The inflammatory response that accompanies infection is usually marked by fever. Fever is a tightly controlled elevation in body temperature above the normal range in response to a central nervous system change in the set point. Defining normal body temperature is somewhat problematic because it is dependent on both physiology and the method of measurement. Normal oral temperature in 99% of the population ranges from 36.0° to 37.7° C, with a circadian variation of 1° C or more between the morning nadir and the evening peak. Mean oral temperature in healthy adults is 36.8° ± 0.4° C, with women exhibiting slightly higher values than men (36.9° vs. 36.7° C). In menstruating women, the morning temperature may rise by 0.6° C with ovulation and remain higher until menses occur. Measured rectal temperatures are 0.4° C higher than oral and 0.8° C higher than aural (tympanic membrane) temperatures. However, considerable individual variability exists. Clinicians generally define significant fever as a temperature higher than 38.3° C (101.0° F). Despite historical claims, fever patterns are not especially helpful in establishing a specific diagnosis.

The majority of acute febrile illnesses lasting less than 2 weeks have an infectious cause. These infections occur predominantly where body surfaces interact with the environment, such as the upper and lower respiratory tracts, gastrointestinal and genitourinary systems, and skin. The majority of acute respiratory and gastrointestinal infections are viral in nature. As the duration of the febrile illness lengthens beyond 3 weeks, other inflammatory illnesses become more prominent in the differential diagnosis. Most chronic febrile illnesses are not caused by infection.


Infectious disease epidemiology depends on the interaction among pathogens, susceptible hosts, and environmental conditions allowing exposure. Most infections are transmitted horizontally between people by contact (e.g., hands, fomites), a common vehicle (e.g., food, water), air (e.g., tuberculosis), or vectors (e.g., mosquitoes).


Agents range from the submicroscopic to the large parasites.


Host Defect Disease or Therapy Associated With Defect Common Etiologic Agent of Infection
Patient factors such as age, immunization history, illnesses, level of nutrition, pregnancy, coexisting illness, and perhaps emotional state all have some impact on the risk of infection.    
Loss of gastric acidity Achlorhydria, histamine blockade  
  Penetrating trauma Staphylococcus spp., Streptococcus spp.
Loss of cutaneous integrity    
Burn Pseudomonas aeruginosa
IV catheter Staphylococcus spp., Streptococcus spp., gram-negative rods, coagulase-negative staphylococci
Implantable device Heart valve Streptococcus spp., coagulase-negative staphylococci, Staphylococcus aureus
Artificial joint Staphylococcus spp., Streptococcus spp., gram-negative rods
Loss of normal bacterial flora Antibiotic use Clostridium difficile, Candida spp.
Impaired clearance; Impaired cough
Poor drainage Urinary tract infection Escherichia coli
Abnormal secretions Cystic fibrosis Chronic pulmonary infection with P. aeruginosa
Neutropenia Hematologicmalignancy, cytotoxic chemotherapy, aplastic anemia, HIV infection Gram-negative enteric bacilli, Pseudomonas spp., Staphylococcus spp., Candida spp.
Chemotaxis Chédiak-Higashi syndrome, Job's syndrome, protein-calorie malnutrition S. aureus, Streptococcus pyogenes, Haemophilus influenzae, gram-negative bacilli
Leukocyte adhesion defects 1 and 2 Bacteria causing skin and systemic infections, gingivitis
Phagocytosis (cellular) Systemic lupus erythematosus (SLE), chronic myelogenous leukemia, megaloblastic anemia Streptococcus pneumoniae, H. influenzae
Splenectomy H. influenzae, S. pneumoniae, other streptococci, Capnocytophaga spp., Babesia 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 syndrome S. aureus, S. pyogenes
Interferon γ receptor defect, interleukin 12 deficiency, interleukin 12 receptor defect Mycobacterium spp., Salmonella spp.
Innate Immunity

Complement system


Congenital liver disease, SLE, nephrotic syndrome S. aureus, S. pneumoniae, Pseudomonas spp., Proteus spp.


