The substantial declines in the burden of malaria in sub-Saharan Africa since 2010 have been attributed primarily to the rapid increase in access and usage of ITNs alongside slower but significant improvements in access to first-line treatment [33]. However, in more recent years the coverage of both interventions has plateaued, with the most recent household surveys analysed here demonstrating sub-optimal levels of ITN usage in many countries (at or below 50%) and even lower rates of treatment seeking for fever. In contrast, supported by the establishment of Gavi, The Vaccine Alliance in 2000 and the WHO’s EPI, uptake of childhood vaccination has steadily increased, although the past decade has seen some stagnation [16, 34]. As demonstrated in this analysis, vaccine coverage is high in most of the 20 countries studied here, with only two countries (Angola and Guinea) reporting under 50% uptake in their most recent DHS. Furthermore, these results demonstrate that coverage of vaccines administered via the EPI is substantially higher than usage of ITNs or fever treatment-seeking rates in the majority of countries, which is consistent with other research [9]. This creates an opportunity to consider roll-out strategies for the introduction of a malaria vaccine that are distinct to implementation programmes for other malaria interventions, to maximize impact by building on the wider reach of the Expanded Programme on Immunization.
As noted elsewhere, the utilization of malaria interventions and uptake of vaccination were found to be strongly associated with demographic and socioeconomic indicators [7,8,9,10, 14, 15]. Perhaps not surprisingly given higher malaria prevalence, those accessing and using ITNs were more likely to reside in rural areas, whereas as higher uptake of the DTP3 vaccine was associated with urban areas, possibly because of better access to healthcare facilities. Uptake of vaccination was also strongly associated with both the mother’s educational level and the wealth quintile, although as noted elsewhere, even at lower levels of education and wealth, the coverage of vaccination remained high [15]. Access to ITNs and ITN usage were also both strongly associated with the mother’s education status and wealth; however, having access to a net but not using it whilst also not being vaccinated with DTP3 was more strongly associated with lower educational status of mothers than with wealth. In addition, vaccine and ITN usage were found to be associated with age. Vaccine coverage may have improved over time so older children were less likely to be vaccinated than younger children and some net campaigns such as through antenatal care may better target younger children.
It was estimated that there are currently 33 million children in these 20 countries who are not using an ITN. Of these, 23 million (70% of the total children without an ITN) are estimated to have received the DTP3 vaccine and hence could be reached by the EPI. If the RTS,S malaria vaccine were made available to just these 23 million children, up to an estimated 9.7 million cases (or 0.44 cases per vaccinated child) could be averted each year (assuming all children who receive the DTP3 vaccine also receive the RTS,S). If the vaccine was also administered to those children with an ITN and who were vaccinated (24 million additional children), up to an estimated additional 10.8 million cases (or 0.47 cases per vaccinated child) could also be averted. Around 40% of the total cases would be averted in the Democratic Republic of Congo and Nigeria, countries which are currently contributing large proportions of malaria cases worldwide. This alone could represent a substantial reduction in the global malaria burden, reducing P. falciparum malaria cases by approximately 4%. However, there are still 9.8 million children across the countries considered who would remain unprotected by either intervention; these “missed children” should remain the focus of initiatives to improve equity in access to both malaria interventions and vaccination.
There are several limitations to this analysis. First, the analysis was only undertaken for 20 of the 27 malaria-endemic countries of interest within sub-Saharan Africa. Those countries for which data were not available contributed around 10% of the Africa malaria burden in 2018 and, therefore, also remain an important target for both malaria interventions and vaccination [6]. Second, due to the different survey designs, vaccination status and access to treatment were not able to be linked at the individual level. Given that both rely on access to health services, it is likely that these may be correlated, although levels of access to treatment remain well below vaccination rates. An alternative equity dimension that may be relevant to consider when targeting malaria interventions could be the potential for access to rapid treatment since both severe disease incidence and malaria mortality have been associated with the time taken to reach care [35, 36]. The definition of treatment used for this analysis is also limited because, depending on the policy within each country, in addition to presenting with a fever, a child would generally need to test positive for malaria using a rapid diagnostic test before being administered treatment. In addition, some health centres may occasionally experience treatment shortages. Third, to estimate the impact of the RTS,S vaccine on malaria burden the mean estimate of vaccine efficacy across the phase 3 trial sites over a 4-year period (39%) was applied. As usage of ITNs during the trial was very high, this likely represents an under-estimate of the true impact of the vaccine in this group of prospective children. A study using RTS,S trial and bed net usage in Malawi estimated that vaccinating a child in urban Lilongwe without a bed net could prevent 1.09 malaria cases, versus 0.67 for a child with a bed net. In rural Lilongwe, 2.59 and 1.59 malaria cases could be averted, respectively [37]. Furthermore, in taking this simple approach to estimating vaccine impact, the differences in vaccine efficacy by endemicity that were observed in the trial, and the potential age-shifting of cases that would likely occur as a result of reduced exposure to infection, were not considered [23]. Fourth, universal malaria vaccine coverage for children who receive the DTP3 vaccine was assumed, which results in the estimate of cases averted being an upper bound. The RTS,S vaccine is delivered as a four-dose schedule, with the first and third doses aligning with existing EPI contact points. Therefore, particularly in the early phase of vaccine introduction, it is possible that vaccine coverage could be lower than that of DTP3. In addition, coverage of the fourth dose is expected to be lower given the reduced health system contact as children become older. Some protection is still conferred from the first three doses (as demonstrated in the phase 3 trial), however the present analysis was not designed to estimate the impact of multiple levels of efficacies. Projected vaccine coverage will be informed by data from the pilot implementation studies as they progress. Fifth, this analysis was based on self-reported vaccination status and ITN use from household surveys across different years, which may not reflect the current situation; as such they are not directly comparable with estimates produced by the WHO (for malaria interventions and vaccination) and UNICEF (for vaccination), which are obtained by triangulating data from a number of sources. Several studies show that self-reporting vaccination often leads to a slight overestimate of true coverage [38, 39]. Finally, this analysis scaled up restricted surveys on intervention coverage in order to obtain regional/national estimates of malaria cases that would be prevented if RTS,S was widely deployed. While this extrapolation of survey data introduces considerable uncertainty, these estimates still provide an indication of wider future RTS,S impact.