scholarly journals Analysis of a Routinely Used Commercial Anti-Chikungunya IgM ELISA Reveals Cross-Reactivities with Dengue in Brazil: A New Challenge for Differential Diagnosis?

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 819
Author(s):  
Monique da Rocha Queiroz Lima ◽  
Raquel Curtinhas de Lima ◽  
Elzinandes Leal de Azeredo ◽  
Flavia Barreto dos Santos

In Brazil, chikungunya emerged in 2014, and by 2016, co-circulated with other arbovirosis, such as dengue and zika. ELISAs (Enzyme-Linked Immunosorbent Assays) are the most widely used approach for arboviruses diagnosis. However, some limitations include antibody cross reactivities when viruses belong to the same genus, and sensitivity variations in distinct epidemiological scenarios. As chikungunya virus (CHIKV) is an alphavirus, no serological cross reactivity with dengue virus (DENV) should be observed. Here, we evaluated a routinely used chikungunya commercial IgM (Immunoglobulin M) ELISA test (Anti-Chikungunya IgM ELISA, Euroimmun) to assess its performance in confirming chikungunya in a dengue endemic area. Samples (n = 340) representative of all four DENV serotypes, healthy individuals and controls were tested. The Anti-CHIKV IgM ELISA test had a sensitivity of 100% and a specificity of 25.3% due to the cross reactivities observed with dengue. In dengue acute cases, the chikungunya test showed an overall cross-reactivity of 31.6%, with a higher cross-reactivity with DENV-4. In dengue IgM positive cases, the assay showed a cross-reactivity of 46.7%. Serological diagnosis may be challenging and, despite the results observed here, more evaluations shall be performed. Because distinct arboviruses co-circulate in Brazil, reliable diagnostic tools are essential for disease surveillance and patient management.

2021 ◽  
Author(s):  
Mirna Burciaga-Flores ◽  
Tanya A. Camacho-Villegas ◽  
Pavel H. Lugo-Fabres ◽  
Abel Gutiérrez-Ortega ◽  
José Esteban Muñoz-Medina ◽  
...  

Abstract Dengue is a viral disease caused by any of the four distinct dengue virus (DENV) serotypes that circulate in many parts of the world. DENV now co-circulates with Zika and Chikungunya viruses (ZIKV and CHIKV) in many regions of the Americas. Having this in mind, plus the fact that DENV clinical diagnosis persists as a difficult task, due to the similarity in symptoms, as well as false-positive results by the cross-reactivity of the IgG and IgM against these three viruses, correct identification of DENV at an early stage of the disease is essential to minimise transmission and prevent potentially devastating sequelae. Here, by phage display, we isolate specific peptides for dengue virus NS1 protein. The specificity of the linear peptides as diagnostic tools for DENV NS1 protein in sera samples was investigated, and the selected peptides showed the ability to recognise DENV, and no cross-reactivity was shown. Moreover, in silico analysis was performed to assess the possible binding modes of these peptides to DENV-NS1, using a molecular docking approach. These peptides are suitable for use in an ELISA assay for dengue virus detection in human serum and the possibility to adapt these peptides to PoC platforms.


2018 ◽  
Vol 9 (4) ◽  
pp. 137
Author(s):  
Geeta B. Shinde ◽  
Sanjay Popere

Aim: To assess the hyperpigmentation after fever and joint pain as a cutaneous marker of chikungunya fever and to assess with serological correlation.Methods: A total of 15 patients comprised of 9 males, 6 females  and  neonate have aged between 14 days to 60 years presented with the pigmentation after the fever subsided were enrolled in the study. The diagnosis of chikungunya was made by detecting virus specific IgM ELISA in the serum.Results: Serological immunoglobulin M enzyme – linked immunosorbent assay (IgM ELISA) test or chikungunya virus was positive in all the patients. Generalized dark coloured pigmentation was the most common finding after the fever subsided. On examination, out of 15 cases, in most of the cases, hyperpigmentation was observed all over the body with the facial involvement. Few cases showed pigmentation over nose, centre of upper lip, on palm, sole, eyelid, dorsum, centrofacial, reticulate pattern on the face and blotchy pigmentation.Conclusion: The presence of pigmentation after fever and joint pain helps to make a retrospective diagnosis of chikungunya fever and this may be considered as a cutaneous marker of chikungunya fever in recent past. 


2020 ◽  
Vol 32 (1) ◽  
Author(s):  
Raai Mahmood ◽  
Khalid Mohamed ◽  
Naba Saeed ◽  
Kadhim Al-Banaa ◽  
Jonathan Zimmerman ◽  
...  

