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Das B, Datta S, Vanlalhmuaka, Reddy PVB. Comprehensive evaluation on progressive development strategies in DENV surveillance and monitoring infection rate among vector population. J Vector Borne Dis 2024; 61:327-339. [PMID: 39374492 DOI: 10.4103/jvbd.jvbd_86_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 02/05/2024] [Indexed: 10/09/2024] Open
Abstract
The elevated rise in dengue infection rate has been a health burden worldwide and it will continue to impact global health for years to come. Accumulated literature holds accountable the geographical expansion of the mosquito species transmitting the dengue virus DENV. The frequency of this viral disease outbreaks has increased rapidly in the recent years, owing to various geo-climatic and anthropological activities. Due to scarcity of any effective control measures, there has been a continuous traceable rise in mortality and morbidity rates. However, it has been reported that the spate of incidences is directly related to density of the virus infected vector (mosquito) population in a given region. In such a scenario, systems capable of detecting virus infected vector population would aid in estimating prediction of outbreak, as well as provide time to deploy suitable management strategies for vector control, and to break the vector-human transmission chain. This would also help in identifying areas, where much improvement is needed for vector management. To this context, we illustrate an exhaustive overview of both gold standards and as well as emerging advents for sensitive and specific mosquito population strategized viral detection technologies. We summarize the cutting-edge technologies and the challenges faced in pioneering to field application. Regardless the proven popularity of the gold standards for detection purpose, they offer certain limitations. Thus with the surge in the infection rate globally, approaches for development of newer advancements and technique upgradation to arrest the infection escalation and for early detection as a part of vector management should be prioritized.
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Affiliation(s)
- Bidisha Das
- Entomology and Biothreat Management Division, Defence Research Laboratory, Tezpur, Assam, India
- Department of Life Science & Bio-Informatics, Assam University Diphu Campus, Diphu, Assam, India
| | - Sibnarayan Datta
- Entomology and Biothreat Management Division, Defence Research Laboratory, Tezpur, Assam, India
| | - Vanlalhmuaka
- Entomology and Biothreat Management Division, Defence Research Laboratory, Tezpur, Assam, India
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Frazer JL, Norton R. Dengue: A review of laboratory diagnostics in the vaccine age. J Med Microbiol 2024; 73. [PMID: 38722305 DOI: 10.1099/jmm.0.001833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2024] Open
Abstract
Background. Dengue is an important arboviral infection of considerable public health significance. It occurs in a wide global belt within a variety of tropical regions. The timely laboratory diagnosis of Dengue infection is critical to inform both clinical management and an appropriate public health response. Vaccination against Dengue virus is being introduced in some areas.Discussion. Appropriate diagnostic strategies will vary between laboratories depending on the available resources and skills. Diagnostic methods available include viral culture, the serological detection of Dengue-specific antibodies in using enzyme immunoassays (EIAs), microsphere immunoassays, haemagglutination inhibition or in lateral flow point of care tests. The results of antibody tests may be influenced by prior vaccination and exposure to other flaviviruses. The detection of non-structural protein 1 in serum (NS1) has improved the early diagnosis of Dengue and is available in point-of-care assays in addition to EIAs. Direct detection of viral RNA from blood by PCR is more sensitive than NS1 antigen detection but requires molecular skills and resources. An increasing variety of isothermal nucleic acid detection methods are in development. Timing of specimen collection and choice of test is critical to optimize diagnostic accuracy. Metagenomics and the direct detection by sequencing of viral RNA from blood offers the ability to rapidly type isolates for epidemiologic purposes.Conclusion. The impact of vaccination on immune response must be recognized as it will impact test interpretation and diagnostic algorithms.
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Affiliation(s)
| | - Robert Norton
- Pathology Queensland, Townsville QLD, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia
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Dhawan S, Dittrich S, Arafah S, Ongarello S, Mace A, Panapruksachat S, Boutthasavong L, Adsamouth A, Thongpaseuth S, Davong V, Vongsouvath M, Ashley EA, Robinson MT, Blacksell SD. Diagnostic accuracy of DPP Fever Panel II Asia tests for tropical fever diagnosis. PLoS Negl Trop Dis 2024; 18:e0012077. [PMID: 38598549 PMCID: PMC11034646 DOI: 10.1371/journal.pntd.0012077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 04/22/2024] [Accepted: 03/18/2024] [Indexed: 04/12/2024] Open
Abstract
BACKGROUND Fever is the most frequent symptom in patients seeking care in South and Southeast Asia. The introduction of rapid diagnostic tests (RDTs) for malaria continues to drive patient management and care. Malaria-negative cases are commonly treated with antibiotics without confirmation of bacteraemia. Conventional laboratory tests for differential diagnosis require skilled staff and appropriate access to healthcare facilities. In addition, introducing single-disease RDTs instead of conventional laboratory tests remains costly. To overcome some of the delivery challenges of multiple separate tests, a multiplexed RDT with the capacity to diagnose a diverse range of tropical fevers would be a cost-effective solution. In this study, a multiplex lateral flow immunoassay (DPP Fever Panel II Assay) that can detect serum immunoglobulin M (IgM) and specific microbial antigens of common fever agents in Asia (Orientia tsutsugamushi, Rickettsia typhi, Leptospira spp., Burkholderia pseudomallei, Dengue virus, Chikungunya virus, and Zika virus), was evaluated. METHODOLOGY/PRINCIPAL FINDINGS Whole blood (WB) and serum samples from 300 patients with undefined febrile illness (UFI) recruited in Vientiane, Laos PDR were tested using the DPP Fever Panel II, which consists of an Antibody panel and Antigen panel. To compare reader performance, results were recorded using two DPP readers, DPP Micro Reader (Micro Reader 1) and DPP Micro Reader Next Generation (Micro Reader 2). WB and serum samples were run on the same fever panel and read on both micro readers in order to compare results. ROC analysis and equal variance analysis were performed to inform the diagnostic validity of the test compared against the respective reference standards of each fever agent (S1 Table). Overall better AUC values were observed in whole blood results. No significant difference in AUC performance was observed when comparing whole blood and serum sample testing, except for when testing for R. typhi IgM (p = 0.04), Leptospira IgM (p = 0.02), and Dengue IgG (p = 0.03). Linear regression depicted R2 values had ~70% agreement across WB and serum samples, except when testing for leptospirosis and Zika, where the R2 values were 0.37 and 0.47, respectively. No significant difference was observed between the performance of Micro Reader 1 and Micro Reader 2, except when testing for the following pathogens: Zika IgM, Zika IgG, and B pseudomallei CPS Ag. CONCLUSIONS/SIGNIFICANCE These results demonstrate that the diagnostic accuracy of the DPP Fever Panel II is comparable to that of commonly used RDTs. The optimal cut-off would depend on the use of the test and the desired sensitivity and specificity. Further studies are required to authenticate the use of these cut-offs in other endemic regions. This multiplex RDT offers diagnostic benefits in areas with limited access to healthcare and has the potential to improve field testing capacities. This could improve tropical fever management and reduce the public health burden in endemic low-resource areas.
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Affiliation(s)
- Sandhya Dhawan
- Mahidol-Oxford Tropical Research Medicine Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Sabine Dittrich
- FIND, Campus Biotech, Geneva, Switzerland
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | | | | | - Aurelian Mace
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR
| | - Siribun Panapruksachat
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR
| | - Latsaniphone Boutthasavong
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR
| | - Aphaphone Adsamouth
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR
| | - Soulignasak Thongpaseuth
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR
| | - Viengmon Davong
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR
| | - Manivanh Vongsouvath
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR
| | - Elizabeth A. Ashley
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR
| | - Matthew T. Robinson
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR
| | - Stuart D. Blacksell
- Mahidol-Oxford Tropical Research Medicine Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR
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Malnero CM, Azevedo RC, Bergmann IE, de Meneses MDF, Cavalcanti AC, Ibáñez LI, Malirat V. Expression of recombinant dengue virus type 1 non-structural protein 1 in mammalian cells and preliminary assessment of its suitability to detect human IgG antibodies elicited by viral infection. J Immunol Methods 2023; 518:113503. [PMID: 37263391 DOI: 10.1016/j.jim.2023.113503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 05/18/2023] [Accepted: 05/25/2023] [Indexed: 06/03/2023]
Abstract
In recent years dengue has become a rapidly growing public health problem worldwide, however, the availability of accurate and affordable diagnostic immunoassays is limited, partly due to the difficulty of producing large quantities of purified antigen. Non-structural protein 1 (NS1) has shown to be a good candidate for inclusion in diagnostic assays and for serosurveys, particularly in endemic countries as a prerequisite for vaccination. In this work the NS1 antigen derived from dengue virus type-1 (DENV1) was expressed in HEK293-T cells and purified by affinity chromatography. The recombinant protein was recovered properly folded as dimers, highly purified and with good yield (1.5 mg/L). It was applied as a serological probe in an indirect ELISA developed in this work to detect human IgG antibodies. Preliminary comparative performance values of 81.1% sensitivity and 83.0% specificity of the developed and preliminary validated iELISA, relative to a commercial kit were obtained, suggesting that the purified recombinant DENV1 NS1 antigen is suitable to detect IgG antibodies, indicative of past DENV infection.
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Affiliation(s)
- Cristian Miguel Malnero
- Centro de Virología Humana y Animal (CEVHAN), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Abierta Interamericana (UAI), Buenos Aires C1287, Argentina
| | - Renata Campos Azevedo
- Department of Virology, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Ingrid Evelyn Bergmann
- Centro de Virología Humana y Animal (CEVHAN), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Abierta Interamericana (UAI), Buenos Aires C1287, Argentina
| | | | - Andrea Cony Cavalcanti
- Department of Virology, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Central Laboratory of Public Health Noel Nutels (LACEN-RJ), Rio de Janeiro, Brazil
| | - Lorena Itatí Ibáñez
- Instituto de Química Física de los Materiales, Medio Ambiente y Energía (INQUIMAE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires (UBA), Buenos Aires C1428EGA, Argentina
| | - Viviana Malirat
- Centro de Virología Humana y Animal (CEVHAN), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Abierta Interamericana (UAI), Buenos Aires C1287, Argentina.
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Gaspar-Castillo C, Rodríguez MH, Ortiz-Navarrete V, Alpuche-Aranda CM, Martinez-Barnetche J. Structural and immunological basis of cross-reactivity between dengue and Zika infections: Implications in serosurveillance in endemic regions. Front Microbiol 2023; 14:1107496. [PMID: 37007463 PMCID: PMC10063793 DOI: 10.3389/fmicb.2023.1107496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 02/24/2023] [Indexed: 03/19/2023] Open
Abstract
Dengue and Zika are arthropod-borne viral diseases present in more than 100 countries around the world. In the past decade, Zika emerged causing widespread outbreaks in new regions, where dengue has been endemic-epidemic for a long period. The wide and extensive dissemination of the mosquito vectors, Aedes aegypti, and Ae. albopictus, favor the co-existence of both infections in the same regions. Together with an important proportion of asymptomatic infections, similar clinical manifestations, and a short time window for acute infection confirmatory tests, it is difficult to differentially estimate both dengue and Zika incidence and prevalence. DENV and ZIKV flavivirus share high structural similarity, inducing a cross-reactive immune response that leads to false positives in serological tests particularly in secondary infections. This results in overestimation of recent Zika outbreaks seroprevalence in dengue endemic regions. In this review, we address the biological basis underlying DENV and ZIKV structural homology; the structural and cellular basis of immunological cross reactivity; and the resulting difficulties in measuring dengue and Zika seroprevalence. Finally, we offer a perspective about the need for more research to improve serological tests performance.
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Affiliation(s)
- Carlos Gaspar-Castillo
- Center for Infectious Diseases Research, National Institute of Public Health, Cuernavaca, Mexico
| | - Mario H. Rodríguez
- Center for Infectious Diseases Research, National Institute of Public Health, Cuernavaca, Mexico
| | - Vianney Ortiz-Navarrete
- Department of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City, Mexico
| | - Celia M. Alpuche-Aranda
- Center for Infectious Diseases Research, National Institute of Public Health, Cuernavaca, Mexico
- Celia M. Alpuche-Aranda,
| | - Jesus Martinez-Barnetche
- Center for Infectious Diseases Research, National Institute of Public Health, Cuernavaca, Mexico
- *Correspondence: Jesus Martinez-Barnetche,
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Performance of VIDAS® Diagnostic Tests for the Automated Detection of Dengue Virus NS1 Antigen and of Anti-Dengue Virus IgM and IgG Antibodies: A Multicentre, International Study. Diagnostics (Basel) 2023; 13:diagnostics13061137. [PMID: 36980445 PMCID: PMC10047366 DOI: 10.3390/diagnostics13061137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 03/13/2023] [Accepted: 03/14/2023] [Indexed: 03/19/2023] Open
Abstract
Dengue is a serious mosquito-transmitted disease caused by the dengue virus (DENV). Rapid and reliable diagnosis of DENV infection is urgently needed in dengue-endemic regions. We describe here the performance evaluation of the CE-marked VIDAS® dengue immunoassays developed for the automated detection of DENV NS1 antigen and anti-DENV IgM and IgG antibodies. A multicenter concordance study was conducted in 1296 patients from dengue-endemic regions in Asia, Latin America, and Africa. VIDAS® dengue results were compared to those of competitor enzyme-linked immunosorbent assays (ELISA). The VIDAS® dengue assays showed high precision (CV ≤ 10.7%) and limited cross-reactivity (≤15.4%) with other infections. VIDAS® DENGUE NS1 Ag showed high positive and negative percent agreement (92.8% PPA and 91.7% NPA) in acute patients within 0–5 days of symptom onset. VIDAS® Anti-DENGUE IgM and IgG showed a moderate-to-high concordance with ELISA (74.8% to 90.6%) in post-acute and recovery patients. PPA was further improved in combined VIDAS® NS1/IgM (96.4% in 0–5 days acute patients) and IgM/IgG (91.9% in post-acute patients) tests. Altogether, the VIDAS® dengue NS1, IgM, and IgG assays performed well, either alone or in combination, and should be suitable for the accurate diagnosis of DENV infection in dengue-endemic regions.
