Nepal TyVAC Trial - Take on Typhoid

On November 20, 2017, Nepal saw the successful launch of a trial aiming to assess the impact of typhoid conjugate vaccines (TCVs) in preventing typhoid among children, vaccinating the first of 20,000 children against typhoid. This vaccination trial is part of the Typhoid Vaccine Acceleration Consortium (TyVAC). Funded by the Bill and Melinda Gates Foundation and managed by University of Maryland, in collaboration with University of Oxford, and PATH, TyVAC aims to generate evidence on TCV impact, and accelerate the use of TCVs in countries with significant typhoid burden. TyVAC Nepal is sponsored by the University of Oxford.
To be able to vaccinate 20,000 children over three months, TyVAC hired 175 local staff and trained them on topics including public engagement, cold chain management, vaccination administration, informed consent, and data management.
Before launching the vaccine trial, project staff conducted community outreach activities in the Lalitpur District of the Kathmandu Valley where the trial would be conducted. Activities ranged from staff going door-to-door and visiting local mothers’ groups to meetings with the district Public Health Division, Mayor and other locally elected representatives. (Bill & Melinda Gates Foundation/Sam Reinders)
The trial team set up 15 clinics to be able to vaccinate 20,000 children in Lalitpur District. Clinic set-up involved cleaning, assembling equipment, installing IT systems, and running a mock clinic with the staff.
Despite several last minute delays, the vaccines arrived safely in Nepal on November 19th, 2017. The trial began the next day. The Patan Academy of Health Sciences, Oxford University Clinical Research Unit and the Nepal Family Development Foundation were all critical in the successful start and ongoing delivery of the trial in Nepal.
The TCV being used in the trial is the recently prequalified Typbar-TCV. New TCVs have several advantages over earlier typhoid vaccines, including the potential ability to provide longer-lasting protection TCVs also require fewer doses, and can be administered to children younger than two years of age, making it the first-ever to be approved for this age group.
Several important local officials attended the opening of the first vaccine clinic, including the Mayor and other local government representatives. Also attending in a show of support for the first vaccine clinic were representatives from the World Health Organization, the Patan Academy of Health Sciences, and the Nepal Paediatric Society. (Bill & Melinda Gates Foundation/Sam Reinders)
Local community leaders were generally supportive of the typhoid vaccination trial in Lalitpur District. Typhoid results in nearly 12 million cases and more than 128,000 deaths globally each year. Countries like Nepal are implementing new preventative strategies to control the disease that most commonly impacts poor communities. (Bill & Melinda Gates Foundation/Sam Reinders)
Families eager to participate in the study and have their child vaccinated wait in a clinic during the first day of the trial. Children and adolescents younger than 15 years of age are disproportionately impacted by typhoid. (Bill & Melinda Gates Foundation/Sam Reinders)
Parents hoping to protect their children from typhoid line up to take part in the study. (Bill & Melinda Gates Foundation/Sam Reinders)
Before they can enrol in the study, the child and their guardian see a trained counsellor who makes sure that they understand what the study involves, and answers any questions they may have. If the guardian is unable to read, the counsellors read the participant information booklet to them. (Bill & Melinda Gates Foundation/Sam Reinders)
Following their appointment, the child and guardian see a member of the trial staff, who receives informed consent and screens the child to ensure they are eligible to take part in the study. (Bill & Melinda Gates Foundation/Sam Reinders)
After enrolling in the study, children receive a general examination to ensure they are fit for vaccination. For children under five, trial staff measure their height and weight. (Bill & Melinda Gates Foundation/Sam Reinders)
All staff are trained in working with children and distraction techniques, including the use of toys, to reduce the distress and pain experienced during vaccination or blood draw. (Bill & Melinda Gates Foundation/Sam Reinders)
Despite many challenges, the first of 20,000 children was vaccinated on the exact date that the team had targeted. (Bill & Melinda Gates Foundation/Sam Reinders)
Of the 20,000 participants, a randomly selected group of 1500 children are also part of a sub study which involves four blood tests, during the study, to check on antibody levels following vaccination. (Bill & Melinda Gates Foundation/Sam Reinders)
All participants receive a diary to take home with them. The diary has space to record any adverse events and provides information about free access to health care if their child gets a fever, and key study contact details. (Bill & Melinda Gates Foundation/Sam Reinders)
Participants all receive access to a doctor and a free blood test if they have a fever for more than two days. This service is available at several community clinics and a hospital-based clinic in Lalitpur District. (Bill & Melinda Gates Foundation/Sam Reinders)
Blood samples from study participants are all initially processed at the Patan Hospital Laboratory. Some samples are sent to laboratories outside of Nepal for analysis when it cannot be done locally. (Bill & Melinda Gates Foundation/Sam Reinders)
For the next two years, the communications team will follow up with all the participating children either on the phone or face-to-face every three months.
Data collected from this trial over the next two years will generate evidence for the impact of TCVs and inform future country introduction plans. Gavi, the Vaccine Alliance approved an $85 million funding window to support the introduction of TCVs in low-income countries that experience a high burden of disease like Nepal. (Bill & Melinda Gates Foundation/Sam Reinders)

