Prospective Study To Determine Accuracy of Rapid Serological Assays for Diagnosis of Acute Dengue Virus Infection in Laos

ABSTRACT There is an urgent need for accurate and simple dengue virus infection diagnostic assays in limited-resource settings of dengue endemicity, to assist patient management. Using a panel of reference samples (S. D. Blacksell, P. N. Newton, D. Bell, J. Kelley, M. P. Mammen, D. W. Vaughn, V. Wuthiekanun, A. Sungkakum, A. Nisalak, and N. P. Day, Clin. Infect. Dis. 42:1127-1134, 2006), we recently evaluated eihgt commercially available immunochromatographic rapid diagnostic tests (RDTs) designed to detect dengue virus-specific immunoglobulin M (IgM) and/or IgG. We found that 6/8 RDTs had sensitivities of less than 50% (range, 6 to 65%), but specificities were generally high. Here, in conjuction with dengue virus serotyping by reverse transcriptase PCR and in the limited-resource setting of Laos, where dengue virus is endemic, we evaluated the same eight RDTs against a previously validated dengue IgM/IgG enzyme-linked immunosorbent assay for diagnosis of acute dengue virus infection. Paired serum samples were collected from 87 patients, of whom 38 had confirmed dengue virus infections (4 had primary infections, 33 had secondary infections, and 1 had an infection of indeterminate status). RDT sensitivity was low, with 7/8 RDTs having admission sample sensitivities of less than 20% (range, 4 to 26%). The majority (6/8) of the RDTs, demonstrated high specificity (>95%). Kappa statistic values ranged from 6 to 54% for the RDTs, demonstrating poor to moderate variation between three operators. No RDT adequately differentiated between primary and secondary dengue virus infections. The findings of this study suggest that currently available RDTs based on the detection of IgM antibodies for the diagnosis of acute dengue virus infections are unlikely to be useful for patient management.

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Immunoglobulin A Antibody Responses in Dengue Patients: a Useful Marker for Serodiagnosis of Dengue Virus Infection

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.10.1235-1237.2005 ◽

2005 ◽

Vol 12 (10) ◽

pp. 1235-1237 ◽

Cited By ~ 14

Author(s):

M. Nawa ◽

T. Takasaki ◽

M. Ito ◽

S. Inoue ◽

K. Morita ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Immunoglobulin A ◽

Antibody Responses ◽

Enzyme Linked Immunosorbent Assay ◽

Virus Infections ◽

Serum Samples ◽

Dengue Virus Infection ◽

Iga Antibody ◽

Antibody Capture

ABSTRACT We determined the usefulness of an immunoglobulin A (IgA) antibody-capture enzyme-linked immunosorbent assay for serodiagnosis of dengue virus infections. The results indicate that the presence of IgA and IgM in serum samples assures recent primary dengue virus infection even with a single serum sample.

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Diagnosis of Dengue Virus Infection by the Visual and Simple AuBioDOT Immunoglobulin M Capture System

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.10.6.1074-1077.2003 ◽

2003 ◽

Vol 10 (6) ◽

pp. 1074-1077 ◽

Cited By ~ 9

Author(s):

Susana Vázquez ◽

Gilda Lemos ◽

Maritza Pupo ◽

Oscar Ganzón ◽

Daniel Palenzuela ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Immunoglobulin M ◽

World Health ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Dengue Virus Infection ◽

