Malaria is spread through the bite of a female Anopheles mosquito infected with the plasmodium parasite. New evidence has shown how the malaria parasite, Plasmodium falciparum,
has been outsmarting Kenya’s health policies for the last 20
years.
It shows the parasite not only remembers the medicines it defeated in the past (such as chloroquine), but is building resistance against the drugs we rely on today, while preparing to fight future treatments.
Scientists from the Kenya Medical Research Institute (Kemri)
and Brown University (US) made this assessment after tracking the parasite’s
resistance to malaria drugs in Kenya between 1998 and 2021 in the most
comprehensive such study in East Africa to date.
They have published their findings in a paper available on the preprint server MedRxiv.
Kenya’s national malaria treatment strategy has changed
multiple times in the past 25 years, but the new findings suggest the parasite has
kept up and sometimes even anticipated new treatments before they came.
“These findings
demonstrate the rapid and dynamic evolution of drug resistance in response to
shifting antimalarial drug pressures,” the scientists said. “They underscore
the need for sustained genomic surveillance in malaria-endemic regions to
inform adaptive treatment strategies.”
The researchers analysed 642 blood samples from malaria
patients across Kenya, collected between 1998 and 2021. They analysed parasites
found in the blood using powerful genetic tools, helping them track how the malaria
parasite has changed in response to Kenya’s shifting drug policies.
They conclude that the parasite is a step ahead.
Kenya changed malaria treatment policy from chloroquine in
the 1990s to sulphadoxine-pyrimethamine (SP) in 1998 and then to
artemisinin-based combination therapies (ACTs) in 2006.
The new findings suggest the parasite was not just reacting
to these changes, but it was anticipating them.
Soon after ACTs were adopted in 2006, mutations that help
the parasite survive Kenya’s preferred drug, artemether-lumefantrine (Coartem), began rising sharply.
The researchers identified the dramatic spread of a mutant
version of the parasite carrying what is known as the MDR1 NFD haplotype. This
is a trio of mutations that make lumefantrine less effective.
“Following the adoption of artemether-lumefantrine (AL) in
2006, we observed a rapid expansion of MDR1 N86N, Y184F, and D1246D alleles
associated with reduced lumefantrine susceptibility,” the researchers
observed.
By 2021, this resistant version had become dominant,
silently outcompeting its more drug-sensitive cousins. No policy at Afya House
had accounted for that, and even now, few malaria treatment guidelines reflect
these shifts.
Even more damning is how the parasite responded when Kenya
retired old drugs. Kenya officially dropped chloroquine (CQ) in 1998 due to
resistance. Yet for eight more years, the resistant mutations stuck around, as
if the parasite knew chloroquine might still be circulating informally.
But the moment ACTs became the main therapy in 2006, the old
chloroquine-resistant mutations started to vanish. The parasite quickly
reverted to its original form (the CQ-sensitive again) as if preparing for a
possible chloroquine comeback.
“We observed a progressive loss of the hallmark CQ-resistant
(CVIET and CVIETS) haplotypes… and the predominance of wild-type alleles,” the
study said.
That is not random evolution but an adaptation that is
smart, calculated, and faster than a bureaucratic response.
SP was officially sidelined in 2006. Yet today, Kenya still
uses it in pregnant women and children under five to prevent malaria. The
parasite, apparently aware, has clung onto the very mutations that render SP
useless.
The study found that DHFR and DHPS mutations associated with
SP resistance are now near-fixation, meaning they are found in nearly all malaria
parasites circulating in Kenya.
“The triple DHFR-IRN (I51-R59-N108) and double DHPS GE
(G437G-E540E) haplotypes associated with high-level SP resistance reached
fixation shortly after SP became frontline therapy in 1998 and have persisted
despite its withdrawal.”
That suggests that even though the government thinks SP is
safe for prevention, the parasite has evolved to ignore it.
“More concerning is the emergence of quadruple DHFR IRNL and
triple DHPS GEG (reported in Rwanda and Tanzania) … which could undermine
SP-based intermittent preventive treatment if they continue to spread.”
The parasite’s next trick may be its deadliest.
The researchers did not find widespread mutations that fully
resist artemisinin, the backbone of today’s ACT drugs. However, they did find
suspicious changes that suggest trouble is brewing.
“We detected UBP1 mutations D1525E and E1528D and AP2MU
mutation S160N, which have all been linked to delayed clearance after treatment
with ACTs,” they warned.
That means artemisinin may start taking longer to clear
infections. This is a key warning sign of resistance. And Kenya has already
confirmed the presence of two fully validated artemisinin resistance mutations
— A675V and C469Y — in samples collected in 2021 and 2022. But those came after
this study ended.
If those mutations spread (and the parasite has shown it
knows how to spread them), the country’s entire malaria response could be
compromised.
The authors have advised Kenya to invest in real-time
molecular surveillance, revise treatment policies quickly based on new
evidence, and prepare for next-generation drug strategies, like triple-drug
therapies.
“Combining enhanced molecular surveillance with therapeutic
efficacy studies (TES) will provide a more comprehensive understanding of drug
resistance evolution and inform future malaria control strategies. This work is
particularly important considering the recent emergence of validated ART-R-associated K13 mutations in Kenya. As ART-R expands regionally and ACT partner
drug and preventative treatment resistance trends continue to evolve, enhanced
genomic surveillance will be critical for guiding adaptive treatment policies
and sustaining malaria control efforts,” they said.
Their paper is titled, “Two decades of molecular
surveillance in Kenya reveal shifting Plasmodium falciparum drug resistance
mutations linked to frontline drug changes.”
Malaria is spread through the bite of a female Anopheles mosquito infected with the plasmodium parasite.
In Kenya, it kills about 10,000 people every year, most of them young children and pregnant women, according to the Ministry of Health and WHO estimates.