**5. Dichlorodiphenyltrichloroethane (DDT)**

DDT is an OC insecticide; it is white, crystalline solid, tasteless, and almost odorless (PAN, 2012). It is a highly hydrophobic molecule, nearly insoluble in water but with good solubili‐ ty in most organic solvents, such as fats and oils. DDT is not present naturally, but is pro‐ duced by the reaction of chloral (CCl3CHO) with chlorobenzene (C6H5Cl) in the presence of sulfuric acid, which acts as a catalyst. DDT was originally synthesised in 1874, but its action as an insecticide was not discovered until 1939. It was the first widely used synthetic pesti‐ cide, employed extensively by allied forces during the Second World War for the protection of military personnel from malaria and typhus, released commercially only in 1945. The Swiss chemist Paul Hermann Müller was awarded the Nobel Prize in Physiology or Medi‐ cine in 1948 for his discovery of the high efficiency of DDT as a contact poison against sever‐ al arthropods.

**Figure 2.** DDT

**4.2. Indoor Residual Spraying (IRS) and Insecticide-Treated Nets (ITNs)**

336 Insecticides - Development of Safer and More Effective Technologies

historically been used for IRS, the first and most well-known being DDT.

tract, synthetic PYs, and Malathion.

of an ITN program (Lines, 1996).

Indoor residual spraying (IRS) with insecticides continues to be the mainstay for malaria control and represents the process of spraying stable formulations of insecticides on the in‐ side walls of certain types of dwellings, those with walls made from porous materials such as mud or wood but not plaster as in city dwellings. Mosquitoes are killed or repelled by the spray, preventing the transmission of the disease. The main purpose of IRS is to reduce ma‐ laria transmission by reducing the survival of malaria vectors, life span of female mosqui‐ toes, thereby reducing density of mosquitoes (WHO, 2006b). Several pesticides have

Space spraying, or fogging, relies on the production of a large number of small insecticidal droplets, that resemble smoke or fog by rapidly heating the liquid chemical, intended to be distributed through a volume of air over a given period of time. When these droplets impact on a target insect, they deliver a lethal dose of insecticide. It is primarily reserved for appli‐ cation during emergency situations to rapidly reduce the population of flying insects in a specific area resulting in decrease of transmission (CDC, 2009). It is effective as a contact poi‐ son with no residual effect, thus it must be repeated at intervals of 5-7 days in order to be fully effective. The application must coincide with the peak activity of adult mosquitoes, be‐ cause resting mosquitoes are often found in areas that are out of reach to the applied insecti‐ cides. The best moment to kill adult mosquitoes by fogging is at dusk, when they are most active in forming swarms. The most commonly used products are natural pyrethrum ex‐

Mosquito nets treated with insecticides—known as insecticide treated nets (ITNs) or bed‐ nets—were developed in the 1980s for malaria prevention. Properly used, a mosquito net effectively offers protection against mosquitoes and other insects, and thus against the diseases they may carry. Two categories of ITNs are available: conventionally treated nets and long-lasting ITNs (LLINs). ITNs are estimated to be twice as effective as untreated nets, and offer greater than 70% protection compared with no net. These nets are impreg‐ nated with PYs, which will double the protection over a non-treated net by killing and re‐ pelling mosquitoes, and are proved to be a cost-effective prevention method against malaria (D'Alessandro et al., 1995). Washing and the associated regular retreatment of the nets determine a rapid loss of efficacy of ITNs, thus limiting the operational effectiveness

Biological activity of LLINs, a relatively new technology, generally retains the efficacy for at least 3 years (WHO, 2005), and can reduce human–mosquito contact, which results in lower sporozoite and parasite rates. Different types of long-lasting insecticide impregnated materi‐ als are under field trials in different countries. Treatments of screens, curtains, canvas tents, plastic sheet, tarpaulin, etc., with insecticides may provide a cheap and practical solution for malaria vector control. Particularly, the residual insecticides in insecticide-treated wall lin‐ ing (ITWL) are durable and can maintain control of insects significantly longer than IRS by providing an effective alternative or additional vector control tool (Munga et al., 2009).

