Tick-borne encephalitis virus (TBEV) – findings on cross reactivity and longevity of TBEV antibodies in animal sera

Klaus, Christine; Ziegler, Ute; Kalthoff, Donata; Hoffmann, Donata; Beer, Martin

doi:10.1186/1746-6148-10-78

Cited by 58 publications

(59 citation statements)

References 30 publications

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“…However, we cannot rule out reinfection during this time period. This correlates with data reported from Klaus et al [49] where the persistence of TBEV antibodies could be demonstrated after 28 months. The present study was restricted to areas of pasturage where sheep and goats breed, which restricted the study area.…”

Section: Discussionsupporting

confidence: 93%

Revealing new tick-borne encephalitis virus foci by screening antibodies in sheep milk

et al. 2020

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Background: Tick distribution in Sweden has increased in recent years, with the prevalence of ticks predicted to spread towards the northern parts of the country, thus increasing the risk of tick-borne zoonoses in new regions. Tickborne encephalitis (TBE) is the most significant viral tick-borne zoonotic disease in Europe. The disease is caused by TBE virus (TBEV) infection which often leads to severe encephalitis and myelitis in humans. TBEV is usually transmitted to humans via tick bites; however, the virus can also be excreted in the milk of goats, sheep and cattle and infection may then occur via consumption of unpasteurised dairy products. Virus prevalence in questing ticks is an unreliable indicator of TBE infection risk as viral RNA is rarely detected even in large sample sizes collected at TBE-endemic areas. Hence, there is a need for robust surveillance techniques to identify emerging TBEV risk areas at early stages.Methods: Milk and colostrum samples were collected from sheep and goats in Örebro County, Sweden. The milk samples were analysed for the presence of TBEV antibodies by ELISA and validated by western blot in which milk samples were used to detect over-expressed TBEV E-protein in crude cell extracts. Neutralising titers were determined by focus reduction neutralisation test (FRNT). The stability of TBEV in milk and colostrum was studied at different temperatures. Results:In this study we have developed a novel strategy to identify new TBEV foci. By monitoring TBEV antibodies in milk, we have identified three previously unknown foci in Örebro County which also overlap with areas of TBE infection reported during 2009-2018. In addition, our data indicates that keeping unpasteurised milk at 4 °C will preserve the infectivity of TBEV for several days. Conclusions:Altogether, we report a non-invasive surveillance technique for revealing risk areas for TBE in Sweden, by detecting TBEV antibodies in sheep milk. This approach is robust and reliable and can accordingly be used to map TBEV "hotspots". TBEV infectivity in refrigerated milk was preserved, emphasising the importance of pasteurisation (i.e. 72 °C for 15 s) prior to consumption.

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Section: Discussionsupporting

confidence: 93%

Revealing new tick-borne encephalitis virus foci by screening antibodies in sheep milk

et al. 2020

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“…Our results confirm that VNT performed in parallel with co‐circulating flaviviruses is more specific than the ELISA tests for WNV antibody detection, supporting the usefulness of this technique as confirmatory method. Furthermore, this study corroborates that cross‐reactions in serological diagnostic methods (including VNT) exist not only between flaviviruses within the same serocomplex (WNV and USUV), but also from different serocomplexes (WNV/USUV and BAGV), as previously observed with other flaviviruses such as Japanese encephalitis virus and tick‐borne encephalitis virus (Klaus, Ziegler, Kalthoff, Hoffmann, & Beer, ; Stiasny, Aberle, & Heinzl, ). These observations may also be relevant when it comes to human diagnosis in areas with co‐circulation of WNV and other flaviviruses such as yellow fever, Japanese encephalitis, zika, dengue or tick‐borne encephalitis viruses in travellers that have visited endemic countries and in people vaccinated against some of these viruses.…”

Section: Discussionsupporting

confidence: 88%

Influence of flavivirus co‐circulation in serological diagnostics and surveillance: A model of study using West Nile, Usutu and Bagaza viruses

