Intended Use

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The Dengue NS1 & IgG/IgM Rapid Test Combo is a rapid chromatographic immunoassay for the qualitative detection of dengue virus NS1 antigen, IgG and IgM antobody in human whole blood, serum, or plasma as an aid in the diagnosis of primary and secondary Dengue infections.

Introduction

Dengue viruses, transmitted by the mosquito, Aedes aegypti and Aedes albopictus mosquitoes, are widely distributed throughout the tropical and subtropical areas of the world. There are four known distinct serotypes (dengue virus 1, 2, 3 and 4). In children, infection is often subclinical or causes a self-limited febrile disease. However, if the patient is infected second times with a different serotype, a more severe disease, dengue hemorrhagic fever or dengue shock syndrome, is more likely to occur. Dengue is considered to be the most important arthropod-borne viral disease due to the human morbidity and mortality it causes. NS1 is a highly-conserved glycoprotein that is present at high concentrations in the sera of dengue-infected patients during the early clinical phase of the disease. NS1 antigen is found from the first day and up to 9 days after onset of fever in sample of primary or secondary dengue infected patients.
 

Contents

• Rapid Test
• Buffer
• Disposable pipettes
• Instruction for use

Storage & Statibility

• The kit should be stored at 2-30°C until the expiry date printed on the sealed pouch.
• The test must remain in the sealed pouch until use.
• Keep away from direct sunlight, moisture and heat.
• Do not freeze.
• Care should be taken to protect the components of the kit from contamination. Do not use if there is evidence of microbial contamination or precipitation. Biological contamination of dispensing equipment, containers or reagents can lead to false results.

Operation

1. Bring tests, specimens, buffer and/or controls to room temperature (15-30°C) before use.
2. Remove the test from its sealed pouch, and place it on a clean, level surface. Label the device with patient or control identification. For best results, the assay should be performed within one hour.
NS1 Antigen:
Transfer 1 drop of sample into the center of the specimen well(s) of the test cassette, then add 1 to 2 drops of buffer, and start the timer.
IgG/IgM Antibody:
Transfer 1 drop of sample into the center of the specimen well(s) of the test cassette, then add 1 to 2 drops of buffer, and start the timer.
3.Wait for the colored band(s) to appear. The result should be read at 10 minutes. Do not interpret the result after 20 minutes.

Detailed Photos

Company Profile

About Us

Dewei Medical Equipment Co., Ltd. is a high-tech enterprise specialized in developing and marketing of Medical Consmuables like Clinical Laboratory analyzer and reagents, Hematology Analyzer and Reagents, Washing Solutions, Urine Sediment Reagents and DNA/RNA Preservation Kits.
During the special period of Corona, Dewei also develop the reagent kits, like Virus Transport Medium with swab, Rapid test and Saliva Collection Kits.
Dewei products are widely used in hospital clinics, disease control centers, blood banks, veterinary clinics, scientific research center and college laboratories.
 

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FAQ

1, Are you a manufacturer?
Yes, we are a manufacturer based in Foshan City, Guangdong province. We have different production lines, more than square meter facility.

2, Can you put our logo or text on the products or packages?
Yes, we can provide OEM goods.

3, Could you provide free samples for our testing before we place an order?
Sure, we'd like to offer free samples for you, but the freight cost should be paid by the buyer.

4, How to make payment?
T/T, D/P, L/C, Paypal, Western Union and Made in China are both acceptable.

5, Which seaport and airport are the nearest to your factory?
The near seaport is Guangzhou Nansha Seaport & Shenzhen Shekou Seaport. And Guangzhou, Shenzhen, & Hongkong Airports are both convenient.

6,  What is your best delivery time?
Depend on your order quantities. 3-20 working days after payment is received.
 

Introduction

Dengue is an acute viral disease caused by a virus transmitted mainly by Aedes aegypti. This arthropod-borne flavivirus has four distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4, which constitute an antigen complex of the Flavivirus genus, Flaviviridae family 11. Peeling RW, Artsob H, Pelegrino JL, Buchy P, Cardosa MJ, Devi S, et al. Evaluation of diagnostic tests: dengue. Nat Rev Microbiol ; 8(12 Suppl):S30-8..

Dengue virus is present in more than 100 countries of the Asia-Pacific, Americas, Middle East, and Africa 22. Da Costa VG, Marques-Silva AC, Moreli ML. A meta-analysis of the diagnostic accuracy of two commercial NS1 antigen ELISA tests for early dengue virus detection. PLoS One ; 9:e.,33. San Martin JL, Brathwaite O, Zambrano B, Solorzano JO, Bouckenooghe A, Dayan GH, et al. The epidemiology of dengue in the americas over the last three decades: a worrisome reality. Am J Trop Med Hyg ; 82:128-35.,44. Zhang H, Li W, Wang J, Peng H, Che X, Chen X, et al. NS1-based tests with diagnostic utility for confirming dengue infection: a meta-analysis. Int J Infect Dis ; 26:57-66., with 3 billion people (40% of the world population) at risk of infection in tropical and subtropical regions, with 50 to 100 million infections per year 22. Da Costa VG, Marques-Silva AC, Moreli ML. A meta-analysis of the diagnostic accuracy of two commercial NS1 antigen ELISA tests for early dengue virus detection. PLoS One ; 9:e.,44. Zhang H, Li W, Wang J, Peng H, Che X, Chen X, et al. NS1-based tests with diagnostic utility for confirming dengue infection: a meta-analysis. Int J Infect Dis ; 26:57-66.,55. World Health Organization. Dengue guidelines for diagnosis, treatment, prevention and control. Geneva: World Health Organization; .. It is an important arthropod-borne viral disease in terms of human morbidity, mortality and economic impact. Many challenges remain concerning disease control and prevention programs based on vector reproduction and elimination, clinical aspects and pathogenesis 55. World Health Organization. Dengue guidelines for diagnosis, treatment, prevention and control. Geneva: World Health Organization; ..

The clinical presentation of dengue infection is highly unspecific varying according to the circulating serotype 55. World Health Organization. Dengue guidelines for diagnosis, treatment, prevention and control. Geneva: World Health Organization; .. Differential diagnosis of dengue in urban areas of large metropolises in Latin America, where malaria is not endemic, includes influenza 66. Blacksell SD, Doust JA, Newton PN, Peacock SJ, Day NP, Dondorp AM. A systematic review and meta-analysis of the diagnostic accuracy of rapid immunochromatographic assays for the detection of dengue virus IgM antibodies during acute infection. Trans R Soc Trop Med Hyg ; 100:775-84.,77. Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev ; 11:480-96.. In Brazil, since 88. Passos SRL, Borges dos Santos MA, Cerbino-Neto J, Buonora SN, Souza TML, de Oliveira RVC, et al. Detection of Zika virus in April patient samples, Rio de Janeiro, Brazil. Emerg Infect Dis ; 23:-1., also zika and chikungunya are co-circulating 99. Campos GS, Bandeira AC, Sardi SI. Zika virus outbreak, Bahia, Brazil. Emerg Infect Dis ; 21:-6., making the diagnosis on a clinical basis unreliable. Thus, diagnostic optimization for adequate clinical management to prevent complications caused by dengue requires better, easier and more efficient rapid tests with good accuracy for case management during the earlier state of infection.

Among the rapid tests, those using the immunochromatographic technique (ICT) to detect the presence of nonstructural protein 1 (NS1) play an important role in early diagnosis of dengue fever (up to seven days from the onset of symptoms) 1010. Lima MRQ, Nogueira RM, Schatzmayr HG, dos Santos FB. Comparison of three commercially available dengue NS1 antigen capture assays for acute diagnosis of dengue in Brazil. PLoS Negl Trop Dis ; 4:e738.. Reference standards such as virus isolation, PCR or PRNT have the great disadvantages of being laborious, time consuming, require specific reagents, equipment, trained personnel and are high cost. ELISA IgM/IgG has been important for health surveillance and distinguishes between primary and secondary infectious in cases previously confirmed by RT-PCR or virus isolation but presents cross-reactivity with other members of the Flaviviradidae family 66. Blacksell SD, Doust JA, Newton PN, Peacock SJ, Day NP, Dondorp AM. A systematic review and meta-analysis of the diagnostic accuracy of rapid immunochromatographic assays for the detection of dengue virus IgM antibodies during acute infection. Trans R Soc Trop Med Hyg ; 100:775-84..

