**7. Host allelochemicals, induction of detoxifying enzymes and insecticide resistance**

Understanding the diversity of insect responses to chemical pressures (plant allelochemicals and insecticides) in their local ecological context represents a key challenge in developing sustainable pest control strategies. Plants and insects have had co-existing relationships for a long time. Insects were suppressed either by other insects or toxins or by plant defence mechanisms in order to create a balance between the insect pest population and host. Each plant species has a unique set of defence traits ranging from morphological to phytochemical parameters that have behavioural and physiological ramifications for a potential herbivore consumer [181, 182]. Therefore, the resistance mechanisms evolved by insects to deal with the chemical defences of plants are similar to those mechanisms that have evolved to resist synthetic insecticides. The chemical structure of some synthetic insecticides is comparable to that of some plant-produced compounds (e.g. pyrethroids and nicotinoids). Insect resistance to plant allelochemicals interferes with their resistance to synthetic insecticides [183]. From the evolutionary perspective, despite the key role of the chemical 'arms race' in driving the coevolution of plants and insects, much research has focused so far on describing the diversity of plant chemicals and their effects on herbivores. Hence, the understanding of insecticide resistance mechanisms as well as taking into account other ecological parameters is important in predicting the spread of insecticide resistance in natural pest populations and in choosing the optimum strategy for managing insect pest populations. Less is known about the multiple mechanisms evolved by insects to overcome these chemical defences (Table 4). These mecha‐ nisms include contact and ingestion avoidance, excretion, sequestration, degradation of the toxin and target site mutation.

Biotransformation of plant toxins is one of the major weapons that insects have evolved in their co-evolutionary arms race with plants [204]. To date, metabolic resistance to plant chemicals has been identified not only in herbivorous insects [194] but also in detrivorous insects such as mosquito larvae feeding plant debris [205]. Metabolic resistance often results from the overproduction of 'detoxification enzymes' that can metabolize plant xenobiotics (allelochemicals). This mechanism is often associated with phenotypic plasticity, as the production of detoxification enzymes is usually induced by the presence of plant xenobiotics in the diet of the insect.

Induction of insect detoxifying enzyme activities by plant allelochemicals is a clear manifes‐ tation of biochemical phenotypic plasticity and has been documented in several instances [206, 207]. Many of the theories and some of the experiments implicitly or explicitly deal with the insect's ability to metabolize plant secondary substances by P450 and other enzymes. In those studies, a 'higher activity of midgut microsomal oxidase enzymes in polyphagous than in

**Table 4.** Plant allelochemicals and associated resistance mechanisms in insects.

In Western Flower Thrips, *Frankliniella occidentalis*, metabolic detoxification of insecticides has been reported by many authors [179]. In *Bemisia tabaci*, metabolic resistance due to enhanced

**7. Host allelochemicals, induction of detoxifying enzymes and insecticide**

Understanding the diversity of insect responses to chemical pressures (plant allelochemicals and insecticides) in their local ecological context represents a key challenge in developing sustainable pest control strategies. Plants and insects have had co-existing relationships for a long time. Insects were suppressed either by other insects or toxins or by plant defence mechanisms in order to create a balance between the insect pest population and host. Each plant species has a unique set of defence traits ranging from morphological to phytochemical parameters that have behavioural and physiological ramifications for a potential herbivore consumer [181, 182]. Therefore, the resistance mechanisms evolved by insects to deal with the chemical defences of plants are similar to those mechanisms that have evolved to resist synthetic insecticides. The chemical structure of some synthetic insecticides is comparable to that of some plant-produced compounds (e.g. pyrethroids and nicotinoids). Insect resistance to plant allelochemicals interferes with their resistance to synthetic insecticides [183]. From the evolutionary perspective, despite the key role of the chemical 'arms race' in driving the coevolution of plants and insects, much research has focused so far on describing the diversity of plant chemicals and their effects on herbivores. Hence, the understanding of insecticide resistance mechanisms as well as taking into account other ecological parameters is important in predicting the spread of insecticide resistance in natural pest populations and in choosing the optimum strategy for managing insect pest populations. Less is known about the multiple mechanisms evolved by insects to overcome these chemical defences (Table 4). These mecha‐ nisms include contact and ingestion avoidance, excretion, sequestration, degradation of the

Biotransformation of plant toxins is one of the major weapons that insects have evolved in their co-evolutionary arms race with plants [204]. To date, metabolic resistance to plant chemicals has been identified not only in herbivorous insects [194] but also in detrivorous insects such as mosquito larvae feeding plant debris [205]. Metabolic resistance often results from the overproduction of 'detoxification enzymes' that can metabolize plant xenobiotics (allelochemicals). This mechanism is often associated with phenotypic plasticity, as the production of detoxification enzymes is usually induced by the presence of plant xenobiotics

Induction of insect detoxifying enzyme activities by plant allelochemicals is a clear manifes‐ tation of biochemical phenotypic plasticity and has been documented in several instances [206, 207]. Many of the theories and some of the experiments implicitly or explicitly deal with the insect's ability to metabolize plant secondary substances by P450 and other enzymes. In those studies, a 'higher activity of midgut microsomal oxidase enzymes in polyphagous than in

activity of insecticide resistance-related enzymes has also been reported [180].

