<p>Prevalence of <em>CYP2C8*2</em> and <em>*3</em> among Eritreans and its Potential Impact on Artesunate/Amodiaquine Treatment</p>

Abstract

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 CYP2C8*2 and *3 , 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 CYP2C8*2 and *3 . Results The allele frequencies of CYP2C8*2 and *3 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 CYP2C8*2 and *3 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.

Influence of Cytochrome P450 (CYP) 2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine treatment of uncomplicated Plasmodium falciparum malaria in Zanzibar

“…The relatively high frequency of CYP2C8*3 in Zanzibar may be related with historical links of these islands with Caucasian populations from the Arabian Peninsula. Similar CYP2C8*3 prevalence may be signi cant in countries along the Sahel region in the northern part of sub-Saharan Africa, bordering the Maghreb countries [32]. Several of these countries (e.g.…”

The Influence of Cytochrome P450 Polymorphisms on Pharmacokinetic Profiles and Treatment Outcomes Among Malaria Patients in Sub-Saharan Africa: A Systematic Review

“…Habtemikael et al 53 carried out a cross-sectional study among malaria patients on artesunate amodiaquine in Eritrea. This study reported lack of association between CYP2C8*2 (805A>T) or CYP2C8*3 (416A>G) and extra pyramidal effects among Eritreans.…”

Current situation of fungal diseases in Eritrea

“…Map of Eritrea, its six administrative regions and the geographic distribution of the sampling points (health facilities in each zone) covering all of the regions of the country 47 …”

“…Intimate contact with domestic animals as well as contact with infected children and shared items such as combs, and towels were among the associated risk factors51 There are also reports of tinea capitis from Eritrean migrants in Switzerland and other European countries, one after returning from a 4-week visit in Eritrea52 and the other immigrants from Eritrea. In F I G U R E 2 Map of Eritrea, its six administrative regions and the geographic distribution of the sampling points (health facilities in each zone) covering all of the regions of the country47 a similar context, a study of tinea capitis in an immigrant paediatric community showed that out of 76 cases, 64 (84%) had a positive culture. The study was conducted among children born in Israel to…”