More often than not, the experience for patients with a fever is to get tested and treated for a typhoid infection. The test is a rapid blood test called the Widal test. The subsequent treatment usually consists of tablets, typically in urban areas, or injections in rural ones.
Typhoid spreads through contaminated food and water and is caused by Salmonella typhi and other related bacteria. Also known as enteric fever, it presents with a high fever, stomach pain, weakness, and other symptoms like nausea, vomiting, diarrhoea or constipation, and a rash. Some people, called carriers, may remain symptom-free and shed the bacteria in their stool for several months to years.
These symptoms mimic those of malaria, dengue, influenza, and typhus, to name a few, each with different treatment modalities. If left untreated, typhoid can be life-threatening. Per the World Health Organisation, 90 lakh people are diagnosed worldwide with typhoid every year and 1.1 lakh die of it. A small 2023 study reported the burden to be 576-1173 cases per 100,000 child-years (one child year is one child being followed up for one year) in urban areas and 35 per 100,000 child years in rural Pune.
How is typhoid fever diagnosed?
The gold standard for diagnosing typhoid — in addition to a detailed medical history and a thorough examination — is to isolate the bacteria from a patient’s blood or bone marrow and grow them in the lab. Stool and urine samples can also yield the same but with lower sensitivity.
However, performing culture tests in smaller clinical settings presents practical problems. Cultures are time-consuming and skill- and resource-intensive. Prior antibiotic treatment can also affect the results of cultures — a common issue due to the indiscriminate use of antibiotics in India. Some PCR-based molecular methods are known to be better but are limited by cost; the need for specialised infrastructure and skilled personnel; and the inability to retrieve live bacteria for further tests.
Against this backdrop, in India, clinicians use the Widal test extensively to diagnose typhoid in both public and private sectors.
As with other infections, our immune system produces antibodies in the blood against the bacteria, causing enteric fever. The Widal test rapidly detects and quantifies these antibodies. It’s a point-of-care test and doesn’t need special skills or infrastructure. Developed in the late 1800s by a French physician, it is no longer used in many countries because of its flaws — flaws that are rendered by the scale of the test’s use in India to be abusive.
Why is the Widal test inappropriate?
A single positive Widal test report doesn’t necessarily mean a typhoid infection is present, and a negative report doesn’t confirm the disease’s absence. To diagnose an active infection, clinicians must test at least two serum samples taken at least 7-14 days apart, so that they may detect a change in concentrations of the antibodies. But getting two samples is rarely feasible and time-consuming.
Second, in areas with high and continuous typhoid burden, certain levels of antibodies against the bacteria may already be present in the blood. Without knowing the baseline cut-off, it isn’t possible to correctly interpret the test. A related issue is that different manufacturers of the test specify different cut-off values in their kits’ user manuals.
Third, the reagents used in the Widal test to reveal the presence of various antibodies can cross-react with antibodies produced against infections by other bacteria, viruses or parasites, or even in typhoid-vaccinated individuals, leading to false positives. Prior antibiotic therapy can also affect antibody levels and yield a false negative.
Correct diagnosis and appropriate treatment of enteric fever are important because serious complications, like severe intestinal bleeding or perforation, can develop within a few weeks if the disease is mismanaged. False negatives can thus delay diagnosis and lead to fatal outcomes.
What are the consequences of the test’s use?
Because of the Widal test’s propensity for erroneous results, the actual burden of typhoid in India remains obfuscated. A lack of awareness of the proper time at which to collect a blood sample, along with a lack of standardisation of kits and poor quality-control compound the problem.
Further, a single test costs a couple hundred rupees. Patients in many States have also reported being charged Rs 500 to Rs 4,000 per dose of antibiotic injections by local healthcare providers following a typhoid diagnosis based on a single Widal test. Patients in both urban and rural areas have reported selling assets to receive these antibiotics.
The irrational use of antibiotics is a major cause of antimicrobial resistance (AMR). Bacteria have also been known to be able to transmit AMR between strains and species, and they are not limited by geographical borders. This is why the threat of AMR in one country represents the threat of AMR everywhere. Some strains of Salmonella are also resistant to multiple drugs. Continued irrational use of the Widal test, which facilitates unnecessary use of antibiotics, will therefore only make it more and more difficult to control this preventable disease while adding to the financial woes of the patients already suffering.
What do we need instead of the Widal test?
We need to discover better point-of-care tests that can replace the Widal test. And until they’re available, clinicians can consider using best-practice heuristics that provide a rational diagnosis and subsequent treatment options based on the regional data of effective antibiotics available against the bacteria.
These options should be coupled with ensuring adequate and safe food and water and functional sanitation to address the disease’s root cause.
Improving access to better diagnostic tests could also address this problem. Doing a blood or bone marrow culture is often not feasible as it requires laboratory infrastructure that most parts of the country lack. Healthcare workers can instead benefit from a ‘hub and spoke’ model, with sample collection sites at the periphery and district hospitals and medical colleges as the hubs that process samples. The latter facilities could also serve as research centres that generate regional prevalence and susceptibility data.
Next, we need better surveillance to stay on top of the AMR caused by the overuse of the Widal test. The Indian Council for Medical Research publishes an annual report highlighting the typhoid bacteria’s resistance patterns. As per the last report, in 2021, the number of samples tested to report susceptibility ranged from one from the ‘East’ region to 126 samples from the ‘North’.
Finally, as typhoid also has symptom-free carriers, constant environmental vigilance and data-sharing are imperative.
Dr. Vasundhara Rangaswamy is a microbiologist and a rural physician. Dr. Parth Sharma is a public health physician, writer, and researcher.
