Cross-Reactivity of Rapid Salmonella Typhi IgM Immunoassay in Dengue Fever Without Co-Existing Infection

Abstract

Introduction: Dengue fever is endemic in developing nations worldwide with as many as 500,000 annual cases of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). A prompt and accurate diagnosis early in the disease course is essential for prompt identification and treatment of severe complications of the dengue virus infection (DVI). We identified cross-reactivity of a rapid IgM test for typhoid fever in patients with febrile illnesses that were determined to be due to dengue virus.Methods: All patients with documented DVI during a recent epidemic in Pakistan also underwent diagnostic testing for Salmonella enterica serovar Typhi. The diagnosis of DVI was made based on clinical findings and the positive results for dengue non-structural protein 1 antigen (NS1Ag) and/or dengue IgM antibody (anti-D IgM) during the acute phase of febrile illness. Patients with positive test results for Salmonella typhi (S. Typhi) IgM also had their blood cultures done.Results: In the group of 322 patients with clinical and serological evidence of DVI, 107 also tested positive for S. Typhi IgM. Blood cultures were negative for S. Typhi bacteria in all patients. Principal disease features included fever, headache, myalgia, retro-orbital pain, and a rash accompanied by thrombocytopenia and leukopenia. Comparisons of clinical and routine laboratory findings between the S. Typhi-positive and negative groups showed no significant differences. Patients testing positive for both NS1Ag and anti-D IgM were significantly more likely to test positive for S. Typhi IgM, even in the absence of typhoid fever. No routine antibiotics were used and all patients survived.Conclusion: One-third of a large group of patients with primary DVI also demonstrated false positive results for typhoid fever. Cross-reactivity of a rapid immunoassay for typhoid fever has not been previously reported in DVI or any other flavivirus infections. Until these findings can be further evaluated, clinicians should be cautious in interpreting S. Typhi rapid immunoassays and have a high index of suspicion of DVI in dengue fever endemic areas.

False sero-positivity of Salmonella typhi Specific Antibody in Dengue and Corona Virus Infected Patients: An Observational Study

“…Many studies had reported that Salmonella typhi somatic and flagella antigen is shared by large number of organism from Enterobacteriaceae family 9,10 and even in several other febrile illness such as Malaria, Tuberculosis, Schistosomiasis and in Dengue virus infection there are reports of false sero positivity of Widal test where there is no signs and symptoms of acute Salmonella infection. 7,[11][12][13] In a recent study by Seema et al 14 had reported around 20% of their COVID-19 positive patients were shown false positive result of Widal test which is similar to our study finding where we reported 20% of our COVID-19 patients had a significant titre of Widal test. Yet in another study from India by Adata et al also find similar finding in their study population.…”

“…Several other investigator also find the similar findings where they reported about 50% of their study population have dengue IgM with significant Widal test titre. 7 We also observed that in case of SARS-COV-2 infected patients around 20% subjects showed titre of anti O≥80 and titre of anti H were ≥160 which is considered as a base line titre of the local population. However, around 18% of the patients had anti O titre of 1: 20 and anti H of 1:40.…”

Performance of Immunodiagnostic Tests for Typhoid Fever: A Systematic Review and Meta-Analysis

“…The antibody decay profiles showed IgG antibodies persisted over 12 months after infection while the IgM and IgA antibodies appeared to decline after 3 to 4 months post infection. Another important limitation of antibody testing is that false positives may occur due to cross-reactivity resulting from other infections [ 33 ].…”

Comparative Studies on the Diagnostic Validity of Widal and Evaluation of Interferon Gamma Response in Patients Investigated for Typhoid Fever

“…This disagreement between blood culture and widal result might be due to the fact that Widal test is based on the reaction of S. Typhi antigens (O and H) to speci c antibodies in patient's serum where cross reactivity with similar antigens is possible. Cross reactivity of widal has been reported in patients with dengue fever by Bhatti et al (2015) where they recruited patients who had clinical and serological evidence of dengue virus infection and subjected them to widal screening test. They found about 33% of the patients with dengue fever to be widal positive with no single Salmonella Typhi bacterium isolated from their blood.…”