We found five systematic reviews with meta-analysis on the subject 44. Zhang H, Li W, Wang J, Peng H, Che X, Chen X, et al. NS1-based tests with diagnostic utility for confirming dengue infection: a meta-analysis. Int J Infect Dis ; 26:57-66.,66. Blacksell SD, Doust JA, Newton PN, Peacock SJ, Day NP, Dondorp AM. A systematic review and meta-analysis of the diagnostic accuracy of rapid immunochromatographic assays for the detection of dengue virus IgM antibodies during acute infection. Trans R Soc Trop Med Hyg ; 100:775-84.,1111. Alagarasu K, Walimbe AM, Jadhav SM, Deoshatwar AR. A meta-analysis of the diagnostic accuracy of dengue virus-specific IgA antibody-based tests for detection of dengue infection. Epidemiol Infect ; 144:876-86.,1212. Lim JK, Alexander N, Di Tanna GL. A systematic review of the economic impact of rapid diagnostic tests for dengue. BMC Health Serv Res ; 17:850.,1313. Shu PY, Huang JH. Current advances in dengue diagnosis. Clin Diagn Lab Immunol ; 11:642-50.. Alagarasu et al. 1111. Alagarasu K, Walimbe AM, Jadhav SM, Deoshatwar AR. A meta-analysis of the diagnostic accuracy of dengue virus-specific IgA antibody-based tests for detection of dengue infection. Epidemiol Infect ; 144:876-86. included only publications on IgA ICT. Another meta-analysis included nine studies on NS1 ICT 44. Zhang H, Li W, Wang J, Peng H, Che X, Chen X, et al. NS1-based tests with diagnostic utility for confirming dengue infection: a meta-analysis. Int J Infect Dis ; 26:57-66. and the systematic review by Blacksell et al. 66. Blacksell SD, Doust JA, Newton PN, Peacock SJ, Day NP, Dondorp AM. A systematic review and meta-analysis of the diagnostic accuracy of rapid immunochromatographic assays for the detection of dengue virus IgM antibodies during acute infection. Trans R Soc Trop Med Hyg ; 100:775-84. assessed a single commercial test (Panbio ICT - Abbott Laboratories) in 11 studies, showing wide variability between them. These reviews point out the high specificity of the ICT, but with heterogeneous sensitivities, requiring a critical assessment that includes the various types of ICT and brands available on the market as well as their evaluation in acute and convalescent samples. In fatal cases, NS1 strip showed better sensitivity (78.3%) than ELISA NS1 1010. Lima MRQ, Nogueira RM, Schatzmayr HG, dos Santos FB. Comparison of three commercially available dengue NS1 antigen capture assays for acute diagnosis of dengue in Brazil. PLoS Negl Trop Dis ; 4:e738..

A recent systematic review 1212. Lim JK, Alexander N, Di Tanna GL. A systematic review of the economic impact of rapid diagnostic tests for dengue. BMC Health Serv Res ; 17:850. on the economic impact of dengue’s ICT favored a relatively obsolete diagnostic strategy based on IgM Panbio for acute cases. However, it identified only two studies, one using primary observational data 1414. Mitra S, Choudhari R, Nori H, Prabhakar AP, Abraham O, Jeyaseelan V, et al. Performance and cost-effectiveness of immunochromatography based rapid diagnostic test (RDT) kits in diagnosis of dengue infection in resource limited set up. Int J Infect Dis ; 21 Suppl 1:450. and the other, a simulation modeling design 1515. Lubell Y, Althaus T, Blacksell SD, Paris DH, Mayxay M, Pan-Ngum W, et al. Modelling the impact and cost-effectiveness of biomarker tests as compared with pathogen-specific diagnostics in the management of undifferentiated fever in remote tropical settings. PLoS One ; 11:e..

In children, when it could be difficult to access blood samples, some studies were carried out in saliva and urine 1616. Andries AC, Duong V, Ong S, Ros S, Sakuntabhai A, Horwood P, et al. Evaluation of the performances of six commercial kits designed for dengue NS1 and anti-dengue IgM, IgG and IgA detection in urine and saliva clinical specimens. BMC Infect Dis ; 16:201.,1717. Musso D, Roche C, Nhan TX, Robin E, Teissier A, Cao-Lormeau VM. Detection of Zika virus in saliva. J Clin Virol ; 68:53-5.. Muso et al. 1717. Musso D, Roche C, Nhan TX, Robin E, Teissier A, Cao-Lormeau VM. Detection of Zika virus in saliva. J Clin Virol ; 68:53-5. suggested that only 19% of the studies detected zika virus in saliva, concluding that it could not replace blood tests. In a recent review, Colonetti et al. 1818. Colonetti T, Rocha BVE, Grande AJ, Alexandre MCM, Dondossola ER, Madeira K, et al. Accuracy of immunoglobulin M and immunoglobulin A of saliva in early diagnosis of dengue: systematic review and meta-analysis. An Acad Bras Ciênc ; 90:-54. included three studies for dengue diagnosis evaluating salivary IgM, which provided sensitivity of 86% and specificity of 93%. Two included studies evaluating salivary IgA showed a pooled sensitivity of 69% and a pooled specificity of 98%. Despite these results and the low methodological quality of the studies included in the meta-analysis, the authors concluded that it is still soon to claim that IgA is better than IgM to diagnose dengue 1818. Colonetti T, Rocha BVE, Grande AJ, Alexandre MCM, Dondossola ER, Madeira K, et al. Accuracy of immunoglobulin M and immunoglobulin A of saliva in early diagnosis of dengue: systematic review and meta-analysis. An Acad Bras Ciênc ; 90:-54..

This study aimed to review the literature on the accuracy of ICT using as the reference test any type of PCR, ELISA, or virus isolation, in suspected dengue cases with up to seven days since the onset of fever for NS1 ICT and with no restriction on the days of fever for IgA, IgM/IgG, or NS1/IgM/IgG ICT.

Methods

This was a systematic literature review of observational diagnostic studies reported in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement 1919. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol ; 62:e1-34.. The protocol was previously registered on the site PROSPERO number CRD.

Data sources and search strategy

The research question was: Are point of care immunochromatographic tests accurate for early detection of dengue infection? Does the test performance vary according to age, sex, dengue serotype, reference tests or whether it is a primary or secondary infection, acute or convalescent phases? These questions guided the eligibility criteria expressed in the PICO (Patient, Intervention, Comparison and Outcomes) format:

Population: blood/serum or plasma samples from patients with febrile illness suspected of dengue with up to seven days of fever in the acute phase of the disease and with no time limit in the convalescent phase;

Intervention (index tests): ICTs with detection of IgA, NS1, IgM/IgG, or NS1/IgM/IgG, read within 60 minutes;

Comparator (reference standard): PCR, ELISA NS1 or IgM, virus isolation, or a combination of two or three of these;

Outcome (diagnostic parameters): sensitivity, specificity, likelihood ratios, and positive and negative predictive values in ICTs for dengue, besides the information on time and effect measures, according to the case.

We excluded articles that: use inappropriate reference tests, index test limited to the detection of IgG antibodies or that takes more than 60 minutes to perform, incomplete description or partial examination of sample, small sample size or insufficient data to calculate accuracy parameters.

In case of doubt we directly contacted the authors. We did not limit the search based on study design nor on language of publication.

Two researchers conducted the searches up to October for journal articles or congress proceedings publications since inception in MEDLINE via PubMed, Science Direct, Scopus, Web of Science, Ovid MEDLINE JBrigs, SCIRUS, BIREME and EMBASE, with no restriction on language or study design. We also searched gray literature using Google Scholar. Our search strategy in MEDLINE via PubMed employed the keywords: (“dengue/diagnosis”[MeSH Terms]) AND (diagnostic reagents and test kits [MeSH Terms]), generating the following strategy: “humans”[MeSH Terms] AND (“Dengue” OR “Dengue Virus”) AND (sensitiv*[Title/Abstract] OR specificity[Title/Abstract] OR “sensitivity and specificity”[Mesh Terms] OR “Reference Values”[Mesh] OR diagnosis*[Title/Abstract] OR diagnosis[Mesh] OR diagnosis[Subheading]) AND (((“Serologic Tests” OR Immunoassay OR “Reagent Kits, Diagnostic”) AND (Bedside OR Rapid)) OR “Point-of-Care Systems” OR “NS1” OR “NS-1” OR “Viral nonstructural proteins” OR Immunochromatogra* OR Immunochromatography OR bioeasy OR bioline OR bioline OR panbio OR core OR ag-strip OR strip OR Duo OR biorad OR “Reagent Strips”). We used equivalent strategies in the other databases and employed Zotero Standalone 4.0 for Windows (https://www.zotero.org/) in the search and filing of references.

Study selection

Initially, three pairs of reviewers (V.E.M./C.A.F.A., L.V.B.F./S.R.L.P., and Y.H.M.H./S.R.L.P.) independently selected the study abstracts. We held consensus meetings, and in case of disagreement, a third reviewer external to the pair judged the article’s relevance. In the second stage, pairs of reviewers (V.E.M./C.A.F.A., V.E.M./S.R.L.P., and Y.H.M.H./S.R.L.P.) read the full-text articles, also independently. Disagreements arising in the consensus meetings of the respective pairs were also resolved with a third external reviewer.

Data extraction and assessment of risk of bias

We designed a standardized form to extract the following variables by the pairs of reviewers: study design, commercial test names, test manufacturing countries, type of detection used, reference test used, number of study participants, number of confirmed dengue cases, non-dengue cases, measures of accuracy, virus serotype, and time since onset of fever.

We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS 2) 2020. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med ; 155:529-36. to assess the quality of the selected articles, risk of bias, and applicability. The tool consists of 14 items distributed across four domains that assess patient selection, index test, reference test, flow and timing.

Data synthesis and analysis

We used the “reference standard” defined in each selected study for comparison with the index test to determine the true-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) values. Diagnostic accuracy, sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), positive (LR+) and negative likelihood ratios (LR-), diagnostic odds ratio (DOR). We estimated positive (PP+) and negative post-test probabilities (PP-) in scenarios of 25%, 50%, and 75% prevalence.

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For each ICT (IgA, NS1, IgM/IgG, NS1/IgM/IgG), we performed a meta-analysis for each measure of diagnostic accuracy listed above, with the respective 95% confidence intervals (95%CI). The analyses were performed with the Winpepi (http://www.brixtonhealth.com/pepi4windows.html) and Stata XIV (https://www.stata.com) packages using the MIDAS command (Meta-analytical Integration of Diagnostic Accuracy Studies) performing the bivariate mixed-effects binary regression modeling framework. Meta-analyses were conducted according to the different analytes and/or brands.

We calculated the I2 statistic to detect significant overall and inter-subgroup heterogeneity 2121. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ ; 327:557-60.. We considered I2 values greater than 50% as high evidence of heterogeneity in data. In the presence of I2 point estimate higher than 50%, we performed meta-analysis using random effects model 2222. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials ; 7:177-88..