**resistance**

366 Insecticides Resistance

toxin and target site mutation.

in the diet of the insect.

monophagous species indicates that the natural function of these enzymes is to detoxify natural insecticides present in the larval food plants'. The estimation of aldrin epoxidation in gut homogenates of last instar larvae from 35 species of Lepidoptera showed that polyphagous species had on average a 15 times higher activity than monophagous species. This trend was seen in sucking insects as well. A 20-fold lower aldrin epoxidase activity was found in the oleander aphid *Aphis nerii* (specialist feeder on two plant families, Asclepiadaceae and Apocynaceae) when compared to the potato aphid *Myzus euphorbiae* or to the green peach aphid *Myzus persicae* (both are generalists found on 30–72 plant families) [208]. A similar type of observation was made for other detoxification enzymes. In mites, predatory mite has a five times lower aldrin epoxidase activity than its herbivorous prey [209]. The toxicity of the natural phototoxin α-terthienyl is inversely proportional to the level of its metabolism in Lepidoptera and is related to diet breadth. Metabolism is highest in *Ostrinia nubilalis*, which feeds on numerous phototoxic Asteraceae; lower in *Helicoverpa virescens*, which has a broad diet, including some Asteraceae that are non-phototoxic; and lowest in *Manduca sexta*, a specialist of Solanaceae [210].

In addition to insecticides, insect carboxylesterases also metabolize many glycosides. Βglucosidase enzyme is active towards a variety of glucosides in fall armyworms, corn ear‐ worms, cabbage loopers and valvet bean caterpillars. The *p*-nitrophenyl β-D-glucoside, 4 methyl umbelliferyl β-D-glucoside, D (+)-cellobiose, D-amygdalin and helicon were preferred substrates whereas sinigrin, phloridzin, α-solanine, tomatine and linamarin were poor substrates for these insects and many other insects reported to date [211]. β-Glycosidases have been shown to play important roles in the survival of certain phytophagous insects [211]. The ability of peach tree borer, *Synanthedon exitiosa,* larvae to survive well on prunasin-containing peach tree is because they can metabolize cyanogenic glycosides through β-glucosidase and detoxify the released cyanide by β-cyanoalanine synthase, thereby allowing them to utilize peach trees [212]. Another example is the larvae of the tiger swallowtail, *Papilio glaucus,* which feeds on quacking aspen, which contains various phenolics glycosides (e.g. salicortin). These larvae hydrolyse the glycosides by β-glucosidase and detoxify the released phenolics aglycone by a highly active esterase, thereby allowing them to survive on aspen [213, 214].

Glutathione S-transferases are also involved in the metabolism of many toxic plant allelo‐ chemicals. These plant allelochemicals may be of many diverse groups including α, βunsaturated carbonyl compounds (e.g. *trans*-cinnamaldehyde, trans-2-hexanal), isothiocyanates (e.g. allylisothiocyanate, benzyl isothiocyanate) and organothiocyanates (e.g. benzyl thiocyanate) as have been documented in some instances [41]. The glutathione Stransferase activities are lower in the specialist insects than in the generalists. In the cruciferadapted cabbage looper for the metabolism of isothiocyanates (plant allelochemical), the activity of this enzyme wasfound to be two- to sixfold higher than that in the fall armyworm [215, 216]. These findings strongly advocate that glutathione S-transferases play an important role in developing resistance towards plant allelochemicals in phytophagous lepidopteran insects [215–217]. Many plant allelochemicals are potent inhibitors of glutathione S-transfer‐ ases in many insects [218]. Many flavonoids, other phenols and α-, β-unsaturated carbonyl compounds are also found to be potent inhibitors of the enzymes.

