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.
Highlights
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)
Patients testing positive for both non-structural protein 1 antigen (NS1Ag) and anti-D IgM were significantly more likely to test positive for S
Making an accurate diagnosis during the acute phase of the febrile illness is essential for prompt intervention since it is difficult to predict whether the patient will progress to the critical phase characterized by a rapid onset of a severe capillary leak, circulatory collapse, and hemorrhage with thrombocytopenia
Summary
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). Current worldwide case burden estimate ranges from 20 to 100 million infections annually, including as many as 500,000 cases of dengue hemorrhagic fever (DHF) and dengue shock syndromes (DSS) [4,5]. An accurate diagnosis of DVI is essential in order to identify, as early as possible, those patients at risk for the critical phase of the infection and possible circulatory collapse, shock, and death. Patients with febrile illnesses often benefit from specific diagnostic laboratory studies for dengue virus and other candidate infectious organisms endemic to the region [11,12]. Concurrent dengue fever and typhoid fever are uncommon [11]
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