We analyzed study heterogeneity graphically and through the I2 test. We explored possible causes of clinical heterogeneity between studies through subgroup analyses: disease phase (acute or convalescent), by the most extensively assessed brand name, and overall quality of studies according dimensions of QUADAS 2 (low versus high or unclear risk of bias) 2020. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med ; 155:529-36..

Assessment of publication bias used the Deeks graph, where p-value < 0.05 was considered significant 2323. Deeks JJ, Macaskill P, Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol ; 58:882-93..

Results

Characteristics of included studies

The initial search identified 3,791 publications. After removing duplicates, we reviewed 3,783 abstracts, and selected 108 articles for reading the full-texts, of which 57 were selected for this review ( Figure 1). The studies assessed multiple ICT brand tests with different analytes: five assessed IgA 2424. Ahmed F, Mursalin H, Alam MT, Amin R, Sekaran SD, Wang SM, et al. Evaluation of ASSURE(R) Dengue IgA Rapid Test using dengue-positive and dengue-negative samples. Diagn Microbiol Infect Dis ; 68:339-44.,2525. Hartono A, Sari SK. Diagnosis of dengue virus infection with IgA anti-dengue rapid tests. Int J Infect Dis ; 16 Suppl:e317-473.,2626. Hernandez SIC, Gonzalez Mateos S, Flores Aguilar H, Lopez Martinez I, Alpuche Aranda C, Ludert JE, et al. Evaluation of a novel commercial rapid test for dengue diagnosis based on specific IgA detection. Diagn Microbiol Infect Dis ; 72:150-5.,2727. Naz A, Zahid D, Murky SN, Nadeem M, Sil BK, Shamsi TS. Evaluation of efficacy of various immunochromatographic rapid tests for dengue diagnosis. Pak J Med Sci ; 30:166-71.,2828. Tan YY, Sekaran SD, Wang SM, Ahmed F, Hossain A, Sil BK. Development of ASSURE Dengue IgA Rapid Test for the detection of anti-dengue IgA from dengue infected patients. J Glob Infect Dis ; 3:233-40., 21 NS1 1010. Lima MRQ, Nogueira RM, Schatzmayr HG, dos Santos FB. Comparison of three commercially available dengue NS1 antigen capture assays for acute diagnosis of dengue in Brazil. PLoS Negl Trop Dis ; 4:e738.,2727. Naz A, Zahid D, Murky SN, Nadeem M, Sil BK, Shamsi TS. Evaluation of efficacy of various immunochromatographic rapid tests for dengue diagnosis. Pak J Med Sci ; 30:166-71.,2929. Blacksell SD, Jarman RG, Bailey MS, Tanganuchitcharnchai A, Jenjaroen K, Gibbons RV, et al. Evaluation of six commercial point-of-care tests for diagnosis of acute dengue infections: the need for combining NS1 antigen and IgM/IgG antibody detection to achieve acceptable levels of accuracy. Clin Vaccine Immunol ; 18:-101.,3030. Buonora SN, Passos SR, do Carmo CN, Quintela FM, de Oliveira DN, dos Santos FB, et al. Accuracy of clinical criteria and an immunochromatographic strip test for dengue diagnosis in a DENV-4 epidemic. BMC Infect Dis ; 16:37.,3131. Chaiyaratana W, Chuansumrit A, Pongthanapisith V, Tangnararatchakit K, Lertwongrath S, Yoksan S. Evaluation of dengue nonstructural protein 1 antigen strip for the rapid diagnosis of patients with dengue infection. Diagn Microbiol Infect Dis ; 64:83-4.,3232. Dussart P, Petit L, Labeau B, Bremand L, Leduc A, Moua D, et al. Evaluation of two new commercial tests for the diagnosis of acute dengue virus infection using NS1 antigen detection in human serum. PLoS Negl Trop Dis ; 2:e280.,3333. Ferraz FO, Bomfim MR, Totola AH, Avila TV, Cisalpino D, Pessanha JE, et al. Evaluation of laboratory tests for dengue diagnosis in clinical specimens from consecutive patients with suspected dengue in Belo Horizonte, Brazil. J Clin Virol ; 58:41-6.,3434. Fry SR, Meyer M, Semple MG, Simmons CP, Sekaran SD, Huang JX, et al. The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach. PLoS Negl Trop Dis ; 5:e.,3535. Hang VT, Nguyet NM, Trung DT, Tricou V, Yoksan S, Dung NM, et al. Diagnostic accuracy of NS1 ELISA and lateral flow rapid tests for dengue sensitivity, specificity and relationship to viraemia and antibody responses. PLoS Negl Trop Dis ; 3:e360.,3636. Jusoh TNAM, Shueb RH. Performance evaluation of commercial dengue diagnostic tests for early detection of dengue in clinical samples. J Trop Med ; :.,3737. Lee H, Ryu JH, Park HS, Park KH, Bae H, Yun S, et al. Comparison of six commercial diagnostic tests for the detection of dengue virus non-structural-1 antigen and IgM/IgG antibodies. Ann Lab Med ; 39:566-71.,3838. Mata VE, Passos SRL, Hökerberg YHM, Berardinelli GM, Dos Santos MAB, Fukuoka LVB, et al. Accuracy and reliability of an NS1 rapid immunochromatographic test for DENV-1 diagnosis at point of care and in the laboratory. BMC Infect Dis ; 17:594.,3939. Najioullah F, Combet E, Paturel L, Martial J, Koulmann L, Thomas L, et al. Prospective evaluation of nonstructural 1 enzyme-linked immunosorbent assay and rapid immunochromatographic tests to detect dengue virus in patients with acute febrile illness. Diagn Microbiol Infect Dis ; 69:172-8.,4040. Osorio L, Ramirez M, Bonelo A, Villar LA, Parra B. Comparison of the diagnostic accuracy of commercial NS1-based diagnostic tests for early dengue infection. Virol J ; 7:361.,4141. Pal S, Dauner AL, Mitra I, Forshey BM, Garcia P, Morrison AC, et al. Evaluation of dengue NS1 antigen rapid tests and ELISA kits using clinical samples. PLoS One ; 9:e.,4242. Pan-ngum W, Blacksell SD, Lubell Y, Pukrittayakamee S, Bailey MS, de Silva HJ, et al. Estimating the true accuracy of diagnostic tests for dengue infection using bayesian latent class models. PLoS One ; 8:e.,4343. Pok KY, Lai YL, Sng J, Ng LC. Evaluation of nonstructural 1 antigen assays for the diagnosis and surveillance of dengue in Singapore. Vector Borne Zoonotic Dis ; 10:-16.,4444. Ramirez AH, Moros Z, Comach G, Zambrano J, Bravo L, Pinto B, et al. Evaluation of dengue NS1 antigen detection tests with acute sera from patients infected with dengue virus in Venezuela. Diagn Microbiol Infect Dis ; 65:247-53.,4545. Shu PY, Yang CF, Kao JF, Su CL, Chang SF, Lin CC, et al. Application of the dengue virus NS1 antigen rapid test for on-site detection of imported dengue cases at airports. Clin Vaccine Immunol ; 16:589-91.,4646. Tricou V, Vu HT, Quynh NV, Nguyen CV, Tran HT, Farrar J, et al. Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses. BMC Infect Dis ; 10:142.,4747. Zainah S, Wahab AH, Mariam M, Fauziah MK, Khairul AH, Roslina I, et al. Performance of a commercial rapid dengue NS1 antigen immunochromatography test with reference to dengue NS1 antigen-capture ELISA. J Virol Methods ; 155:157-60., 12 IgM/IgG 2727. Naz A, Zahid D, Murky SN, Nadeem M, Sil BK, Shamsi TS. Evaluation of efficacy of various immunochromatographic rapid tests for dengue diagnosis. Pak J Med Sci ; 30:166-71.,3434. Fry SR, Meyer M, Semple MG, Simmons CP, Sekaran SD, Huang JX, et al. The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach. PLoS Negl Trop Dis ; 5:e.,4848. Aikat A, Sarkar A, Tudu N, Moitra S, Pal PP, Sarkar TK. Diagnostic dilemma of dengue fever: how much reliability are there in rapidity. J Indian Med Assoc ; 109:543-5.,4949. Berry N, Chakravarti A, Gur R, Mathur MD. Serological investigation of a febrile outbreak in Delhi, India, using a rapid immunochromatographic test. J Clin Microbiol ; 36:-6.,5050. Blacksell SD, Newton PN, Bell D, Kelley J, Mammen Jr. MP, Vaughn DW, et al. The comparative