Status of malaria vaccine development
Policy-makers in countries where malaria is endemic are facing increasingly complex decisions about which vaccines and malaria prevention measures to include in national immunization and malaria control programmes. Several new vaccines and malaria preventive measures are already competing for limited financing in developing countries. African countries with endemic malaria should be ready to make a national policy decision on the introduction of RTS,S/AS01, a first-generation malaria vaccine, by 2015. (1) If clinical trials progress according to schedule, that same year the World Health Organization (WHO) will issue a policy recommendation on the public health use of this vaccine based on the findings of the full Phase III efficacy trial in progress, which will be available in late 2014. (2) The vaccine's manufacturers are targeting infants in malaria-endemic African countries who undergo routine vaccination through the Expanded Programme on Immunization (EPI) at 6, 10 and 14 weeks of age, with the possibility of a booster dose being needed at 9-18 months. At present WHO is assessing the evidence base for a policy position on this vaccine. The type of critical data that it will take into account during this process is shown in Box 1.
Cost-effectiveness is an important consideration in public health decision-making. This article summarizes critical parameters driving malaria vaccine cost-effectiveness predictions and discusses major uncertainties that remain in the cost-effectiveness modelling arena. It also highlights the need for ongoing work by modelling groups to further refine cost-effectiveness predictions.
Box 1. Critical questions for formulation of policy on a new
* What is the evidence that RTS,S/AS01 vaccination is not
associated with serious adverse reactions in children aged less
than 17 months?
* What level of protection against clinical malaria does RTS,S/AS01
confer on infants 6 to 14 weeks of age, over 30 months of
follow-up, when co-administered with routine infant vaccines in
sub-Saharan African settings?
* What is the evidence that a booster dose of RTS,S/AS01 at 18
months is needed to maintain benefit following a 3-dose primary
* Is there evidence that the efficacy of RTS,S/AS01 varies in
different transmission settings?
* Do available data support a WHO policy recommendation to
introduce RTS,S/AS01 into routine immunization programmes in
malaria-endemic countries? What is the optimal schedule? What
flexibility is there for interrupted and delayed schedules?
* What is the evidence that co-administration leads to non-inferior
responses for both RTS,S/ AS01 and existing EPI vaccines?
* What is the evidence that RTS,S/AS01, when administered at 6,10
and 14 weeks of age, provides at least as much protection against
hepatitis B as the available hepatitis B vaccines?
* How cost-effective is RTS,S/AS01 as a preventive measure in
addition to LLINs?
EPI, Expanded Programme on Immunization; LLIN, long lasting
insecticide-treated nets; WHO, World Health Organization.
The RTS,S/AS01 vaccine is intended for use in conjunction with existing measures for malaria prevention, such as the use of long-lasting insecticide-treated nets (LLINs), which is known to be highly cost-effective. A recent systematic review (3) of cost-effectiveness studies of the use of insecticide-treated nets reported a median cost per disability-adjusted life year (DALY) averted of 27 United States dollars (US$) (range: 8-110). LLINs have been associated with reduced all-cause mortality in African children under the age of5 years (4) and are known to greatly reduce malaria transmission. (5) So, in countries that have successfully scaled up the use of LLINs, implemented rapid malaria diagnostic testing and facilitated access to effective artemisinin-based combination therapy, how will policy-makers decide whether or not to introduce RTS,S/AS01 as an additional malaria control measure? …