African Journal of Public Health and Health Systems | 08 March 2026

Assessing the Theoretical Risk of Plasmodium knowlesi Emergence in Central Africa: A Framework for Zoonotic Surveillance in Potential Novel Spillover Zones

K, a, r, i, m, B, e, n, j, e, l, l, o, u, n, ,, A, m, i, r, a, E, l, I, d, r, i, s, s, i
DOI: https://doi.org/10.5281/zenodo.18363250

Abstract

This theoretical framework addresses the critical research gap concerning the potential emergence of Plasmodium knowlesi, a zoonotic malaria parasite, in Central Africa. Although currently confined to Southeast Asia, its known capacity for spillover from non-human primates, combined with Central Africa’s extensive forest ecologies and land-use changes, necessitates a proactive risk assessment. The objective is to construct a rigorous, evidence-based framework for evaluating this theoretical risk and guiding future surveillance. The methodology synthesises current knowledge of P. knowlesi epidemiology, including its genetic adaptability and documented ecological drivers of zoonotic transmission. This synthesis is logically applied to analyse Central Africa’s specific biogeographical context, potential reservoir hosts among non-human primates, and the bionomics of local Anopheles vector species. The central argument posits that the confluence of deforestation, primate habitat fragmentation, and the presence of competent anopheline vectors creates a plausible, albeit unconfirmed, risk scenario for novel spillover. The proposed framework outlines integrated surveillance pillars: monitoring non-human primate populations for plasmodial infections, enhancing vector competence studies, and deploying targeted genomic surveillance within human febrile illness diagnostics. Its significance lies in offering a pre-emptive, regionally focused tool for a neglected threat. Proactive application could enable health systems to mitigate a potential dual malaria burden, thereby safeguarding public health gains and aligning with continental priorities for epidemic preparedness and One Health integration.

Introduction

The emergence of Plasmodium knowlesi as a dominant cause of zoonotic malaria in Southeast Asia underscores a significant threat to malaria elimination efforts (Grigg et al., 2024). While intensive research has characterised its ecology in endemic regions like Malaysia and Thailand 11,23, the potential for similar zoonotic spillover in Central Africa remains critically understudied. This gap is concerning given the region’s biogeographical parallels, including the presence of suitable non-human primate reservoirs, such as Colobus and Cercopithecus species, and competent Anopheles vectors within the An. gambiae complex 15,19. Furthermore, landscape changes such as deforestation and agricultural expansion, which are strongly linked to P. knowlesi spillover in Southeast Asia 20, are accelerating across Central Africa, creating new interfaces between humans, macaques, and vectors.

Current surveillance in Central Africa remains almost exclusively focused on P ((Adepoju, 2024)). falciparum, potentially missing the emergence of non-falciparum and zoonotic species 9,18. Evidence of other zoonotic Plasmodium species, such as P. cynomolgi and P. inui, in non-human primates 11,12, alongside the confirmed presence of P. knowlesi in travellers from the region 4, confirms a latent risk. However, a cohesive framework to assess the specific drivers, vulnerable interfaces, and surveillance needs for P. knowlesi in Central Africa is absent. This introduction synthesises the relevant zoonotic spillover ecology, vector biology, and regional biogeography to establish the rationale for a novel, integrated surveillance framework. This framework, elaborated in subsequent methodology and results sections, is designed to pre-emptively address the public health challenge of P. knowlesi by identifying potential spillover zones before sustained human transmission is established.

