Table 1 Inclusion and exclusion criteria

Cases

 Inclusion criteria:

  • Subjects are ≥16 years old;

  • Subjects report a tick-bite acquired within the last 2 months;

  • Subjects report an objectified (measured rectally, axillary, orally or tympanic) fever (defined as ≥38.0 °C) within the last 4 weeks, developed in the course of 4 weeks after tick-bite;

  • Subjects live or stay in the Netherlands during the course of the study.

 Exclusion criteria:

  • Subjects with evident signs or symptoms of another cause of the fever besides a TBD;

  • Subjects unable to provide informed consent or do not have sufficient proficiency of the Dutch language.

Tick-bite controls (A)

 Inclusion criteria:

  • Subjects are ≥16 years old;

  • Subjects report a tick-bite acquired within the last 2 months;

  • Subjects frequency match to cases by gender, age, province of residence and month of tick-bite acquirement;

  • Subjects live or stay in the Netherlands during the course of the study.

 Exclusion criteria:

  • Subjects develop an objectified (measured rectally, axillary, orally or tympanic) temperature > 37.3 °C within 4 weeks after the tick-bite;

  • Subjects with evident signs or symptoms of a currant infectious disease;

  • Subjects unable to provide informed consent or do not have sufficient proficiency of the Dutch language.

Population background controls (B)

 Inclusion criteria:

  • Subjects are ≥16 years old;

  • Subjects participating in the national serosurvey PIENTER-3 of the National Institute for Public Health and Environment (RIVM) of the Netherlands;

  • Subjects frequency match to cases by gender and age.

 Exclusion criterium:

  • Subjects unable to give informed consent or do not have sufficient proficiency of the Dutch, English, French, Spanish, Arabian, Turkish or Papiamentu language.

Healthy blood donors (C)

 Inclusion criteria:

  • Subjects are ≥18 years old;

  • Subjects presenting as a healthy blood donor at the national blood bank Sanquin;

  • Subjects frequency match to cases by gender, age and province of residence.

 Exclusion criterium:

  • Subjects unable to give informed consent.