Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak - Final Report.

BACKGROUND: In 2016, the response to a yellow fever outbreak in Angola and the Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As a result, a fractional dose of the 17DD yellow fever vaccine (containing one fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The goal of this study was to assess the immune response to the fractional dose in a large-scale campaign. METHODS: We recruited participants in four age strata at six vaccination sites. We assessed neutralizing antibody titers against yellow fever virus in blood samples obtained before vaccination and at 1 month and 1 year after vaccination, using a plaque reduction neutralization test with a 50% cutoff (PRNT50). Participants with a PRNT50 titer of 10 or higher were considered to be seropositive. Those with a baseline titer of less than 10 who became seropositive at follow-up were classified as having undergone seroconversion. Participants who were seropositive at baseline and who had an increase in the titer by a factor of 4 or more at follow-up were classified as having an immune response. RESULTS: Among 716 participants who completed the 1-month follow-up, 705 (98%; 95% confidence interval [CI], 97 to 99) were seropositive after vaccination. Among 493 participants who were seronegative at baseline, 482 (98%; 95% CI, 96 to 99) underwent seroconversion. Among 223 participants who were seropositive at baseline, 148 (66%; 95% CI, 60 to 72) had an immune response. Lower baseline titers were associated with a higher probability of having an immune response (P<0.001). Among 684 participants who completed the 1-year follow-up, 666 (97%; 95% CI, 96 to 98) were seropositive for yellow fever antibody. The distribution of titers among the participants who were seronegative for yellow fever antibody at baseline varied significantly among age groups at 1 month and at 1 year (P<0.001 for both comparisons). CONCLUSIONS: A fractional dose of the 17DD yellow fever vaccine was effective at inducing seroconversion in participants who were seronegative at baseline. Titers remained above the threshold for seropositivity at 1 year after vaccination in nearly all participants who were seropositive at 1 month after vaccination. These findings support the use of fractional-dose vaccination for outbreak control. (Funded by the U.S. Agency for International Development and the Centers for Disease Control and Prevention.).

Yellow Fever Outbreak - Kongo Central Province, Democratic Republic of the Congo, August 2016.

On April 23, 2016, the Democratic Republic of the Congo's (DRC's) Ministry of Health declared a yellow fever outbreak. As of May 24, 2016, approximately 90% of suspected yellow fever cases (n = 459) and deaths (45) were reported in a single province, Kongo Central Province, that borders Angola, where a large yellow fever outbreak had begun in December 2015. Two yellow fever mass vaccination campaigns were conducted in Kongo Central Province during May 25-June 7, 2016 and August 17-28, 2016. In June 2016, the DRC Ministry of Health requested assistance from CDC to control the outbreak. As of August 18, 2016, a total of 410 suspected yellow fever cases and 42 deaths were reported in Kongo Central Province. Thirty seven of the 393 specimens tested in the laboratory were confirmed as positive for yellow fever virus (local outbreak threshold is one laboratory-confirmed case of yellow fever). Although not well-documented for this outbreak, malaria, viral hepatitis, and typhoid fever are common differential diagnoses among suspected yellow fever cases in this region. Other possible diagnoses include Zika, West Nile, or dengue viruses; however, no laboratory-confirmed cases of these viruses were reported. Thirty five of the 37 cases of yellow fever were imported from Angola. Two-thirds of confirmed cases occurred in persons who crossed the DRC-Angola border at one market city on the DRC side, where ≤40,000 travelers cross the border each week on market day. Strategies to improve coordination between health surveillance and cross-border trade activities at land borders and to enhance laboratory and case-based surveillance and health border screening capacity are needed to prevent and control future yellow fever outbreaks.

The role of the economic environment in kidney transplant outcomes.

The relationship between global economic indicators and kidney allograft and patient survival is unknown. To investigate possible relationships between the two, we analyzed kidney transplant recipients receiving transplants between January of 1995 and December of 2002 (n = 105,181) in the USA using Cox regression models. We found that: The Dow Jones Industrial Average had a negative association with outcome at one year post-transplant (HR 1.03 and 1.06, p < 0.001 for graft and recipient survival, respectively) but changed to a protective effect in the late period (HR 0.77, p < 0.001, and HR 0.83, p < 0.001 for graft and recipient survival, respectively, five yr after transplantation). Unemployment rate had a protective effect at the time of transplantation (HR 0.97, p < 0.005) and at one year after transplantation (HR 0.95, p < 0.005) but changed to the opposite in the late period at the fifth post-transplant year (HR 1.35, p < 0.001, and HR 1.20, p < 0.001, for graft and recipient survival respectively). The Consumer Price Index measured at different post-transplant time points seems to have had a protective effect on the graft (HR 0.77, p < 0.001 at five yr) and recipient (HR 0.83, p < 0.001 at five yr) survival. Beyond three yr after transplantation, when some of the recipients lose Medicare benefits, economic downturns might have a negative association with the kidney graft and recipient survival.

The association between recipient alcohol dependency and long-term graft and recipient survival.

BACKGROUND: The causative role of alcohol consumption in renal disease is controversial, and its effect on renal graft and recipient survival has not been previously studied. METHODS: We analysed the association between pre-transplant [at the time of end-stage renal disease (ESRD) onset] alcohol dependency and renal graft and recipient survival. The United States Renal Data System (USRDS) records of kidney transplant recipients 18 years or older transplanted between 1 January 1995 and 31 December 2002 were examined. We used Kaplan-Meier analysis and Cox regression models adjusted for covariates to analyse the association between pre-transplant alcohol dependency and graft and recipient survival. RESULTS: In an entire study cohort of 60 523, we identified 425 patients with a history of alcohol dependency. Using Cox models, alcohol dependency was found to be associated with increased risk of death-censored graft failure [hazard ratio (HR) 1.38, P < 0.05] and increased risk of transplant recipient death (HR 1.56, P < 0.001). Subgroup analysis demonstrated an association of alcohol-dependency with recipient survival and death-censored graft survival in males (but not in females), and in both white and non-white racial subgroups. CONCLUSIONS: We concluded that alcohol dependency at the time of ESRD onset is a risk factor for renal graft failure and recipient death.

The impact of recipient history of cardiovascular disease on kidney transplant outcome.

Cardiovascular disease (CVD) leads to increased mortality rates among renal transplant recipients; however, its effect on allograft survival has not been well studied. The records from the United States Renal Data System and the United Network for Organ Sharing from January 1, 1995, through December 31, 2002, were examined in this retrospective study. The outcome variables were allograft survival time and recipient survival time. The primary variable of interest was CVD, defined as the presence of at least one of the following: cardiac arrest, myocardial infarction, dysrhythmia, congestive heart failure, ischemic heart disease, peripheral vascular disease, and unstable angina. The Cox models were adjusted for potential confounding factors. Of the 105,181 patients in the data set, 20,371 had a diagnosis of CVD. The presence of CVD had an adverse effect on allograft survival time (HR 1.12, p < 0.001) and recipient survival time (HR 1.41, p < 0.001). Among the subcategories, congestive heart failure (HR 1.14, p < 0.005) and dysrhythmia (HR 1.26, p < 0.05) had adverse effects on allograft survival time. In addition to increasing mortality rates, CVD at the time of end-stage renal disease onset is also a significant risk factor for renal allograft failure. Further research is needed to evaluate the role of specific forms of CVD in allograft and recipient outcome.