Genetic and genomic tools to fight vector-borne diseases: A conversation with Prof Charles Wondji
Prof Charles Wondji has nearly 20 years of experience working in the field of vector-borne disease control, notably malaria, focusing on improving the understanding of the biology and genetics of mosquito vectors.
Q: Could you tell us a little bit about yourself and the focus of your current research?
Charles Wondji (CW): I am a research scientist with nearly 20 years of experience working in the field of vector-borne disease control, notably malaria, focusing on improving the understanding of the biology and genetics of mosquito vectors. I am currently a Professor of genetics and vector biology at the Liverpool School of Tropical Medicine and a Wellcome Trust Senior Research Fellow. 3 years ago I also became the Executive Director of the Centre for Research in Infectious Diseases (CRID), a young and dynamic research centre in Cameroon, where I moved to from the UK, 5 years ago. My research focuses on using genetic and genomic tools to characterise mosquito populations and help control vectors of diseases such as malaria, dengue or Zika. We mainly aim at understanding the genetic basis of insecticide resistance by detecting molecular resistance markers using genomic tools and designing suitable molecular assays to track resistance in field populations to assess its impact on control interventions in Africa (fitness cost, evolution of resistance, experimental hut field trials). I have acted as a sponsor of several fellows (Wellcome Trust, DELTA, PIIVEC) across Africa as part of my goal of contributing to capacity building. I am currently a member of the WHO prequalification team in vector control of the external scientific advisory committee (ESAC) of IVCC.
Q: Why is genetic epidemiology research important for progress in malaria surveillance and control?
CW: Genetic epidemiology research is critical for progress in malaria surveillance and control because it provides important genetic information on vector and parasite populations to guide the choice of the best tools to maximise the success of control interventions. For example, the information provided by genetic epidemiology research can inform on the level of resistance to key insecticides or risk of cross-resistance between classes of insecticides. Similarly, it can inform of the risk and extent of drug resistance and its spread. Moreover, genetic epidemiology studies can also help design the tools needed for efficient surveillance of vector and parasite populations. For example, it can help detect the DNA-based resistance markers and use these to design simple field applicable molecular diagnostic assays. Such tests are crucial to enable control programs to detect and track the spread of such resistance more efficiently and to adapt their control strategies accordingly.
Q: How can genetic epidemiology facilitate the management of insecticide resistance in Africa?
CW: Malaria prevention still relies extensively on mosquito control using insecticides. Therefore, it is crucial to detect the genetic variants driving resistance to main insecticide classes in Africa to enable the design of field applicable diagnostic tools to detect and track the spread of resistance and assess their impact on control intervention and malaria transmission. This is the domain of genetic epidemiology which facilitates the management of insecticide resistance by providing a good understanding of the ways by which resistance to insecticide operates in field populations of mosquitoes. Through genetic epidemiology, scientists identify the genes that enable mosquitoes to survive insecticide exposure. This information is then used to ultimately design simple DNA-based diagnostic tool (kit) that can be used to directly monitor insecticide resistance in important malaria vectors across Africa. Such diagnostic tools play a critical role in the planning and management of control programs of malaria vectors and help to reduce the burden of this disease. Unlike currently existing WHO bioassays which only detect resistance once it is well established in the population, these molecular diagnostic tools will allow control programs to detect and track resistance at an early stage, which is an essential requirement of resistance management efforts.
Q: How could genetic epidemiology research improve the operational decisions made by National Malaria Control Programmes (NMCPs)?
CW: Genetic epidemiology studies can greatly improve the decisions made by NMCPs by allowing them to make evidence-based decisions in the implementation and surveillance of their interventions. Indeed, the control tools and information generated by genetic epidemiology research such as the underlying genetic basis of insecticide resistance, the speed and direction of spread of resistance, alternative insecticide combinations to use to combat existing resistance, are very useful to NMCPs to improve the control of the major malaria vectors. These genetic tools allow NMCPs to detect resistance at an early stage and with any stage of the mosquito and therefore have the ability to design alternative resistance strategies to combat such resistance before it is too late. The current monitoring tool based on WHO bioassay alone cannot provide such an early alert system so vital for resistance management.
