Distinguishing Zika and Dengue Viruses through Simple Clinical Assessment, Singapore (original) (raw)
2018, Emerging infectious diseases
https://doi.org/10.3201/EID2408.171883
Sign up for access to the world's latest research
checkGet notified about relevant papers
checkSave papers to use in your research
checkJoin the discussion with peers
checkTrack your impact
Abstract
Dengue virus and Zika virus coexist in tropical regions in Asia where healthcare resources are limited; differentiating the 2 viruses is challenging. We showed in a case-control discovery cohort, and replicated in a validation cohort, that the diagnostic indices of conjunctivitis, platelet count, and monocyte count reliably distinguished between these viruses.
Related papers
Accuracy of Zika virus disease case definition during simultaneous Dengue and Chikungunya epidemics
PloS one, 2017
Zika is a new disease in the American continent and its surveillance is of utmost importance, especially because of its ability to cause neurological manifestations as Guillain-Barré syndrome and serious congenital malformations through vertical transmission. The detection of suspected cases by the surveillance system depends on the case definition adopted. As the laboratory diagnosis of Zika infection still relies on the use of expensive and complex molecular techniques with low sensitivity due to a narrow window of detection, most suspected cases are not confirmed by laboratory tests, mainly reserved for pregnant women and newborns. In this context, an accurate definition of a suspected Zika case is crucial in order for the surveillance system to gauge the magnitude of an epidemic. We evaluated the accuracy of various Zika case definitions in a scenario where Dengue and Chikungunya viruses co-circulate. Signs and symptoms that best discriminated PCR confirmed Zika from other labor...
Multiplexed biomarker panels discriminate Zika and Dengue virus infection in humans
Molecular & cellular proteomics : MCP, 2017
Zika virus (ZIKV) and dengue virus (DENV) are closely related flaviviruses that cause widespread, acute febrile illnesses, notably microcephaly for fetuses of infected pregnant women. Detecting the viral cause of these illnesses is paramount to determine risks to patients, counsel pregnant women, and help fight outbreaks. A combined diagnostic algorithm for ZIKV and DENV requires Reverse transcription polymerase chain reaction (RT-PCR) and IgM antibody detection. RT-PCR differentiates between DENV and ZIKV infections during the acute phases of infection, but differentiation based on IgM antibodies is currently nearly impossible in endemic areas. We have developed a ZIKV/DENV protein array and tested it with serum samples collected from ZIKV- and DENV-infected patients and healthy subjects in Puerto Rico. Our analyses reveal a biomarker panel that are capable of discriminating ZIKV and DENV infections with high accuracy, including Capsid protein from African ZIKV strain MR766, and ot...
Viruses
Zika virus (ZIKV) is the mosquito-transmitted virus that the WHO declared a Public Health Emergency of International Concern in 2016 due to the consequence of microcephaly from infected pregnancies. The incidence of Zika infection has been unclear in many countries because most infected people have nonspecific febrile illnesses. This study’s aim is to investigate the incidence of symptomatic Zika virus infections from the archived samples of a dengue cohort study of children in central Thailand from 2006 to 2009. We performed Zika NS1 immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) screening to identify symptomatic Zika infections in paired acute/convalescent serum samples. Symptomatic Zika infections were confirmed by reverse transcription polymerase chain reactions (RT-PCR) of acute serum samples. The comparison of the Zika NS1 IgG ELISA results between acute and convalescent samples showed 290/955 (30.4%) seropositive cases. Zika RT-PCR results were positive in 28 ...
