Health Integration of Groundwater Microbial Resistomes in River Basin Management for Environmental and Public Health

1. Introduction

Groundwater is not only a source of fresh water but also a supplier to approximately 2.2 billion people for drinking water and domestic purposes worldwide [1]. Groundwater supports agricultural activities, wetlands, springs, and rivers, and sustains ecosystems during dry seasons [2, 3]. Groundwater plays an important role in all aspects of life. Nevertheless, previous studies have stressed that groundwater can be contaminated, resulting in the global transmission of infections, with predictable annual cases of acute gastrointestinal infections rising to millions [1]. Additionally, the intensity of farm animals, wastewater systems, and the presence of children in households were substantially related to the occurrence of antimicrobial-resistant Escherichia coli in private groundwater supplies [4]. These findings suggest that land use and human activities can directly influence the quality of groundwater. Moreover, groundwater-borne antibiotic-resistant genes (ARGs) are of significant concern to the health of the people, adding to the existing high global burden of infection by resistant organisms [4].

Although antimicrobial compounds have been widely used to prevent and treat infectious diseases, the occurrence of antimicrobial resistance (AMR) continues to pose a significant threat to public and animal health, especially in less developed countries [5]. This resistance is often driven by ARGs, which equip microorganisms with mechanisms to withstand treatment [6]. All resistance genes, including those possessed by pathogenic and non-pathogenic bacteria called antimicrobial-resistant bacteria (ARB), as well as those broadly dispersed in the environment, constitute the microbial resistome, which serves as a reservoir from which resistance traits spread among microorganisms [6, 7]. Furthermore, the intensive usage of antimicrobials in healthcare, animal husbandry, and veterinary practices leads to their consistent release into the aquatic environment [8], and this can, in turn, cause the emergence of ARGs and ARB, which diminish the therapeutic prospects against infections [9]. Groundwater quality has been compromised by AMR in subsurface environments, originating from anthropogenic sources, including industrial discharges, landfills, hospitals, livestock production, agricultural activities, and wastewater facilities, which can potentially gain access to aquifers [10, 11]. Likewise, ARGs found in groundwater close to landfills offer confirmation that landfills are an overlooked reservoir of antibiotic resistance (AR), triggering ARG propagation via contaminated flowing groundwater such as springs [12].

Groundwater is closely linked with surface waters through hydrological connections and forms an integral component of river basin systems [13]. Other solutions to water problems depend on factors such as the capacities of the institutions that manage them, prevailing socio-political conditions, legal frameworks, and subnational and local water problems [14]. Both water and contaminants move between aquifers, streams, springs, and rivers within hyporheic zones where surface water and groundwater mix [15]. Recharge areas offer alternative pathways for the filtration of contaminants, antimicrobial residues, and ARGs into groundwater [16]. According to Yang [17], it is necessary to develop a correlation between antibiotics, their metabolites, and conventional water quality parameters. Incorporating groundwater microbial resistomes into river basin management (RBM) enables a more comprehensive assessment of AMR risks by capturing subsurface processes that influence water quality, ecosystem integrity, and animal and human exposure pathways [18].

Groundwater acts as a meeting point where animal production, human activities, and environmental processes interact to create and disseminate AMR [4]. Subsequently, this aligns closely with One Health principles, offering opportunities to link microbial ecology, environmental monitoring, the monitoring and mitigation of groundwater, and public health protection within a unified management approach [19, 20]. Despite growing recognition of the environmental dimensions of AMR, groundwater microbial resistomes remain largely excluded from routine surveillance and RBM frameworks. This chapter provides a comprehensive overview of AMR in groundwater systems using an integrated One Health approach. It underscores the interconnected role of animals, humans, and environmental health in the spread of resistance and discusses current monitoring approaches, supports proactive decision-making, informs policy development, and outlines future research priorities. This chapter contributes to a broader understanding of groundwater as a critical yet often overlooked component of the global AMR problem.

2. One Health and RBM

The One Health approach recognizes that human, animal, and ecosystem health are intrinsically interconnected and interdependent [20, 21]. It plays a role in many contemporary health and sustainability challenges, particularly in aquatic environments, AMR, and ecological decline, which occur due to connections around these areas. It thus cannot be tackled via single-sector strategies [22]. River basins that contain groundwater and surface water are dynamic ecological units, which are vital focal points for AMR surveillance and management [23]. Simultaneously, RBM demonstrates a strategy for controlling water settings at the catchment scale. This, therefore, aligns with integrated governance methods that promote adaptive and coordinated water management [24, 25]. RBM typifies a settings-based approach in addressing AMR, influencing human health, animals, and environmental domains [26]. This integration can identify the sources, pathways, and receptors of AMR within a defined river basin [27].