Capture Elisa ◽

Igm Antibodies ◽

Health Organization

ABSTRACT The Dengue IgM Capture ELISA (MAC-ELISA) is the immunoenzymatic system recommended by the Pan American Health Organization and the World Health Organization for the serological diagnosis of dengue virus infection due to its high sensitivity, ease of performance, and use of a single acute-phase serum sample. However, tests with this enzyme-linked immunosorbent assay (ELISA) system are time-consuming and require equipment for washing, incubation, and reading of the results. AuBioDOT is a multistep visual diagnostic immunoassay that uses technology based on the immunoglobulin M (IgM) capture ELISA principle. This system uses white polyethylene opaque plates as the solid phase, colloidal gold as the marker, and silver ion amplification. It does not require special equipment, it is totally manually operated, and it can be performed in less than 1 h. The sensitivity and specificity of AuBioDOT for the detection of anti-dengue virus IgM antibodies were studied with a panel of 336 serum samples (150 serum samples from patients with suspected or serologically confirmed dengue virus infection, 186 serum samples from healthy blood donors and patients without dengue virus infection). The results were compared with those obtained by the MAC-ELISA. A sensitivity of 97.7% and a specificity of 97.1% were obtained. The concordance of the two tests was 97.3%, with a kappa index of 0.94. The application of AuBioDOT for the detection of anti-dengue virus IgM antibodies is recommended as an alternative method for the diagnosis of dengue virus infection, both for clinical diagnosis and for seroepidemiological surveillance. The system is useful under field conditions and in laboratories and requires little equipment.

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Artificial Receptors in Serologic Tests for the Early Diagnosis of Dengue Virus Infection

Clinical Chemistry ◽

10.1373/clinchem.2005.064501 ◽

2006 ◽

Vol 52 (8) ◽

pp. 1486-1491 ◽

Cited By ~ 50

Author(s):

Dar-Fu Tai ◽

Chung-Yin Lin ◽

Tzong-Zeng Wu ◽

Jyh-Hsiung Huang ◽

Pei-Yun Shu

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Nonstructural Protein ◽

Sample Pretreatment ◽

Virus Infections ◽

Serum Samples ◽

Dengue Virus Infection ◽

Artificial Receptors ◽

Nonstructural Protein 1 ◽

Sensitive Sensor

Abstract Background: Because of the range and nonspecificity of clinical presentations of dengue virus infections, we felt there was a need to create diagnostic tests. We used artificial receptors for the virus to develop serologic assays to detect dengue virus infection. Methods: We coated a quartz crystal microbalance (QCM) with molecularly imprinted polymers specific for nonstructural protein 1 of flavivirus. These artificial receptors were specifically created on a QCM chip by polymerization of monomers and were cross-linked in the presence of the epitope site of nonstructural protein 1. We tested serum samples from patients with confirmed cases of dengue reported to the Center for Disease Control in Taipei. Samples were diluted 100-fold; no other sample pretreatment was used. The QCM response was compared with results of monoclonal ELISA. Results: QCM signals were >15 Hz in 18 of 21 (86%) of dengue samples and in 0 of 16 control samples. The correlation (r2) of the QCM response and the ELISA result was 0.73. Within-run and run-to-run imprecisions (CV) were 4%–28% and 10%–32%, respectively. Conclusions: The described assay offers a serologic technique for diagnosis of early viremia. The results illustrate the potential of well-organized polymers on the highly sensitive sensor system for diagnostic and biotechnological applications.

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Serotype-Cross-Reactive Immunoglobulin M Responses in Dengue Virus Infections Determined by Enzyme-Linked Immunosorbent Assay

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.7.5.774-777.2000 ◽

2000 ◽

Vol 7 (5) ◽

pp. 774-777 ◽

Cited By ~ 18

Author(s):

Masaru Nawa ◽

Ken-Ichiro Yamada ◽

Tomohiko Takasaki ◽

Toshitaka Akatsuka ◽

Ichiro Kurane

Keyword(s):

Dengue Virus ◽

Japanese Patients ◽

Immunoglobulin M ◽

Enzyme Linked Immunosorbent Assay ◽

Virus Infections ◽

Serum Samples ◽

Reverse Transcription Pcr ◽

Virus Serotype ◽

Dengue Virus Serotypes ◽

Antibody Capture

ABSTRACT We developed immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assays (ELISAs) with four monovalent dengue virus antigens. We attempted to determine whether IgM responses in dengue virus infections are serotype specific or serotype cross-reactive. Serum samples from 14 confirmed dengue cases were examined. In these 14 cases, which consisted of 12 Japanese and 2 non-Japanese patients, infecting dengue virus serotypes were defined by reverse transcription-PCR. Thirteen of the 14 cases were IgM positive in ELISA. IgM responses were serotype cross-reactive in these 13 cases but were highest against infecting dengue virus serotype in 9 of the 13 cases. These results indicate that IgM responses are generally dengue serotype cross-reactive but that IgM levels are highest against the infecting serotype in most dengue cases.

