Comparative Efficacy of Various Diagnostic Modalities for Confirming Acute Dengue Viral Infection Against 04 Serotypes

Research Article | DOI: https://doi.org/10.31579/2690-1897/133

Comparative Efficacy of Various Diagnostic Modalities for Confirming Acute Dengue Viral Infection Against 04 Serotypes

  • Humaira Zafar 1*
  • Irfan Ali Mirza 2

1 Professor of Pathology, Microbiologist, HITEC-IMS, Taxilla, Pakistan
2 Professor of Pathology, Consultant Microbiologist, Head of Microbiology Department, Armed Forces Institute of Pathology, National University of Medical Sciences, Rawalpindi.

*Corresponding Author: Humaira Zafar. Professor of Pathology, Microbiologist, HITEC-IMS, Taxilla,Pakistan.

Citation: Humaira Zafar, Irfan Ali Mirza. (2022). Comparative Efficacy of Various Diagnostic Modalities for Confirming Acute Dengue Viral Infection Against 04 Serotypes, J. Surgical Case Reports and Images, 5(7) DOI: 10.31579/2690-1897/133

Copyright: © 2022 Humaira Zafar. This is an open-access article distributed under the terms of The Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 11 November 2022 | Accepted: 29 November 2022 | Published: 11 December 2022

Keywords: dengue viral infection; diagnosis; meta analysis; systematic reviews; NS1Ag; ELISA; RT- PCR; Conventional PCR

Abstract

Background & Introduction: Dengue viral infection is a Global health problem. In the absence of vaccine and anti-viral, early diagnosis and management harbors great significant. Therefore the current systematic review was planned to identify the most accurate diagnostic modality for acute infection.

Objective: To compare the efficacy of various lab diagnostic tests for confirming  acute dengue viral infection against 04 serotypes.

Methodology: This systematic review was carried out by following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.  Final sample size was 07 (N). However it was extracted by narrowing down 24 (n) studies by four steps i.e identification, screening, eligibility and inclusion criteria. Latest published researches form last five years were included by using various search engines e.g Pubmed,  Pakmedinet, Cochrane data base, Google scholar and open google search.

Results: Out of 07(N) studies, three (n=04) strongly supported that diagnostic efficacy was highest for RT – PCR followed by NS1 Ag ELISA and than IgM ELISA. One (n=01) study emphasized single-tag hybridization-printed array strip (STH-PAS), a most accurate rapid diagnostic test. In one more study rapid diagnostic test (RDTs) was correlated with the economical burden for surveillance system. 

Conclusion: It is concluded that diagnostic accuracy from highest to lowest is for RTPCR > NS1 ELISA>IgM ELISA

Introduction

Dengue viral infection is still amongst the Global health challenges. In the absence of vaccine or specific anti virals, only relying measure is early diagnosis and prompt supportive management to reduce the morbidity and mortality rates. A study report by Anwar etal (2022), showed the evaluation for 1738 individuals suspected of having dengue infection. The commonly used modalities were Nonstructural protein-1 antigens (NS1- Ag), IgG, and IgM antibodies and RT-PCR techniques. A high prevelance of  DENV-3 serotype was seen followed by serotype (DENV-4), seen in only  in 1% of cases. The correlation with clinical features revealed a high incidence of fever (100%), myalgia (100%), headache (61.31%), vomiting (34.63%), and rashes in all positive cases [1]. 

The laboratory tests varies from the detection of virus itself either by direct inoculation on live cell lines or polymerization chain reaction, to identification antigens i.e NS1- Ag or antibodies i.e IgM and IgG. However, after four to five days of illness, serum estimation for dengue IgM:IgG is commonly a preferred test [2]. Most of them are very costly, time consuming ones. In the published report by Hassan M etal (2022), significance of inelastic light scattering by molecular vibrations by Raman spectroscopy was highlighted. The technique helps in identification of spectral chemical signatures of cells and tissues to confirm the diagnosis [3].

