Red deer reveal spatial risks of Crimean-Congo haemorrhagic fever virus infection

In press.Crimean-Congo haemorrhagic fever virus (CCHFV) continues to cause new human cases in Iberia while its spatial distribution and ecological determinants remain unknown. The virus remains active in a silent tick-animal cycle to which animals contribute maintaining the tick populations and the virus itself. Wild ungulates, in particular red deer, are essential hosts for Hyalomma ticks in Iberia, which are the principal competent vector of CCHFV. Red deer could be an excellent model to understand the ecological determinants of CCHFV as well as to predict infection risks for humans because it is large, gregarious, abundant and the principal host for Hyalomma lusitanicum. We designed a cross-sectional study, analysed the presence of CCHFV antibodies in 1444 deer from 82 populations, and statistically modelled exposure risk with host and environmental predictors. The best-fitted statistical model was projected for peninsular Spain to map infection risks. Fifty out of 82 deer populations were seropositive, with individual population prevalence as high as 88%. The highest prevalence of exposure to CCHFV occurred in the southwest of the Iberian Peninsula. Climate and ungulate abundance were the most influential predictors of the risk of exposure to the virus. The highest risk regions were those where H. lusitanicum is most abundant. Eight of the nine primary human cases occurred in or bordering these regions, demonstrating that the model predicts human infection risk accurately. A recent human case of CCHF occurred in northwestern Spain, a region that the model predicted as low risk, pointing out that it needs improvement to capture all determinants of the CCHFV infection risk. In this study, we have been able to identify the main ecological determinants of CCHFV, and we have also managed to create an accurate model to assess the risk of CCHFV infection.This study has been funded by the Spanish Ministry for the Science and Innovation (MCI) through projects CGL2017-89866-R & E-RTA2015-0002-C02-02, and by the Regional Government of Castilla-La Mancha and the European Social Fund (ESF) through project SBPLY/19/180501/000321. RC-M, LC-M, SJ-R and JM-G would like to thank the MCI, ESF and the University of Castilla-La Mancha for their support through contracts PRE2018-083801, PEJ2018-003155-A, 2018/12504 and BES-2015-072206, respectively. BC was supported by FCT-Fundação para a Ciência e Tecnologia (2020.04872.BD). DG-B would like to thank MCI and Instituto de Salud Carlos III (CD19CIII/00011) for funding him.Peer reviewe

Circulation of Crimean-Congo Hemorrhagic Fever Virus in the Former Yugoslav Republic of Macedonia Revealed by Screening of Cattle Sera Using a Novel Enzyme-linked Immunosorbent Assay

<div><p>Background</p><p>There are only few assays available for the detection of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)-specific antibodies in animals, and data about diagnostic sensitivity and specificity are incompletely documented for most of these tests. This is unfortunate since CCHFV antibodies in animals can be used as indicator for virus circulation in a geographic area and therewith potential risk of human exposure. This paper therefore reports on a novel ELISA for the detection of CCHFV-specific antibodies in cattle and on its application for testing ruminant sera from the Former Yugoslav Republic of Macedonia.</p><p>Principal Findings</p><p>A highly sensitive and specific ELISA was developed to detect CCHFV-specific IgG antibodies in cattle. The assay was validated by using 503 negative serum samples from a country where CCHFV has never been detected until now, and by using 54 positive serum samples. The positive sera were verified by using two commercially available assays (for testing human serum) which we have adapted for use in animals. The sensitivity of the novel ELISA was 98% and its specificity 99%. The presence of Hyalomma ticks was demonstrated in the Former Yugoslav Republic of Macedonia and depending on the region antibody prevalence rates up to 80% were detected in the cattle population.</p><p>Conclusion</p><p>This article describes a fully validated, highly sensitive and specific ELISA for the detection of CCHFV-specific IgG antibodies in cattle. Using this assay, CCHFV-specific antibodies were detected for the first time in cattle in the Former Yugoslav Republic of Macedonia, giving evidence for an active circulation of this virus in the country. Supporting this conclusion, the occurrence of the main vector of CCHFV was demonstrated in the present work for the first time in Former Yugoslav Republic of Macedonia.</p></div

Results of the new ELISA for serum samples from cattle.

<p>Comparative analysis of the results of the new ELISA and the combined result of the adapted commercial reference assays (IFA and ELISA) for serum samples from cattle. The negative serum samples from Germany have been defined as negative and have not been tested in one of the reference assays.</p><p>Results of the new ELISA for serum samples from cattle.</p

Seroprevalence in different regions of Former Yugoslav Republic of Macedonia.

<p>The map illustrates the prevalence of Crimean-Congo Hemorrhagic Fever Virus specific antibodies in cattle in four regions of the Former Yugoslav Republic of Macedonia. The ticks show in which regions Hyalomma ticks have been identified and the crossed out tick shows where no Hyalomma ticks have been identified. (Figure modified from Wikimedia Commons [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003519#pntd.0003519.ref018" target="_blank">18</a>]).</p

Results of the adapted commercial ELISA for serum samples from cattle.

<p>Comparative analysis of the results of the adapted commercial ELISA and the adapted commercial IFA for serum samples from cattle. The negative serum samples from Germany have been defined as negative and have not been tested in the IFA.</p><p>Results of the adapted commercial ELISA for serum samples from cattle.</p

Results of the tick collection.

<p>The table shows the collected number of ticks of the genus <i>Hyalomma</i> and <i>Rhipicephalus</i> for the different regions. The overall number of ticks is shown as well as the number of males and females.</p><p>Results of the tick collection.</p

Results of the different assays used in the seroepidemiological study.

<p>The numbers of positive, negative and equivocal results of each test are shown for every region. The final result is a combination of the results of the individual assays.</p><p>Results of the different assays used in the seroepidemiological study.</p

Gamow-Teller beta decay of the very neutron-deficient N=50 nuclide &quot;9&quot;8Cd

Available from TIB Hannover: RO 801(91-31) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman