West Nile and Usutu virus seroprevalence in Hungary: A nationwide serosurvey among blood donors in 2019.

In Hungary, West Nile virus (WNV) has been responsible for 459 laboratory confirmed human cases between 2004 and 2019, while the first human Usutu virus (USUV) infection was confirmed only in 2018. A comprehensive serosurvey was conducted among blood donors to assess the WNV and USUV seroprevalence in 2019, one year after the largest European WNV epidemic. Altogether, 3005 plasma samples were collected and screened for WNV and USUV specific Immunoglobulin G (IgG) antibodies by Enzyme-Linked Immunosorbent Assay (ELISA). All reactive samples were further tested for tick-borne encephalitis virus IgG antibodies by ELISA. Indirect immunofluorescence test and microneutralization assay were used as confirmatory methods. Overall, the WNV seroprevalence was 4.32%, and in five blood donors USUV seropositivity was confirmed. The highest seroprevalence was measured in Central, Eastern and Southern Hungary, while the Western part of the country proved to be less affected. There was a statistically strong association between the WNV seroprevalence of 2019 and the cumulative incidence in the period of 2004 and 2019 calculated for every NUTS 3 region. The last WNV serological screening was performed in 2016 and the prevalence of anti-WNV IgG proved to be 2.19%. One year after the 2018 WNV outbreak, a significant increase in seroprevalence was observed in the Hungarian population and evidence for USUV seropositivity was also obtained. The spatial pattern of seroprevalence can support the identification of high-risk areas raising awareness of the need for increased surveillance, such as screening vector, equine, and avian populations. The communication with general practitioners and other professionals in primary health care services can support the early identification of acute human cases. Education and awareness-raising on the importance of protection against mosquito vectors amongst residents are also important parts of preventive measures.

New geographical area on the map of Crimean-Congo hemorrhagic fever virus: First serological evidence in the Hungarian population.

Crimean-Congo hemorrhagic fever (CCHF) is an emerging tick-borne disease that is endemic in Africa, Asia, the Middle East, and the Balkan region of Europe; the disease is spreading northwards following widespread distribution of the main vector, Hyalomma marginatum, which was first found in Hungary in 2011. The aim of this pilot sero-surveillance study was to assess CCHF seroprevalence in Hungary. A total of 2700 serum samples obtained from healthy volunteer blood donors were screened using an in-house immunofluorescence assay and a commercially available ELISA kit. We found ten (0.37 %) seropositive donors. The western and central regions proved to be the most affected areas, with a prevalence of 2.97 %. Higher positivity was found among male donors (0.55 %) and younger donors (18-34 years; 0.78 %). Based on these results, a more extended surveillance focusing on specific at-risk populations and animals is advised. The results should also raise the awareness of clinicians and other high-risk populations, such as foresters and hunters, about the emerging threat of CCHF in Hungary.

West Nile Virus Seroprevalence Among Blood Donors in Hungary.

Background and Objectives: West Nile virus (WNV) is one of the most important viral zoonotic infections in Hungary; however, no transfusion-transmitted WNV infections have been confirmed so far. In 2016, the number of clinical cases of WNV reported was 44, but the seasonal WNV screening of whole-blood donors has not yet been implemented. Our aims were to assess the WNV RNA reactivity and the prevalence of WNV-specific antibodies in the samples of blood donors collected in 2016. Materials and Methods: WNV RNA with Cobas TaqScreen and anti-WNV antibody determination from plasma samples of 2112 donors was performed. Cross-reactivity to tick-borne encephalitis virus was excluded. WNV neutralization test was used for the confirmation of anti-WNV IgG reactive results, and the presence of anti-WNV IgM antibodies was also determined. Results: None of the samples showed WNV RNA reactivity. The total weighted anti-WNV IgG prevalence was 2.34% (95% confidence interval 1.65-3.03), and in addition, three donors were found to be IgM positive. There was a comparable tendency between the data of WNV seroprevalence and cumulative incidence in six out of seven statistical regions in Hungary. Conclusion: Our results show a comparable data with publications that estimated the WNV seroprevalence in some other European endemic areas. As protective measures, both the 30-day deferral of blood donors who spent at least 24 h in WNV-exposed areas and the exclusion of affected Hungarian territories from blood donation are enforced by the Hungarian National Blood Transfusion Service. Our study is the first comprehensive serological survey to obtain actual data about WNV seroprevalence in the Hungarian human population.