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Machain-Williams C, Reyes-Solis GC, Blitvich BJ, Laredo-Tiscareño V, Dzul-Rosado AR, Kim S, AbuBakar S. Evaluation of an Immunoglobulin E Capture Enzyme-Linked Immunosorbent Assay for the Early Diagnosis of Dengue. Viral Immunol 2023; 36:101-109. [PMID: 36862827 DOI: 10.1089/vim.2022.0110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/04/2023] Open
Abstract
Dengue virus (DENV) is the etiological agent of dengue, the most important mosquito-transmitted viral disease of humans worldwide. Enzyme-linked immunosorbent assays (ELISAs) designed to detect DENV IgM are commonly used for dengue diagnosis. However, DENV IgM is not reliably detected until ≥4 days after illness onset. Reverse transcription-polymerase chain reaction (RT-PCR) can diagnose early dengue but requires specialized equipment, reagents, and trained personnel. Additional diagnostic tools are needed. Limited work has been performed to determine whether IgE-based assays can be used for the early detection of vector-borne viral diseases, including dengue. In this study, we determined the efficacy of a DENV IgE capture ELISA for the detection of early dengue. Sera were collected within the first 4 days of illness onset from 117 patients with laboratory-confirmed dengue, as determined by DENV-specific RT-PCR. The serotypes responsible for the infections were DENV-1 and DENV-2 (57 and 60 patients, respectively). Sera were also collected from 113 dengue-negative individuals with febrile illness of undetermined etiology and 30 healthy controls. The capture ELISA detected DENV IgE in 97 (82.9%) confirmed dengue patients and none of the healthy controls. There was a high false positivity rate (22.1%) among the febrile non-dengue patients. In conclusion, we provide evidence that IgE capture assays have the potential to be explored for early diagnosis of dengue, but further research is necessary to address the possible false positivity rate among patients with other febrile illnesses.
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Affiliation(s)
- Carlos Machain-Williams
- Laboratorio de Arbovirologia, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi," Universidad Autónoma de Yucatan, Merida, Yucatan, Mexico
| | - Guadalupe C Reyes-Solis
- Laboratorio de Arbovirologia, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi," Universidad Autónoma de Yucatan, Merida, Yucatan, Mexico
| | - Bradley J Blitvich
- Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA
| | - Viridiana Laredo-Tiscareño
- Laboratorio de Arbovirologia, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi," Universidad Autónoma de Yucatan, Merida, Yucatan, Mexico.,Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA
| | | | - Sungmin Kim
- Department of Infectious Diseases in Internal Medicine, Sejong Chungnam National University Hospital, School of Medicine, Chungnam National University, Sejong, Korea
| | - Sazaly AbuBakar
- Tropical Infectious Diseases Research and Education Centre (TIDREC), Higher Institution Center of Excellence (HICOE), Universiti Malaya, Kuala Lumpur, Malaysia
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Reduction in Anti-Dengue Virus IgG Antibody Levels with the Use of a Larvicide for Vector Control in Rural Lao People's Democratic Republic. Trop Med Infect Dis 2022; 8:tropicalmed8010020. [PMID: 36668927 PMCID: PMC9862626 DOI: 10.3390/tropicalmed8010020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/10/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022] Open
Abstract
The Lao People’s Democratic Republic is an endemic area of dengue, with cases reported in urban and rural areas every year. In this study, we indirectly evaluated the efficacy of a larvicide (SumiLarvTM 2MR discs) that was used for vector control against Aedes mosquitoes. Villages in a rural area of Lao PDR were selected as study areas, non-intervention and intervention villages. At the intervention village, the larvicide was used to treat refillable water containers for 27 months (October 2017 to February 2020), while at the non-intervention villages were no treatment. The serum samples of villagers from both villages were randomized to collect in the pre-intervention and in post-intervention periods. An enzyme-linked immunosorbent assay (ELISA) was used to examine anti-dengue virus (DENV) IgG antibody levels in serum samples. Recombinant DENV serotype 2 non-structural protein1 was used as an antigen for the ELISA, the optical density (OD) values were analyzed for comparison. The results showed that the OD values decreased significantly (p < 0.01) between the pre-intervention and post-intervention periods at the intervention site. The treatment of water storage containers in rural areas with SumiLarvTM 2MR discs may help to protect residents from Aedes mosquito bites, and hence, reduce DENV infections.
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A systematic review and meta-analysis on the accuracy of rapid immunochromatographic tests for dengue diagnosis. Eur J Clin Microbiol Infect Dis 2022; 41:1191-1201. [PMID: 35988010 DOI: 10.1007/s10096-022-04485-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 08/12/2022] [Indexed: 11/03/2022]
Abstract
Rapid immunochromatographic tests are frequently used to diagnose dengue due to their easy use, low cost, and fast response. A high level of accuracy is essential for rapid diagnostic tests to support their large-scale use. Thus, this systematic review aims to evaluate the accuracy of rapid dengue diagnostic tests. The investigation was run through the following databases: LILACS, Medline (Pubmed), CRD, The Cochrane Library, Trip Medical Database, and Google Scholar. To solve difficulties, two independent reviewers performed document screening and selection. ELISA assay was adopted as a reference test because of several methodologic advantages. Seventeen articles were included accordingly, reckoning 6837 participating individuals. The receiver operating characteristic (ROC) and Forest Plot were conducted to evaluate the sensitivity and specificity for each analyzed parameter (anti-dengue IgM, IgG, and NS1 antigen). The risk of bias and quality of evidence were assessed as moderate using QUADAS-2 and Grading of Recommendations Assessment, Development, and Evaluation (GRADE), respectively. The sensitivity of IgM concerning the studied tests ranged from 13.8 to 90%, while that of NS1 ranged from 14.7 to 100% (95% CI). The antibodies with NS1 presented increased sensitivity; pooled data show that the association of the three analytes bestows the best result, with a combined sensitivity of 90% (CI 95%: 87-92%) and a pooled specificity of 89% (CI 95%: 87-92%). Thus, the present review provides relevant knowledge for decision-making between available rapid diagnostic tests.
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Amornchai P, Hantrakun V, Wongsuvan G, Boonsri C, Yoosuk S, Nilsakul J, Blacksell SD, West TE, Lubell Y, Limmathurotsakul D. Sensitivity and specificity of DPP® Fever Panel II Asia in the diagnosis of malaria, dengue and melioidosis. J Med Microbiol 2022; 71:001584. [PMID: 35994523 PMCID: PMC7613707 DOI: 10.1099/jmm.0.001584] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 07/13/2022] [Indexed: 12/25/2022] Open
Abstract
Introduction. Rapid diagnostic tests (RDTs) that can facilitate the diagnosis of a panel of tropical infectious diseases are critically needed. DPP® Fever Panel II Asia is a multiplex lateral flow immunoassay comprising antigen and IgM panels for the diagnosis of pathogens that commonly cause febrile illness in Southeast Asia.Hypothesis/Gap Statement. Accuracy of DPP® Fever Panel II Asia has not been evaluated in clinical studies.Aim. To evaluate the sensitivity and specificity of DPP® Fever Panel II Asia for malaria, dengue and melioidosis.Methodology. We conducted a cohort-based case-control study. Both cases and controls were derived from a prospective observational study of patients presenting with community-acquired infections and sepsis in northeast Thailand (Ubon sepsis). We included 143 and 98 patients diagnosed with malaria or dengue based on a positive PCR assay and 177 patients with melioidosis based on a culture positive for Burkholderia pseudomallei. Controls included 200 patients who were blood culture-positive for Staphylococcus aureus, Escherichia coli or Klebsiella pneumoniae, and cases of the other diseases. Serum samples collected from all patients within 24 h of admission were stored and tested using the DPP® Fever Panel II Asia antigen and IgM multiplex assays. We selected cutoff values for each individual assay corresponding to a specificity of ≥95 %. When assessing diagnostic tests in combination, results were considered positive if either individual test was positive.Results. Within the DPP® Fever Panel II Asia antigen assay, a combination of pLDH and HRPII for malaria had a sensitivity of 91 % and a specificity of 97 %. The combination of dengue NS1 antigen and dengue antibody tests had a sensitivity of 61 % and a specificity of 91 %. The B. pseudomallei CPS antigen test had a sensitivity of 27 % and a specificity of 97 %. An odds ratio of 2.34 (95 % CI 1.16-4.72, P=0.02) was observed for the association between CPS positivity and mortality among melioidosis patients.Conclusion. The performance of the DPP® Fever Panel II Asia for diagnosis of malaria was high and that for dengue and melioidosis was relatively limited. For all three diseases, performance was comparable to that of other established RDTs. The potential operational advantages of a multiplex and quantitative point-of-care assay are substantial and warrant further investigation.
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Affiliation(s)
- Premjit Amornchai
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Viriya Hantrakun
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Gumphol Wongsuvan
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Chaiyaporn Boonsri
- Medical Department, Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand
| | - Sasinaphon Yoosuk
- Medical Department, Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand
| | - Jiraporn Nilsakul
- Pathology Department, Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand
| | - Stuart D. Blacksell
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - T. Eoin West
- Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, Washington, USA
- Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Yoel Lubell
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Direk Limmathurotsakul
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
- Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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Needs SH, Sirivisoot S, Jegouic S, Prommool T, Luangaram P, Srisawat C, Sriraksa K, Limpitikul W, Mairiang D, Malasit P, Avirutnan P, Puttikhunt C, Edwards AD. Smartphone multiplex microcapillary diagnostics using Cygnus: Development and evaluation of rapid serotype-specific NS1 detection with dengue patient samples. PLoS Negl Trop Dis 2022; 16:e0010266. [PMID: 35389998 PMCID: PMC8989202 DOI: 10.1371/journal.pntd.0010266] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 02/18/2022] [Indexed: 11/18/2022] Open
Abstract
Laboratory diagnosis of dengue virus (DENV) infection including DENV serotyping requires skilled labor and well-equipped settings. DENV NS1 lateral flow rapid test (LFT) provides simplicity but lacks ability to identify serotype. A simple, economical, point-of-care device for serotyping is still needed. We present a gravity driven, smartphone compatible, microfluidic device using microcapillary film (MCF) to perform multiplex serotype-specific immunoassay detection of dengue virus NS1. A novel device-termed Cygnus-with a stackable design allows analysis of 1 to 12 samples in parallel in 40 minutes. A sandwich enzyme immunoassay was developed to specifically detect NS1 of all four DENV serotypes in one 60-μl plasma sample. This test aims to bridge the gap between rapid LFT and laboratory microplate ELISAs in terms of sensitivity, usability, accessibility and speed. The Cygnus NS1 assay was evaluated with retrospective undiluted plasma samples from 205 DENV infected patients alongside 50 febrile illness negative controls. Against the gold standard RT-PCR, clinical sensitivity for Cygnus was 82% in overall (with 78, 78, 80 and 76% for DENV1-4, respectively), comparable to an in-house serotyping NS1 microplate ELISA (82% vs 83%) but superior to commercial NS1-LFT (82% vs 74%). Specificity of the Cygnus device was 86%, lower than that of NS1-microplate ELISA and NS1-LFT (100% and 98%, respectively). For Cygnus positive samples, identification of DENV serotypes DENV2-4 matched those by RT-PCR by 100%, but for DENV1 capillaries false positives were seen, suggesting an improved DENV1 capture antibody is needed to increase specificity. Overall performance of Cygnus showed substantial agreement to NS1-microplate ELISA (κ = 0.68, 95%CI 0.58-0.77) and NS1-LFT (κ = 0.71, 95%CI 0.63-0.80). Although further refinement for DENV-1 NS1 detection is needed, the advantages of multiplexing and rapid processing time, this Cygnus device could deliver point-of-care NS1 antigen testing including serotyping for timely DENV diagnosis for epidemic surveillance and outbreak prediction.
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Affiliation(s)
- Sarah Helen Needs
- Reading School of Pharmacy, University of Reading, Whiteknights, Reading, United Kingdom
| | - Sirintra Sirivisoot
- Division of Dengue Hemorrhagic Fever Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sophie Jegouic
- Reading School of Pharmacy, University of Reading, Whiteknights, Reading, United Kingdom
| | - Tanapan Prommool
- Molecular Biology of Dengue and Flaviviruses Research Team, Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand
| | - Prasit Luangaram
- Molecular Biology of Dengue and Flaviviruses Research Team, Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand
| | - Chatchawan Srisawat
- Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Kanokwan Sriraksa
- Pediatric Department, Khon Kaen Hospital, Ministry of Health, Khon Kaen, Thailand
| | - Wannee Limpitikul
- Pediatric Department, Songkhla Hospital, Ministry of Health, Songkhla, Thailand
| | - Dumrong Mairiang
- Division of Dengue Hemorrhagic Fever Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Molecular Biology of Dengue and Flaviviruses Research Team, Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand
- Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Prida Malasit
- Division of Dengue Hemorrhagic Fever Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Molecular Biology of Dengue and Flaviviruses Research Team, Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand
- Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Panisadee Avirutnan
- Division of Dengue Hemorrhagic Fever Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Molecular Biology of Dengue and Flaviviruses Research Team, Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand
- Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chunya Puttikhunt
- Division of Dengue Hemorrhagic Fever Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Molecular Biology of Dengue and Flaviviruses Research Team, Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand
- Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Alexander Daniel Edwards
- Reading School of Pharmacy, University of Reading, Whiteknights, Reading, United Kingdom
- Capillary Film Technology Ltd, Billingshurst, West Sussex, United Kingdom
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Lai SC, Huang YY, Wey JJ, Tsai MH, Chen YL, Shu PY, Chang SF, Hung YJ, Hou JN, Lin CC. Development of Novel Dengue NS1 Multiplex Lateral Flow Immunoassay to Differentiate Serotypes in Serum of Acute Phase Patients and Infected Mosquitoes. Front Immunol 2022; 13:852452. [PMID: 35309328 PMCID: PMC8931297 DOI: 10.3389/fimmu.2022.852452] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 02/14/2022] [Indexed: 11/25/2022] Open
Abstract
Dengue is among the most rapidly spreading arboviral disease in the world. A low-cost, easy to use point-of-care diagnostic tool for the detection and differentiation of dengue virus serotypes could improve clinical management, disease prevention, epidemiological surveillance, and outbreak monitoring, particularly in regions where multiple serotypes co-circulate. Despite widespread deployment, no commercial dengue antigen diagnostic test has proven effective in differentiating among dengue virus serotypes. In the current study, we first established mAb pairs and developed a multiplex lateral flow immunoassay for the simultaneous detection of the dengue viral NS1 antigen and identification of serotype. The proposed system, called Dengue serotype NS1 Multiplex LFIA, provides high sensitivity and specificity. In testing for JEV, ZIKV, YFV, WNV, and CHIKV, the multiplex LFIA gave no indication of cross- reactivity with cell culture supernatants of other flaviviruses or chikungunya virus. In analyzing 187 samples from patients suspected of dengue infection, the detection sensitivity for serotype D1 to D4 was 90.0%, 88.24%, 82.61%, and 83.33% and serotype specificity was 98.74%, 96.13%, 99.39%, and 97.04%, respectively. Our multiplex LFIA can also identify mono- and co-infection of different serotype of dengue viruses in mosquitoes. The proposed Multiplex LFIA provides a simple tool for the rapid detection of dengue serotypes and in the differential diagnosis of fever patients in regions where medical resources are limited and/or multiple DENVs co-circulate.