accuracy of 8 commercial rapid immunochromatographic assays for the diagnosis of acute dengue virus infection. Clin Infect Dis ; 42:-34.,5151. Branch SL, Levett PN. Evaluation of four methods for detection of immunoglobulin M antibodies to dengue virus. Clin Diagn Lab Immunol ; 6:555-7.,5252. Cohen AL, Dowell SF, Nisalak A, Mammen Jr. MP, Petkanchanapong W, Fisk TL. Rapid diagnostic tests for dengue and leptospirosis: antibody detection is insensitive at presentation. Trop Med Int Health ; 12:47-51.,5353. Congpuong K, Chuchan S, Kwangthong S, Kangchaingone Y, Darakapong A. Appropriate laboratory tests for the diagnosis of dengue infection at a general hospital in Southern Thailand. Asian Biomed (Res Rev News) ; 2:289-95.,5454. Martinez-Vega RA, Diaz-Quijano FA, Coronel-Ruiz C, Yebrail Gomez S, Villar-Centeno LA. Evaluation of PANBIO rapid immunochromatographic cassette for dengue diagnosis in a Colombian endemic area. Biomedica ; 29:616-24.,5555. Nga TTT, Thai KTD, Phuong HL, Giao PT, Hung LQ, Binh TQ, et al. Evaluation of two rapid immunochromatographic assays for diagnosis of dengue among Vietnamese febrile patients. Clin Vaccine Immunol ; 14:799-801.,5656. Pun R, Shah Y, Gupta GP, Sherchand SP, Pandey BD. Prognostic value of rapid test for diagnosis of dengue in Nepalese patients during epidemic. Kathmandu Univ Med J (KUMJ) ; 10:7-10.,5757. Yusuf NW, Kausar N, Akbar R, Iqbal N. Comparison of diagnostic efficacy of rapid diagnostic devices for dengue virus infection: a piolt study. J Ayub Med Coll Abbottabad ; 20:26-8., and 25 NS1/IgM/IgG 2929. Blacksell SD, Jarman RG, Bailey MS, Tanganuchitcharnchai A, Jenjaroen K, Gibbons RV, et al. Evaluation of six commercial point-of-care tests for diagnosis of acute dengue infections: the need for combining NS1 antigen and IgM/IgG antibody detection to achieve acceptable levels of accuracy. Clin Vaccine Immunol ; 18:-101.,3636. Jusoh TNAM, Shueb RH. Performance evaluation of commercial dengue diagnostic tests for early detection of dengue in clinical samples. J Trop Med ; :.,3737. Lee H, Ryu JH, Park HS, Park KH, Bae H, Yun S, et al. Comparison of six commercial diagnostic tests for the detection of dengue virus non-structural-1 antigen and IgM/IgG antibodies. Ann Lab Med ; 39:566-71.,4040. Osorio L, Ramirez M, Bonelo A, Villar LA, Parra B. Comparison of the diagnostic accuracy of commercial NS1-based diagnostic tests for early dengue infection. Virol J ; 7:361.,4646. Tricou V, Vu HT, Quynh NV, Nguyen CV, Tran HT, Farrar J, et al. Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses. BMC Infect Dis ; 10:142.,5858. Andries AC, Duong V, Ngan C, Ong S, Huy R, Sroin KK, et al. Field evaluation and impact on clinical management of a rapid diagnostic kit that detects dengue NS1, IgM and IgG. PLoS Negl Trop Dis ; 6:e.,5959. Gan VC, Tan LK, Lye DC, Pok KY, Mok SQ, Chua RC, et al. Diagnosing dengue at the point-of-care: utility of a rapid combined diagnostic kit in Singapore. PLoS One ; 9:e.,6060. Garg A, Garg J, Singh DV, Dhole TN. Can rapid dengue diagnostic kits be trusted? A comparative study of commercially available rapid kits for serodiagnosis of dengue fever. J Lab Physicians ; 11:63-7.,6161. Huits R, Soentjens P, Maniewski-Kelner U, Theunissen C, Van Den Broucke S, Florence E, et al. Clinical utility of the nonstructural 1 antigen rapid diagnostic test in the management of dengue in returning travelers with fever. Open Forum Infect Dis ; 4:ofw273.,6262. Hunsperger EA, Sharp TM, Lalita P, Tikomaidraubuta K, Cardoso YR, Naivalu T, et al. Use of a rapid test for diagnosis of dengue during suspected dengue outbreaks in resource-limited regions. J Clin Microbiol ; 54:-5.,6363. Jang WS, Kwak SY, May WL, Yang DJ, Nam J, Lim CS. Comparative evaluation of three dengue duo rapid test kits to detect NS1, IgM, and IgG associated with acute dengue in children in Myanmar. PLoS One ; 14:e.,6464. Kikuti M, Cruz JS, Rodrigues MS, Tavares AS, Paploski IAD, Silva MMO, et al. Accuracy of the SD BIOLINE Dengue Duo for rapid point-of-care diagnosis of dengue. PLoS One ; 14:e.,6565. Krishnananthasivam S, Fernando AN, Tippalagama R, Tennekoon R, Man JD, Seneviratne D, et al. Evaluation of a commercial rapid test kit for detection of acute dengue infection. Southeast Asian J Trop Med Public Health ; 46:602-10.,6666. Kyaw AK, Ngwe Tun MM, Naing ST, Htet KKK, Htwe TT, Khaing YY, et al. Evaluation of commercially available three dengue rapid diagnostic test kits for diagnosis of acute dengue virus infection at the point-of-care setting in Myanmar. J Virol Methods ; 273:.,6767. Parham LA, Sánchez C, López MJ, Lorenzana I. Evaluation of two parameters for dengue diagnosis in Honduran patients. Am J Trop Med Hyg ; 91(5 Suppl 1):429.,6868. Liu LT, Dalipanda T, Jagilly R, Wang YH, Lin PC, Tsai CY, et al. Comparison of two rapid diagnostic tests during a large dengue virus serotype 3 outbreak in the Solomon Islands in . PLoS One ; 13:e.,6969. Pal S, Dauner AL, Valks A, Forshey BM, Long KC, Thaisomboonsuk B, et al. Multicountry prospective clinical evaluation of two enzyme-linked immunosorbent assays and two rapid diagnostic tests for diagnosing dengue fever. J Clin Microbiol ; 53:-102.,7070. Sanchez-Vargas LA, Sanchez-Marce EE, Vivanco-Cid H. Evaluation of the SD BIOLINE Dengue Duo rapid test in the course of acute and convalescent dengue infections in a Mexican endemic region. Diagn Microbiol Infect Dis ; 78:368-72.,7171. Sandoval JJV, Amores DR, Ramudo SV, Gutiérrez NC, Tirado MGG. Evaluation of the SD Dengue Duo diagnosis system for detection of NS1 protein and IgM and IgG dengue antibodies. Rev Cubana Med Trop ; 64:27-34.,7272. Shih HI, Hsu HC, Wu CJ, Lin CH, Chang CM, Tu YF, et al. Applications of a rapid and sensitive Dengue DUO Rapid Immunochromatographic Test kit as a diagnostic strategy during a dengue type 2 epidemic in an urban city. PLoS One ; 11:e.,7373. Shukla MK, Singh N, Sharma RK, Barde PV. Utility of dengue NS1 antigen rapid diagnostic test for use in difficult to reach areas and its comparison with dengue NS1 ELISA and qRT-PCR. J Med Virol ; 89:-50.,7474. Simonnet C, Okandze A, Matheus S, Djossou F, Nacher M, Mahamat A. Prospective evaluation of the SD BIOLINE Dengue Duo rapid test during a dengue virus epidemic. Eur J Clin Microbiol Infect Dis ; 36:-7.,7575. Tontulawat P, Pongsiri P, Thongmee C, Theamboonlers A, Kamolvarin N, Poovorawan Y. Evaluation of rapid immunochromatographic NS1 test, anti-dengue IgM test, semi-nested PCR and IgM ELISA for detection of dengue virus. Southeast Asian J Trop Med Public Health ; 42:570-8.,7676. Vickers I, Harvey K, Nelson K, Brown M, Bullock-DuCasse M, Lindo J. Evaluation of OneStep Dengue NS1 RapiDip InstaTest and OneStep Dengue Fever IgG/IgM RapiCard InstaTest during the course of a dengue type 1 epidemic. Diagn Microbiol Infect Dis ; 89:271-5.,7777. Vickers IE, Harvey KM, Brown MG, Nelson K, DuCasse MB, Lindo JF. The performance of the SD BIOLINE Dengue DUO(R) rapid immunochromatographic test kit for the detection of NS1 antigen, IgM and IgG antibodies during a dengue type 1 epidemic in Jamaica. J Biomed Sci ; 22:55. ( Table 1). The total number exceeds since some studies evaluated more than one ICT brand tests and type of analyte. Those articles evaluating NS1/IgM/IgG estimated not only the accuracy parameters for the three analytes, but also for each analyte separately.

