Objectives Research Staff Publications

Parasitological Research

Resistance markers

One of the major factors contributing to the continuing worldwide malaria burden has been the emergence and rapid spread of resistance to both chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) in the human malaria parasite, Plasmodium falciparum.  In response to these increasing levels of antimalarial drug resistance the WHO recommended that artemisinin combination therapy (ACT) become standard antimalarial policy.  Recent studies have shown that the efficacy of an ACT is compromised if the artemisinin derivative is combined with an ineffective partner drug.  It is therefore imperative that the efficacy of the partner drugs is closely monitored to ensure that effective ACTs are being utilised.

In 2004 the ACT, artesunate plus SP replaced CQ as the antimalarial of choice in Mozambique.  Phased ACT implementation commenced in Matutuine District, Maputo Province in 2004 and by 2006 all districts within this province had shifted to artesunate plus SP. Unfortunately by 2007 the roll out of this ACT in the neighbouring province, Gaza Province, had yet to start.

rior to ACT implementation in Maputo Province, studies conducted by the MRP showed the prevalence of two of the five mutations essential for SP in-vivo resistance were at baseline levels.  This finding supported the use of artesunate plus SP in Maputo Province.  However, through continual surveillance for these five resistance markers, it was found that the prevalence of the dhps markers began increasing following ACT introduction. 

By 2007 the prevalence of all five mutations was well over 30% which is an early warning sign of imminent SP therapeutic failure and potential reduced efficacy of artesunate plus SP.  Based on this finding it was recommended that the first line antimalarial treatment, particularly in Maputo Province, be changed to an ACT that did not contain SP as a partner drug.  The Provincial Ministry of Health in Maputo Province heeded this recommendation and will changing their first line antimalarial treatment to artemether plus lumefantrine in 2008.

The routine monitoring of SP resistance marker prevalence in Gaza Province commenced in 2006.  Despite artesunate plus SP being the official malaria treatment policy, most health facilities within this province were still treating malaria patients with SP.  It was therefore not surprising to find that the baseline levels of the five mutations associated with SP resistance were well over 40%, within this province.  Given the high prevalence of the SP resistance markers, SP should be replaced as soon as possible in this province with ACT that does not contain SP.

This study highlighted the problems with regards to drug policy implementation. Even though the official treatment is supported by the decision makers, implementation at grass roots level is extremely difficult in areas with poor health infrastructure.

The data collected in Maputo province has shown that against a background of resistance to a partner drug, the addition of an artemisinin derivative does not halt or reduce the spread of the markers associated with resistance to the partner drug.