[The first use of iv. idarucizumab for dabigatran reversal in Hungary]. / A dabigatran-antidótum, az intravénás idarucizumab elso hazai alkalmazása.

At present, the direct thrombin inhibitor dabigatran is the only one amongst the new direct anticoagulants which has an effective, specific reversal agent. The novel agent idarucizumab is a humanized, monoclonal antibody fragment binds to dabigatran within minutes thereby offers an opportunity to induce a safe, long-lasting reverse of the anticoagulant effects of dabigatran. The authors describe the first use of idarucizumab in Hungary (23. 05. 2016) in an old female patient with non-valvular paroxysmal atrial fibrillation of high stroke risk-score and renal dysfunction who was taking dabigatran (2 x 110 mg/day) when an acute abdomen developed requiring emergency cholecystectomy. Patient received the antidote (idarucizumab 2 x 2.5 g/50 ml iv.) two hours before the surgical intervention, and she did not have any uncontrollable, life-threatening bleeding during the surgery. The high activated partial thromboplastin time relating to anticoagulative influence before the surgery normalized completely after administration of the antidote. Antagonizing dabigatran with idarucizumab was feasible and safe without any side effects. The patient received dabigatran therapy again after her recovery. Orv. Hetil., 2017, 158(10), 387-392.

Phylogenetic analysis of a transfusion-transmitted hepatitis A outbreak.

A transfusion-associated hepatitis A outbreak was found in the first time in Hungary. The outbreak involved five cases. Parenteral transmission of hepatitis A is rare, but may occur during viraemia. Direct sequencing of nested PCR products was performed, and all the examined samples were identical in the VP1/2A region of the hepatitis A virus genome. HAV sequences found in recent years were compared and phylogenetic analysis showed that the strain which caused these cases is the same as that had spread in Hungary recently causing several hepatitis A outbreaks throughout the country.

Effect of some new thioglycosides on endotoxin-induced disseminated intravascular coagulation in rabbits.

Disseminated intravascular coagulation (DIC) is a systemic thrombohemorrhagic disorder seen in association with many clinical situations, e.g. sepsis, malignancy, obstetrical complications and intravascular hemolysis. In our model, disseminated intravascular coagulation was induced in rabbits by two consecutive intravenous bolus injections of endotoxin from Escherichia coli, 80 and 40 microg/kg. The control group was treated with 0.9% saline. The activity of thioglycosides was compared to unfractionated heparin (UFH) and efegatran with and without administration of endotoxin. Drugs were administered in the following doses: heparin 50 and 100 IU/kg/h i.v. infusion; efegatran 0.25 and 0.5 mg/kg/h i.v. infusion; GYKI 39521 (RGH-1875) as well as GYKI 39541 (RGH-1962) 12.5 and 25 mg/kg per os. Thioglycosides did not modify coagulation parameters in this model [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT)] as compared with endotoxin/vehicle group. The changes in TFPI level after administration of thioglycosides and heparin were similar in the mentioned model to those without endotoxin. Endotoxin-induced changes of leukocyte count were not affected by GYKI 39521 and GYKI 39541 treatment in our model. Diminution of fibrinogen level and platelet count was prevented by GYKI 39521 and GYKI 39541. Fibrin degradation products and fibrinolysis were significantly decreased by GYKI 39521 and GYKI 39541. The thioglycosides may have a lower risk of bleeding in the treatment of disseminated intravascular coagulation than heparin.