Figure 1
Flowchart of the included studies.

Although planned, stratified analysis was not available in original studies, except for different analytes.

The 57 studies were performed mainly in Asia (33; 57.9%) and the Americas (18; 31.6%), only one in Oceania and mostly (94.1%) published in English.

The included studies analyzed 29 ICTs, using as the reference tests RT-PCR, real-time PCR, semi-nested PCR, NS1 ELISA, IgM ELISA, IgG ELISA, IgM antibody capture enzyme-linked immunosorbent assay (MAC ELISA IgM), IgG antibody capture enzyme-linked immunosorbent assay (GAC ELISA IgG), or virus isolation ( Table 1).

Quality assessment of the studies

According to the assessment of methodological quality conducted with the QUADAS 2 tool, of the 57 included studies, only six 2929. Blacksell SD, Jarman RG, Bailey MS, Tanganuchitcharnchai A, Jenjaroen K, Gibbons RV, et al. Evaluation of six commercial point-of-care tests for diagnosis of acute dengue infections: the need for combining NS1 antigen and IgM/IgG antibody detection to achieve acceptable levels of accuracy. Clin Vaccine Immunol ; 18:-101.,3030. Buonora SN, Passos SR, do Carmo CN, Quintela FM, de Oliveira DN, dos Santos FB, et al. Accuracy of clinical criteria and an immunochromatographic strip test for dengue diagnosis in a DENV-4 epidemic. BMC Infect Dis ; 16:37.,3838. Mata VE, Passos SRL, Hökerberg YHM, Berardinelli GM, Dos Santos MAB, Fukuoka LVB, et al. Accuracy and reliability of an NS1 rapid immunochromatographic test for DENV-1 diagnosis at point of care and in the laboratory. BMC Infect Dis ; 17:594.,3939. Najioullah F, Combet E, Paturel L, Martial J, Koulmann L, Thomas L, et al. Prospective evaluation of nonstructural 1 enzyme-linked immunosorbent assay and rapid immunochromatographic tests to detect dengue virus in patients with acute febrile illness. Diagn Microbiol Infect Dis ; 69:172-8.,6969. Pal S, Dauner AL, Valks A, Forshey BM, Long KC, Thaisomboonsuk B, et al. Multicountry prospective clinical evaluation of two enzyme-linked immunosorbent assays and two rapid diagnostic tests for diagnosing dengue fever. J Clin Microbiol ; 53:-102.,7878. Prado PS, Almeida Junior JTD, Abreu LT, Silva CG, Souza LDC, Gomes MC, et al. Validation and reliability of the rapid diagnostic test 'SD Bioeasy Dengue Duo' for dengue diagnosis in Brazil: a phase III study. Mem Inst Oswaldo Cruz ; 113:e. did not show risk of bias, and 25 (43.8%) of the them showed high risk of bias regarding the patient selection process ( Figure 2), mainly due to case-control design. Ten of them showed high risk of bias concerning flow and timing, mainly for excluding patients from analysis or for adopting inappropriate intervals between index and reference tests. Concerning reference standard, 31 studies were unclear and three showed high risk of bias, mainly due to not informing about blinding.

Figure 2
Quality assessment and risk of bias of the selected studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS 2).

However, we did not find any major conflicts that could compromise applicability in relation to patients included, index or reference tests in these studies from those targeted by our review questions.

Rapid immunochromatographic tests with IgA detection

A total of 2,051 samples from patients with suspected dengue virus infection were analyzed (median 342, interquartile range [IQR]: 100-914) in the five studies selected for this part of the review 2424. Ahmed F, Mursalin H, Alam MT, Amin R, Sekaran SD, Wang SM, et al. Evaluation of ASSURE(R) Dengue IgA Rapid Test using dengue-positive and dengue-negative samples. Diagn Microbiol Infect Dis ; 68:339-44.,2525. Hartono A, Sari SK. Diagnosis of dengue virus infection with IgA anti-dengue rapid tests. Int J Infect Dis ; 16 Suppl:e317-473.,2727. Naz A, Zahid D, Murky SN, Nadeem M, Sil BK, Shamsi TS. Evaluation of efficacy of various immunochromatographic rapid tests for dengue diagnosis. Pak J Med Sci ; 30:166-71.,27,2828. Tan YY, Sekaran SD, Wang SM, Ahmed F, Hossain A, Sil BK. Development of ASSURE Dengue IgA Rapid Test for the detection of anti-dengue IgA from dengue infected patients. J Glob Infect Dis ; 3:233-40.. One of them showed results in acute and convalescent samples 2424. Ahmed F, Mursalin H, Alam MT, Amin R, Sekaran SD, Wang SM, et al. Evaluation of ASSURE(R) Dengue IgA Rapid Test using dengue-positive and dengue-negative samples. Diagn Microbiol Infect Dis ; 68:339-44.. Pooled estimate of the IgA tests showed a sensitivity of 88% and specificity of 90% ( Table 2). It was not possible to assess publication bias for these tests due to the small number of studies included in the analysis. The pooled estimate in the acute phase showed slightly higher sensitivity (92.8 vs. 88) and the same specificity (90%) compared with the analysis which included convalescent samples. The performance of this test for screening was better than NS1 or IgM/IgG due to better sensitivity ( Table 2), but lower than tests with three analytes.

Forest plots ( Figure 3) showed similar results between studies, except for one case-control 2626. Hernandez SIC, Gonzalez Mateos S, Flores Aguilar H, Lopez Martinez I, Alpuche Aranda C, Ludert JE, et al. Evaluation of a novel commercial rapid test for dengue diagnosis based on specific IgA detection. Diagn Microbiol Infect Dis ; 72:150-5. which included mainly primary infections compared to secondary infections (5:1), despite high statistical heterogeneity (I2 = 93%). IgA ICT tests in scenarios with prevalence of 25% showed the positive post-test probability still moderately high (75%) compared to conclusive (90% and 96%) results in epidemic scenarios ( Table 2). Besides that, the negative post-test probabilities were reasonable up to 12% and 18% even in outbreaks ( Table 2).

Figure 3
Forest plot for the meta-analysis of rapid immunochromatographic tests (ICT) according to dengue diagnostic analyte.

Only one study 2626. Hernandez SIC, Gonzalez Mateos S, Flores Aguilar H, Lopez Martinez I, Alpuche Aranda C, Ludert JE, et al. Evaluation of a novel commercial rapid test for dengue diagnosis based on specific IgA detection. Diagn Microbiol Infect Dis ; 72:150-5. reported the serotypes tested ( Table 1). This study assessed the performance according to serotype (DENV-1 and 2), showing heterogeneous sensitivities (Sn = 52.4% in DENV-1 and 73.9% in DENV-2).

Three studies 2424. Ahmed F, Mursalin H, Alam MT, Amin R, Sekaran SD, Wang SM, et al. Evaluation of ASSURE(R) Dengue IgA Rapid Test using dengue-positive and dengue-negative samples. Diagn Microbiol Infect Dis ; 68:339-44.,2626. Hernandez SIC, Gonzalez Mateos S, Flores Aguilar H, Lopez Martinez I, Alpuche Aranda C, Ludert JE, et al. Evaluation of a novel commercial rapid test for dengue diagnosis based on specific IgA detection. Diagn Microbiol Infect Dis ; 72:150-5.,2727. Naz A, Zahid D, Murky SN, Nadeem M, Sil BK, Shamsi TS. Evaluation of efficacy of various immunochromatographic rapid tests for dengue diagnosis. Pak J Med Sci ; 30:166-71. included primary and secondary dengue infection cases without stratified analysis.

Rapid immunochromatographic tests with NS1 detection

Tests based exclusively on NS1 evaluated three brands up to : Bio-Rad, Panbio, Alere/Bio_Easy. These totalized 21 studies up to the seventh day of the disease 1010. Lima MRQ, Nogueira RM, Schatzmayr HG, dos Santos FB. Comparison of three commercially available dengue NS1 antigen capture assays for acute diagnosis of dengue in Brazil. PLoS Negl Trop Dis ; 4:e738.,2727. Naz A, Zahid D, Murky SN, Nadeem M, Sil BK, Shamsi TS. Evaluation of efficacy of various immunochromatographic rapid tests for dengue diagnosis. Pak J Med Sci ; 30:166-71.,3030. Buonora SN, Passos SR, do Carmo CN, Quintela FM, de Oliveira DN, dos Santos FB, et al. Accuracy of clinical criteria and an immunochromatographic strip test for dengue diagnosis in a DENV-4 epidemic. BMC Infect Dis ; 16:37.,3131. Chaiyaratana W, Chuansumrit A, Pongthanapisith V, Tangnararatchakit K, Lertwongrath S, Yoksan S. Evaluation of dengue nonstructural protein 1 antigen strip for the rapid diagnosis of patients with dengue infection. Diagn Microbiol Infect Dis ; 64:83-4.,3232. Dussart P, Petit L, Labeau B, Bremand L, Leduc A, Moua D, et al. Evaluation of two new commercial tests for the diagnosis of acute dengue virus infection using NS1 antigen detection in human serum. PLoS Negl Trop Dis ; 2:e280.,3333. Ferraz FO, Bomfim MR, Totola AH, Avila TV, Cisalpino D, Pessanha JE, et al. Evaluation of laboratory tests for dengue diagnosis in clinical specimens from consecutive patients with suspected dengue in Belo Horizonte, Brazil. J Clin Virol ; 58:41-6.,3434. Fry SR, Meyer M, Semple MG, Simmons CP, Sekaran SD, Huang JX, et al. The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach. PLoS Negl Trop Dis ; 5:e.,3535. Hang VT, Nguyet NM, Trung DT, Tricou V, Yoksan S, Dung NM, et al. Diagnostic accuracy of NS1 ELISA and lateral flow rapid tests for dengue sensitivity, specificity and relationship to viraemia and antibody responses. PLoS Negl Trop Dis ; 3:e360.,3636. Jusoh TNAM, Shueb RH. Performance evaluation of commercial dengue diagnostic tests for early detection of dengue in clinical samples. J Trop Med ; :.,3737. Lee H, Ryu JH, Park HS, Park KH, Bae H, Yun S, et al. Comparison of six commercial diagnostic tests for the detection of dengue virus non-structural-1 antigen and IgM/IgG antibodies. Ann Lab Med ; 39:566-71.,3838. Mata VE, Passos SRL, Hökerberg YHM, Berardinelli GM, Dos Santos MAB, Fukuoka LVB, et al. Accuracy and reliability of an NS1 rapid immunochromatographic test for DENV-1 diagnosis at point of care and in the laboratory. BMC Infect Dis ; 17:594.,3939. Najioullah F, Combet E, Paturel L, Martial J, Koulmann L, Thomas L, et al. Prospective evaluation of nonstructural 1 enzyme-linked immunosorbent assay and rapid immunochromatographic tests to detect dengue virus in patients with acute febrile illness. Diagn Microbiol Infect Dis ; 69:172-8.,4040. Osorio L, Ramirez M, Bonelo A, Villar LA, Parra B. Comparison of the diagnostic accuracy of commercial NS1-based diagnostic tests for early dengue infection. Virol J ; 7:361.,4141. Pal S, Dauner AL, Mitra I, Forshey BM, Garcia P, Morrison AC, et al. Evaluation of dengue NS1 antigen rapid tests and ELISA kits using clinical samples. PLoS One ; 9:e.,4242. Pan-ngum W, Blacksell SD, Lubell Y, Pukrittayakamee S, Bailey MS, de Silva HJ, et al. Estimating the true accuracy of diagnostic tests for dengue infection using bayesian latent class models. PLoS One ; 8:e.,4343. Pok KY, Lai YL, Sng J, Ng LC. Evaluation of nonstructural 1 antigen assays for the diagnosis and surveillance of dengue in Singapore. Vector Borne Zoonotic Dis ; 10:-16.,4444. Ramirez AH, Moros Z, Comach G, Zambrano J, Bravo L, Pinto B, et al. Evaluation of dengue NS1 antigen detection tests with acute sera from patients infected with dengue virus in Venezuela. Diagn Microbiol Infect Dis ; 65:247-53.,4545. Shu PY, Yang CF, Kao JF, Su CL, Chang SF, Lin CC, et al. Application of the dengue virus NS1 antigen rapid test for on-site detection of imported dengue cases at airports. Clin Vaccine Immunol ; 16:589-91.,4646. Tricou V, Vu HT, Quynh NV, Nguyen CV, Tran HT, Farrar J, et al. Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses. BMC Infect Dis ; 10:142.,4747. Zainah S, Wahab AH, Mariam M, Fauziah MK, Khairul AH, Roslina I, et al. Performance of a commercial rapid dengue NS1 antigen immunochromatography test with reference to dengue NS1 antigen-capture ELISA. J Virol Methods ; 155:157-60.,5050. Blacksell SD, Newton PN, Bell D, Kelley J, Mammen Jr. MP, Vaughn DW, et al. The comparative accuracy of 8 commercial rapid immunochromatographic assays for the diagnosis of acute dengue virus infection. Clin Infect Dis ; 42:-34., one of which 3434. Fry SR, Meyer M, Semple MG, Simmons CP, Sekaran SD, Huang JX, et al. The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach. PLoS Negl Trop Dis ; 5:e. presented the results of two settings, one in Malaysia and the other in Vietnam. The tests were assessed in 6,618 samples from patients with suspected dengue (median 241). Of 21 studies, 18 reported the serotypes tested, totaling 852 samples of DENV-1, 582 DENV-2, 501 DENV-3, and 510 DENV-4 ( Table 1), but did not show stratified performance analysis.

