There are five Plasmodium species known to cause human malaria in Africa. The dominant species is Plasmodium falciparum, causing over 246 million clinical cases each year in Africa. It is this species that is currently the target of elimination efforts.
A challenge to malaria elimination is the large reservoir of asymptomatic infections that fuel malaria transmission to anopheline mosquitoes. These partially immune and asymptomatic individuals can be infected with P. falciparum in combination with what are known as the minor species, Plasmodium malariae and Plasmodium ovale spp.
A more complex reality
With the application of molecular surveillance, it is increasingly evident that individuals of all ages can carry multiple malaria parasite species at once, along with multiple genetically-distinct parasites of the same species. In reality, we’re not dealing with just one parasite but a diverse community of malaria parasites in a person living in Africa. The extent of this diversity is currently unknown but critical to understand to efficiently achieve malaria elimination.
This is especially true in high-transmission areas, where virtually everyone is infected and constantly exposed to new infections. For over a decade, our team has studied P. falciparum infections in asymptomatic people and we’ve discovered this hidden reservoir to be far larger and more diverse than we thought. Importantly, this complex reservoir fuels a highly-resilient parasite population that dampens the impact of short-term control efforts.
So we asked ourselves, what about the other parasite species?
A fresh perspective
Instead of oversimplifying, we decided to think differently. What if we treat malaria infections more like metagenomes? As a community of different parasite species and strains. We took inspiration from other fields such as microbiome research and began conceptually framing malaria infections as rich, complex communities of microorganisms within a single ecological niche (i.e. host).
This shift in perspective raised a key question. Just how complex are infections in high-transmission settings? How prevalent are the major and minor species, and how many strains do they include? Equally important, if our goal is to eliminate the disease, what’s lurking in the asymptomatic reservoir?
What we found
These questions led to this study in the Bongo District in northern Ghana. Our collaborative team uncovered extensive hidden reservoirs of malaria parasites, the majority of which are subclinical and submicroscopic, yet still potentially capable of sustaining transmission (in the case of P. falciparum) or posing future risks (in the case of minor species). Current standard approaches underestimate both how widespread these parasites are and the true complexity of infections.
Applying a metagenomic lens, we found that people often carry multiple species and diverse genotypes simultaneously, with a small subset having extremely complex infections. We believe this pattern likely also exists in other high-transmission areas globally.
We also noted a significant gap. Global surveillance tools like the Malaria Atlas Project currently don’t include data on minor species at all and, without this information, policymakers may be making decisions without a full understanding of the parasite landscape and its complexities.
Why it matters
We submitted this work to the Health in Africa collection because malaria disease burden is heaviest here and this is also where understanding within-host complexity is most relevant.
This study is a reminder that malaria in high-transmission areas is not the case of one parasite, but a rich, complex ecosystem. Ignoring this complexity risks underestimating the problem, leading to ineffective solutions. For malaria elimination to succeed, we need surveillance and mapping to accurately capture the asymptomatic reservoir of all species, not just the usual suspects.
Our next steps should be to push for inclusion of minor species in global datasets and to refine methods to measure complexity accurately, including hidden malaria reservoirs.