Emergence of dengue and Zika virus : travellers as sentinels for global epidemics

Tutkimustuotos: OpinnäyteVäitöskirja


Dengue virus (DENV) serotypes 1-4 are mosquito-borne flaviviruses that are increasingly being diagnosed from travellers returning from subtropical and tropical regions. At present, 50-100 cases of dengue are diagnosed annually in Finland. A mosquito-borne flavivirus, Zika virus (ZIKV), was considered to be a relatively harmless virus found in Africa and Asia with low case numbers and mild disease associations. Since 2013, however, ZIKV has emerged and swept across Polynesia, the Americas and the Caribbean, causing massive outbreaks with new severe complications becoming apparent. Amongst these new complications, neurological symptoms have been observed in adults and, alarmingly, congenital infections resulting in severe developmental disorders, including microcephaly. Due to environmental changes and globalisation, the distribution areas of vectors of DENV and ZIKV have spread towards north, which emphasises the risk of introduction of new MBVs to new areas. This thesis aimed to explore the best possible practices in dengue and Zika diagnostics by studying the available methods of choice, their combinations and different sample materials collected from Finnish traveller patients at different phases of the illness. Additionally, this thesis includes studies exploring the molecular epidemiology of DENV and ZIKV and detailed characterization of a congenital ZIKV infection patient case. The detection kinetics of DENV NS1 antigen and RNA was explored from serum, urine and saliva samples. It was observed that NS1 antigen was detectable from the sera of travellers for notably longer periods than reported for populations living in endemic areas. Urine and saliva were demonstrated to be potential sample materials for DENV diagnostics. Urine, in particular, provides new opportunities for molecular diagnostics of DENV as the time window for detection of viral RNA is notably later during the infection when compared to serum samples. It was observed that also ZIKV RNA detection was successful from urine whereas the serum sample taken at the same time point remained negative. Nowadays, urine is considered to be a suitable sample material in diagnostics. By studying traveller patients, the DENV strain responsible for the Madeiran outbreak in 2012 was identified as DENV-1, most likely of South American origin. The characterization of a virus from a Finnish traveller revealed the circulation of ZIKV in the Maldives for the first time. This case was followed by a few additional traveller cases identified elsewhere. Subsequently, the local authorities conducted surveillance studies and confirmed local transmission of ZIKV by detecting the virus from local mosquitoes. Study in this thesis was among the first reports to provide concrete evidence for the causality between ZIKV infection in a pregnant woman and malformations of central nervous system in the foetus. In this study the virus was isolated from the brain tissue of the foetus. The mother’s viremia was noticed to be prolonged, an observation that later studies have confirmed to be a common phenomenon. Mother’s viremia was detectable weeks before the abnormalities in brain development were visible. The evidence provided by the studies herein, along with other recently published data, have shown that there is a need to update the diagnostic guidelines.
Painoksen ISBN978-951-51-3914-6
Sähköinen ISBN978-951-51-3915-3
TilaJulkaistu - 2017
OKM-julkaisutyyppiG5 Tohtorinväitöskirja (artikkeli)


M1 - 109 s. + liitteet


  • Antibodies, Viral
  • +blood
  • Antigens, Viral
  • +analysis
  • Biomarkers
  • Brain
  • +pathology
  • +virology
  • Dengue
  • +diagnosis
  • +epidemiology
  • Dengue Virus
  • +genetics
  • +isolation & purification
  • Disease Outbreaks
  • Fetus
  • +abnormalities
  • Fever
  • +etiology
  • Microcephaly
  • Pregnancy Complications, Infectious
  • RNA, Viral
  • Saliva
  • Sensitivity and Specificity
  • Sequence Analysis, DNA
  • Serum
  • Serotyping
  • Viral Nonstructural Proteins
  • Viremia
  • Urine
  • Travel
  • Zika Virus
  • Zika Virus Infection
  • +complications
  • +urine
  • 3111 Biolääketieteet

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