Trends in Plasmodium falciparum resistance markers to sulfadoxine-pyrimethamine and amodiaquine over ten years of seasonal malaria chemoprevention in Moissala Health District, Chad

BACKGROUND

Seasonal Malaria Chemoprevention (SMC) has been implemented in Moissala Health District, southern Chad, since 2013 using the standard regimen of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ). Although not the sole determinant, SMC can play an important role in generating parasite drug resistance. Three studies spanning a ten-year period were conducted to monitor evolving trends of molecular markers of resistance to SP and AQ in implementation areas.

METHODS

In 2014, 2021, and 2023, a total of 136, 256, and 219 blood samples, respectively, were collected from children with clinical malaria residing in eight health zones. Samples were analysed for known molecular mutations associated with emerging Plasmodium falciparum resistance to SP (dhfr N51I, C59R, and S108N; dhps A437G and K540E) and to AQ (pfcrt K76T and pfmdr-1 N86Y).

RESULTS

The proportion of triple dhfr mutants was very high in 2014 and 2021 (100% and 96.9%, respectively), but significantly lower in 2023 (83.9%, p < 0.001). The proportion of quadruple mutants (triple dhfr + dhps A437G) significantly increased from 28.0% in 2014 to 41.0% in 2021 and 47.9% in 2023 (p < 0.001). The proportion of quintuple mutants (triple dhfr + double dhps) was low and did not significantly increase over the years studied (7.6%, 2.8%, and 5.9% in 2014, 2021, and 2023, respectively). The proportion of samples with the pfcrt K76T mutation decreased from 44.6% in 2014 to approximately 11% in 2021 and 2023, while the proportion of samples with the pfmdr-1 N86Y mutation remained consistently low across all three studies. One sample in 2014 exhibited all seven point-mutations investigated, while none were detected in samples in 2021 or 2023.

CONCLUSION

Surveillance of molecular markers of resistance conducted over a ten-year period in Moissala Health District indicates that SP and AQ remain effective despite prolonged use. However, the rise in quadruple mutants-linked to partial SP resistance-is concerning, and monitoring is needed to detect any increase in quintuple mutants, which confer stronger resistance. These findings underscore the importance of sustained molecular surveillance to guide policy decisions and enable timely adaptations of SMC strategies as resistance patterns evolve.

KEYWORDS

Plasmodium falciparum; Amodiaquine; Chad; Malaria; Molecular markers of resistance; Seasonal malaria chemoprevention; Sulfadoxine-pyrimethamine.