1. Fever: What, Why, How?

2. Definition of fever Common medical sign and patient felt symptom Elevated temperature of > 37.2 0 C (mid-morning oral) or > 37.8 0 C (other times of the day). The core temperature is elevated due to re-setting the thermoregulatory set-point in the hypothalamus. This elevation is controlled hyperthermia/ pyrexia as opposed to uncontrolled hyperthermia which results from failed thermoregulatory mechanisms ie: body produces or absorbs more heat than it can dissipate eg. Heatstroke, NMS and serotonin syndrome with some drugs, overheating while wearing PPE, thyrotoxicosis and pheochromocytoma.

3. Fever: What’s normal? SiteNormal ( 0 C)Fever ( 0 C) Axilla36.4>36.9 Oral36.8>37.3 Rectal37.3>37.7 From this we can see there are some places that we shouldn’t go near Skin temp Peripheral receptors Hypothalamus thermostat Effector mechanisms that increase/ decrease temp Via lateral spinothalamic tract Core temp Central thermoreceptors

4. Causes of fever Influenza HIV Malaria Pyelonephritis Dengue fever Infective mononucleosis SLE Sarcoidosis IBD Kawasaki disease Leukaemia/ Lymphoma Hepatobiliary sepsis Infective endocarditis PID CMV Drug hypersensitivities

5. Causes of fever Persistent fever that escapes diagnosis is called Pyrexia of Unknown Origin (PUO/ FUO) Fevers of less than 3 days duration are often due to self-limiting viral infection of respiratory tract, although pneumonia and UTI’s (esp. in females) are also common causes.

6. Fever in recently returned traveller: Murtagh Probability diagnosis for Australia: Malaria 27% Respiratory tract infection (eg. Influenza) 24% Gastroenteritis 14% Dengue fever 8% Bacterial pneumonia 4%

7. Fever in recently returned traveller: Murtagh Serious disorders not to be missed Malaria TB Typhoid Encephalitis Bacterial meningitis Melioidosis Amoebiasis HIV seroconversion

8. Fever in recently returned traveller: Murtagh Pitfalls (often missed) CMV EBV Infective endocarditis Dengue

9. Mechanisms of fever Endogenous pyrogens are also known as cytokines and are part of the innate immune system, as produced by macrophages after their TLR’s are activated. The major endogenous pyrogens are IL-1, IL-6 and TNFa. Exogenous pyrogens include LPS and other endotoxins from bacteria. LPS is bound by LPS binding protein (an acute phase protein) and this complex binds to the CD14 receptors of macrophages, resulting in cytokine release (IL- 1, IL-6 and TNFa). All these cytokines eventually end up interacting with endothelial receptors on vessel walls or microglial cells to activate the arachidonic acid pathway.

10. Mechanisms of fever Arachidonic acid  Prostaglandin H2  Prostaglandin E2 with the help of COX-2 and PGE2 synthase enzymes

11. Mechanisms of fever PGE2 acts on the Prostaglandin EP3 receptors in the preoptic area of the hypothalamus,  stimulation of the sympathetic output evoking non-shivering thermogenesis to produce body heat coupled with peripheral vasoconstriction to decrease heat loss.

12. Biological role of fever Fever plays an important role in body’s defences against infection since fever: Activates T-cell production Increases effectiveness of some IFN Limits the replication of some viruses/ bacteria Increases phagocytosis Increased Ig production Some study actually found reduced mortality in those infections with significant fever… But you die when temp rises over 43 0 C

13. CASE study in fever: You are a SMO in ED at Mareeba hospital P.C. BM, an irritable, but tired 11 year old girl presents with her worried parents and a 24 hour history of fever. Her main concern is headache and body aches and pains with an itchy rash especially on her lower extremities.

14. CASE study in fever: P.C.Hx. BM has just come back from 2 weeks of camping in her school holidays when she started complaining of a headache and fevers. Her parents noticed she seemed very tired and treated the headache and fevers with paracetamol, ibuprofen and increased water intake, which appeared to work for a while. Over the past few days they have worsened and headache is now 8/10 pain and is now accompanied by generalized myalgia. Eye movement is painful. Her parents brought her in quickly because they think its Dengue fever – since she had it while overseas 18 months ago, they confirm she experienced some diarrhoea.

15. CASE study in fever: DDx?

16. CASE study in fever: DDx? Gastroenteritis? Malaria? Measles? Melioidosis? Dengue? DHF? Meningitis?

17. CASE study in fever: DDx Gastroenteritis? – why the rash? Malaria? – no resp symptoms Measles? – no cough Melioidosis? – no resp symptoms Dengue? DHF? Meningitis? – no neck stiffness

18. CASE study in fever: Medical Hx? Prev. Dengue fever illness 18 months ago after family trip to Southeast Asia

19. CASE study in fever: O/E Temp: 40 0 C Bilateral cervical and inguinal lymphadenopathy Tender abdomen BP 90/50, HR 88, RR 23 No organomegaly While examining the patient, she vomits and has a nose bleed straight shortly thereafter

20. CASE study in fever: Dx = Early stage of Dengue Haemorrhagic Fever

21. Incubation periods of travel related infections Short (<10 days) Influenza Dengue Yellow fever Plague

22. Incubation periods of travel related infections Intermediate (10-21 days) Malaria Typhoid fever Scrub typhus Q fever African trypanosomiasis

23. Incubation periods of travel related infections Long (>21 days) Malaria Hepatitis Rabies Schistosomiasis TB