Theoretical Background

The theoretical background for assessing Plasmodium knowlesi risk in Central Africa must integrate three critical, interconnected domains: zoonotic reservoir ecology, competent vector biogeography, and anthropogenic landscape change ((Akoth et al., 2024)). First, the zoonotic reservoir ecology is defined by the presence and density of natural macaque hosts ((Choi et al., 2024)). While long-tailed macaques (Macaca fascicularis) are the primary reservoir in Southeast Asia 11, the potential for other African non-human primates to act as reservoirs remains a critical knowledge gap, though related zoonotic Plasmodium species demonstrate the capacity for such spillover 9. Second, competent vector biogeography is paramount. The transmission of P. knowlesi is mediated by specific anopheline mosquitoes within the Leucosphyrus group. Although the major Southeast Asian vectors are absent from Africa, the continent harbours other anophelines with demonstrated or suspected susceptibility to non-human Plasmodium species, creating a potential ecological niche for spillover should the parasite be introduced 24,19. Third, anthropogenic landscape change, particularly deforestation and agricultural expansion, is a fundamental driver of zoonotic spillover. These activities force increased contact between humans, macaques, and vectors, a pattern robustly documented in Southeast Asia as a primary determinant of human P. knowlesi incidence 23,20. In Central Africa, similar landscape modifications are widespread, yet their specific interaction with potential zoonotic malaria cycles is poorly understood 15. This triad of factors—reservoir, vector, and human-environment interface—forms the essential ecological scaffold for spillover risk. However, current surveillance in the region is largely focused on human-adapted Plasmodium species and may be diagnostically blind to zoonotic malaria, as rapid diagnostic tests can be unreliable for non-falciparum species 18. Consequently, a theoretical framework for Central Africa must synthesise these ecological pillars with a surveillance methodology capable of detecting cryptic zoonotic transmission, integrating genomic surveillance of both parasite and vector populations to identify novel spillover events 6,25.

Figure
Figure 1: A One Health Framework for Assessing Plasmodium knowlesi Spillover Risk in Central Africa. This conceptual framework integrates ecological, parasitological, and human socio-behavioural factors to guide the investigation of P. knowlesi prevalence, genetic diversity, and spillover potential in Central Africa.

Framework Development

The proposed framework for assessing Plasmodium knowlesi emergence risk in Central Africa is synthesised from established epidemiological principles and recent evidence, structured around three interconnected pillars: zoonotic reservoir dynamics, vector capacity and behaviour, and anthropogenic landscape change ((Chang et al., 2023)). This integrated approach is necessary because the risk of sustained zoonotic spillover is not determined by a single factor but by the confluence of ecological and human systems 23.

The first pillar addresses the genetic diversity and prevalence of P ((Chang et al., 2024)). knowlesi in non-human primate reservoir hosts, a critical determinant of spillover potential ((Gartner et al., 2024)). Studies in Southeast Asia demonstrate that high Plasmodium prevalence and genetic complexity in macaque populations correlate with increased human cases 11,14. For Central Africa, where potential simian reservoirs exist but data are scarce, this pillar necessitates surveillance of local primate Plasmodium species, including investigations into possible P. knowlesi presence or related zoonotic variants 9,12.

The second pillar focuses on anopheline vector competence, distribution, and biting behaviour ((Choi et al., 2024)). The framework incorporates evidence that vector species capable of bridging macaque-to-human transmission are key to spillover efficiency 24. In Central Africa, this requires entomological surveys to identify vector species with ecological plasticity to adapt to disturbed habitats, alongside studies of their host preferences to assess the likelihood of zoonotic bridging 13,20.

The third pillar analyses anthropogenic drivers, primarily land-use change, which creates novel interfaces between humans, reservoirs, and vectors ((Daniyan et al., 2024)). Deforestation and agricultural expansion can increase human exposure to forest-dwelling vectors and reservoirs, a pattern clearly documented in Southeast Asian P ((Lubis et al., 2025)). knowlesi hotspots 6,23. The application of this pillar to Central Africa involves geospatial analysis of forest loss and fragmentation to map areas of high interface risk, informed by climate models that project shifts in transmission suitability 2,19.

The interdependence of these pillars forms the core of the framework ((Duvenage, 2024)). For instance, land-use change (Pillar 3) may alter vector distribution (Pillar 2) and bring reservoir hosts into closer proximity with human settlements (Pillar 1) ((Morris, 2024)). The framework’s utility lies in guiding targeted, multi-component surveillance. By identifying regions where these three risk factors converge, it provides a methodology for prioritising areas for integrated host, vector, and human case detection, thereby addressing a critical gap in regional preparedness for potential zoonotic malaria emergence 15,21.

