Epidemiology and distribution of tick-borne encephalitis.

Tick-borne encephalitis (TBE) is the main tick-borne virus infection in Eurasia. It is prevalent across the entire continent from Japan to France and occurs in endemic foci. Expansion of prevalence in areas including northern Russia, Sweden, and Finland has been observed in recent years. Ticks are the most important vectors and may transmit the TBE virus to animals and humans. TBE can also be transmitted to humans in milk containing the virus. TBE has been implicated as a travel-acquired illness and there are isolated reports of its occurrence in countries outside the known areas of prevalence. Therefore, TBE should be included in the differential diagnosis for all central nervous system diseases inside or outside endemic areas.

Rabies in South Africa and the FIFA Soccer World Cup: travelers' awareness for an endemic but neglected disease.

Rabies is endemic on every continent except Antarctica and is also considered to be a significant health problem in Africa, including South Africa. With the upcoming FIFA Soccer World Cup to be held in 2010 in cities throughout South Africa, this review depicts the rabies situation in South Africa and discusses what travelers visiting the games should know about rabies and rabies prophylaxis before or after an exposure to a potential rabid animal occurs.

30 Years of rabies vaccination with Rabipur: a summary of clinical data and global experience.

Rabies poses a threat to more than 3.3 billion people worldwide and is estimated to cause about 60,000 deaths a year. However, according to the WHO, it is still one of the most neglected diseases in developing countries. Human rabies vaccinations are critical components of pre-exposure and post-exposure prophylaxis. Rabipur [corrected], the first purified chick embryo cell-culture vaccine, was licensed in Germany in 1984, and later in more than 60 countries worldwide [corrected].The immunogenicity, efficacy and safety of Rabipur have been assessed in numerous clinical trials in pre- and post-exposure regimens, using both intramuscular and intradermal routes of administration. The trial populations have involved adults and children, including healthy volunteers and individuals bitten by laboratory-proven rabid animals, malnourished children and immunocompromised individuals. Extensive, worldwide clinical experience with Rabipur over the past 30 years has shown the vaccine to be immunogenic, effective and generally well tolerated.

[Prevalence of antibodies against Tick-Borne Encephalitis virus in dogs from Saxony, Germany]. / Zum Vorkommen von Antikörpern gegen das Frühsommer-Meningoenzephalitis- Virus bei Hunden in Freistaat Sachsen, Deutschland.

Tick-borne encephalitis (TBE) is the most important tick-transmitted viral disease in Europe and is caused by the TBE virus (TBEV), a member of the Flaviviridae family. In Germany, the vast majority of human TBE cases occurs in the south in so-called risk areas. However, in areas with only sporadic TBE cases, the respective risk assessment is hard to achieve. We therefore intend to use the prevalence of antibodies against TBEV in dogs as an indicator to trace such TBE endemic areas. Between August 2012 and March 2014, a total of 331 blood sera were collected from dogs all over Saxony, which hadn't left the state for the past five years. For the detection of antibodies against TBE-virus a commercial ELISA was used. Ten sera with positive or borderline ELISA results were retested by serum neutralization test. All seven ELISA-positive serum samples could be verified to contain TBE-virus-specific antibodieswith SNT titres between 1:15 and more than 1:40. We therefore found 2.1% seroprevalence in our samples. We conclude, that dogs can very well be used as sentinels, especially in areas with only sporadic TBE cases, although larger sample sizes are desired.

Five year follow-up after primary vaccination against tick-borne encephalitis in children.

BACKGROUND: A first tick-borne encephalitis (TBE) vaccine booster in children is currently suggested 3 years after completing either a conventional (doses on Days 0, 28 and 300) or accelerated conventional (doses on Days 0, 14 and 300) TBE immunization schedule. This recommendation, however, may not be appropriate in cases where different TBE vaccines have been used interchangeably during the primary immunization series. METHODS: To provide robust data to better inform such recommendations, TBE antibody persistence was evaluated after 3-5 years in four groups of children (aged 5-15 years): two groups previously primed with three doses of Encepur(®) Children (conventional/accelerated conventional schedule); and two groups previously primed with two doses of FSME-IMMUN(®) followed by a third dose of Encepur(®) Children (conventional/accelerated conventional schedule). Immunogenicity was evaluated using neutralization (NT) assays based on both vaccine antigens as well as on the Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: In the two Encepur(®) Children groups (full series), protective NT titers of ≥10 were detected in 98-100% of children up to 5 years after their last primary vaccination, irrespective of schedule. In contrast, only 65-70% subjects in the FSME-IMMUN(®) Junior groups (mixed series) displayed NT titers ≥10 after 3 years. Thus, due to lower probability of achieving/maintaining long-term protective antibody levels (recently defined by the World Health Organization as an NT titer ≥10) after this time point, both FSME-IMMUN Junior groups were discontinued. CONCLUSION: A strong antibody response persists for at least 5 years after full primary vaccination with Encepur(®) Children. The study thus provides support for extending the time interval for a first booster dose after primary vaccination (conventional/accelerated conventional schedule) with Encepur(®) Children from 3 to 5 years.

