Dengue: A review of laboratory diagnostics in the vaccine age.

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.

Triple Trouble.

We present a case of a 24-year-old female recently diagnosed with acute leukemia who came with complaints of fever for 14 days, progressive lower limb weakness, and multiple episodes of vomiting in the last 1 day. In nerve conduction studies, a diagnosis of Guillain-Barré syndrome (GBS) was established. Fever with thrombocytopenia workup revealed a positive dengue nonstructural protein 1 (NS1) and immunoglobulin M (IgM) report. Immunophenotyping confirmed pre-B acute lymphoblastic leukemia (ALL). As leukemia is an immunocompromised state, the peripheral nervous system vulnerability is increased, or infection could precipitate an immune neuropathy. About 10% of adult ALL presents with central nervous system (CNS) leukemias; a higher incidence is seen in mature B ALL. There is some evidence to suggest immunosuppression secondary to intensive chemotherapy (vincristine-induced dying back neuropathy), which was not started in our case. This rare combination in a short period of time with a worsening situation paralyzed the line of management. Few reports described GBS in patients with dengue in adults. The association of Guillan-Barre syndrome and ALL could be coincidental or has a pathophysiological basis and is under basic investigation.

DengueSeq: a pan-serotype whole genome amplicon sequencing protocol for dengue virus.

BACKGROUND: The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes. RESULTS: We developed primer schemes for the four dengue virus serotypes, which can be combined into a pan-serotype approach. We validated both approaches using genetically diverse virus stocks and clinical specimens that contained a range of virus copies. High genome coverage (>95%) was achieved for all genotypes, except DENV2 (genotype VI) and DENV 4 (genotype IV) sylvatics, with similar performance of the serotype-specific and pan-serotype approaches. The limit of detection to reach 70% coverage was 10-100 RNA copies/µL for all four serotypes, which is similar to other commonly used primer schemes. DengueSeq facilitates the sequencing of samples without known serotypes, allows the detection of multiple serotypes in the same sample, and can be used with a variety of library prep kits and sequencing instruments. CONCLUSIONS: DengueSeq was systematically evaluated with virus stocks and clinical specimens spanning the genetic diversity within each of the four dengue virus serotypes. The primer schemes can be plugged into existing amplicon sequencing workflows to facilitate the global need for expanded dengue virus genomic surveillance.

Dengue en paciente de 32 días de vida. Reporte de un caso poco habitual / Dengue fever in a 32-day-old patient. A rare case report

El dengue es una enfermedad viral transmitida por la picadura del mosquito Aedes aegypti. El comportamiento del dengue en Argentina es epidémico; la mayoría de los casos se observan en los meses de mayor temperatura. Hasta la semana epidemiológica (SE) 20/2023, se registraron en Argentina 106 672 casos; se vieron afectadas 18 de las 24 provincias que conforman el país. Dentro de los principales grupos de riesgo, se incluyen los menores de 2 años. Reconocer los signos, síntomas e identificar los factores de riesgo es fundamental para el manejo de casos con mayor riesgo de gravedad. Presentamos el caso de una paciente de 32 días de vida que se internó por síndrome febril sin foco, con diagnósticos diferenciales de meningitis viral y sepsis, evolucionó con leucocitosis, plaquetopenia, hipoalbuminemia, asociado a exantema y edemas. Se llegó al diagnóstico de dengue por la clínica, epidemiologia e IgM positiva.

Dengue fever is a viral disease transmitted by the Aedes aegypti mosquitoes. In Argentina, dengue fever is an epidemic disease; most cases are reported during the hot months.Until epidemiological week (EW) 20/2023, 106 672 cases were reported across 18 of the 24 provinces of Argentina. Children younger than 2 years are among the main groups at risk. Recognizing signs and symptoms and identifying risk factors is fundamental for the management of cases at a higher risk of severity. Here we describe the case of a 32-day-old female patient who was hospitalized due to febrile syndrome without a source, who had a differential diagnosis of viral meningitis and sepsis and progressed to leukocytosis, thrombocytopenia, hypoalbuminemia in association with rash and edema. The diagnosis of dengue fever was established based on clinical, epidemiological, and positive IgM data.