Q: You have been working on the population genetics of the malaria vectors since the year 2000. Where are we now? Where are the main knowledge gaps?
CW: Progress has been made since I started working in this field in the year 2000 during my PhD deciphering the genetic differentiation patterns between M and S forms in An. gambiae. Then, we reported that these two forms were genetically differentiated even within the forest chromosomal form (Wondji et al 2002). These two forms have since been erected as two independent species (An. gambiae and An. coluzzii) despite the continued introgression between them as in the case of kdr shown to have passed from An. gambiae to coluzzii. Patterns of gene flow have also been extensively established between populations of major vectors across the continent using different markers including microsatellites, reduced representation markers (ddRADseq) and whole genome sequencing and a recent work using whole-genome sequencing of thousands of mosquitoes revealed the extraordinary genetic diversity of these vectors (An. gambiae genome consortium, 2017 Nature) highlighting their great ability to adapt to different conditions and selection pressure. The advent of whole-genome sequencing has also allowed to detect regions of the genome under selection notably footprints of the scale-up of insecticide-based interventions such as insecticide-treated nets (Barnes et al 2017 PLoS Genetics). In general, reduced gene flow has been observed between populations from different African regions of Africa particularly for a species such as An. funestus for which southern African populations are genetically differentiated from other regions. Such differentiation is also observed for the spread of resistance genes and markers. Overall, it remains to establish if this differentiation is an unstable situation maintained mainly via isolation by distance in which case different resistance fronts could spread overtime potentially generating or spreading multiple-resistant mosquitoes possessing several resistance mechanisms. However, if other factors are the main limiters of gene flow including physical barriers (e.g. rift valley) or evolutionary adaptive factors (chromosomal inversions) then this is unlikely although it could negatively impact the implementation of alternative approaches such as gene drive. Therefore, to better predict future direction and speed of spread of genes of interest, it is necessary to decipher the causes of these restrictions to gene flow in major malaria vectors.
Q: In your opinion, which are the main challenges we are currently facing in this area of research?
CW: The main challenges are the difficulty of getting funding for such research which some funders consider to be too basic research at times, whereas it is clearly informative to help design evidence-based control strategies. The high genetic diversity of mosquito populations is also a challenge as it provides to mosquitoes a vast array of genetic plasticity across their distribution range leading to high complexity of molecular basis of insecticide resistance with a high variation of mechanisms between populations of mosquitoes. For example, the genes conferring insecticide resistance in West African mosquito population are different from those found in southern populations, so even when a diagnostic tool for resistance detection is designed in one region it does not necessarily apply in other regions where different genes are driving resistance. Another challenge is the presence of multiple important vectors e.g. Anopheles gambiae, Anopheles funestus, Anopheles arabiensis etc., all often exhibiting different behaviours and/or resistance mechanisms further complicating research efforts.
Q: How do you think genetic epidemiology can be helpful in the context of the COVID-19 pandemic in malaria-endemic settings?
CW: I think that the same principles applied for malaria control could also be introduced for the management of COVID-19 as use of genetic epidemiology could inform on the origin of the main Coronavirus strains in those countries. This knowledge could help assess any increased risk in terms of virulence or help identify the hotspots responsible for the spread. It could also help identify the main corridor of transmission by analysis the genetic diversity pattern of the strains between locations and places and/or people the most at risk.
Q: In your opinion, which are the next steps that the malaria community should take in order to advance towards malaria elimination?
CW: These steps should focus on diagnostic, treatment, vaccine, but importantly on prevention through efficient vector control including innovative control approaches in pipeline such as gene drive. I believe that malaria will not be eliminated with a single magic bullet but rather by having a robust toolbox providing flexibility to control programs to tailor their interventions according to their epidemiological/environmental context.
Prof Charles Wondji is a Professor of genetics and vector biology at the Liverpool School of Tropical Medicine and a Wellcome Trust Senior Research Fellow. He is also the Executive Director of the Centre for Research in Infectious Diseases (CRID) in Cameroon.