PLoS currents, 2018
The current triple epidemic caused by dengue, zika and chikungunya constitutes a serious health problem in Brazil. The aim of this study was to investigate acute samples (up to the 7 days of symptoms) from patients presenting acute fever syndrome suspected as arboviral infection and characterize the clinical and laboratorial profile during the co-circulation of dengue, zika and chikungunya in Campo Grande, Mato Grosso do Sul (MS), midwest region of Brazil. All suspected cases (n=134) were tested by using serological and molecular diagnostic tests including DENV, ZIKV and CHIKV RT-PCR, Dengue nonstructural protein 1 (NS1) antigen capture ELISA, anti- DENV IgM ELISA and anti-CHIKV IgM ELISA. In addition, clinical, hematological and biochemical parameters of infected patients were analyzed. It was observed that 79.1% of the blood samples were confirmed for ZIKV and/or DENV infection Of those, 38.0% patients were DENV monoinfected, 26.8% were ZIKV monoinfected and 13.4% were DENV/ZIKV ...
Six Cases of Zika/Dengue Coinfection in a Brazilian Cohort, 2015–2019
Viruses, 2020
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 neuro...
International Journal of Infectious Diseases, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
PLOS Neglected Tropical Diseases, 2021
Background Our purpose was to provide a detailed clinical description, of symptoms and laboratory abnormalities, and temporality in patients with confirmed Zika and dengue infections, and other acute illnesses of unidentified origin (AIUO). Methods/ Principal findings This was a two-year, multicenter, observational, prospective, cohort study. We collected data from patients meeting the Pan American Health Organization’s modified case-definition criteria for probable Zika infection. We identified Zika, dengue chikungunya by RT-PCR in serum and urine. We compared characteristics between patients with confirmed Zika and dengue infections, Zika and AIUO, and Dengue and AIUO at baseline, Days 3,7,28 and 180 of follow-up. Most episodes (67%) consistent with the PAHO definition of probable Zika could not be confirmed as due to any flavivirus and classified as Acute Illnesses of Unidentified Origin (AIUO). Infections by Zika and dengue accounted for 8.4% and 16% of episodes. Dengue patients...
The American Journal of Tropical Medicine and Hygiene
Zika virus (ZIKV) serological diagnostics are compromised in areas where dengue viruses (DENV) cocirculate because of their high levels of protein sequence homology. Here, we describe the characterization of a Zika blockade-of-binding ELISA (Zika BOB) and a Zika microneutralization assay (Zika MN) for the detection of ZIKV nonstructural protein 1 (NS1)-specific antibodies and ZIKV neutralizing antibodies, respectively. Zika BOB and Zika MN cutoffs were established as 10 and 100 endpoint titers, respectively, using samples collected pre-and post-virologically confirmed ZIKV infection from subjects living in DENV-endemic areas. Specificity of the assays was equally high, whereas sensitivity of Zika BOB was lower than that of Zika MN, especially in samples collected > 6 months post-infection. Immunosurveillance analysis, using combined results from both Zika BOB and Zika MN, carried out also in DENVendemic regions in Colombia, Honduras, Mexico, and Puerto Rico before (2013-2014) and after (2017-2018) ZIKV introduction in the Americas suggests unapparent ZIKV seroprevalence rates ranged from 25% to 80% over the specified period of time in the regions investigated.
Loading Preview
Sorry, preview is currently unavailable. You can download the paper by clicking the button above.
References (11)
- Ooi EE, Goh KT, Gubler DJ. Dengue prevention and 35 years of vector control in Singapore. Emerg Infect Dis. 2006;12:887-93. http://dx.doi.org/10.3201/eid1206.051210
- Musso D, Gubler DJ. Zika virus. Clin Microbiol Rev. 2016;29:487- 524. http://dx.doi.org/10.1128/CMR.00072-15
- Fisher D, Cutter J. The inevitable colonisation of Singapore by Zika virus. BMC Med. 2016;14:188. http://dx.doi.org/10.1186/ s12916-016-0737-9
- Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis. 2008;14:1232-9. http://dx.doi.org/10.3201/ eid1408.080287
- Ho HJ, Wong JGX, Mar Kyaw W, Lye DC, Leo YS, Chow A. Diagnostic accuracy of parameters for Zika and dengue virus infections, Singapore. Emerg Infect Dis. 2017;23:2085-8. http://dx.doi.org/10.3201/eid2312.171224
- Schuler-Faccini L, Ribeiro EM, Feitosa IM, Horovitz DD, Cavalcanti DP, Pessoa A, et al.; Brazilian Medical Genetics Society-Zika Embryopathy Task Force. Possible association between Zika virus infection and microcephaly-Brazil, 2015. MMWR Morb Mortal Wkly Rep. 2016;65:59-62. http://dx.doi.org/ 10.15585/mmwr.mm6503e2
- Simmons CP, Farrar JJ, Nguyen vVC, Wills B. Dengue. N Engl J Med. 2012;366:1423-32. http://dx.doi.org/10.1056/ NEJMra1110265
- Pan American Health Organization/World Health Organization. Zika resources: case definitions. [cited 2017 Oct 17].