Several investigations have emphasized the integration of freshwater into a single health surveillance approach, including basin-scale monitoring, as essential for elucidating the spatial and temporal dynamics of AMR transmission within watershed settings [28–30]. Microbial resistome analysis, together with RBM, makes it possible to produce actionable data that facilitate intervention in both environmental monitoring and public health [31]. The collective pool of ARGs within subsurface microbial communities constitutes a groundwater microbial resistome that is widely recognized as a critical indicator of environmental health and AMR dynamics [32].

According to the One Health RBM framework, groundwater serves not only as a reservoir but also as a conduit for ARG dissemination, with horizontal gene transfer (HGT) aiding in the distribution of AMR in microbial populations [33, 34]. Integrating groundwater resistome monitoring into RBM enables early detection of emerging resistance threats, enhances understanding of environmental drivers influencing AMR propagation, and supports evidence-based decision-making for water safety and public health protection [30, 35]. One Health and RBM provide an interdisciplinary framework for addressing AMR in groundwater systems by linking environmental processes with human and animal health. This integrated approach facilitates the development of sustainable, basin-scale management strategies and underscores the need to move beyond fragmented methodologies toward coordinated, systems-based management of water resources and microbial risks in the environment [28, 30].

3. Sources and pathways of AMR in groundwater

Environmental pollutants come from a multitude of sources (anthropogenic and systemic), including municipal solid waste generated in urban areas, agricultural runoff containing synthetic fertilizers, pesticides, and manure from livestock, industrial effluent discharged from manufacturing, mining, and electric utility operations releasing heavy metals and toxic chemicals into the environment, and biomedical waste from medical facilities containing hazardous drugs [4, 36]. After they are disposed of, environmental pollutants begin to degrade within landfills, producing toxic gases and harmful leachates that seep into adjacent soils and subterranean water aquifers. Eventually, all this contamination is transported through various natural pathways for pollution dissemination throughout larger systems of terrestrial and aquatic ecosystems using surface run-off, ground water recharge, and precipitation processes. Figure 4 below is the conceptual flow diagram illustrating the possible contamination pathways Figure 1.

In a study of groundwater in Kisumu, Kenya, Escherichia coli was found in 98% of samples, and sulfamethoxazole was detected in 14.3% of sources, indicating a risk of antibiotic contamination and resistant pathogens [37]. In a similar study, Andrade [4] synthesized available studies from around the world to clarify the environmental context influencing ARB prevalence, circulation, and drivers of ARB in groundwater sources, such as boreholes and wells. The study noted that 80.2% of groundwater isolates were resistant to at least one antibiotic, while 57.2% were resistant to three or more. In some provinces in South Africa, including the Northwest and Eastern Cape, multidrug-resistant (MDR) E. coli has been observed in groundwater [38; 39], which is a serious public health concern. Contaminants leach into aquifers and enter them through human activity, where temperature is reduced and light is absent, making it easier for resistant microbes to persist [40]. Rainfall can enhance the concentration levels of ARG contaminants in groundwater, which is a major drinking source for 2.2 billion people [41]. Therefore, ARB poses a significant, though undermonitored, public health risk.

The effect of pharmaceutical production facilities and aquaculture operations introduces higher concentrations of antibiotics, with no other option but to release them into the environment. This creates abundant selective pressure, which can actually enable the emergence of AR [42]. In South Africa, industrial discharge, particularly from the pharmaceutical, manufacturing, and agricultural industries, is a major but not properly regulated factor contributing to AMR [43]. The WWTPs do not have the efficiency to remove ARB or ARGs from production effluents, and thus these contaminants regularly leach into groundwater and surface waters [44, 45]. Drug-manufacturing wastewater usually contains a high concentration of pharmaceutical ingredients in the form of active pharmaceutical ingredients. As a result, it represents a compelling selective environment that highlights the emergence of MDR bacteria [46]. Although often classified as municipal waste, hospital-generated wastewater is technically a hazardous industrial and clinical stream; it serves as a primary conduit for high-priority AR microorganisms into WWTPs [47]. A large part of the wastewater treatment infrastructure in South Africa is failing or performing below standard [48]. Consequently, poorly treated effluents are introduced into natural systems directly, including active pharmaceutical compounds, ARB, and ARGs [49].