Congenital Neisseria spp., gram-negative rods

C6, C7, C8

Congenital, SLE Neisseria meningitidis, N. gonorrhoeae

Alternative pathway

Sickle cell disease S. pneumoniae, Salmonella spp.

Toll-like receptor 4

Congenital Gram-negative bacilli

Interleukin 1 receptor–associated kinase (IRAK) 4

Congenital S. pneumoniae, S. aureus, other bacteria

Mannan-binding lectin

Congenital N. meningitidis, other bacteria
Adaptive Immunity 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. However, the genetic basis of susceptibility to infectious diseases is more complex than these examples of defects in any single gene would suggest. Human predisposition to infectious diseases involves a spectrum ranging from monogenic to polygenic traits that are the subject of ongoing study.

T lymphocyte deficiency/dysfunction

Thymic aplasia, thymic hypoplasia, Hodgkin's disease, sarcoidosis, lepromatous leprosy Listeria monocytogenes, Mycobacterium spp., Candida spp., Aspergillus spp., Cryptococcus neoformans, herpes simplex virus, varicella-zoster virus
AIDS Pneumocystis, cytomegalovirus, herpes simplex virus, Mycobacterium avium-intracellulare, C. neoformans, Candida spp.
Mucocutaneous candidiasis Candida spp.
Purine nucleoside phosphorylase deficiency Fungi, viruses

B cell deficiency/dysfunction

Bruton's X-linked agammaglobulinemia S. pneumoniae, other streptococci
Agammaglobulinemia, chronic lymphocytic leukemia, multiple myeloma, dysglobulinemia H. influenzae, N. meningitidis, S. aureus, Klebsiella pneumoniae, E. coli, Giardia lamblia, Pneumocystis, enteroviruses
Selective IgM deficiency S. pneumoniae, H. influenzae, E. coli
Selective IgA deficiency G. lamblia, hepatitis virus, S. pneumoniae, H. influenzae

Mixed T and B cell deficiency/dysfunction

Common variable hypogammaglobulinemia Pneumocystis, cytomegalovirus, S. pneumoniae, H. influenzae, various other bacteria
Ataxia-telangiectasia S. pneumoniae, H. influenzae, S. aureus, rubella virus, G. lamblia
Severe combined immunodeficiency S. aureus, S. pneumoniae, H. influenzae, Candida albicans, Pneumocystis, varicella-zoster virus, rubella virus, cytomegalovirus
Wiskott-Aldrich syndrome Agents of infections associated with T and B cell abnormalities
X-linked hyper-IgM syndrome Pneumocystis, cytomegalovirus, Cryptosporidium parvum



The reservoir is the normal habitat in which the agent lives and multiplies. It is where the agent propagates itself in nature. (A dead end host is not a reservoir.) The four types of reservoirs are:

  • Symptomatic cases
  • Carriers
    • Inapparent throughout history
    • Incubatory
    • Convalescent
  • Animals

    • Direct zoonoses
    • Cyclozoonoses
    • Metazoonones
    • Saprozoonoses
  • Inanimate objects
    • Water
    • Food
    • Soil
    • Air
    • Fomites

Portals of infection include the 

  • Respiratory tract (upper and lower)
  • Conjunctiva (lining of the eyes and eyelids)
  • Urogenital tract
  • Gastrointestinal tract (upper and lower)
  • Placenta (mother to child transmission)
  • Skin (broken and unbroken skin)

Modes of transmission include: 

  • Contact (requiring proximity to an infected host or discharge from an infected host)
  • Vehicle (an inanimate intermediate carrier)
  • Vector (an animate intermediate carrier, often an insect)
    • Mechanical
    • Developmental
    • Propagative
    • Cyclopropagative

Dynamics of Transmission

  • Common vehicle
  • Serial


Immunity includes all factors that alter the likelihood of infection and disease once the agent is encountered. There are two types of immunity: innate immunity & acquired immunity. Innate immunity is immunity the host is born with. It includes physical barriers to infection (e.g., skin) chemical barriers to infection (e.g., acidity of the stomach), cellular barriers to infection (e.g., macrophages) and other physiologic responses (e.g., inflammation). Acquired immunity is immunity developed after exposed to an agent. It includes a humoral component (e.g., antibodies) and cellular component (e.g., lymphocytes).