On November 20, 2017, Nepal saw the successful launch of a trial aiming to assess the impact of typhoid conjugate vaccines (TCVs) in preventing typhoid among children, vaccinating the first of 20,000 children against typhoid. This vaccination trial is part of the Typhoid Vaccine Acceleration Consortium (TyVAC). Funded by the Bill and Melinda Gates Foundation, TyVAC aims to generate evidence on TCV impact, and accelerate the use of TCVs in countries with significant typhoid burden.

To be able to vaccinate 20,000 children over three months, TyVAC hired 175 local staff and trained them on topics including public engagement, cold chain management, vaccination administration, informed consent, and data management.

Before launching the vaccine trial, project staff conducted community outreach activities in the Lalitpur District of the Kathmandu Valley where the trial would be conducted. Activities ranged from staff going door-to-door and visiting local mothers’ groups to meetings with the district’s Public Health Division and locally elected representatives.

The trial team set up 15 clinics to be able to vaccinate 20,000 children in Lalitpur District. Clinic set-up involved cleaning, assembling equipment, installing IT systems, and running a mock clinic with the staff.

Despite several last minute delays, the vaccines arrived safely in Nepal on November 19th, 2017. The trial began the next day.

The TCV being used in the trial is the recently prequalified Typbar-TCV. New TCVs have several advantages over earlier typhoid vaccines, including the ability to provide longer-lasting protection, require fewer doses, and be administered to children younger than two years of age, making it the first-ever to be approved for this age group.

Several important local officials attended the opening of the first vaccine clinic, including the mayor of Kathmandu and other local government representatives. Also attending in a show of support for the first vaccine clinic were representatives from the World Health Organization, the Patan Academy of Health Sciences, and the Nepal Paediatric Society.

Local community leaders displayed excitement for the typhoid vaccination trial in Lalitpur District. Typhoid results in nearly 12 million cases and more than 128,000 deaths globally each year. Countries like Nepal are implementing new preventative strategies to control the disease that most commonly impacts poor communities.

Families eager to participate in the study and have their child vaccinated wait in a clinic during the first day of the trial. Children and adolescents younger than 15 years of age are disproportionately impacted by typhoid.

Parents hoping to protect their children from typhoid line up to receive the TCV.

Before they can enroll in the study, the child and their guardian see a trained counsellor who makes sure that they understand what the study involves, and answers any questions they may have. If the guardian is unable to read, the counsellors make sure to read the participant information booklet to them.

Following their appointment the counsellor, the child and guardian see a member of the trial staff, who takes their informed consent and screens the child to ensure they are eligible to take part in the study.

After enrolling in the study, children receive a general examination to ensure they are fit for vaccination. For children under five, trial staff make sure to measure their height and weight.

Trial staff have many tasks, including distracting children with toys, candy, or bright objects to reduce their distress during vaccination.

Of the 20,000 children volunteers, a randomly selected group of 1500 children are also part of a sub study which involves four blood tests to check on antibody levels following vaccination.

All participants receive a diary to take home with them. The diary has space to record any adverse events and provides information about free access to health care if their child gets a fever, and key study contact details.

Participants all receive access to a doctor and a free blood test if they have a fever for more than two days. This service is available at several community clinics and a hospital-based clinic in Lalitpur District.

Blood samples from study participants are all initially processed at the Patan Hospital Laboratory. Some samples are sent to laboratories outside of Nepal for analysis when it cannot be done locally.

For the next two years, the communications team will follow up with all the participating children either on the phone or face-to-face every three months.

Data collected from this trial over the next two years will generate evidence for the impact of TCVs and inform future country introduction plans. Gavi, the Vaccine Alliance approved an $85 million funding window to support the introduction of TCVs in low-income countries that experience a high burden of disease like Nepal.