# Pyrexia of Unknown Origin Infectious Causes

> Pyrexia of unknown origin from infections for NEET-PG Microbiology, covering PUO criteria, infective causes seen in India and a stepwise diagnostic work-up.

- Canonical URL: https://prepelephant.com/topics/neet-pg/microbiology/pyrexia-of-unknown-origin-infectious-causes
- Exam / course: NEET-PG · Subject: Microbiology
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-15
- Last updated: 2026-10-15
- Reference basis: Harrison's Principles of Internal Medicine; Ananthanarayan and Paniker's Textbook of Microbiology; ICMR Standard Treatment Workflows
- How to cite: "Pyrexia of Unknown Origin Infectious Causes", PrepElephant, https://prepelephant.com/topics/neet-pg/microbiology/pyrexia-of-unknown-origin-infectious-causes

## Direct answer

Pyrexia of unknown origin (PUO) is a fever exceeding 38.3°C lasting more than three weeks, with no diagnosis after a week of in-hospital investigation. In India, infections form the largest group of causes in most series, with tuberculosis, enteric fever, brucellosis, abscesses, infective endocarditis and visceral leishmaniasis the usual suspects. Work-up succeeds by targeting the likeliest infection from history and examination, not by ordering every test at once.

## What you must remember

- **Classic definition:** temperature exceeding 38.3°C on several occasions, persisting beyond three weeks, with no cause found after one week of inpatient investigation, as set out by Petersdorf and Beeson.
- **Four categories:** classic, nosocomial, neutropenic and HIV-associated PUO; the category decides which causes to pursue first.
- **Commonest group:** infections lead in classic PUO series from India, with tuberculosis (including abdominal disease) and abscesses among the top causes.
- **Mantoux caveat:** a positive tuberculin test reflects BCG or past infection and cannot prove active disease on its own; a negative result does not exclude it.
- **Brucellosis clue:** raw milk, animal contact and undulant fever with arthralgia or sacroiliitis; blood culture needs extended incubation, and agglutination or ELISA serology confirms it.
- **Endocarditis clue:** fever with a new or changing murmur, splinter haemorrhages, Janeway lesions or Osler nodes; blood cultures come before antibiotics, then echocardiography and Duke criteria.
- **Visceral leishmaniasis:** prolonged fever with splenomegaly, pancytopenia and hypergammaglobulinaemia in endemic belts; the rK39 rapid test screens, and Leishman-Donovan bodies on splenic or marrow aspirate confirm.
- **HIV in every PUO:** test with counselling and consent under NACO protocols, because HIV-associated opportunistic infection reshapes the whole differential.

## A stepwise work-up from history to targeted tests

The sequence starts with cheap, high-yield steps and keeps invasive sampling for the end. Each step should either exclude a major category or point to one specific test.

1. **Exposure history:** ask about travel, rural or forest stays, rodents, farm animals, raw milk, floodwater, insect bites, occupation and sexual or injecting-drug history, because each maps onto particular organisms.
2. **Focused examination:** search for an eschar, rash, lymphadenopathy, splenomegaly, a new murmur, jaundice, joint swelling and neurological signs, since each finding narrows the list sharply.
3. **Screening panel:** send a CBC with peripheral smear, a malaria smear or rapid test, blood cultures drawn before antibiotics, urine culture, liver and renal function tests and a chest radiograph.
4. **Targeted tests:** order by the working diagnosis, such as bone marrow culture for enteric fever because serology is unreliable, IgM ELISA for scrub typhus and the microscopic agglutination test for leptospirosis.
5. **Imaging and sampling:** use contrast CT of the abdomen and chest for occult abscess or nodes, echocardiography for valve disease, and image-guided biopsy of liver, spleen or lymph node when non-invasive tests fail.
6. **Restrained empiric therapy:** avoid broad antibiotics unless the patient is unstable, because they lower culture yield and blur the diagnosis.
7. **Reassessment on a fixed date:** re-examine at a set review and repeat tests if the picture changes.

## Where the exam tries to catch you

Most PUO questions turn on the exact definition and on the test that is truly diagnostic.

- **Trap:** calling any fever lasting over three weeks PUO — **Correct:** the classic definition also requires a week of inpatient investigation with no diagnosis, so an outpatient fever is not PUO by definition.
- **Trap:** treating a positive Mantoux as proof of active tuberculosis — **Correct:** BCG and past exposure both cause positivity, so active disease needs culture, GeneXpert or histology.
- **Trap:** accepting a negative Widal as excluding enteric fever — **Correct:** Widal is nonspecific and often unreliable, so blood or bone marrow culture decides the diagnosis.

## Frequently asked questions

### What temperature defines pyrexia of unknown origin?
Pyrexia of unknown origin is classically defined as a temperature exceeding 38.3°C on several occasions. The fever must persist for more than three weeks, with no diagnosis after one week of in-hospital investigation.

### Which infections top the list of causes of pyrexia of unknown origin in India?
Tuberculosis, including extrapulmonary and abdominal forms, is among the leading causes of pyrexia of unknown origin in Indian series. Enteric fever, abscesses and infective endocarditis also feature prominently, while brucellosis is a recognised but less frequent cause.

### Why is blood culture important in the work-up of pyrexia of unknown origin?
Blood culture detects bacteraemia, fungaemia and enteric fever, and it yields most when drawn before antibiotics. Slow-growing organisms such as Brucella need extended incubation, so the request should say so.

### How does infective endocarditis present as pyrexia of unknown origin?
Infective endocarditis can cause fever with no obvious murmur, particularly in intravenous drug users or patients with prosthetic valves. Serial blood cultures and echocardiography, read against Duke criteria, settle the diagnosis.

### Which rapid test helps in visceral leishmaniasis in endemic areas?
The rK39 rapid diagnostic test detects antibodies against a recombinant antigen and is widely used in the kala-azar belts of India. Leishman-Donovan bodies on splenic or bone marrow aspirate remain the confirmatory reference.