Prevalence of CYP2C8*2 and *3 among Eritreans and its Potential Impact on Artesunate/Amodiaquine Treatment.

12 Nov 2020
Habtemikael L, Russom M, Bahta I, Mihreteab S, Berhane A, Mårtensson A, Gil JP

Background

In Eritrea, artesunate-amodiaquine is the first-line treatment against uncomplicated malaria. Amodiaquine, which is mainly bio-transformed by CYP2C8, is known to be associated with adverse events of different severity. Extrapyramidal events are among the less common but have been reported with non-negligible frequency in Eritrea. This study was conducted to investigate the allele frequencies of and , both associated with decreased amodiaquine metabolism, among the Eritrean population.

Methods

During September-November 2018, dried blood samples from 380 participants and 17 patients who previously had experienced extrapyramidal symptoms following treatment of artesunate-amodiaquine were collected and PCR-RFLP genotyped for and .

Results

The allele frequencies of and were determined as 5.9% (95% CI: 4.4-7.8) and 4.6% (95% CI: 3.2-6.3), respectively. Four out of the 17 patients with extrapyramidal reactions showed to be carriers of the alleles.

Conclusion

and frequencies among Eritreans were found to be intermediate between the documented for Caucasian and African populations. These findings, along with the alleles not being decisive for the occurrence of extrapyramidal events, might be of importance regarding the amodiaquine-containing malaria treatment in Eritrea. Furthermore, it suggests a significant proportion of slow amodiaquine metabolizers in the Sahel region, information of potential interest in the context of amodiaquine-involving seasonal malaria chemoprevention.