The pooled estimates for all NS1 tests showed sensitivity of 74%, and higher specificity of 99%. The lower sensitivity values were obtained for NS1 Bioeasy in a Brazilian sample of DENV-4 outbreak 3030. Buonora SN, Passos SR, do Carmo CN, Quintela FM, de Oliveira DN, dos Santos FB, et al. Accuracy of clinical criteria and an immunochromatographic strip test for dengue diagnosis in a DENV-4 epidemic. BMC Infect Dis ; 16:37. as well as for the brand Asan 3737. Lee H, Ryu JH, Park HS, Park KH, Bae H, Yun S, et al. Comparison of six commercial diagnostic tests for the detection of dengue virus non-structural-1 antigen and IgM/IgG antibodies. Ann Lab Med ; 39:566-71..

Bio-Rad Dengue Rapid Test was used for NS1 detection in 14 of the 21 studies 1010. Lima MRQ, Nogueira RM, Schatzmayr HG, dos Santos FB. Comparison of three commercially available dengue NS1 antigen capture assays for acute diagnosis of dengue in Brazil. PLoS Negl Trop Dis ; 4:e738.,3131. Chaiyaratana W, Chuansumrit A, Pongthanapisith V, Tangnararatchakit K, Lertwongrath S, Yoksan S. Evaluation of dengue nonstructural protein 1 antigen strip for the rapid diagnosis of patients with dengue infection. Diagn Microbiol Infect Dis ; 64:83-4.,3232. Dussart P, Petit L, Labeau B, Bremand L, Leduc A, Moua D, et al. Evaluation of two new commercial tests for the diagnosis of acute dengue virus infection using NS1 antigen detection in human serum. PLoS Negl Trop Dis ; 2:e280.,3333. Ferraz FO, Bomfim MR, Totola AH, Avila TV, Cisalpino D, Pessanha JE, et al. Evaluation of laboratory tests for dengue diagnosis in clinical specimens from consecutive patients with suspected dengue in Belo Horizonte, Brazil. J Clin Virol ; 58:41-6.,3535. Hang VT, Nguyet NM, Trung DT, Tricou V, Yoksan S, Dung NM, et al. Diagnostic accuracy of NS1 ELISA and lateral flow rapid tests for dengue sensitivity, specificity and relationship to viraemia and antibody responses. PLoS Negl Trop Dis ; 3:e360.,3939. Najioullah F, Combet E, Paturel L, Martial J, Koulmann L, Thomas L, et al. Prospective evaluation of nonstructural 1 enzyme-linked immunosorbent assay and rapid immunochromatographic tests to detect dengue virus in patients with acute febrile illness. Diagn Microbiol Infect Dis ; 69:172-8.,4040. Osorio L, Ramirez M, Bonelo A, Villar LA, Parra B. Comparison of the diagnostic accuracy of commercial NS1-based diagnostic tests for early dengue infection. Virol J ; 7:361.,4141. Pal S, Dauner AL, Mitra I, Forshey BM, Garcia P, Morrison AC, et al. Evaluation of dengue NS1 antigen rapid tests and ELISA kits using clinical samples. PLoS One ; 9:e.,4343. Pok KY, Lai YL, Sng J, Ng LC. Evaluation of nonstructural 1 antigen assays for the diagnosis and surveillance of dengue in Singapore. Vector Borne Zoonotic Dis ; 10:-16.,4444. Ramirez AH, Moros Z, Comach G, Zambrano J, Bravo L, Pinto B, et al. Evaluation of dengue NS1 antigen detection tests with acute sera from patients infected with dengue virus in Venezuela. Diagn Microbiol Infect Dis ; 65:247-53.,4545. Shu PY, Yang CF, Kao JF, Su CL, Chang SF, Lin CC, et al. Application of the dengue virus NS1 antigen rapid test for on-site detection of imported dengue cases at airports. Clin Vaccine Immunol ; 16:589-91.,4646. Tricou V, Vu HT, Quynh NV, Nguyen CV, Tran HT, Farrar J, et al. Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses. BMC Infect Dis ; 10:142.,4747. Zainah S, Wahab AH, Mariam M, Fauziah MK, Khairul AH, Roslina I, et al. Performance of a commercial rapid dengue NS1 antigen immunochromatography test with reference to dengue NS1 antigen-capture ELISA. J Virol Methods ; 155:157-60.,5050. Blacksell SD, Newton PN, Bell D, Kelley J, Mammen Jr. MP, Vaughn DW, et al. The comparative accuracy of 8 commercial rapid immunochromatographic assays for the diagnosis of acute dengue virus infection. Clin Infect Dis ; 42:-34. (4,678 samples). Sensitivity ranged from 49.4% 3939. Najioullah F, Combet E, Paturel L, Martial J, Koulmann L, Thomas L, et al. Prospective evaluation of nonstructural 1 enzyme-linked immunosorbent assay and rapid immunochromatographic tests to detect dengue virus in patients with acute febrile illness. Diagn Microbiol Infect Dis ; 69:172-8. to 98.9% 3131. Chaiyaratana W, Chuansumrit A, Pongthanapisith V, Tangnararatchakit K, Lertwongrath S, Yoksan S. Evaluation of dengue nonstructural protein 1 antigen strip for the rapid diagnosis of patients with dengue infection. Diagn Microbiol Infect Dis ; 64:83-4. and specificity from 91% 3535. Hang VT, Nguyet NM, Trung DT, Tricou V, Yoksan S, Dung NM, et al. Diagnostic accuracy of NS1 ELISA and lateral flow rapid tests for dengue sensitivity, specificity and relationship to viraemia and antibody responses. PLoS Negl Trop Dis ; 3:e360. to 100% in 8 studies 3232. Dussart P, Petit L, Labeau B, Bremand L, Leduc A, Moua D, et al. Evaluation of two new commercial tests for the diagnosis of acute dengue virus infection using NS1 antigen detection in human serum. PLoS Negl Trop Dis ; 2:e280.,3333. Ferraz FO, Bomfim MR, Totola AH, Avila TV, Cisalpino D, Pessanha JE, et al. Evaluation of laboratory tests for dengue diagnosis in clinical specimens from consecutive patients with suspected dengue in Belo Horizonte, Brazil. J Clin Virol ; 58:41-6.,3535. Hang VT, Nguyet NM, Trung DT, Tricou V, Yoksan S, Dung NM, et al. Diagnostic accuracy of NS1 ELISA and lateral flow rapid tests for dengue sensitivity, specificity and relationship to viraemia and antibody responses. PLoS Negl Trop Dis ; 3:e360.,3939. Najioullah F, Combet E, Paturel L, Martial J, Koulmann L, Thomas L, et al. Prospective evaluation of nonstructural 1 enzyme-linked immunosorbent assay and rapid immunochromatographic tests to detect dengue virus in patients with acute febrile illness. Diagn Microbiol Infect Dis ; 69:172-8.,4141. Pal S, Dauner AL, Mitra I, Forshey BM, Garcia P, Morrison AC, et al. Evaluation of dengue NS1 antigen rapid tests and ELISA kits using clinical samples. PLoS One ; 9:e.,4343. Pok KY, Lai YL, Sng J, Ng LC. Evaluation of nonstructural 1 antigen assays for the diagnosis and surveillance of dengue in Singapore. Vector Borne Zoonotic Dis ; 10:-16.,4545. Shu PY, Yang CF, Kao JF, Su CL, Chang SF, Lin CC, et al. Application of the dengue virus NS1 antigen rapid test for on-site detection of imported dengue cases at airports. Clin Vaccine Immunol ; 16:589-91.,4646. Tricou V, Vu HT, Quynh NV, Nguyen CV, Tran HT, Farrar J, et al. Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses. BMC Infect Dis ; 10:142.. The pooled estimate for the Bio-Rad Dengue Rapid Test showed sensitivity of 79% and specificity of 100% ( Table 2). The post-test probability after a positive result in NS1-based ICT was above 95% in three different hypothetical scenarios of dengue prevalence of 25%, 50% and 75%.