 All the ones mentioned above have different pros and cons. Therefore the current systematic review was planned to identify the most accurate diagnostic modality for confirming  acute dengue viral infection against 04 serotypes 

Materials and Methods

This systematic review was carried out by PRISMA guidelines – 2019.  Total 24 studies were selected and included for study. The search was carried out in four stages i.e identification, screening, eligibility and final included ones. The details are shown in figure- I. 

Certain MESH key words were used for searching the relevant literature review. These key words were Dengue viral Infection, Diagnosis, Meta Analysis, Systematic Reviews, NS1Ag, ELISA, PCR. The meta-analysis, systematic review, original articles, review articles and guidelines published in impact factor journals in last 05 years were included. Special focus was given to the articles with a patients of any age group and having symptoms of dengue infection. However, editorials,   letter to editor, case reports, commentary, case series report and short  communications were excluded. Special care was taken to exclude manuscripts having details of co infections with  yellow fever, tick borne fever and Japanese Encephalitis.

Twenty four studies (n=24) were included for the systematic review. Out of 20 (n) , 09 (n) were selected from PUBMED, 02 (n)  from Cochrane Data Base, 07 (n) from Google scholar, 01 (n) from open google search and 01 (n) was selected from Pakmedinet. 04 (n) articles were selected by snowball method form one meta analysis. For standardization of selected articles, critical appraisal was done for finally selected 07 (N) articles. The salient points for 07 selected articles are shown in tables I-A and I-B.

                                                                    Figure 1: PRISMA 2009 Flow Diagram Showing Literature search for  Systematic Review 

Results

The extracted results including narration of salient features are tabulated in tables I-A and Table I – B. Out of 07(N) studies, three (n=04) strongly supported that diagnostic efficacy was highest for RT – PCR followed by NS1 Ag  by ELISA and IgM antibodies detection by ELISA. One (n=01) study emphasized single-tag hybridization-printed array strip (STH-PAS), a most accurate rapid diagnostic test. One (n=01) study emphasized the utility of Raman Spectroscopy. One (n=01) study highlighted the utility of peptide biomarker identification via microarray. Nutshell of all included studies was to opt a diagnostic modality having rapid turnaround time, provision of quantitative data, less chances of false positive, lastly increased sensitivity and specificity.

Discussion

diseases, influencing many tropical and subtropical regions  around the Globe [9].  The increasing estimated incidence i.e 390 million infections per anum and 3.9 billion people in 128 countries are at high risk of acquiring Infection [10]. 

Comparatively a published report by WHO for the year 2021, narrated an increased incidence upto 5.2 million cases per anum. 11 The variation attributes to difficultly in succesful surveillance and identification of true positive case. The under reporting super added by deficiency in diagnostic tools are making the scenario worsen.  Its clinical manifestations mimics with those of other microbial infections, hence requiring accurate confirmation by laboratory tests [9].

Tracing back the history till date and in light of published data, it was evaluated that many lab tests are existing to confirm the diagnosis of dengue infection. The current systematic review highlighted that they start from the detection of dengue virus by culture till molecular level identification. Every one harbors pros and cons. Commonly identified tests include dengue viral culture, dengue viral RNA identification by RT- PCR, Non structural protein identification i.e NS1 antigen (NS1-Ag), IgM and IgG identification by third generation and capture ELISA, Significance of ratio for IgM and IgG, IgA level estimation, significance of peptide biomarkers via microarray and Ramman spectroscopy [3-8].  comparing all the findings with published data supports the evidence that for accurate lab confirmation test, cost effective, rapid and highly sensitive test should be the choice for confirming dengue infection [10,11].

Furthermore analyzing results of current study by comparison with other published data supported that though little costly but accurate lab diagnosis should only be focused on molecular characterization by RT-PCR. Moreover, further genomic amplification will be enhanced by real time (qRT-PCR), which superseded conventional PCR by its rapid turnaround time, provision of quantitative data, less chances of false positive, lastly increased sensitivity and specificity [12].

Conclusion

It is concluded that diagnostic accuracy from highest to lowest is for RT-PCR > NS1- ELISA>IgM ELISA

References

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