Status of the Artemisinin Resistance-Associated PfATPase6 S769N Mutation in Plasmodium Falciparum Infections of Lusaka Urban District; Zambia

ABSTRACT

Objective: Artemisinin derivatives constitute a key component of the present-day treatment for Plasmodium falciparum malaria. In Zambia the national malaria policy was revised in 2003 to replace chloroquine mono-treatment with artemisinin combination therapy (ACT). Resistance to artemisinin is associated with a S769N point mutation in the sarcoendoplasmic reticulum calcium-dependant ATPase6 (SERCA-PfATPase6) gene of P. falciparum. However; the baseline or current levels of this mutation in Zambia remain unknown. The present study was aimed at determining the prevalence of the putative artemisinin resistance marker and the extent to which the recommended ACT (artemether-lumefantrine) was in use in Lusaka Urban district. Design: This was a cross sectional prospective study. Using a nested PCR and allele specific restriction enzyme digestion strategy; P. falciparum infections from ten sites in Lusaka urban district were assayed for the prevalence of the PfATPase6 S769N mutation. The availability of current ACT and the extent to which it has been used since introduction were assessed using interview by questionnaire. Main Outcome: The PfATPase6 S769N mutation was not found on any of the infections analyzed in the present study. Artemether-lumefantrine ACT was readily available in both government-owned health centres and private drug stores as first line malaria treatment in Lusaka urban district. Conclusion: The absence of the PfATPase6 S769N mutation suggests 100artemisinin sensitivity unless a different resistance mechanism exists. Continued resistance monitoring and investigation of other potential molecular markers is recommended as wider ACT use is scaled up in the country