- Centers for Disease Control and Prevention; National Notifiable Diseases Surveillance System. Zika virus disease and Zika virus infection 2016 case definition, Approved June 2016 [cited 2017 Oct 17]. https://wwwn.cdc.gov/nndss/conditions/zika/case- definition/2016/06/
- Waggoner JJ, Gresh L, Vargas MJ, Ballesteros G, Tellez Y, Soda KJ, et al. Viremia and clinical presentation in Nicaraguan patients infected with Zika virus, chikungunya virus, and dengue virus. Clin Infect Dis. 2016;63:1584-90. http://dx.doi.org/10.1093/cid/ciw589
- Address for correspondence: Louis Yi Ann Chai, National University Health System-Division of Infectious Diseases, University Medicine Cluster, NUHS Tower Block, 1E Kent Ridge Rd, Singapore 119228, Singapore; email: chailouis@hotmail.com
Related papers
Zika Virus Disease Comparing Children and Adults in a Dengue-Endemic Setting
The American Journal of Tropical Medicine and Hygiene, 2021
ABSTRACTAcute Zika virus (ZIKV) infection may mimic dengue virus (DENV) infection. We aimed to study the clinical difference of ZIKV disease among suspected non-severe DENV patients comparing children and adults. Patients with acute illness suspected of DENV disease plus no evidence of plasma leakage at the Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand, were enrolled from December 2016 to September 2018. Clinical data including DENV rapid diagnostic test (RDT) results were collected. Zika virus diagnosis was confirmed by real-time reverse transcription PCR on urine. Of 291 (180 pediatric and 111 adult) cases enrolled, 27 (10 pediatric and 17 adult) confirmed ZIKV cases were found. Rash was more frequent among pediatric ZIKV than pediatric non-ZIKV cases (100% versus 60%, P = 0.01). Rash, arthralgia, and conjunctivitis were more frequent among adult ZIKV than adult non-ZIKV cases (100% versus 29.8%, 64.7% versus 26.6%, 52.9% versus 9.7%, all P < 0.01, respecti...
Comprehensive Evaluation of Differential Serodiagnosis between Zika and Dengue Viral Infections
Journal of Clinical Microbiology, 2018
Diagnostic testing for Zika virus (ZIKV) or dengue virus (DENV) infection can be accomplished by a nucleic acid detection method; however, a negative result does not exclude infection due to the low virus titer during infection depending on the timing of sample collection. Therefore, a ZIKV- or DENV-specific serological assay is essential for the accurate diagnosis of patients and to mitigate potential severe health outcomes.
Clinical and Laboratory Profile of Zika Virus Infection in Dengue Suspected Patients: A case series
Journal of Clinical Virology, 2016
Background: The Zika virus (ZIKV) is an emerging arthropod-borne virus related to the dengue virus (DENV), and shows a similar clinical profile as other arboviral diseases, such as dengue and chikungunya virus (CHIKV). Historically, ZIKV has been associated with sporadic cases of human infection, but is now responsible for outbreaks worldwide. In Brazil, cases have been reported since 2015, with some cases causing severe disease. Objective: To identify clinical symptoms of Zika in patients in Dengue suspected patients. Study design: Description of a series of cases, wherein we analyzed 100 clinical samples collected from patients who exhibited acute febrile disease for ≤5 days, from January to February 2016. Results: In this study, we report 13 cases of ZIKV infection in adults presenting dengue-like symptoms in a DENV endemic area. All patients presented with fever, with myalgia being the second most frequently observed symptom. Two patients had rashes, but none of them had conjunctivitis. Other less frequent manifestations included headache, arthralgia, diarrhea, and nausea. Conclusion: The co-circulation of ZIKV and DENV is a serious public health concern, since it represents both a clinical and diagnostic challenge in endemic areas, as well as in the field of travel medicine.