Molecular identification and phylogenetic analysis of chikungunya virus among dengue-negative patients in Kolkata, India.

Dengue and chikungunya are co-circulating vector-borne diseases that share a significant number of clinical symptoms. To identify variables to aid physicians in making rapid and effective diagnostic decisions, we performed molecular diagnosis of the chikungunya virus and examined the clinical manifestations of chikungunya cases to identify the prevalence among dengue-negative individuals in Kolkata. Dengue suspected patients' samples were collected during January 2020-December 2021 and Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) methods have been performed to confirm the prevalence of chikungunya infection among dengue-negative patients. By performing phylogenetic analysis, comparing clinical classifications, identifying disease aetiology using clinical and laboratory factors, and evaluating the time course of several clinical variables, we have evaluated the clinical manifestations linked to dengue and chikungunya virus infections. Chikungunya infection was found in 15.1% and 6.3% of the 635 dengue-negative patients, as determined by ELISA and RT-PCR, respectively. Arthritis and myalgia were more common in chikungunya-infected patients at the time of hospital admission while conjunctivitis, photosensitivity, arthralgia, Anorexia, fatigue, retro-orbital pain, vomiting, dermatitis, or swollen glands were significantly presented as an overlapping symptom. Although dengue and chikungunya infections have significant clinical overlap, basic clinical and laboratory criteria can predict these diseases at presentation for proper management. Effective management enables doctors to treat and care for patients properly and contributes to the development of control measures for these infections in a medical setting.

Kirigami tripod-based electrode for the development of highly stretchable dengue aptasensor.

Kirigami is one of the interesting paper art forms and the modified sub-class of origami. Kirigami paper art is widely employed in a variety of applications, and it is currently being used in biosensors because of its outstanding advantages. This is the first study on the use of a Kirigami-based aptasensor for DENV (Dengue virus)-antigen detection. In this study, the kirigami approach has been utilized to develop a stretchable, movable, and flexible sensor. The constructed stretchable-kirigami electrode helps in adjusting the connection of electrodes without disturbing the electrochemical cell zone during the experiment. To increase the sensitivity of this biosensor we have synthesized Ag-NPs (Silver nanoparticles) via chemical methods and characterized their results with the help of TEM & UV-Vis Spectroscopy. Different electrochemical approaches were used to validate the sensor response i.e., CV (Cyclic voltammetry) and LSV (Linear sweep voltammetry), which exhibited great detection capability towards dengue virus with the range of 0.1 µg/ml to 1000 µg/ml along with a detection limit of 0.1 µg/ml and showing no reactivity to the chikungunya virus antigen, making it more specific to the DENV antigen. Serum (healthy-human) was also successfully applied to validate the results of the constructed aptasensor. Integration of the Kirigami approach form with the electrochemical aptasensor that utilizes a 3-E setup (three-electrode setup) which is referred to as a tripod and collectively called Kirigami-tripod-based aptasensor. Thus, the developed integrated platform improves the sensors capabilities in terms of cost efficiency, high stretchability, and sensitivity.

Ophthalmic manifestations as the first presenting feature in dengue fever: a 10-year study.

