Typhoid fever is caused by the bacterium Salmonella typhi. A related illness is caused by a close cousin, Salmonella paratyphi. Spread occurs via contaminated food and water, often in areas with poor sanitation and hygiene. Typhoid fever is characterized by high fever, generalized weakness, abdominal pain, and severe headache. Left untreated, the infection can lead to complications such as intestinal perforation and even death. Treatment involves antibiotics. Prevention focuses on good hygiene practices, food safety, screening and identifying carriers especially among food handlers, and, in some cases, vaccination.
In Southeast Asia, Typhoid poses several challenges. Diagnosis requires astute and experienced clinicians. Confirmatory tests such as blood cultures, stool cultures and bone marrow culture are rarely available except for select cities with bustling healthcare hubs. The majority of healthcare providers are expected to make a diagnosis based on clinical suspicion and a few basic lab tests.
If you are living in or traveling through Southeast Asia, chances are a doctor has ordered a Widal test for you when you’ve had a fever.
The Widal test is a serological test used to diagnose typhoid fever and other salmonella infections. It detects antibodies in the blood that are produced as a response to the Salmonella type and paratyphi bacterial antigens. The test works by mixing the patient's blood (specifically, the serum) with these specific bacterial antigens. If the antibodies in the serum react with the antigens, the curdling, or agglutination, indicates a positive result, suggesting a current or past infection with Salmonella typhi or Salmonella paratyphi.
The Widal Test has been around for over 100 years, is widely available, and is relatively inexpensive. So what’s the problem?
False positives can occur due to previous infections, vaccinations, unrelated infections and a host of other factors. When we analyze the performance of the Widal test, we see it has average specificity, very good negative predictive value, and very poor positive predictive value for the diagnosis of Typhoid fever. In lay terms: If it lights up positive, it may or may not be Typhoid/Paratyphoid fever. In fact, it may have nothing to do with an infection at all. However, if the test is negative, it can be helpful in excluding Typhoid/Paratyphoid fever.
The problem is, most doctors (and patients), when faced with illness with fever and a positive Widal test, will want antibiotics to ‘cure the Typhoid’, when in fact it may not be Typhoid at all. That’s Mistake Number One.
Mistake Number Two happens when the real reason behind the illness and fever remains undiagnosed. In fact, about 1 in 7 patients with malaria were found to have a positive Widal test - not because they were so unlucky to have concurrent Typhoid fever, but because the Widal test was confused and spat out a false positive result. So, Mistake Number One would be assuming an illness in Typhoid when it is not; Mistake Number Two - potentially far more serious - occurs when we stop looking for the real underlying infection, which will go unchecked and untreated, with potentially fatal consequences.
It is absolutely imperative that clinicians use the Widal test one piece of supportive data, in addition to clinical data based on the patient’s story, symptoms and signs. The diagnosis of Typhoid (or Paratyphoid) should never be made solely on the basis of a positive Widal test - an unfortunate reality that happens far too often in Southeast Asia, leading to the Conundrum of Double Errors. If at all, the Widal test is better suited to exclude Typhoid/Paratyphoid, than to diagnose it.
The next time you fall ill with a strange febrile illness and someone waves a positive Widal test in your face, talk to your friendly neighborhood Infectious Diseases and Tropical Medicine expert.