Pyrexia of Unknown Origin by Dr. Rakesh

1. By Dr. Rakesh
Prasad Sah
Associate
Professor,
Microbiology
Pyrexia of Unknown Origin

2. FEVER
• A person to have a fever when he or she has a measured temperature of
100.4° F (38° C) or greater, or feels warm to the touch, or gives a history of
feeling feverish. (By CDC)

3. Infection, Injury, Trauma, Toxin, Inflammation
Kupffer cells and Leukocytes
Pyrogenic Cytokines (IL-1, IL-6, IL-10, TNF, IFN)
Hypothalamus (Production PGE2)  Rise in cAMP (acts as neurotransmitter)
Fever
Increase Set point
(Activation of vasomotor centre neurons)
(Peripheral vasoconstriction and heat production)

5. Introduction
• With the advent of modern diagnostic tools, the definition of fever of
unknown origin (FUO) has changes over time.
• Petersdorf and Beeson Classification
– Temperature >38.30C (more than 1010F) on several occasions.
– For a duration of more than 3 weeks.
– Failure to reach diagnosis despite one week of inpatient investigation.
Used for more than 30 years but later in 1990s, it was revised

6. The Definition was updated by Durack and Street in 1991 as:-
• Fever of unknown origin is defined as
– Fever of more than 38.30C (1010F) or greater lasting for 3 weeks or more that
remains undiagnosed after 3 days of in-hospital testing or during two or more
out patient visits of hospital.
• In addition FUO classified
– Classic FUO
– Nosocomial FUO
– Neutropenic FUO
– HIV relataed FUO

7. Third Definition
• Fever of ≥38.30C (≥1010F) on several occasions (at least two occasions).
• ≥ 3 weeks
• No known immunocompromised state
• For diagnosis, include comprehensive history taking, repeated physical examination and
following obligatory investigations:
– CBC
– ESR and CRP
– Electrolytes
– KFT
– LFT
– Protein Electrophoresis
– Enzymes (alkaline phosphatese, aminotransferase, creatine phosphokinase, lactate dehydrogenase)
•Three blood cultures (different sites, several hours
apart)
•Urine culture
•Radiological : X-ray and abdominal ultrasonography
•Tuberculin skin test or interferon gamma

8. Causes of FUO
• Infections
– Enteric Fever
– UTI
– Lung abscess and other deep
abscess
– Septicemia (Pneumonia, infective
endocarditis)
– Tuberculosis
– Relapsing fever
• Infections
– Lepotospirosis
– Brucellosis
– Rickettsial infections
– Q fever
– Scrub typhus
– Mycoplasma infections
– Chlamydia infections
Bacterial

9. • Malaria
• Hepatic amoebiasis or liver abscess
• Visceral leishmaniasis (Kala-azar)
• Filariasis
• Toxoplasmosis
• Trypanosomiasis (only in tropical Africa)
Parasitic infections

10. • Infectious mononucleosis
• Cytomegalovirus infection
• Epstein-barr virus (EBV) infections
• Viral Hepatitis
• Herpes simplex virus (HSV) infection
• Rubella and other infection without typical rash
• Dengue
• HIV infection
Viral Infections

11. Fungal infections
Candidiasis
Cryptococcosis
Coccidioidomycosis
Aspergillosis

12. Neoplasms
Hypernephroma Hepatoma
Hodgkin’s lymphoma
Leukemia
Non-Hodgkins’s lymphoma
Disseminated malignancy

13. • Metabolic disorders
• Thermoregulatory disorders.
Non-infectious inflammatory disorders
Miscellaneous Causes
SLE (Systemic lupus erythematosus)
Rhematoid arthritis
Granulomatous diseases

14. Laboratory Diagnosis
• Clinical history and physical examination  carried out  help in selection of
appropriate specimens.
• Specimens
– Blood
– Urine
– Sputum
– Pus
• Collection
– Before antimicrobial therapy
– In sterile container under aseptic conditions
– Blood  blood culture bottle and sterile vial for serology
– Mid-stream urine  sterile universal container

15. Microscopy
Peripheral Blood Smear (PBS)
Leishmaniasis (amastigote forms or LD bodies)
Malaria (ring stage and
gametocytes)

16. Microscopy
Peripheral Blood Smear (PBS)
Filariasis
(microfilaria)
Toxoplasmosis
(tachyzoites)
Infectious
mononucleosis

17. Peripheral Blood
Smear (PBS)
Malaria (ring stage
and gametocytes)
Leishmaniasis
(amastigote forms
or LD bodies)
Filariasis
(microfilaria)
Infectious
mononucleosis
Toxoplasmosis
(tachyzoites)

18. Slide Title
• a
Stool wet
mount
Ova Cyst Trophozoite

19. • Gram Staining
– Sputum
– Pus
– Other specimens
• Ziehl-Neelsen (ZN) staining
– Mycobacterium tuberculosis
• Periodic acid-schiff (PAS) staining
– Done for detection of fungi
Causative agents

20. Culture
• Isolating causative organism
• For Bacteria
• Blood Culture
– Enteric fever and brucellosis
– 5ml blood  50 ml of glucose broth  incubate at 370C for 24 hrs 
S/c on Blood agar and MacConkey agar

21. • Urine Culture
• Sputum culture
• Pus culture
• For fungal infections
– SDA or BHI agar
– LPCB
• For Viral infections
– Culture

22. Serology
• Widal test  Enteric fever
• Standard agglutination test (SAT)  Brucellosis
• Cold agglutination test Mycoplasma infections
• Microscopic agglutination test Leptospirosis
• Microimmunofluroscence test Chlamydial infections
• Paul-Bunnel test  Infectious mononucleosis (EBV infection)
• ELISA

23. • Molecular methods
– PCR
• Other tests for Diagnosis
– CBC ()
– ESR (infection)
– Radiological methods (X-ray TB, CT & MRITumors)
– Histopathology (TB and neoplasm)
– ECG and Echocardiography (rheumatic fever and Infective endocarditis)

24. Thank You