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Dichlorodiphenyltrichloroethane (DDT) is the most widespread, persistent pollutant and endocrine disruptor on the planet. Although DDT has been found to block androgen receptors, the effects of its low-dose exposure in different periods of ontogeny on the male reproductive system remain unclear. We evaluate sex steroid hormone production in the pubertal period and after maturation in male Wistar rats exposed to low doses of o,p'-DDT, either during prenatal and postnatal development or postnatal development alone. Prenatally and postnatally exposed rats exhibit lower testosterone production and increased estradiol and estriol serum levels after maturation, associated with the delayed growth of gonads. Postnatally exposed rats demonstrate accelerated growth of gonads and higher testosterone production in the pubertal period. In contrast to the previous group, they do not present raised estradiol production. All of the exposed animals exhibit a reduced conversion of progesterone to 17OH-progesterone after sexual maturation, which indicates putative attenuation of sex steroid production. Thus, the study reveals age-dependent outcomes of low-dose exposure to DDT. Prenatal onset of exposure results in the later onset of androgen production and the enhanced conversion of androgens to estrogens after puberty, while postnatal exposure induces the earlier onset of androgen secretion.

Cationic liposome - CpG DNA complexes (lipoplexes) are known as stimulators of innate immunity via Toll-like receptor 9 (TLR9)-triggered activation of the nuclear factor kappa B (NF-κB) pathway. More recent reports suggest that DNA lipoplexes also engage DNA sensors in the cytosol leading to the stimulation of the interferon response factor (IRF) pathway. In this study a range of lipoplexes were formulated by using an invariable helper lipid, three different cationic lipids (DOTAP, DOTMA and DDA) and three different CpG-containing plasmids of different sizes. These lipoplexes exhibited similar hydrodynamic diameters, zeta-potentials and plasmid loading rates, despite the different lipid blends and CpG-containing plasmids. Binding and uptake of liposomal lipids by J774.A1 macrophages and JAWSII dendritic cells increased significantly (up to 4-fold) upon lipoplex formation. Cellular plasmid DNA uptake via lipoplexes compared to naked DNA was increased up to 18-fold. Analysis of signal transduction pathway activation in J774-DUAL™ reporter cells by liposomes or naked CpG plasmid DNA compared to their derived lipoplexes showed only minor activation of the NF-κB pathway, while the IRF pathway displayed massive activation factors of up to 46-fold. DOTAP- and DOTMA lipoplexes also led to massive interferon-alpha and -beta secretion of J774A.1 macrophages and JAWSII dendritic cells, which is a hallmark of IRF pathway activation. Cellular distribution studies on DOTAP lipoplexes suggest delivery of plasmid DNA via vesicular compartments into the cytosol. Taken together, the CpG plasmid DNA lipoplexes generated in this study appear to selectively stimulate DNA receptors activating the IRF pathway, while bypassing TLR9 and NF-κB activation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Malaria prevalence has significantly reduced since 2000, largely due to the scale-up of vector control interventions, mainly indoor residual spraying (IRS) and long-lasting insecticide-treated nets (LLINs). Given their success, these tools remain the frontline interventions in the fight against malaria. Their effectiveness relies on three key ingredients: the intervention, the mosquito vector and the end-user. Regarding the intervention, factors such as the insecticide active ingredient(s) used and the durability and/or bio-efficacy of the tool over time are critical. For the vectors, these factors include biting and resting behaviours and the susceptibility to insecticides. Finally, the end-users need to accept and properly use the intervention. Whilst human attitude and behaviour towards LLINs are well-documented both during and after distribution, only initial coverage is monitored for IRS and in a few geographic settings the residual efficacy of the used product. Here, the historical evidence on end-users modifying their wall surfaces post-spraying is presented, a behaviour that has the potential to reduce actual IRS coverage, effectiveness and impact, as fewer people are truly protected. Therefore, clear guidelines on how to monitor IRS acceptability and/or coverage, both before, during and after spraying, are urgently needed as part of the Monitoring and Evaluation of malaria programmes.

While, dichlorodiphenyl-trichloroethane (DDT) water dispersible powder (WDP) 75% is considered as the high performance long lasting formulation for indoor residual spraying (IRS), no information is available regarding the comparative epidemiological effectiveness of the two DDT formulations when used for IRS in Indian conditions. The current study was undertaken to compare the effectiveness of IRS using DDT WDP 75% @ one g active ingredient (AI)/m 2 with that using DDT WDP 50% @ one g AI/m 2 in controlling Anopheles fluviatilis and An. culicifacies, the primary vectors of malaria in the selected endemic areas of Odisha State. Although, cone-bioassay mortality after 8 months of post spraying on DDT 75% sprayed surfaces as well as on sprayed but mud plastered surfaces was higher than DDT 50%, the six entomological parameters viz. resting density indoors and outdoors, trap density indoors, parous rate, human blood index and infection rate of An. fluviatilis and An. culicifacies did not show any statistically significant difference in reduction/ changes from pre- to post-spray period between the two DDT formulations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Redox reactions play a central role in the metabolism of an organism. It is vital to maintain redox homeostasis in response to the fluctuation of redox shift in various biological contexts. NADPH-dependent reducing capacity is one of the key factors contributing to the redox homeostasis. To understand the redox capacity and its impact on mosquito fecundity and susceptibility to insecticides in Anopheles gambiae, we examined the dynamics of elevated oxidative state via induction by paraquat (PQ) and the inhibition of NADPH regeneration by 6-aminonicotinamide (6AN). In naïve conditions, inherent oxidative capacity varies between individuals, as measured by GSSG/GSH ratio. The high GSSG/GSH ratio was negatively correlated with fecundity. Both PQ and 6AN feeding increased GSSG/GSH ratio and elevated protein carbonylation, a marker of oxidative damage. Both pro-oxidants lowered egg production. Co-feeding the pro-oxidants with antioxidant lycopene attenuated the adverse effects on fecundity, implying that oxidative stress was the cause of this phenotype. Pre-feeding with 6AN increased insecticide susceptibility in DDT resistant mosquitoes. These results indicate that oxidative state is delicate in mosquitoes, manipulation of NADPH pool may adversely affect fecundity and insecticide detoxification capacity. This knowledge can be exploited to develop novel vector control strategies targeting fecundity and insecticide resistance.

Pentachlorophenol (PCP) and Dichlorodiphenyltrichloroethane (DDT) are environmental contaminants found in human blood. Previous studies have shown that PCP and DDT inhibit the lytic function of highly purified human natural killer (NK) lymphocytes and decrease the expression of several surface proteins on NK cells. Interleukin-1 βeta (IL-1β) is a cytokine produced by lymphocytes and monocytes, and anything that elevates its levels inappropriately can lead to chronic inflammation, which among other consequences can increase tumor development and invasiveness. Here, PCP and DDT were examined for their ability to alter secretion of IL-1β from immune cell preparations of various complexity: NK cells; monocyte-depleted (MD) peripheral blood mononuclear cells (PBMCS); and PBMCs. Cells were exposed to concentrations of PCP ranging from 5 to 0.05 µM and DDT concentrations of 2.5-0.025 μM for 24, 48 h, and 6 days. Results showed that both PCP and DDT increased IL-1β secretion from all of the immune cell preparations. The specific concentrations of PCP and DDT that increased IL-1β secretion varied by donor. Immune cells from all donors showed compound-induced increases in IL-1β secretion at one or more concentration at one or more length of exposure. The mechanism of PCP stimulation of IL1-β secretion was also addressed, and it appears that the MAPKs, ERK1/2 and p38, may be utilized by PCP to stimulate secretion of IL-1β.