Diagnostic Accuracy of Parameters for Zika and Dengue Virus Infections, Singapore
Emerging infectious diseases, 2017
Singapore experienced its first documented Zika virus outbreak in 2016. We identified clinical and laboratory parameters that increase the probability for Zika or dengue virus infection. Early during the illness, combinations of key parameters obtained through clinical assessment and hematologic tests can help distinguish between these infections.
Clinical Infectious Diseases
Background. The explosive spread of Zika virus (ZIKV) and associated microcephaly present an urgent need for sensitive and specific serodiagnostic tests, particularly for pregnant women in dengue virus (DENV)-endemic regions. Recent reports of enhanced ZIKV replication by dengue-immune sera have raised concerns about the role of previous DENV infection on the risk and severity of microcephaly and other ZIKV complications. Methods. Enzyme-linked immunosorbent assays (ELISAs) based on ZIKV and DENV nonstructural protein 1 (NS1) were established to test acute, convalescent phase, and post-convalescent phase serum/plasma samples from reverse-transcription polymerase chain reaction-confirmed cases including 20 primary ZIKV, 25 ZIKV with previous DENV, 58 secondary DENV, and 16 primary DENV1 infections. Results. ZIKV-NS1 immunoglobulin M (IgM) and immunoglobulin G (IgG) ELISAs combined can detect ZIKV infection with a sensitivity of 95% and specificity of 66.7%. The ZIKV-NS1 IgG cross-reactivity by samples from secondary DENV infection cases ranged from 66.7% to 28.1% (within 1 month to 1-2 years post-illness, respectively). Addition of DENV1-NS1 IgG ELISA can distinguish primary ZIKV infection; the ratio of absorbance of ZIKV-NS1 to DENV1-NS1 IgG ELISA can distinguish ZIKV with previous DENV and secondary DENV infections with a sensitivity of 87.5% and specificity of 81.3%. These findings were supported by analysis of sequential samples. Conclusions. An algorithm for ZIKV serodiagnosis based on 3 simple ELISAs is proposed to distinguish primary ZIKV, ZIKV with previous DENV, and secondary DENV infections; this could be applied to serodiagnosis for ZIKV, serosurveillance, and monitoring ZIKV infection during pregnancy to understand the epidemiology, pathogenesis, and complications of ZIKV in dengue-endemic regions.
Evaluation of Two Serological Assays for Diagnosing Zika Virus Infection
Diagnostics, 2021
Zika virus (ZIKV) emerged and spread rapidly in South American countries during 2015. Efforts to diagnose ZIKV infection using serological tools were challenging in dengue-endemic areas because of antigenic similarities between both viruses. Here, we assessed the performance of an in-house developed IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) and the plaque reduction neutralization test (PRNT) to diagnose ZIKV infection. Acute and convalescent paired serum samples from 51 patients who presented with clinical symptoms suggestive of an arbovirus illness in dengue-endemic areas of Honduras, Venezuela, Colombia and Peru were used in the assessment. Samples were tested for ZIKV, dengue and chikungunya virus using a variety of laboratory techniques. The results for the ZIKV-RNA screening and seroconversion detected by the microneutralization test were used to construct a composite reference standard. The overall sensitivity and specificity for the MAC-ELISA were 93....