The components of the immune system are described on p. 47 of the text and include:

  • Physical barriers: skin, mucosa, mucus sheaths, respiratory tract cilia, cough and gag reflex
  • Chemical barriers: acidity of stomach and vagina, enzymes in saliva and GI tract, lipids, interferons, and other miscellaneous biologically active substances
  • Cellular and physiologic barriers: macrophages, polymorphs, reticular endothelial cells, NK cells, inflammation, fever.

Immunization is the act of acquiring immunity. It can be acquired passively (e.g., maternal transfer, therapeutic transfer) or actively (e.g., natural exposure, vaccination). Acquisition of active immunity is described in  the text. Immunity can be acquired naturally or artificially. In either case, the host is exposed to an antigen (foreign protein), the antigen is recognized, and the host builds a complex immune response to neutralize the antigen.

Vaccines artificially expose the host to antigens which then elicit an immune response. There are two types of vaccines: killed vaccines and modified live vaccines. Killed vaccines are composed of agent antigens but not living agent. Modified live vaccines are composed of non-virulent, living strains of the agent. For example, polio vaccine comes in both killed (Salk vaccine) and the modified-live (Sabin vaccine) forms. The Salk vaccine, developed in 1955, is made by cultivating three strains of the virus in monkey tissue. The virus is then separated from the tissue, stored for a week, and killed with formaldehyde. This killed vaccine is given by injection and requires 4 inoculations. The modified-live Sabin vaccine is an attenuated strain of living agent. It is thus capable of causing infection, but not disease. The Sabin vaccine is given orally and is the primary type of polio vaccine in use today since it is easier to administer and elicits a stronger response than the Salk vaccine (partially because viral multiplication creates a larger stimulus for response). The Salk vaccine is now mostly of historic interest.

Toxoids are harmless derivatives of microbiologic toxins that simulate an active immune response to toxins released by pathogens and other poisonous sources. For example, the tetanus toxoid immunizes the individual against the poison produced by the bacteria Clostridium tetaniC. tetani usually enters the body through a puncture, cut, or open wound and then releases a toxin that affects the motor nerves, which stimulate the muscles. Regular vaccination with the toxoid is needed to ensure immunity and thus prevent the painful spasms of muscles, including "locking" of the jaw so that the mouth cannot open (lockjaw) and death that otherwise might results.


  • Infection - entry and multiplication of a microorganism or parasite in the body of a host.
  • Infectious disease - infection + signs and symptoms.
  • Contamination - presence of a living agent on the exterior of the body or on an article of clothing.
  • Reservoir - the normal habitat where the agent lives and multiplies. It is where the agent propagates itself in nature. A dead-end host or temporary resting place of the agent is not a reservoir.
  • Carrier - a person or animal that harbor an infectious agent yet manifest no discernible signs of infection.
  • Zoonosis - an infections naturally transmitted between nonhuman animals and humans.
  • Portal - an entry and exit site into or out of the host for an agent. The six portals for agents are (1) the respiratory tract, (2) the conjunctiva (lining around the eyes), (3) urogenital tract, (4) gastrointestinal tract, (5) tranplacental (mother to child), (6) and skin.
  • Transmission - the mechanism by which an agent is spread from one host to another. The forms of transmission are described in the book.
  • Immunity - host factors that alter the likelihood of infection and disease after the agent is encountered.





Infection results when an exogenous agent ie, not normally found on or in the body, is introduced into a host from the environment or when an endogenous agent (ie, one that may be routinely cultured from a specific anatomic site but that does not normally cause disease in the host; microbiota) overcomes innate host immunity to cause disease.

Of the thousands of species of viruses, bacteria, fungi, and parasites, only a tiny portion is involved in disease of any kind. These are called pathogens. Among pathogens, there are degrees of potency called virulence.

Non-Specific Host Defense Mechanisms