#### **5.1. Production and use**

While the post-war period also saw the introduction of most of the other major families of insecticides still in use today, DDT remained the most extensively used insecticide through‐ out the world until the mid 1960s. By this time, it had been credited with a number of signif‐ icant public health successes, including the eradication of malaria from the United States and Europe (Attaran & Maharaj, 2000). DDT is currently being produced in three countries: India, China, and the Democratic People's Republic of Korea (North Korea). By far the larg‐ est amounts are produced in India for the purpose of disease vector control. In China, the average annual production during the period 2000–2004 was 4,500 metric tons of DDT, but 80–90% was used in the production of Dicofol, an acaricide, and around 4% was used as ad‐ ditive in antifouling paints. The remainder was meant for malaria control and was exported (PAN, 2012).

#### **5.2. Cost-effectiveness**

Both the effectiveness and costs of DDT are dependent on local settings and deserve careful consideration in relation to alternative products or methods (Walker, 2000). DDT has been known as the only insecticide that can be used as a single application in areas where the ma‐ laria transmission season is > 6 months. However, information is lacking on the potential variability in residual action of DDT (e.g., due to sprayable surface, climatic conditions, so‐ cial factors). Direct costs of IRS are the procurement and transport of insecticide, training of staff, operations, awareness-raising of communities, safety measures, monitoring of efficacy and insecticide resistance, monitoring of adverse effects on health and the environment, and storage and disposal. Apart from the direct costs, it is essential that the unintended costs of DDT to human health and the environment are included in the cost assessment. In addition, contamination of food crops with DDT could negatively affect food export. A comprehen‐ sive cost assessment of DDT versus its alternatives should include the potential costs of at‐ mospheric transport and chronic health effects.

Many insect species have developed resistance to DDT. The first cases of resistant flies were known to scientists as early as 1947, although this was not widely reported at the time (Met‐ calf, 1989). Since the introduction of DDT for mosquito control, DDT resistance at various levels has been reported from > 50 species of anopheline mosquitoes, including many vec‐ tors of malaria (Hemingway & Ranson, 2000). Unless due attention is paid to the role of in‐ secticide resistance in the breakdown of the malaria eradication campaign of the 1960s,

DDT as Anti-Malaria Tool: The Bull in the China Shop or the Elephant in the Room?

http://dx.doi.org/10.5772/53241

339

In the past, the use of DDT in agriculture was considered a major cause of DDT resistance in malaria vectors, as many vectors breed in agricultural environments. By 1984 a world sur‐ vey showed that 233 species, mostly insects, were resistant to DDT (Metcalf, 1989). Today, with cross resistance to several insecticides, it is difficult to obtain accurate figures on the situation regarding the number of pest species resistant to DDT. At present, DDT resistance is thought to be triggered further by the use of synthetic PYs (Diabate et al., 2002). This is due to a mechanism of cross-resistance between PYs and DDT, the so-called sodium channel mutation affecting neuronal signal transmission, which is governed by the *kdr* (knock-down resistance) gene (Martinez-Torres et al., 1998). The *kdr* gene is being reported from an in‐ creasing number of countries; thus, even in countries without a history of DDT use, resist‐ ance to DDT is emerging in populations of malaria vectors (WHO, 2006a). Contemporary data from sentinel sites in Africa indicate that the occurrence of resistance to DDT is wide‐ spread, especially in West and Central Africa. In Asia, the resistance to DDT is particularly

Part of the success of DDT can be attributed to its persistence in the environment, thus re‐ ducing the need for frequent application. DDT is one of nine persistent organic pollutants (POPs) which bioaccumulate and are transported by air and water currents from warmer climates to temperate zones, where they have never been used. DDT has low to very low rates of metabolism and disposition, depending on ambient temperatures: the process of degradation is dramatically slowed down in cooler climates. It is degraded slowly into its main metabolic products, 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and dichloro‐ diphenyldichloroethane (DDD), which have similar physicochemical properties but differ in

DDT is emitted through volatilization and runoff. It is more volatile in warmer than in colder parts of the world, which through long-range atmospheric transport results in a net deposition and thus gradual accumulation at high latitudes and altitudes (Harrad, 2001). Loss through runoff is low because DDT is extremely hydrophobic and has a strong affinity for organic matter in soils and aquatic sediment but is virtually insoluble in water. However, when applied to aquatic ecosystems, DTT is quickly absorbed by or‐ ganisms and by soil or it evaporates, leaving little amount of DDT dissolved in the water itself (Agency for Toxic Substances and Disease Registry, 2002). Half-lives of DDT have been reported in the range of 3–7 months in tropical soils (Varca & Magallona 1994; Wan‐

resistance may once again undermine malaria control.

widespread in India.

biological activity.