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Affiliation(s)
- Szu-Chia Lai
- Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan
| | - Yu-Yine Huang
- Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan
| | - Jiunn-Jye Wey
- Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan
| | - Meng-Hung Tsai
- Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan
| | - Yi-Ling Chen
- Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan
| | - Pei-Yun Shu
- Center for Diagnostics and Vaccine Development, Centers for Disease Control, Ministry of Health and Welfare, Taipei City, Taiwan
| | - Shu-Fen Chang
- Center for Diagnostics and Vaccine Development, Centers for Disease Control, Ministry of Health and Welfare, Taipei City, Taiwan
| | - Yi-Jen Hung
- Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan
| | - Jiu-Nan Hou
- Diagnostic Device Group, Trison Technology Corporation, Taoyuan City, Taiwan
| | - Chang-Chi Lin
- Institute of Preventive Medicine, National Defense Medical Center, New Taipei City, Taiwan
- Institute of Microbiology and Immunology, National Defense Medical Center, Taipei City, Taiwan
- *Correspondence: Chang-Chi Lin, ;
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13
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Lima MRQ, Nunes PCG, Dos Santos FB. Serological Diagnosis of Dengue. Methods Mol Biol 2022; 2409:173-196. [PMID: 34709642 DOI: 10.1007/978-1-0716-1879-0_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
A reliable and specific diagnosis is imperative in viral diagnosis, both for clinical management and surveillance, and to ensure that early treatment and control measures are carried out. The number of days of illness is important to choose the most appropriate method to be used and for the correct interpretation of the results obtained. Specific IgM is elicited after that period, indicating an active infection and usually lasts up to 3 months. However, in DENV secondary infections, IgM levels may be significantly lower or undetectable. After 10-12 days, a lifetime specific IgG is produced. Routinely, the laboratory diagnosis of DENV infections can be performed by viral isolation and/or detection of viral nucleic acid, serological assays for the detection of specific antibodies (IgM/IgG), antigen (NS1) and the detection of viral antigens in tissues, which are suitable during certain phases of the disease. For serological diagnosis, serum, plasma, or cerebrospinal fluid (CSF) samples may be investigated. If the test is carried out a few days after collection, the specimens can be stored at 4 °C, since the immunoglobulins are stable in serum or plasma. If the storage period is extended, the material must be kept at -20 °C or -70 °C. In serology, several methods can be used to detect specific viral antigens and/or antibodies, produced by the host in response to DENV infection. Routinely, serological tests include the hemagglutination inhibition (HI) assay, the plaque reduction neutralizing test (PRNT), the gold standard assay for dengue immune response characterization, and ELISAs to detect IgM (MAC-ELISA) and IgG (IgG-ELISA).
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Affiliation(s)
- Monique R Q Lima
- Laboratório Estratégico de Diagnóstico (LED), Centro de Desenvolvimento Científico, Instituto Butantan, São Paulo, Brazil
| | - Priscila C G Nunes
- Laboratório Municipal de Saúde Pública (LASP), Laboratório de Virologia e Biotério, Subsecretaria de Vigilância, Fiscalização Sanitária e Controle de Zoonoses, Rio de Janeiro, Brazil
- Superintendência de Informações Estratégicas de Vigilância em Saúde (SIEVS/RJ), Secretaria Estadual de Saúde, Rio de Janeiro, Brazil
| | - Flávia B Dos Santos
- Laboratório de Imunologia Viral (LIV), Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil.
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刘 金, 李 晓, 王 海, 唐 时, 万 成. [Dengue virus E protein-based luciferase immunosorbent assay for detecting dengue virus IgG antibody]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2021; 41:1747-1751. [PMID: 34916204 PMCID: PMC8685698 DOI: 10.12122/j.issn.1673-4254.2021.11.22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Indexed: 06/14/2023]
Abstract
OBJECTIVE To establish a luciferase immunosorbent assay (DENV-LISA) based on dengue virus (DENV) E protein, a specific antigen of DENV, for detection of DENV IgG antibody. METHODS The fused expression plasmids of DENV1-E1 and DENV2-E2 with luciferase were constructed. The plasmids were transfected into 293T cells, and the fusion protein containing the specific antigen and luciferase was obtained for establishing DENV-LISA. The specificity and sensitivity of DENV-LISA were assessed and compared with those of commercial DENV IgG antibody detection kit (ELISA). RESULTS The established DENV-LISA had a positive detection rate of 32.4% and a specificity of 96.6%, showing a similar positive detection rate with the commercial ELISA kit (35.3%; P>0.05). DENV-LISA was capable of detecting positive samples with a 1: 6400 dilution with a high sensitivity. The test values of DENV-LISA did not differ significantly between plates or within plates in the same batch (P> 0.05), suggesting a good reproducibility of the test. CONCLUSION The luciferase immunosorbent assay based on DENV E protein has high specificity and sensitivity for detecting DENV IgG antibody, and can be used for early screening, surveillance and epidemiological investigation of DENV infection.
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Affiliation(s)
- 金月 刘
- />南方医科大学公共卫生学院，广东 广州 510515School of Public Health, Southern Medical University, Guangzhou 510515, China
| | - 晓霞 李
- />南方医科大学公共卫生学院，广东 广州 510515School of Public Health, Southern Medical University, Guangzhou 510515, China
| | - 海鹰 王
- />南方医科大学公共卫生学院，广东 广州 510515School of Public Health, Southern Medical University, Guangzhou 510515, China
| | - 时幸 唐
- />南方医科大学公共卫生学院，广东 广州 510515School of Public Health, Southern Medical University, Guangzhou 510515, China
| | - 成松 万
- />南方医科大学公共卫生学院，广东 广州 510515School of Public Health, Southern Medical University, Guangzhou 510515, China
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15
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Capeding MR, de Boer M, Damaso S, Guignard A. Assessing the burden of dengue among household members in Alaminos, Laguna, the Philippines: a prospective cohort study. ASIAN BIOMED 2021; 15:213-222. [PMID: 37551324 PMCID: PMC10388797 DOI: 10.2478/abm-2021-0027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Background The incidence of dengue is increasing rapidly and is a challenging health issue in the Philippines. Epidemiological data are largely based on a passive-surveillance reporting system, which leads to substantial under-reporting of cases. Objectives To estimate dengue infection and disease incidence prospectively at the community level in an endemic area of the Philippines using an active surveillance strategy. Methods We implemented active surveillance in the highly endemic community of Alaminos, Laguna. The study consisted of a 1-year follow-up with 2 visits scheduled at the start and end of the study, as well as regular active surveillance in between and unscheduled visits for suspected cases. Blood samples were collected and analyzed to detect dengue during the first scheduled visit and all unscheduled visits, and clinical examination was performed at all visits (registered at clinicaltrials.gov NCT02766088). Results We enrolled 500 participants, aged from 6 months to 50 years; 76.2% were found positive for immunoglobulin G (95% confidence interval [CI], 71.9-80.0), with 92.0% among those aged 9-17 years. Active (weekly) surveillance identified 4 virologically confirmed cases of dengue (incidence proportion 0.8; 95% CI 0.3-2.1); all in participants aged ≤14 years. Conclusions Routine surveillance programs such as sentinel sites are needed to characterize the entire clinical spectrum of symptomatic dengue, disease incidence, and transmission in the community.
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Affiliation(s)
- Maria Rosario Capeding
- Department of Microbiology, Research Institute for Tropical Medicine, Muntinlupa, 1781Metro Manila, Philippines
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16
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Pereira SS, Andreata-Santos R, Pereira LR, Soares CP, Félix AC, de Andrade PDMJC, Durigon EL, Romano CM, Ferreira LCDS. NS1-based ELISA test efficiently detects dengue infections without cross-reactivity with Zika virus. Int J Infect Dis 2021; 112:202-204. [PMID: 34555500 DOI: 10.1016/j.ijid.2021.09.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 09/01/2021] [Accepted: 09/06/2021] [Indexed: 10/20/2022] Open
Abstract
OBJECTIVES The aim of this study was to achieve greater specificity of dengue virus (DENV) serological tests based on a recombinant antigen derived from non-structural protein 1 (ΔNS1) with regard to cross-reactive Zika virus (ZIKV) anti-NS1 antibody responses. This is of relevance in endemic regions for the serological discrimination of both DENV and ZIKV, such as Brazil and other tropical countries. METHODS The ΔNS1 proteins were obtained as recombinant antigens and were evaluated as solid-phase-bound antigens in the ELISA test to detect anti-NS1 IgG antibodies. The performance of the ∆NS1-based DENV IgG ELISA was assessed with both mouse and human serum samples previously exposed to DENV or ZIKV. RESULTS The ∆NS1-based DENV IgG ELISA detected anti-DENV NS1 IgG without cross-reactivity with ZIKV-positive serum samples. The sensitivity and specificity of the assay determined using samples previously characterized by real-time PCR (qRT-PCR) or plaque reduction neutralization assay (PRNT) were 82% and 93%, respectively. CONCLUSION The ∆NS1-based DENV IgG ELISA conferred enhanced diagnostic specificity for anti-DENV serological tests and may be particularly useful for serological analyses in endemic regions for both DENV and ZIKV transmission.
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Affiliation(s)
- Samuel Santos Pereira
- Vaccine Development Laboratory, Microbiology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Robert Andreata-Santos
- Vaccine Development Laboratory, Microbiology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Lennon Ramos Pereira
- Vaccine Development Laboratory, Microbiology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Camila Pereira Soares
- Laboratory of Clinical and Molecular Virology, Microbiology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Alvina Clara Félix
- Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, São Paulo, Brazil
| | | | - Edison Luís Durigon
- Laboratory of Clinical and Molecular Virology, Microbiology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Camila Malta Romano
- Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, São Paulo, Brazil; Hospital das Clínicas HCFMUSP (LIM 52), Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Luís Carlos de Souza Ferreira
- Vaccine Development Laboratory, Microbiology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
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Competitive ELISA for a serologic test to detect dengue serotype-specific anti-NS1 IgGs using high-affinity UB-DNA aptamers. Sci Rep 2021; 11:18000. [PMID: 34504185 PMCID: PMC8429655 DOI: 10.1038/s41598-021-97339-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 08/24/2021] [Indexed: 02/08/2023] Open
Abstract
Serologic tests to detect specific IgGs to antigens related to viral infections are urgently needed for diagnostics and therapeutics. We present a diagnostic method for serotype-specific IgG identification of dengue infection by a competitive enzyme-linked immunosorbent assay (ELISA), using high-affinity unnatural-base-containing DNA (UB-DNA) aptamers that recognize the four categorized serotypes. Using UB-DNA aptamers specific to each serotype of dengue NS1 proteins (DEN-NS1), we developed our aptamer-antibody sandwich ELISA for dengue diagnostics. Furthermore, IgGs highly specific to DEN-NS1 inhibited the serotype-specific NS1 detection, inspiring us to develop the competitive ELISA format for dengue serotype-specific IgG detection. Blood samples from Singaporean patients with primary or secondary dengue infections confirmed the highly specific IgG detection of this format, and the IgG production initially reflected the serotype of the past infection, rather than the recent infection. Using this dengue competitive ELISA format, cross-reactivity tests of 21 plasma samples from Singaporean Zika virus-infected patients revealed two distinct patterns: 8 lacked cross-reactivity, and 13 were positive with unique dengue serotype specificities, indicating previous dengue infection. This antigen-detection ELISA and antibody-detection competitive ELISA combination using the UB-DNA aptamers identifies both past and current viral infections and will facilitate specific medical care and vaccine development for infectious diseases.
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18
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Pradeep SP, Hoovina Venkatesh P, Manchala NR, Vayal Veedu A, Basavaraju RK, Selvasundari L, Ramakrishna M, Chandrakiran Y, Krishnamurthy V, Holigi S, Thomas T, Ross CR, Dias M, Satchidanandam V. Innate Immune Cytokine Profiling and Biomarker Identification for Outcome in Dengue Patients. Front Immunol 2021; 12:677874. [PMID: 34335578 PMCID: PMC8318829 DOI: 10.3389/fimmu.2021.677874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 06/22/2021] [Indexed: 11/21/2022] Open
Abstract
Background Early biomarkers of progression to severe dengue are urgently required to enable effective patient management and control treatment costs. Innate immune cells, which comprise the earliest responders to infection and along with the cytokines and chemokines they secrete, play a vital role in orchestrating the subsequent adaptive immune response and have been implicated in the enhancement of infection and “cytokine storm” associated with dengue severity. We investigated the early innate immune cytokine profile of dengue patients during acute phase of disease in a prospective blinded study that included subjects with acute dengue and febrile controls from four major hospitals in Bengaluru, India along with healthy controls. We used intracellular cytokine staining and flow cytometry to identify innate immune biomarkers that can predict progression to severe dengue. Results Dengue infection resulted in enhanced secretion of multiple cytokines by all queried innate immune cell subsets, dominated by TNF-α from CD56+CD3+ NKT cells, monocyte subsets, and granulocytes along with IFN-γ from CD56+CD3+ NKT cells. Of note, significantly higher proportions of TNF-α secreting granulocytes and monocyte subsets at admission were associated with mild dengue and minimal symptoms. Dengue NS1 antigenemia used as a surrogate of viral load directly correlated with proportion of cytokine-secreting innate immune cells and was significantly higher in those who went on to recover with minimal symptoms. In patients with secondary dengue or those with bleeding or elevated liver enzymes who revealed predisposition to severe outcomes, early activation as well as efficient downregulation of innate responses were compromised. Conclusion Our findings suggested that faulty/delayed kinetics of innate immune activation and downregulation was a driver of disease severity. We identified IFN-γ+CD56+CD3+ NKT cells and IL-6+ granulocytes at admission as novel early biomarkers that can predict the risk of progression to severity (composite AUC = 0.85–0.9). Strong correlations among multiple cytokine-secreting innate cell subsets revealed that coordinated early activation of the entire innate immune system in response to dengue virus infection contributed to resolution of infection and speedy recovery.