Several recent studies tested SD Duo Bioline ICT but only showed NS1 results. We opted to describe these on Table 1, but to exclude them from the meta-analyses since there was not blinding of other analyte results in the same cassette.

Assessment of the individual studies did not show publication bias (p-value = 0.09).

Rapid immunochromatographic tests with IgM/IgG detection

Seven studies assessed tests with both IgM/IgG detection 2727. Naz A, Zahid D, Murky SN, Nadeem M, Sil BK, Shamsi TS. Evaluation of efficacy of various immunochromatographic rapid tests for dengue diagnosis. Pak J Med Sci ; 30:166-71.,4848. Aikat A, Sarkar A, Tudu N, Moitra S, Pal PP, Sarkar TK. Diagnostic dilemma of dengue fever: how much reliability are there in rapidity. J Indian Med Assoc ; 109:543-5.,5050. Blacksell SD, Newton PN, Bell D, Kelley J, Mammen Jr. MP, Vaughn DW, et al. The comparative accuracy of 8 commercial rapid immunochromatographic assays for the diagnosis of acute dengue virus infection. Clin Infect Dis ; 42:-34.,5151. Branch SL, Levett PN. Evaluation of four methods for detection of immunoglobulin M antibodies to dengue virus. Clin Diagn Lab Immunol ; 6:555-7.,5252. Cohen AL, Dowell SF, Nisalak A, Mammen Jr. MP, Petkanchanapong W, Fisk TL. Rapid diagnostic tests for dengue and leptospirosis: antibody detection is insensitive at presentation. Trop Med Int Health ; 12:47-51.,5353. Congpuong K, Chuchan S, Kwangthong S, Kangchaingone Y, Darakapong A. Appropriate laboratory tests for the diagnosis of dengue infection at a general hospital in Southern Thailand. Asian Biomed (Res Rev News) ; 2:289-95.,5454. Martinez-Vega RA, Diaz-Quijano FA, Coronel-Ruiz C, Yebrail Gomez S, Villar-Centeno LA. Evaluation of PANBIO rapid immunochromatographic cassette for dengue diagnosis in a Colombian endemic area. Biomedica ; 29:616-24., using 2,597 samples (median 178). Seven studies identified the dengue serotypes, with a total of 251 DENV-1, 176 DENV-2, 193 DENV-3, and 77 DENV-4. Most studies except one evaluating exclusively IgM/IgG ICT were published up to ( Table 1).

These tests presented the lowest values of pooled estimates of sensitivity (54%), with inadequate values of negative likelihood ratios (NLR > 0.4) ( Table 2). Thus, the post-test probabilities after negative results were inconclusive, particularly for epidemic scenarios of prevalence. In the convalescent phase of the disease, the pooled estimate of accuracy showed, as expected, higher sensitivity (Sn = 62.6%, 95%CI: 36.7-82.9), than in the acute phase, 53.8% (95%CI: 41.4-65.8), and high specificity in all phases of the disease (94% and 94.7%,). Specificity was lower for recent studies 2727. Naz A, Zahid D, Murky SN, Nadeem M, Sil BK, Shamsi TS. Evaluation of efficacy of various immunochromatographic rapid tests for dengue diagnosis. Pak J Med Sci ; 30:166-71.,5454. Martinez-Vega RA, Diaz-Quijano FA, Coronel-Ruiz C, Yebrail Gomez S, Villar-Centeno LA. Evaluation of PANBIO rapid immunochromatographic cassette for dengue diagnosis in a Colombian endemic area. Biomedica ; 29:616-24..

Panbio Dengue Duo IgM/IgG was the most widely assessed test, with pooled sensitivity and specificity of 56% and 90% ( Figure 3; Table 2).

We detected no publication bias (p = 0.13).

Rapid immunochromatographic tests with simultaneous NS1/IgM/IgG detection

Ten studies that assessed that type of test included a total of 3,361 patients (median 447) with suspected dengue, with 289 DENV-1, 225 DENV-2, 52 DENV-3 and 39 DENV-4 3636. Jusoh TNAM, Shueb RH. Performance evaluation of commercial dengue diagnostic tests for early detection of dengue in clinical samples. J Trop Med ; :.,3737. Lee H, Ryu JH, Park HS, Park KH, Bae H, Yun S, et al. Comparison of six commercial diagnostic tests for the detection of dengue virus non-structural-1 antigen and IgM/IgG antibodies. Ann Lab Med ; 39:566-71.,4040. Osorio L, Ramirez M, Bonelo A, Villar LA, Parra B. Comparison of the diagnostic accuracy of commercial NS1-based diagnostic tests for early dengue infection. Virol J ; 7:361.,4646. Tricou V, Vu HT, Quynh NV, Nguyen CV, Tran HT, Farrar J, et al. Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses. BMC Infect Dis ; 10:142.,5858. Andries AC, Duong V, Ngan C, Ong S, Huy R, Sroin KK, et al. Field evaluation and impact on clinical management of a rapid diagnostic kit that detects dengue NS1, IgM and IgG. PLoS Negl Trop Dis ; 6:e.,5959. Gan VC, Tan LK, Lye DC, Pok KY, Mok SQ, Chua RC, et al. Diagnosing dengue at the point-of-care: utility of a rapid combined diagnostic kit in Singapore. PLoS One ; 9:e.,6969. Pal S, Dauner AL, Valks A, Forshey BM, Long KC, Thaisomboonsuk B, et al. Multicountry prospective clinical evaluation of two enzyme-linked immunosorbent assays and two rapid diagnostic tests for diagnosing dengue fever. J Clin Microbiol ; 53:-102.,7070. Sanchez-Vargas LA, Sanchez-Marce EE, Vivanco-Cid H. Evaluation of the SD BIOLINE Dengue Duo rapid test in the course of acute and convalescent dengue infections in a Mexican endemic region. Diagn Microbiol Infect Dis ; 78:368-72.,7777. Vickers IE, Harvey KM, Brown MG, Nelson K, DuCasse MB, Lindo JF. The performance of the SD BIOLINE Dengue DUO(R) rapid immunochromatographic test kit for the detection of NS1 antigen, IgM and IgG antibodies during a dengue type 1 epidemic in Jamaica. J Biomed Sci ; 22:55.,7979. Carter MJ, Emary KR, Moore CE, Parry CM, Sona S, Putchhat H, et al. Rapid diagnostic tests for dengue virus infection in febrile Cambodian children: diagnostic accuracy and incorporation into diagnostic algorithms. PLoS Negl Trop Dis ; 9:e. ( Table 1).

The best performance was observed for these tests with pooled positive and negative likelihood ratios, of 19.2 and 0.09, respectively. The post-test probability after negative and positive results in endemic (25%) and epidemic (75%) scenarios of dengue prevalence were below 25% and above 85%, respectively. The pooled estimate of sensitivity was 91% and specificity, 96% ( Table 2). Carter et al. 7979. Carter MJ, Emary KR, Moore CE, Parry CM, Sona S, Putchhat H, et al. Rapid diagnostic tests for dengue virus infection in febrile Cambodian children: diagnostic accuracy and incorporation into diagnostic algorithms. PLoS Negl Trop Dis ; 9:e. obtained the poorest performance in sensitivity. After excluding it, the pooled results were unchanged, Sn = 92% (87-95%) and Sp = 96% (92-98%).

Some recent studies also reported results for each analyte separately even when testing ICT composed of a cassette with three analytes. We describe these “only results” on Table 1 without including these meta-analyses, since this was only a statistical analysis and not a practical use of a test with a single analyte in a cassette.

We observed no asymmetry in the assessment of publication bias in the studies (p-value = 0.09).

Discussion

This was a systematic review addressing the dengue virus detection methods in commercially available ICTs, obtained through a search of nine large databases, with 57 studies included. One strategy used to increase the tests’ performance was the simultaneous test of the three analytes NS1, IgM, and IgG 4040. Osorio L, Ramirez M, Bonelo A, Villar LA, Parra B. Comparison of the diagnostic accuracy of commercial NS1-based diagnostic tests for early dengue infection. Virol J ; 7:361.,4646. Tricou V, Vu HT, Quynh NV, Nguyen CV, Tran HT, Farrar J, et al. Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses. BMC Infect Dis ; 10:142.,5656. Pun R, Shah Y, Gupta GP, Sherchand SP, Pandey BD. Prognostic value of rapid test for diagnosis of dengue in Nepalese patients during epidemic. Kathmandu Univ Med J (KUMJ) ; 10:7-10.,5858. Andries AC, Duong V, Ngan C, Ong S, Huy R, Sroin KK, et al. Field evaluation and impact on clinical management of a rapid diagnostic kit that detects dengue NS1, IgM and IgG. PLoS Negl Trop Dis ; 6:e.,6767. Parham LA, Sánchez C, López MJ, Lorenzana I. Evaluation of two parameters for dengue diagnosis in Honduran patients. Am J Trop Med Hyg ; 91(5 Suppl 1):429.,7171. Sandoval JJV, Amores DR, Ramudo SV, Gutiérrez NC, Tirado MGG. Evaluation of the SD Dengue Duo diagnosis system for detection of NS1 protein and IgM and IgG dengue antibodies. Rev Cubana Med Trop ; 64:27-34.. In our review, these ICTs showed high pooled estimates, better than those of IgA ICTs. Among the ICTs with serological detection assessed in this review, those with IgA detection stood out as having the best accuracy, with high pooled sensitivity and specificity in the acute phase compared to IgM/IgG ICT.