**5.5. Environmental issues**

#### **5.3. Mechanism of action**

The basic mechanism of action for most pesticides is an alteration in the transfer of a signal along a nerve fiber and across the synapse from one nerve to another or from a nerve to a muscle fiber. The transfer of a signal along a nerve occurs by changes in the electrical poten‐ tial across the nerve cell membrane which is created by the movement of ions in and out of the cell. At the terminal end of a nerve, the signal is transferred across the synapse to the next nerve cell by the release of neurotransmitters. Different classes of pesticides inhibit this process in different ways, but the end result is an alteration in normal nerve signal propaga‐ tion. OCs pesticides act primarily by altering the movement of ions across the nerve cell membranes, thus changing the ability of the nerve to fire.

The WHO has designated DDT as a Class II pesticide, based on its LD50 of 250 mg/kg (WHO, 1996). The mechanism by which DDT causes neurotoxicity is well studied. In in‐ sects DTT opens sodium ion channels in neurons, causing them to burn spontaneously. By causing repetitive firing of nerve cells, the cells eventually are unable to fire in re‐ sponse to a signal. DDT produces tremors and incoordination at low doses, convulsions at higher doses caused by the repetitive discharge (over-firing) of the nerves. Effects of chronic exposures to DDT are difficult to identify because they are general nervous sys‐ tems alterations that can occur through many causes (apathy, headache, emotional labili‐ ty, depression, confusion and irritability).

#### **5.4. Resistance issues**

As the number and size of programs that use DDT for indoor spraying increase, insecticide resistance is a matter of growing concern. Insects with certain mutations in their sodium channel gene are resistant to DDT and other similar insecticides. DDT resistance is also con‐ ferred by up-regulation of genes expressing cytochrome P450 in some insect species (Den‐ holm et al., 2002).

Many insect species have developed resistance to DDT. The first cases of resistant flies were known to scientists as early as 1947, although this was not widely reported at the time (Met‐ calf, 1989). Since the introduction of DDT for mosquito control, DDT resistance at various levels has been reported from > 50 species of anopheline mosquitoes, including many vec‐ tors of malaria (Hemingway & Ranson, 2000). Unless due attention is paid to the role of in‐ secticide resistance in the breakdown of the malaria eradication campaign of the 1960s, resistance may once again undermine malaria control.

In the past, the use of DDT in agriculture was considered a major cause of DDT resistance in malaria vectors, as many vectors breed in agricultural environments. By 1984 a world sur‐ vey showed that 233 species, mostly insects, were resistant to DDT (Metcalf, 1989). Today, with cross resistance to several insecticides, it is difficult to obtain accurate figures on the situation regarding the number of pest species resistant to DDT. At present, DDT resistance is thought to be triggered further by the use of synthetic PYs (Diabate et al., 2002). This is due to a mechanism of cross-resistance between PYs and DDT, the so-called sodium channel mutation affecting neuronal signal transmission, which is governed by the *kdr* (knock-down resistance) gene (Martinez-Torres et al., 1998). The *kdr* gene is being reported from an in‐ creasing number of countries; thus, even in countries without a history of DDT use, resist‐ ance to DDT is emerging in populations of malaria vectors (WHO, 2006a). Contemporary data from sentinel sites in Africa indicate that the occurrence of resistance to DDT is wide‐ spread, especially in West and Central Africa. In Asia, the resistance to DDT is particularly widespread in India.

#### **5.5. Environmental issues**

**5.2. Cost-effectiveness**

**5.3. Mechanism of action**

mospheric transport and chronic health effects.

338 Insecticides - Development of Safer and More Effective Technologies

membranes, thus changing the ability of the nerve to fire.

ty, depression, confusion and irritability).

**5.4. Resistance issues**

holm et al., 2002).

