Rapid testing requires clinical evaluation for accurate diagnosis of dengue disease: A passive surveillance study in Southern Malaysia

• Main Authors: Ngim, Chin Fang, Husain, Syed M. Tupur, Hassan, Sharifah Syed, Dhanoa, Amreeta, Ahmad, Siti Aisyah Abdul, Mariapun, Jeevitha, Wan Ismail, Wan Fadhilah, Botross Henien, Nevein Philip, Jahan, Nowrozy Kamar, Pong, Lian Yih, Elshahawi, Hesham, Hontz, Robert D., Warkentein, Tyler, Mohd Yunos, Nor'azim
• Format: Article
• Published: Public Library of Science 2021
• Subjects: QL Zoology; RA Public aspects of medicine; RC Internal medicine
• Online Access: http://eprints.um.edu.my/34549/

Background Dengue fever is the most common mosquito-borne infection worldwide where an expanding surveillance and characterization of this infection are needed to better inform the healthcare system. In this surveillance-based study, we explored the prevalence and distinguishing features of dengue fever amongst febrile patients in a large community-based health facility in southern peninsular Malaysia. Methods Over six months in 2018, we recruited 368 adults who met the WHO 2009 criteria for probable dengue infection. They underwent the following blood tests: full blood count, dengue virus (DENV) rapid diagnostic test (RDT), ELISA (dengue IgM and IgG), nested RT-PCR for dengue, multiplex qRT-PCR for Zika, Chikungunya and dengue as well as PCR tests for Leptopspira spp., Japanese encephalitis and West Nile virus. Results Laboratory-confirmed dengue infections (defined by positive tests in NS1, IgM, high-titre IgG or nested RT-PCR) were found in 167 (45.4%) patients. Of these 167 dengue patients, only 104 (62.3%) were positive on rapid diagnostic testing. Dengue infection was significantly associated with the following features: family or neighbours with dengue in the past week (AOR: 3.59, 95% CI:2.14-6.00, p<0.001), cutaneous rash (AOR: 3.58, 95% CI:1.77-7.23, p<0.001), increased temperature (AOR: 1.33, 95% CI:1.04-1.70, p = 0.021), leucopenia (white cell count < 4,000/<mu>L) (AOR: 3.44, 95% CI:1.72-6.89, p<0.001) and thrombocytopenia (platelet count <150,000/mu L)(AOR: 4.63, 95% CI:2.33-9.21, p<0.001). Dengue infection was negatively associated with runny nose (AOR: 0.47, 95% CI:0.29-0.78, p = 0.003) and arthralgia (AOR: 0.42, 95% CI:0.24-0.75, p = 0.004). Serotyping by nested RT-PCR revealed mostly mono-infections with DENV-2 (n = 64), DENV-1 (n = 32) and DENV-3 (n = 17); 14 co-infections occurred with DENV-1/DENV-2 (n = 13) and DENV-1/DENV-4 (n = 1). Besides dengue, none of the pathogens above were found in patients' serum. Conclusions Acute undifferentiated febrile infections are a diagnostic challenge for community-based clinicians. Rapid diagnostic tests are increasingly used to diagnose dengue infection but negative tests should be interpreted with caution as they fail to detect a considerable proportion of dengue infection. Certain clinical features and haematological parameters are important in the clinical diagnosis of dengue infection. Author summary With the rise in dengue infection worldwide, dengue fever remains an important diagnosis among patients presenting with fever in the community. We conducted a passive surveillance study in a large community clinic in southern Malaysia. Adults with fever who met the WHO 2009 criteria for probable dengue infection underwent blood tests that were able to detect dengue fever accurately, including rapid diagnostics tests, serology, and molecular tests. Nearly half (45.4%) of the patients were confirmed to suffer from dengue infection in which the widely-used rapid tests were negative in a considerable proportion of dengue-infected patients. This underlines the importance of recognizing clinical and laboratory features suggestive of dengue fever. We found that a history of family or neighbours with dengue infection in the past week, skin rash, a higher temperature, leucopenia (white cell count < 4,000/mu L) and thrombocytopenia (platelet count <150,000/<mu>L) were significantly associated with dengue fever whereas runny nose and arthralgia were features that suggest non-dengue conditions. These features in addition to rapid diagnostic kits are useful to guide community based health care workers in the diagnosis of patients presenting with undifferentiated fever.