Purpose: To report patients who first presented with various ocular manifestations and eventually ascertained to have underlying dengue. Methods: A prospective study was conducted at multiple tertiary eye-care centers in India from 2012 to 2022. Cases reporting initially with ocular features along with fever/past history of fever over the last two weeks or with clinical features of dengue were selected. After an ophthalmological examination, patients underwent complete serological and biochemical analysis and those with reduced platelet counts were evaluated for dengue. Results: Out of 564 cases, 15 patients were verified to be afflicted with dengue eventually. A rising trend of cases was seen every year and out of 15 cases, eight cases were reported during the Covid-19 pandemic (from 2020 to 2022), but were COVID-negative. 9 cases presented with acute redness followed by diminished vision. Seven cases presented a history of fever over the last few days and one had traveled from dengue endemic area. The various ocular presentations included subconjunctival hemorrhage, viral keratitis, anterior uveitis, sixth-nerve palsy, and vitreous hemorrhage. On serological examination, all 15 patients were detected to have low platelets. All cases responded well with supportive treatment and the ocular features subsided in all within a couple of weeks with good visual recovery. Conclusion: In a tropical nation, such as India, with endemic dengue zones and increasing figures of dengue lately, ophthalmologists must include dengue fever among the differential diagnoses in various ocular presentations like subconjunctival hemorrhage, viral keratitis, anterior uveitis, sixth nerve palsy, and vitreous hemorrhage. Abbreviations: DHF = dengue hemorrhagic fever, PCR = polymerase chain reaction, RT-PCR = real-time automated reverse transcriptase (RT-PCR), SD = standard deviation, MAC-ELIS = IgM antibodies capture enzyme-linked immunosorbent assay, RE = right eye, LE = left eye, CECT = Contrast-enhanced computed tomography.

Detection of dengue in German tourists returning from Ibiza, Spain, related to an autochthonous outbreak, August to October 2022.

In February 2023, German public health authorities reported two dengue cases (one confirmed, one probable) and four possible cases who travelled to Ibiza, Spain, in late summer/autumn 2022; the infection was probably acquired through mosquito bites. Case 1 visited Ibiza over 1 week in late August with two familial companions; all three developed symptoms the day after returning home. Only Case 1 was tested; dengue virus (DENV) infection was confirmed by presence of NS1 antigen and IgM antibodies. Case 2 travelled to Ibiza with two familial companions for 1 week in early October, and stayed in the same town as Case 1. Case 2 showed symptoms on the day of return, and the familial companions 1 day before and 3 days after return; Case 2 tested positive for DENV IgM. The most probable source case had symptom onset in mid-August, and travelled to a dengue-endemic country prior to a stay in the same municipality of Ibiza for 20 days, until the end of August. Dengue diagnosis was probable based on positive DENV IgM. Aedes albopictus, a competent vector for dengue, has been present in Ibiza since 2014. This is the first report of a local dengue transmission event on Ibiza.

Clinical and laboratory profile of Expanded Dengue Syndrome: experience of 2019 outbreak from Dhaka, Bangladesh.

BACKGROUND OBJECTIVES: Bangladesh is afflicted with periodic dengue outbreak every few years and one of the worst upsurges was recorded in 2019 during which there was an increasing trend of dengue with unusual symptoms which were not so common before. This study aims to describe the experience of three tertiary care centres of Dhaka regarding the clinical and laboratory, hospital outcome and management profile of the Expanded Dengue Syndrome (EDS) cases admitted from the 2019 outbreak. METHODS: The current work was a cross-sectional observational study which took place from August 1 to December 31 2019 at three major tertiary care centres in Dhaka, Bangladesh. Out of total 2017 screened dengue cases, 49 met the inclusion criteria and 39 were enrolled after taking informed written consent. Data was analysed using Microsoft Excel and Graph pad prism 9.3.1. A probability value of p<0.05 was considered statistically significant. RESULTS: Out of the 39 cases, majority were male (79.49%) with median (±IQR) age of 33(±9) years. Hypertension (4; 10.26%) was the most commonly associated co-morbidity. Among the systemic manifestations, most prevalent was hepatitis (38.49%) followed by encephalopathy (12.82%). Majority of the patients were suffering from primary infection (85%). Case fatality rate was 15.38%. Hepatitis and meningoencephalitis were the predominant cause of death. This study records the only known case report of Acute respiratory dress syndrome (ARDS) complicating dengue from Bangladesh. None of the patients from our cohort were managed by steroids. Only two (5.13%) out of 39 cases received antibiotics. INTERPRETATION CONCLUSION: In the year 2019, an unusual rise in EDS cases with about 15.4% fatalities were observed in this study. Hepatitis was the most common presentation and cause of death. Here, we report the first ARDS case encountered in Bangladesh. Despite the multifaceted presentation of EDS, indiscriminate use of antibiotics and steroid was minimal. Early recognition of multifarious features of EDS is important for choosing the targeted treatment option which can avert many deaths. The results of this study underline the necessity for more in-depth research into the risk factors that are contributing to mortality in EDS cases.