Abstract Background Serum IgM (immunoglobulin M) testing is commonly used to diagnose acute viral infections. However, most clinicians are unaware of the vagaries of IgM testing, including antigenic cross-reactivity between multiple viruses and risk misdiagnosis. Case presentation We report a case of infectious mononucleosis with concomitantly positive IgM for EBV, CMV, VZV, and HSV. A 26-year-old man presented with acute infectious mononucleosis picture. His blood work showed a total bilirubin level of 7.7 mg/dl, ALT 1077 U/L, AST 806 U/L, ALP 325 U/L, and INR 1.0. Monospot was positive; peripheral blood smear showed atypical lymphocytes; however, because EBV infectious mononucleosis does not typically cause elevation of liver enzymes over 1000, other etiologies were explored. Tests for hepatitis A, B, C, HIV, ANA, and ASMA returned negative. IgM for EBV-VCA, CMV, HSV, and VZV all returned positive, and the diagnosis of EBV IM was called into question. Subsequent tests of CMV and HSV PCR for viral load were negative (VZV was not clinically suspected), and later on, EBV-EBNA returned negative and EBV-VCA IgM and IgG returned positive, confirming the diagnosis of acute EBV infection. Conclusion We believe that IgM seropositivity can result from cross-reactivity among several viruses (especially herpes viruses), and although often relied on, a positive IgM should not serve as the sole determinant for diagnosis of acute viral infections.


Animals ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 8
Author(s):  
Marcin Śmiałek ◽  
Michał Gesek ◽  
Daria Dziewulska ◽  
Jowita Samanta Niczyporuk ◽  
Andrzej Koncicki

Transmissible viral proventriculitis (TVP) of chickens is manifested in decreased body weight gains, poor feed conversion and weight diversity. Although TVP etiology has not been defined, a Birnaviridae family member, named chicken proventricular necrosis virus (CPNV) is considered as a potential factor of a disease. This study was undertaken in order to reproduce TVP and to evaluate its etiology. Broiler chickens of the TVP-infected group were inoculated with TVP positive proventriculi homogenate on the 24th day of life. Samples were collected, on infection day and 14 days post-infection (dpi). The 14 dpi anatomo- and histopathological evaluation, revealed that we have succeeded to reproduce TVP. TVP-infected birds gained 30.38% less body weight. In the TVP-infected group a seroconversion against picornaviruses, fowl adenoviruses (FAdV) and infectious bursal disease viruses (IBDV) was recorded with an ELISA test. Using RT-PCR and PCR, CPNV was detected in proventriculi and FAdV in spleens and livers of infected birds, 14 dpi. Our study supports that CPNV is involved in the development of TVP. We did not record the presence of IBDV in TVP or control birds, despite our recording of a seroconversion against IBDV in TVP infected birds. CPNV and IBDV belong to the same family, which allows us to assume serological cross-reactivity between them. The role of FAdV needs further evaluation.


2021 ◽  
Vol 6 (1) ◽  
pp. 12
Author(s):  
Hisham A Imad ◽  
Juthamas Phadungsombat ◽  
Emi E Nakayama ◽  
Sajikapon Kludkleeb ◽  
Wasin Matsee ◽  
...  

Chikungunya virus is an Alphavirus belonging to the family Togaviridae that is transmitted to humans by an infected Aedes mosquito. Patients develop fever, inflammatory arthritis, and rash during the acute stage of infection. Although the illness is self-limiting, atypical and severe cases are not uncommon, and 60% may develop chronic symptoms that persist for months or even for longer durations. Having a distinct periodical epidemiologic outbreak pattern, chikungunya virus reappeared in Thailand in December 2018. Here, we describe a cohort of acute chikungunya patients who had presented to the Bangkok Hospital for Tropical Diseases during October 2019. Infection was detected by a novel antigen kit and subsequently confirmed by real-time RT-PCR using serum collected at presentation to the Fever Clinic. Other possible acute febrile illnesses such as influenza, dengue, and malaria were excluded. We explored the sequence of clinical manifestations at presentation during the acute phase and associated the viral load with the clinical findings. Most of the patients were healthy individuals in their forties. Fever and arthralgia were the predominant clinical manifestations found in this patient cohort, with a small proportion of patients with systemic symptoms. Higher viral loads were associated with arthralgia, and arthralgia with the involvement of the large joints was more common in female patients.