Water soaking into the ground (infiltration) and washing through soil (leaching) are pivotal but often unheeded mechanisms for AMR, one of which involves drug residues, resistant bacteria, and their genes flowing from the surface to groundwater. This can contaminate drinking water supplies [50]. Recent studies suggest that manure fertilization adds antimicrobial-resistant genes (ARGs) to agriculture’s upper layers of soil and transfers them, indirectly, to all other species through nutrients [51, 52]. The application of manure supports the horizontal transfer of ARGs to indigenous microorganisms and induces the vertical migration of ARGs into deeper soil, as well as their leaching downstream to groundwater [53, 54]. While several studies on this phenomenon have been published and analyzed, the mechanisms responsible for the vertical transport and leaching of ARGs in response to rainfall in long-term fertilized soil profiles are still poorly characterized. In the same manner, Zang [55] has indicated that long-term manure application in soil is one of the principal causes of ARG pollution and thus threatens groundwater quality. The vertical migration and leaching of these genes during rain events need to be localized with mitigation strategies.

Groundwater provides a vital source of water supply in many emerging contexts, often serving as a more stable replacement for suboptimal surface water sources [56]. Furthermore, the prevalence of antibiotic usage and antibiotic ARGs in developed nations also results in a substantial imbalance in how the region is organized [57]. Therefore, a systematic investigation into ARG concentrations in groundwater systems is necessary, with a focus on the possible influence on ecological stability and human health [58]. Groundwater contains lower levels of antibiotics and ARGs than soil and surface waters as environmental compartments; however, it is still capable of posing a severe threat to human health and ecosystems [41]. A more stringent risk analysis of antibiotics and ARGs is required to protect human, animal, and environmental health within aquatic systems [57]. While the origins of these contaminants are well established, their environmental fate, including pathways of transmission, is not well understood for ARGs [59]. This calls for basic studies to investigate the transport pathways of ARGs in groundwater settings. Moreover, predictive modeling of the occurrence and migration of antimicrobial agents should be the focal aim of forthcoming studies to classify the transition from surface to underground water [60].

4. Methods for groundwater resistome surveillance

Monitoring groundwater involves certain cumbersome and meticulous processes, as the location of this water reserve can be a contributing factor that affects the implementation of management interventions. Microbial contamination brings about the accumulation of various pathogens and potentially leads to other modified inorganic pollutants. For instance, the presence of microplastics has been well-documented in groundwater settings, including boreholes and springs; however, there are several knowledge gaps [61]. Furthermore, before identifying hotspots, risk interpretation should be carried out based on the outcome of the molecular analysis [62]. The following is a step-by-step procedural sequence that can be adopted for the surveillance of the groundwater resistome.

4.6 Molecular analysis

• Performing quantitative polymerase chain reaction (qPCR) for targeted ARG quantification.

• Conducting shotgun metagenomic sequencing to profile microbial communities and resistome diversity.

• Include negative controls to detect contamination.

4.6.1 qPCR screening

Targeting the quantification of known ARGs.

• Extracting bacterial DNA from groundwater samples.

• Apply quantitative PCR assays for common ARG markers (such as bla and tet).

• Normalize gene copy numbers to 16S rRNA for microbial load.

4.6.2 ARG database alignment

Identify and classify resistance determinants using curated databases.

• Aligning sequences against CARD, ResFinder, and ARG-ANNOT.

• Annotating ARG classes (beta-lactam, tetracycline, macrolide).

• Quantifying abundance and diversity indices.

4.6.3 Mobile genetic elements

Assessment of potential for HGT.

• Detect plasmids, integrons, and transposons in metagenomic data.

• Map cooccurrence of ARGs with mobile genetic elements (MGEs).

• Evaluate transferability risk across microbial taxonomy.

4.6.4 Database annotation

• Compare sequences against ARG databases (CARD, ResFinder, ARGs-OAP) and MGE repositories (ISfinder, ACLAME).

• Identify plasmids, integrons, and transposons linked to ARG mobility.

4.6.5 Metagenomic sequencing

Comprehensive profiling of microbial communities and resistomes.

