Fever I

• Whether embraced or feared, fever plays an important role in the physiologic response during illness.
• In fact, the ability to mount a febrile response to infection has been shown to increase survival rates in many animal species.
• Even many cold-blooded animals show an innate ability to increase body temperature in response to infection. For example, to raise body temperature during certain illnesses, lizards may remain in the sun and fish tend to swim in warmer water.
• Fever may have a positive effect on host leukocyte mobility and activity, activation of T lymphocytes, and production of interferon.
• Fever also may inhibit bacterial and viral function.
• However, these theoretical advantages come at the cost of hypermetabolism, increased insensible fluid loss, and general discomfort.
• Thus, fever is just one of many acute-phase responses to infection, and although the advantages of fever are well founded in animal models in terms of survival, its role in humans should be considered in the context of the individual patient and not on the basis of survival of the species.
• It is responsible for 25-50% of hospital visits in children
• It is known to generate fright in parents often leading them to carry out actions that are of no benefit or harmful (fever phobia)
• FEVER IS A SYMPTOM OF A DISEASE AND NOT A DISEASE ON ITS OWN!!!

• Temperature: the degree of heat as an inherent quality of objects expressed as hotness or coldness relative to something else.
• Simply put, temperature refers to the measurement of the degree of how hot or cold a place or object is.
• Fever represents a perception of an elevated temperature
• “a state of elevated core temperature, which is often, but not necessarily, part of the defensive responses of multicellular organisms (host) to the invasion of live (microorganisms), or inanimate matter recognized as pathogenic or alien by the host”.
• Fever is a controlled increase in body temperature over the normal values for an individual
• Fever is defined by a rectal temperature ≥38.0°C or axillary temperature > 37.5°C.

• Fever is a common, yet frightening, physiologic response that has been the source of great consternation throughout the history of medicine.
• Hippocrates described it as the body’s defence mechanism of “cooking off” an excess of one of the bodily humors (blood, yellow bile phlegm, black bile)
• In the 19th century, Sydenham described fever as “nature’s engine which she brings into the field for removing her enemy”

• This refers to the body temperature at which chemical enzymatic reactions are optimal.
• An intricate interaction among autonomic, endocrine, and behavioral mechanisms allows normal body temperature to remain relatively constant despite large variations in several factors, including ambient temperature and physical activity.
• Normal body temperature is maintained between 36.6 and 37.5C (axillary).
• A Homeothermic animal is one that maintains a constant internal body temperature, usually within a narrow range of temperatures while a poikilothermic animal is one that varies its internal temperature within a wide range of temperatures, usually as a result of variation in the environmental temperature.
• The center of the temperature control system lies in the thermoregulatory center of the hypothalamus.
• This specialized group of neurons maintains the body’s temperature “set point” by acting as a central thermostat.
• As a result of input from both peripheral receptors and the temperature of blood around the hypothalamus, the thermoregulatory center modulates various body mechanisms to maintain the physiologic set point.

• Heat generation
• Muscular activity
• Specific dynamic action
• Environmental sources
• Metabolism
• Heat loss
• Conduction
• Thermal gradient
• Tissue conductance
• Horripilation
• Clothing
• Convection
• Radiation
• Evaporation
• Vaporisation of 1 g of water leads to loss of 0.6kcal
• Insensible water loss
• Loss in urine and faeces

• Normal core temperature undergoes a regular circadian fluctuation of 0.5-0.7 °C.
• Lowest around 6am and highest around 5-7pm
• Lowest during sleep and slightly higher in the awake but relaxed state, and rises with activity.
• In young children, temperature regulation is less precise

Pyrogens

• Endogenous pyrogens
• Prostaglandins
• Exogenous pyrogens
• Microorganisms
• Toxins
• Foreign substances, etc
• Others
• Antigen-antibody complexes
• Certain androgenic steroid metabolites,
• Inflammatory bile acids,
• Complement, and
• Various lymphocyte-derived molecules

Hypothalamic set-point is altered by

• Interleukin 1
• Tumor necrosis factor α
• Interleukin 6
• Interferon β
• Interferon γ