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Affiliation(s)
- Sai Pallavi Pradeep
- Department of Microbiology and Cell Biology, Indian Institute of Science, Bengaluru, India
| | | | - Nageswar R Manchala
- Division of Infectious Diseases Unit, St. John's Research Institute, St. John's Medical College, Bengaluru, India
| | - Arjun Vayal Veedu
- Division of Infectious Diseases Unit, St. John's Research Institute, St. John's Medical College, Bengaluru, India
| | - Rajani K Basavaraju
- Department of Medicine, Kempegowda Institute of Medical Sciences and Research Centre, Bengaluru, India
| | | | - Manikanta Ramakrishna
- Department of Medicine, Bengaluru Medical College and Research Institute, Bengaluru, India
| | - Yogitha Chandrakiran
- Department of Medicine, Kempegowda Institute of Medical Sciences and Research Centre, Bengaluru, India
| | | | - Shivaranjani Holigi
- Department of Medicine, Bengaluru Medical College and Research Institute, Bengaluru, India
| | - Tinku Thomas
- Department of Biostatistics, St. John's Medical College, Bengaluru, India
| | - Cecil R Ross
- Department of Medicine, St. John's Medical College, Bengaluru, India
| | - Mary Dias
- Department of Microbiology, St. John's Medical College, Bengaluru, India
| | - Vijaya Satchidanandam
- Department of Microbiology and Cell Biology, Indian Institute of Science, Bengaluru, India
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Evaluation of VIDAS ® Diagnostic Assay Prototypes Detecting Dengue Virus NS1 Antigen and Anti-Dengue Virus IgM and IgG Antibodies. Diagnostics (Basel) 2021; 11:diagnostics11071228. [PMID: 34359311 PMCID: PMC8307080 DOI: 10.3390/diagnostics11071228] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 07/02/2021] [Accepted: 07/05/2021] [Indexed: 01/24/2023] Open
Abstract
Dengue is a serious tropical disease caused by the mosquito-borne dengue virus (DENV). Performant, rapid, and easy-to-use assays are needed for the accurate diagnosis of acute DENV infection. We evaluated the performance of three prototype assays developed for the VIDAS® automated platform to detect dengue NS1 antigen and anti-dengue IgM and IgG antibodies. Positive and negative agreement with competitor enzyme-linked immunosorbent assays (ELISA) and rapid diagnostic tests (RDT) was evaluated in 91 Lao patients (57 adults, 34 children) with acute DENV infection. The VIDAS® NS1 assay showed the best overall agreement (95.6%) with the competitor NS1 ELISA. Both VIDAS® NS1 and NS1 ELISA assays also demonstrated high sensitivity relative to DENV RNA RT-PCR set as gold standard (85.7% and 83.9%, respectively). In contrast, NS1 RDT was less sensitive relative to DENV RNA RT-PCR (72.7%). The overall agreement of VIDAS® IgM and IgG assays with the competitor assays was moderate (72.5% for IgM ELISA, 76.9% for IgG ELISA, and 68.7% for IgM and IgG RDT). In most analyses, test agreements of the VIDAS® assays were comparable in adults and children. Altogether, the VIDAS® dengue prototypes performed very well and appear to be suitable for routine detection of dengue NS1 antigen and anti-dengue IgM/IgG antibodies.
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Kabir MA, Zilouchian H, Younas MA, Asghar W. Dengue Detection: Advances in Diagnostic Tools from Conventional Technology to Point of Care. BIOSENSORS 2021; 11:206. [PMID: 34201849 PMCID: PMC8301808 DOI: 10.3390/bios11070206] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/05/2021] [Accepted: 06/15/2021] [Indexed: 06/02/2023]
Abstract
The dengue virus (DENV) is a vector-borne flavivirus that infects around 390 million individuals each year with 2.5 billion being in danger. Having access to testing is paramount in preventing future infections and receiving adequate treatment. Currently, there are numerous conventional methods for DENV testing, such as NS1 based antigen testing, IgM/IgG antibody testing, and Polymerase Chain Reaction (PCR). In addition, novel methods are emerging that can cut both cost and time. Such methods can be effective in rural and low-income areas throughout the world. In this paper, we discuss the structural evolution of the virus followed by a comprehensive review of current dengue detection strategies and methods that are being developed or commercialized. We also discuss the state of art biosensing technologies, evaluated their performance and outline strategies to address challenges posed by the disease. Further, we outline future guidelines for the improved usage of diagnostic tools during recurrence or future outbreaks of DENV.
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Affiliation(s)
- Md Alamgir Kabir
- Asghar-Lab, Micro and Nanotechnology in Medicine, College of Engineering and Computer Science, Boca Raton, FL 33431, USA; (M.A.K.); (H.Z.)
- Department of Computer & Electrical Engineering and Computer Science, Florida Atlantic University, Boca Raton, FL 33431, USA
| | - Hussein Zilouchian
- Asghar-Lab, Micro and Nanotechnology in Medicine, College of Engineering and Computer Science, Boca Raton, FL 33431, USA; (M.A.K.); (H.Z.)
- College of Medicine, University of Central Florida, Orlando, FL 32827, USA
| | | | - Waseem Asghar
- Asghar-Lab, Micro and Nanotechnology in Medicine, College of Engineering and Computer Science, Boca Raton, FL 33431, USA; (M.A.K.); (H.Z.)
- Department of Computer & Electrical Engineering and Computer Science, Florida Atlantic University, Boca Raton, FL 33431, USA
- Department of Biological Sciences (Courtesy Appointment), Florida Atlantic University, Boca Raton, FL 33431, USA
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21
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DeAntonio R, Amaya‐Tapia G, Ibarra‐Nieto G, Huerta G, Damaso S, Guignard A, de Boer M. Incidence of dengue illness in Mexican people aged 6 months to 50 years old: A prospective cohort study conducted in Jalisco. PLoS One 2021; 16:e0250253. [PMID: 33951076 PMCID: PMC8099064 DOI: 10.1371/journal.pone.0250253] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 04/01/2021] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND AND OBJECTIVES The burden of dengue virus (DENV), a mosquito-borne pathogen, remains difficult to assess due to misdiagnosis and underreporting. Moreover, the large proportion of asymptomatic dengue cases impairs comprehensive assessment of its epidemiology even where effective surveillance systems are in place. We conducted a prospective community-based study to assess the incidence of symptomatic dengue cases in Zapopan and neighboring municipalities in the state of Jalisco, Mexico. METHODS Healthy subjects aged 6 months to 50 years living in households located in the Zapopan and neighboring municipalities were enrolled for a 24-month follow-up study (NCT02766088). Serostatus was determined at enrolment and weekly contacts were conducted via phone calls and home visits. Participants had to report any febrile episode lasting for at least two days. Suspected dengue cases were tested by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), detection of non-structural protein 1 (NS1), anti-DENV immunoglobulin G and M (IgG and IgM) assays. RESULTS A total of 350 individuals from 87 households were enrolled. The overall seroprevalence of anti-DENV IgG at enrolment was 19.4% (95% confidence interval [CI] 14.5-25.6) with the highest seroprevalence rate observed in the adult group. Over the 27-month study period from July 2016 to September 2018, a total of 18 suspected dengue cases were reported. Four cases were confirmed by RT-qPCR and serotyped as DENV-1. A fifth case was confirmed by the NS1 assay. The 13 remaining suspected cases were tested negative by these assays. Based on the 5 virologically confirmed cases, symptomatic dengue incidence proportion of 1.4% (95%CI 0.5-3.8) was estimated. No severe cases or hospitalizations occurred during the study. CONCLUSION Community-based active surveillance was shown as efficient to detect symptomatic dengue cases. CLINICAL TRIAL REGISTRATION NCT02766088.
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Affiliation(s)
| | - Gerardo Amaya‐Tapia
- Department of Infectious Diseases, Hospital General de Occidente, Zapopan, Mexico
| | | | | | | | | | - Melanie de Boer
- Vaccines, GSK, Rockville, Maryland, United States of America
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22
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Chong ZL, Soe HJ, Ismail AA, Mahboob T, Chandramathi S, Sekaran SD. Evaluation of the Diagnostic Accuracy of a New Biosensors-Based Rapid Diagnostic Test for the Point-Of-Care Diagnosis of Previous and Recent Dengue Infections in Malaysia. BIOSENSORS 2021; 11:129. [PMID: 33921935 PMCID: PMC8143448 DOI: 10.3390/bios11050129] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/03/2021] [Accepted: 04/06/2021] [Indexed: 12/21/2022]
Abstract
Dengue is a major threat to public health globally. While point-of-care diagnosis of acute/recent dengue is available to reduce its mortality, a lack of rapid and accurate testing for the detection of previous dengue remains a hurdle in expanding dengue seroepidemiological surveys to inform its prevention, especially vaccination, to reduce dengue morbidity. This study evaluated ViroTrack Dengue Serostate, a biosensors-based semi-quantitative anti-dengue IgG (immunoglobulin G) immuno-magnetic agglutination assay for the diagnosis of previous and recent dengue in a single test. Blood samples were obtained from 484 healthy participants recruited randomly from two communities in Petaling district, Selangor, Malaysia. The reference tests were Panbio Dengue IgG indirect and capture enzyme-linked immunosorbent assays, in-house hemagglutination inhibition assay, and focus reduction neutralization test. Dengue Serostate had a sensitivity and specificity of 91.1% (95%CI 87.8-93.8) and 91.1% (95%CI 83.8-95.8) for the diagnosis of previous dengue, and 90.2% (95%CI 76.9-97.3) and 93.2% (95%CI 90.5-95.4) for the diagnosis of recent dengue, respectively. Its positive predictive value of 97.5% (95%CI 95.3-98.8) would prevent most dengue-naïve individuals from being vaccinated. ViroTrack Dengue Serostate's good point-of-care diagnostic accuracy can ease the conduct of dengue serosurveys to inform dengue vaccination strategy and facilitate pre-vaccination screening to ensure safety.
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Affiliation(s)
- Zhuo Lin Chong
- Centre for Communicable Diseases Research, Institute for Public Health, National Institutes of Health, Ministry of Health, Persiaran Setia Murni, Setia Alam, Shah Alam 40170, Selangor, Malaysia
| | - Hui Jen Soe
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Jalan Profesor Diraja Ungku Aziz, Kuala Lumpur 50603, Malaysia; (H.J.S.); (A.A.I.); (T.M.); (S.C.)
| | - Amni Adilah Ismail
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Jalan Profesor Diraja Ungku Aziz, Kuala Lumpur 50603, Malaysia; (H.J.S.); (A.A.I.); (T.M.); (S.C.)
| | - Tooba Mahboob
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Jalan Profesor Diraja Ungku Aziz, Kuala Lumpur 50603, Malaysia; (H.J.S.); (A.A.I.); (T.M.); (S.C.)
| | - Samudi Chandramathi
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Jalan Profesor Diraja Ungku Aziz, Kuala Lumpur 50603, Malaysia; (H.J.S.); (A.A.I.); (T.M.); (S.C.)
| | - Shamala Devi Sekaran
- Faculty of Medical & Health Sciences, UCSI University, Jalan Menara Gading, Cheras, Kuala Lumpur 56000, Malaysia
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23
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Alexander N, Carabali M, Lim JK. Estimating force of infection from serologic surveys with imperfect tests. PLoS One 2021; 16:e0247255. [PMID: 33661951 PMCID: PMC7932155 DOI: 10.1371/journal.pone.0247255] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Accepted: 02/04/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND The force of infection, or the rate at which susceptible individuals become infected, is an important public health measure for assessing the extent of outbreaks and the impact of control programs. METHODS AND FINDINGS We present Bayesian methods for estimating force of infection using serological surveys of infections which produce a lasting immune response, accounting for imperfections of the test, and uncertainty in such imperfections. In this estimation, the sensitivity and specificity can either be fixed, or belief distributions of their values can be elicited to allow for uncertainty. We analyse data from two published serological studies of dengue, one in Colombo, Sri Lanka, with a single survey and one in Medellin, Colombia, with repeated surveys in the same individuals. For the Colombo study, we illustrate how the inferred force of infection increases as the sensitivity decreases, and the reverse for specificity. When 100% sensitivity and specificity are assumed, the results are very similar to those from a standard analysis with binomial regression. For the Medellin study, the elicited distribution for sensitivity had a lower mean and higher variance than the one for specificity. Consequently, taking uncertainty in sensitivity into account resulted in a wide credible interval for the force of infection. CONCLUSIONS These methods can make more realistic estimates of force of infection, and help inform the choice of serological tests for future serosurveys.
