![\"DENGUE\"](\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/files\/2014\/11\/DENGUE-298x300.png\")
<\/a><\/p>\n–Phase 3 trial of vaccine efficacy. RCT in 5 countries in Asia-Pacific region\u00a0(Indonesia, Malaysia, Philippines, Thailand, Vietnam), where 70% of the global dengue cases occur.\u00a0tetravalent recombinant\u00a0live-attenuated\u00a0vaccine (CYD-TDV) given at months 0, 6, 12.<\/p>\n
\u200b–Primary objective: assess protective efficacy against symptomatic, virologically-confirmed dengue at least 28 days after 3rd shot.\u00a025 month follow-up.<\/p>\n
\u00a0–10275 children aged 2-14 randomized to vaccine or placebo in 2:1 ratio. 250 cases of virologically-confirmed dengue developed (4.7% of the kids, highest in the Philippines and Thailand)<\/p>\n
–Vaccine had\u00a056.5% efficacy overall.<\/p>\n
–Efficacy higher in kids with pre-existing dengue neutralizing antibodies than those seronegative, in older than younger ages (33.7% in those 2-5 years old vs 74.4% in those 12-14). small differences by country (from 51.1% in Vietnam to 79.0% in Malaysia)<\/p>\n
–28 (5%) of the confirmed cases had dengue hemorrhagic fever, 8 in the vaccine group and 20 in the control group (but there were twice as many kids in the vaccine group with the 2:1 randomization), so that vaccine efficacy against hemorrhagic fever was 80% after only 1 injection and 88.5% after 3 injections. overall milder cases in the vaccinated group (eg, fewer\u00a0hosp admissions and\u00a0length of stay)<\/p>\n
\u200b–Pretty dramatic differences in efficacy by serotype: from nonsignificant 35% efficacy in serotype 2 infections, to (all significant) 50% for serotype 1, 75.3% for serotype 4 and 78.4% for serotype 3 (the most common infection was with serotype 1 (51 cases), followed by serotype 2 (38 cases), serotype 4 (17) and serotype 3 (10) — these differences in serotype efficacy explained the differences in vaccine efficacy in the different countries.<\/p>\n
–647 adverse events (402 in vaccine group and 245 in controls), with not much difference between groups<\/p>\n
So, pretty impressive results for serotypes 1,3,4. Unclear why no response to serotype 2 (mean titers were actually higher for 2 than the other serotypes), though a prior study in Thailand which did not find the vaccine to be effective was likely because of their predominance of serotype 2. Particularly notable\u00a0is the decrease in disease severity. Though the vast majority received 3 shots, those who received only one had pretty much the same efficacy (may be related to the fact that so many had already had dengue before, and the vaccine provided priming effect). This finding, as well as the fact that the vaccine worked best in those who already had neutralizing antibodies and in\u00a0older kids, suggests that the primary utility of the vaccine may be in those who already had infection and therefore\u00a0some pre-existing immunity, and that the target of the vaccine might\u00a0be in the highly-endemic regions.<\/p>\n
NEJM had a good clinical review of dengue (see\u00a0N Engl J Med 2012;366:1423-32<\/strong>)<\/p>\n Geoff<\/p>\n","protected":false},"excerpt":{"rendered":" Dengue vaccine […]<\/p>\n