BACKGROUND
Yellow fever vaccine is highly effective with a single dose, but vaccine supply is limited. The minimum dose requirements for seroconversion remain unknown.
METHODS
In this double-blind, randomized, noninferiority trial in Uganda and Kenya, we assigned adults with no history of yellow fever vaccination or infection to receive vaccination with the Institut Pasteur de Dakar 17D-204 yellow fever vaccine at a standard dose (13,803 IU) or at a fractional dose of 1000 IU, 500 IU, or 250 IU. The primary outcome was seroconversion at 28 days after vaccination with each fractional dose as compared with the standard dose, evaluated in a noninferiority analysis. Seroconversion was defined as an antibody titer at day 28 that was at least four times as high as the antibody titer before vaccination, as measured by a plaque reduction neutralization test. We conducted noninferiority analyses in the per-protocol and intention-to-treat populations. Noninferiority was shown if the lower boundary of the 95% confidence interval for the difference in the incidence of seroconversion between the fractional dose and the standard dose was higher than -10 percentage points.
RESULTS
A total of 480 participants underwent randomization (120 participants in each group). The incidence of seroconversion was 98% (95% confidence interval [CI], 94 to 100) with the standard dose. The difference in the incidence of seroconversion between the 1000-IU dose and the standard dose was 0.01 percentage points (95% CI, -5.0 to 5.1) in the intention-to-treat population and -1.9 percentage points (95% CI, -7.0 to 3.2) in the per-protocol population; the corresponding differences between the 500-IU dose and the standard dose were 0.01 percentage points (95% CI, -5.0 to 5.1) and -1.8 percentage points (95% CI, -6.7 to 3.2), and those between the 250-IU dose and the standard dose were -4.4 percentage points (95% CI, -9.4 to 0.7) and -6.7 percentage points (95% CI, -11.7 to 1.6). A total of 111 vaccine-related adverse events were reported: 103 were mild in severity, 7 were moderate, and 1 was severe. The incidence of adverse events was similar in the four groups.
CONCLUSIONS
A yellow fever vaccination dose as low as 500 IU was noninferior to the standard dose of 13,803 IU for producing seroconversion within 28 days.
Ebola haemorrhagic fever (EHF) is infamous for its high case-fatality proportion (CFP) and the ease with which it spreads among contacts of the diseased. We describe the course of the EHF outbreak in Masindi, Uganda, in the year 2000, and report on response activities.
METHODS
We analysed surveillance records, hospital statistics, and our own observations during response activities. We used Fisher's exact tests for differences in proportions, t-tests for differences in means, and logistic regression for multivariable analysis.
RESULTS
The response to the outbreak consisted of surveillance, case management, logistics and public mobilisation. Twenty-six EHF cases (24 laboratory confirmed, two probable) occurred between October 21st and December 22nd, 2000. CFP was 69% (18/26). Nosocomial transmission to the index case occurred in Lacor hospital in Gulu, outside the Ebola ward. After returning home to Masindi district the index case became the origin of a transmission chain within her own extended family (18 further cases), from index family members to health care workers (HCWs, 6 cases), and from HCWs to their household contacts (1 case). Five out of six occupational cases of EHF in HCWs occurred after the introduction of barrier nursing, probably due to breaches of barrier nursing principles. CFP was initially very high (76%) but decreased (20%) due to better case management after reinforcing the response team. The mobilisation of the community for the response efforts was challenging at the beginning, when fear, panic and mistrust had to be countered by the response team.
CONCLUSIONS
Large scale transmission in the community beyond the index family was prevented by early case identification and isolation as well as quarantine imposed by the community. The high number of occupational EHF after implementing barrier nursing points at the need to strengthen training and supervision of local HCWs. The difference in CFP before and after reinforcing the response team together with observations on the ward suggest a critical role for intensive supportive treatment. Collecting high quality clinical data is a priority for future outbreaks in order to identify the best possible FHF treatment regime under field conditions.