Tag Archives: #meded

Zoonotic infections

When I was an aspiring Infectious Disease fellow, I marveled at how the ID doctors would come up with diseases that no one else had thought of. How did they do that?

They obtain a detailed patient history. (It’s the ID doctors equivalent of a procedure!)

Contact or exposure to certain animals are associated with certain diseases.

These are examples of some of the questions to ask to ascertain whether your patient has been in contact with specific animals:
– Do you have any pets? Do you have frequent contact with anyone else’s pets?
– Do you have contact with any farm or wild animals?
– What do you do for work (farmer, veterinarian, kennel worker, biologists, etc)?
– What do you do for fun (hunting, fishing, cave explorer, raising chickens, etc)?

I’ve created an easy graphic to give you an idea of some diseases that are associated with different animals your patients might encounter. This is to help you quickly look up which infections you should consider in your differential if your patient reports an exposure to one of these animals.

*This list does not include ALL pathogens. This is just a list of the most common plus others to think about in certain situations. In places outside of North America, this list may look
**This is not intended to take the place of a formal infectious disease consult.
***Use this chart in the context of the clinical presentation. It does not mean you should test for all these infections in every patient, but rather gives you a quick reminder to consider them in your differential.

Was this helpful? Did I miss something? Tell me what you’re thinking with a comment!


1. Centers for Disease Control and Prevention. Healthy Pets Healthy People. http://www.cdc.gov/healthypets/pets/cats.html (Accessed on Feb 23, 2019).
2. Day MJ. Pet-Related Infections. Am Fam Physician. 2016; 94(10):794-802.
3. Goldstein EJC and Abrahamian FM. Diseases Transmitted by Cats. Microbiol Spectr. 2015; 3(5).
4. Chomel BB. Emerging and Re-emerging Zoonoses of Dogs and Cats. Animals (Basel). 2014; 4(3):434-445.
5. Dyer JL, Yager P, Orciari L et al. Rabies surveillance in the United States during 2013. J Am Vet Med Assoc. 2014; 245(10):1111-1123.
6. Boseret G, Losson B, Mainil JG, et al. Zoonoses in pet birds: review and perspectives. Vet Res. 2013; 44(1): 36.
7. Kwon-Chung KJ, Fraser JA, Doering TL, et al. Cryptococcus neoformans and Cryptococcus gattii, the Etiologic Agents of Cryptococcosis. Cold Spring Harb Perspect Med. 2014; 4(7):a019760.
8. National Association of State Public Health Veterinarians, Inc. (NASPHV), Centers for Disease Control and Prevention (CDC). Compendium of measures to prevent disease associated with animals in public settings, 2011: National Association of State Public Health Veterinarians, Inc. MMWR Recomm Rep 2011; 60:1.
9. Kotton CN. Zoonoses from pets other than dogs and cats. UpToDate. Published Jan 2019. Accessed on Feb 23, 2019.

Non-infectious causes of fever

This post is co-written with the guest writer Ahmed Abdul Azim, MD.

Not all fevers are caused by infections.

It is important that every patient presenting with fever is evaluated for an infection….. but what do you do when no infection is found?


Why are non-infectious causes of fever important to know?

If a patient is treated for a presumed infectious fever when they don’t have an infection:

  • there is a delay in identifying the correct diagnosis
  • they are exposed to prolonged courses of unnecessary antibiotics


Definition of fever

Fever = 38.3°C (101°F) or above1

Pyrogenic agents = substances that can induce a fever.
a) Exogenous pyrogens – external substances that activate our immune system to induce a fever (ex. microbial toxins)
b) Endogenous pyrogens – cytokines that induce fever in our body
(ex. IL-1, IL-6, tumor necrosis factor, IFN-α, ciliary neutrotrophic factor, and likely others)


Non-infectious causes of fever:

1. Rheumatologic/autoimmune – activation of immune system that stimulates the production of pyrogenic cytokines
– the cause of ~30% of fevers of unknown origin

a) Adult-onset Still’s disease – younger patients, daily fevers >39°C, rash, arthritis
b) Giant cell arteritis – older patients, vision changes, jaw claudication
c) Others – polyarteritis nodosa, Takayasu’s arteritis, granulomatosis with polyangiitis, etc.

2. Malignancy – tumor cells release pyrogenic cytokines

a) Lymphomas and leukemias – most common; seen in high burden of disease
b) Myelodysplastic syndromes
c) Renal cell carcinoma – ~20% of cases present with fevers
d) Hepatocellular carcinoma or liver metastases
e) Atrial myxomas

3. Drug-induced fever – 3-5% of drug-related adverse reaction in hospitalized patients include fevers6
– typically occurs 7-10 days after drug initiation, but can be as soon as 24 hours and as far away as a few years from drug initiation7
– patients typically appear “inappropriately” well
– eosinophilia (>500/mm3) occurs in 20-25% of patients with drug-induced fevers10

a) Hypersensitivity reaction – due to activation of T cell immune response by drug, its metabolite, or the formation of an immune complex
– typically occurs ~3-10 days after drug exposure
– typically resolves 72-96 hours after discontinuation of drug (but can be more delayed)
– symptoms will recur immediately upon rechallenge