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Affiliation(s)
- Neal Alexander
- MRC International Statistics and Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Mabel Carabali
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
| | - Jacqueline K. Lim
- Global Dengue and Aedes-transmitted Diseases Consortium (GDAC), International Vaccine Institute, Seoul, Korea
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Epidemiology of dengue fever in Gabon: Results from a health facility-based fever surveillance in Lambaréné and its surroundings. PLoS Negl Trop Dis 2021; 15:e0008861. [PMID: 33566822 PMCID: PMC7875424 DOI: 10.1371/journal.pntd.0008861] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 10/08/2020] [Indexed: 11/19/2022] Open
Abstract
Background In Africa, information on dengue is limited to outbreak reports and focused on some countries with continuing transmission in West and East Africa. To estimate the proportion of dengue-positive cases among febrile patients and identify clinical indicators of dengue cases, we conducted passive facility-based fever surveillance in a catchment area population of 70,000 residents of Lambaréné and its surroundings in Gabon. Methods Non-malarial febrile patients with current fever or history of fever (≤7 days) between 1 and 55 years of age, were enrolled at Albert Schweitzer Hospital (ASH). Acute (visit 1, day of enrollment) and convalescent blood samples were collected between 10 and 21 days after enrollment. Acute/convalescent samples were tested with IgM/IgG ELISA, and a selected subset of acute samples with RT-PCR. Results Among 682 non-malarial febrile patients enrolled, 119 (17.4%) were identified as dengue-positive (94 dengue-confirmed and 25 dengue-probable cases). Of these dengue-positive cases, 14 were confirmed with PCR, and based on serotyping, two infections were identified to be DENV-2 and two were DENV-3. The majority of our enrolled patients were <25 years of age and close to 80% of our dengue-positive cases were <15 years of age. In adjusted analyses, retro-orbital pain and abdominal pain were 2.7 and 1.6 times more frequently found among dengue-positive cases, compared to non-dengue cases. Conclusion Lambaréné is not considered dengue-endemic. However, one in six non-malarial febrile episodes was found to be dengue-positive in the study period. Dengue should be considered more frequently in clinicians’ diagnosis among non-malarial febrile patients in Lambaréné. Given the lack of data on dengue in Gabon, additional prospective and longitudinal studies would help to further define the burden and patterns of dengue for improved case detection. In Africa, information on dengue is limited to outbreak reports focused on some countries in West and East Africa. To estimate the proportion of dengue-positive cases among febrile patients and identify clinical indicators of dengue cases, we conducted passive health facility-based fever surveillance in a catchment area population of 70,000 residents of Lambaréné and its surroundings, Gabon. Among the patients with negative malaria RDT results, those with current fever or history of fever (≤7 days) between 1 and 55 years of age were enrolled at Albert Schweitzer Hospital (ASH). Two samples were collected with an interval of 10 to 21 days after enrollment. Samples underwent different testing for dengue confirmation. Among 682 febrile patients enrolled, 17.4% were identified as dengue-positive. Of these dengue-positive cases, we found DENV-2 and DENV-3 serotypes. Close to 80% of our dengue-positive cases were < 15 years old. Retro-orbital pain and abdominal pain were more commonly found among dengue-positive cases, compared to non-dengue cases. Lambaréné is not considered dengue-endemic. However, one in six non-malarial febrile episodes was found to be dengue-positive in the study period. Clinicians should consider dengue more frequently among non-malarial febrile patients. Given the lack of data on dengue in Gabon, more data should be generated to understand the burden and patterns of dengue for improved case detection.
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25
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Kulkarni R, Modak M, Gosavi M, Wani D, Mishra AC, Arankalle VA. Comparative assessment of commercial enzyme-linked immunosorbent assay & rapid diagnostic tests used for dengue diagnosis in India. Indian J Med Res 2021; 151:71-78. [PMID: 32134017 PMCID: PMC7055168 DOI: 10.4103/ijmr.ijmr_613_18] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Background & objectives: Dengue diagnosis is routinely carried out by detection of dengue virus (DENV) antigen NS1 and/or anti-DENV IgM antibodies using enzyme-linked immunosorbent assays (ELISAs) and rapid diagnostic tests (RDTs). This study was aimed at evaluation of quality of diagnostic assays currently in use in India for the identification of DENV infection. Methods: During 2016 dengue season (July-November) in Pune, India, comparative assessment of a few immunoassays was undertaken using (i) WHO-approved Panbio-Dengue-Early-(NS1)-ELISA and Panbio-Dengue-IgM-Capture-ELISA as reference tests, and (ii) Bayesian latent class analysis (BLCA) which assumes that no test is perfect. The assays included J.Mitra-Dengue-NS1-Ag-MICROLISA (JME-NS1), J.Mitra-Dengue-IgM-MICROLISA (JME-IgM), and two RDTs, namely, J.Mitra-Dengue-Day- 1-Test (JM-RDT) and SD-BIOLINE-Dengue-Duo (SDB-RDT). Serum samples from patients seeking dengue diagnosis (n=809) were tested using the diagnostic kits. The presence of NS1 and/or IgM was taken as evidence for dengue-positive diagnosis. Results: Panbio-NS1/IgM-ELISAs identified 38.6 per cent patients as dengue positive. With Panbio-ELISA as reference, all the tests were less sensitive for IgM detection, while for NS1, JM-RDT was less sensitive. For combined diagnosis (both markers), sensitivity of all the tests was low (55.7-76.6%). According to BLCA, Panbio-ELISA was 84 per cent sensitive for NS1, 86 per cent specific for IgM and 87 per cent specific for combined diagnosis. Accordingly, performance of the other tests was substantially improved with BLCA; however, sensitivity of both the RDTs for IgM detection remained unacceptable. The NS1 ELISAs and RDTs detected all four DENV serotypes, JME being most efficient. All IgM tests exhibited higher sensitivity in secondary infections. Interpretation & conclusions: These results confirmed superiority of ELISAs, and testing for both NS1 and IgM markers for dengue diagnosis, and emphasized on improvement in sensitivity of RDTs.
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Affiliation(s)
- Ruta Kulkarni
- Department of Communicable Diseases, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Meera Modak
- Department of Medical Microbiology, Bharati Medical College & Research Center, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Mrunal Gosavi
- Department of Communicable Diseases, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Dileep Wani
- Department of Immunohaematology & Blood Transfusion, Bharati Medical College & Research Center, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Akhilesh C Mishra
- Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Vidya A Arankalle
- Department of Communicable Diseases, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
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Chen HW, Maldonado TD, Lee CR, Williams M, Defang GN, Ellison DW, Van De Wyngaerde M, Rooney CM, Wu SJL. Independent Evaluation of Two Prototype Immunochromatographic Tests for Dengue Fever Developed by InBios. Mil Med 2021; 187:e655-e660. [PMID: 33428750 DOI: 10.1093/milmed/usaa553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 12/02/2020] [Accepted: 12/08/2020] [Indexed: 11/14/2022] Open
Abstract
INTRODUCTION Dengue fever, caused by any of the four dengue viruses (DENV1-4), is endemic in more than 100 countries around the world. Each year, up to 400 million people get infected with dengue virus. It is one of the most important arthropod-borne viral diseases. Dengue's global presence poses a medical threat to deploying military personnel and their dependents. An accurate diagnosis followed by attentive supportive care can improve outcomes in patients with severe dengue disease. Dengue diagnostic tests based on PCR and ELISA platforms have been developed and cleared by the U.S. FDA. However, these diagnostic assays are laborious and usually require highly trained personnel and specialized equipment, which presents a significant challenge when conducting operations in austere and resource-constrained areas. InBios International, Inc. (Seattle, WA) has developed two rapid and instrument-free immunochromatographic test prototype devices (multiplex and traditional formats) for dengue diagnosis. MATERIALS AND METHODS To determine the performance of the InBios immunochromatographic tests, 183 clinical samples were tested on both prototype devices. Both assays were performed without any instruments and the results were read in 20 minutes. RESULTS The traditional format had better overall performance (sensitivity: 97.4%; specificity: 90%) than the multiplex format (sensitivity: 86.9%; specificity: 63.3%). The traditional format was superior in serotype-specific detection with 100% overall sensitivity for DENV1, DENV3, and DENV4 and 93.3% sensitivity for DENV2 compared to the multiplex format (91.7%, 78.3%, 83.3%, and 96.3% for DENV1, 2, 3, and 4, respectively). The traditional format was easier to read than the multiplex format. The multiplex format was simpler and faster to set up than the traditional format. CONCLUSIONS The InBios traditional format had a better overall performance and readability profile than the multiplex format, while the multiplex format was easier to set up. Both formats were highly sensitive and specific, were easy to perform, and did not require sophisticated equipment. They are ideal for use in resource-limited settings where dengue is endemic. Based on our overall assessment, the traditional format should be considered for further development and used in the upcoming multicenter clinical trial toward FDA clearance.
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Affiliation(s)
- Hua-Wei Chen
- Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910, USA
| | - Tania D Maldonado
- Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910, USA
| | - Cheng-Rei Lee
- Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910, USA
| | - Maya Williams
- Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910, USA
| | - Gabriel N Defang
- Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910, USA
| | - Damon W Ellison
- Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
| | | | - Calli M Rooney
- U.S. Army Medical Materiel Development Activity, Fort Detrick, MD 21702, USA
| | - Shuenn-Jue L Wu
- Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910, USA
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Eligio-García L, Crisóstomo-Vázquez MDP, Caballero-García MDL, Soria-Guerrero M, Méndez–Galván JF, López-Cancino SA, Jiménez-Cardoso E. Co-infection of Dengue, Zika and Chikungunya in a group of pregnant women from Tuxtla Gutiérrez, Chiapas: Preliminary data. 2019. PLoS Negl Trop Dis 2020; 14:e0008880. [PMID: 33347432 PMCID: PMC7785221 DOI: 10.1371/journal.pntd.0008880] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 01/05/2021] [Accepted: 10/13/2020] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION Dengue, Zika and Chikungunya are RNA Arboviruses present in some areas of Mexico, mainly in the endemic state of Chiapas that is characterized by presence of the vector that transmit them and an ecology that favors high transmission. According to the national epidemiological surveillance system, Dengue has intensified since 2018 and outbreaks continue in various states while for Zika and Chikungunya a decrease in cases has been reported in recent years. The main objective of this study was to determine the incidence of Dengue, Zika and Chikungunya infections during pregnancy in the state of Chiapas. PRINCIPAL FINDINGS The presence of previous and current infections and coinfections diagnosed by molecular (RT-PCR) and immunological (ELISA for IgG determination) techniques indicates a wide circulation of viruses in asymptomatic people, specifically in pregnant women showing that silent infections in dry season contributes to the preservation of viruses. CONCLUSIONS From 136 studied samples, 27.7% tested positive for DENV, 8% for ZIKV and 24.1% for CHIKV by RTPCR and the values of IgG in sera show that 83.9% were positive for IgG antibodies against DENV, 65% against ZIKV and 59.1% against CHIKV. Results demonstrated presence of ZIKV and CHIKV, not detected by the epidemiological surveillance system, so the importance of establishing proactive epidemiological systems more strict, especially because these infections in pregnant women can cause severe health problems for newborn children.
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Affiliation(s)
- Leticia Eligio-García
- Laboratorio de Investigación en Parasitología. Hospital Infantil de México “Federico Gómez”. CdMx. México
| | | | | | - Mariana Soria-Guerrero
- Laboratorio de Investigación en Parasitología. Hospital Infantil de México “Federico Gómez”. CdMx. México
| | | | | | - Enedina Jiménez-Cardoso
- Laboratorio de Investigación en Parasitología. Hospital Infantil de México “Federico Gómez”. CdMx. México
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Marbán-Castro E, Arrieta GJ, Martínez MJ, González R, Bardají A, Menéndez C, Mattar S. High Seroprevalence of Antibodies against Arboviruses among Pregnant Women in Rural Caribbean Colombia in the Context of the Zika Virus Epidemic. Antibodies (Basel) 2020; 9:antib9040056. [PMID: 33096597 PMCID: PMC7709128 DOI: 10.3390/antib9040056] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 08/27/2020] [Accepted: 09/09/2020] [Indexed: 12/03/2022] Open
Abstract
Mosquito-borne viruses such as dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV) have spread in recent decades. We aimed to assess seroprevalence of arboviral infections in pregnant women living in Cereté, Caribbean Colombia. In 2016 a cross-sectional facility-based sero-survey study was performed among pregnant women (N = 90). Most of them (66%) reported at least one symptom or sign compatible with arboviral infection over the previous 15 days. All screened women had a positive IgG for DENV, 89% for ZIKV, and 82% for CHIKV. One woman tested positive for ZIKV IgM. This study shows the high exposure among pregnant women to arboviruses in endemic areas, shown by the high seroprevalence of past arboviral infections. Given the evidence on the potential risks of these arboviral infections on pregnancy and infant outcomes, these results highlight the need for continuous epidemiological surveillance of arboviral diseases, particularly among those most of risk of their harmful consequences.
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Affiliation(s)
- Elena Marbán-Castro
- ISGlobal, Hospital Clínic, Universitat de Barcelona, 08036 Barcelona, Spain; (M.J.M.); (R.G.); (A.B.); (C.M.)
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain
- Correspondence: ; Tel.: +34-93-227-5400 (ext. 4142)
| | - Germán J. Arrieta
- Corporación Universitaria del Caribe (CECAR), Grupo de Salud Pública, Sincelejo 700001, Colombia;
- Clínica Salud Social, Sincelejo 700001, Colombia;
| | - Miguel J. Martínez
- ISGlobal, Hospital Clínic, Universitat de Barcelona, 08036 Barcelona, Spain; (M.J.M.); (R.G.); (A.B.); (C.M.)
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain
| | - Raquel González
- ISGlobal, Hospital Clínic, Universitat de Barcelona, 08036 Barcelona, Spain; (M.J.M.); (R.G.); (A.B.); (C.M.)
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain
| | - Azucena Bardají
- ISGlobal, Hospital Clínic, Universitat de Barcelona, 08036 Barcelona, Spain; (M.J.M.); (R.G.); (A.B.); (C.M.)
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain
- Centro de Investigação em Saúde de Manhiça (CISM), Manhiça 1929, Mozambique
| | - Clara Menéndez
- ISGlobal, Hospital Clínic, Universitat de Barcelona, 08036 Barcelona, Spain; (M.J.M.); (R.G.); (A.B.); (C.M.)
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain
- Centro de Investigação em Saúde de Manhiça (CISM), Manhiça 1929, Mozambique
| | - Salim Mattar
- Clínica Salud Social, Sincelejo 700001, Colombia;
- Instituto de Investigaciones Biológicas del Trópico, Universidad de Córdoba, Montería 230002, Colombia
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Six Cases of Zika/Dengue Coinfection in a Brazilian Cohort, 2015-2019. Viruses 2020; 12:v12101201. [PMID: 33096849 PMCID: PMC7588971 DOI: 10.3390/v12101201] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 10/18/2020] [Accepted: 10/18/2020] [Indexed: 01/07/2023] Open
Abstract
Brazil is one of the countries which has been most affected by dengue epidemics. This scenario became more challenging with the emergence of Zika virus after 2014. The cocirculation of dengue and Zika viruses makes their diagnosis and treatment a challenge for health professionals, especially due to their similar clinical outcomes. From 2015 to 2019, we followed a cohort of 2017 participants in Goiania, Goias, Central Brazil. Febrile cases were monitored weekly, and after identification of fever, the physician performed a home visit for clinical evaluation and collection of blood/urine for diagnosis of acute dengue/Zika infection in suspected cases. Dengue acute infection was investigated by NS1 antigen and real time RT-PCR and seroconversion of anti-dengue IgM. ZIKV infection was confirmed by real time RT-PCR. Six cases of Zika/dengue coinfection among participants were reported. The clinical outcomes were suggestive for both DENV and ZIKV infection. No coinfected patient had neurological clinical manifestation, warning signs or need for hospitalization. A continuous specific laboratory confirmation for both dengue and Zika viruses should be enforced as part of the surveillance systems even in the presence of very suggestive cases of dengue fever, minimizing the risk of a late detection of ZIKV circulation.