Background: Indoor Residual Spraying (IRS) and Long-Lasting Insecticidal nets (LLINs) are major malaria vector control tools in Ethiopia. However, recent reports from different parts of the country showed that populations of Anopheles arabiensis, the principal malaria vector, have developed resistance to most families of insecticides recommended for public health use which may compromise the efficacy of both of these key vector control interventions. Thus, this study evaluated the efficacy of DDT IRS and LLINs against resistant populations of An. arabiensis using experimental huts in Asendabo area, southwestern Ethiopia., Methods: The susceptibility status of populations of An. arabiensis was assessed using WHO test kits to DDT, deltamethrin, malathion, lambda-cyhalothrin, fenitrothion and bendiocarb. The efficacy of LLIN (PermaNet 2.0), was evaluated using the WHO cone bioassay. Moreover, the effect of the observed resistance against malaria vector control interventions (DDT IRS and LLINs) were assessed using experimental huts., Results: The findings of this study revealed that populations of An. arabiensis were resistant to DDT, deltamethrin, lambda-cyhalothrin and malathion with mortality rates of 1.3%, 18.8%, 36.3% and 72.5%, respectively but susceptible to fenitrothion and bendiocarb with mortality rates of 98.81% and 97.5%, respectively. The bio-efficacy test of LLIN (PermaNet 2.0) against An. arabiensis revealed that the mosquito population showed moderate knockdown (64%) and mortality (78%). Moreover, mosquito mortalities in DDT sprayed huts and in huts with LLINs were not significantly different (p > 0.05) from their respective controls., Conclusion: The evaluation of the efficacy of DDT IRS and LLINs using experimental huts showed that both vector control tools had only low to moderate efficacy against An. arabiensis populations from Ethiopia. Despite DDT being replaced by carbamates for IRS, the low efficacy of LLINs against the resistant population of An. arabiensis is still a problem. Thus, there is a need for alternative vector control tools and implementation of appropriate insecticide resistance management strategies as part of integrated vector management by the national malaria control program.

Recent understanding of the pathogenesis of tuberculosis allows the possible application of immunotherapy for the treatment of tuberculosis. Therapies that would upregulate the host antimycobacterial immune response and/or attenuate T-cell suppressive and macrophage-deactivating cytokines may prove to be useful in the treatment of tuberculosis. ESAT6, 6-kDa early secreted antigenic target, is a potent protective antigen and is considered as major target for long-lived memory cells. In the present study the immunotherapeutic potential of ESAT-6 has been evaluated in mouse model of experimental tuberculosis. In the present study the ESAT-6 protein was cloned in Escherichia coli using pET23a(+) plasmid and purified by Ni(2+)-NTA chromatography. Further, the immunotherapeutic potential of the recombinant ESAT-6 (in terms of CFU enumeration in the target organs and histopathological analysis of lungs) was evaluated against experimental tuberculosis. The recombinant ESAT-6 with C-terminal histidine-tag and free N-terminus mimics the natural form of ESAT-6 has been successfully cloned and purified. The recombinant ESAT-6 protein adjuvanted with dimethyl dioctadecylammonium bromide (DDA) moderately reduced the bacterial load in the target organs of infected mice. Further, the formulation (ESAT-6-DDA) was able to act synergistically when given in combination with antituberculosis drugs. This recombinant ESAT-6 showed good immunotherapeutic potential against experimental tuberculosis and can be used as an adjunct to the conventional antituberculosis chemotherapy., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This work investigates the influence of drug absorption route (intestinal lymphatics vs. blood supply) on drug pharmacokinetics and tissue distribution. To achieve this aim, the pharmacokinetics and tissue distribution of model compounds [1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane, DDT; halofantrine] and lipids were assessed following intravenous delivery in lymph lipoproteins or plasma, and were found to differ significantly. For DDT, the clearance (CL) and volume of distribution (Vd ) were higher, whereas for halofantrine, CL and V(d) were lower, after entry in lymph versus plasma due, in particular, to differences in adipose tissue and liver uptake. In a recent study, halofantrine CL and V(d) were similar following entry in lymph or entry in plasma into the systemic circulation of animals predosed with lymph, whereas in the current study, predosing lymph did not influence DDT CL and V(d). For compounds such as DDT, changes to the route of absorption may thus directly impact on pharmacokinetics and tissue distribution, whereas for halofantrine factors that influence lymphatic transport may, by altering systemic lipoprotein concentrations, indirectly impact pharmacokinetics and tissue distribution. Ultimately, careful control of dosing conditions (formulation, prandial state), and thus the extent of lymphatic transport, may be important in assuring reproducible efficacy and toxicity for lymphatically transported drugs., (Copyright © 2013 Wiley Periodicals, Inc.)

Emerging evidence suggests that chronic exposure to DDT and its derivatives is associated with a variety of human disorders such as anemia. The present study demonstrated that p,p'-DDT caused microcystic anemia in a dose-dependent manner (0, 5, 50, and 500 ppm) in the long-term study up to 2 years. To elucidate the mechanism(s) by which p,p'-DDT induces anemia, certain hematological parameters were assessed in rats fed specific doses of p,p'-DDT for 2 weeks, and the effect of lipopolysaccharide on anemia of inflammation was also examined in p,p'-DDT-treated rats. The parameters included the content of hemoglobin per reticulocyte, mean corpuscular volume of reticulocytes and mature erythrocytes, corpuscular hemoglobin concentration mean of mature erythrocytes, and saturation levels of transferrin and iron. During the 2-week treatment period, hypochromic microcytic reticulocytes and hypochromic normocytic mature erythrocytes were observed in p,p'-DDT-treated rats, with no evidence of alteration in plasma iron levels. p,p'-DDT enhanced microcytosis of reticulocytes, as well as mature erythrocytes, which occurred due to severe hypoferremia resulting from anemia of inflammation; however, plasma iron levels were attenuated probably through the inhibition of interleukin-6. Our data suggests that long-term treatment with p,p'-DDT induces microcytic anemia, possibly because of the impairment of iron utility in erythrocytes.

Background: Current efforts are underway to quantify the chemical concentration in a treated air space that elicits a spatial repellent (deterrent) response in a vector population. Such information will facilitate identifying the optimum active ingredient (AI) dosage and intervention coverage important for the development of spatial repellent tools--one of several novel strategies being evaluated for vector-borne disease control. This study reports initial findings from air sampling experiments conducted under field conditions to describe the relationship between air concentrations of repellent AIs and deterrent behavior in the dengue vector, Aedes aegypti., Methods: Air samples were taken inside and outdoors of experimental huts located in Pu Tuey Village, Kanchanaburi Province, Thailand in conjunction with mosquito behavioral evaluations. A mark-release-recapture study design using interception traps was used to measure deterrency of Ae. aegypti against 0.00625% metofluthrin coils and DDT-treated fabric (2g/m2) within separate experimental trials. Sentinel mosquito cohorts were positioned adjacent to air sampling locations to monitor knock down responses to AI within the treated air space. Air samples were analyzed using two techniques: the U.S. Environmental Protection Agency (USEPA) Compendium Method TO-10A and thermal desorption (TD)., Results: Both the USEPA TO-10A and TD air sampling methods were able to detect and quantify volatized AIs under field conditions. Air samples indicated concentrations of both repellent chemicals below thresholds required for toxic responses (mortality) in mosquitoes. These concentrations elicited up to a 58% and 70% reduction in Ae. aegypti entry (i.e., deterrency) into treated experimental huts using metofluthrin coils and DDT-treated fabric, respectively. Minimal knock down was observed in sentinel mosquito cohorts positioned adjacent to air sampling locations during both chemical evaluations., Conclusions: This study is the first to describe two air sampling methodologies that are appropriate for detecting and quantifying repellent chemicals within a treated air space during mosquito behavior evaluations. Results demonstrate that the quantity of AI detected by the mosquito vector, Ae. aegypti, that elicits repellency is far lower than that needed for toxicity. These findings have important implications for evaluation and optimization of new vector control tools that function through mosquito behavior modification as opposed to mortality.

