The Fever Files: Series Introduction

Fevers can be Hollywood hits. Just think back to the all-star casts of Contagion (2011), where a bat virus caused a novel encephalitis, and Outbreak (1995), where a fictional orthomyxovirus spread by monkey from Zaire to California. In both cases, the military stepped in as vaccines were rapidly developed.

For this article, we’ll omit science fiction, like alien fungi (The Invasion, 2007) and zombie-inducing bioweapons (28 Days Later, 2002). But even fictitious infections seem all the more real after the coronavirus pandemic, with recent world events mimicking box-office hits to frightening accuracy.

Infections are often difficult to pinpoint, but can rapidly cause critical illness in the form of sepsis, a life-threatening condition that happens when the body’s immune system has an extreme response to infection that causes injury to its own organs.

Given that sepsis is the most common complication of infection and has been designated a Global Health Threat by the World Health Organization, EMS World has green-lit a new series: The Fever Files.

Case-based and jam-packed with real-life circumstances, The Fever Files will stretch your clinical prowess when it comes to spotting infection. Although you may not have the tools to definitively cure these infections when you see them in the field, your sleuthing may very well help to protect you and your partner, trigger triage nurses to jump-start care pathways and clue in emergency departments to the underlying culprit before sepsis sets in.

Welcome to the Fever Files.

First up, what is pyrexia, commonly known as a fever.

Body Mechanisms Behind a Fever

Your body’s temperature is regulated by the thermoregulatory center in the hypothalamus, a small endocrine gland that sits atop the pituitary gland and below the third ventricle, a few inches behind your eyeballs. It’s about the size of an almond.

Your hypothalamus is your body’s thermostat. Certain things can set the thermostat higher, leading to fever. Things like infection and inflammation release chemicals into the bloodstream, like interleukins, prostaglandins, and cytokines, which trigger the hypothalamus to set the thermostat higher.

This differs from environmental drivers of temperature For example, a hyperthermic patient with heat stroke and a body temperature of 39.9 degrees Celsius / 103.8 Fahrenheit does not have a fever. They are hyperthermic, but their thermostat hasn’t reset – rather, their cooling mechanisms can’t keep up with the outside world.  The word “hyperthermia” applies when the hypothalamus set-point is unrelated to a rising temperature.

I wouldn’t bother fighting with a triage nurse who says your heat stroke patient is febrile – but technically, a fever is caused by an internal process, not an external one, and hyperthermia refers to a failure of the hypothalamus.

Five Causes of Fever  

1. Infection

2. Autoimmune disease

3. Malignancy

4. Thrombosis

5. Drug response

When confronted with a case in the Fever Files, you’ll likely have tunnel vision on infectious causes; this will serve you well (most of the time!)

Let’s start with some basics to help improve your sleuthing skills when faced with a Fever of Unknown Origin. As is true for nearly all clinical cases, a focused yet thorough clinical history and physical exam will often yield a differential diagnosis.

Five Questions to Understand Fever

1. When did you first notice the fever?

2. How frequently have you been experiencing the fever?

3. Is there a pattern to the fever?

4. Does anything seem to trigger or exacerbate the fever?

5. What is the actual temperature and peak temperature of the fever?

Five Features of Fever 

1. Malaise or fatigue 

2. Nausea or vomiting

3. Night sweats or rigors/chills 

4. Weight loss

5. Skin changes, lumps, or swelling

Five Most Common Sources of Infection

1. Central nervous system: meningitis, brain abscess, spinal epidural abscess 

2. Resp: pneumonia, tuberculosis, common cold

3. Gastrointestinal: enteritis, colitis, proctatitis 

4. Genitourinary: urinary tract infection, infected kidney stone, pyelonephritis 

5. Skin: cellulitis, abscess, necrotizing fasciitis

Less Commonly, Five Other Organs Can Harbor Infections

1. Cardiac: pericarditis and endocarditis 

2. Hepatic: liver abscesses and hepatitis

3. Musculoskeletal: osteomyelitis and myositis 

4. Biliary tract: cholecystitis, ascending cholangitis

5. Bloodstream: bacteremia, viremia, fungemia

None of that should be a surprise to you. But let’s up our game by considering these additional questions when trying to identify infectious causes of fever.

Five Exposure/Risk Questions 

1. Have you been exposed to anyone who is sick?

2. Have you been exposed to contaminated water or food? 

3. Have you had any contact with animals, wild or domestic, including farm animals?

4. Have you had sexual activity recently? 

5. Have you used intravenous or intranasal drugs recreationally?

Five Travel Questions 

1. Where and when? (Pro tip: Travel doesn’t have to be “out of the country” and it doesn’t have to be “recent.")

2. Did you have any vaccines or prophylaxis? 

3. Did you swim or come in contact with animals? 

4. Did you protect yourself from insect bites (bed netting, clothing, bug spray) 

5. Did you have sex, get a tattoo or piercing, or sustain any breaks to the skin?

Importantly, we want to know about the host’s immune system. Consider these questions: 

1. Are you fully vaccinated? 

2. Do you have any conditions that affect your immune system? 

3. Do you take any medication that might affect your immune system?

Lastly, you’ve likely heard patients report something along the lines of: 

“My doctor said I had pneumonia, but these antibiotics aren’t working.” 

“Last time I was sick, I took antibiotics and they made me feel better.” 

When people have viral infections, they usually get worse until they are fed up and see a healthcare practitioner. Depending on the resources of the clinic, they may or not may have any confirmatory testing; things like urinary cultures, throat swabs, or chest x-rays. Often, they will be prescribed an antibiotic, and a few days later will feel better. But guess what – viruses get better on their own, so it’s impossible to know if the antibiotic-treated an underlying bacterial infection, or if the viral infection just got better on its own but was temporally associated with antibiotic use. The inverse can happen too – some viruses take weeks to get better, and people might think their antibiotic isn’t working. Well, they’re right! But not because they are on the wrong antibiotic or the wrong dose. When people report ongoing fevers despite antibiotics, dig a little deeper into why they were prescribed the antibiotic.

Over the next few cases of the Fever Files, we’ll hone our infectious disease investigative skills before moving on to non-infectious causes of fever. Happy sleuthing! 

Blair Bigham worked for a decade as a flight paramedic on four continents, a job he misses every day. He is now an ER and ICU physician at the University of Toronto and a public health researcher at the Dalla Lana School of Public Health. @BlairBigham blairbigham.com