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Raafat N, Blacksell SD, Maude RJ. A review of dengue diagnostics and implications for surveillance and control. Trans R Soc Trop Med Hyg 2020; 113:653-660. [PMID: 31365115 PMCID: PMC6836713 DOI: 10.1093/trstmh/trz068] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 06/11/2019] [Accepted: 06/27/2019] [Indexed: 12/13/2022] Open
Abstract
Dengue is the world’s most common arboviral infection, with almost 4 billion people estimated to be living at risk of dengue infection. A recently introduced vaccine is currently recommended only for seropositive individuals in a restricted age range determined by transmission intensity. With no effective dengue vaccine for the general population or any antiviral therapy, dengue control continues to rely heavily on vector control measures. Early and accurate diagnosis is important for guiding appropriate management and for disease surveillance to guide prompt dengue control interventions. However, major uncertainties exist in dengue diagnosis and this has important implications for all three. Dengue can be diagnosed clinically against predefined lists of signs and symptoms and by detection of dengue-specific antibodies, non-structural 1 antigen or viral RNA by reverse transcriptase–polymerase chain reaction. All of these methods have their limitations. This review aims to describe and quantify the advantages, uncertainties and variability of the various diagnostic methods used for dengue and discuss their implications and applications for dengue surveillance and control.
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Affiliation(s)
- Nader Raafat
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Rajthevee, Bangkok, Thailand
| | - Stuart D Blacksell
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Rajthevee, Bangkok, Thailand.,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Richard J Maude
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Rajthevee, Bangkok, Thailand.,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.,Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA
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Production of Proteins prM/M and E of Dengue Virus-3 in Pichia pastoris: Simplified Purification and Evaluation of Their Use as Antigens in Serological Diagnosis of Dengue. FERMENTATION 2020. [DOI: 10.3390/fermentation6030088] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Dengue is a major arbovirus affecting humans today. With the growing number of cases, it is essential to have large-scale production of antigens for the development of diagnostic kits for the rapid detection of patients infected by the virus and consequent proper medical intervention for them. In this work, we express the prM/M and E proteins of dengue virus-3 in yeast Pichia pastoris KM71H. The proteins were produced in soluble form in the supernatant of the culture and were purified by precipitation with ammonium sulfate. The fraction of 80% of ammonium sulfate was used as an antigen in an indirect enzyme-linked immunosorbent assay (ELISA), providing a sensitivity of 82.61% and a specificity of 89.25%. Thus, the methodology proposed here showed promise for obtaining antigens of dengue viruses and creating quick and inexpensive diagnostic tests, which is of great value since large portions of the areas affected by this disease are economically neglected.
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Tan W, Liew JWK, Selvarajoo S, Lim XY, Foo CJ, Refai WF, Robson N, Othman S, Hadi HA, Mydin FHM, Malik TFA, Lau YL, Vythilingam I. Inapparent dengue in a community living among dengue-positive Aedes mosquitoes and in a hospital in Klang Valley, Malaysia. Acta Trop 2020; 204:105330. [PMID: 31917959 DOI: 10.1016/j.actatropica.2020.105330] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 01/05/2020] [Accepted: 01/05/2020] [Indexed: 12/25/2022]
Abstract
The public health burden of dengue is most likely under reported. Current dengue control measures only considered symptomatic dengue transmission. Hence, there is a paucity of information on the epidemiology of inapparent dengue. This study reports that many people have been unknowingly exposed to dengue infection. Almost 10% and 70% of individuals without any history of dengue infection and living in a dengue hotspot, in Selangor, Malaysia, were dengue IgM and IgG positive respectively. When dengue-positive mosquitoes were detected in the hotspot, 11 (6.3%) of the 174 individuals tested were found to have dengue viremia, of which 10 were asymptomatic. Besides, upon detection of a dengue-infected mosquito, transmission was already widespread. In a clinical setting, it appears that people living with dengue patients have been exposed to dengue, whether asymptomatic or symptomatic. They can either have circulating viral RNA and/or presence of NS1 antigen. It is also possible that they are dengue seropositive. Collectively, the results indicate that actions taken to control dengue transmission after the first report of dengue cases may be already too late. The current study also revealed challenges in diagnosing clinically inapparent dengue in hyperendemic settings. There is no one best method for diagnosing inapparent dengue. This study demonstrates empirical evidence of inapparent dengue in different settings. Early dengue surveillance in the mosquito population and active serological/virological surveillance in humans can go hand in hand. More studies are required to investigate the epidemiology, seroprevalence, diagnostics, and control of inapparent dengue. It is also crucial to educate the public, health staff and medical professionals on asymptomatic dengue and to propagate awareness, which is important for controlling transmission.
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Chong ZL, Sekaran SD, Soe HJ, Peramalah D, Rampal S, Ng CW. Diagnostic accuracy and utility of three dengue diagnostic tests for the diagnosis of acute dengue infection in Malaysia. BMC Infect Dis 2020; 20:210. [PMID: 32164538 PMCID: PMC7069157 DOI: 10.1186/s12879-020-4911-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 02/20/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Dengue is an emerging infectious disease that infects up to 390 million people yearly. The growing demand of dengue diagnostics especially in low-resource settings gave rise to many rapid diagnostic tests (RDT). This study evaluated the accuracy and utility of ViroTrack Dengue Acute - a new biosensors-based dengue NS1 RDT, SD Bioline Dengue Duo NS1/IgM/IgG combo - a commercially available RDT, and SD Dengue NS1 Ag enzyme-linked immunosorbent assay (ELISA), for the diagnosis of acute dengue infection. METHODS This prospective cross-sectional study consecutively recruited 494 patients with suspected dengue from a health clinic in Malaysia. Both RDTs were performed onsite. The evaluated ELISA and reference tests were performed in a virology laboratory. The reference tests comprised of a reverse transcription-polymerase chain reaction and three ELISAs for the detection of dengue NS1 antigen, IgM and IgG antibodies, respectively. The diagnostic performance of evaluated tests was computed using STATA version 12. RESULTS The sensitivity and specificity of ViroTrack were 62.3% (95%CI 55.6-68.7) and 95.0% (95%CI 91.7-97.3), versus 66.5% (95%CI 60.0-72.6) and 95.4% (95%CI 92.1-97.6) for SD NS1 ELISA, and 52.4% (95%CI 45.7-59.1) and 97.7% (95%CI 95.1-99.2) for NS1 component of SD Bioline, respectively. The combination of the latter with its IgM and IgG components were able to increase test sensitivity to 82.4% (95%CI 76.8-87.1) with corresponding decrease in specificity to 87.4% (95%CI 82.8-91.2). Although a positive test on any of the NS1 assays would increase the probability of dengue to above 90% in a patient, a negative result would only reduce this probability to 23.0-29.3%. In contrast, this probability of false negative diagnosis would be further reduced to 14.7% (95%CI 11.4-18.6) if SD Bioline NS1/IgM/IgG combo was negative. CONCLUSIONS The performance of ViroTrack Dengue Acute was comparable to SD Dengue NS1 Ag ELISA. Addition of serology components to SD Bioline Dengue Duo significantly improved its sensitivity and reduced its false negative rate such that it missed the fewest dengue patients, making it a better point-of-care diagnostic tool. New RDT like ViroTrack Dengue Acute may be a potential alternative to existing RDT if its combination with serology components is proven better in future studies.
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Affiliation(s)
- Zhuo Lin Chong
- Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
- Institute for Public Health, National Institutes of Health, Ministry of Health, Setia Alam, Selangor Malaysia
| | - Shamala Devi Sekaran
- Faculty of Medicine and Biomedical Sciences, MAHSA University, Jenjarom, Selangor Malaysia
| | - Hui Jen Soe
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Devi Peramalah
- Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Sanjay Rampal
- Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Chiu-Wan Ng
- Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Lee H, Ryu JH, Park HS, Park KH, Bae H, Yun S, Choi AR, Cho SY, Park C, Lee DG, Lim J, Lee J, Lee S, Shin S, Park H, Oh EJ. Comparison of Six Commercial Diagnostic Tests for the Detection of Dengue Virus Non-Structural-1 Antigen and IgM/IgG Antibodies. Ann Lab Med 2019; 39:566-571. [PMID: 31240885 PMCID: PMC6660329 DOI: 10.3343/alm.2019.39.6.566] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 03/29/2019] [Accepted: 06/09/2019] [Indexed: 12/12/2022] Open
Abstract
ELISAs and rapid diagnostic tests (RDTs) are widely used for diagnosing dengue virus (DENV) infection. Using 138 single blood samples, we compared the ability to detect non-structural (NS)-1 antigen and anti-DENV IgM/IgG antibodies among (1) DENV Detect NS1 ELISA, DENV Detect IgM capture ELISA and DENV Detect IgG ELISA (InBios International, Inc.); (2) Anti-Dengue virus IgM Human ELISA and Anti-Dengue virus IgG Human ELISA (Abcam); (3) Dengue virus NS1 ELISA, Anti-Dengue virus ELISA (IgM) and Anti-Dengue virus ELISA (IgG) (Euroimmun); (4) Asan Easy Test Dengue NS1 Ag 100 and Asan Easy Test Dengue IgG/IgM (Asan Pharm); (5) SD BIOLINE Dengue Duo (Standard Diagnostics); and (6) Ichroma Dengue NS1 and Ichroma Dengue IgG/IgM (Boditech Med). For NS1 antigen detection, InBios and Euroimmun showed higher sensitivities (100%) than the RDTs (42.9–64.3%). All tests demonstrated variable sensitivities for IgM (38.1–90.5%) and IgG (65.7–100.0%). InBios and Boditech Med demonstrated higher sensitivity (95.6% and 88.2%, respectively) than the other tests for combined NS1 antigen and IgM antibody. Five NS1 antigen tests had good agreement (92.8–98.6%) without showing positivity for chikungunya. However, all IgG tests demonstrated potential false-positivity with variable ranges. Clinical laboratories should note performance variations across tests and potential cross-reactivity.
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Affiliation(s)
- Hyeyoung Lee
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Department of Laboratory Medicine, Catholic Kwandong University International St. Mary's Hospital, Incheon, Korea
| | - Ji Hyeong Ryu
- Department of Convergence Medical Science, Graduate School, The Catholic University of Korea, Seoul, Korea
| | - Hye Sun Park
- Department of Convergence Medical Science, Graduate School, The Catholic University of Korea, Seoul, Korea
| | - Ki Hyun Park
- Department of Convergence Medical Science, Graduate School, The Catholic University of Korea, Seoul, Korea
| | - Hyunjoo Bae
- Department of Convergence Medical Science, Graduate School, The Catholic University of Korea, Seoul, Korea
| | - Sojeong Yun
- Department of Convergence Medical Science, Graduate School, The Catholic University of Korea, Seoul, Korea
| | - Ae Ran Choi
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sung Yeon Cho
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chulmin Park
- Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Dong Gun Lee
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.,Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jihyang Lim
- Department of Laboratory Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jehoon Lee
- Department of Laboratory Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seungok Lee
- Department of Laboratory Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea Seoul, Korea
| | - Soyoung Shin
- Department of Laboratory Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea Seoul, Korea
| | - Haeil Park
- Department of Laboratory Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Eun Jee Oh
- Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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Comparison of Two Commercial ELISA Kits for the Detection of Anti-Dengue IgM for Routine Dengue Diagnosis in Laos. Trop Med Infect Dis 2019; 4:tropicalmed4030111. [PMID: 31349636 PMCID: PMC6789465 DOI: 10.3390/tropicalmed4030111] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 07/12/2019] [Accepted: 07/22/2019] [Indexed: 11/17/2022] Open
Abstract
The endemicity of Dengue virus (DENV) infection remains a major public health problem in Lao PDR. In this study, we compared two commercial anti-dengue IgM ELISA kits, Panbio® Dengue IgM Capture ELISA (Panbio Kit, Alere, Waltham, MA, USA) and DEN DetectTM MAC-ELISA (InBios kit, InBios International, Inc., Seattle, WA, USA), in the context of diagnosis of patients admitted to hospital with clinical dengue presentation. Two panels of paired blood samples were tested. Panel A was composed of 54 dengue confirmed patients (by DENV real-time RT-PCR) and 11 non-dengue dengue patients (other infections confirmed by corresponding PCR results). Panel B included 74 patients randomly selected from consecutive patients admitted to Mahosot Hospital in 2008 with suspicion of dengue fever according to WHO criteria. Results from panel A showed significantly better sensitivity for Panbio kit (64.8%; 95%CI: 50.6–77.3%) than for InBios kit (18.5%; 95%CI: 9.3–31.4%) when testing admission sera. Sensitivity was increased for both kits when combining results from admission and convalescent sera. Concordant results were obtained from panel B with fair agreement (κ = 0.29) between both kits when testing single admission samples, and moderate agreement (κ = 0.5) when combining results from admission and convalescent sera.
