring chloroquine-resistant malaria. If such
important details in the history are overlooked, inappropriate treatment may result
in the death of the patient. Likewise, the chance of acquiring a sexually
transmitted disease can be greatly affected by a relatively minor variation in sexual
practices, such as the method used for contraception. Knowledge of the
relationship between specific risk factors and disease allows the physician to
influence a patient's health even before the development of infection by
modification of these risk factors and—when a vaccine is available—by
immunization.

Many specific host factors influence the likelihood of acquiring an
infectious disease. Age, immunization history, prior illnesses, level of nutrition,
pregnancy, coexisting illness, and perhaps emotional state all have some impact on
the risk of infection after exposure to a potential pathogen. The importance of
individual host defense mechanisms, either specific or nonspecific, becomes
apparent in their absence, and our understanding of these immune mechanisms is
enhanced by studies of clinical syndromes developing in immunodeficient patients
(Table 113-1). For example, the higher attack rate of meningococcal disease


among people with deficiencies in specific complement proteins of the so-called

membrane attack complex (see "Adaptive Immunity," below) than in the general
population underscores the importance of an intact complement system in the
prevention of meningococcal infection.

Table 113-1 Infections Associated with Selected Defects in Immunity

Host Defect

Disease

or

Therapy

Associated with Defect

Common
Etiologic

Agent

of

Infection

NONSPECIFIC IMMUNITY

Impaired cough

Rib

fracture,

neuromuscular dysfunction

Bacteria

causing

pneumonia, aerobic and
anaerobic oral flora

Loss of gastric
acidity

Achlorhydria, histamine
blockade

Loss

of

Penetrating

Salmonella

spp.,

enteric pathogens

trauma,

Staphylococcus


cutaneous integrity

athlete's foot

Burn

spp., Streptococcus spp.

Pseudomonas
aeruginosa

Intravenous catheter

Staphylococcus
spp., Streptococcus spp.,
gram-negative

rods,

coagulase-negative
staphylococci

Implantable

Heart valve

device

Streptococcus spp.,
coagulase-negative
staphylococci,
Staphylococcus aureus

Artificial joint

Staphylococcus
spp., Streptococcus spp.,
gram-negative rods

Loss of normal

Antibiotic use

Clostridium


bacterial flora

difficile, Candida spp.

Impaired
clearance

Poor drainage

Urinary tract infection

Escherichia coli

Abnormal

Cystic fibrosis

Chronic pulmonary

secretions

infection

with

P.

aeruginosa

INFLAMMATORY RESPONSE

Neutropenia

Hematologic
malignancy,

Gram-negative
cytotoxic enteric

bacilli,

chemotherapy, aplastic anemia, Pseudomonas

spp.,

HIV infection

spp.,

Staphylococcus
Candida spp.

Chemotaxis

Chédiak-Higashi
syndrome,

Job's

S.

syndrome, Streptococcus

aureus,
pyogenes,


protein-calorie malnutrition

Haemophilus influenzae,
gram-negative bacilli

Leukocyte

adhesion

defects 1 and 2

Bacteria

causing

and

systemic

skin

infections, gingivitis

Phagocytosis
(cellular)

Systemic

lupus

Streptococcus

erythematosus (SLE), chronic pneumoniae,
myelogenous

H.

leukemia, influenzae

megaloblastic anemia

Splenectomy

—

H. influenzae, S.
pneumoniae,

other

streptococci,
Capnocytophaga
Babesia

spp.,
microti,

Salmonella spp.

Microbicidal
defect

Chronic granulomatous
disease

Catalase-positive
bacteria

and

fungi:


staphylococci,

E.

coli,

Klebsiella

spp.,

P.

aeruginosa,

Aspergillus

spp., Nocardia spp.

