Crash course: PUO, Fever in the returning traveller

Question 1

What is pyrexia of unknown origin?

Answer 1

Repeated pyrexia >38.3ᵒC for >3w without a known cause, despite at least 1w of Ix

Question 2

What are the 4 classifications of PUO?

Answer 2

Classical

Nosocomial PUO: fever >24h, no fever on admission

Neutropaenic PUO: neutrophil count <500

HIV-associated PUO: >4w OP or >3d IP

Question 3

Give 3 causes of classical PUO

Answer 3

Infection
Malignancy
Collagen vascular disease

Question 4

Give 4 causes of nosocomial PUO

Answer 4

C diff enterocolitis
Drug induced
PE
Septic thrombophlebitis

Question 5

Give 4 causes of neutropenic PUO

Answer 5

Opportunistic bacteria
Aspergillosis
Candidiasis
Herpes virus

Question 6

Give 4 causes of HIV associated PUO

Answer 6

CMV
MAC
PCP
Kaposi sarcoma

Question 7

Give 4 other causes of fever

Answer 7

Non-obvious infections: unusual infections/ foci

AI conditions: rheum, vasculitis, Still’s

Malignancy: haem ca

Rare familial diseases: periodic fever syndromes, Fabry’s

Question 8

What is the cause of Typhoid fever? How is it transmitted? When does it present?

Answer 8

Salmonella typhi or Salmonella paratyphi

Classically travel from India

Faeco-oral route

After 1-2w incubation

Question 9

Give 5 non-specific signs of Typhoid fever

Answer 9

Fever
Malaise
Headache
Epistaxis
Constipation

Question 10

Give 4 more specific signs indicative of Typhoid fever

Answer 10

Faget’s sign: relative bradycardia (would expect ↑ with fever)

Rose spots

Hepatosplenomegaly

Cytopenias

Question 11

Why does Typhoid cause GI disease?

Answer 11

Typhoid resides in Peyer’s patches

Question 12

What investigations are used for typhoid fever?

Answer 12

Blood culture (stool -ve in early disease)

Serology (Widal test in developing countries)

GS: Bone marrow culture

Question 13

What is treatment for Typhoid fever?

Answer 13

IV Ceftriaxone
Fluoroquinolones: Ciprofloxacin

Question 14

What go to inflammatory cause of PUO should be considered in young patients and old patients?

Answer 14

Young: Adult-onset Stills
Old: GCA

Question 15

What is Dengue fever caused by? What is this associated with? How is it transmitted? When does it present?

Answer 15

1 of 4 Dengue serovars
Travel from SE Asia
Mosquito bites
After 2w incubation

Question 16

Give 4 non-specific signs/ symptoms of Dengue

Answer 16

Fevers
Rigors
Myalgia
Weakness

Question 17

Give 2 buzzwords associated with Dengue presentation

Answer 17

Retro-orbital headache
Sunburn rash

Question 18

What are the 2 rare but severe syndromes Dengue can present with? How?

Answer 18

Dengue shock syndrome
Dengue haemorrhage fever

If get infected with different serovar, preformed Ab to original serovar carries the virus to T, B cells + macrophages
Dengue spread to more cells it can infect

Question 19

What is malaria?

Answer 19

Parasitic infection caused by Plasmodium spp.
Falciparum
Vivax + Ovale
Knowlesi
Malariae

Question 20

How does malaria present?

Answer 20

Variable incubation dependent on species

Paroxysms of fever + rigors

Propensity for effecting liver: jaundice, hepatosplenomegaly, haemolytic anaemia, haemoglobinuria

Question 21

Name 5 potentially fatal complications of malaria

Answer 21

Shock
ARDS
Cerebral malaria
Blackwater fever
DIC

Question 22

What is blackwater fever?

Answer 22

Complication of malaria
Pronounced haemolysis
Leak lots of Hb into urine
Damages kidney + causes production of v dark black urine

Question 23

What investigations are used for malaria?

Answer 23

3x Blood smears: Thick + Thin blood films = GS

Question 24

Whats the difference between thick and thin blood smears?

Answer 24

Thick: high sensitivity, best initial test

Thin: lower sensitivity, high specificity, confirmatory test

Question 25

What is the lifecycle of plasmodium falciparum?

Answer 25

1. Bitten by mosquito- releases Sporozoites into blood
2. Sporozoites travel to liver + “set up shop”: Infect hepatocytes forming Hepatic Schizont (big ball of developing malaria parasites)
3. Gets increasingly bigger
4. Schizont ruptures, releasing loads of immature parasite into blood stream
5. Each parasite goes into a RBC + matures, turning into erythrocytic schizont
6. Erythrocytic shizont gets bigger + bigger, once fully developed, ruptures RBC, releasing more immature parasites that go on to infect more RBCs

Question 26

Why are there paroxysms of fever in malaria?

Answer 26

Cycle of invading RBCs/ rupture

Fevers, rigors, really unwell is due to RBCs rupturing + causing acute inflammation

Feel better when the immature parasites are invading new RBCs + developing

Question 27

How does the lifecycle of plasmodium vivax and ovale differ to falciparum?

Answer 27

Produce Hypnozoites

When infecting the liver, instead of all the parasites forming schizonts, rupturing + releasing parasites, some become quiescent

Hypnozoites can become reactivated years later, presenting with an acute malaria, having not been exposed to it since infection

Ramifications for Tx
Antimalarials that treat the active parasite in the blood don’t kill hypnozoites
Need slightly different Tx if vivax or ovale

Question 28

What is the treatment for severe falciparum malaria?

Answer 28

IV Artesunate

Question 29

Give 4 features of clinically severe malaria

Answer 29

Parasitaemia >2%
Hypoglycaemia
Metabolic/ lactic acidosis
Severe anaemia

Question 30

If non-severe, what is the treatment for falciparum malaria?

Answer 30

Artemesin combination therapy or chloroquine

Most common ACT= Artemether + Lumefantrine

Question 31

What additional drug is required for vivax and ovale?

Answer 31

Subsequent primaquine to kill hypnozoites