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.
Zomba Central Hospital, Malawi.
OBJECTIVE
To determine diagnostic management and outcomes of pulmonary tuberculosis (PTB) suspects admitted to adult wards.
DESIGN
A retrospective, cross-sectional review of medical records of patients admitted to hospital between July and September 2010.
RESULT
There were 141 PTB suspects. Sputum examination was requested and performed in 67 (48%) suspects, but none were smear-positive. Chest X-ray (CXR) was requested and performed in 26 (39%) suspects whose sputum smears were negative. Eleven suspects had a CXR suggestive of PTB: two were started on TB treatment and eight died before treatment started. Human immunodeficiency virus (HIV) status was known for 50 patients (35% of all suspects) on admission, all of whom were HIV-positive. HIV testing was requested for 37 patients, but was only performed in 12, five of whom were HIV-positive. Only one patient was referred for antiretroviral treatment. There were 41 (29%) deaths, eight of whom had probable TB and were not treated. In the remaining 33 patients who died, only nine (27%) had sputum smears examined and four (12%) had a CXR.
CONCLUSION
The study shows inadequacies in the diagnostic management of PTB suspects in the Zomba Central Hospital, but suggests opportunities for improvement.