Response to Activation of Cold Thermosensitive Neurons

• Behavioural responses
• Adoption of fetal position
• Seeking warm or thick clothing
• Drinking warm fluids
• Prefers hot bath
• Close body contact
• Irritable
• Increase heat from brown fat (non shivering thermogenesis)
• Shivering thermogenesis
• Vasoconstriction

Response to Activation of Hot Thermosensitive Neurons

• Behavioural responses
• Prefers cold bath
• Undresses
• Opens windows and prefers being outdoors
• Avoids close body contact
• Prefers being under a fan
• Sweating
• Vasodilatation

Related Terminologies

• Hyperthermia
• Hyperthermia is elevated temperature resulting from unregulated overproduction of heat or impaired heat-shedding mechanisms.
• Malignant Hyperthermia
• Malignant hyperthermia is an inherited disorder of muscular sarcoplasmic reticulum in which sustained muscle contraction and heat production occur after administration of succinylcholine or certain inhalation anesthetic agents.
• Heat Exhaustion
• fatigue, malaise, headache, dizziness, hypotension, tachycardia, nausea, and vomiting, usually resulting from intravascular volume depletion owing to sweat losses.
• Heat Stroke
• Heat stroke is elevated temperature (sometimes >40.0°C) along with mental status changes ranging from confusion to coma.
• Hypothermia
• Core temperature less than 35.0°C
• Subnormal temperature
• Temperature between 35.0°C and 36.5°C

• Fever with localizing signs
• Fever without localizing signs
• Fever of Unknown Origin

Fever with localizing signs

• Also known as Fever of short duration: Fever with an identified aetiology
• Forms the majority of febrile episodes
• Associated signs of localized infection, i.e. heat swelling discharge at ears, nose, skin throat, cough, vomiting diarrhoea, rash.

Fever without localizing signs

• Fever without localizing signs or symptoms, usually of acute onset and present for <1 wk
• Also known as Fever without a focus
• Careful history & examination fail to reveal cause
• Suggestive of occult cause or prodromal illness

Fever of Unknown Origin

• Also known as Fever of undetermined origin
• It is defined as fever documented by a health care provider and for which the cause could not be identified after 3 wk of evaluation as an outpatient or after 1 wk of evaluation in hospital
• Hx, Exam & preliminary investigations fail to reveal cause.
• Infection may eventually become apparent
• 25% no cause will be found prior to resolution.

• Infections
• Autoimmune/ Connective tissue disorders
• Trauma
• Neoplasms
• Drugs / Immunisation
• Endocrine
• Factitious fever
• Aetiology unknown

Infections

• RTI
• UTI
• MSS infections
• Gastroenteritis
• Endocarditis/pericarditis/myocarditis
• Meningitis
• Conjuctivitis
• Lymphadenitis
• Dental infections
• Cellulitis
• Tuberculosis
• Abscesses
• Sepsis
• Malaria
• Helminthiasis
• Viral infections
• Measles,
• Mumps,
• Chickenpox,
• Adenovirus,
• HIV
• Hepatitis

Autoimmune Disorders

• Rheumatoid arthritis
• SLE
• Sjogren syndrome
• Behcet syndrome
• Myasthenia gravis
• Rheumatoid arthritis
• SLE
• Sjogren syndrome
• Behcet syndrome
• Myasthenia gravis

Neoplasms

• Leaukaemia
• Lymphoma
• Neuroblastoma
• Phaeochromocytoma
• CNS tumours
• Histiocytosis

Endocrine

• Hyperthyroidism
• Diabetes insipidus
• Diabetes mellitus

Harmful:

• Discomfort
• Convulsions
• Cardiorespiratory decompensation
• Fever phobia

Beneficial:

• Modest fever can accelerate a variety of immunologic responses, including
• Phagocytosis,
• Leukocyte chemotaxis,
• Lymphocyte transformation,
• Interferon production
• Gonococci and some treponemes are killed at high temperatures induced in experimental animals
• In addition, fever appears to hamper the growth of some types of pneumococci and some viruses.
• Fever is also associated with a decrease in the amount of free serum iron, which is an essential nutrient for many pathogenic bacteria.

