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Pyrexia of Unknown Origin


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A basic idea about PUO from a Microbiology point of view. It does have some slides taken from Slideshare itself :)

Published in: Health & Medicine
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Pyrexia of Unknown Origin

  1. 1. Pyrexia of Unknown Origin -M.Sathish Kumar
  2. 2. Fever • Fever is an elevation of the body temperature that exceeds the normal variation and occurs in conjunction with an increase in temperature in the hypothalamic set point. • This is different from Hyperpyrexia, which is an uncontrolled increase in body temperature that exceeds the capacity of the body to lose heat, with the hypothalamic set point being unchanged.
  3. 3. Pyrexia of Unknown Origin • Pyrexia of unknown origin (PUO) was defined by Petersdorf and Beeson in 1961 as • temperatures higher than 38.3°C on several occasions, • a duration of fever of more than 3 weeks, • failure to reach a diagnosis despite 1 week of in- patient investigation.
  4. 4. Causes for PUO • M – Metabolic/ Miscellanous • I - Infectious • D – Degenerative, Drugs • N - Neoplastic • I – Inflammatory • G – Genetic, Granulomatous • H - Hematopoietic • T - Trauma
  5. 5. Infectious Causes Bacteria : 1. M.tuberculosis 2. Salmonella species 3. Brucella 4. Chlamydia psittaci 5. Leptospira 6. Rickettsia 7. Coxiella burnetti 8. Mycoplasma 9. Atypical Mycobacteria Viruses: 1. CMV 2. EBV 3. Arboviruses 4. Enteroviruses 5. HIV Fungi: 1. Candida albicans 2. Cryptococcus neoformans 3. Histoplasma capsulatum 4. Aspergillus spp. 5. Coccidioides immitis 6. Pneumocystis jiroveci Parasites: 1. Plasmodium – Malaria 2. Leishmania 3. Trypanosoma 4. Toxoplasma 5. Wuchereria bancrofti 6. Babesia microti
  6. 6. Other Causes Neoplasms: 1) Lymphoma 2) Leukemia 3) Myeloma 4) Colon cancer 5) Renal cancer 6) Liver Cancer Genetic: 1) Fabry Disease 2) Familial Mediterranean Fever Trauma due to any procedures: 1) Dental abscess 2) Pelvic abscess or Abdominal abscess Inflammatory: 1) Juvenile Rheumatoid Arthritis 2) SLE 3) Polyarteritis Nodosa 4) Temporal Arteritis 5) Inflammatory Bowel Disease 6) Sarcoidosis Drugs: 1) Erythromycin 2) Isoniazid 3) Penicillin 4) Atropine 5) Captopril 6) Methyldopa 7) Hydralazine Miscellanous: 1) Factitious fever (Munchausen syndrome!)
  7. 7. Just Diagnosed a patient with PUO. What’s the treatment? Considering there are about 200 causes for PUO, you can always use the Trial and Error method!!
  8. 8. Approach to a Patient with PUO • Detailed History Taking • Complete Physical Examination • Lab Investigations
  9. 9. History Taking 1. Duration and pattern of fever 2. Age of patient 3. Sexual history 4. Contact with other ill people 5. Vaccination history 6. Travel history 7. Animal / insect exposure 8. Previous treatment including blood products
  10. 10. Lab Investigations Specimen Collection 1) Blood 2) Urine 3) Sputum 4) Pus 5) Feces,CSF and other specimens Microscopy Culture Serology Other Tests X-Ray, CT Skin Test Biopsy
  11. 11. Specimen Collection • Collection – All the specimens should be collected preferably prior to antibiotic therapy. – These specimens are to be collected in a sterile containers under aseptic conditions – Blood is collected in blood culture bottles for culture and in a sterile vial for serology.
  12. 12. BLOOD CBC ESR Microscopy Culture Serology
  13. 13. Blood Microscopy: -Thin smear -Thick smear
  14. 14. Malaria
  15. 15. Amastigotes - Leishmaniasis
  16. 16. Trypomastigotes - Trypanosomiasis
  17. 17. Microfilaria - Filariasis
  18. 18. Blood Culture Sterile Vial containers (30 ml): Used for collecting Blood
  19. 19. BLOOD CULTURE: Procedure: – Take 5 ml of blood in each bottle of 50 ml of glucose broth + 50 ml taurocholate broth – Incubate these broths at 37ºC for 24 hours – Subcultures are made on Blood agar from (glucose broth) and MacConkey agar (from taurocholate broth). – For infective endocarditis, 3 samples in a 24 hr period are collected.
  20. 20. Blood Agar MacConkey Agar Blood agar and MacConkey agar are incubated at 37ºC for 24 hours
  21. 21. Blood Culture • Multiple blood samples (no fewer than three and rarely more than six, including samples for anaerobic culture) should be cultured in the laboratory for at least 2 weeks to ensure that any HACEK group organisms that may be present have time to grow .Chlamydia psittaci and Coxiella can cause culture – negative Endocarditis. – Streptococcus viridans, HACEK group organisms are normally implicated in endocarditis.
  22. 22. Chlamydia – McCoy cell culture