2018 ◽  
Vol 3 (3) ◽  
pp. 95 ◽  
Author(s):  
Stuart Blacksell ◽  
Hugh Kingston ◽  
Ampai Tanganuchitcharnchai ◽  
Meghna Phanichkrivalkosil ◽  
Mosharraf Hossain ◽  
...  

Here we estimated the accuracy of the InBios Scrub Typhus Detect™ immunoglobulin M (IgM) ELISA to determine the optimal optical density (OD) cut-off values for the diagnosis of scrub typhus. Patients with undifferentiated febrile illness from Chittagong, Bangladesh, provided samples for reference testing using (i) qPCR using the Orientia spp. 47-kDa htra gene, (ii) IFA ≥1:3200 on admission, (iii) immunofluorescence assay (IFA) ≥1:3200 on admission or 4-fold rise to ≥3200, and (iv) combination of PCR and IFA positivity. For sero-epidemiological purposes (ELISA vs. IFA ≥1:3200 on admission or 4-fold rise to ≥3200), the OD cut-off for admission samples was ≥1.25, resulting in a sensitivity (Sn) of 91.5 (95% confidence interval (95% CI: 96.8–82.5) and a specificity (Sp) of 92.4 (95% CI: 95.0–89.0), while for convalescent samples the OD cut-off was ≥1.50 with Sn of 66.0 (95% CI: 78.5–51.7) and Sp of 96.0 (95% CI: 98.3–92.3). Comparisons against comparator reference tests (ELISA vs. all tests including PCR) indicated the most appropriate cut-off OD to be within the range of 0.75–1.25. For admission samples, the best Sn/Sp compromise was at 1.25 OD (Sn 91.5%, Sp 92.4%) and for convalescent samples at 0.75 OD (Sn 69.8%, Sp 89.5%). A relatively high (stringent) diagnostic cut-off value provides increased diagnostic accuracy with high sensitivity and specificity in the majority of cases, while lowering the cut-off runs the risk of false positivity. This study underlines the need for regional assessment of new diagnostic tests according to the level of endemicity of the disease given the high levels of residual or cross-reacting antibodies in the general population.


Author(s):  
Pooja Babaso Kamble

Nadi Pariksha is the most effective diagnostic tool known in the medical field. It is cost effective,  accurate,  safe,  and gives quick results. We can conduct Nadi Pariksha on healthy individuals as well as all patients irrespective of stage of the disease also,  and even pregnant woman,  children,  elderly can undergo without any harm or side effects. However,  this technique is not being widely practised at present,  because of lack of training,  practise and knowledge about it in the present day among Ayurveda vaidyas. An iconic factor for identification of a physician,  irrespective of the time,  Region,  Nadi Pariksha can be highlighted as a common factor or even System of Medicine or Civilization of the known world. Thus,  we can perceive that Nadi Pariksha or the pulse examination remains as an effective diagnostic tool since ages. Nadi Pariksha was not been discussed among the Brihatrayees of Ayurveda. Acharya Sharangdhara was the first to document in the doctrines of Ayurveda. Thus Acharya Sharangdhara is considered as ‘The Founder of Nadi Pariksha’in Ayurveda. Nadi Pariksha was titled under the Pancha-Nidana by Acharya Sharangdhara and Ashta Sthana Pariksha by Acharya Yogaratnakara. It was the Foremost among all the other diagnostic tools mentioned by him. Later Acharyas like Acharya Bhava Mishra,  Acharya Yogaratnakara,  Acharya Basavaraja,  Acharya Kanada Maharishi,  and Acharya Ravana have contributed in giving more descriptions and importance. In the recent days Dr. Vasant lad and Dr. Sarvadeva Upadhaya’s research work interest and scope of Nadi Pariksha.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Stef J. Koppelman ◽  
Ashley L. Lardizabal ◽  
Lynn Niemann ◽  
Joe L. Baumert ◽  
Steve L. Taylor