*H. theivora, E. flavescens* and *S. dorsalis* all are polyphagous in nature. *H. theivora* known to feed on at least sixteen different plant families reported till date [11]. Similarly, *E flavescens* is also polyphagous [11]. *S. dorsalis* has been documented to attack more than 150 hosts from at least 40 different plant families [219]. Hence, these pests are exposed to a wide variety of plant allelochemicals of diverse groups having the potential to induce the activity of these resistancerelated enzymes. A higher level of detoxifying enzyme activity in *H. theivora* has been reported when reared on two alternative hosts, i.e. *Mikania micrantha* (Asteraceae) and *Psidium guaja‐ va* (Myrtaceae), than on tea [220]. Over the four hundred million years of co-evolution with plants, phytophagous insects have developed diverse resistance mechanisms to cope with plant chemical defences. Because insects face a geographical mosaic of chemical environments, from non-toxic to highly toxic plants, the costs associated with resistance traits vary with the probability of encountering a toxin. Moreover, other selection pressures, such as the presence or absence of competitors and predators, can also influence the costs and selection of particular resistance traits. Thus, the complexity of the local community composition is a key factor in maintaining the diversity of adaptive mechanisms to plant xenobiotics. These mechanisms are more plastic and complex compared with those involved in resistance to insecticides, perhaps because environments in which insecticides are heavily used also tend to have communities of low diversity and complexity. However, because some detoxification enzymes are involved in plant toxins and insecticides metabolism, cross-resistance mechanisms can be predicted to be observed under specific environmental conditions. Deciphering the impact of allelochem‐ icals in cross-resistance mechanisms with insecticides at a local scale, and comparing the molecular and evolutionary mechanisms of resistance to phytotoxins and synthetic insecti‐ cides, represent promising areas of research for developing long-term sustainable insect control strategies for the effective management of pest concern [220].


**5. Clinical status of children with HIV/AIDS**

Health-related quality of life (HRQOL) is increasingly recognized as an important measure for assessing the burden of chronic diseases (Hays et al., 2000). HIV-specific parameters, such as low CD4 cell count and high virus load, have previously been shown to adversely affect HRQOL in some studies of HIV-infected patients (Casado et al., 2011; Niuwerk et al., 2001).

Other studies show weak HRQOL associations with disease stage and CD4 cell count (Niuwerk et al., 2001). Similarly, the effect of HAART on HRQOL has been assessed with some studies (Call et al., 2000).

According to international definitions on the concept of childhood affected by HIV/AIDS, participating minors must comply with the following affectation categories as criteria of population inclusion, nonexcluding amongst themselves: 1. HIV/AIDS seropositive and/or seronegative children, and adolescents, orphaned by HIV/AIDS (father, mother, or both deceased because of the disease). 2. HIV seropositive children and adolescents. 3. HIV seropositive and/or seronegative children and adolescents, cohabitating with HIV seropositive individuals.

80 children were HIV-positive in five Colombia cities. 80% (N=64) were receiving antiretroviral therapy and most 34.9% (N=30) had HIV load undetectable or low 20% (N=15) (See Table 4). As we mentioned earlier, Colombian children affected with HIV/AIDS have a good level of health because all these children are affiliated to the social security health and are receiving Highly Active Antiretroviral Treatment (HAART); 80% (N=64) children are receiving HAART (See Table 4).

Table 4. Viral Load and Antiretroviral Therapy in HIV-positive children.

Affectation Situation of HIV/AIDS in Colombian Children 279

Table 6. Barriers of Health Services in Colombian families affected with HIV/AIDS.

87.4% of Families affected with HIV reports that health attention has not been denied (See

**(N=286) F % YES** 36 12.6 % **NO** 250 87.4 %

The low rate of disclosure of HIV status to children found in the study indicates that it is a priority to develop disclosure clinical model in the Colombian context. For this reason since 2008 our institution is conducting the investigation: "Evaluation of the effects of a disclosure clinical model in HIV-positive children 7 – 18 years old in adherence to treatment and psychological adjustment". Research Project awarded with the Fellowship for Research from the Department of Research and Projects. Awarded in the 2008 Call for Proposals for

This research aims to provide a clinical model to help affected families overcome fears that lead them to delay the delivery of HIV diagnosis. Mainly, caregivers want to avoid psychological or emotional harm to child and they fear that child tell the diagnosis to others

Table 7. Denial of Health Services in Colombian families affected with HIV/AIDS.

**Discretion and Confidentiality Service (N=286)**

**Home Care (N=286)**

**Entity that subsidizes Antiretroviral Therapy (N=64)**

**Acquisition of Antiretroviral Therapy with own money (N=64)**

Doctorate Programs at Universidad del Norte

and be discriminated against.

**Denial of Health Services**

Table 7).

**7. Conclusion**

**Barriers to Health Services Category N %**

Yes 265 92.7% No 20 7% Sometimes 1 0.3%

Monthly 4 1.4% 2 to 3 months 14 4.9% Every 6 months 7 2.4% 1 time per year 16 5.6% Never 245 85.7%

lender (EPS) 6 10.4%

(ARS) 33 50.6%

Yes 4 6.7% No 60 93.3%

21 32.5%

Subsidized by the foundation 4 6.5%

Subsidized by the health

Subsidized insurance scheme

Subsidized by distrital or departamental health secretary