• Perform shotgun sequencing using Illumina or Nanopore platforms.

• Assemble reads into contigs for taxonomic and functional annotation.

• Capture rare and novel ARGs beyond qPCR’s scope.

4.6.6 Risk prioritization

• Integrate molecular data with hydrochemical and land-use parameters.

• Use quantitative risk scoring to rank hotspots by potential human and ecological exposure.

• Map results for management intervention and policy feedback.

Also, integrating abundance, mobility, and pathogenicity into risk indices by

• Applying computational pipelines (for instance, MetaRanker) for unified risk scoring.

• Ranking hotspots by ARG load and transfer potential.

• Prioritizing sites for management intervention and policy feedback Figure 2.

For decades, several groundwater surveillance methods have been developed to offset the probable limitations of existing procedures. A brief comparison of the surveillance methods for groundwater resistome is summarized in Table 1. Many studies have shown that qPCR has high management relevance for routine monitoring of relevant ARGs, while the gold standard for the total resistome is shotgun metagenomics, which is also considered moderately high in management relevance for research and risk assessment.

Method	Principle	Strengths	Limitations	Management relevance	Key references
Culture-based methods	Isolation on selective agar and phenotypic AST, as well as PCR of presumptive isolates	Detects viable, clinically significant bacteria Provision of isolates for WGS Direct connection to public health risk Regulatory accepted Low cost	Misses unculturable ARG host Bias to fast growers Culturable bacteria amount to only about 1% Slow duration takes about two to seven days	High for compliance. WHO/CDC standard for groundwater also informs treatment/discharge decisions	WHO, [64], GDWQ 4th edition
qPCR	Amplifies specific ARG and 16S targets (with primers/probes)	The fast process takes about two to four hours High sensitivity (<10 copies) Low cost for target Quantitative for trends	Primers bias No host ID Targeted only, misses novel ARGs PCR inhibitors in groundwater	High for routine monitoring of priority ARGs, including blaTEM, sul1, and tetA, in aquifers/wells. Used in surveillance studies with known targets	WHO GDWQ surveillance framework
High-throughput qPCR HT-qPCR	Microfluidic arrays running 100 to 1,000 assays	Lower cost/target Quantitative and high throughput Broad coverage (100s of ARGs and MGEs) Good for profiling the resistome	Complicated data analyses High cost for equipment No taxonomic linkage Skip novel genes (primer-dependent)	High for temporal trends and basin-scale mapping, it can identify resistome hotspots across multiple groundwater points	Commonly cited in environmental resistome studies (2015–2024)[65]
Shotgun metagenomics	Untargeted DNA and ARG annotation versus CARD/ResFinder	No primer bias Links ARG to host via MAGs/contigs Community structure data Unbiased (novel and relevant ARGs)	Bioinformatics expertise Needs high sequencing depth Detection limit [104 cells per L] Expensive	Medium-high for research and risk assessment. Gold standard for total resistome. Can discover emerging threats and pathogen linkages	CARD, ResFinder databases for annotationAdel-Glil et al. [66]
Mobile sequencing nanopore	Real-time nanopore sequencing in field/lab	No PCR needed Long reads link ARG-MGE-host Portable, field-deployable Rapid (6–24 hours: sample to data)	Lower throughput Needs power or internet Bioinformatics required Error rate (5–10%) vs Illumina	Accuracy improving. Fast on-site data for groundwater contamination events. Suitable for outbreak response and remote sites	Field validation studies 2018–2025
Microbial source tracking MST	qPCR and dPCR of host-associated markers to identify fecal source	Explains why ARGs are present IDs source (human–livestock–wildlife) Guides remediation Combines with ARG qPCR	Extra cost Tracks fecal only, not environmental ARGs Needs validation Marker specificity varies regionally	Delineates septic tank, WWTP, and farm impact. High priority for groundwater protection. Directly informs land-use and wellhead protection policies	WHO, 2016 GDWQ catchment risk approach
Bioinformatics tools	Databases and pipelines (CARD, ARG-ANNOT, ResFinder, ShortBRED)	Enable meta-analyses Standardized annotation Updated with new mechanisms Free or open source	Quality depends on input Database bias to clinical genes False positive risk Steep learning curve	Essential for comparable and validated groundwater resistome data across regions per year, sequencing methods are needed	CARD, ResFinder, and ARG-ANNOT databases.Adel-Glil et al. [2]

Table 1.