Background & Objectives: In the present study, an attempt was made to find reasons of ineffectiveness of indoor residual spray to interrupt malaria transmission by investigating the behaviour of two variants of Anopheles stepnesi, viz. type form and mysorensis in rural areas of Rajasthan, India., Methods: Both low malarious (DDT spray from 1958 to 1976) and high malarious (DDT spray from 1958 to April 2006) villages were selected for the study in Arid zone district Jodhpur, Rajasthan during March-April 2006. Resting behaviour of the species during all its movement rhythms covering 24 h period related to: (i) swarming/ mating; (ii) pre- and post-biting rest; (iii) after feed resting between hoping movements; (iv) night and day time resting and; (v) diel activity movements in response to temperature changes, were carried out., Results: The results showed that household objects like cupboards, furnitures, hanging clothes, goods stacked on loft, stored clothes, cobwebs and floor were the dominant resting sites both in sprayed and unsprayed villages. About 95 and 97% of An. stephensi preferred to rest on household objects of unsprayed and sprayed villages respectively. There was no significant difference in resting behaviour of the species in both groups of villages (p >0.05). The pre-biting resting time was recorded as 5 to 15 min whereas post-biting resting time lasted for 15 to 25 min. After biting outdoor (in courtyard--open to sky) species starts entering the rooms at around 2330 hrs. It was observed that during III quarter (0100 to 0400 hrs) maximum species entered into the room were 56% in unsprayed and 62% in sprayed villages. Statistically there was no significant difference in the entry of mosquitoes (p >0.05) in both the groups of villages., Conclusion: Before DDT era, An. stephensi was found resting at all heights of the walls inside the human dwellings. Present study revealed that An. stephensi is trying to avoid sprayable surfaces and tend to rest on unsprayable surfaces during all its movement rhythms starting from swarming, pre-/post-biting and during hopping movements in the courtyard and thereafter household objects inside the room as final day time resting. It was concluded that changed behaviour of resting of An. stephensi on unsprayable objects in sprayed rooms largely accounted for failure of malaria control. Control of An. stephensi, thus requires an integrated vector control strategy based upon interesectoral, environmental, larviciding with chemical/biolarvicide and use of larvivorous fish wherever feasible. Such a control strategy offers cost-effective and sustainable option than indoor residual spray.

Numerous environmental pressures have precipitated long-term population reductions of many insect species. Population declines in aerially foraging insectivorous birds have also been detected, but the cause remains unknown partly because of a dearth of long-term monitoring data on avian diets. Chimney swifts (Chaetura pelagica) are a model aerial insectivore to fill such information gaps because their roosting behaviour makes them easy to sample in large numbers over long time periods. We report a 48-year-long (1944-1992) dietary record for the chimney swift, determined from a well-preserved deposit of guano and egested insect remains in Ontario (Canada). This unique archive of palaeo-environmental data reflecting past chimney swift diets revealed a steep rise in dichlorodiphenyltrichloroethane (DDT) and metabolites, which were correlated with a decrease in Coleoptera remains and an increase in Hemiptera remains, indicating a significant change in chimney swift prey. We argue that DDT applications decimated Coleoptera populations and dramatically altered insect community structure by the 1960s, triggering nutritional consequences for swifts and other aerial insectivores.

Introduction: We report on the analysis of 4,4'-dichlorodiphenyltrichloroethane (4,4'-DDT) and its metabolites in thatch and branch samples constituting the wall materials of dwellings from South African subtropical areas. This approach was used to assess the exposure to DDT in the residents of the dwellings after indoor residual spraying (IRS) following recommended sanitation practices against malaria vectors., Discussion: Examination of the distributions of DDT compounds (2,4'-DDT, 4,4'-DDT and its metabolites) in 43 dwellings from the area of Manhiça (Mozambique) has shown median concentrations of 19, 130, and 23 ng/g for 2,4'-DDT, 4,4'-DDT, and 4,4'-DDE, respectively, in 2007 when IRS implementation was extensive. The concentrations of these compounds at the onset of the IRS campaign (n = 48) were 5.5, 47, and 2.2 ng/g, respectively. The differences were statistically significant and showed an increase in the concentration of this insecticide and its metabolites. Calculation of 4,4'-DDT in the indoor air resulting from the observed concentrations in the wall materials led to the characteristic values of environments polluted with this insecticide.

Background: Malaria control remains a challenge in sub-Saharan Africa. In 2006, the World Health Organization (WHO) reinforced the recommendation of indoor residual spraying (IRS) with dichlorodiphenyltrichloroethane (DDT) to reduce malaria transmission. The National Malaria Control Programme has been reporting high coverage rates of IRS in Mozambique. It is important to establish to what extent these rates are a reflection of community acceptability, and to explore the factors associated with adherence, in order to recommend suitable approaches for interventions of this nature., Objective: To understand the implementation process, reception and acceptability of the IRS program in Manhiça district, Southern Mozambique., Methods: Qualitative data was collected through in-depth interviews, participant observation of IRS activities, informal interviews, and focus group discussions. Study participants comprised householders, community leaders, health care providers, sprayers, and community members. Qualitative data analysis was based on grounded theory. Secondary data from the Manhiça Demographic Surveillance System was used to complement the qualitative data., Results: IRS was well received in most neighbourhoods. The overall coverage rates varied between 29% and 41% throughout the study period. The factors related to adherence to IRS were: immediate impact on insects in general, trust and obedience in the health authority, community leaders' influence, and acquaintance with the sprayers. Fighting malaria was not an important motivation for IRS adherence. There was a perception of limited efficacy of IRS against mosquitoes, but this did not affect adherence. Non-adherence to the intervention was mainly due to the unavailability of key householders, disagreement with the procedures, and the perception that spraying increased the burden of insects. Most respondents strongly favoured bed nets over IRS., Conclusion: The study suggests that the contribution of IRS to malaria and mosquito control is not entirely perceived by the beneficiaries, and that other as cost effective interventions such as insecticide-treated nets are favoured over IRS. Adherence to IRS was found to be influenced by socio-political factors. There is a need to redefine the community sensitization approaches in order to make IRS a genuinely participative, acceptable, and sustainable programme.

Based upon the goal of scientific literacy and the importance of socioscientific issues (SSIs), the purpose of this study was to investigate the Taiwanese public's awareness of, inclinations to buy/use, and their attitudes towards three attributes of SSIs including genetically modified food (GM food), organic food, and DDT and malaria (DDT). Data from a total of 865 participants across ten populations (six different educational levels and four different vocations) were validated and analyzed. The results revealed that the awareness regarding GM food and DDT increased with the levels of education. The inclinations to buy/use and the attitudes towards the three SSIs, were not related to levels of education, vocation or gender, but were related to attributes of the SSIs. The implications for education and policy development are discussed.

