Pyrexia of unknown
origin and Fever in
returning traveller
Dr Richard Drew
Research Fellow
Dept Clinical Microbiology
What is PUO
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Originally defined in 1961 by Petersdorf and
Beeson
Fever >38.3C on 3 or more occasions
 Fever for more then three weeks
 Uncertain diagnosis after one week in hospital
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Very rare nowadays in hospital
How to solve the problem
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History
Physical examination
Blood tests
Imaging
Endoscopy and tumour markers
Aetiology
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Infections
Malignancies
Connective tissue disorders
History
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Fever: Pattern, periodicity, how was it measured
Associated symptoms such as sweating, vomiting,
headaches etc.
Target specific organ systems if patient has problems in
that system
Past med and surg hx. NB prostheses in situ
Medications/ vaccines
Family hx of hereditary diseases, connective tissue
disorders or recent illnesses (TB/ AIDS)
Sexual history
Occupation, pets, travel
Examination
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Full physical examination is needed. Should be very
detailed and review all systems.
For exams make sure to examine:
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Hands for stigmata of infective endocarditis
Retinal exam for candidiasis or toxoplasmosis
Teeth (infective endo or abscess)
Lymphadenopathy (AIDS or chronic infections)
Hepatosplenomegaly (Lymphoma/leukaemia)
Breast/testicular exams
Any sore joints
Infections
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Tuberculosis
HIV/AIDS
Abscess
Osteomyelitis
Infective Endocarditis
tuberculosis
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Classical prevention is fever, haemoptysis, cough, weight loss
and night sweats
Risk Factors: Alcoholic, homeless, drug abuser, immigrant
On exam can have pleural rub, pleural effusion and
lymphadenopathy. Check if BCG vaccinated
Do Mantoux test, CXR and sputum for AFB and TB culture.
Treatment is 4 drug regimen (RIPE) and inform public health
Isolate patient for 2 weeks in negative pressure room and wear
FFP3 masks
Always consider in differential of patient with cough and PUO
HIV/ AIDS
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No classical presentation. Can present with
fever, weight loss, sweats, lymphadenopathy or
with opportunistic infection
Hx: Sexual contacts, Birthplace, Maternal hx if
child, Exposure events, occupation
O/E Full exam. Lymph nodes and spleen
Ix: HIV antibody test and HIV viral load, CD4
count
Mx: Refer to ID team. HAART
Osteomyelitis
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Infection of the bone
Spontaneous osteomyelitis is rare apart from in
Sickle cell disease patients
Consider if prosthesis is in situ or if there is a
history of preceeding compound fractures
FBC, ESR, Imaging of joint, bone biopsy
Mx: Targeted antimicrobial therapy and
prosthesis removal
Non-infectious causes
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Malignancies
Lymphoma
 Leukaemia
 Solid organ tumours
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Connective tissue disorders
Still’s disease
 Giant cell arteritis
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Malignancies
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Leukaemia/Lymphoma
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Solid Organ tumours
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Hx: fever, sweats, weight loss, fatigue
O/E, Lymph nodes, hepatosplenomegaly
Ix: Bone Marrow aspirate, blood smear, FBC
Mx: Chemotherapy+/- Bone Marrow transplant
Target the particular organ you feel is involved.
Connective tissue disorders
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Hx: Fatigue, unexplained rashes, arthralgia, myalgia
O/E arthralgia, uveitis, Raynaud’s phenomenon
Ix: ESR
Mx: Steroids, NSAIDs
Investigations
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Basic tests
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FBC: WCC, blood smear,
bone marrow aspirate
ESR, CRP: Non-specific markers of inflammation
CXR, Mammogram, Pap smear if relevant, Mantoux,
Micro: Blood cultures (3 sets)
Other tests to consider
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The clue is in the history as to what tests are needed
HIV test, viral and bacterial serology
CT thorax/ abdomen
Tumour markers
Echocardiogram
Management
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Determine if critically ill. If not can hold off on
antibiotics
Don’t feel need to just treat a temperature
Clue is in the history and the exam and then
order relevant tests. Do not send random
serological tests off. Often these will cause more
trouble then you want!!!
Returning Traveller
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Very common problem
Geosentinel data review (Clin Infect Dis. 2007)
of 25,000 ill returning travellers
28% had fever and 26% of these needed admission
 Malaria was the most common diagnosis
 Considerable geographical variation
 17% had vaccine preventable diseases
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Will discuss methods of diagnosing the
condition and not each disease in detail
History
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Crucial. Will help to narrow down possible list of diseases.
Don’t always get distracted by history of recent travel. May be
more common diagnosis
Exposure: Duration, exact location, urban/rural, type of
accomadation
Timing: Consider incubation period and onset of symtoms. 66%
of dengue presents within one week of return. 34% of hepA
presents within 6 weeks
Food history is important
Sexual history is important
Vaccine history
Examination
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Full examination as per previous PUO talk
Need to consider the risk of a transmissible organism
Consider isolating patient until diagnosis is known
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Critical if considering a viral haemorrhagic fever
Signs that should trigger full resuscitation and
precautions
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Bleeding symptoms, respiratory symptoms
Hypotension
Signs of meningitis or raised intracranial pressure
Evaluation
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Thick and Thin smears for malaria
FBC: Look for raised white cells
Renal profile: Dehydration, renal failure
Liver profile: hepatitis
Coagulation screen
CXR if respiratory symptoms
Top 5 diagnoses (Geosentinel)
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Malaria
Dengue Fever
EBV/CMV mononucleosis
Rickettsia
Typhoid
Clinical Case 1
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26yr IVDA from Dublin
Self discharged twice before
from hospital having been
admitted with fever
Reports to have had fever
and night sweats for about 4
weeks.
Has lost 2 stone in 3 months
Some visible skin sores and
needle marks
Pulse 110bpm, Temp 36C,
BP 100/60
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Differential diagnosis
History
Examination
Lab tests at 3am
Lab tests the following day
Infection Control
Management
Public Health
Clinical Case 2
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Returning GOAL
worker. 28 yr male.
Worked for 12 months
in rural clinic in Rwanda
2 episodes of infectious
diarrhoea while there
Presented to ED three
days after coming home
Looks very unwell. Non
blanching skin rash
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Differential diagnosis
History
Examination
Lab tests at 3am
Lab tests the following
day
Infection Control
Management
Public Health