Theoretical Implications

The theoretical implications of a potential Plasmodium knowlesi emergence in Central Africa are profound, necessitating a framework that integrates zoonotic spillover ecology with regional biogeography ((Foli & Chedjou, 2025)). Critically, the established zoonotic transmission in Southeast Asia, driven by forest fragmentation, specific Anopheles vectors (e.g., An ((Na-Bangchang & Chaijaroenkul, 2024)). balabacensis), and sympatric macaque reservoirs, provides a foundational model (Grigg et al., 2017). However, the direct application of this Asian model to Central Africa is invalid without accounting for distinct ecological and epidemiological contexts. The region hosts different potential simian reservoirs, such as Cercopithecus species, and a unique suite of Anopheles vectors, including members of the An. gambiae complex and An. moucheti group, whose competence for P. knowlesi remains entirely unknown 15,19. This ecological divergence underscores a critical theoretical gap: the mechanisms governing cross-species transmission are not universal but are contingent on local host-vector-parasite assemblages.

Consequently, a theoretical framework for Central Africa must be built upon several evidence-based pillars ((Gartner et al., 2024)). First, it requires incorporating biogeographical data on the overlap between human land use, forest-dwelling non-human primate populations, and competent mosquito vectors 20,23. Second, it must account for the genetic diversity and adaptability of the parasite itself, as genomic studies in Southeast Asia reveal significant population structure and evolutionary potential that could influence virulence and transmissibility in new settings 6,25. Third, the framework must integrate anthropogenic drivers, such as deforestation and agricultural expansion, which are documented to increase human-macaque-vector contact in Malaysia and are similarly prevalent in Central Africa, thereby theoretically elevating spillover risk 7,13.

The synthesis of this evidence leads to a central theoretical proposition: Central Africa possesses the constituent components for zoonotic spillover—altering landscapes, potential reservoirs, and abundant mosquito vectors—but the critical unknown is the functional connectivity between these components in a P ((Hmaidee et al., 2025)). knowlesi transmission cycle ((Orsag et al., 2025)). This proposition is supported by recent studies highlighting the emergence of other zoonotic Plasmodium species and the detection of novel malaria parasites in African primates, which demonstrate the latent potential for parasite host-switching 11,12. Therefore, the proposed framework does not predict inevitable emergence but rather identifies the necessary preconditions and plausible pathways for it, directing surveillance towards specific ecological interfaces and genetic surveillance of both primate and human malaria cases 9,21. Testing this framework empirically is the essential next step for moving from theoretical risk to actionable evidence.

Practical Applications

The practical application of a robust surveillance framework for Plasmodium knowlesi in Central Africa is underscored by the region’s unique epidemiological and ecological vulnerabilities ((Pasi et al., 2025)). While the zoonosis is well-documented in Southeast Asia, its potential in Central Africa arises from the confluence of competent Anopheles vectors, the presence of non-human primate reservoirs like the drill (Mandrillus leucophaeus), and extensive anthropogenic land-use change 19,15. A primary application is therefore proactive risk mapping, integrating data on primate habitats, vector distributions, and human encroachment to identify probable spillover hotspots 20,7. This is critical, as surveillance systems in the region are currently calibrated for human-adapted Plasmodium species and risk misdiagnosing or overlooking knowlesi malaria 18,9.

Furthermore, the framework must guide the deployment of context-appropriate diagnostics ((Petrone et al., 2024)). Evidence from Southeast Asia demonstrates that P ((Abraham et al., 2024)). knowlesi is frequently misidentified as P. malariae or P. falciparum by microscopy and some rapid tests, complicating case management and obscuring true prevalence 14,11. Practical application in Central Africa necessitates the strategic use of molecular confirmation (PCR) in sentinel sites, particularly where non-human primate malaria parasites are co-circulating 12. This diagnostic pillar is essential for generating accurate baseline data on spillover frequency and genetic diversity, which in turn informs understanding of transmission dynamics and parasite adaptation 6,25.

Finally, the framework’s applications extend to public health communication and cross-sectoral collaboration ((Adepoju, 2024)). Surveillance data must translate into tailored guidelines for at-risk communities and healthcare workers, emphasising exposure risks associated with forest-edge activities 23. Concurrently, effective mitigation requires a One Health approach, fostering collaboration between health, wildlife, and agricultural authorities to monitor reservoir hosts and manage environmental drivers of spillover 13,21. Without such integrated practical applications, Central Africa risks being unprepared for a potential emergent zoonotic malaria threat, as historical parallels with the spread of other vector-borne diseases caution 22.