  23. 23. Blood Culture • Lysis-centrifugation blood culture techniques should be employed in cases where prior antimicrobial therapy or fungal or atypical mycobacterial infection is suspected. • Blood culture media should be supplemented with L-cysteine or pyridoxal to assist in the isolation of nutritionally variant streptococci. • It should be noted that sequential cultures positive for multiple organisms may reflect self- injection of contaminated substances.
  24. 24. Urine • Urinary Tract infections constitute some of the major Nosocomial infections. This is more common in women, and could be due to any congenital defects or due to catheterisation.
  25. 25. Urine Culture • A calibrated volume of midstream urine specimen is inoculated on: – blood agar – MacConkey agar •Incubated at 37ºC for 24 hours *In renal tuberculosis, culture should be performed in Lowenstein Jensen medium* Urine cultures, including cultures for mycobacteria, fungi, and CMV, are indicated.
  26. 26. • Bacteria usually cause most of the Urinary tract infections. Apart from these, unusual causes that have to be suspected are: • Adenovirus • Candida albicans • Parasites: -T.vaginalis -S.hematobium -E.vermicularis
  27. 27. S.Hematobium in centrifuged urine
  28. 28. Sputum Culture •Sputum is inoculated on blood agar and MacConkey agar plate •Incubated at 37 C for 24 hours •In case of TB, specimen is cultured in LJ medium
  29. 29. Specimens Specimens to be collected: • pulmonary secretions: sputum, bronchioscopic aspirations • A series of early morning sputum specimens are to be collected over a 3 day period. • ideal amount for mycobacterium= 5-10 mL of sputum
  30. 30. Ziehl Neelsen Stain – Acid fast bacilli
  31. 31. PUO involving the respiratory tract • Respiratory infections which are difficult to diagnose are those which are caused by: • Bacteria – M.tuberculosis, Klebsiella, Mycoplasma • Fungi – Histoplasma, Blastomyces, C.immitis • Parasites – P.westermani, A.lumbricoides, A.duodenale.
  32. 32. P.westermani in sputum
  33. 33. • ZN staining is also used for determining the presence of Cryptosporidium and Isospora, which cause diarrhoea in AIDS.
  34. 34. CSF Collection The patient lies on his or her side, with knees pulled up toward the chest, and chin tucked downward. After the back is cleaned, local anesthetic will be injected into the lower spine. A spinal needle is inserted, usually into the lower back area at the level of L3 and L4 Once the needle is properly positioned, CSF pressure is measured and a sample is collected. The needle is removed, the area is cleaned, and a bandage is placed over the needle site. The person is often asked to lie down for a short time after the test.
  35. 35. CSF Collection and Distribution Tube 1 Cell count Tube 2 Stat gram stain and culture Tube 3 Glucose and protein Tube 4 Cell count Tube 5 (optional) Virology, mycology and cytology cerebrospinal fluid can be tested for: •Herpes virus, with use of the polymerase chain reaction (PCR) to amplify and detect viral nucleic acid •recurrent fevers with lymphocytic meningitis (Mollaret's meningitis)
  36. 36. Bacterial and viral meningitis viral infections that can lead to meningitis include mumps, herpesvirus (such as Epstein-Barr virus, herpes simplex viruses, and varicella-zoster virus—the cause of chickenpox and shingles), measles, and influenza.
  37. 37. CSF Naked eye Turbidity Microscopy Gram Stain ZN stain India Ink Wet Mount Culture Chocolate agar, Blood agar,LJ medium. For viruses, Tissue culture, animal inoculation etc.
  38. 38. Meningitis-Causes Viruses : 1.Enteroviruses ( Polio, ECHO, Cox sackie) 2. Paramyxoviruses 3. Herpes viruses 4.Arboviruses Fungi: 1.Cryptococcus neoformans 2.Aspergillus 3.Histoplasma and Coccidioides Parasites: 1.Naeglaria fowleri 2.Acanthameba Bacteria Neonates and Infants Group B streptococci E.Coli H.Influenza Listeria monocytogenes Children 1.H.influenza 2.N.meningitis Adults 1.S.pneumoniae 2.N.meningitis
  39. 39. Naeglaria in CSF
  40. 40. Serology • Useful in: – Infectious mononucleosis- Paul-Bunnell test – Enteric fever – Widal Test – Hepatitis A, B infections - ELISA – CMV infections - ELISA
  41. 41. Immunologic Tests LE cell phenomenon Antinuclear antibody test SLE
  42. 42. Other Tests 1.Skin tests 2.Biopsy 3.Liver Function, Kidney Function tests etc.
  43. 43. Mantoux Skin Test using a needle and syringe to inject 0.1 ml of 5 tuberculin units of liquid tuberculin between the layers of the skin (intradermally), usually on the forearm
  44. 44. The induration (raised area) is what is measured. NOT the erythema (red area
  45. 45. Biopsy • Biopsy of the organs like lung, liver, GI and urinary tract can be done based on the symptoms pertaining to the organ system.