1. Pyrexia of Unknown Origin
-M.Sathish Kumar

3. 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.

5. 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.

7. Causes for PUO
• M – Metabolic/ Miscellanous
• I - Infectious
• D – Degenerative, Drugs
• N - Neoplastic
• I – Inflammatory
• G – Genetic, Granulomatous
• H - Hematopoietic
• T - Trauma

8. 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

9. 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!)

11. 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!!

12. Approach to a Patient with PUO
• Detailed History Taking
• Complete Physical Examination
• Lab Investigations

13. 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

14. 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

15. 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.

16. BLOOD
CBC
ESR
Microscopy
Culture
Serology

17. Blood
Microscopy:
-Thin smear
-Thick smear

18. Malaria

19. Amastigotes - Leishmaniasis

20. Trypomastigotes - Trypanosomiasis

21. Microfilaria - Filariasis

22. Blood Culture
Sterile Vial containers (30 ml): Used for
collecting Blood

23. 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.

24. Blood Agar MacConkey Agar
Blood agar and MacConkey agar are
incubated at 37ºC for 24 hours

25. 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.

26. Chlamydia – McCoy cell culture

27. 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.

28. 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.

29. 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.

30. • 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

31. S.Hematobium in centrifuged urine

32. 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

33. 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

34. Ziehl Neelsen Stain – Acid fast bacilli

35. 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.

36. P.westermani in sputum

37. • ZN staining is also used for determining the
presence of Cryptosporidium and Isospora,
which cause diarrhoea in AIDS.

38. 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.

39. 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)

40. 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.

41. 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.

42. 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

43. Naeglaria in CSF

44. Serology
• Useful in:
– Infectious mononucleosis- Paul-Bunnell
test
– Enteric fever – Widal Test
– Hepatitis A, B infections - ELISA
– CMV infections - ELISA

45. Immunologic Tests
LE cell phenomenon
Antinuclear antibody test
SLE

46. Other Tests
1.Skin tests
2.Biopsy
3.Liver Function, Kidney
Function tests etc.

47. 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

48. The induration (raised area) is what is
measured.
NOT the erythema (red area

49. Biopsy
• Biopsy of the organs like lung, liver, GI and
urinary tract can be done based on the
symptoms pertaining to the organ system.

50. A NEW TYPE OF FEVER IS SAID TO BE SPREADING
RAPIDLY FOR THE PAST TWO WEEKS!
CAN U GUESS?