Widal test Clouding India’s Sense of its Typhoid Fever Problem

Context

The usage of the Widal test has declined in many countries due to inherent flaws. However, the widespread use of the test in India highlights its limitations.

Typhoid Fever 

Typhoid fever is also called enteric fever, is a bacterial infection that can spread throughout the body, affecting many organs.

• Spread: Typhoid spreads through contaminated food and water and is caused by Salmonella typhiand which is related to the bacteria that cause salmonella food poisoning.
• Symptoms: 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.
• Typhoid Disease Burden: If left untreated, typhoid can be life-threatening. As per the World Health Organisation, 90 lakh people are diagnosed worldwide with typhoid every year and 1.1 lakh die of it. 
  • A 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.

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Diagnosis of Typhoid Fever

• In addition to a detailed medical history and a thorough examination, the process includes isolating 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.
• Concerns with Culture Tests: Cultures are time-consuming and skill- and resource-intensive.  Prior antibiotic treatment can also affect the results of cultures.
• PCR Based Methods: Some PCR-based molecular methods are known to be better but are limited by cost, the need for specialized infrastructure and skilled personnel  and the inability to retrieve live bacteria for further tests.

Widal Test

Clinicians in India widely use the Widal test for diagnosing typhoid across both public and private healthcare sectors.

• Antibodies detection: Similar to other infections, our immune system generates antibodies in response to the bacteria responsible for enteric fever. 
  • The Widal test rapidly detects and quantifies these antibodies. It serves as a point-of-care test and does not require specialized skills or infrastructure. 

Concerns Related to the Widal Test

• Ineffectiveness of Single Diagnosis: A positive result from a single Widal test does not definitively indicate the presence of a typhoid infection, and conversely, a negative result does not confirm the absence of the disease.
  • To diagnose an active infection accurately, clinicians need to test at least two serum samples collected at intervals of 7-14 days. However, obtaining two samples is often impractical and time-intensive.
• Standardization of Widal Test Cut-off Values: In areas with high and continuous typhoid burden, certain level of antibodies against the bacteria may already be present in the blood. 
  • Interpreting the test accurately is not feasible without knowledge of the baseline cut-off. 
  • Additionally, various manufacturers of the test specify different cut-off values in their kit’s user manuals, further complicating interpretation.
• Impact of Reagents: 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 positive results. 
  • Prior antibiotic treatment 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.

Consequences of the Test’s Use

• Challenges in Determining Typhoid Prevalence in India: Due to the inaccuracy of the results, the true prevalence of typhoid in India remains unclear. 
  • Insufficient awareness regarding the optimal timing for blood sample collection, coupled with a lack of standardization of kits and inadequate quality control, exacerbates the issue.
• Economic Burden on patients: A single test costs a couple hundred rupees. 
  • Patients in many states 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.
• Irrational Use of Antibiotics: It is a major cause of antimicrobial resistance (AMR). Bacteria have been known to be able to transmit AMR between strains and species, and they are not limited by geographical borders. 
  • Thus, 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 make it more and more difficult to control this preventable disease.

Way Forward

• Adoption of Best-Practice Strategies: Better point-of-care tests need to be discovered that can replace the Widal test. 
  • Until they’re available, clinicians can use best-practice strategies 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: Doing a blood or bone marrow culture is often not feasible as it requires laboratory infrastructure lacking in most parts of the country. 
  • 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.

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• Improved Surveillance: To effectively combat AMR attributed to the overutilization of the Widal test, improved surveillance measures are imperative. 
  • As per the latest report of Indian Council for Medical Research from 2021, the number of samples tested to determine susceptibility varied widely, ranging from one in the ‘East’ region to 126 samples in the ‘North’.
  • Given that typhoid also has symptom-free carriers, constant environmental vigilance and data-sharing are crucial.

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