Malaria is the most prevalent vector borne disease worldwide, and predominantly affects third world and developing countries . Many of these countries experience limited economic growth, which is, in part, exacerbated by the effects of malaria. The impact of malaria can be seen by decreased levels of productivity in home and work environments and by the added strain that this disease places on already overburdened health care systems .
The two major malaria vectors in southern Africa are Anopheles arabiensis and Anopheles funestus. Anopheles gambiae can be found in the northern-most parts of this sub-region . Malaria in South Africa is hypoendemic. The primary malaria vector, An. funestus, is controlled by an indoor residual spraying (IRS) campaign that currently adopts a mosaic approach using DDT (dichloro-diphenyl-trichloroethane), carbamates and pyrethroids . This approach was adopted after pyrethroid resistance was identified in South African and southern Mozambican An. funestus populations [5, 6]. Pyrethroid resistance in this species was closely associated with a dramatic increase in malaria incidence in South Africa during the period 1995 – 2000. Prior to this period, only DDT was used for IRS, but mounting international pressure to discontinue its use led to the implementation of pyrethroids as the insecticide of choice . DDT was re-introduced for IRS in South Africa post 2000 and a five- to six-fold decrease in malaria incidence was recorded for the period 2001 to 2005 . The development of insecticide resistance in other malaria vector populations in South Africa  induces additional cause for concern, and an understanding of the mode, expression and inheritance of insecticide resistance mechanisms has become increasingly important.
Insecticide resistance in insect populations is predominantly based on improved enzymatic sequestration and detoxification as well as by the alteration of insecticide target sites leading to insecticide insensitivity . Improved enzymatic detoxification has been linked to three broad classes of enzymes, namely monooxygenases, glutathione-S-transferases (GSTs) and non-specific esterases. Pyrethroid resistance in Culex quinquefasciatus , Culex pipiens pipiens , An. gambiae  and An. funestus [6, 13] has been linked to the increased activity of cytochrome P450s, members of the monooxygenase class of detoxification enzymes.
The P450 monooxygenases are a superfamily of enzymes that have been implicated in the detoxification of xenobiotics and endogenous metabolic products in insects . Clusters of cytochrome P450 genes have been associated with pyrethroid resistance based on the chromosomal mapping of quantitative trait loci or QTLs [15, 16]. In southern African An. funestus, a QTL associated with pyrethroid resistance can be found on chromosome 2R. This position corresponds to the locality of a cluster of genes belong to the CYP6 class of P450 enzymes . CYP6P9, located within this cluster, has been shown to be highly over-expressed in a pyrethroid resistant strain of An. funestus , confirming the importance of these enzymes in insecticide resistance.
Current evidence suggests a direct link between the increased expression of detoxification genes and the development of pyrethroid resistance in southern African An. funestus . Since many major biological processes affect gene expression it is possible that insecticide detoxification gene expression may be stimulated by processes other than insecticide exposure. The upregulation of cytochrome P450s in response to a blood meal has been demonstrated in C. pipiens  and Aedes aegypti . It is hypothesized that the detoxification of xenobiotics and toxic blood components in the An. funestus midgut may inadvertently result in an increased ability to tolerate insecticide intoxication.