The American Journal of Tropical Medicine and Hygiene
Serological cross-reactivity has proved to be a challenge to diagnose Zika virus (ZIKV) infections in dengue virus (DENV) endemic countries. Confirmatory testing of ZIKV IgM positive results by plaque reduction neutralization tests (PRNTs) provides clarification in only a minority of cases because most individuals infected with ZIKV were previously exposed to DENV. The goal of this study was to evaluate the performance of a ZIKV/DENV DUO IgM antibody capture ELISA (MAC-ELISA) for discriminating between DENV and ZIKV infections in endemic regions. Our performance evaluation included acute and convalescent specimens from patients with real-time reverse transcription polymerase chain reaction (RT-PCR)-confirmed DENV or ZIKV from the Sentinel Enhanced Dengue Surveillance System in Ponce, Puerto Rico. The ZIKV/DENV DUO MAC-ELISA specificity was 100% for DENV (N = 127) and 98.4% for ZIKV (N = 275) when specimens were tested during the optimal testing window (days post-onset of illness [DP...
Innovative and new approaches to laboratory diagnosis of Zika and dengue: a meeting report
The Journal of infectious diseases, 2017
Epidemics of dengue, Zika, and other arboviral diseases are increasing in frequency and severity. Current efforts to rapidly identify and manage these epidemics are limited by the short diagnostic window in acute infection, the extensive serologic cross-reactivity among flaviviruses, and the lack of point-of-care diagnostics to detect these viral species in primary care settings. The Partnership for Dengue Control organized a workshop to review the current landscape of Flavivirus diagnostics, identified current gaps, and developed strategies to accelerate the adoption of promising novel technologies into national programmes. The rate-limiting step to bringing new diagnostics tools to the market is access to reference materials and well-characterized clinical samples to facilitate performance evaluation. We suggest the creation of an international laboratory response consortium for flaviviruses with a de-centralized biobank of well-charachterized samples to facilitate assay validatio...
Rapid antigen tests for dengue virus serotypes and Zika virus in patient serum
Science translational medicine, 2017
The recent Zika virus (ZIKV) outbreak demonstrates that cost-effective clinical diagnostics are urgently needed to detect and distinguish viral infections to improve patient care. Unlike dengue virus (DENV), ZIKV infections during pregnancy correlate with severe birth defects, including microcephaly and neurological disorders. Because ZIKV and DENV are related flaviviruses, their homologous proteins and nucleic acids can cause cross-reactions and false-positive results in molecular, antigenic, and serologic diagnostics. We report the characterization of monoclonal antibody pairs that have been translated into rapid immunochromatography tests to specifically detect the viral nonstructural 1 (NS1) protein antigen and distinguish the four DENV serotypes (DENV1-4) and ZIKV without cross-reaction. To complement visual test analysis and remove user subjectivity in reading test results, we used image processing and data analysis for data capture and test result quantification. Using a 30-μ...
Pakistan Journal of Medical Sciences
Objective: To detect ZIKV using reverse transcription-polymerase chain reaction (RT-PCR) among clinical samples tested negative for Dengue virus (DENV) by RT-PCR in Punjab, 2016. Methods: A descriptive cross-sectional study was carried out for duration of two months. Total of 506 samples were collected within seven days from onset of illness from all over hospitals of Punjab, Pakistan of which 350 were selected simply randomly to test for presence of ZIKV by using “Trioplex Real-Time RT-PCR Assay (Trioplex)”. Cohen’s kappa coefficient (κ) and 95% confidence interval (CI) were used to assess the degree of concordance between DENV positive results of non-structural protein 1 (NS1) and IgM solid-phase enzyme immunoassay (ELISA). Results: No samples were positive for any ZIKV, DENV or Chikungunya virus (CHIKV) by Trioplex. Among the 350 samples, 26 samples were positive concordant and the degree of concordance between NS1- and IgM-ELISA was 13% and κ coefficient was -0.71 (95% CI -0.79,...
