Seasonal vaccination against malaria: a potential use for an imperfect malaria vaccine

Abstract

In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal. Seasonal malaria chemoprevention (SMC), which involves administration of a full course of malaria treatment to young children at monthly intervals during the high transmission season, is proving to be an effective malaria control measure in these areas. However, SMC does not provide complete protection and it is demanding to deliver for both families and healthcare givers. Furthermore, there is a risk of the emergence in the future of resistance to the drugs, sulfadoxine-pyrimethamine and amodiaquine, that are currently being used for SMC. Substantial progress has been made in the development of malaria vaccines during the past decade and one malaria vaccine, RTS,S/AS01, has received a positive opinion from the European Medicines Authority and will soon be deployed in large-scale, pilot implementation projects in sub-Saharan Africa. A characteristic feature of this vaccine, and potentially of some of the other malaria vaccines under development, is that they provide a high level of efficacy during the period immediately after vaccination, but that this wanes rapidly, perhaps because it is difficult to develop effective immunological memory to malaria antigens in subjects exposed previously to malaria infection. A potentially effective way of using malaria vaccines with high initial efficacy but which provide only a short period of protection could be annual, mass vaccination campaigns shortly before each malaria transmission season in areas where malaria transmission is confined largely to a few months of the year.

Keywords: Seasonal malaria chemoprevention; Seasonal malaria transmission; Seasonal malaria vaccination.

Fig. 1

A map of sub-Saharan Africa showing the areas where malaria transmission is likely to be highly seasonal. Orange areas indicate where more than 60% of annual rainfall occurs within 3 months of the year, and where malaria incidence is estimated to exceed 100 cases per 1000 children per year (adapted from Cairns et al. [1])

Fig. 2

The transient nature of the protection provided by RTS,S/AS01 and the associated changes in anti-CSP antibody concentration following primary vaccination and administration of a booster dose modelled on the basis of the results of phase 2 and phase 3 RTS,S/AS01 efficacy trials. d Shows anti-CSP antibody titres and f shows the percentage efficacy after primary and booster immunization. Red lines indicate infants vaccinated at the age of 6–12 weeks, blue lines those vaccinated at the age of 5–17 months. Dotted lines indicate children who recived a booster dose and solid lines those who did not (From White et al. [14])

Fig. 3

Design of a trial to compare the efficacy of seasonal vaccination with RTS,S/AS01 with SMC with SP + AQ and the impact of the two interventions combined on the incidence of clinical malaria in children under 5 years of age in Burkina Faso and Mali