IgA tests showed the best performance in triage of patients in acute phase of the disease. They were twice as positive among cases with up to seven days of dengue fever when compared to those in the convalescent phase. Still, these studies did not analyze the tests according to phase of disease (acute/convalescent), thus making it impossible to claim that this same performance would be maintained in the initial days of the disease.

The current review showed an excellent pooled specificity (99%-100%) in the acute phase of the disease in ICTs with exclusive detection of NS1, six times more positive among dengue cases when compared to IgA ICTs during the same phase of the disease. These findings corroborate those of Lima et al. 1010. Lima MRQ, Nogueira RM, Schatzmayr HG, dos Santos FB. Comparison of three commercially available dengue NS1 antigen capture assays for acute diagnosis of dengue in Brazil. PLoS Negl Trop Dis ; 4:e738., who suggested the best performance of NS1 to confirm dengue cases in the acute phase of disease.

The systematic review published by Alagarasu et al. 1111. Alagarasu K, Walimbe AM, Jadhav SM, Deoshatwar AR. A meta-analysis of the diagnostic accuracy of dengue virus-specific IgA antibody-based tests for detection of dengue infection. Epidemiol Infect ; 144:876-86. assessed IgA ICTs, including three studies with lower estimate sensitivity of 72% and similar specificity (89%). However, the wide confidence intervals in the measures of accuracy both in our review and in Alagarasu et al. 1111. Alagarasu K, Walimbe AM, Jadhav SM, Deoshatwar AR. A meta-analysis of the diagnostic accuracy of dengue virus-specific IgA antibody-based tests for detection of dengue infection. Epidemiol Infect ; 144:876-86. make its use for screening questionable.

In recent years, several authors have questioned the use of IgM/IgG serology to detect dengue and other flaviviruses, due to the tests’ proven cross-reaction with the Zika, yellow fever, and chikungunya viruses, thus limiting their use in scenarios with co-circulation of these viruses 66. Blacksell SD, Doust JA, Newton PN, Peacock SJ, Day NP, Dondorp AM. A systematic review and meta-analysis of the diagnostic accuracy of rapid immunochromatographic assays for the detection of dengue virus IgM antibodies during acute infection. Trans R Soc Trop Med Hyg ; 100:775-84.,8080. Dejnirattisai W, Supasa P, Wongwiwat W, Rouvinski A, Barba-Spaeth G, Duangchinda T, et al. Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus. Nat Immunol ; 17:-8.,8181. Steinhagen K, Probst C, Radzimski C, Schmidt-Chanasit J, Emmerich P, van Esbroeck M, et al. Serodiagnosis of Zika virus (ZIKV) infections by a novel NS1-based ELISA devoid of cross-reactivity with dengue virus antibodies: a multicohort study of assay performance, to . Euro Surveill ; 21:..

The systematic review by Zhang et al. 44. Zhang H, Li W, Wang J, Peng H, Che X, Chen X, et al. NS1-based tests with diagnostic utility for confirming dengue infection: a meta-analysis. Int J Infect Dis ; 26:57-66. showed pooled estimates to these NS1 ICTs similar to our review, with Sn = 71% and Sp = 99%. Both in Zhang et al. 44. Zhang H, Li W, Wang J, Peng H, Che X, Chen X, et al. NS1-based tests with diagnostic utility for confirming dengue infection: a meta-analysis. Int J Infect Dis ; 26:57-66. and in our review, the performance of NS1 ICT in scenarios with 25%, 50%, and 75% of dengue prevalence pointed to increasing positive post-test probability, ranging from 99 to 100%. When used in screening, these tests should be coupled with a diagnostic algorithm in order to optimize their performance, due to the high number of false-negatives 44. Zhang H, Li W, Wang J, Peng H, Che X, Chen X, et al. NS1-based tests with diagnostic utility for confirming dengue infection: a meta-analysis. Int J Infect Dis ; 26:57-66..

The accuracy of IgM/IgG ICTs had the worst performance and studies about this ICT were interrupted in . The systematic review by Blacksell et al. 66. Blacksell SD, Doust JA, Newton PN, Peacock SJ, Day NP, Dondorp AM. A systematic review and meta-analysis of the diagnostic accuracy of rapid immunochromatographic assays for the detection of dengue virus IgM antibodies during acute infection. Trans R Soc Trop Med Hyg ; 100:775-84. assessed the Panbio ICT in the acute phase of the disease and the summary measures were superior to those in our review. Among other factors, these differences can be attributed to the samples’ characteristics related to the convalescent phase or samples with mostly primary infection 66. Blacksell SD, Doust JA, Newton PN, Peacock SJ, Day NP, Dondorp AM. A systematic review and meta-analysis of the diagnostic accuracy of rapid immunochromatographic assays for the detection of dengue virus IgM antibodies during acute infection. Trans R Soc Trop Med Hyg ; 100:775-84.,1111. Alagarasu K, Walimbe AM, Jadhav SM, Deoshatwar AR. A meta-analysis of the diagnostic accuracy of dengue virus-specific IgA antibody-based tests for detection of dengue infection. Epidemiol Infect ; 144:876-86..

Only two studies included in this review reported a potential conflict of interest 3131. Chaiyaratana W, Chuansumrit A, Pongthanapisith V, Tangnararatchakit K, Lertwongrath S, Yoksan S. Evaluation of dengue nonstructural protein 1 antigen strip for the rapid diagnosis of patients with dengue infection. Diagn Microbiol Infect Dis ; 64:83-4.,4646. Tricou V, Vu HT, Quynh NV, Nguyen CV, Tran HT, Farrar J, et al. Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses. BMC Infect Dis ; 10:142.. Only one 3131. Chaiyaratana W, Chuansumrit A, Pongthanapisith V, Tangnararatchakit K, Lertwongrath S, Yoksan S. Evaluation of dengue nonstructural protein 1 antigen strip for the rapid diagnosis of patients with dengue infection. Diagn Microbiol Infect Dis ; 64:83-4. reported sensitivity results that differed from the pooled sensitivity in our review.

In addition to the review’s originality, one of its strengths was the scope of the literature search, which included all types of commercially available ICTs for dengue detection, with subgroup analysis according to the ICT detection method in each of the principal commercial ICTs, and when possible, according to the phase of the disease (acute/convalescent).

The review’s limitations include the low methodological quality of the included studies and the lack of data for adequate characterization of the samples (27/34, 79.4%), either by age bracket (21/34, 61.8%) or dengue serotype (16/34, 47.1%), which prevented such subgroup analyses. Another limitation was the high heterogeneity detected in all the types of ICTs that were assessed, possibly due to the differences between the characteristics of the samples included by the studies. These differences were related to the age of the included patients, predominant type of infection (primary or secondary), serotypes assessed, disease phase assessed by the tests (acute/convalescent), and different reference tests (real-time PCR, RT-PCR, in-house ELISA, MAC-ELISA, among others). This heterogeneity may not be explained by the different reference standards since only three studies did not used at least one test with high specificity (100% for RT-PCR or ELISA NS1) 1010. Lima MRQ, Nogueira RM, Schatzmayr HG, dos Santos FB. Comparison of three commercially available dengue NS1 antigen capture assays for acute diagnosis of dengue in Brazil. PLoS Negl Trop Dis ; 4:e738.. Thus, the sensitivity of ICTs does not seem to be penalized by the reference standards. Similarly, the almost perfect specificities of ICTs were not influenced by non-optimal sensitivities (89.5%) of reference tests.

The three systematic reviews that included ICTs pointed to the same limitations described above 44. Zhang H, Li W, Wang J, Peng H, Che X, Chen X, et al. NS1-based tests with diagnostic utility for confirming dengue infection: a meta-analysis. Int J Infect Dis ; 26:57-66.,66. Blacksell SD, Doust JA, Newton PN, Peacock SJ, Day NP, Dondorp AM. A systematic review and meta-analysis of the diagnostic accuracy of rapid immunochromatographic assays for the detection of dengue virus IgM antibodies during acute infection. Trans R Soc Trop Med Hyg ; 100:775-84.,1111. Alagarasu K, Walimbe AM, Jadhav SM, Deoshatwar AR. A meta-analysis of the diagnostic accuracy of dengue virus-specific IgA antibody-based tests for detection of dengue infection. Epidemiol Infect ; 144:876-86.. Guidelines like the Standards for Reporting Diagnostic Accuracy Studies (STARD) 8282. Cohen JF, Korevaar DA, Altman DG, Bruns DE, Gatsonis CA, Hooft L, et al. STARD guidelines for reporting diagnostic accuracy studies: explanation and elaboration. BMJ Open ; 6:e. and tools like QUADAS 2 2020. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med ; 155:529-36. have contributed to the standardization of reporting by accuracy studies, as indicated by Blacksell et al. 8383. Blacksell SD. Commercial dengue rapid diagnostic tests for point-of-care application: recent evaluations and future needs? J Biomed Biotechnol ; :.. We emphasize that peer-reviewed journals and regulatory agencies should require the use of both these guidelines in order to assist future reviews and the elaboration of recommendations or protocols. Future studies should investigate cost-effectiveness, decision tree or a combination of multiple tests, including ICT in the diagnostic algorithm.

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