Groundwater resistome surveillance methods.

A comparison of culture-based methods, qPCR, high-throughput qPCR, shotgun metagenomics, mobile sequencing, microbial source tracking (MST), and bioinformatics tools, including their strengths, limitations, and management relevance.

5. Implications for environmental and public health

The aquatic environment is regarded as a primary environmental reservoir and propagating pathway for AMR because of the mixing of microbes, ARGs, antimicrobial compounds, and bacteria. This dynamic interaction consequently affects the expansion and persistence of the environmental resistome [67]. Although ARGs in aquatic environments, including surface water bodies [68] and groundwater [4], have been increasingly explored, groundwater systems remain largely overlooked despite their vulnerability to rapid contamination transport [69]. Groundwater comprises 97% of the global freshwater and acts as a critical source of drinking water worldwide [11, 70]. Therefore, this underscores its major importance within a One Health framework, as contamination of groundwater directly affects human health, agricultural production, and ecosystem stability.

Nonetheless, groundwater is affected by various physicochemical properties such as soil constituents, perviousness, adjoining aquifers, and land use events [71]. These properties collectively regulate the introduction, pathway, and persistence of the antibiotic resistome in the ground [72]. Besides, anthropogenic activities aggravate the situation by introducing impurities with possibly bioactive properties, including antibiotics and personal care products, which compromise groundwater quality and pose a health risk to the public [18]. Furthermore, distinct environmental conditions of groundwater are influenced by low nutrient availability as well as anaerobic conditions, which help develop a diverse microbiological community in groundwater, subsequently lessening the rate of antibiotic breakdown [53, 73]. According to Zainab [5], the prolonged persistence of antibiotics creates selective pressure that encourages the proliferation of ARB and ARGs in groundwater.

Furthermore, HGT plays a significant role in the spread of AR traits within the groundwater microbial community and facilitates the conversion of bacterial susceptibility into resistant forms [72]. This process enhances the resilience and adaptability of the resistome, increasing the probability of transmission to human and animal populations through waste use [74]. The hyporheic region is an environmentally functional area where the interaction between shallow groundwater and surface water plays a crucial role in sustaining and regulating groundwater ecosystem health [74]. Therefore, monitoring and characterizing the ARG dynamics in the hyporheic zone are important for identifying pollution sources and mitigating risks to environmental and public health.

6. Integrating resistome data into RBM and policy

It is noteworthy to understand the ARG distribution and dynamics for managing their dissemination and supporting the water governance framework [75]. The integration of resistome data into RBM and policy requires translating genomic information on ARGs into operational tools that directly inform monitoring, risk assessment, and regulatory decision-making [75, 76]. Monitoring programs should be prioritized by officials to detect emerging AMR hotspots and further track the occurrence of ARGs over time. This will support the risk assessment of the dissemination of ARGs in wastewater and agricultural activities and prevent morbidity and mortality due to infections. The occurrence of ARGs in river basins is a highly connected system across spatial and temporal scales [55]. Presently, it has been revealed that human activities have had the utmost impact on the spatial dissemination of these genes [77, 78], along with microbial ecologies, and, lastly, abiotic factors [54]. In addition, ARGs are strongly influenced by land use and hydrological conditions, making them critical indicators for basin-scale environmental management. Thus, it supports targeted management actions and informed decision-making regarding water resource protection [55].

Resistome data can be integrated into risk-based RBM approaches by linking the occurrence, distribution, and mobility of ARGs to environmental and public health risks [79, 80]. Existing monitoring systems can be expanded to incorporate MGEs as complementary indicators. This will allow RBMs to detect contamination patterns that are not captured by conventional indicators, facilitating the improvement of the resolution and effectiveness of water quality assessments [55]. By detecting dominant sources of resistance, river basin authorities can implement targeted control measures such as improving wastewater treatment processes, regulating effluent discharge, and adopting sustainable agricultural practices aimed at reducing AMR contamination in the environment and aquatic milieu at large [81]. This enhances the precision and efficiency of basin-scale interventions. Recently, it was reported that water quality policies lack a standardized approach for monitoring and regulating AMR, including the absence of ARG-based indicators in policy frameworks [31, 82].

