Use of the Widal test is leading to misdiagnosis, say these authors

Nepal has been facing a harsh second wave of covid-19 since April 2021. Hospitals have already been overwhelmed with covid-19 patients. As a result, most febrile patients who do not have shortness of breath or desaturation have been advised not to visit hospitals. There is no easy access to the SARS-CoV-2 polymerase chain reaction tests (PCR) to confirm whether patients have covid-19. In any case, many people do not want a PCR test for fear of being isolated and stigmatized if they are positive. As a result many febrile patients with mild symptoms opt to visit local health clinics where they get basic laboratory tests done, which includes a Widal test to rule out the ubiquitous typhoid fever. [1]

The Widal test is an old, cheap, but unreliable serological test used for typhoid fever. It is available at many health centres in Nepal. In typhoid endemic areas, this test yields many false positive results leading to misdiagnosis of typhoid fever. [2] Yet there is widespread use of Widal test in Nepal (and other areas in the world of typhoid fever endemicity) for febrile patients. Health workers in Nepal consider this test confirmatory, and patients demand that this well-known test is done to rule out typhoid fever. The use of this test has escalated during the covid-19 pandemic with an increase in the number of febrile patients presenting at local healthcare clinics. The concern is that this is giving people a false confirmatory diagnosis of typhoid fever in suspected covid-19 patients, particularly in those who present with undifferentiated fever and gastrointestinal symptoms.

This misdiagnosis has led to the inappropriate use of antibiotics, such as cephalosporins and azithromycin, which increase the risk of antimicrobial resistance. The lack of early correct diagnosis also delays the initiation of appropriate treatment for covid-19 such as dexamethasone in the event of deterioration with increased oxygen requirement. The resulting development of complications with increased mortality has been reported in some parts of Nepal recently. [1] Furthermore, the false diagnosis of typhoid fever means patients do not self isolate, and therefore risk spreading covid-19 to others. In a pandemic like covid-19, early detection of cases and prompt isolation is of the utmost importance to break the transmission chain.

The use of the Widal test for febrile illnesses in Nepal has previously led to under recognition of other typhoid-like illnesses such as murine and scrub typhus. This resulted in increased mortality during the large earthquake of April 2015 in Nepal possibly because people and rodents (which carry mites with the infective microbe in scrub typhus) lived in close proximity in temporary shelters after the earthquake. [3] The subsequent call discouraging the use of the Widal test has clearly not been heard and the consequences of misdiagnosis are being seen again in the current covid-19 pandemic. Although this problem is anecdotally being reported in Nepal, because of the rampant use of this test, there is every likelihood that similar stories are being played out in many parts of the Indian Subcontinent where the incidence of typhoid is 500 per 100,000 population. [4]

We call for healthcare workers to avoid using this unreliable test, and for policy makers to phase out the test from the country. Unfortunately, other available rapid diagnostic tests for typhoid also lack sufficient diagnostic accuracy to be recommended in place of the Widal test. [5] Reliable point-of-care and accurate diagnostic tests for febrile illnesses like typhoid are urgently needed. [6]

Sudeep Adhikari, Department of Internal Medicine, Pyuthan Hospital, Pyuthan, Nepal.

Buddha Basnyat, Oxford University Clinical Research Unit, Patan Hospital, Kathmandu, Nepal, and Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford.

Christopher M Parry, Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, and Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University. 

Abhilasha Karkey, Oxford University Clinical Research Unit, Patan Hospital, Kathmandu, Nepal, and Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University.

Competing interests: none declared.

References:

1. Yadav B. 11 Covid–19 suspects died in a rural municipality in 10 days. The Kathmandu Post. 2021 May 13; [online] Available at: <https://kathmandupost.com/province-no-2/2021/05/13/as-many-as-11-covid-19-suspects-died-in-jagarnathpur-in-past-10-days> [Accessed 24 May 2021]. 
2. Olopoenia LA, King AL. Widal agglutination test− 100 years later: still plagued by controversy. Postgraduate Medical Journal. 2000 Feb 1;76(892):80–4.
3. Basnyat B. Typhoid versus typhus fever in post-earthquake Nepal. The Lancet Global Health. 2016 Aug 1;4(8):e516–7.
4. Basnyat B, Qamar FN, Rupali P, Ahmed T, Parry CM. Enteric fever. BMJ. 2021;372:n437.
5. Wijedoru L, Mallett S, Parry CM. Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever. Cochrane Database of Systematic Reviews. 2017(5).
6. Mather RG, Hopkins H, Parry CM, Dittrich S. Redefining typhoid diagnosis: what would an improved test need to look like?. BMJ Global Health. 2019 Oct 1;4(5):e001831.