Reporte de caso de dengue clásico a predominio de sintomatología dermatológica en el marco de la epidemia en la provincia de Misiones 2023-2024 / Case of classic dengue with predominance of dermatologic symptoms in the 2023-2024 epidemic in the province of Misiones

Se presenta un caso femenino de dengue clásico (DC) en el marco de la epidemia 2023-2024 en la provincia de Misiones, con predominio de síntomas dermatológicos de exantemas máculo papulosos, habonosos y eritrodérmicos sobre los síntomas sindrómicos cardinales. Las lesiones presentan componente humoral y de extravasación, sin diátesis ni componentes purpúricos apreciables, presentando una rápida y efectiva evolución al eritema y la normalización con tratamiento antihistamínico y corticoide parenteral. De la misma manera se evalúan alteraciones analíticas hematológicas y hepáticas de gran magnitud, con escasa repercusión clínica, que se mensuran en función del riesgo relativo al dengue hemorrágico (DH) y el pronóstico de la paciente. (AU)

A female case of classic dengue (DC) is presented in the context of the 2023-2024 epidemic in the province of Misiones, with a predominance of dermatologic symptoms of maculopapular, hives, and erythrodermic rashes overlapping the cardinal syndromic symptoms. The lesions have a humoral and extravasation component, without any significant diathesis or purpuric components, showing rapid and effective progression to erythema and normalization with antihistamine and parenteral corticosteroid treatment. Similarly, hematologic and hepatic analytical alterations of great magnitude are evaluated, with little clinical impact, measured in terms of relative risk for hemorrhagic dengue (HD) and the prognosis of the patient. (AU)

The Potential of Immature Platelet Fraction as a Prognostic Marker in Dengue Infection.

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Smartphone-Integrated Wireless Portable Potentiostat to Develop 5th-Generation Dengue Pocket Aptasensor toward Portronicx-Approach.

Smartphones' widespread availability and worldwide connection are advancing the idea of mobile-based healthcare and promise to transform the business of biosensors. Biosensors based on smartphones have been investigated in several ways, including employing a smartphone in place of a detector or as an instrumental interface. The current work demonstrates the first successful detection of dengue virus using a smartphone-based pocket sensor combined with a wireless potentiostat. The platform developed comprises a smartphone, a wireless portable potentiostat, an Android app, and a three-electrode setup. The combination of portable diagnostic with electronic application is referred to as "Portronicx", and this is the first time that the term "Portronicx" has been used in a dengue sensor, so the current study has the potential to be commercialized in the market with the tag line "Portronicx-commercialization" in the future. Miniaturization improves alternative setup options in terms of instrument size, affordability, mobility, touch-mobile display, and design versatility. The current work proved the excellent combination of a wireless potentiostat with an aptasensor to detect dengue antigen within 20 s with good LOD (0.1 µg/mL) and easy to carry in their pockets. The created platform also performed effectively in human serum. This study replaced all of the instruments with a lightweight touch smartphone, paving the way for the production of fifth-generation electrochemical aptasensors, with potential implications for healthcare applications on the verge of commercialization.

Dengue encephalopathy in an adult due to dengue virus type 1 infection.

BACKGROUND: Dengue is an important public health problem, which caused by the dengue virus (DENV), a single-stranded RNA virus consisted of four serotypes. Central nervus system (CNS) impairment in dengue usually results from DENV-2 or DENV-3 infection, which lead to life-threatening outcomes. Furthermore, neurological complications due to DENV-1 was rare especially in adult patients. CASE PRESENTATION: A 44-year-old man without comorbidities had lethargy after hyperpyrexia and a positive DENV NS1 antigen was detected for confirming the diagnosis of dengue on day 8 of onset. Then logagnosia, decreased muscle strength, delirium and irritability were occurred even radiographic examination were normal. He was treated with low-dose hormone, sedatives and gamma goblin with a short duration of 6 days. The cerebrospinal fluid (CSF) tests were persistent normal. However, presence of DENV-1 RNA was confirmed both in CSF and serum. Furthermore, the complete sequence of the DENV isolated from the patient's serum was performed (GenBank No.: MW261838). The cytokines as IL-6, IL-10 and sVCAM-1 were increased in critical phase of disease. Finally, the patient was discharged on day 24 of onset without any neurological sequelae. CONCLUSION: Encephalopathy caused by a direct CNS invasion due to DENV-1 during viremia was described in an adult patient. Treatment with low-dose hormone and gamma goblin was helpful for admission.

