Limitations of rapid diagnostic testing in the work-up of dengue infection – a case report

Rapid diagnostic testing (RDT) is valuable in the work-up for dengue infection, in view of reducing turnaround time whilst detecting the presence of nonstructural (NS) antigens and IgM/IgG immunoglobulins. Nevertheless, when antibody titers are borderline, this may present as a source of consternation due to the ambiguity of results. We present a case of a patient with end-stage renal failure planned for renal transplant who developed fever as an inpatient. His physician suspected dengue due to thrombocytopenia and a CareUSTM Dengue Combo kit initially reported NS1 antigen/IgM negative but IgG positive. Realtime polymerase chain reaction (PCR) for viral nucleic acids was performed which was negative. This case highlights limitations in the use of RDT for suspected dengue cases particularly in the setting of immunocompromised patients, and potential issues encountered using rapid diagnostic kits, which need to be recognised. A 42-year-old Asian male with a background of endstage renal failure (ESRF) secondary to IgA nephropathy and glomerulosclerosis was planned for renal transplant as an inpatient. He had a previous renal transplant performed 7 years ago complicated by antibody-mediated rejection and subsequent progression to ESRF. At the point of admission, he was on an immunosuppression regimen consisting of prednisolone, mycophenolate and tacrolimus. Pre-operatively, his haemoglobin was 10.8 g/L (13.1–16.6 g/L), white blood cell count 3.6 × 109/L (3.8–10.0 × 109/L), and platelet count was 184 × 109/L (164–387 × 109/L). In view of our South-east Asian climate whereby dengue infection is endemic, dengue testing is performed routinely in Singapore as part of the virological workup for both potential donor and recipient in preparation for an organ transplant. Dengue PCR testing is further mandated within 48–72 h of live organ donation by Ministry of Health, Singapore Guidelines. In our laboratory, a bench top CareUSTM Dengue Combo kit is used for RDT of dengue for transplant recipients. The patient’s physician ordered an initial (first) pre-operative RDT dengue test which revealed negative NS protein 1 and IgM, but was positive for IgG suggesting previous exposure to dengue virus. Two days later, this was followed up by a dengue virus reverse transcriptase PCR (RT-PCR), which was negative, but another test (second RDT) was ordered which now showed a very faint band over IgG. The medical technologist initially reported this as negative but after a query from the clinician and subsequent knowledge that the previous IgG was positive, the report was then amended to that of positive. On day 2 of admission for the kidney transplant, the patient developed pyrexia of 38.0 °C accompanied with right-sided abdominal pain. Serum procalcitonin was 50.43 μg/L (<0.5 μg/L), C-reactive protein was 83 mg/L (0–10 mg/L) and lactate was 2.5 mmol/L (0.7–2.1 mmol/L). A computed tomography (CT) of the abdomen was performed, revealing the presence of graft pyelonephritis but otherwise no appendicitis. His renal transplant was cancelled. A day later, his physicians re-ordered a third RDT dengue which was now clearly negative (no faint lines) for all immunoglobulins and NS1 antigen. Urine cultures demonstrated growth of Proteus mirabilis, confirming a urinary tract infection, to which the patient responded well to meropenem as per susceptibility pattern, and was subsequently discharged. We retrieved the last RDT specimen and performed a Panbio® dengue IgG indirect ELISA *Corresponding author: Dr. Shaun S. Tan, Department of Laboratory Medicine, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119228, Singapore, Phone: +65 83331713, E-mail: shaun_sy_tan@nuhs.edu.sg Sharon Saw, Gabriel Yan, Ai Teng Chong, Zhixin Yang, Ai Ping Tan and Sunil K. Sethi: Department of Laboratory Medicine, National University Hospital, Singapore, Singapore Anantharaman Vathsala: National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore; and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Clin Chem Lab Med 2020; 58(10): e245–e246