Background & Objectives: Visceral leishmaniasis, commonly known as kala-azar is endemic in Bihar state, India. Current vector control programme in Bihar focuses mainly on spraying the sandfly infested dwellings with DDT. The Government of India in collaboration with WHO has fixed the target 2015 for total elimination of kala-azar. The present study was carried out to see the impact of DDT and improved IEC in the containment of vector density vis-à-vis disease transmission., Methods: Before the start of the spraying operations training was imparted to all the medical and paramedical personnel regarding the methods of spraying operations. Pre- and post-sandfly density was monitored in four selected districts. Incidences of kala-azar cases were compared for pre- and post-spray periods. Social acceptability and perceptions of households was collected through questionnaires from 500 randomly selected households in the study districts., Results: House index in three study districts reduced considerably during post-spray when compared to pre-spray. Kala-azar incidence in many districts was reduced after the DDT spray. Either partial or complete refusal was reported in 14.4%, while 35% were not satisfied with the suspension concentration and coverage; and 46.6% were found satisfied with the spraying procedure., Interpretation & Conclusion: Strengthening the IEC activities to sensitise the community, proper training of health personnel, monitoring of spray, good surveillance, proper treatment of cases and two rounds of DDT spray with good coverage in the endemic districts up to three years are essential to achieve the desired total elimination of kala-azar in Bihar state.

Objective: To investigate the presence of knock down resistance (kdr) mutation, its frequency distribution in the principal vector of bancroftian filariasis, Culex quinquefasciatus from northeastern India, and to relate kdr genotypes with susceptibility and/or resistance to DDT and deltamethrin in this vectors., Methods: Adult female mosquitoes were collected by aspiration from human dwellings in two villages, Benganajuli and Rikamari, and two military establishments, Field Units I and II. Insecticide susceptibility tests were performed following WHO methods with 4% DDT and 0.05% deltamethrin. Molecular identification of kdr mutation and genotyping of kdr locus was performed by allele-specific PCR (AS-PCR) and direct sequencing in a subset of samples., Results: Mosquitoes were resistant to DDT and showed 11.9-41.2% mortality, whereas the knock down bioassay for deltamethrin suggests complete susceptibility to this insecticide in all study sites except Benganajuli. The result of AS-PCR confirmed the presence of three genotypes: susceptible (SS), resistant (RR) and heterozygous (SR) in the population. Genotype frequencies at kdr locus for DDT-resistant individuals conformed with the Hardy-Weinberg proportion, whereas DDT and deltamethrin susceptible individuals differed significantly (P < 0.05). The efficacy of AS-PCR in detecting the correct genotype was not encouraging., Conclusions: This is the first report from India on kdr genotyping in C. quinquefasciatus, and it confirms the occurrence of kdr allele in this vector in northeastern India. This finding has serious implications for the filariasis control programmes in India.

During 1946-1950, the Rockefeller Foundation conducted a large-scale experiment in Sardinia to test the feasibility of indigenous vector species eradication. The interruption of malaria transmission did not require vector eradication, but with a goal of developing a new strategy to fight malaria, the choice was made to wage a rapid attack with a powerful new chemical. Costing millions of dollars, 267 metric tons of DDT were spread over the island. Although malaria was eliminated, the main objective, complete eradication of the vector, was not achieved. Despite its being considered almost eradicated in the mid-1940s, malaria 60 years later is still a major public health problem throughout the world, and its eradication is back on the global health agenda.

Avian species have the possible risk of embryonic exposure to persistent, lipophilic environmental contaminants, such as dichlorodiphenyltrichloroethane (DDT), by transfer of chemicals accumulated in mother birds to eggs. To model developmental and reproductive disorders of wild birds living in contaminated areas, we exposed Japanese quails in ovo to o,p'-DDT prior to incubation. A positive estrogenic substance diethylstilbestrol (DES; 1 and 10 ng/g of egg) and o,p'-DDT (1-100 microg/g of egg) were injected into the yolk before incubation. Treatment with o,p'-DDT (10 or 100 microg/g) but not with DES significantly reduced the hatchability of eggs. After sexual maturation, o,p'-DDT affected eggshell formation in female quails but had little influence on laying; high doses of o,p'-DDT significantly reduced eggshell strength, shell weight, and shell thickness, and several females treated with 100 microg o,p'-DDT/g laid eggs lacking shells. Diethylstilbestrol decreased egg production itself but had little effect on the eggshell. Both o,p'-DDT and DES caused dose-dependent shortening of the left oviduct and abnormal development of the right oviduct in females, while testis asymmetry was observed in males treated with a high dose of DES. In the uterus of the oviduct, the mRNAs for calcium-regulating factors osteopontin and calbindin D28K were reduced by both treatments, particularly that with o,p'-DDT. The results indicated that transovarian exposure to o,p'-DDT could bring about population declines in avian species through loss of fecundity caused by depression of hatchability and dysfunction of the reproductive tract.

Biting patterns of natural populations of Anopheles minimus s.l. females entering experimental huts treated with DDT and deltamethrin were carried out at Pu Teuy Village, Sai Yok District, Kanchanaburi Province, western Thailand. Two experimental huts, control and treatment, were constructed in the fashion of local Thai homes. Pre-spray biting activity of An. minimus females peaked at 19:00-22:00. Post-treatment exposure continued to show greater landing activity during the first half of the evening. An overall greater proportion of An. minimus females entered the hut treated with deltamethrin compared to DDT. The hut fitted with DDT-treated net panels showed a 71.5% decline in attempted blood feeding, whereas exposure to deltamethrin-treated panels resulted in a 42.8% human-landing reduction. DDT exhibited significantly more pronounced (P < 0.05) effects in overall reduction of biting activity than did deltamethrin.

Dichlorodiphenyltrichloroethane (DDT) has been used as an insecticide to prevent the devastation of malaria in tropical zones. However, many reports suggest that DDT may act as an endocrine disruptor and may have possible carcinogenic effects. Cyclooxygenase-2 (COX-2) acts as a link between inflammation and carcinogenesis through its involvement in tumor promotion. In the present study, we examined the effect of o,p'-DDT on COX-2 gene expression and analyzed the molecular mechanism of its activity in murine RAW 264.7 macrophages. Exposure to o,p'-DDT markedly enhanced the production of prostaglandin E(2) (PGE(2)), a major COX-2 metabolite, in murine macrophages. Furthermore, o,p'-DDT dose-dependently increased the levels of COX-2 protein and mRNA. Transfection with human COX-2 promoter construct, electrophoretic mobility shift assays and DNA-affinity protein-binding assay experiments revealed that o,p'-DDT activated the activator protein 1 (AP-1) and cyclic AMP response element (CRE) sites, but not the NF-kappaB site. Phosphatidylinositol 3 (PI3)-kinase, its downstream signaling molecule, Akt, and mitogen-activated protein kinases (MAPK) were also significantly activated by the o,p'-DDT-induced AP-1 and CRE activation. These results demonstrate that o,p'-DDT induced COX-2 expression via AP-1 and CRE activation through the PI3-K/Akt/ERK, JNK, and p38 MAP kinase pathways. These findings provide further insight into the signal transduction pathways involved in the carcinogenic effects of o,p'-DDT.

Background & Objectives: Jiroft district has subtropical climate and prone to seasonal malaria transmission with annual parasite index (API) 4.2 per 1000 in 2006. Anopheles stephensi Liston is a dominant malaria vector. The monitoring of insecticide susceptibility and irritability was conducted using discriminative dose as described by WHO., Methods: The IV instar larvae were collected from different larval breeding places and transported to the temporary insectary, fed with Bemax and then 2-3 days-old emerged and sugar-fed adults were used for susceptibility and irritability tests employing WHO methods and kits to organochlorine (OC) and pyrethroid (PY) insecticides., Results: Mortality rates of field strain of An. stephensi were 91.3 +/- 0.14 and 90 +/- 0.47% to DDT and dieldrin, respectively at one hour exposure time but was susceptible to all pyrethroids tested. The average number of take-offs per min per adult was 2.09 +/- 0.13 for DDT, 0.581 +/- 0.05 for dieldrin, 1.85 +/- 0.08 for permethrin, 1.87 +/- 0.21 for lambda-cyhalothrin, 1.53 +/- 0.13 for cyfluthrin, and 1.23 +/- 0.1 for deltamethrin., Interpretation & Conclusion: Currently, deltamethrin is being used for indoor residual spraying against malaria vectors in the endemic areas of Iran. The findings revealed that the main malaria species is susceptible to all pyrethroids including deltamethrin, permethrin, cyfluthrin and lambda-cyhalothrin but was tolerant to DDT and dieldrin. This report and the finding are coincided with results of previous studies carried out during 1957-61 in the same area. Irritability tests to OC and PY insecticides revealed the moderate level of irritability to DDT compared to pyrethroids and dieldrin. Monitoring for possible cross-resistance between OC and PY insecticides should come into consideration for malaria control programme.