Evaluation of rabies immunogenicity and tolerability following a purified chick embryo cell rabies vaccine administered concomitantly with a Japanese encephalitis vaccine.

BACKGROUND: For individuals traveling at short notice to rabies and Japanese encephalitis (JE) endemic countries, concomitant administration of travel vaccines within a short period is often required. METHODS: The aim of this study was to determine whether an accelerated (one-week: Days 1-8) pre-exposure rabies (Rabipur(®), Novartis Vaccines) vaccination regimen administered concomitantly with a Japanese encephalitis (JE) vaccination (Ixiaro(®), Valneva) regimen, is non-inferior to the standard (four-week: Days 1, 8, 29) rabies regimen administered alone or concomitantly with the JE vaccine. Healthy adults (18 to ≤ 65 years) were randomized into Rabies + JE-Standard, Rabies + JE-Accelerated, Rabies-Standard and JE-Standard groups. Relative immunogenicity for rabies in each regimen was assessed using the rapid fluorescent focus inhibition test. Safety was evaluated up to and including Day 57. RESULTS: Non-inferior immunogenicity for rabies was established between the Rabies + JE-Accelerated group compared to both the Rabies-Standard and Rabies + JE-Standard groups; as well as between the Rabies + JE-Standard regimen and the Rabies-Standard regimen. By Day 57, adequate neutralizing levels were achieved by 97-100% of subjects across all groups. Adverse events (AEs) were comparable for all groups. CONCLUSIONS: An accelerated pre-exposure rabies and JE vaccination regimen is non-inferior to the standard four-week rabies regimen and may thus provide a more convenient regimen for individuals traveling to endemic countries at short notice. NCT01662440.

New foci of tick-borne encephalitis virus in Europe: consequences for travellers from abroad.

Tick-borne encephalitis (TBE) virus is endemic in many European countries. To assess the risk of infection by TBE virus, maps of TBE foci are a helpful tool for travellers. The TBE reporting system is insufficient in some countries leading to incomplete data, low awareness and underestimation of the risk of infection. In TBE endemic countries with a low vaccine coverage rate, the number of reported TBE cases is increasing and new TBE foci are emerging in a number of European countries. People living in and travellers going into such areas might be more exposed to TBE virus than estimated, based on the current epidemiological maps.

Cross-neutralization of antibodies induced by vaccination with Purified Chick Embryo Cell Vaccine (PCECV) against different Lyssavirus species.

BACKGROUND: Rabies is a neglected zoonotic disease caused by viruses belonging to the genus lyssavirus. In endemic countries of Asia and Africa, where the majority of the estimated 60,000 human rabies deaths occur, it is mainly caused by the classical rabies virus (RABV) transmitted by dogs. Over the last decade new species within the genus lyssavirus have been identified. Meanwhile 15 (proposed or classified) species exist, including Australian bat lyssavirus (ABLV), European bat lyssavirus (EBLV-1 and -2), Duvenhage virus (DUVV), as well as Lagos bat virus (LBV) and Mokola virus (MOKV) and recently identified novel species like Bokeloh bat lyssavirus (BBLV), Ikoma bat lyssavirus (IKOV) or Lleida bat lyssavirus (LLBV). The majority of these lyssavirus species are found in bat reservoirs and some have caused human infection and deaths. Previous work has demonstrated that Purified Chick Embryo Cell Rabies Vaccine (PCECV) not only induces immune responses against classical RABV, but also elicits cross-neutralizing antibodies against ABLV, EBLV-1 and EBLV-2. MATERIAL & METHODS: Using the same serum samples as in our previous study, this study extension investigated cross-neutralizing activities of serum antibodies measured by rapid fluorescent focus inhibition test (RFFIT) against selected other non-classical lyssavirus species of interest, namely DUVV and BBLV, as well as MOKV and LBV. RESULTS: Antibodies developed after vaccination with PCECV have neutralizing capability against BBLV and DUVV in the same range as against ABLV and EBLV-1 and -2. As expected, for the phylogenetically more distant species LBV no cross-neutralizing activity was found. Interestingly, 15 of 94 serum samples (16%) with a positive neutralizing antibody titer against RABV displayed specific cross-neutralizing activity (65-fold lower than against RABV) against one specific MOKV strain (Ethiopia isolate), which was not seen against a different strain (Nigeria isolate). CONCLUSION: Cross-neutralizing activities partly correlate with the phylogenetic distance of the virus species. Cross-neutralizing activities against the species BBLV and DUVV of phylogroup 1 were demonstrated, in line with previous results of cross-neutralizing activities against ABLV and EBLV-1 and -2. Potential partial cross-neutralizing activities against more distant lyssavirus species like selected MOKV strains need further research.

