Ring Vaccination During DRC Ebola Outbreak Reinforces Vaccine Efficacy

Non-randomized evidence on standard Ebola virus disease (EVD) control measures and ring vaccination in eastern Democratic Republic of Congo (DRC) reinforced previous randomized evidence of vaccine efficacy 10 or more days after vaccination, researchers found.

Among 265,183 participants who were vaccinated with the Ebola Zaire vaccine (Ervebo) from August 2018 through January 2020, the EVD onset rate during days 10 to 29 was 0.16 per 1,000 (in 32 of 194,019 participants) among contacts as well as contacts-of-contacts who were still disease-free at day 10, reported Jean-Jacques Muyembe, MD, PhD, of Université de Kinshasa in DRC, and colleagues.

This rate was lower than the rate of 4.64 per 1,000 (in 21 of 4,528 participants), previously seen among ring members in Guinea when vaccination was delayed until 21 days after ring formation (rate ratio 0.04, 95% CI 0.02-0.06), they noted in the New England Journal of Medicine.

“Given the size of the outbreak [in DRC from 2018 to 2020], this situation provided an opportunity to assess the efficacy of the combined effects of ring vaccination plus case isolation and the other infection-control methods,” Muyembe and colleagues wrote. “Ring members (including all identified contacts and contacts-of-contacts) were vaccinated immediately with no randomized comparator group, so no unbiased assessment of efficacy was expected.”

“Because the 2018-2020 outbreak persisted for so long, some 200,000 members of almost 2,000 rings were vaccinated and followed for EVD onset (more than 20 times as many recipients of immediate vaccination as were included in the Guinea study),” they wrote. “Hence, the DRC findings with respect to the incidence of EVD during two time periods — from 0 to 9 days and from 10 days or more after vaccination — can both be assessed reliably.”

In the study by Muyembe and colleagues, there were 434 cases of EVD (0.2 per ring) diagnosed, and almost all of these cases were within 0 to 9 days (380) or 10 to 29 days (32) after vaccination. There were 22 additional cases diagnosed after day 29 during an average of 170 more days of follow-up.

The sooner that control measures — including ring vaccination — were initiated after EVD onset in an index case, the sooner EVD rates fell, Muyembe and colleagues reported.

In an analysis that compared two similar-sized groups — 31,027 contacts who were vaccinated within 8 days after an index case (median 6 days) and 26,536 who were vaccinated later (median 12 days) — a comparison could not be made between these groups at either the period within 12 days after an index case or 24 days or more after an index case because the risks were so low in both groups.

However, during the periods between 12 and 17 days as well as between 18 and 23 days after an index case, incidence rate was lower in the earlier-vaccination group than in the later-vaccination group. There were 68 cases versus 103 during days 12 through 17 after an index case (rate ratio 0.55, 95% CI 0.40-0.76) and two cases versus 53 during days 18 through 23 (rate ratio 0.03, 95% CI 0.01-0.11).

Additional findings included that EVD risk among contacts was lower in males than in females (rate ratio 0.62, 95% CI 0.50-0.77), lower in children than in adults, similar in pregnant women compared with men and nonpregnant women, and lower if an index case was a vaccine recipient (rate ratio 0.43, 95% CI 0.29-0.65), Muyembe and colleagues reported. Within each subgroup, there was a decrease in the incidence of EVD approximately 10 days after vaccination.

Among vaccinated healthcare or front-line workers within the rings, there was a 30-day rate of EVD of 1.9 per 1,000 (in 22 of 11,835 workers), similar to a rate of 2.0 per 1,000 among other contacts or contacts-of-contacts (in 364 of 182,564 others). After day 30, respective rates were 0.4 per 1,000 (in 5 of 11,835 workers) compared with 0.1 per 1,000 (in 17 of 182,564 others).

Vaccinated healthcare or front-line workers who were not in rings had a 30-day rate of EVD of 0.1 per 1,000 (in 8 of 58,861 workers) and a rate of 0.3 per 1,000 (in 20 of 58,861 workers) after day 30.

Overall, among 102,515 vaccine recipients who were monitored on days 0, 3, and 21 for safety, there were no safety concerns identified with the vaccine, Muyembe and colleagues reported.

“Ring vaccination is effective, operationally efficient, and dose-sparing in comparison with population vaccination and is practicable for teams operating in insecure contexts,” they concluded.

For the study, researchers assessed the incidence of EVD within the first 9 days after vaccination, during days 10 to 29, and at later time periods. They established 1,853 rings around new cases or clusters within 21 days after onset of symptoms in the index case and offered vaccination to the ring members. Those who received vaccines were monitored for EVD onset until the end of the outbreak in mid-2020.