Importantly, integration must contemplate groundwater-surface water connectivity since it has a greater influence on the dissemination of ARGs [54]. Practically, monitoring of ARGs in the river basin facilitates surveillance systems, supports risk assessment, enables predictive modeling, and informs policy development [73]. Resistome data becomes an operational component of water governance [83]. This incorporation is critical for developing adaptive, One Health–informed RBM techniques that efficiently moderate the distribution of AR and protect both ecological and human health.

7. Challenges, knowledge gaps, and future directions

Yet, the integration of groundwater microbial resistome data in aquatic environments within One Health demonstrates significant opportunities to address AMR and ARG; however, numerous challenges and knowledge gaps limit implementation [84, 85]. These challenges highlight the need for coordinated and multidisciplinary approaches for AMR surveillance in the environment and its management [83]. The limited exploration of groundwater resistomes is one of the main challenges compared to surface water, as groundwater is regularly considered a protected resource despite evidence of its role as a hotspot for AMR and ARGs [85, 68]. This further results in an incomplete representation of the dissemination of resistance within river basins [84]. Moreover, standardized methods for the molecular detection and profiling of ARGs in groundwater systems contribute to the existing limitations [86, 87]. Regarding the One Health perspective, there is insufficient integration of environmental, human, and animal health data in assessing risks associated with groundwater resistomes [83]. This constrains the development of risk-based management strategies and limits the inclusion of resistome data in public health decision-making.

Imminent studies should prioritize the creation of integrated investigative frameworks that explicitly include groundwater resistomes within river basin assessments [84]. It is quite necessary to establish risk-based thresholds for ARGs in groundwater and connected surface water systems, supported by interdisciplinary research that integrates environmental resistome data with epidemiological evidence [86, 88]. In low-resource settings, where reliance on groundwater is high, capacity building and technological innovation are essential for advancing groundwater resistome integration [89]. Developing cost-effective and scalable detection methods will enable broader adoption of resistome monitoring [83]. In parallel, strengthening data-sharing platforms and interdisciplinary collaboration will support One Health implementation at the basin scale [89]. Policy directions should focus on embedding groundwater resistome data into river basin governance frameworks, including integrated management strategies for current water resources and national AMR action plans [89, 90].

8. Conclusion

Groundwater resistomes represent an important and often overlooked component of AMR surveillance. Since groundwater serves as a reservoir of AMR and ARG, it can contribute to the occurrence and dissemination of resistance across animals, humans, and environmental health. The global burden of AMR dictates a shift in focus from specific approaches toward integrated strategies that identify the interconnectedness of animal, human, and environmental health. Groundwater should be recognized as part of the broader AMR landscape for comprehensive surveillance and management.

Groundwater microbial resistomes are recognized as active components of AMR dynamics, which challenge the traditional boundaries of environmental monitoring and call for a redefinition of how water systems are managed. Embedding resistome intelligence into RBM can strengthen risk-based monitoring and support the identification of contamination hotspots and resistance sources. This can enhance strategies, inform groundwater protection measures, and further enhance coordination across humans, animals, agricultural, environmental, and veterinary sectors with in One Health perspective. Consequently, this transition has the potential to strengthen water safety frameworks, enhance the resilience of aquatic systems, and reduce long-term public health risks associated with AMR. However, realizing this potential depends on bridging persistent gaps between scientific capability and policy implementation.

This chapter advances the perspective that effective management of AMR requires moving beyond detection toward integration. Future progress depends on the use of standardized indicators, institutional coordination, data-sharing mechanisms, policy uptake, and practical tools for low-resource settings. Addressing these barriers will be vital for translating scientific knowledge into actionable management strategies. Ultimately, integrating groundwater microbial resistomes into RBM represents more than a technical improvement; it reflects a conceptual shift in how AMR is understood and managed. By aligning environmental intelligence with policy action under a One Health framework, this approach offers a pathway toward more adaptive, informed, and sustainable protection of both ecosystem integrity and public health.

Acknowledgements

South African Medical Research Council (SAMRC) supported the Postdoctoral Fellow as a researcher by funding received from the South African National Treasury through SAMRC Extramural Postdoctoral Programme under the Division of Research Capacity Development. We're also grateful to the National Research Foundation (NRF) for financial support. The content hereof is the sole responsibility of the authors and does not necessarily represent the official views of the SAMRC or the NRF.

Funding

We are grateful to the South African Medical Research Council, the Department of Science, Technology and Innovation of South Africa, and the National Research Foundation of South Africa for financial support.

Glossary