Flavivirus Infections in Travelers : Insights into Prevention of Japanese Encephalitis and Diagnostics of Dengue

The mosquito-borne flavivirus infections Japanese encephalitis (JE) and dengue pose a considerable disease burden in the tropical and subtropical regions of the world. Sometimes these infections also affect international travelers visiting areas endemic for the diseases. This thesis addresses the prevention of Japanese encephalitis and diagnostics of dengue, with a focus on traveler s health. The main aim was to find solutions to some practical clinical questions, and thus provide clinically important new data on travel-associated flavivirus infections. The first three studies assessed the immunogenicity of two inactivated JE vaccines, the new Vero cell derived (JE-VC) and the traditional mouse brain derived (JE-MB) preparation, in 120 Finnish and Swedish adult travelers, by determining the pre- and post-vaccination titers of JE virus neutralizing antibodies with plaque-reduction neutralization test (PRNT). A PRNT50 titer ≥10 was considered protective. Study I addressed the boosting capacity of the SA14-14-2 based JE-VC vaccine in subjects previously primed with the Nakayama strain based JE-MB preparation. The response rates were 91% after a homologous (JE-MB) and 95%-98% after a heterologous booster dose (JE-VC). Among those with no seroprotection at baseline, a higher proportion of JE-MB primed (100%) than non-primed (40%) subjects seroconverted after a single JE-VC dose. The data suggest that a single JE-VC dose suffices for boosting JE-MB immunity, and call for re-evaluation of guidelines recommending two JE-VC doses for JE-MB primed subjects. Study II demonstrated that both JE-VC and JE-MB elicit neutralizing antibodies, not only against the vaccine genotype, but also against heterologous JE virus genotypes. The seroprotection rates against the heterologous strains were 93%-97% after JE-VC, and 83%-92% after JE-MB primary series. The data imply that the two vaccines are expected to confer seroprotection against all major JE virus genotypes circulating. Study III evaluated long-term seroprotection after JE-VC primary and booster vaccinations. Two years after primary immunization, 93% of vaccinees were seroprotected against the vaccine strain but only 73% against the emerging genotype GI. JE-MB primed vaccinees were seroprotected against both vaccine (100%) and non-vaccine (89%-95%) genotype strains two years after the heterologous JE-VC booster dose, further supporting the use of a single JE-VC dose for boosting JE-MB immunity. Study IV explored the diagnostic markers of dengue in 93 Finnish traveler patients. The duration of viremia (9 days, 95% CI: 8-10) and NS1 antigenemia (15 days, 95% CI: 12-20) were longer than reported in endemic settings, presumably due to a high proportion of primary infections among travelers. The data support use of test combinations, e.g. antibody and NS1 detection, for efficient diagnostics. The relative levels of viremia and NS1 antigenemia were associated with some central clinical parameters, suggesting these virologic markers as predictors of the clinical manifestations in travelers dengue.

Grantor dc:publisher

Helsingin yliopisto

Year dc:date.issued

2013

Author dc:creator

• Erra, Elina

• lääketiede

Statement dc:rights

• Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
• This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited.
• Publikationen är skyddad av upphovsrätten. Den får läsas och skrivas ut för personligt bruk. Användning i kommersiellt syfte är förbjuden.

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10138/40790

OAI record oai:identifier

https://helda.helsinki.fi/server/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Ahelda.helsinki.fi%3A10138%2F40790