Study design and participants
typhoid, typhoid fever, febrile illness, fever
BLOOD, TYPHOID FEVER, FEBRILE ILLNESS, TYPHOID
Participant eligibility, enrolment, and population definitions in the comparator randomised trial have been described previously.Briefly, in the randomised trial per-protocol sample, 27 882 Malawian children in Blantyre aged 9 months to 12 years were randomly assigned (1:1) to receive a single dose of Vi-TT or meningococcal capsular group A conjugate vaccine (MenA) from Feb 21 to Sept 27, 2018. Participants (13 945 in the Vi-TT group and 13 937 in the MenA group; median age at vaccination 6 years; 14 198 [51%] of 27 882 participants were female) were followed up for blood culture-confirmed typhoid fever with passive surveillance. Participants who presented with febrile illness at outpatient health centres and tertiary facilities in two urban townships (Ndirande and Zingwangwa) in Blantyre, Malawi had a blood culture sample collected if they met one of the following protocol-defined specimen collection criteria: subjective fever for at least 72 h, measured fever of at least 38°C, or hospitalisation with history of fever of any duration. Blood culture results were classified as follows: positive for typhoid, negative for typhoid but positive for a non-typhoid pathogen, or negative for any pathogen or positive for contaminants. All facilities within the study area with blood culture capacity were included in the randomised trial. Vaccine efficacy results for participants followed up until April 3, 2020 (ie, 18–24 months after vaccination), have been reported previously.In the test-negative design, only participants with at least one blood culture specimen collected were considered for the vaccine effectiveness analysis. Because some participants had more than one episode with a blood culture specimen collected, three test-negative design samples were selected, corresponding to three different analysis approaches to estimate the vaccine effectiveness, as described previously, as follows: participant-based analysis sample without censoring for typhoid (test-negative design A); participant-based analysis sample with censoring for typhoid (test-negative design B); and specimen-based analysis sample (test-negative design C).