Higher Population Coverage with Typhoid Conjugate Vaccine is Needed to Induce Herd Protection: Evidence from a Cluster-Randomized Trial in Urban Bangladesh

Introduction: A cluster randomized trial (CRT) in Bangladesh found that Vi-tetanus toxoid (Vi-TT) vaccine conferred 85% protection to vaccinees at 18 months of follow-up; however, it failed to confer significant herd protection to non-vaccinees. Methods: In the CRT, children aged 9 months to <16 years from 150 clusters received one dose of either Vi-TT or Japanese encephalitis vaccine. To evaluate whether herd protection was evident, we analyzed two years of follow-up data by quartiles of clusters with ascending levels of Vi-TT coverage. Results: The average vaccine coverage across all clusters was 69% among targeted children and 20% in the entire population. Vi-TT provided 83% (95%CI: 74%,89%) total protection among vaccinees, 12% (95%CI: -17%,34%) indirect protection among non-vaccinees, and 53% (95%CI: 40%,63%) overall protection among entire population, irrespective of vaccine coverage. Significant herd protection (47%; 95%CI: 3%,71%) was observed only in the highest quartile of vaccine coverage in the entire population (range 21.5%-26%). No herd protection was evident among targeted children (<16 years), including the highest coverage quartile (72.1%-78.9%), where protection was -8% (95%CI: -108%,44%). Conclusion: Vaccine herd protection, essential for typhoid conjugate vaccines to achieve high overall protection, was evident only in clusters with higher, albeit still modest, coverage in the entire population. Since even high coverage among children <16 years did not generate significant herd protection, higher vaccine coverage across all age groups, including vaccination of adults, may be necessary for TCVs to confer the combined direct and herd protection required for effective typhoid control.