The use of DDT to control malaria has been a contentious practice for decades. This controversy centers on concerns over the ecological harm caused by DDT relative to the gains in public health from its use to prevent malaria. Given the World Health Organization's recent policy decisions concerning the use of DDT to control malaria, it is worth reviewing the historical context of DDT use. Ecological concerns focused on evidence that DDT ingestion by predatory birds resulted in eggs with shells so thin they were crushed by adult birds. In addition, DDT spraying to control malaria allegedly resulted in cats being poisoned in some areas, which led to increased rodent populations and, in turn, the parachuting of cats into the highlands of the island of Borneo to kill the rodents, a story that influenced the decision to ban DDT spraying. I focus on this story with the intention of grounding the current debate on lessons from the past.

In previous studies, we detected a dichlorodiphenyltrichloroethane (DDT) derivative in the serum of children with sexual precocity after migration from developing countries. Recently, we reported that DDT stimulated pulsatile gonadotropin-releasing hormone (GnRH) secretion and sexual maturation in the female rat. The aim of this study was to delineate the mechanisms of interaction of endocrine-disrupting chemicals including DDT with GnRH secretion evoked by glutamate in vitro. Using hypothalamic explants obtained from 15-day-old female rats, estradiol (E2) and DDT caused a concentration-related increase in glutamate-evoked GnRH release while p,p'-dichlorodiphenyldichloroethene and methoxychlor had no effect. The effective DDT concentrations in vitro were consistent with the serum concentrations measured in vivo 5 days after exposure of immature rats to 10 mg/kg/day of o,p'-DDT. Bisphenol A induced some stimulatory effect, whereas no change was observed with 4-nonylphenol. The o,p'-DDT effects in vitro were prevented partially by a selective antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtype of glutamate receptors. A complete prevention of o,p'-DDT effects was caused by an estrogen receptor (ER) antagonist as well as an aryl hydrocarbon receptor (AHR) antagonist and inhibitors of protein kinases A and C and mitogen-activated kinases. While an intermittent incubation with E2 caused no change in amplification of the glutamate-evoked GnRH release for 4 h, continuous incubation with E2 or o,p'-DDT caused an increase of this amplification after 3.5 h of incubation. In summary, DDT amplifies the glutamate-evoked GnRH secretion in vitro through rapid and slow effects involving ER, AHR, and AMPA receptor mediation.

Objective: To assess the effectiveness of impregnated mosquito nets, indoor residual spraying and larval control relative to the impacts of climate variability in the decline of malaria cases in Eritrea., Methods: Monthly data on clinical malaria cases by subzoba (district) in three zobas (zones) of Eritrea for 1998-2003 were used in Poisson regression models to determine whether there is statistical evidence for reduction in cases by DDT, malathion, impregnated nets and larval control used over the period, while analysing the effects of satellite-derived climate variables in the same geographic areas., Results: Both indoor residual spraying (with DDT or malathion) and impregnated nets were independently and significantly negatively associated with reduction in malaria cases, as was larval control in one zoba. Malaria cases were significantly positively related to differences in current and previous months' vegetation (NDVI) anomalies. The relationship to rainfall differences 2 and 3 months previously was also significant, but the direction of the effect varied by zoba. Standardized regression coefficients indicated a greater effect of climate in the zoba with less intense malaria transmission., Conclusion: The results support the view that both indoor residual spraying and impregnated nets have been independently effective against malaria, and that larval control was also effective in one area. Thus climate, while significant, is not the only explanation for the recent decline in malaria cases in Eritrea. If appropriate statistical approaches are used, routine surveillance data from cases attending health facilities can be useful for assessing control programme success and providing estimates of the effectiveness of individual control measures. Effectiveness estimates suitable for use in cost-effectiveness analysis have been obtained.

This is a comparative study of the mechanisms by which three different rodent non-genotoxic carcinogens modulate connexin-mediated gap junction intercellular communication in male rat liver in vivo. In the case of the peroxisome proliferating agent Wy-14,643, a non-hepatotoxic dose of 50mg/kg led to a marked loss of inter-hepatocyte dye transfer associated with a loss of both Cx32 and Cx26 protein expression. In contrast, p,p'-dichlorodiphenyltrichloroethane (DDT) at a non-hepatotoxic dose (25mg/kg) was not found to alter Cx32 or Cx26 expression or to produce a measurable Cx32 serine phosphorylation but did give a small, significant reduction of cell communication. Carbon tetrachloride (CCl(4)) did not affect cell communication (despite a small significant reduction of Cx32 content) at a non-hepatotoxic dose. Both loss of communication and Cx32 expression was observed only at a dose that caused hepatocyte toxicity as evidenced by increased serum alanine aminotransferase activity. Overall, the findings emphasise that loss of gap junctional communication in vivo can contribute to carcinogenesis by non-genotoxic carcinogens through different primary mechanism. In contrast to Wy-14,643 and DDT, the results with CCl(4) are consistent with a requirement for hepatotoxicity in its carcinogenic action.

Rabbit does (7-9 per group) were treated daily per orum from gestation day 15 through post-natal week 4 to provide per kg body wt 25 micaromol (low) or 250 micromol (high) p,p'-DDT or a mixture of DDT and vinclozolin (12.5 and 125 micromol each). Developmental as well as post-pubertal reproductive sequelae of male progeny were studied. Testicular descent in some pups was impaired by DDT. Serum LH or testosterone was not affected. FSH was lower in mixture- but not in DDT-exposed rabbits. Lack of sexual interest, penile erection and ejaculation were observed in some mixture rabbits. Sperm counts were unaffected, but morphologically normal spermatozoa were fewer; nuclear and acrosomal morphogenesis was disrupted. Atypical germ cells resembling carcinoma in situ were found. Also considering data for vinclozolin [Veeramachaneni DNR, Palmer JS, Amann RP, Kane CM, Higuchi TT, Pau K-YF. Disruption of sexual function, FSH secretion, and spermiogenesis in rabbits following developmental exposure to vinclozolin, a fungicide. Reproduction 2006;131:805-16], we concluded that DDT causes cryptorchidism and germ cell atypia, vinclozolin permanently disrupts FSH secretion and sexual function, and the mixture causes the full spectrum of dysgenesis.

A high-fat meal induces transient hyperlipidemia characterized by elevated triglyceride-rich lipoproteins (TRL) which are composed mainly of chylomicrons. The purpose of this work was to investigate the effect of this transient hyperlipidemia on the pharmacodynamics of lipophilic drugs, using DDT as a model compound since it binds extensively to TRL and has a distinct neurotoxic effect. The postprandial hyperlipidemia in rats was induced by oral administration of peanut oil and was monitored by measurement of plasma triglyceride levels. The control group received water instead of oil. The rats received a continuous intravenous infusion of DDT (10 mg/h) until onset of a predefined pharmacodynamic endpoint (facial muscle tremor). Plasma and brain samples were then obtained and assayed for DDT. Rats with postprandial hyperlipidemia required higher dose of DDT to induce onset of facial muscle tremor. At the pharmacodynamic endpoint, oil treated rats had significantly higher concentrations of DDT in plasma and in the chylomicron fraction, but DDT brain concentrations were the same in both groups. In conclusion, a high-fat meal induces postprandial hyperlipidemia that may significantly alter the pharmacological profile of lipophilic compounds that bind to TRL. This is due to alteration of the distribution characteristics of the lipophilic compound through its association with postprandial lipoproteins. However, this pharmacokinetic phenomenon did not affect the concentration-effect relationship at the site of action in the brain.

