Uncovering the Silent Spread of Plasmodium ovale and Plasmodium malariae in Africa
An Introduction to Malaria's Overlooked Parasites
When we think of malaria in Africa, our attention immediately focuses on Plasmodium falciparum—the deadly parasite responsible for the majority of severe cases and deaths. This singular focus is understandable but has created what scientists might call "the ears of the African elephant" phenomenon: while we've been staring at the imposing bulk of P. falciparum, we've largely overlooked other significant parasites that have been hiding in plain sight.
Recent groundbreaking research from West Africa reveals an unexpected reality—high rates of infection with Plasmodium ovale and Plasmodium malariae, even in apparently healthy populations 1 . These neglected species are circulating at astonishing rates, forming complex mixed infections, and potentially complicating malaria elimination efforts across the continent.
The story of these cryptic parasites isn't just about scientific curiosity—it has real-world implications for how we diagnose, treat, and ultimately hope to eliminate malaria from its last strongholds.
With mass vaccination campaigns against P. falciparum on the horizon, understanding the full spectrum of human-infecting Plasmodium species has never been more critical. What researchers are discovering challenges fundamental assumptions about malaria transmission and reminds us that in science, what we don't know can be just as important as what we do know.
Traditional malaria surveillance has created a significant blind spot by focusing primarily on symptomatic P. falciparum infections, missing the silent transmission of other Plasmodium species.
Uncovering Malaria's Hidden Realm
The groundbreaking research that first revealed the astonishing prevalence of these cryptic parasites took place in Benin, West Africa 1 . Published in Malaria Journal, this study took a novel approach to malaria surveillance by focusing on asymptomatic blood donors—a population that typically flies under the radar of conventional malaria monitoring systems that target febrile patients.
Traditional malaria surveillance predominantly focuses on symptomatic cases, creating a significant blind spot in our understanding of transmission dynamics. Asymptomatic individuals can serve as silent reservoirs of infection, maintaining transmission cycles even when clinical cases appear to decline.
The Benin study leveraged this approach by examining 1,235 blood donations collected over ten months across six departmental blood centers 1 . This large sample size, collected across different seasons, provided an unprecedented window into the true prevalence of all Plasmodium species circulating in a supposedly healthy adult population.
The research team faced a significant challenge: how to accurately detect exposure to specific Plasmodium species when microscopy and rapid diagnostic tests are notoriously unreliable for non-falciparum infections, especially at low parasite densities.
Their innovative solution centered on developing species-specific recombinant proteins for serological testing 1 .
The team engineered recombinant versions of MSP1 (merozoite surface protein 1) for P. falciparum, P. ovale, and P. malariae, plus AMA1 (apical membrane antigen 1) for P. falciparum 1 . These proteins, critical to the parasite's invasion of red blood cells, elicit strong antibody responses in infected individuals.
By using these recombinant antigens in ELISA tests (dubbed RecELISA), the researchers could identify species-specific antibody responses, effectively creating a historical record of exposure to each parasite species, even if the infection had been cleared or was present at undetectable levels 1 .
The methodology was rigorously validated using samples from French travelers with confirmed malaria infections 1 , ensuring the tests could accurately distinguish between the different Plasmodium species before being applied to the Beninese samples.
Widespread Exposure to Cryptic Species
When the results from the Benin study were analyzed, they revealed a startling picture of malaria transmission that had previously been almost entirely overlooked. The high seroprevalence of non-falciparum species suggested these parasites were circulating far more widely than traditional surveillance had indicated.
P. falciparum
(native antigen)
P. malariae
P. ovale
All three species
Based on 1,235 microscopically negative blood donors in Benin 1
Among the 1,235 microscopically negative African blood donors, the research team found that 85% presented antibodies directed to native P. falciparum antigen 1 . But the real surprises emerged when they looked at the non-falciparum species:
These figures were remarkably high for parasites traditionally considered to be "minor" players in the malaria landscape. The findings suggested that exposure to these species was not the exception but rather the norm in this population.
The surprising findings from Benin were later corroborated by a massive 2018 nationwide study in Nigeria, which examined blood samples from 31,234 children under 15 years of age 4 .
This research employed sophisticated molecular diagnostic techniques including PCR to detect active infections, along with serological methods similar to the Benin study.
| Parameter | P. malariae | P. ovale |
|---|---|---|
| Active Infection Rate | 6.6% | 1.4% |
| Seroprevalence | 34.2% | 12.1% |
Perhaps most notably, the Nigerian study found that the vast majority of non-falciparum infections were mixed with P. falciparum 4 . This finding has important implications for treatment, as standard therapies for falciparum malaria may not completely clear these co-infecting species, particularly the dormant liver stages of P. ovale.
