Immunogenicity and toxicity of yellow fever vaccines : a systematic review

Abstract

BACKGROUND Yellow fever (YF) is a non-contagious, mosquito borne haemorrhagic fever caused by a single-strand RNA flaviviruses. YF is endemic in the tropics primarily in South America and Africa although the vectors are present in Asia, Europe, Pacific and Middle East. Human beings serve as viraemic hosts for mosquito infection. YF carries a high burden of disease, particularly in developing countries with up to 200 000 cases reported annually and a case fatality rate of 20-50%.The pathogenesis is poorly understood and little research has been conducted .There is no known cure or specific treatment for YF and prevention remains the mainstay the public health approach in terms of effectiveness and cost. The World Health Organisation (WHO) conventions have made vaccination mandatory for travel to endemic countries to prevent outbreaks and transmission to susceptible individuals. YF vaccine is one of the oldest vaccines known and in use and is derived from an attenuated virus strain 17D originally produced in the 1930s. The vaccine has historically been considered effective and safe. However, severe life-threatening side effects to the vaccine have been reported in the past 20 years. Acute vaccinerelated viscerotropic (AVD) and neurotropic (AND) side effects have been reported globally particularly in the elderly. The adverse reactions typically present as YF- like illness resulting in multi-organ failure with death as a possible outcome. OBJECTIVES To estimate the immunogenicity and toxicity of 17D and 17DD YF vaccines by summarizing the available data from randomised controlled trials. STUDY DESIGN A summary of randomized controlled trials (RCT) of YF vaccine immunogenicity and safety and tolerability was obtained using standard meta-analysis methodologies. METHODS A comprehensive literature search was conducted in order to identify trial that met with predetermined inclusion and exclusion criteria. Features of each study were noted taking into account the type of vaccine used, the duration of follow up, assignment to intervention, blinding and randomization methods. Three studies were eventually pooled and effect size estimates reported in each study were noted and analysed using meta-analysis software, MIX. Reports on the side effects post vaccination were summarized and analysed. RESULTS The difference in outcomes between the standard 17DD YF vaccines intervention, traded as Arilvax ® and the 17D YF vaccines traded as YF-Vax ® and Stamaril ® was negligible in terms of effect size. Effect sizes that considered the means between the treatment and control groups demonstrated a difference that favoured the control group viz. Arilvax ®. The pooled results also showed significant publication bias most likely attributable to the small number of studies considered. The pooled and annotated forest plot supported the available literature in confirming the effectiveness of YF vaccines in conferring immunity. A summary of tolerability events CONCLUSIONS This study has confirmed the effectiveness of YF vaccines in terms of immunogenicity and also demonstrated that YF vaccines are well tolerated and safe The small number of study units considered in this study presented challenges for analysis and for interpretation but highlighted the need for more research to be conducted in this area. The results are in keeping with the existing body of evidence supporting the robustness of the immunological response to YF vaccination. The safety and tolerability of the vaccine established in this study was also consistent with known literature. There are important implications for further research and implementation that became evident such as the need for further studies to be conducted in African populations where the burden of disease is highest.