Both the effectiveness and costs of DDT are dependent on local settings and deserve careful consideration in relation to alternative products or methods (Walker, 2000). DDT has been known as the only insecticide that can be used as a single application in areas where the ma‐ laria transmission season is > 6 months. However, information is lacking on the potential variability in residual action of DDT (e.g., due to sprayable surface, climatic conditions, so‐ cial factors). Direct costs of IRS are the procurement and transport of insecticide, training of staff, operations, awareness-raising of communities, safety measures, monitoring of efficacy and insecticide resistance, monitoring of adverse effects on health and the environment, and storage and disposal. Apart from the direct costs, it is essential that the unintended costs of DDT to human health and the environment are included in the cost assessment. In addition, contamination of food crops with DDT could negatively affect food export. A comprehen‐ sive cost assessment of DDT versus its alternatives should include the potential costs of at‐

The basic mechanism of action for most pesticides is an alteration in the transfer of a signal along a nerve fiber and across the synapse from one nerve to another or from a nerve to a muscle fiber. The transfer of a signal along a nerve occurs by changes in the electrical poten‐ tial across the nerve cell membrane which is created by the movement of ions in and out of the cell. At the terminal end of a nerve, the signal is transferred across the synapse to the next nerve cell by the release of neurotransmitters. Different classes of pesticides inhibit this process in different ways, but the end result is an alteration in normal nerve signal propaga‐ tion. OCs pesticides act primarily by altering the movement of ions across the nerve cell

The WHO has designated DDT as a Class II pesticide, based on its LD50 of 250 mg/kg (WHO, 1996). The mechanism by which DDT causes neurotoxicity is well studied. In in‐ sects DTT opens sodium ion channels in neurons, causing them to burn spontaneously. By causing repetitive firing of nerve cells, the cells eventually are unable to fire in re‐ sponse to a signal. DDT produces tremors and incoordination at low doses, convulsions at higher doses caused by the repetitive discharge (over-firing) of the nerves. Effects of chronic exposures to DDT are difficult to identify because they are general nervous sys‐ tems alterations that can occur through many causes (apathy, headache, emotional labili‐

As the number and size of programs that use DDT for indoor spraying increase, insecticide resistance is a matter of growing concern. Insects with certain mutations in their sodium channel gene are resistant to DDT and other similar insecticides. DDT resistance is also con‐ ferred by up-regulation of genes expressing cytochrome P450 in some insect species (Den‐

Part of the success of DDT can be attributed to its persistence in the environment, thus re‐ ducing the need for frequent application. DDT is one of nine persistent organic pollutants (POPs) which bioaccumulate and are transported by air and water currents from warmer climates to temperate zones, where they have never been used. DDT has low to very low rates of metabolism and disposition, depending on ambient temperatures: the process of degradation is dramatically slowed down in cooler climates. It is degraded slowly into its main metabolic products, 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and dichloro‐ diphenyldichloroethane (DDD), which have similar physicochemical properties but differ in biological activity.

DDT is emitted through volatilization and runoff. It is more volatile in warmer than in colder parts of the world, which through long-range atmospheric transport results in a net deposition and thus gradual accumulation at high latitudes and altitudes (Harrad, 2001). Loss through runoff is low because DDT is extremely hydrophobic and has a strong affinity for organic matter in soils and aquatic sediment but is virtually insoluble in water. However, when applied to aquatic ecosystems, DTT is quickly absorbed by or‐ ganisms and by soil or it evaporates, leaving little amount of DDT dissolved in the water itself (Agency for Toxic Substances and Disease Registry, 2002). Half-lives of DDT have been reported in the range of 3–7 months in tropical soils (Varca & Magallona 1994; Wan‐ diga, 2001) and up to 15 years in temperate soils (Ritter et al., 1995). The half-life of each of its metabolic products is similar or longer.