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Can rapid dengue diagnostic kits be trusted? A comparative study of commercially available rapid kits for serodiagnosis of dengue fever

Journal of Laboratory Physicians ◽

10.4103/jlp.jlp_140_18 ◽

2019 ◽

Vol 11 (01) ◽

pp. 063-067 ◽

Cited By ~ 5

Author(s):

Atul Garg ◽

Jaya Garg ◽

Dharam Singh ◽

TN Dhole

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Febrile Illness ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Dengue Virus Infection ◽

Medical College ◽

Study Results ◽

Ns1 Antigen ◽

Low Sensitivity

Abstract BACKGROUND: Dengue virus infection is an important emerging disease of the tropical and subtropical regions and is mainly diagnosed by serological detection of NS1 antigen and IgM antidengue antibodies. Since enzyme-linked immunosorbent assay (ELISA) facilities are not easily available at most diagnostic centers, so most of them use various commercially available rapid diagnostic tests (RDTs) kits. AIMS AND OBJECTIVES: This study was designed to access the diagnostic accuracy of four commercially available and widely used RDTs for serodiagnosis of dengue virus infection in Indian laboratories. SUBJECTS AND METHODS: The study was conducted at Department of Microbiology, G.S.V.M Medical College, Kanpur, India, to estimate the sensitivity and specificity of following RDTs: (1) Dengue Cassette (Panbio, Australia), (2) Bioline Dengue Duo (SD Diagnostics, Korea), (3) Dengue Day 1 test (J Mitra and Co., India), and (4) Dengucheck Duo (Tulip Diagnostics, India) on 72 confirmed dengue serum samples that were positive by dengue reverse transcription-polymerase chain reaction, dengue NS1, and IgM ELISA along with 80 serum samples from nondengue febrile illness patients. RESULTS: The majority of the RDTs demonstrated low sensitivity but good specificity for detecting NS1 antigen. Detection of antidengue IgM antibodies by RDTs demonstrated low sensitivity ranging from 27.8% to 77.7%. However, specificity was generally higher (50%–86.2%) and more consistent across the assays. CONCLUSION: The study results differed markedly from the RDTs manufacturers’ claimed performance characteristics. Therefore, the RDT results should be interpreted cautiously and ELISA should be performed as far as possible for serodiagnosis of dengue virus infection.

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Specific IgM and IgG responses in primary and secondary dengue virus infections determined by enzyme-linked immunosorbent assay

Epidemiology and Infection ◽

10.1017/s0950268805005753 ◽

2005 ◽

Vol 134 (4) ◽

pp. 820-825 ◽

Cited By ~ 50

Author(s):