Chédiak-Higashi

S.

syndrome

γreceptor

interleukin

deficiency,

S.

pyogenes

Interferon
defect,

aureus,

interleukin

Mycobacterium

12 spp., Salmonella spp.
12

receptor defect

INNATE IMMUNITY

Complement system

C3

Congenital liver disease,
SLE, nephrotic syndrome

S.

aureus,

S.

pneumoniae,
Pseudomonas
Proteus spp.

spp.,


C5

Congenital

Neisseria

spp.,

gram-negative rods

C6, C7, C8

Congenital, SLE

Neisseria
meningitidis,

N.

gonorrhoeae

Alternative

Sickle cell disease

pathway

pneumoniae,

Salmonella spp.

Toll-like

Congenital

receptor 4

Interleukin

S.

Gram-negative
bacilli

1

Congenital

receptor–associated

S. pneumoniae, S.
aureus, other bacteria

kinase (IRAK) 4

Mannan-binding
lectin

Congenital

N.
other bacteria

meningitidis,


ADAPTIVE IMMUNITY

T

lymphocyte

Thymic aplasia, thymic

Listeria

deficiency/dysfunction hypoplasia, Hodgkin's disease, monocytogenes,
sarcoidosis,

lepromatous Mycobacterium

leprosy

spp.,

Candida spp., Aspergillus
spp.,

Cryptococcus

neoformans,

herpes

simplex virus, varicellazoster virus

AIDS

Pneumocystis,

cytomegalovirus,

herpes

simplex
Mycobacterium

virus,
avium-

intracellulare,
neoformans,

C.
Candida

spp.

Mucocutaneous

Candida spp.


candidiasis

Purine

nucleoside

Fungi, viruses

phosphorylase deficiency

B

cell

Bruton's

X-linked

deficiency/dysfunction agammaglobulinemia

S.

pneumoniae,

other streptococci

Agammaglobulinemia,

H. influenzae, N.

chronic lymphocytic leukemia, meningitidis, S. aureus,
multiple

myeloma, Klebsiella pneumoniae, E.

dysglobulinemia

coli,

Giardia

lamblia, Pneumocystis,
enteroviruses

Selective

IgM

deficiency

Selective IgA deficiency

S. pneumoniae, H.
influenzae, E. coli

G.
hepatitis
pneumoniae,

lamblia,
virus,

S.
H.


influenzae

Mixed T and B
cell

Common

variable

hypogammaglobulinemia

Pneumocystis,
S.

pneumoniae,

deficiency/dysfunction

cytomegalovirus,

H.

influenzae, various other
bacteria

Ataxia-telangiectasia

S. pneumoniae, H.
influenzae,

S.

aureus,

rubella virus, G. lamblia

Severe

combined

immunodeficiency

S.

aureus,

pneumoniae,
influenzae,
albicans,

S.
H.

Candida
Pneumocystis,

varicella-zoster

virus,

rubella

virus,

cytomegalovirus

Wiskott-Aldrich

Agents

of


syndrome

infections associated with
T and B cell abnormalities

X-linked
syndrome

hyper-IgM

Pneumocystis,
cytomegalovirus,
Cryptosporidium parvum

Medical care itself increases the patient's risk of acquiring an infection in
several ways: (1) through contact with pathogens during hospitalization, (2)
through breaching of the skin (with intravenous devices or surgical incisions) or
mucosal surfaces (with endotracheal tubes or bladder catheters), (3) through

introduction of foreign bodies, (4) through alteration of the natural flora with
antibiotics, and (5) through treatment with immunosuppressive drugs.

Infection involves complicated interactions of microbe and host and
inevitably affects both. In most cases, a pathogenic process consisting of several
steps is required for the development of infections. Since the competent host has a
complex series of barricades in place to prevent infection, the successful pathogen
must use specific strategies at each of these steps. The specific strategies used by
bacteria, viruses, and parasites (Chap. 114) have some remarkable conceptual


similarities, but the strategic details are unique not only for each class of
microorganism but also for individual species within a class.