ducting a re-evaluation of health risks of DDT, but progress has been slow (PAN, 2012). Nevertheless, in 2006 it approved the use of DDT, particularly indoor residual spraying of walls, in areas endemic for malaria for health-related reasons (WHO, 2006a; WHO, 2006b), although it also carefully drew up major guidelines (WHO 2000). Currently, DDT represents one the main stays to achieve goals of Global Eradication Program launched in 2007 by the Bill and Melinda Gates Foundation, the World Health Organization (WHO) and the Roll Back Malaria association (Roberts & Enserink, 2007; Greenwood, 2008; Khadjavi et al., 2010; Prato et al., 2012). However, in the recent years the possible effects of DDT on human health have been a hot topic of discussion inside malaria research community, as certified by the large number of available publications and intense correspondence among scientists (e.g., Blair et al., 2009; Burton, 2009; van den Berg, 2009; Tren & Roberts, 2010; Bouwman et al., 2011; Tren & Roberts, 2011). The debate is heavily polarized, and three main viewpoints can be identified, as suggested by Bouwman et al. (Bouwman et al., 2011): anti-DDT, centrist-

DDT as Anti-Malaria Tool: The Bull in the China Shop or the Elephant in the Room?

http://dx.doi.org/10.5772/53241

341

DDT opponents usually claim for DDT elimination because of environmental and health concerns. However, Tren & Roberts (Tren & Roberts, 2011) pointed that the "activist groups currently promote an anti-DDT agenda routinely hyping supposed human health and envi‐ ronmental harm from DDT and ignoring studies that find no association between DDT and such harm". As an example, Tren & Roberts mentioned the Biovision's "Stop DDT" project engaged to achieve a world-wide ban on DDT (Biovision, 2011), which apparently was con‐ nected to the Secretariat of the Stockholm Convention's promotion of an arbitrary deadline for cessation of DDT production by 2020 (United Nations Environment Programme, 2007). Another representative example of a recent anti-DDT action is given by a court case occur‐ red in Uganda (Lewis, 2008): a petition filed in Kampala's High Court accused the Ugandan government of not following DDT spraying guidelines, whether those of the WHO or those of Uganda's National Environment Management Authority. In that case, it appears evident that the big matter was not DDT itself as a molecule, but its incorrect use. In this context, a major point questioned by anti-DDT scientists is that also IRS workers are highly exposed to DDT, since prescribed personal protection procedures and safe practices are not always fol‐ lowed, because of uncomfortable working conditions. Not wearing masks or gloves and fre‐ quent wiping of sweaty faces with the same cloth increases dermal and inhalation uptake leading to very high exposure (Bowman et al., 2011). Indeed, DDT serum levels in IRS work‐ ers in South Africa were high compared with the general population living in DDT-sprayed houses (Bouwman et al., 1991). On the other hand, Bimenya et al. (Bimeneya et al., 2010) did not found any DDT increase in serum of Ugandan DDT applicators over an entire spray sea‐ son, stating that effective exposure reduction is possible when protective clothing is used and strict adherence to WHO guidelines (WHO, 2000) is observed. Nevertheless, the WHO's review of human health aspects of DDT use in IRS concluded that "for households where IRS is undertaken, there was a wide range of DDT and DDE serum levels between studies. Generally, these levels are below potential levels of concern for populations" (WHO, 2011b), and none of the thousands of studies conducted to find possible human health effects of

DDT, and pro-DDT.

**6.1. Anti-DDT point of view**

The global risk of adverse effects to human health and the environment has led the inter‐ national community to mandate the UN Environment Programme (UNEP) to convene an intergovernmental negotiating committee (INC) for a POPs Convention to phase out pro‐ duction and use (UNEP, 1997a; UNEP, 1997b). As a result of these environmental con‐ cerns, the use of DDT was increasingly restricted or banned in most developed countries after 1970.

DDT and its metabolic products present in the global environment have originated mostly from its previous large-scale use in agriculture and domestic hygiene. Because DDT is cur‐ rently allowed only for indoor spraying for disease vector control, its use is much smaller than in the past. Nevertheless, DDT sprayed indoors may end up in the environment (e.g., when mud blocks of abandoned houses are dissolved in the rain). Even today, DDT remains so widespread in the environment that it is likely that exposure to it is unavoidable. While exposure in the industrialised world has fallen dramatically, exposure remains high in some developing countries where DDT continues to be used in vector control.

DDT is very fat-soluble and could therefore be found in fatty foods such as meat and diary products. Even in countries across North America and Northern Europe, where its use has been banned for over a decade DDT residues are still often found in food. This is because of environmental persistence, illegal use, or importation of contaminated food from regions where DDT is still used.