The current study has examined whether drugs that are transported to the systemic circulation via the intestinal lymph (and therefore associate with lipoproteins within the enterocyte) are accessible to enterocyte-based metabolic processes. The impact of changes to the mass of lipid present within the enterocyte-based lymph lipid precursor pool (LLPP) on the extent of enterocyte-based drug metabolism has also been addressed. Low (5 mg oleic acid/h) or high [20 mg oleic acid/5.2 mg lyso-phosphatidylcholine/h] lipid dose formulations containing halofantrine (which is lymphatically transported and metabolized) or dichlorodiphenyltrichloroethane (DDT) (which is lymphatically transported and relatively metabolically inert) and radiolabeled oleic acid were infused into the duodenum of lymph duct-cannulated rats. After 5 h, drug and radiolabeled oleic acid were removed from the infusions, allowing calculation of the first order turnover rate constants describing drug and oleic acid transport from the LLPP into lymph from the washout profiles. In one group of animals, bolus doses of ketoconazole were also administered to inhibit cytochrome P450-based metabolism. The rate constant describing halofantrine transport from the LLPP into the lymph was lower than that of oleic acid, whereas these differences were abolished in the presence of ketoconazole. DDT and oleic acid exhibited similar turnover rate constants. The data therefore suggest that enterocyte-based metabolism removes halofantrine from the LLPP before transport into the lymph. Furthermore, enhancing the lymphatic transport of halofantrine by coadministration of larger quantities of lipid reduced the difference between the turnover rate constant for halofantrine and oleic acid and seemed to reduce the extent of enterocyte-based metabolism.

Under a multicentre study conducted by the Indian Council of Medical Research, 1712 samples of wheat grain/flour were collected from urban and rural areas in 11 states representing different geographical regions of India. These samples were analysed for residues of DDT (2,2-bis (p-chlorophenyl)-1,1,1-trichloro ethane) and different isomers of HCH (1,2,3,4,5,6-hexachloro cyclohexane, a mixture of isomers) by gas-liquid chromatography. Residues of DDT were detected in 59.4% of 1080 samples of wheat grain and in 78.2% of 632 samples of wheat flour. Different isomers of HCH were present in about 45-80% of the samples of wheat grain/flour. Medians of DDT and total HCH, respectively, for pooled samples of wheat grain were 0.013 and 0.035 mg kg(-1), while those for wheat flour were 0.01 and 0.02 mg kg(-1). Estimated daily intakes of DDT and different isomers of HCH through the consumption of wheat contaminated at their median and 90th percentiles constituted a small proportion of their acceptable daily intakes. Amongst the pesticide residues analysed, statutory maximum residue limits have been fixed only for gamma-HCH in wheat in India, as 0.1 mg kg(-1) in wheat grain and zero in wheat flour. Residue levels of gamma-HCH exceeded these maximum residue limits in five of 1080 samples of wheat grain and in 340 of 632 samples of wheat flour. The failure to meet the requirement of the gamma-HCH maximum residue limit in large number of wheat flour samples was attributed to the fixation of practically unachievable zero limit. Comparing the previous studies and the present one, the levels of residues of DDT and HCH in wheat were significantly decreased.

The bioconcentration and distribution pattern of p,p'-DDT 1,1,1-1trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)-ethane] and its main metabolites (p,p'-DDD [1,1-dichloro-2,2-bis (4-chlorophenyl) ethane] and p,p'-DDE [1,1-dichloro-2,2-bis (4-chlorophenyl) in adipose tissue, liver, brain, kidney, thymus, and testis were examined in young rats after 10 days of intraperitoneal injection of 50 and 100 mg of p,p'-DDT/kg of body weight. Analyses were performed by high-resolution gas chromatography. p,p'-DDT was found to be accumulated in a dose-dependent manner with the highest concentration in adipose tissue. However, in brain, the accumulation of pesticide was low and remained unchanged at the higher dose. This difference may relate to the protective role of the blood-brain barrier, which limits the access of the xenobiotic in the cerebral compartment, and to the differential tissue lipid composition. Although tissues concentration of p,p'-DDE and p,p'-DDD correlated positively to total p,p'-DDT levels, the active role in detoxification of pollutants may explain why p,p'-DDD is more abundant in liver than in the rest of organs. On the contrary, in brain, the concentration of p,p'-DDE is higher than that of p,p'-DDD, suggesting that the metabolism of the parent insecticide proceeds via more than one pathway.

Previously we reported a tendency for reduction of the development of glutathione-S-transferase placental form (GST-P) positive foci, recognized as preneoplastic changes in rat liver, by a low dose of 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT), which belongs to the same group of hepatic cytochrome P-450 inducers as phenobarbital and is itself a non-genotoxic hepatocarcinogen. In order to clarify the biological significance of this phenomenon, we investigated the reproducibility and changes in other parameters using an initiation-promotion model in which male F344 rats were treated with DDT at doses of 0, 0.005, 0.5, 500 ppm in the diet for 11 or 43 weeks after initiation of hepatocarcinogenesis with N-diethylnitrosamine (DEN). When 500 ppm DDT was applied, the formation of GST-P positive foci and tumor were markedly elevated. In contrast, induction of GST-P positive foci and liver tumors tended to be inhibited at a dose of 0.005 ppm, correlating with protein levels of cytochrome P450 2B1 and 3A2 (CYP2B1 and 3A2) and generation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage. mRNA levels for 8-oxoguanine glycosylase 1 (OGG1), an 8-OHdG repair enzyme, connexin 32 (Cx32), a major component of Gap junctions, and hepatic nuclear factor 1alpha (HNF-1alpha), a Cx32 regulator, were inversely correlated with GST-P positive foci and tumor formation. These results indicate that low dose DDT may indeed exhibit inhibitory effects on chemically initiated-rat hepatocarcinogenicity, in contrast to the promotion observed with high doses, and that this is related to changes in metabolizing enzymes, cell communication, and DNA damage and its repair.

Indoor residual house-spraying (IRS) mainly with dichlorodiphenyltrichloroethane (DDT) was the principal method by which malaria was eradicated or greatly reduced in many countries in the world between the 1940s and 1960s. In sub-Saharan Africa early malarial eradication pilot projects also showed that malaria is highly responsive to vector control by IRS but transmission could not be interrupted in the endemic tropical and lowland areas. As a result IRS was not taken to scale in most endemic areas of the continent with the exception of southern Africa and some island countries such as Reunion, Mayotte, Zanzibar, Cape Verde and Sao Tome. In southern Africa large-scale malarial control operations based on IRS with DDT and benzene hexachloride (BHC) were initiated in a number of countries to varying degrees. The objective of this review was to investigate the malarial situation before and after the introduction of indoor residual insecticide spraying in South Africa, Swaziland, Botswana, Namibia, Zimbabwe and Mozambique using historical malarial data and related information collected from National Malaria Control Programmes, national archives and libraries, as well as academic institutions in the respective countries. Immediately after the inception of IRS with insecticides, dramatic reductions in malaria and its vectors were recorded. Countries that developed National Malaria Control Programmes during this phase and had built up human and organizational resources made significant advances towards malarial control. Malaria was reduced from hyper- to meso-endemicity and from meso- to hypo-endemicity and in certain instances to complete eradication. Data are presented on the effectiveness of IRS as a malarial control tool in six southern African countries. Recent trends in and challenges to malarial control in the region are also discussed.

