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

PLoS Negl Trop Dis. 2021 May 20;15(5):e0009445. doi: 10.1371/journal.pntd.0009445. eCollection 2021 May.

Abstract

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/μL) (AOR: 3.44, 95% CI:1.72-6.89, p<0.001) and thrombocytopenia (platelet count <150,000/μL)(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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / blood
  • Antigens, Viral / blood
  • Blood Cell Count
  • Cross-Sectional Studies
  • Dengue / diagnosis*
  • Dengue / epidemiology*
  • Dengue / virology
  • Dengue Virus / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fever / diagnosis
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Malaysia / epidemiology
  • Male
  • Middle Aged
  • Polymerase Chain Reaction

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Immunoglobulin G
  • Immunoglobulin M

Grants and funding

This study was funded by the Armed Forces Health Surveillance Division (AFHSD) - Global Emerging Infections Surveillance and Response System (GEIS) to the US Naval Medical Research Unit 2 (PROMIS ID: P0064_18_NA_07; 2016-2018) (https://www.med.navy.mil/sites/nmrca/SitePages/Home.aspx) and approved for human use under by Naval Medical Research Center (NMRC) IRB (NMRR-19-514-47307) and HRPO no. 2018.003. The contract (N4034517P0197) was awarded to NMY. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.