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36
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Schüttoff T, Adam A, Reiche S, Jassoy C. Enhancing the concordance of two commercial dengue IgG ELISAs by exchange of the calibrator sample. J Clin Virol 2019; 118:1-5. [PMID: 31301516 DOI: 10.1016/j.jcv.2019.07.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 07/01/2019] [Accepted: 07/04/2019] [Indexed: 01/05/2023]
Abstract
BACKGROUND Dengue IgG testing is being recommended before dengue vaccination. Presently, the diagnostic method of choice is the dengue IgG ELISA. OBJECTIVE Determine the test performance and concordance of two commercial dengue IgG ELISA kits. STUDY DESIGN A diagnostic study to examine the sensitivity, specificity, accuracy and concordance of the Panbio Dengue Indirect IgG ELISA kit and the NovaLisa Dengue IgG ELISA kit. Sera (483) were from dengue-endemic regions in Sudan. Test performance characteristics were determined when tests were performed as indicated in the test kits and when the Panbio calibrator sample was used for both tests. RESULTS The sensitivity of the Panbio and the NovaLisa ELISA was 91.1% and 99.0% and the specificity was 79.4% and 50.9%. The Panbio test was slightly more accurate (87.5% compared with 84.0%). Quantitative measurement readings of the tests correlated. The calibrator samples gave different cutoff values. Replacing the NovaLisa cutoff sample with the Panbio calibrator sample raised the accuracy of the NovaLisa assay to 88% and increased the concordance of the tests from 82.8 to 93%. CONCLUSIONS The study shows that the two dengue IgG ELISAs differed clearly in sensitivity and specificity and gave discordant results for 17.2% of the sera. For the most part the discrepancy depended on the calibrator sample. The findings indicate that an optimized dengue IgG calibrator standard can enhance accuracy and concordance of commercial dengue ELISAs. An optimized standard calibrator would make dengue IgG seroprevalence testing more reliable.
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Affiliation(s)
- Tom Schüttoff
- Institute for Virology, University Clinics and Medical Faculty, University of Leipzig, 04103 Leipzig, Germany
| | - Awadalkareem Adam
- Institute for Virology, University Clinics and Medical Faculty, University of Leipzig, 04103 Leipzig, Germany
| | - Sven Reiche
- Institute for Virology, University Clinics and Medical Faculty, University of Leipzig, 04103 Leipzig, Germany
| | - Christian Jassoy
- Institute for Virology, University Clinics and Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
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Development of an Enzyme-Linked Immunosorbent Assay for Rapid Detection of Dengue Virus (DENV) NS1 and Differentiation of DENV Serotypes during Early Infection. J Clin Microbiol 2019; 57:JCM.00221-19. [PMID: 30971466 PMCID: PMC6595446 DOI: 10.1128/jcm.00221-19] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 04/03/2019] [Indexed: 12/01/2022] Open
Abstract
Dengue fever, caused by infections with the dengue virus (DENV), affects nearly 400 million people globally every year. Early diagnosis and management can reduce the morbidity and mortality rates of severe forms of dengue disease as well as decrease the risk of wider outbreaks. Dengue fever, caused by infections with the dengue virus (DENV), affects nearly 400 million people globally every year. Early diagnosis and management can reduce the morbidity and mortality rates of severe forms of dengue disease as well as decrease the risk of wider outbreaks. Although the early diagnosis of dengue can be achieved using a number of commercial NS1 detection kits, none of these can differentiate among the four dengue virus serotypes. In this study, we developed an enzyme-linked immunosorbent assay (ELISA) for the detection of dengue virus (DENV) NS1 by pairing a serotype-cross-reactive monoclonal antibody (MAb) with one of four serotype-specific MAbs in order to facilitate the rapid detection of NS1 antigens and the simultaneous differentiation of DENV serotypes. A total of 146 serum samples obtained from patients suspected to be in the acute phase of DENV infection were used to evaluate the clinical application of our novel test for the detection and serotyping of DENV. The overall sensitivity rate of our test was 84.85%, and the sensitivity rates for serotyping were as follows: 88.2% (15/17) for DENV serotype 1 (DENV1), 94.7% (18/19) for DENV2, 75% (12/16) for DENV3, and 66.6% (6/9) for DENV4. Moreover, there was no cross-reactivity among serotypes, and no cross-reactivity was observed in sera from nondengue patients. Thus, our test not only enables the rapid detection of the dengue virus but also can distinguish among the specific serotypes during the early stages of infection. These results indicate that our ELISA for DENV NS1 is a convenient tool that may help elucidate the epidemiology of DENV outbreaks and facilitate the clinical management of DENV infections.
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Al-Raddadi R, Alwafi O, Shabouni O, Akbar N, Alkhalawi M, Ibrahim A, Hussain R, Alzahrani M, Al Helal M, Assiri A. Seroprevalence of dengue fever and the associated sociodemographic, clinical, and environmental factors in Makkah, Madinah, Jeddah, and Jizan, Kingdom of Saudi Arabia. Acta Trop 2019; 189:54-64. [PMID: 30244133 DOI: 10.1016/j.actatropica.2018.09.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Revised: 09/14/2018] [Accepted: 09/16/2018] [Indexed: 01/23/2023]
Abstract
This study aimed to estimate the seroprevalence of anti-dengue IgG antibodies in Makkah, Al Madinah, Jeddah, and Jizan; and to identify the associated demographic, clinical, and environmental independent risk factors. A community-based household serosurvey conducted between September 20, 2016 and January 31, 2017. A multi-stage stratified cluster sampling was used to select 6596 participants from Makkah, Madinah, Jeddah, and Jizan. Blood samples were drawn from all participants to detect anti-dengue IgG antibodies. A semi-structured questionnaire was used to collect information on demographic, clinical, and environmental data. Multivariate logistic regression was carried out to identify independent risk factors of dengue seropositivity. The dengue seroprevalence (95% confidence intervalI) was 26.7% (25.6%, 27.8%), with the highest (33.6%) and lowest (14.8%) rates in Jizan and Madinah, respectively, and reaching 50% or more in several districts of the four cities. Demographic predictors of seroprevalence included: dwelling in Makkah (odds ratio [OR] = 2.19, p < 0.001) or Jizan (OR = 2.17, p < 0.001); older age (OR = 3.91, p < 0.001 for age>30 years); housing type (OR = 1.84 and 1.82, p < 0.001 for popular and social houses, respectively); and number of household occupants (OR = 0.86 and 0.71 for 6-10 [p = 0.042] and 11-20 [p = 0.002] occupants, respectively). Environmental predictors included the absence of pest control works in residency area (OR = 1.39, p = 0.002), presence of mosquitoes in the home (OR = 1.39, p = 0.001), and absence of awareness campaigns (OR = 1.97, p < 0.001). One in four inhabitants of the Western region of Saudi Arabia was seropositive for the dengue virus. Implementation of behavior-based educational programs is recommended, involving the population in the identification and eradication of vector sources and promoting appropriate behaviors that prevent the spread.
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Salivary Detection of Dengue Virus NS1 Protein with a Label-Free Immunosensor for Early Dengue Diagnosis. SENSORS 2018; 18:s18082641. [PMID: 30103543 PMCID: PMC6111667 DOI: 10.3390/s18082641] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2018] [Revised: 08/04/2018] [Accepted: 08/08/2018] [Indexed: 12/30/2022]
Abstract
Dengue virus (DENV) is a highly pathogenic, arthropod-borne virus transmitted between people by Aedes mosquitoes. Despite efforts to prevent global spread, the potential for DENV epidemics is increasing world-wide. Annually, 3.6 billion people are at risk of infection. With no licensed vaccine, early diagnosis of dengue infection is critical for clinical management and patient survival. Detection of DENV non-structural protein 1 (NS1) is a clinically accepted biomarker for the early detection of DENV infection. Unfortunately, virtually all of the laboratory and commercial DENV NS1 diagnostic methods require a blood draw for sample analysis, limiting point-of-care diagnostics and decreases patient willingness. Alternatively, NS1 in human saliva has been identified for the potential early diagnosis of DENV infection. The collection of saliva is simple, non-invasive, painless, and inexpensive, even by minimally trained personnel. In this study, we present a label-free chemiresistive immunosensor for the detection of the DENV NS1 protein utilizing a network of single-walled carbon nanotubes functionalized with anti-dengue NS1 monoclonal antibodies. NS1 was successfully detected in adulterated artificial human saliva over the range of clinically relevant concentrations with high sensitivity and selectivity. It has potential application in clinical diagnosis and the ease of collection allows for self-testing, even within the home.
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Targeting vaccinations for the licensed dengue vaccine: Considerations for serosurvey design. PLoS One 2018; 13:e0199450. [PMID: 29944696 PMCID: PMC6019750 DOI: 10.1371/journal.pone.0199450] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 06/07/2018] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The CYD-TDV vaccine was unusual in that the recommended target population for vaccination was originally defined not only by age, but also by transmission setting as defined by seroprevalence. WHO originally recommended countries consider vaccination against dengue with CYD-TDV vaccine in geographic settings only where prior infection with any dengue serotype, as measured by seroprevalence, was >170% in the target age group. Vaccine was not recommended in settings where seroprevalence was <50%. Test-and-vaccinate strategies suggested following new analysis by Sanofi will still require age-stratified seroprevalence surveys to optimise age-group targeting. Here we address considerations for serosurvey design in the context of vaccination program planning. METHODS To explore how the design of seroprevalence surveys affects estimates of transmission intensity, 100 age-specific seroprevalence surveys were simulated using a beta-binomial distribution and a simple catalytic model for different combinations of age-range, survey size, transmission setting, and test sensitivity/specificity. We then used a Metropolis-Hastings Markov Chain Monte-Carlo algorithm to estimate the force of infection from each simulated dataset. RESULTS Sampling from a wide age-range led to more accurate estimates than merely increasing sample size in a narrow age-range. This finding was consistent across all transmission settings. The optimum test sensitivity and specificity given an imperfect test differed by setting with high sensitivity being important in high transmission settings and high specificity important in low transmission settings. CONCLUSIONS When assessing vaccination suitability by seroprevalence surveys, countries should ensure an appropriate age-range is sampled, considering epidemiological evidence about the local burden of disease.
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Rodriguez-Manzano J, Chia PY, Yeo TW, Holmes A, Georgiou P, Yacoub S. Improving Dengue Diagnostics and Management Through Innovative Technology. Curr Infect Dis Rep 2018; 20:25. [PMID: 29882167 PMCID: PMC5992235 DOI: 10.1007/s11908-018-0633-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW Dengue continues to be a major global public health threat. Symptomatic infections can cause a spectrum of disease ranging from a mild febrile illness to severe and potentially life-threatening manifestations. Management relies on supportive treatment with careful fluid replacement. The purpose of this review is to define the unmet needs and challenges in current dengue diagnostics and patient monitoring and outline potential novel technologies to address these needs. RECENT FINDINGS There have been recent advances in molecular and point-of-care (POC) diagnostics as well as technologies including wireless communication, low-power microelectronics, and wearable sensors that have opened up new possibilities for management, clinical monitoring, and real-time surveillance of dengue. Novel platforms utilizing innovative technologies for POC dengue diagnostics and wearable patient monitors have the potential to revolutionize dengue surveillance, outbreak response, and management at population and individual levels. Validation studies of these technologies are urgently required in dengue-endemic areas.
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Affiliation(s)
- Jesus Rodriguez-Manzano
- Centre for Bio-inspired Technology, Department of Electrical and Electronic Engineering, Imperial College London, London, UK
| | - Po Ying Chia
- Communicable Diseases Centre, Institute for Infectious Disease and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Tsin Wen Yeo
- Communicable Diseases Centre, Institute for Infectious Disease and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technical University, Singapore, Singapore
| | - Alison Holmes
- Department of Medicine, Imperial College London, London, UK
| | - Pantelis Georgiou
- Centre for Bio-inspired Technology, Department of Electrical and Electronic Engineering, Imperial College London, London, UK
| | - Sophie Yacoub
- Department of Medicine, Imperial College London, London, UK.
- Singapore-MIT Alliance for Research and Technology, Singapore, Singapore.
- Oxford University Clinical Research Unit, Wellcome Trust Asia Programme, Ho Chi Minh City, Vietnam.
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Reliable Serological Testing for the Diagnosis of Emerging Infectious Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1062:19-43. [PMID: 29845523 DOI: 10.1007/978-981-10-8727-1_3] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Climate change, increased urbanization and international travel have facilitated the spread of mosquito vectors and the viral species they carry. Zika virus (ZIKV) is currently spreading in the Americas, while dengue virus (DENV) and chikungunya virus (CHIKV) have already become firmly established in most tropical and also many non-tropical regions. ZIKV, DENV and CHIKV overlap in their endemic areas and cause similar clinical symptoms, especially in the initial stages of infection. Infections with each of these viruses can lead to severe complications, and co-infections have been reported. Therefore, laboratory analyses play an important role in differential diagnostics. A timely and accurate diagnosis is crucial for patient management, prevention of unnecessary therapies, rapid adoption of vector control measures, and collection of epidemiological data.There are two pillars to diagnosis: direct pathogen detection and the determination of specific antibodies. Serological tests provide a longer diagnostic window than direct methods, and are suitable for diagnosing acute and past infections, for disease surveillance and for vaccination monitoring. ELISA and indirect immunofluorescence test (IIFT) systems based on optimized antigens enable sensitive and specific detection of antibodies against ZIKV, DENV and CHIKV in patient serum or plasma. In recent years, Euroimmun (Lübeck, Germany) has developed numerous test systems for the serological diagnosis of (re-)emerging diseases, including a very sensitive and specific anti-ZIKV ELISA.
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Variants in the TNFA, IL6 and IFNG genes are associated with the dengue severity in a sample from Colombian population. BIOMEDICA 2017; 37:486-497. [DOI: 10.7705/biomedica.v37i4.3305] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 12/09/2016] [Indexed: 01/26/2023]
Abstract
Introducción. La composición genética del huésped determina, entre otros aspectos, el perfil clínico del dengue, lo cual se debería al efecto de variantes en los genes que codifican citocinas proinflamatorias.Objetivo. Evaluar la asociación entre las variantes de tres polimorfismos en los genes candidatos TNFA, IL6 e IFNG con la gravedad del dengue en una población colombiana.Materiales y métodos. Se evaluaron los polimorfismos rs1800750, rs2069843 y rs2069705 de los genes TNFA, IL6 e IFNG, respectivamente, en 226 pacientes con dengue. Los genotipos se tipificaron usando la reacción en cadena de la polimerasa (PCR) y los polimorfismos de la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism, RFLP). Para determinar el riesgo de diferentes fenotipos del dengue, se compararon las frecuencias alélicas con la prueba de ji al cuadrado, y los genotipos y los haplotipos, con regresión logística. Por último, los análisis se ajustaron utilizando datos de autoidentificación o del componente genético ancestral.Resultados. El alelo A del rs2069843, ajustado por autoidentificación, se asoció con casos de dengue hemorrágico en afrocolombianos. En la muestra completa, dicho polimorfismo, ajustado por componente genético ancestral, fue reproducible. Además, hubo asociaciones significativas entre las combinaciones alélicas GGT y GAC de los rs1800750, rs2069843 y rs2069705 en pacientes con dengue hemorrágico, con ajuste por componente genético ancestral y sin él. Además, la combinación alélica AGC produjo 58,03 pg/ml más de interleucina 6 que la GGC, independientemente de los componentes genéticos europeo, amerindio y africano.Conclusión. Las variantes de los polimorfismos GGT y GAC de los rs1800750, rs2069843 y rs2069705 en los genes TNFA, IL6 e IFNG, respectivamente, se correlacionaron con la gravedad del dengue en esta muestra de población colombiana.