A. SA-NGASANG ◽

S. ANANTAPREECHA ◽

A. A-NUEGOONPIPAT ◽

S. CHANAMA ◽

S. WIBULWATTANAKIJ ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Secondary Infection ◽

Enzyme Linked Immunosorbent Assay ◽

Virus Infections ◽

Dengue Virus Infection ◽

Provincial Hospital ◽

Secondary Infections ◽

Positive Rate ◽

Specific Igg

IgM- and IgG-capture ELISAs are widely used as diagnostic tests for confirmation of dengue virus infection. The positive rate of anti-dengue IgM and IgG detection was examined in primary and secondary dengue virus infections in the setting of a provincial hospital using IgM- and IgG-capture ELISAs. Disease day 1 was defined as the day of onset of symptoms. In total, 232 plasma samples were collected from 106 confirmed dengue cases consisting of 12 primary and 94 secondary infections. In primary infection, anti-dengue IgM was detected in 4 out of 5 samples collected on disease day 5 and in all the 21 samples collected on disease day 6 or later. Specific IgG was detected in 2 out of 5 samples collected on day 12, and in 5 out of 6 samples collected on disease days 13–15, but was not detected in samples collected on disease day 10 or earlier. In secondary infection, IgM was not detected in the samples on disease days 2 and 3, but detected in 20 out of 79 samples collected on days 4–6, in 44 out of 65 on disease days 7–11 and in 40 out of 51 samples on disease days 12–14. In contrast, specific IgG was detected in 21 out of 60 samples on disease days 4 and 5, in 13 out of 19 on disease day 6, in 62 out of 65 on disease days 7–11 and in all the samples collected on disease day 12 or later. The result indicate that seroconversion rates of IgM and IgG are different between primary and secondary infections, and suggest that detection of specific IgM and IgG is necessary for determining dengue virus infection and for differentiating primary and secondary dengue infections.

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Evaluation of a New Commercially Available Immunoglobulin M Capture Enzyme-Linked Immunosorbent Assay for Diagnosis of Dengue Virus Infection

Journal of Clinical Microbiology ◽

10.1128/jcm.00351-13 ◽

2013 ◽

Vol 51 (9) ◽

pp. 3102-3106 ◽

Cited By ~ 16

Author(s):

M. Namekar ◽

E. M. Ellis ◽

M. O'Connell ◽

J. Elm ◽

A. Gurary ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Immunosorbent Assay ◽

Immunoglobulin M ◽

Enzyme Linked Immunosorbent Assay ◽

Dengue Virus Infection

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Diagnosis of Dengue Virus Infection by Detection of Specific Immunoglobulin M (IgM) and IgA Antibodies in Serum and Saliva

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.10.2.317-322.2003 ◽

2003 ◽

Vol 10 (2) ◽

pp. 317-322 ◽

Cited By ~ 83

Author(s):

Angel Balmaseda ◽

María G. Guzmán ◽

Samantha Hammond ◽

Guillermo Robleto ◽

Carolina Flores ◽

...

Keyword(s):

Dengue Virus ◽

Immunoglobulin M ◽

Antibody Detection ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Serum Samples ◽

Diagnostic Modality ◽

Iga Antibodies ◽

Specific Immunoglobulin ◽

Feasible Alternative

ABSTRACT To evaluate alternative approaches to the serological diagnosis of dengue virus (DEN) infection, the detection of DEN-specific immunoglobulin M (IgM) and IgA antibodies in serum and saliva specimens was assessed in 147 patients with symptoms of DEN infection seen at the Ministry of Health in Nicaragua. Seventy-two serum samples were determined to be positive for anti-DEN antibodies by IgM capture enzyme-linked immunosorbent assay, the routine diagnostic procedure. Serum and saliva specimens were obtained from 50 healthy adults as additional controls. IgM was detected in the saliva of 65 of the 72 serum IgM-positive cases, 6 of the 75 serum IgM-negative cases, and none of the control group, resulting in a sensitivity of 90.3% and a specificity of 92.0% and demonstrating that salivary IgM is a useful diagnostic marker for DEN infection. Detection of IgA in serum may be another feasible alternative for the diagnosis of DEN infection, with serum IgA found in 68 (94.4%) of the IgM-positive cases. In contrast, detection of IgA in saliva was not found to be a useful tool for DEN diagnosis in the present study. Further studies of the kinetics of antibody detection in another set of 151 paired acute- and convalescent-phase serum samples showed that DEN-specific IgA antibodies were detected in more acute-phase samples than were IgM antibodies. Thus, we conclude that DEN-specific IgA in serum is a potential diagnostic target. Furthermore, given that saliva is a readily obtainable, noninvasive specimen, detection of DEN-specific salivary IgM should be considered a useful, cheaper diagnostic modality with similar sensitivity and specificity to IgM detection in serum.

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