General Approach to Infectious Diseases Evaluation

Infections are disorders or diseases caused by microorganisms such as bacteria, viruses, fungi, or parasites. Infections manifest themselves by a myriad of signs and symptoms in a variety of combinations. It is not possible to discuss in a meaningful way the various permutations and combinations of signs and symptoms associated with infectious diseases. However, some signs and symptoms are, rightly or wrongly, widely regarded as cardinal manifestations of infection and are discussed here.

Fever

Fever is defined as an elevation of normal body temperature. Definitions of normal temperature have evolved over the years through studies that have attempted to incorporate potential confounding factors such as time of day, age, gender, and body site of temperature measurement in their evaluations. Based on data from these studies, fever is defined as an oral temperature of ≥37.2°C (99.0°F) in the morning or an oral temperature of ≥37.8°C (100°F) at any time during the day.

Fever is a component of a complex physiologic reaction often, but not exclusively, in response to invasion by microorganisms or their products. Body temperature is regulated by a complex process that involves a variety of body structures, including the immune system, heat and cold receptors in the skin and organs, and the spinal cord and the brain. Thus fever may be caused by a variety of other noninfectious conditions ( Table 1.1 ). Alternatively, fever may not be present though the patient clearly has an infection (e.g., typhoid fever, tularemia, brucellosis, and dengue).

Take-Home Points Box 1.1

Take-Home Points:

1.
Infections commonly present with fever.
2.
Infections can present without fever.
3.
There are many noninfectious causes of fever.

TABLE 1.1

Noninfectious Causes of Fever

Disease Conditions	Examples
Malignancies	Lymphoproliferative disorders Renal cell cancer Hepatocellular cancer
Autoimmune/connective tissue diseases	Vasculitis Temporal arteritis Systemic lupus erythematosus Sarcoidosis Still disease
Thromboembolic disease	Deep venous thrombosis Pulmonary emboli Acute stroke
Drugs	Antibiotics Antineoplastics Allopurinol Contrast dye Interferon
Others	Inflammatory bowel disease Gout Rheumatic fever

Leukocytosis

The stem cells in the bone marrow that form the various blood cells—hematopoietic stem cells—produce erythroblasts, megakaryoblasts, lymphoblasts, and myeloblasts. Erythroblasts further differentiate into red blood cells, megakaryoblasts into platelets, and lymphoblasts into lymphocytes. Myeloblasts differentiate into monocytes and granulocytes, and granulocytes are further categorized into neutrophils, basophils, and eosinophils. The term white blood cell (WBC) denotes the cells derived from lymphoblasts and myeloblasts. Upon maturation, most (80% to 90%) of the WBCs remain in the bone marrow, a few (2% to 3%) circulate freely in the peripheral blood, and the remainder are stored in the spleen or deposited along the walls of the blood vessels.

Leukocytosis—an increase in the total number of WBCs due to any cause—is a reaction to a wide range of events that result in the release of various cytokines, which in turn mediate the release of leukocytes and their precursors from the marrow, spleen, and vessel walls. A rise in the absolute number of neutrophils is most commonly responsible for the overall leukocytosis, but increases in the numbers of the other components of WBCs—lymphocytes, monocytes, eosinophils, or basophils—may also play a role.

Infections are common causes of leukocytosis. However, leukocytosis can also be the result of a variety of other stimuli and conditions, including malignancies, inflammatory conditions, drugs, stress, and trauma ( Table 1.2 ).

TABLE 1.2

Noninfectious Causes of Leukocytosis

Disease Conditions	Examples
Malignancies	Lymphoproliferative disorders Renal cell cancer Sarcoma
Autoimmune/connective tissue diseases	Vasculitis Rheumatoid arthritis Systemic lupus erythematosus
Physiologic	Strenuous exercise Emotional disorders Pregnancy
Drugs	Corticosteroids Epinephrine Endotoxin Lithium Ranitidine Serotonin Histamine Heparin Acetylcholine
Others	Inflammatory bowel disease Rheumatic fever Acute hemorrhage

Occasionally, the magnitude of leukocytosis exceeds 50,000 cells/mm ³ , requiring distinguishing it from leukemia. This is called a leukemoid reaction and is commonly caused by severe infections.

At times, leukopenia (a decrease in total WBCs) and not leukocytosis may be the presenting feature of certain infections. These infections include influenza, infectious mononucleosis, HIV, rickettsiosis, ehrlichiosis, typhoid fever, tuberculosis (TB), brucellosis, tularemia, leishmaniasis, and malaria. Sepsis, or any overwhelming infection, can also present with leukopenia.

Take-Home Points Box 1.2

Take-Home Points:

1.
Infections commonly present with leukocytosis.
2.
Infections can also present with leukopenia.
3.
There are many noninfectious causes of leukocytosis.

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