Q: My 63 years old mother is suffering from fever for the last two months. We have consulted three different doctors but her condition is not improving. Her temperature remains between 99 and 100 degrees Fahrenheit. Her widal is positive and the TO is 1:160 and TH is 1:160; AH and BH is up to 1:40 and all other tests are in normal range like LFT, RFT, Lipid profile, T3, T4, TSH. Her ESR is 57 mm. What should we do?

A:There are several causes of fever of unknown aetiology (also known as pyrexia of unknown origin or PUO). These could be classified as infective, inflammatory, malignant causes. Among the infective causes of PUO typhoid is a possibility, especially in endemic countries such as India. However, Widal test [which is a bacterial agglutination test which utilises the somatic (O) antigen of Salmonella typhi and flagellar (H) antigens of Salmonella typhi and Salmonella paratyphi A and B] on its own cannot be relied upon for a sensitive or specific diagnosis of typhoid or enteric fever.

The value of a single serology result from Widal test is extremely limited, as the test can often be falsely positive due to serological cross reactivity due to infection with related non-typhoidal Salmonella species of bacteria, or even because of unrelated infections (such as malaria, dengue, tuberculosis, brucellosis) or non-infective clinical conditions (chronic liver diseases) and vaccinations (especially previous typhoid vaccination). It is difficult to know the baseline Widal sero-reactivity of individuals living in areas where typhoid/paratyphoid fever is common, therefore interpretation based on the result of a single test is often not possible. A paired serology based on an acute and a convalescent sample taken 2-3 weeks apart is more helpful, and a 4 fold rise in titre has some diagnostic value.

Although typhoid is a possibility your mother may have any of the conditions that give rise to fever of unknown origin. It was useful to know that the liver, renal, thyroid functions along with lipid profile have been checked and reported to be normal. The rise in ESR may indicate infection, but is not a specific marker of infective process, and could be affected by inflammatory conditions as well. ESR is more useful to monitor disease activity, rather than to diagnose a disease. I suggest you consult an experienced physician who will help you to reach a diagnosis with more sensitive and specific tests. The definitive diagnosis of typhoid is reliant on the isolation of the causative bacterium by microbiological culture from blood, stool or other body fluids.

Reference: Postgrad Med J 2000;76:80–84