Pyrexia of Unknown Origin
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This document discusses fever of unknown origin (FUO). It defines FUO as a fever over 38.3°C for more than 3 weeks without a diagnosis after tests. The definition has changed over time but now includes comprehensive history, exams, and obligatory initial tests like blood tests and cultures. Potential causes of FUO are discussed, including infections by bacteria, viruses, parasites and fungi, as well as non-infectious inflammatory disorders and cancers. Diagnostic tests for FUO include blood and other specimen cultures, microscopy of samples, staining techniques like Gram staining and Ziehl-Neelsen staining, and serological tests. Molecular methods like PCR may also be used in diagnosis.
Pyrexia of Unknown Origin
- 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
- 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 & MRITumors) – Histopathology (TB and neoplasm) – ECG and Echocardiography (rheumatic fever and Infective endocarditis)
- 24. Thank You