Seafood is a frequent cause of allergic reactions to food globally. The presence of undeclared trace amounts of clam can cause allergic reactions in sensitive individuals. Limited tools are available to test food products for the presence of traces of clam. We report on the development of a sandwich ELISA that can detect and quantify clam protein in food. Antisera against a mix of two commercially important clam species, Atlantic Surf (Spisula solidissima) and ocean quahog (Arctica islandica), were raised in rabbit and sheep. A sandwich ELISA was constructed with this antisera, and sensitivity and specificity were evaluated. Also, model food products spiked with clam protein were analyzed to assess the performance of the ELISA. Comparison was made with a commercially available ELISA for crustacea. The lower limit of quantification of the sandwich ELISA is 2.5 ppm clam protein in food samples, allowing the detection of low amounts of clam that may trigger a reaction in clam allergic patients. The sandwich ELISA was highly specific with cross-reactivity only noted for other molluscan shellfish (mussel and scallop). Clam protein in tomato juice and potato cream soup was detected well with recoveries ranging from 65 to 74% and from 74 to 113%, respectively. However when potato cream soup was retorted, the recover fell to 20%, imposing the risk of underestimating the clam content of a food product. A commercially available crustacean ELISA test was not suitable to detect clam protein. The sandwich ELISA described here is suitable for detection and quantification of clam protein in food products. Care should be taken with food products that have been retorted as the results may be underestimated.


Author(s):  
Yaniv Lustig ◽  
Shlomit Keler ◽  
Rachel Kolodny ◽  
Nir Ben-Tal ◽  
Danit Atias-Varon ◽  
...  

Abstract Background Coronavirus disease 2019 (COVID-19) and dengue fever are difficult to distinguish given shared clinical and laboratory features. Failing to consider COVID-19 due to false-positive dengue serology can have serious implications. We aimed to assess this possible cross-reactivity. Methods We analyzed clinical data and serum samples from 55 individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To assess dengue serology status, we used dengue-specific antibodies by means of lateral-flow rapid test, as well as enzyme-linked immunosorbent assay (ELISA). Additionally, we tested SARS-CoV-2 serology status in patients with dengue and performed in-silico protein structural analysis to identify epitope similarities. Results Using the dengue lateral-flow rapid test we detected 12 positive cases out of the 55 (21.8%) COVID-19 patients versus zero positive cases in a control group of 70 healthy individuals (P = 2.5E−5). This includes 9 cases of positive immunoglobulin M (IgM), 2 cases of positive immunoglobulin G (IgG), and 1 case of positive IgM as well as IgG antibodies. ELISA testing for dengue was positive in 2 additional subjects using envelope protein directed antibodies. Out of 95 samples obtained from patients diagnosed with dengue before September 2019, SARS-CoV-2 serology targeting the S protein was positive/equivocal in 21 (22%) (16 IgA, 5 IgG) versus 4 positives/equivocal in 102 controls (4%) (P = 1.6E−4). Subsequent in-silico analysis revealed possible similarities between SARS-CoV-2 epitopes in the HR2 domain of the spike protein and the dengue envelope protein. Conclusions Our findings support possible cross-reactivity between dengue virus and SARS-CoV-2, which can lead to false-positive dengue serology among COVID-19 patients and vice versa. This can have serious consequences for both patient care and public health.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S302-S303 ◽  
Author(s):  
Samantha Manuel ◽  
Liane Virginia-Cova ◽  
Loubiela Joseph ◽  
Chris Roggeveen ◽  
Radjin Steingrover

Abstract Background Zika virus (ZIKV) was introduced in the Caribbean island of Curacao in January 2016. A commercially available ZIKV IgM and IgG ELISA was evaluated on patients that were PCR-positive for ZIKV. Methods ZIKV infection was established by PCR in urine samples. Samples from PCR-positive patients were selected for validation of a ZIKV NS1 IgG and IgM ELISA. Patients with a follow-up sample ≥ 2 weeks after initial presentation were used to assess the sensitivity of the assay. Samples of 15 historical controls with serological evidence of Dengue, Chikungunya or an unrelated viral infection were included to establish specificity and cross-reactivity. Results Fourteen patients with positive ZIKV PCR diagnosis had repeated serum samples drawn ≥ 2 weeks after the initial sample. The combined results of these repeated IgM and IgG tests resulted in a sensitivity of 92%. One pregnant female showed no presence of IgG or IgM in any of the two samples. Testing of the panel of historical ZIKV-negative controls resulted in a specificity of 100% in both the quantitative and semi-quantitative setting of the ELISA. One patient with known high-titers of antibodies against Chikungunya virus in the respective panel displayed borderline reactive results for ZIKV IgG in both quantitative and semi-quantitative setting of the assay. Conclusion In this PCR-positive ZIKV cohort of patients, the newly available ZIKV NS1 ELISA displayed excellent performance characteristics. Cross-reactivity was indicated for Chikungunya in one case. No cross-reactivity was found for Dengue virus infection. One pregnant female showed no signs of developing anti-ZIKV IgM or IgG in this study. In the light of intrauterine pathogenesis, the lack of development of maternal IgG during ZIKV infection is a concern. Disclosures All authors: No reported disclosures.


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