Low Rate of Asymptomatic Dengue Infection Detected in Coastal Kenya Using Pooled Polymerase Chain Reaction Testing.

Asymptomatic dengue virus (DENV) infections have important public health implications but are challenging to identify. We performed a cross-sectional study of reverse transcription quantitative polymerase chain reaction on pooled sera of asymptomatic individuals from the south coast of Kenya at two time periods to identify cases of asymptomatic viremia. Among 2,460 samples tested in pools of 9 or 10, we found only one positive case (0.04% incidence). Although pooling of samples has the potential to be a cost-effective and time-efficient method for asymptomatic DENV detection, mass cross-sectional pooled testing may not provide accurate data on rates of asymptomatic infection, likely owing to a decrease in the sensitivity with pooling of samples, a short period of viremia, or testing in the absence of an outbreak.

Point-of-care dengue detection: polydopamine-modified electrode for rapid NS1 protein testing for clinical samples.

Early diagnosis of dengue infection by detecting the dengue virus non-structural protein 1 (DENV-NS1) is important to the patients to initiate speedy treatment. Enzyme-linked immunosorbent assay (ELISA)-based NS1 detection and RT-PCR are time-consuming and too complex to be employed in remote areas of dengue-endemic countries. Meanwhile, those of NS1 rapid test by lateral flow assay suffer from low detection limit. Electrochemical-based biosensors using screen-printed gold electrodes (SPGEs) have become a reliable detection method to convey both ELISA's high sensitivity and rapid test portability. In this research, we developed an electrochemical biosensor for DENV-NS1 detection by employing polydopamine (PDA)-modified SPGE. The electrodeposition of PDA on the surface of SPGE serves as a bioconjugation avenue for anti-NS1 antibody through a simple and low-cost immobilization procedure. The biosensor performance was evaluated to detect DENV-NS1 protein in PBS and human serum through a differential pulse voltammetric (DPV) technique. The developed sensing platform displayed a low limit of detection (LOD) of 1.63 pg mL-1 and a wide linear range of 10 pg mL-1 to 1 ng mL-1 (R2 ∼ 0.969). The sensing platform also detected DEV-NS1 from four different serotypes in the clinical samples collected from dengue patients in India and Indonesia, with acceptable sensitivity, specificity, and accuracy values of 90.00%, 80.95%, and 87.65%, respectively. This result showcased the facile and versatile method of PDA coating onto the surface of screen-printed gold electrodes for a miniaturized point-of-care (PoC) detection device.

Cryptic circulation of chikungunya virus in São Jose do Rio Preto, Brazil, 2015-2019.

