This study aims to design, develop and optimise a non-invasive, saliva sample-based point-of-care lateral flow test for use in low and middle income settings that can return a qualitative result on whether an individual has or has not immunity to tetanus within 10-15mins. If successful, this approach would not require blood sampling or laboratory facilities, empower personalised decision making on vaccine needs and support the development of population level data-driven public health policies.

The development of non-invasive point-of-care (POC) diagnostic testing for the detection of protective immunity to tetanus would empower LMICs to identify immunity gaps and individuals who are a priority for vaccination and generate sero-epidemiology models for future public health decision around tetanus control. Given tetanus antigen is included as polyvalent vaccine formulations for infants as part of the WHO EPI schedule for LMICS, the absence of anti-tetanus toxoid antibody might also indicate missed vaccine doses that would have conferred protection to other infectious diseases.

This is a cross-sectional, non-interventional, biological sampling study. This study will be conducted at the Center for Family Health Research in Kigali, Rwanda, in collaboration with Rwanda Biomedical Centre, the national health implementation agency for Rwanda, and the University of Birmingham, United Kingdom. WHO/UNICEF estimates DTP3 coverage in Rwanda at 97% following extensive SIA activity after vaccination coverage dropped to 88% in 2021. Rwanda hosts a significant number of refugees (135,000 at the end of April 2024), nearly half of these are children and many are from the Democratic Republic of the Congo where only just over half of children are fully immunised.

The overall aim of this study is to assess the real-world performance and the diagnostic clinical accuracy of a novel, saliva-based, point-of-care lateral flow test in determining the immune status to tetanus for individuals in Rwanda.

Participants will be recruited from the following groups:

• Group A: Healthy children aged 5-10 years (n=250)
• Group B: Healthy younger adults aged 18-25 years (n=35)
• Group C: Healthy pregnant women (n=30)
• Group D: Adults with known immune suppression (see table 1) aged 18-45 years (n=75)

Inclusion Criteria:

• Able and willing to provide informed consent to take part in the study; either directly or from a parent/guardian, where appropriate
• [Group A] Aged 5-10 years inclusive, and determined as healthy by a member of the study team
• [Group B] Aged 18-25yrs inclusive, and determined as healthy by a member of the study team
• [Group C] Currently pregnant at any stage of pregnancy, prior to receipt of a tetanus booster vaccine in pregnancy, and determined as healthy by a member of the study team and safe to provide a blood sample
• [Group D] Adults aged 18-45 years with one or more of the medical conditions that may affect antibody response to vaccination.

Exclusion Criteria:

• Participants or parents/guardians unwilling or unable to provide informed consent to take part

• Unwilling or unable to comply with study procedures

• Have a bleeding disorder deemed significant by study doctor

• [Groups A, B and C only] Any health condition which, in the opinion of a study physician which could

  1. mean blood sampling has the potential for harm and/or
  2. affect immune response to a vaccine for example known/suspected impairment of immune function (with the exception of Group D)

The data that support the findings of this study are not openly available to protect the confidentiality of study participants. Fully anonymised data are, however, available from the authors upon reasonable request.

Data requests can be submitted starting immediately after article publication and the data will be made accessible for up to 5 years. Extensions will be considered on a case-by-case basis.

Access to trial IPD can be requested by qualified researchers engaging in independent scientific research and will be provided following review and approval of a methodologically sound research proposal. Data must be required to achieve the aims in the approved proposal. Data requests should be directed to c.a.green.2@bham.ac.uk.