Recruitment, study visits, vaccinations, data collection and sampling
diarrhoea, nausea, fever, abdominal pain, vomiting, travel-related, cramping, TD, diarrhoeal
CHOLERA
The trial was advertised in newspapers and electronic media with a link to the study website, where those interested were encouraged to fill in a contact request. The Finnish media also published several news releases and interviews on TV and the internet, and in newspapers. The nurses called all those who had left a contact request, provided them with further information and conducted a preliminary screening for eligibility. The pre-screened candidates then attended visit V0 for eligibility assessment and informed consent. For inclusion in the study, the volunteers had to: be ≥18 and ≤65 years of age, agree to regular intake of atovaquone + proguanil (Malarone®) as antimalarial prophylaxis according to prescription guidelines, not have travelled to ETEC endemic areas over the past year and not have taken Dukoral or other cholera or ETEC vaccines within 3 years. Detailed inclusion/exclusion criteria are provided in Participation included a pre-travel phase with four visits (V0–V3), a 12-day journey (excluding travel days) to Grand Popo, Benin, with three mandatory visits (B1–B3) and a 1-month post-travel follow-up period with two visits (V4 and V5) (In Benin, the participants attended three regular visits (B1–B3) and provided a routine stool sample on the fourth day of travel. Visit B1 scheduled within 24 h (or at the maximum 48 h) of arrival included detailed instructions for diarrhoea reporting and stool collection procedures. Travellers’ diarrhoea was defined as passing ≥3 unformed/liquid stools within 24 h together with having one or more of the following gastrointestinal symptoms: fever, abdominal pain, cramping, nausea and vomiting. During each TD episode, the participants delivered samples from the third and fourth stools (if available). They were instructed to contact the subinvestigator at low threshold 24/7 and, if needed, pay an unscheduled visit/ask the subinvestigator for a visit in case of TD or other health issues. During and after their stay in Benin (for 12 days in Benin and 12 days after), the participants recorded their diarrhoeal episodes, assessing severity and reporting related symptoms and concomitant medication on health cards (HC1 and HC2) by hour. Vaccine efficacy calculations were based on episodes occurring between arrival in Benin and 6 days after return to Finland (19 days in all).The follow-up period in Finland comprised visits V4 on Days 1–6 and V5 on Days 30 ± 5 after return. Routine blood and stool samples were collected on V4 (and V5 for exploratory studies). If TD occurred within 6 days after travel, additional stool samples were collected from the third and fourth stools of the episode.Data on demographics were collected by questionnaire Q1 before travel. Questionnaire Q2 collected on V4 dealt with travel-related items not covered in HCs. Questionnaire Q3 spanned the period from return to approximately Day 30. Part of Q1 and all of Q2, Q3 and QU4 were devised to meet the exploratory objectives. See 