Malaria-carrying mosquitoes are always on the move. They’re also evolving to resist insecticides and live in more diverse environments. Identifying which species of mosquitoes are present in an area is trickier than it seems because many mosquitoes are difficult to tell apart by eye. This is why genome sequencing has become an established method for accurately confirming which species of mosquitoes are present in an area.
Mosquito surveillance efforts typically focus on the major malaria vectors present in a population, often overlooking new or unexpected species. Now, secondary vectors are gaining attention thanks to advanced genomic and molecular identification tools.
Using whole genome sequencing (WGS) data from the Malaria Vector Genome Observatory, researchers recently identified An. coluzzii mosquitoes among samples collected from five counties in Kenya. They then analysed their genome sequences to understand their genetic structure and whether resistance to commonly used insecticides was present.
What did they find and why does it matter?
Interestingly, the researchers point out that An. coluzzii mosquitoes may have been present in Kenya for a while – since at least 2006. The previous inability to detect them is likely due to vector surveillance and identification practices that have traditionally focused on well-known primary vectors.
“Because the Anopheles gambiae complex cannot be distinguished based on morphology, Anopheles species identification commonly relies on just a few molecular markers. Using restricted information can limit the discovery of new species but also miss species when we don’t expect to find them,” explains Dr Kelly Bennett, a senior data scientist at the Genomic Surveillance Unit, Wellcome Sanger Institute and a co-first author of the publication.
Dr Luna Kamau, a Senior Principal Research Scientist and Deputy Director at the Kenya Medical Research Institute (KEMRI), who is the other first author of the publication, confirms this hunch.
“The detection of this species in samples collected as far back as 2006 points to the deficiencies of historical approaches to malaria vector surveillance and identification which have focused on historically known primary vectors using limited genetic markers,” says Dr Kamau.
The genetic analysis revealed that there wasn’t a strong population genetic differentiation between An. coluzzii from Kenya and those from West and Central Africa. This suggests that the Kenyan mosquitoes are part of a connected population range that spans a vast area across Africa.
Meet the mosquito
Anopheles coluzzii is a member of the Anopheles gambiae species complex, a group consisting of several mosquitoes that look very similar to each other. Even trained entomologists cannot distinguish adult An. coluzzii mosquitoes from other species within the complex, such as An. arabiensis and funestus, just by looking at them.
Within this group, An. coluzzii is one of the most common species responsible for transmitting malaria in Sub-Saharan Africa. They’re found in West and Central Africa, and have been spotted as far east as Somalia, but hadn’t been recorded in Kenya until now. Its spread, role in malaria transmission, and insecticide resistance vary by location, similar to other An. gambiae complex mosquitoes.
The researchers also discovered high levels of mutations that are likely to make these mosquitoes resistant to DDT and pyrethroid insecticides. However, the ace-1 mutation which is involved in their resistance to other insecticides (organophosphates and carbamates) wasn’t found in the Kenyan mosquitoes.
An. coluzzii is a vector of Plasmodium falciparum, the most dangerous malaria parasite. They are also adaptable to arid environments and can thrive in both rural and urban settings. Its presence in Kenya could mean increased malaria transmission, particularly if they have previously been absent in some areas. This can complicate malaria control efforts in a region that is already heavily burdened by the disease.
The high levels of insecticide resistance mutations found in An. coluzzii could pose a significant challenge to malaria control. Current strategies heavily rely on insecticides, such as those used in insecticide-treated nets and indoor residual sprays. This means that National Malaria Control Programmes (NMCPs) would need to reassess the insecticides used in the region.
Dr Kamau reflects on the next steps for malaria vector control in light of the discovery:
To integrate genomics into routine vector surveillance, countries will need to invest in capacities and resources for scalability. Developing and validating targeted amplicon-sequencing panels for routine surveillance, along with adopting affordable, portable sequencing technologies, could expedite this process.”
Dr Bennett emphasises that routine genomic surveillance is key to supporting ongoing entomological monitoring.
High-throughput sequencing is a valuable tool in our artillery because we can simultaneously identify species, their insecticide resistance mechanisms, and how genetic variants are shared between populations. This information can then provide an early warning system for insecticide resistance and can be used to facilitate decisions on targeted vector control.”
The power of open genomic data
This discovery was made possible by analysing large genomic datasets and the open sharing of the Anopheles gambiae 1000 Genomes project data. Platforms like the MalariaGEN Malaria Vector Genome Observatory allow researchers and public health practitioners to access and contribute valuable genetic information, foster collaboration, and accelerate discoveries.
“Our work highlights the critical role of genomics in bringing greater resolution, not just to the present and shifting vector distributions but also to the molecular, ecological, and evolutionary processes that drive adaptive changes,” says Dr Kamau. “This is integral to understanding the resilience of the malaria transmission system and will inform the design and implementation of effective vector control.”
As researchers continue to explore the geographical distribution and impact of An. coluzzii, this finding demonstrates the dynamic nature of malaria vectors and the need for new ways to prevent and control malaria.
For more detailed information, access the full Malaria Journal publication here: https://malariajournal.biomedcentral.com/articles/10.1186/s12936-024-04950-x
Join us for our next Journal Club on 27th August, where Dr Kelly Bennett will explore findings from this study in detail: https://sanger.zoom.us/webinar/register/9417229610614/WN_945Tc5ONTuib0ar99_C8nQ
