Cost-Effectiveness of the Introduction of a Pre-Erythrocytic Malaria Vaccine into the Expanded Program on Immunization in Sub-Saharan Africa: Analysis of Uncertainties Using a Stochastic Individual-Based Simulation Model of Plasmodium falciparum Malaria

Abstract

We predict the effects of introduction of a pre-erythrocytic vaccine against Plasmodium falciparum into a malaria-endemic population in Africa. We use a stochastic simulation model that includes components of transmission, parasitology, and clinical epidemiology of malaria and was validated using the results of field trials of the RTS,S/AS02A vaccine. The results suggest that vaccines with efficacy similar to that of RTS,S/AS02A have a substantial impact on malaria morbidity and mortality during the first decade after their introduction, but have negligible effects on malaria transmission at levels of endemicity typical for sub-Saharan Africa. The main benefits result from prevention of morbidity and mortality in the first years of life. Vaccines with very short half-life or low efficacy may have little overall effect on incidence of severe malaria. A similar approach can be used to make predictions for other strategies for deployment of the vaccine and to other types of malaria vaccines and interventions.

The public health impact of malaria vaccine RTS,S in malaria endemic Africa: country-specific predictions using 18 month follow-up Phase III data and simulation models

“…9 and 10 and Additional file 2: Figures S16-S23). Previous analyses have found that public health impact of pre-erythrocytic vaccines will be highest at intermediate transmission intensities, where there are enough infections to make prevention worthwhile but where the parasite challenge is not so great as to drown the effect of the vaccine [9, 17]. The current analysis indicates that there is a strong general increase in impact with average level of transmission at the country level, indicating that in only a few countries (for example, Burkina Faso) are substantial proportions of the population in the range where vaccine effectiveness is compromised by an overwhelming parasitological challenge.…”

“…The reason is that a recommendation on the use of RTS,S is expected as early as the end of 2015. Previously the public health impact of introducing the RTS,S vaccine into routine vaccination schedules in Africa has been difficult to predict because available clinical trial data were inadequate for accurately estimating the kinetics of vaccine protection, and this uncertainty in the vaccine profile meant that geographically specific predictions of likely impact [17] were mainly of value to indicate general principles and data gaps. Site- and time- specific data from 18 months of follow-up of the Phase III trials [1] have now enabled us to estimate the vaccine profile accurately enough for quantitative predictions of impact at national level to have sufficient plausibility for guiding policy decision as well as for informing subsequent implementation decisions by ministries of health.…”

“…These models take into account levels of herd immunity and long-term effects of vaccination or other infection blocking interventions, such as deferral of events to older ages, and suggest that vaccination with pre-erythrocytic vaccines such as RTS,S via the Expanded Program of Immunisation (EPI), could substantially reduce paediatric morbidity and mortality during the first decade of vaccine use. The benefits of RTS,S are likely to be highest with levels of transmission entomological inoculation rate (EIR) between 2 to 50, which corresponds to intermediate levels of transmission in our model [9, 11, 14–17]. The EIR at the start of a vaccination program is critical, irrespective of how it has come about, or of whether transmission is increasing or decreasing [18], while herd immunity is likely to be negligible [9, 11].…”

“…The EIR at the start of a vaccination program is critical, irrespective of how it has come about, or of whether transmission is increasing or decreasing [18], while herd immunity is likely to be negligible [9, 11]. A probabilistic sensitivity analysis [17] indicated that the EIR distribution, decay rate of vaccine effects and model for severe disease are important drivers of uncertainty in public health impact.…”

Malaria vaccine

“…According to this report, the use of RTS,S/AS01 could be highly cost-effective in many settings with low to moderate transmission, depending on the price of the vaccine and the duration of the vaccine's protection. 13 Malaria Vaccine Technology Road Map 2013 has envisaged the world as aiming for a licensed vaccine by 2030 that would reduce malaria cases by 75% and be capable of eliminating malaria.…”