1) Antimicrobials – most common cause of drug fever
– minocycline, beta-lactams (penicillin-based > cephalosporins10), sulfonamides, nitrofurantoin
2) Anticonvulsants – carbamazepine, phenytoin, phenobarbital
3) Allopurinol
4) Others

DRESS syndrome – a severe type of drug hypersensitivity reaction
(typically occurs 2-6 weeks after drug exposure)

b) Administration-related – typically last <48 hours

1) Vaccines – stimulation of the immune system → release of pyrogenic cytokines
2) Amphotericin B – exogenous pyrogenic agents

c) Pharmacologic action of the drug – transient fever; self-resolving

1) Anti-neoplastic agents – cause severe and rapid tumor cell lysis → release of endogenous pyrogenic agents → inflammatory response (fever)
2) Antimicrobials – cause rapid death of microbes → microbial cell lysis → release of exogenous pyrogenic substances → inflammatory response (fever)
–  ex. Jarisch-Herxeimer reaction in syphilis treatment with penicillin

d) Altered thermoregulation – disturbance of the central hypothalamic thermoregulation function and/or increased heat production

1) Exogenous thyroid hormone
2) Anticholinergic drugs
3) Sympathomimetic agents

cold winter tablet hot

e) Idiosyncratic drug reactions

1) Serotonin syndromes – linezolid, SSRIs
2) Neuroleptic malignant syndrome
– anti-psychotics, dopamine antagonists
3) Malignant hyperthermia syndrome
– inhaled anaesthetics, paralytic agents
4) G-6-PD deficiency – dapsone, primaquine, nitrofurantoin, etc.

4. Other causes

1) Transfusion of blood cells – RBCs, platelets, WBCs
2) Central fevers – fevers due to central thermodysregulation due to CNS damage
– more common with CNS hemorrhage and brain tumors11
– fever onset within 72 hours of sustaining CNS hemorrhage
3) Thromboembolism – typically <102°F
4) Endocrine – thyroid storm; adrenal insufficiency
5) Pulmonary – ARDS, aspiration pneumonitis, cryptogenic organizing pneumonia
6) Intra-abdominal – acute pancreatitis, cholecystitis, mesenteric ischemia

*Non-infectious causes of fevers are diagnoses of exclusion. A patient MUST have an appropriate workup for infectious causes prior to considering any of the non-infectious causes of fever.

*A lot of these diagnoses need to be made based on clinical symptoms and signs and requires a high degree of suspicion.

*Fever is a sign of an underlying inflammatory process.



  1. O’Grady NP, Barie PS, Bartlett JG, et al. Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Crit Care Med. 2008; 36(4):1330-1349.
  2. Dekker AR, Verheij TJ, and van der Velden AW. Inappropriate Antibiotic Prescription for Respiratory Tract Indications: Most Prominent in Adult Patients. Family Practice. 2015; 32(4):401-407.
  3. Mackowiak PA, Wasserman SS, and Levine MM. A Critical Appraisal of 98.6°F, the Upper Limit of the Normal Body Temperature, and Other Legacies of Carl Reinhold August Wunderlich. JAMA. 1992; 268(12):1578-1580.
  4. Obermeyer Z, Samra JK, and Mullainathan S. Individual Differences in Normal Body Temperature: Longitudinal Big Data Analysis of Patient Records. BMJ. 2017; 359:j5468.
  5. Westbrook A, Pettila V, Nichol A, et al. Transfusion Practice and Guidelines in Australian and New Zealand Intensive Care Units. Intensive Care Med. 2010; 36(7):1138-1146.
  6. Lipsky, BA and Hirschmann JV. Drug Fever. JAMA. 1981; 245(8):851-854.
  7. Mackowiak, PA. Southwestern Internal Medicine Conference: Drug Fever: Mechanisms, Maxims and Misconceptions. Am J Med Sci. 1987; 294(4):275-286.
  8. Patel, RA and Gallagher JC. Drug fever. Pharmacotherapy. 2010; 30(1):57-69.
  9. Johnson DH and Cunha BA. Drug fever. Infect Dis Clin North Am. 1996; 10(1):85-91.
  10. Oizumi K, Onuma K, Watanabe A, et al. Clinical Study of Drug Fever Induced by Parenteral Administration of Antibiotics. Tohoku J Exp Med. 1989; 159(1): 45-56.
  11. Hocker SE, Tian L, Li G, et al. Indicators of Central Fever in the Neurologic Intensive Care Unit. JAMA Neurology. 2013; 70(12):1499-1504.
  12. Porat R and Dinarello CA. Pathophysiology and treatment of fever in adults. In Baron EL, ed. UpToDate. Waltham, Mass.: UpToDate, 2018. [https://www.uptodate.com/contents/pathophysiology-and-treatment-of-fever-in-adults]. Accessed Dec 26, 2018.