BACKGROUND: Chikungunya virus (CHIKV) has spread across Brazil with varying incidence rates depending on the affected areas. Due to cocirculation of arboviruses and overlapping disease symptoms, CHIKV infection may be underdiagnosed. To understand the lack of CHIKV epidemics in São José do Rio Preto (SJdRP), São Paulo (SP), Brazil, we evaluated viral circulation by investigating anti-CHIKV IgG seroconversion in a prospective study of asymptomatic individuals and detecting anti-CHIKV IgM in individuals suspected of dengue infection, as well as CHIKV presence in Aedes mosquitoes. The opportunity to assess two different groups (symptomatic and asymptomatic) exposed at the same geographic region aimed to broaden the possibility of identifying the viral circulation, which had been previously considered absent. METHODOLOGY/PRINCIPAL FINDINGS: Based on a prospective population study model and demographic characteristics (sex and age), we analyzed the anti-CHIKV IgG seroconversion rate in 341 subjects by ELISA over four years. The seroprevalence increased from 0.35% in the first year to 2.3% after 3 years of follow-up. Additionally, we investigated 497 samples from a blood panel collected from dengue-suspected individuals during the 2019 dengue outbreak in SJdRP. In total, 4.4% were positive for anti-CHIKV IgM, and 8.6% were positive for IgG. To exclude alphavirus cross-reactivity, we evaluated the presence of anti-Mayaro virus (MAYV) IgG by ELISA, and the positivity rate was 0.3% in the population study and 0.8% in the blood panel samples. In CHIKV and MAYV plaque reduction neutralization tests (PRNTs), the positivity rate for CHIKV-neutralizing antibodies in these ELISA-positive samples was 46.7%, while no MAYV-neutralizing antibodies were detected. Genomic sequencing and phylogenetic analysis revealed CHIKV genotype ECSA in São José do Rio Preto, SP. Finally, mosquitoes collected to complement human surveillance revealed CHIKV positivity of 2.76% of A. aegypti and 9.09% of A. albopictus (although it was far less abundant than A. aegypti) by RT-qPCR. CONCLUSIONS/SIGNIFICANCE: Our data suggest cryptic CHIKV circulation in SJdRP detected by continual active surveillance. These low levels, but increasing, of viral circulation highlight the possibility of CHIKV outbreaks, as there is a large naïve population. Improved knowledge of the epidemiological situation might aid in outbreaks prevention.

Clinical Manifestations of Dengue in Children and Adults in a Hyperendemic Region of Colombia.

Dengue is the most common arboviral disease in the world. Traditionally, it has affected more adults, but the incidence in children has increased in recent years. Colombia is no stranger to this change; therefore, we aimed to find the differences in signs, symptoms, and clinical, hematological, and hemogram characteristics between children under 12 years old and individuals aged 12 years and older in an endemic region of Colombia in 2020-2022. The analyses were conducted with baseline data, corresponding to a cross-sectional design. Multiple correspondence analysis was used for general, dermatological, and clinical symptom profiles. Discriminant analysis was used for laboratory profiles. Multiple correspondence analysis was applied to nominal categorical data, employing Euclidean distances to analyze age groups. Discriminant analysis was applied to a training sample and validated on a test sample. The overall agreement of the model's discrimination, sensitivity, specificity, and fit indicators was calculated. The results indicated that individuals under 12 years exhibited distinct dermatological and clinical features, including rash, pruritus, hypotension, lymphocyte count, and platelet count, compared with those aged 12 years and older. In contrast, those 12 years and older were profiled for general and clinical symptoms such as pain (back pain, retro-orbital pain, headache), dizziness, chills, hematuria, tachypnea, and elevated/high hematocrit, hemoglobin, and basophil values. These findings are crucial to understanding the high incidence in children; they also facilitate rapid understanding of the disease in clinical care settings and differentiate it from other febrile outbreaks. This will affect disease control, particularly in severe cases, and reduce mortality.

Systematic review and meta-analysis: assessing the accuracy of rapid immunochromatographic tests in dengue diagnosis.

The objective of this systematic review is to analyze the diagnostic accuracy of rapid dengue diagnostic tests. The search was conducted in the following databases: LILACS, Medline (Pubmed), CRD, The Cochrane Library, Trip Medical Database and Google Scholar. ELISA and PCR assays were adopted as reference methods. Thirty-four articles were included in this systematic review. Receiver operating characteristic (ROC) and Forest Plot were performed to evaluate sensitivity and specificity for each parameter analyzed (NS1, IgM and IgG). The results revealed that the combined analysis of the IgM antibody with the NS1 antigen resulted in greater sensitivity than the isolated analysis of IgM. The three analytes together showed the best performance, with a combined sensitivity of 90 % (95 % CI: 89-92 %) using ELISA as a comparator. Thus, the present review provides relevant knowledge for decision-making between the available rapid diagnostic tests.