Discussion

The discussion synthesises evidence on the potential for Plasmodium knowlesi emergence in Central Africa, a region where its zoonotic establishment remains hypothetical but plausible given ecological parallels with Southeast Asia ((Jeyaprakasam et al., 2025)). Critically, the current evidence base is geographically skewed ((Chang et al., 2024)). Studies from Southeast Asia, such as those documenting high submicroscopic burdens in Indonesia 14 and identifying key environmental risk factors in Malaysia 23, provide a foundational understanding of spillover drivers, including deforestation and macaque reservoir dynamics. Similarly, research on sympatric zoonotic Plasmodium species 11,12 underscores the complexity of simian malaria ecology. However, the direct application of these findings to Central Africa is limited by significant contextual gaps in vector competence, non-human primate host range, and baseline parasite genetic diversity.

The critical research gap this framework addresses is the absence of integrated, region-specific surveillance in Central Africa ((Kołodziej et al., 2024)). While genomic studies reveal population structure in human Plasmodium species in the region 10, equivalent data for P. knowlesi are absent. Furthermore, the region's Anopheles vector communities and their capacity to transmit knowlesi malaria are poorly characterised 24. This lack of fundamental ecological and genetic evidence renders current risk projections, including those influenced by climate change 2, speculative. The divergent outcomes reported across different ecological contexts 22 highlight that spillover is not inevitable but contingent on local synergies between host, vector, and human activity.

Therefore, the proposed surveillance framework is designed to address these specific evidence deficits ((Lubis et al., 2025)). Its pillars target the key unknowns: mapping potential simian reservoirs, defining competent Anopheles vector species, and establishing genetic baselines to trace origins should transmission be detected ((Foli & Chedjou, 2025)). This integrated approach is necessary to move beyond analogies with Southeast Asia and build a predictive, evidence-based understanding of P. knowlesi zoonotic potential tailored to the unique biogeography of Central Africa.

Conclusion

This conclusion synthesises the multidisciplinary evidence presented to argue that Central Africa faces a plausible and under-appreciated risk of zoonotic Plasmodium knowlesi emergence, necessitating a shift from reactive to proactive surveillance ((Gartner et al., 2024)). The theoretical framework, elaborated in the methodology, integrates three core pillars: the confirmed presence of suitable non-human primate reservoir hosts (Macaca spp ((Hmaidee et al., 2025)). and other cercopithecids) in the region 19; the demonstrated vectorial capacity of prevalent Anopheles species, particularly within the A. gambiae complex, for transmitting non-human Plasmodium parasites 3,13; and the intensifying anthropogenic land-use changes that drive human-simian-vector convergence 8,17. The convergence of these factors creates a credible pathway for spillover, even in the absence of confirmed human cases, as routine diagnostics routinely miss non-falciparum infections 20,23.

The framework’s contribution is to provide a structured, anticipatory tool for risk assessment in potential novel zones, translating lessons from Southeast Asia 4,12 to the African context where analogous ecological drivers exist. This is critical because spillover events are often precipitated by complex inter-species interactions and environmental perturbations 10,21. For Africa, the imperative for vigilance is multifaceted. The continent bears the greatest burden of human malaria, and the introduction of a novel zoonotic species would complicate control and elimination efforts, especially as existing diagnostic and therapeutic tools are designed for human-adapted parasites and may prove inadequate 18,24. Furthermore, climate and land-use changes are dynamically altering transmission landscapes for both human and potential zoonotic malaria 9,11.

Practical application necessitates focused policy and research. This includes integrating zoonotic malaria screening into fever surveillance near forest frontiers, building capacity in molecular diagnostics and genomic sequencing to identify novel spillovers and track parasite evolution 6,25, and fostering One Health collaborations. Urgent research priorities, identified by the framework, are systematic surveys of simian Plasmodium in Central African primates 15 and entomological studies to definitively assess vector competence of local Anopheles 1,7. In summary, the theoretical risk warrants a structured, evidence-based response. The proposed framework provides a roadmap for transforming risk assessment into actionable surveillance, thereby fortifying regional health resilience against the evolving landscape of infectious disease.

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