Related topics
Cited by
High-resolution proteomics identifies potential new markers of Zika and dengue infections
Distinguishing between Zika and dengue virus infections is critical for treatment and anticipation of complications. However, existing biomarkers have high error rates. To identify new potential diagnostic signatures, we used next-generation proteomics to profile 122 serum samples from 62 Zika or dengue patients. We quantified >500 proteins and identified 26 proteins that were significantly differentially expressed. These proteins typically function in infection and wound healing, with several also linked to pregnancy and brain. Integrating machine learning approaches, we used 7 proteins to predict ZIKV infection correctly in 72% of the cases, outperforming other tools. The three most predictive proteins were Platelet Factor 4 Variant 1, Fibrinogen Alpha, and Gelsolin. Finally, we showed that temporal changes in protein signatures from the same patient can disambiguate some diagnoses and serve as indicators for past infections. Taken together, we demonstrate that serum proteomics...
SARS-CoV-2 and arbovirus infection: a rapid systematic review
Sao Paulo Medical Journal
Since the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, the coronavirus disease (COVID-19) has spread worldwide. On March 11, 2020, the World Health Organization declared the outbreak of the COVID-19 disease to be a pandemic event and a Public Health Emergency of International Concern. In the meantime, its epidemiological picture has been constantly changing. Up to July 9, 2020, almost 12 million cases had been confirmed, with 545,481 deaths, in 213 countries and territories around the world, as reported to the World Health Organization (WHO). 1,2 Amidst this pandemic, the world still needs to deal with the burden of various other diseases that present overlapping occurrences. Whether these are communicable or non-communicable, much remains to be learned regarding how to manage them all, so as to simultaneously mitigate issues relating to healthcare system saturation. In particular, countries located in tropical and subtropical regions, where arboviral diseases occur abundantly, are still dealing with these old endemics, which for some countries are epidemic diseases. 3-6 Individuals affected by these various diseases may present clinical features that range from subclinical to severe forms, such as encephalitic or hemorrhagic forms, with very significant fatality rates. 5 It has been estimated that more than two billion people live in environments suitable for arbovirus dissemination. 7 Throughout the world, epidemiologists have been warning of temporal coincidence between endemic peaks and outbreaks relating to arboviruses and COVID-19. 8,9 The constantly evolving knowledge of COVID-19 and its characteristics suggests that it and arboviral diseases share similarities with regard to clinical manifestations and laboratory findings. 4,7 So far, dengue fever
BMC Infectious Diseases
Background Dengue, Chikungunya, and Zika are co-endemic in Honduras and are often misdiagnosed due to similar clinical and epidemiological behavior. Most arboviral infections reported in primary care are based on clinical diagnoses without laboratory confirmation. Therefore, the accuracy of physicians’ diagnoses and the factors that affect them needs to be evaluated. Methods A cross-sectional study with convenience sampling at primary healthcare centers was conducted from June to September 2016 and 2017. Clinical data and dried blood spots on Whatman 903 filter paper from 415 arboviral cases and 248 non-arboviral febrile cases were collected. Viral RNA was extracted from a 6-mm DBS paper disc and confirmed by RT-qPCR and sequencing. Results Only 30.84% of diagnostic accuracy was observed in physicians in primary care when comparing arboviral clinical diagnosis with RT-qPCR detection. Moreover, in Dengue and Zika clinical cases, only 8.23% and 27.08% were RT-qPCR confirmed, respectiv...
Trends in ELISA-Based Flavivirus IgG Serosurveys: A Systematic Review
Tropical Medicine and Infectious Disease
Flaviviruses include virus species that are major public health threats worldwide. To determine the immunity landscape of these viruses, seroprevalence studies are often performed using IgG ELISA, which is a simple and rapid alternative to the virus neutralization test. In this review, we aim to describe the trends in flavivirus IgG ELISA-based serosurveys. A systematic literature review using six databases was performed to collate cohort and cross-sectional studies performed on the general population. A total of 204 studies were included in this review. The results show that most studies were performed on dengue virus (DENV), whereas Japanese Encephalitis Virus (JEV) was the least studied. For geographic distribution, serosurveys followed known disease prevalence. Temporally, the number of serosurveys increased after outbreaks and epidemics except for JEV, for which studies were performed to demonstrate the effectiveness of vaccination campaigns. Commercial kits were more commonly ...