Fever Patterns

• High grade fever – Temperature >39.0°C
• Moderate grade fever – Temperature 38.1 – 38.9°C
• Low grade fever - Temperature 37.6 – 38.0°C
• Hyperpyrexia – temperature ≥ 40°C

Intermittent fever

• It is an exaggerated circadian rhythm that includes a period of normal temperatures on most days
• Quotidian, tertian, quartan

Continuous fever

• Fever is present throughout the day however difference between peak and trough temperature is less than 1°C

Remittent fever

• Fever is present throughout the day however difference between peak and trough temperature is greater than 1°C

Pel Ebstein fever:

• Swinging pyrexia characterised by a week of high pyrexia followed by a week of low pyrexia

Other Features

• Reduced apetite
• Thermotactic behaviour
• Tachycardia
• Relative tachycardia: Tachycardia out of proportion to the degree of fever. Eg myocarditis
• Relative bradycardia(Temperature – pulse dissociation):
• Pulse remains low despite fever. Seen in infective endocarditis, typhoid fever, brucellosis, leptospirosis, acure rheumatic fever with heart block, drug fever
• Discomfort
• Irritability
• Hallucinations
• Cold extremities
• Febrile seizures
• Associated symptoms to localize to a system

Investigating the Febrile Child

Depends on the suspected cause

May include

• Full blood count
• Blood film for malaria parasite
• RDT for malaria
• Blood culture
• Urine culture
• Stool culture
• CSF culture
• Serologic assays
• Swabs

• Thermometry refers to the measurement of temperature.
• The term ‘thermometer’ refers to an instrument used to measure temperature.
• Objective definitions of fever have been based on the development of a variety of thermometers, and identification of different sites for valid measurement of body temperature.
• In the time of Hippocrates, only the hand was used to detect the “heat” or “cold” of the human body, although fever and chills were known as signs of morbid processes.
• In Alexandrine medicine times, the pulse was observed as an index of disease, and the clinical importance of evaluating the pulse was said to have superseded that of a crude assessment of temperature.
• In the Middle Ages, the four bodily “humours” (i.e. black and yellow bile, blood and phlegm) were individually assigned the qualities of hot, cold, dry and moist, and thus fever again re-acquired its clinical import.
• Galileo, 1592 devised a crude temperature-measuring instrument, but it had no scale and therefore no numerical readings.
• Furthermore, the readings of this early contraption for measuring temperature could be affected by the atmospheric pressure.
• Subsequently, a giant leap was presumably achieved by Santorio (Sanctorio Sanctorius) who invented a mouth thermometer in 1625.
• Sanctorio devices required a long time to measure oral temperatures
• Christian Huygens, 1665 added a scale extending from the freezing point to the boiling point of water, the original centigrade system.
• Gabriel Daniel Fahrenheit who described the Fahrenheit scale, based his new scale on a mixture of ice and ammonium chloride as the lower point.
• He found mercury more useful than water, as it expanded and contracted more rapidly.
• In 1742, the Swedish astronomer Anders Celsius reintroduced the centigrade scale into practice, but despite improvements in design of the thermometer, its use remained largely neglected until the late 19th century.
• In 1869, Carl Wunderlich published temperature recordings from over 1 million readings in over 25,000 patients made with a foot-long thermometer used in the axilla. He established a range of normal temperature from 36.2 to 37.5°C.
• Besides the disadvantage of the size of the thermometers used then, having to read the temperature in-situ was a major disadvantage.
• Aitkin in 1852 made a mercury instrument with a narrower tube sited above a bulb reservoir. This was to ensure that the mercury did not drop back after removing the instrument from the site while the reading was being taken.
• Subsequently, it was left then to Thomas Clifford Allbutt to design in 1866, a conveniently portable 6-inch clinical thermometer, able to record a temperature in five minutes.
• It replaced a foot-long model, which required 20 minutes to determine a patient's temperature.

