Persistent Fever Causes and FUO (Fever of Unknown Origin)

Humans are warm-blooded animals that maintain a stable body temperature regardless of the temperature fluctuations in the outside environment. Maintenance of the core body temperature within a narrow range is essential for the biochemical life processes within the human body. Body temperature measurements are usually done by using a thermometer.

Variations in Body Temperature

It is important to note that different regions of the body give slightly different temperature readings. The normal temperature of the human body (measured orally) is about 37.5 °C (or 99 °F). However, measuring body temperature by inserting a thermometer in the rectum will result in a normal reading of about 38 °C (or 100 °F).

Body temperature can also be obtained by inserting a thermometer in the underarm region (axilla). Axillary temperature measurement is usually the least accurate. Rectal temperature is thought to be the most reliable. Oral temperature becomes unreliable in elderly patients. Body temperature also varies with the time of the day. In adults, there is a variation of about 0.6 °C in body temperature throughout the day. In children, the variation throughout the day is about 0.5 °C.

To summarize, the generally accepted normal human body temperature is about 37.5 °C. However, temperature readings in the range of 36.5 – 38 °C are considered normal. This range accounts for variations in temperature readings according to the site of measurement, the time of measurement, and also individual variation in the human population.

When is high body temperature a fever?

Fever refers to a condition in which the core body temperature rises above the normal range. Although one may be tempted to diagnose fever by touching the skin of a person or through reports of “feeling feverish”, it is best to use temperature measurements with a thermometer to diagnose the existence and seriousness of fever.

A rectal temperature that is above 38.2 °C in adults (and above 38 °C in children ) in considered to be an indication of mild to moderate fever. A rectal temperature that is higher than 40 °C indicates high fever. In infants that are less than 8 weeks old, a body temperature that is greater than 38.3 °C should be considered as high fever.

A high fever that does not “break” or respond to any medication should be treated as a medical emergency. Such a condition is potentially fatal, and requires immediate medical intervention.

Read more on how to bring down a fever.

Causes of Fever

The hypothalamus in the brain contains a thermoregulatory center that is responsible for maintenance of the core body temperature within a narrow range (known as the set point). During fever, this body temperature set point in the hypothalamus gets raised, and changes in physiological processes ensue to match the temperature of the blood to the new and higher set point.

For example, vasoconstriction occurs in the peripheral regions of the body in an effort to conserve heat. A person starts feeling cold and begins to shiver. The rapid muscular contractions that constitute the act of shivering generates more heat. The affected individual also takes measures to keep warm such as wearing heavy clothing. All these events raise the temperature of the blood till it matches the higher set point in the hypothalamus.

Fever is a sign of many different conditions. Infections are the most common cause of fever. Bacteria that cause infections release substances into the blood that cause fever. Such fever-inducing substances are technically referred to as pyrogens. It is important to note that slight and temporary changes in body temperature are normal. Such transient changes in body temperature may occur due to physical activity, hormonal changes, environmental factors, and emotional factors.

Continuous or Persistent Fever

When the body temperature stays above 37.7 °C (or 100 °F) for more than 24 hours, the condition is referred to as continuous fever. During continuous fever, the temperature does not stay constant. But the fluctuations in temperature occur beyond the normal range of body temperature. Fever that persists for a maximum of 4-7 days is referred to as acute fever.

Usually acute fevers last for less than 4 days. However, fever may extend up to 7 days in case of a severe infection. Unlike acute fever, chronic fever lasts for a long period of time. Fever can either be intermittent or continuous. Intermittent fever is characterized by bouts of fever interspersed with periods when the body temperature drops. However, in continuous fever, the body temperature remains high and does not subside to a normal level.


Infections are the most common cause of high fevers. Severe or progressing infections are usually characterized by continuous high fever. In the absence of any treatment, serious complications (such as sepsis) may occur.


Trauma can cause an impairment of the thermoregulatory center in the hypothalamus. Disruption of the thermoregulatory center can result in continuous fever as the mechanisms responsible for cooling down the body do not function properly.


Both illicit and medicinal drugs can cause persistent drug-induced hyperthermia or fever. This is more likely to happen when the drugs are taken for a long period of time. Unsupervised usage of weight-loss medicines can also cause fever.

Unknown Fever

Some fevers are non-specific. They occur without any other accompanying signs or symptoms. In these cases, medical investigations may not be able to reveal the underlying cause of the fever. Such fevers are referred to as unknown fevers. Unknown fevers may either be acute or chronic.

Acute fevers with unknown causes are self-limiting in nature. They resolve spontaneously without any medical treatment. Chronic fevers with unknown causes can either be low-grade or high-grade fevers. Such persistent fevers do not present with any other signs or symptoms. Diagnostic tests for various potential causes fail to identify the exact cause in these cases.

A chronic fever with no identifiable cause is generally classified as “fever of unknown origin” (abbreviated as FUO). Fever of unknown origin is defined by doctors based on the following criteria:

  • Recurrent episodes of fever that span a period of 3 weeks or more.
  • A body temperature that is higher than 38.3 °C.
  • No cause identified after more than two outpatient visits.
  • No cause identified after three days of inpatient evaluation.

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