Llorente

García-Irazábal

Pérez‐Ramírez

et al. 2019

Transbound Emerg Dis

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This study aims at assessing the serological cross‐reactions existing between three mosquito‐borne flaviviruses with avian reservoirs co‐circulating in Europe: West Nile (WNV), Usutu (USUV) and Bagaza (BAGV). The study is useful for a better interpretation of serological results in diagnostics and surveillance. Serum samples obtained from a natural host, the red‐legged partridge (Alectoris rufa), experimentally infected with WNV, USUV or BAGV were analysed using two commercially available WNV competition ELISAs suitable for serological surveillance, and by the confirmatory virus neutralization test (VNT). The ELISAs examined showed different levels of specificity for WNV, as judged by cross‐reaction observed with the other flaviviruses. By VNT, virus‐specific antibodies were confirmed in 80%, 50% or 0% of sera from WNV‐, BAGV‐, or USUV‐inoculated birds, respectively. The results indicate how the co‐circulation of cross‐reacting flaviviruses may affect the outcomes of WNV serological surveillance when applying currently available serological tools. On the one hand, the choice of the ELISA test for antibody screening should consider the differences found in specificity, since one test is more specific for WNV while the other one is more suitable for detection of a broader range of flavivirus antibodies. On the other hand, besides corroborating that cross‐neutralization occurs between flaviviruses from different serocomplexes (WNV/USUV and BAGV), this study points out that cross‐neutralization between WNV and USUV is not symmetric, and reveals the difficulty to identify USUV infections serologically. This finding indicates that actual USUV infections might be underestimated in the current diagnostic schemes.

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“…Possible previous infection with WNV is difficult to exclude as these horses had an unknown infection date and were not selected based on clinical symptoms. This may have resulted in more horses having lower TBEV antibody responses due to infections months or years in the past or a faster decline of TBEV antibodies post‐infection compared to WNV (Klaus et al., , ).…”

Section: Discussionmentioning

confidence: 99%

A Serological Protein Microarray for Detection of Multiple Cross-Reactive Flavivirus Infections in Horses for Veterinary and Public Health Surveillance

Cleton

Maanen

Bergervoet

et al. 2016

Transbound Emerg Dis

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The genus Flavivirus in the family Flaviviridae includes some of the most important examples of emerging zoonotic arboviruses that are rapidly spreading across the globe. Japanese encephalitis virus (JEV), West Nile virus (WNV), St. Louis encephalitis virus (SLEV) and Usutu virus (USUV) are mosquito-borne members of the JEV serological group. Although most infections in humans are asymptomatic or present with mild flu-like symptoms, clinical manifestations of JEV, WNV, SLEV, USUV and tick-borne encephalitis virus (TBEV) can include severe neurological disease and death. In horses, infection with WNV and JEV can lead to severe neurological disease and death, while USUV, SLEV and TBEV infections are mainly asymptomatic, however, and induce antibody responses. Horses often serve as sentinels to monitor active virus circulation in serological surveillance programmes specifically for WNV, USUV and JEV. Here, we developed and validated a NS1-antigen protein microarray for the serological differential diagnosis of flavivirus infections in horses using sera of experimentally and naturally infected symptomatic as well as asymptomatic horses. Using samples from experimentally infected horses, an IgG and IgM specificity of 100% and a sensitivity of 95% for WNV and 100% for JEV was achieved with a cut-off titre of 1 : 20 based on ROC calculation. In field settings, the microarray identified 93-100% of IgG-positive horses with recent WNV infections and 87% of TBEV IgG-positive horses. WNV IgM sensitivity was 80%. Differentiation between closely related flaviviruses by the NS1-antigen protein microarray is possible, even though we identified some instances of cross-reactivity among antibodies. However, the assay is not able to differentiate between naturally infected horses and animals vaccinated with an inactivated WNV whole-virus vaccine. We showed that the NS1-microarray can potentially be used for diagnosing and distinguishing flavivirus infections in horses and for public health purposes within a surveillance setting. This allows for fast, cheap, syndrome-based laboratory testing for multiple viruses simultaneously for veterinary and public health purposes.

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Tick-borne encephalitis virus (TBEV) – findings on cross reactivity and longevity of TBEV antibodies in animal sera

Cited by 58 publications

References 30 publications

Revealing new tick-borne encephalitis virus foci by screening antibodies in sheep milk

Revealing new tick-borne encephalitis virus foci by screening antibodies in sheep milk

Influence of flavivirus co‐circulation in serological diagnostics and surveillance: A model of study using West Nile, Usutu and Bagaza viruses

A Serological Protein Microarray for Detection of Multiple Cross-Reactive Flavivirus Infections in Horses for Veterinary and Public Health Surveillance

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