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Progress and Challenges towards Point-of-Care Diagnostic Development for Dengue. J Clin Microbiol 2017; 55:3339-3349. [PMID: 28904181 DOI: 10.1128/jcm.00707-17] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Dengue detection strategies involve viral RNA, antigen, and/or antibody detection. Each strategy has its advantages and disadvantages. Optimal, user-friendly, rapid diagnostic tests based on immunochromatographic assays are pragmatic point-of-care tests (POCTs) in regions where dengue is endemic where there are limited laboratory capabilities and optimal storage conditions. Increasingly, there is a greater public health significance for a multiplexing assay that differentiates dengue from Zika or pathogens with similar clinical presentations. Although there have been many assay/platform developments toward POCTs, independent validation and implementation remain very limited. This review highlights the current key progress and challenges toward the development of a dengue POCT.
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Chatterjee SS, Sharma A, Choudhury S, Chumber SK, Bage R, Parkhe N, Khanduri U. Dengue fever in a south Asian metropolis: a report on 219 cases. IRANIAN JOURNAL OF MICROBIOLOGY 2017; 9:174-185. [PMID: 29225757 PMCID: PMC5719512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
BACKGROUND AND OBJECTIVES Yearly epidemics of Dengue fever occur post-monsoon in India's capital, Delhi. A prospective observational study was conducted during the outbreak months to understand the epidemiology and outcome of this infection and its economic impact. MATERIALS AND METHODS Febrile hospitalized (n=219) patients with dengue fever diagnosed by a combination of MAC-ELISA, GAC-ELISA and NS1Antigen-ELISA were enrolled. Epidemiologic (including economic) parameters, clinical, radiological and laboratory manifestations were noted and patients followed up over the period of hospital stay. Patient management means and outcome were recorded and analysed. RESULTS As per WHO-2009, 153 (69.9%) and 27 (12.3%) patients were classified as dengue with warning signs and Severe Dengue respectively while according to WHO-1997 guidelines 39 (17.8%) and 18 (8.2%) patients were classified as DHF and DSS respectively. 216 patients were from the city while three were travellers; hospitalization was more frequent among the young and male gender. Fever, vomiting, aches and abdominal pain were the most common troublesome manifestations; classical dengue triad was present in 55 (25.1%) patients; hemorrhagic, neurologic and mucocutaneous manifestations were present in 44 (20.1%), 8 (3.7%) and 70 (32%) patients. Ascitis, pleural effusion, and Gall bladder wall oedema was found in 53 (24.2%), 31 (14.1%) and 45 (20.5%) patients respectively. Mortality was 1.4% (3 deaths); in addition there was an intra-uterine fetal death; mean expenditure per patient during the illness was US$ 377.25. CONCLUSION Dengue virus infection results in immense morbidity and substantial mortality.
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Affiliation(s)
- Shiv Sekhar Chatterjee
- Department of Laboratory Diagnostic Services, St Stephen Hospital, Delhi, India,Corresponding author: Dr. Shiv Sekhar Chatterjee, Assistant Professor, Department of Laboratory Diagnostic Services, St Stephen Hospital, Delhi, India. Tel: +9103325644070, +919748732366,
| | - Ankush Sharma
- Department of Laboratory Diagnostic Services, St Stephen Hospital, Delhi, India
| | | | | | - Ras Bage
- Department of Medicine, St Stephen Hospital, Delhi, India
| | - Nittin Parkhe
- Department of Radiology, St Stephen Hospital, Delhi, India
| | - Uma Khanduri
- Department of Laboratory Diagnostic Services, St Stephen Hospital, Delhi, India
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Ayukekbong JA, Oyero OG, Nnukwu SE, Mesumbe HN, Fobisong CN. Value of routine dengue diagnosis in endemic countries. World J Virol 2017; 6:9-16. [PMID: 28239567 PMCID: PMC5303857 DOI: 10.5501/wjv.v6.i1.9] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Revised: 11/24/2016] [Accepted: 12/09/2016] [Indexed: 02/05/2023] Open
Abstract
Dengue is one of the most common arthropod-borne viral diseases in humans and it is a leading cause of illness and death in the tropical and subtropical regions of the world. It is thought to account for 400 million cases annually among approximately 3.97 billion people at risk of infection in 128 endemic countries. Despite the global prevalence of the disease, the availability of a vaccine is limited in most countries in the endemic areas. Most endemic countries in South America, South East Asia and Africa serve as attractive touristic sites for people from non-endemic countries who become infected and export the virus to dengue-free regions. Dengue fever typically resembles malaria and in endemic countries most cases of dengue are treated as presumptive malaria. Consequently, routine dengue diagnosis among persons with fever will offer early treatment and reduce the burden of the disease. Also, routine testing among travellers from endemic countries will reduce importation and prevent the geographical expansion of dengue. In this essay, we seek to highlight the usefulness of routine dengue testing in endemic countries.
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Inan H, Poyraz M, Inci F, Lifson MA, Baday M, Cunningham BT, Demirci U. Photonic crystals: emerging biosensors and their promise for point-of-care applications. Chem Soc Rev 2017; 46:366-388. [PMID: 27841420 PMCID: PMC5529146 DOI: 10.1039/c6cs00206d] [Citation(s) in RCA: 187] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Biosensors are extensively employed for diagnosing a broad array of diseases and disorders in clinical settings worldwide. The implementation of biosensors at the point-of-care (POC), such as at primary clinics or the bedside, faces impediments because they may require highly trained personnel, have long assay times, large sizes, and high instrumental cost. Thus, there exists a need to develop inexpensive, reliable, user-friendly, and compact biosensing systems at the POC. Biosensors incorporated with photonic crystal (PC) structures hold promise to address many of the aforementioned challenges facing the development of new POC diagnostics. Currently, PC-based biosensors have been employed for detecting a variety of biotargets, such as cells, pathogens, proteins, antibodies, and nucleic acids, with high efficiency and selectivity. In this review, we provide a broad overview of PCs by explaining their structures, fabrication techniques, and sensing principles. Furthermore, we discuss recent applications of PC-based biosensors incorporated with emerging technologies, including telemedicine, flexible and wearable sensing, smart materials and metamaterials. Finally, we discuss current challenges associated with existing biosensors, and provide an outlook for PC-based biosensors and their promise at the POC.
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Affiliation(s)
- Hakan Inan
- Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Stanford University School of Medicine, Department of Radiology, Canary Center at Stanford for Cancer Early Detection, 3155 Porter Drive, Palo Alto, CA 94304, USA.
| | - Muhammet Poyraz
- Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Stanford University School of Medicine, Department of Radiology, Canary Center at Stanford for Cancer Early Detection, 3155 Porter Drive, Palo Alto, CA 94304, USA. and Department of Electrical Engineering, Stanford University, Stanford, CA, USA
| | - Fatih Inci
- Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Stanford University School of Medicine, Department of Radiology, Canary Center at Stanford for Cancer Early Detection, 3155 Porter Drive, Palo Alto, CA 94304, USA.
| | - Mark A Lifson
- Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Stanford University School of Medicine, Department of Radiology, Canary Center at Stanford for Cancer Early Detection, 3155 Porter Drive, Palo Alto, CA 94304, USA.
| | - Murat Baday
- Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Stanford University School of Medicine, Department of Radiology, Canary Center at Stanford for Cancer Early Detection, 3155 Porter Drive, Palo Alto, CA 94304, USA.
| | - Brian T Cunningham
- Department of Electrical and Computer Engineering, Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
| | - Utkan Demirci
- Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Stanford University School of Medicine, Department of Radiology, Canary Center at Stanford for Cancer Early Detection, 3155 Porter Drive, Palo Alto, CA 94304, USA. and Department of Electrical Engineering (by courtesy), Stanford University, Stanford, CA, USA
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Ortega GA, Pérez-Rodríguez S, Reguera E. Magnetic paper – based ELISA for IgM-dengue detection. RSC Adv 2017. [DOI: 10.1039/c6ra25992h] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
“Magnetic Paper – Based ELISA” for IgM-dengue antibodies detection provide a system with improved analytical response.
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Affiliation(s)
- G. A. Ortega
- Center for Applied Science and Advanced Technology of IPN
- Legaria Unit
- Mexico City
- Mexico
- University of Havana
| | - S. Pérez-Rodríguez
- National Autonomous University of Mexico
- Biomedical Research Institute
- Mexico City
- Mexico
| | - E. Reguera
- Center for Applied Science and Advanced Technology of IPN
- Legaria Unit
- Mexico City
- Mexico
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Chatterjee SS, Sharma A, Choudhury S, Chumber SK, Kaur M, Bage R, Parkhe N, Khanduri U. Significance of IgG optical density ratios (index value) in single reactive anti-Dengue virus IgG capture ELISA. IRANIAN JOURNAL OF MICROBIOLOGY 2016; 8:395-400. [PMID: 28491251 PMCID: PMC5420395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
BACKGROUND AND OBJECTIVES A single reactive IgG anti-Dengue virus ELISA test in the absence of IgM antibodies or NS1 antigen may denote current infection or past exposure to the virus. To determine whether IgG index value can be used to identify true current dengue infection we conducted a prospective observational study. MATERIALS AND METHODS Suspected dengue patients (n =1745) were tested in their first specimen by MAC-ELISA, GAC-ELISA and NS1 antigen ELISA. Patients with MAC-ELISA and NS1Antigen non-reactive but GAC-ELISA reactive results (n =57) in their first test were followed up and repeated sampling was asked for IgG index values were calculated according to the manufacturer's instruction and classified as: low (2.2-2.5), medium (2.5-4.0) and high (>4.0). RESULTS 16 out of 57 patients (28.1%) had low IgG Index value whereas 26 cases (45.6%) were categorized as medium and 15(26.3%) were classified as patients with high IgG index. Nine patients with paired reactive serology or antigen positive status were categorised as serologically confirmed dengue fever, 11 patients as not dengue with categorical evidence of other infections while the rest 37 casas with clinical, radiological and laboratory parameters suggestive of dengue but no serological confirmation as possible dengue. Among confirmed, possible and non-Dengue cases, 33.3, 32.4 and 0.0% had high Index value in comparison with 22.2, 29.7 and 27.3% showing low Index values, respectively. CONCLUSION Our results suggested a high IgG response in favour of true dengue infection than past exposure while no conclusions should drawn from a low or medium reactive GAC-ELISA results in the absence of IgM antibodies and NS1 Ag.
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Affiliation(s)
- Shiv Sekhar Chatterjee
- Corresponding author: Shiv Sekhar Chatterjee MD, FNB, Department of Laboratory Diagnostic Services, Stephen Hospital, Delhi, India; Microbiology, Nil Ratan Sircar Medical College, Kolkata, India. Tel: +919748732366, +913325644070, Fax: +91-33-2265-8179,
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Martínez-Vega RA, Rodriguez-Morales AJ, Bracho-Churio YT, Castro-Salas ME, Galvis-Ovallos F, Díaz-Quijano RG, Luna-González ML, Castellanos JE, Ramos-Castañeda J, Diaz-Quijano FA. A prospective cohort study to assess seroprevalence, incidence, knowledge, attitudes and practices, willingness to pay for vaccine and related risk factors in dengue in a high incidence setting. BMC Infect Dis 2016; 16:705. [PMID: 27887591 PMCID: PMC5124319 DOI: 10.1186/s12879-016-2055-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2016] [Accepted: 11/22/2016] [Indexed: 12/30/2022] Open
Abstract
Background Dengue is one of the most important vector-borne diseases in the world, causing significant morbidity and economic impact. In Colombia, dengue is a major public health problem. Departments of La Guajira, Cesar and Magdalena are dengue endemic areas. The objective of this research is to determine the seroprevalence and the incidence of dengue virus infection in the participating municipalities from these Departments, and also establish the association between individual and housing factors and vector indices with seroprevalence and incidence. We will also assess knowledge, attitudes and practices, and willingness-to-pay for dengue vaccine. Methods A cohort study will be assembled with a clustered multistage sampling in 11 endemic municipalities. Approximately 1000 homes will be visited to enroll people older than one year who living in these areas, who will be followed for 1 year. Dengue virus infections will be evaluated using IgG indirect ELISA and IgM and IgG capture ELISA. Additionally, vector indices will be measured, and adult mosquitoes will be captured with aspirators. Ovitraps will be used for continuous estimation of vector density. Discussion This research will generate necessary knowledge to design and implement strategies with a multidimensional approach that reduce dengue morbidity and mortality in La Guajira and other departments from Colombian Caribbean.
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Affiliation(s)
- Ruth Aralí Martínez-Vega
- Organización Latinoamericana para el Fomento de la Investigación en Salud, Bucaramanga, Santander, Colombia.,School of Medicine, Universidad de Santander, Bucaramanga, Santander, Colombia
| | - Alfonso J Rodriguez-Morales
- Organización Latinoamericana para el Fomento de la Investigación en Salud, Bucaramanga, Santander, Colombia.,Public Health and Infection Research Group, Faculty of Health Sciences, Universidad Tecnológica de Pereira, Pereira, Risaralda, Colombia
| | - Yalil Tomás Bracho-Churio
- Organización Latinoamericana para el Fomento de la Investigación en Salud, Bucaramanga, Santander, Colombia
| | - Mirley Enith Castro-Salas
- Organización Latinoamericana para el Fomento de la Investigación en Salud, Bucaramanga, Santander, Colombia
| | - Fredy Galvis-Ovallos
- Organización Latinoamericana para el Fomento de la Investigación en Salud, Bucaramanga, Santander, Colombia
| | | | | | | | - José Ramos-Castañeda
- Centro de Investigaciones sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico
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