The aim of the presented study was to compare the effect of o,p'-DDT [1,1-dichloro-2,2-bis-(p,p'-chlorophenyl)-ethylene] and p,p'-DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)-ethane] and their metabolites DDE and DDD on estradiol secretion by ovarian follicles, the target organs of environmental estrogens. Theca interna (Tc) and granulosa cells (Gc) were collected from medium size porcine follicles and cultured as a monolayer. The cells were initially cultured for 24 h to allow attachment to the plates and then media were changed for the new ones and o,p'-DDT and p,p'-DDT and their metabolites: o,p'-DDE, p,p'-DDE and o,p'-DDD were added at doses of 4, 40, 400 ng and 4 microg/ml medium to investigate dose-dependent effects. Media were collected after 24 h and frozen for estradiol content determination. When the effect of single and repeated exposure was investigated, the lowest dose of 4 ng/ml and the highest one of 4 microg/ml were chosen on the basis of the results of Experiment 1. o,p'-DDT exerted antiestrogenic action at all doses used while its metabolites and p,p'-DDT and its metabolites decreased estradiol secretion only when present in the medium at a dose of 4 ng/ml. The highest doses caused the increase in estradiol secretion. Parent o,p'-DDT and its metabolites showed antiestrogenic action after single exposure to 4 ng/ml while parent p,p'-DDT and its metabolites caused estrogenic action. All investigated compounds, except o,p'-DDT, increased estradiol secretion after single exposure to the dose of 4 microg/ml. Repeated exposure resulted in a massive antiestrogenic action of all investigated chemicals. In conclusion, our study points to time-dependent effect of DDT and its metabolites on ovarian follicles with the strongest estrogenic properties observed after single exposure and antiestrogenic action caused by repeated exposure. Given the duration of folliculogenesis, one can imagine many different potential mechanisms by which DDT could influence steroidogenesis.

We reviewed the use of simple mathematical models to estimate the duration of Plasmodium falciparum infection after transmission has been interrupted. We then fit an exponential decay model to repeated cross-sectional survey data collected from three historical trials of indoor residual spraying against malaria: one from two contiguous districts in Tanzania-Kenya (Pare Taveta) carried out in 1954, the others in West Papua (1953), and the Garki project in northern Nigeria (1972-1973). A cross-sectional analysis of these datasets gave overall estimates of 602 days (95% confidence interval [CI] = 581-625) for the infection duration in Pare Taveta, 734 days (95% CI = 645-849) in West Papua, and 1,329 days (95% CI =1,193-1,499) for Garki. These estimates are much greater than the most widely quoted figures for the duration of untreated P. falciparum infections. Although these may be exaggerated because some reinfections occurred despite intensive vector control, prevalence was still decreasing when all these projects ended. Longitudinal survival analysis of the Garki data gave much shorter estimates of duration (186 days, 95% CI = 181-191), but effects of imperfect detection of parasites by microscopy severely bias these estimates. Estimates of infection duration for different age groups showed considerable variation but no general age trend. There was also no clear relationship between malaria endemicity and infection duration. Analyses of successive sampling from the same individuals with parasite typing are needed to obtain more reliable estimates of infection duration in endemic areas. Periods of several years may be required to evaluate long-term effects of interventions on malaria prevalence.

Permethrin and DDT resistance in Anopheles gambiae s.s. associated with a leucine-serine knockdown resistance (kdr) mutation in the voltage-gated sodium channel gene was discovered recently in western Kenya where a large scale permethrin-impregnated bed net (ITN) program has been implemented. Collections of An. gambiae s.l. were made from intervention and control villages prior to and after onset of the program. The kdr genotypes were determined using allele-specific polymerase chain reaction diagnostic tests. In An. gambiae s.s., the frequency of the kdr mutation prior to ITN introduction was approximately 3-4% in western Kenya and zero in samples from the coast. After ITN introduction, the kdr mutation increased in ITN and neighboring villages from approximately 4% to approximately 8%, but remained unchanged in villages at least 20 km distant and was not detected in coastal Kenya. The identical leucine-serine mutation was found in a single An. arabiensis individual among 658 tested. The leucine-phenylalanine kdr mutation common in west African An. gambiae populations was not detected in An. gambiae s.l. from Kenya. Implications for the population structure and control of An. gambiae are discussed.

Susceptibility status of Indian kala-azar vector Phlebotomus argentipes after DDT spray from endemic areas of Muzaffarpur and Vaishali district and unsprayed non-endemic area of Patna district, Bihar, India were compared. Higher Lc50 viz. 2.6% and 3.2% and LT50, values 51.0 and 69.0 minutes to 4% DDT were observed for P. argentipes of Muzaffarpur and Vaishali district, whereas P. argentipes of Patna district was 100% susceptible to same concentration, indicating increased tolerance in P. argentipes. It is concluded DDT resistant P. argentipes, particularly in endemic zone growing. The possible explanation could be long-term insecticidal pressure.

The aim of the present work was to investigate whether DDT and its metabolites are able to induce apoptosis of human peripheral blood mononuclear cells (PBMC) both in vitro and in vivo. Cells isolated from healthy individuals were incubated in the presence of increasing concentrations of p'p-DDT, p'p-DDE, or p'p-DDD (0-150 microg/mL) for different intervals. Apoptosis was then determined by flow cytometry (DNA cell content analysis) and fluorescence microscopy (Hoechst staining). A significant level of apoptosis was induced by DDT, DDD, and DDE at 80 microg/mL compared to controls, reaching a maximum effect at 100 microg/mL. We began to detect apoptosis at 12h, with a maximum effect at 24h of incubation. These results were confirmed using the TUNEL assay in cells treated with the three compounds tested as well as with o'p-DDT at 100 microg/mL and 24h of incubation. Our data demonstrate that DDT and its metabolites are able to induce apoptosis of human PBMC in vitro. Therefore, we performed a preliminary study in children exposed to this insecticide. When compared to a control population, the exposed children had higher levels of DDT, DDD, and DDE in blood and also had a higher frequency of apoptosis. In the exposed children, a weak positive association was found between the frequency of apoptosis and the exposure to DDT and DDE. Our results showed that more studies are needed in people exposed to DDT, as apoptosis may cause serious public health effects such as immunosuppression.

In this study, DDT-induced DNA damage on blood cells was analyzed both in vitro and in vivo. Peripheral blood mononuclear cells (PBMC) were isolated from healthy donors and incubated in the presence of three different concentrations (40, 80, and 100 microg/mL) of p,p'-DDT, p,p'-DDE, and p,p'-DDD at three different treatment times (24, 48, and 72 h). Then, DNA damage was assessed by the single-cell electrophoresis assay (comet assay) as well as by flow cytometry detection of hypodiploid cells (DNA content assay). All compounds induced significant DNA damage as shown by the comet assay. Accordingly, cells exposed to DDT, DDE, and DDD showed a significant increase in the percentage of hypodiploid cells compared with untreated PBMC. In agreement with the in vitro data, a significant correlation between blood levels of DDT, DDD, and DDE and DNA damage (comet assay) was found in women with different amounts of environmental exposure. This association remained significant after controlling for nutritional status, smoking habits, alcohol ingestion, and reported exposure to other pesticides. Although the precise biological importance remains to be explained, our results strongly suggest that DDT and its metabolites are able to induce DNA damage in PBMC both in vitro and in vivo.