Types of thermometers

• Liquid-in-glass
• Thermistor-based electronic clinical thermometers
• Liquid crystal indicator-based thermometers
• Tympanic membrane thermometers
• Chemical thermometers

Sites of Temperature Measurement

• Invasive
• Pulmonary artery
• Bladder
• Oesophagus
• Non-invasive
• Rectal
• Oral
• Axillary
• Tympanic
• Skin

Definition of Fever with various Devices

• Axillary >37.5C
• Rectal>=38.0C
• Tympanic >37.6C
• Oral >37.5C

Rectal Thermometry

• Considered the non-invasive gold standard
• Rectal measurements have long been regarded as the most practical and accurate means of obtaining routine estimates of core temperature
• The rationale for taking measurements of temperatures in the rectum is based on the rich vascular supply of the rectum, via the superior, middle and inferior rectal arteries which coalesce in the wall of the rectum to form a vascular plexus.

• Rectal temperatures were initially measured with a liquid-in-glass thermometer, but the digital modification now provides an accurate alternative
• Modern devices have a flexible tip to prevent rectal trauma

Steps

• Thermometer is cleaned with 70% alcohol prior to insertion
• It is adequately lubricated with a lubricant before insertion
• The child lies on the back or front on the mother’s lap
• The device is introduced 2-3cm into the rectum and the child restrained until recordings are obtained.

Advantages

• Measures “core temperature”
• Requires minimal training
• Fairly accurate

Disadvantages

• Slow to change i.e. rectal lag
• Hygiene
• Unacceptability to parents and healthcare workers
• Risk of infection transmission
• Possible rectal perforation

Axillary Thermometery

• Most popular method
• Relies on thermometer being against the axillary artery
• Is a site of convenience rather than accuracy
• May use mercury or digital thermometers
• Fraught with issues of unreliability

Steps

• Clean device
• Abduct the arm
• Insert in axillary pocket
• Arm adducted and left in place for 3-5 minutes for a final reading

Advantages

• Easy to use
• Rated favourably by parents and HCW
• Minimal risk of transmission of infection
• Fairly accurate in the non-asphyxiated newborn
• Strongly influenced by environmental conditions and operator techniques

Disadvantages

• Inaccurate
• Unreliable

Oral Thermometry

• Relies on the thermometer being in the lingual pocket against the lingual artery.
• The sublingual site is easily accessible and reflects the temperature of the lingual arteries.
• The temperature of the sublingual pocket is relevant clinically because its main artery is a branch of the external carotid artery and, like its parent artery, it responds promptly to changes in core temperature.
• It would however appear that the accuracy of oral thermometry increases with the age of the child, primarily due to compliance, as well as the ability of the child to use the proper technique.

Advantages

• Accurate: The general view is that the accuracy of oral thermometry lies somewhere between that of axillary and rectal thermometry.
• Reflection of core temperature
• Acceptable to parents and HCW

Disadvantages

• Oral temperature is easily influenced by a recent ingestion of food or drink and mouth breathing.
• Oral thermometry relies on the mouth remaining sealed, with the tongue depressed for 3-4 min, which is a difficult task in young children.
• This method of temperature measurement cannot be used in young pre-school children, or indeed in the unconscious or uncooperative patients.

Tympanic Thermometry

• The tympanic membrane is perused by a branch of the internal carotid that comes off a branch that supplies the hypothalamus.
• Thought to represent the ideal thermometer, however field use has demonstrated varied accuracy.
• Initial devices were in direct contact with the TM
• Current devices use infrared radiation for temperature detection

Tympanic Thermometry

• The tympanic membrane is perused by a branch of the internal carotid that comes off a branch that supplies the hypothalamus.
• Thought to represent the ideal thermometer, however field use has demonstrated varied accuracy.
• Initial devices were in direct contact with the TM
• Current devices use infrared radiation for temperature detection

Advantages

• Fairly accurate
• Reliable
• Acceptable
• Not affected by wax, otitis media, foreign bodies
• Hygienic

Disadvantages

• Expensive devices
• Questions about device standards
• Methodological concerns