APPLIED MICROBIOLOGY

Pyrexia of Unknown Origin (PUO)

The normal body temperature is 37°C (98.8°F). The elevation of body temperature above the normal is
considered as fever. When fever persists or lasts for 10 days or more without any obvious cause then it
is termed as PUO or fever of unknown origin (FUO).

Types of PUO

Classical PUO - Fever (>38.3°C) on several occasions and more than three weeks duration
Nosocomial PUO - Fever (>38.3°C) on several occasions in hospitalised patient; infection neither
present nor incubating at the time of admission to hospital
Neutropenic PUO - Fever (>38.3°C) on several occasions; neutrophil count <500/ cu mm in peri-
pheral blood
HIV-associated PUO - Fever on several occasions (>38.3°C). More than three weeks as outpatient
or more than three days as inpatient. HIV serology positive.

Causes of PUO

Infectious
Causes Non Infectious Causes
• Neoplasms such as lymphoma, leukaemia, hepatoma
and other forms of cancer
• Collagen diseases such as systemic lupus rythematosus,
rheumatic fever etc.
• Metabolic disorders such as gout and porphyria
• Anaemia
• Drug induced fever, e.g. sulphonamide reaction
• Central nervous system abnormalities
• Allergic reactions such as serum sickness
• Alcoholic patient with liver disease
• Granulomatous diseases such as sarcoidosis, Crohn's
disease, granulomatous hepatitis etc.
• Vascular diseases such as arteritis, cerebrovascular
accidents, myocardial infarction, pulmonary
thromboembolism
• Trauma such as crush injury, head injury
• Miscellaneous causes-dehydration, hypothalamic
lesions, thyroiditis, etc.
• Heat fever-during summer days body temperature in
young children and old people may become elevated
towards early afternoon
• Psychogenic fever, i.e. fictitious fever

Infectious
Causes
A. Bacterial Causes
• Mycobacterium tuberculosis B. Viral Causes
• Salmonella sp. · Cytomegalovirus
• Brucella sp. · Epstein-Barr virus
• Chlamydia psittaci · Hepatitis A and B viruses
• Leptospira sp. · Arboviruses
• Borrelia sp. · Enteroviruses
• Rickettsia sp. · Adenoviruses
• Neisseria sp. · Myxoviruses
• Francisella tularensis · Human immunodeficiency virus (HIV)
• Mycoplasma sp. · Haemorrhagic fever viruses
• Streptococci
• Pneumococci
• Bacteroides sp.
• Listeria monocytogenes
• Legionella pneumophila
• Treponema pallidum
• Coxiella burnetii
• Atypical mycobacteria

C. Fungal Causes D. Parasitic Causes

· Candida albicans · Malarial parasites
· Cryptococcus neoformans · Leishmania sp.
· Histoplasma capsulatum · Trypanosoma sp.
· Aspergillus sp. (In tropical Africa)
· Coccidioides immitis · Toxoplasma gondii
· Pneumocystis carinii · Entamoeba histolytica
· Filarial parasites

Clinical Features
In persons with acute febrile illness (microbial infection), the symptoms are:
o Chills followed by rapid rise of temperature
o Flushing of tissue
o Intense sweating
o Malaise
o Lethargy
o Weakness
o Shock

In persons with neoplastic disease, the symptoms are:

o Emaciation
o Fever
o Chills
o Weight loss
o Headache
o Photophobia
o General malaise

Systemic symptoms in fever are:

o Pain in back
o Generalized myalgias
o Arthralgia without arthritis
o Sometimes delirium and convulsions

Laboratory Diagnosis in PUO

A. Routine Screening Tests
These include estimation of haemoglobin, total leucocyte count, differential leucocyte count, ESR
and eosinophil count which may give an indication regarding the type of infection for e.g. Atypical
mononuclear cells suggests glandular fever, Eosinophilia suggests parasitic infections

B. Biochemical Investigations
These include liver function tests such as: Aminotransferase-in viral hepatitis, Alkaline
phosphatase-in brucellosis, alpha-fetoprotein in hepatoma

C. Microbiological Investigations

1. Blood Culture

2. Urine Examination
· Routine microscopy-pus cells
· Z-N stain-to rule out tuberculosis
· Routine culture-for bacterial infection · Culture on L-J for tubercle bacilli

3. Stool Examination
Stool microscopy-for detecting ova and cyst · Stool culture-to rule out GIT infections

4. Sputum Examination
· Z-N stain-to rule out tuberculosis
· Routine culture and culture on L-J medium to rule out bacterial and mycobacterial
causes
D. Examination of Body Fluids

E. Serological Tests
Serological tests are important in the diagnosis of viral infections, collagen disorders and also in
some bacterial, fungal and protozoal infections. The serological tests commonly used in PUO are:
o Widal test-for enteric fever
o VDRL test-for syphilis
o Weil-Felix test-for rickettsial infections
o Bmcella agglutination test and complement fixation test (CFT)-for brucellosis
o Paul-Bunnel test-for infectious mononucleosis
o ASa test-for streptococci
o RA test-for rheumatoid arthritis
o Neutralization test-for viral infections