Key Research Reagents for Uncovering Hidden Parasites
The groundbreaking discoveries about non-falciparum malaria species depended on specialized research tools and reagents that enabled scientists to detect what conventional methods missed. Here we explore the key components of the "scientific toolkit" that made these insights possible.
Rethinking Malaria Control in Africa
The discovery of widespread exposure to P. ovale and P. malariae has profound implications for malaria control and elimination strategies across Africa. These findings come at a critical juncture, as many countries scale up interventions targeting P. falciparum specifically.
With the ongoing rollout of the RTS,S/AS01 malaria vaccine targeting P. falciparum, the high prevalence of non-falciparum species presents a potential complication 2 .
As of March 2023, approximately 1.5 million children had received at least one dose of the RTS,S vaccine in Ghana, Kenya, and Malawi 2 . While this represents significant progress, the vaccine offers no protection against P. ovale or P. malariae, meaning these species could potentially fill the ecological niche vacated by P. falciparum as vaccine coverage increases.
The Benin researchers specifically noted that determining seroprevalence for these cryptic species is "an appropriate tool to estimate their incidence, at the eve of upcoming anti-P. falciparum vaccination campaigns" 1 . This suggests that baseline data on non-falciparum transmission should be collected in areas implementing mass vaccination to monitor for potential epidemiological shifts.
Current malaria diagnosis in many African countries, including Nigeria, relies predominantly on rapid diagnostic tests (RDTs) that detect HRP2 antigen specific to P. falciparum 4 .
These tests leave non-falciparum infections undiagnosed and untreated, creating a reservoir of infection that sustains transmission.
Similarly, standard treatments for uncomplicated malaria in Nigeria are artemisinin combination therapies (ACTs) with broad-spectrum activity against non-falciparum Plasmodium species 4 . However, these treatments do not target the hypnozoites of P. ovale, which require an 8-aminoquinoline such as primaquine or tafenoquine for successful anti-relapse therapy 4 .
The widespread prevalence of P. ovale revealed by serological studies suggests that many patients may be experiencing relapses that are misclassified as new infections.
The findings on non-falciparum malaria come as some African regions make significant progress toward elimination. Lagos State, Nigeria, recently announced that it is nearing malaria elimination, positioning itself to become the first West African geopolitical zone to achieve this milestone 6 .
Lagos has diligently waged a "war against malaria" for the past 20 years, with remarkable results: malaria prevalence among fever patients has plummeted from 15-20% to just 1-2% 6 . The state's strategy has transitioned to a "test, treat, and track" approach that prioritizes accurate diagnosis of the actual cause of fever, which in Lagos is now rarely malaria 6 .
The Lagos success story demonstrates that malaria elimination in Africa is achievable with strong political commitment and evidence-based strategies. However, the high seroprevalence of non-falciparum species documented in other regions suggests that elimination may require species-specific approaches that address the unique biological characteristics of P. ovale and P. malariae.
The surprising discovery of high seroprevalence of P. ovale and P. malariae in West African populations represents a paradigm shift in our understanding of malaria transmission. These cryptic species, long overshadowed by their deadly cousin P. falciparum, are now emerging as significant components of the malaria ecosystem in Africa—the "ears of the African elephant" we've largely overlooked.
The findings from Benin and Nigeria underscore the importance of looking beyond obvious disease manifestations to understand the full complexity of pathogen transmission. Asymptomatic infections and low-density parasitemias may play a far greater role in sustaining malaria transmission than previously appreciated, particularly as control efforts intensify against P. falciparum.
"If it is a child that has pneumonia... and you now give anti-malaria medicine without doing a test. What will happen to that child? That child will die quickly of pneumonia" 6 . This statement highlights the critical importance of accurate diagnosis and species-specific treatment—principles that apply equally to the challenge of addressing non-falciparum malaria species.
The "unexpected high seroprevalence" of P. ovale and P. malariae serves as both a warning and an opportunity: a warning that our current surveillance and control strategies have blind spots, and an opportunity to develop more comprehensive approaches that address the full complexity of malaria transmission. As we enter what many hope will be the final chapter in humanity's long battle against malaria, listening to these whispers from the field may make the difference between success and failure.