Resistance has greatly reduced DDT's effectiveness. WHO guidelines require that absence of resistance must be confirmed before using the chemical. Resistance is largely due to agricultural use, in much greater quantities than required for disease prevention. According to one study that attempted to quantify the lives saved by banning agricultural use and thereby slowing the spread of resistance, "it can be estimated that at current rates each kilo of insecticide added to the environment will generate 105 new cases of malaria."
Resistance was noted early in spray campaigns. Paul Russell, a former head of the Allied Anti-Malaria campaign, observed in 1956 that "resistance has appeared [after] six or seven years." DDT has lost much of its effectiveness in Sri Lanka, Pakistan, Turkey and Central America, and it has largely been replaced by organophosphate or carbamate insecticides, e.g. malathion or bendiocarb.
In many parts of India, DDT has also largely lost its effectiveness. Agricultural uses were banned in 1989, and its anti-malarial use has been declining. Urban use has halted completely. Nevertheless, DDT is still manufactured and used, and one study had concluded that "DDT is still a viable insecticide in indoor residual spraying owing to its effectivity in well supervised spray operation and high excito-repellency factor."
Studies of malaria-vector mosquitoes in KwaZulu-Natal Province, South Africa found susceptibility to 4% DDT (the WHO susceptibility standard), in 63% of the samples, compared to the average of 86.5% in the same species caught in the open. The authors concluded that "Finding DDT resistance in the vector An. arabiensis, close to the area where we previously reported pyrethroid-resistance in the vector An. funestus Giles, indicates an urgent need to develop a strategy of insecticide resistance management for the malaria control programmes of southern Africa."
DDT can still be effective against resistant mosquitoes, and the avoidance of DDT-sprayed walls by mosquitoes is an additional benefit of the chemical. For example, a 2007 study reported that resistant mosquitoes avoided treated huts. The researchers argued that DDT was the best pesticide for use in IRS (even though it did not afford the most protection from mosquitoes out of the three test chemicals) because the others pesticides worked primarily by killing or irritating mosquitoes—encouraging the development of resistance to these agents. Others argue that the avoidance behavior slows the eradication of the disease. Unlike other insecticides such as pyrethroids, DDT requires long exposure to accumulate a lethal dose; however its irritant property shortens contact periods. "For these reasons, when comparisons have been made, better malaria control has generally been achieved with pyrethroids than with DDT." In India, with its outdoor sleeping habits and frequent night duties, "the excito-repellent effect of DDT, often reported useful in other countries, actually promotes outdoor transmission."