Co-administration of a meningococcal glycoconjugate ACWY vaccine with travel vaccines: a randomized, open-label, multi-center study.

BACKGROUND: Potential interactions between vaccines may compromise the immunogenicity and/or safety of individual vaccines so must be assessed before concomitant administration is recommended. In this study, the immunogenicity and safety of travel vaccines against Japanese encephalitis (JEV) and rabies (PCECV) administered together with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine were evaluated (NCT01466387). METHOD: Healthy adults aged 18 to ≤60 years were randomized to one of four vaccine regimens: JEV + PCECV + MenACWY-CRM, JEV + PCECV, PCECV or MenACWY-CRM. Immunogenicity at baseline and 28 days post-complete vaccination was assessed by serum bactericidal assay using human complement or neutralization tests. Adverse events (AEs) were collected throughout the study period. RESULTS: JEV + PCECV + MenACWY-CRM was non-inferior to JEV + PCECV. Post-vaccination seroprotective neutralizing titers or concentrations were achieved in 98-99% (JE) and 100% (rabies) of subjects across the vaccine groups. Antibody responses to vaccine meningococcal serogroups were in the same range for MenACWY-CRM and JEV + PCECV + MenACWY-CRM. Rates of reporting of AEs were similar for JEV + PCECV and JEV + PCECV + MenACWY-CRM. CONCLUSIONS: MenACWY-CRM was administered with an inactivated adjuvanted JE and a purified chick embryo cell-culture rabies vaccine without compromising immunogenicity or safety of the individual vaccines. These data provide evidence that MenACWY-CRM could be effectively incorporated into travel vaccination programs. TRIAL NUMBER: NCT01466387.

Tick-borne encephalitis (TBE) trends in epidemiology and current and future management.

Tick-borne encephalitis (TBE) is considered an international health issue, as the number of risk areas and reported cases across Europe, Russia, and parts of Asia continues to increase. The incidence of TBE has fluctuated considerably from year to year in many countries, but in the past decade the number of TBE cases has significantly increased in the Baltic states, the Czech Republic, and Germany, in addition to occurring in countries previously considered to be free from TBE, such as Denmark (specifically the main island of Zealand), France, and Italy. A number of factors have been suggested to explain the increase in incidence, including climate change, and increased travel and outdoor pursuits, placing people in increased contact with infected ticks. There is no causal treatment available once infected, but TBE can be effectively prevented by vaccination, for which several vaccines are widely available. Three vaccination schedules are available for immunization against TBE, and the recommendations for TBE vaccination vary considerably across the countries in which TBE foci are found. However, plans are in place to raise awareness of TBE and to standardize the vaccination programme across Europe, with the aim of reducing the number of future cases of TBE.

Long-term immunity after vaccination against tick-borne encephalitis with Encepur using the rapid vaccination schedule.

148 of 157 invited adult subjects who had participated in previous studies were enrolled in this extension study for evaluation of immunogenicity and safety of the second TBE booster immunization. All subjects had been previously immunized in studies with Chiron's formerly marketed TBE vaccine (containing polygeline as the stabilizer) according to the rapid vaccination schedule (i.e. primary immunization on days 0, 7, 21 and first booster immunization at month 15). All subjects were administered the second booster with Chiron's new TBE vaccine, which is free of protein-derived stabilizers, 36 months after the first booster vaccination applied at study month 15. Blood samples were taken prior to booster and 1 month later. In 145 out of 148 subjects, blood samples suitable for measurements of TBE antibodies (ELISA assay) were provided. Prior to second booster immunization with Chiron's new TBE vaccine, TBE antibodies (GMTs) had remained at a high level and were far above the detection limit of the used ELISA test. All subjects were still seropositive prior to the second booster immunization. The second booster immunization resulted in a further increase of TBE antibodies. The booster vaccination with Chiron's new TBE vaccine was well tolerated by all the vaccinees. Neither febrile post-immunization reactions nor unexpected adverse events or serious adverse events were reported. To summarize, these data clearly show that the TBE vaccination with this new TBE vaccine can be used safely to boost subjects pre-immunized with the former TBE vaccine formulation. Long-lasting immunity following this second TBE booster immunization can be concluded.