Journal article
A cluster randomized non-inferiority field trial on the immunogenicity and safety of tetanus toxoid vaccine kept in controlled temperature chain compared to cold chain
Background: In resource-poor settings, cold
chain requirements present barriers for vaccine delivery. We
evaluated the immunogenicity and safety of tetanus toxoid (TT)
vaccine in “Controlled Temperature Chain” (CTC; up to 40 °C for
<30 days before administration), compared to standard cold chain
(SCC; 2–8 °C). Prior to the study, stability parameters of TT–CTC
were shown to meet international requirements. Methods: A cluster
randomized, non-inferiority trial was conducted in Moïssala
district, Chad, December 2012–March 2013. Thirty-four included
clusters were randomized to CTC or SCC. Women aged 14–49 years,
eligible for TT vaccination and with a history of ≤1 TT dose,
received two TT doses 4 weeks apart. Participants were blinded to
allocation strategy. Tetanus antibody titers were measured using
standard ELISA at inclusion and 4 weeks post-TT2. Primary outcome
measures were post-vaccination seroconversion and fold-increase in
geometric mean concentrations (GMC). Non-inferiority was by
seroconversion difference (TTSCC − TTCTC) <5% and ratio of GMCs
(TTSCC/TTCTC) <1.5. Adverse events were monitored at health
centers and at next contact with participants. Results: A total of
2128 women (CTC = 1068; SCC = 1060) were recruited. Primary
intention to vaccinate analysis included 1830 participants; 272 of
these were included in the seroconversion analysis. Seroconversion
was reached by >95% of participants; upper 95%CI of the
difference was 5.6%. Increases in GMC were over 4-fold; upper 95%CI
of GMC ratio was 1.36 in the adjusted analysis. Few adverse events
were recorded. Conclusions: This study demonstrates the
immunogenicity and safety of TT in CTC at <40 °C for <30
days. The high proportion of participants protected at baseline
results in a reduction of power to detect a 5% non-inferiority
margin. However, results at a 10% non-inferiority margin, the
comparable GMC increases and vaccine\'s stability demonstrated in
the preliminary phase indicate that CTC can be an alternative
strategy for TT delivery in situations where cold chain cannot be
maintained.
Authors
Languages
- English
Publication year
2014
Publisher
Elsevier
Journal
Vaccine
Volume
47
Type
Journal article
Categories
- Vaccines & delivery devices
Diseases
- Tetanus
Countries
- Chad
Tags
- Controlled temperature chain (CTC)
WHO Regions
- African Region
Topic references
CTC_JOURNAL