A comparative study on the reliability of toxicokinetic parameters for predicting hepatotoxicity was conducted in male F344 rats receiving a single (106 mg/kg by gavage) or 7-day repeated (1000 ppm in feed, 97 mg/kg/day) administration of p,p'-DDT. DDT was selected as the test substance because it is known as a hepatotoxic agent and its metabolic pathway is well documented. Concentrations of DDT and its metabolites (DDE and DDD) in the plasma, brain, and liver were measured at various time intervals during the study and the results were compared with the area under the concentration-time curve (AUC) in relation to hepatotoxic response. Increases in the absolute and relative (ratio to body weight) liver weights were observed as a typical toxic response after a single or repeated exposure to DDT. The coefficient (R2) of correlation between the increases in the relative liver weight and the concentrations or AUC of DDT and its metabolites in the plasma and liver was estimated. The values of R2 between the relative liver weight and AUC of DDT or the total DDT (T-DDT) in the plasma and liver were found to be more consistent and higher than those with their concentrations in the repeated dose study. In addition, the R2 values in correlation with their AUCs after a single exposure were lower than those in the repeated dose study. These results indicate that the AUC of DDT or T-DDT in the plasma and liver would be more reliable than their concentrations for predicting hepatotoxicity caused by DDT, especially in the repeated dose study.

A monitoring study was conducted to assess the magnitude of DDT [(1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane)] and HCH (hexachlorocyclohexane) contamination of bovine milk from the central tropical region of Mexico as the chemicals are extensively used in livestock and public-health programmes. Among pesticide residues analysed, the milk samples collected from Tlalixcoyan showed a mean level of gamma-HCH (0.128 mg x kg(-1)), which was significantly higher than residues in milk samples from Medellin (0.049 mg x kg(-1)) and Paso San Juan (0.022 mg x kg(-1)). The mean level of pp'-DDE in Medellin samples (0.039 mg x kg(-1)) was significantly higher than in Paso San Juan (0.018 mg x kg(-1)) and Tlalixcoyan (0.024 mg x kg(-1)) milk samples. The pp'-DDT mean level from Medellin milk samples (0.089 mg x kg(-1)) was significantly higher than the levels detected in the other two areas. The highest mean Sigma-DDT level detected in Medellin samples (0.146 mg x kg(-1)) was three times the FAO/WHO tolerance level. The highest acceptable daily intakes calculated for Sigma-DDT were 0.017 microg x kg(-1) bw day(-1) for adults and 0.530 microg x kg(-1) bw day(-1) for infants; for gamma-HCH residues, they were 0.021 microg x kg(-1) bw day(-1) for adults and 0.666 microg x kg(-1) bw day(-1) for infants, indicating that infants are more exposed to pesticide residues. Results indicate that cattle exposure to HCH and DDT results in high levels in dairy milk and a potential health risk for consumers.

This study was conducted to examine the effects of dietary carbohydrate [starch or sucrose (500 g/kg diet)] and myo-inositol (2 g/kg diet) on metabolic changes in rats fed 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT) (0.7 g/kg diet). Dietary DDT enhanced serum and hepatic lipids and hepatic thiobarbituric acid reactive substances (TBA-RS), elevated hepatic activities of lipogenic enzymes such as malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PD) and fatty acid synthetase (FAS), increased hepatic cytochrome P-450 content and the activities of drug-metabolizing enzymes such as aminopyrine N-demethylase, glutathione S-transferase and 4-nitrophenol-UDP glucuronosyltransferase (4NP-UDPGT) and raised hepatic ascorbic acid and serum copper. Dietary sucrose promoted the increases in hepatic concentrations of total lipids, triglyceride and cholesterol, hepatic activity of ME, hepatic TBA-RS, cytochrome P-450 content and serum copper due to DDT feeding when compared to DDT administered in a starch based diet. Dietary myo-inositol significantly depressed the rises in hepatic concentrations of total lipids, triglyceride and cholesterol and the activities of ME and G6PD due to DDT feeding regardless of dietary carbohydrate quality. Dietary starch supplemented with myo-inositol potentiated the enhancements in hepatic activities of Phase II drug-metabolizing enzymes such as glutathione S-transferase and 4NP-UDPGT due to DDT feeding. These results suggest that dietary starch and myo-inositol can protect DDT fed rats against an accumulation of hepatic lipids, which might be mainly ascribed to the depression of hepatic lipogenesis. In addition, the present study implies that the supplementation of myo-inositol to high starch diet might improve the function of drug-metabolizing enzymes exposed to DDT.

Laying hens were administered orally with a single dose of p,p'-(DDT) (1 mg/kg bodyweight). The concentrations (microg/g) of DDT or its metabolites, p,p'-(DDE) and p,p'-(DDD), in the main tissues involved in egg formation (blood, liver, ovary, and oviducts) and egg yolk, collected 1 day after DDT dosing, were determined by normal-phase high-performance liquid chromatography. The limits of detection were 0.04 microg/g for DDT, 0.07 microg/g for DDE and 0.06 microg/g for DDD. In extractable fats from the above tissues and egg yolk, DDT and DDE were transferred/distributed throughout the tissues and egg yolk. DDD was detected only in the liver. The findings indicate that DDT is metabolized instantaneously to DDE/ DDD in the hen's body and they are transferred rapidly into the egg-forming tissues and egg yolk. Among the four tissues and yolk fats examined, the DDT levels were high in the ovary, oviduct and egg yolk; the DDE levels were high in the liver, ovary and oviduct and lowest in the yolk (P < 0.01).

The aim of study was evaluation of the concentration of dermally applied (14)C DDT in the organs of rats, and evaluation of histological and ultrastructural changes after the dermal application of unlabelled DDT standard in the organs of rats, in which the presence of this pesticide was determined by the radio-isotopic method. (14)C DDT of radiochemical purity of 97% was applied in the study. The activity of the preparation per 1 cm(2) of the tail skin was 22.2 KBq--(175.38 microg DDT). The material for the study was taken directly after single exposure and 6 h, 8 h, 10 h, 12 h, 14 h, 18 h and 20 h after exposure. The following organs were taken for the determination of radioactivity of tissues: brain, heart, lung, liver, kidney, skin at the site of exposure. Unlabelled chemically pure, DDT (99.7%) was used to evaluate histological and ultrastructural changes after dermal application. Experimental animals received an oil emulsion of DDT (10 mg/9 cm(2)), applied to the skin of the tail for 4 weeks. The time of exposure was 4h daily. The animals of the control group were dermally exposed to the emulsion at the same time and under the same conditions. 4 h after dermal exposure it was observed that the preparation applied on the surface of 9 cm(2) in the amount of 1.578 microg was present in the skin in the amount of 1 microg/9 cm(2) (0.11 microg/cm(2)), i.e. 0.063% of (14)C DDT applied dose. Directly after dermal application lasting 4 h the greatest amount of (14)C DDT was noted in the liver--0.285 microg, i.e. 0.033 micrcog/g. Histopatological and ultrastructural changes were observed in the liver, kidney, lungs and heart.

The cost-effectiveness of lambdacyhalothrin-treated nets in comparison with conventional DDT spraying for malaria control among migrant populations was evaluated in a malaria hyperendemic area along the Thai-Myanmar border. Ten hamlets of 243 houses with 948 inhabitants were given only treated nets. Twelve hamlets of 294 houses and 1,315 population were in the DDT area, and another 6 hamlets with 171 houses and 695 inhabitants were in the non-DDT-treated area. The impregnated net program was most cost-effective (US$1.54 per 1 case of prevented malaria). Spraying with DDT was more cost-effective than malaria surveillance alone ($1.87 versus $2.50 per 1 case of prevented malaria). These data suggest that personal protection measures with insecticide-impregnated mosquito net are justified in their use to control malaria in highly malaria-endemic areas in western Thailand.