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The Challenge of Parasite Control
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
In some cases, less toxic compounds persist in the environment for a relatively short time and must therefore be applied more often. Pyrethroids, for instance, break down in only a few days under most environmental conditions. Although this rapid breakdown helps to limit their damage to aquatic environments, it indicates that these compounds must be used regularly to maintain vector control. The effective dose of these organic chemicals can, however, be reduced by combining them with piperonyl butoxide, which interacts synergistically with pyrethroids. Piperonyl butoxide has no insecticide activity by itself, but by inhibiting the invertebrate detoxification system involving cytochrome P450, the target vectors become less able to break down the insecticide. This means that less insecticide can be used to achieve the same outcome.
Some Case Histories
Published in Jacques Derek Charlwood, The Ecology of Malaria Vectors, 2019
According to the World Health Organization, 69% of the estimated 663 million malaria cases averted during the past 15 years were attributed to the use of LLINs, 10% to IRS and the remaining 21% to artemisinin combination therapy (ACT) (WHO, 2015a). The development of resistance by the principal vectors of malaria to the pyrethroid insecticides used on mosquito nets is potentially a very serious problem for malaria control. Nowhere is this of greater concern than in the areas around Lake Victoria in Tanzania. The kdr gene is ‘fixed’ in A. gambiae, the principal vector in the region, A. gambiae. The mosquitoes also show extremely high levels of metabolic resistance to pyrethroids, DDT and bendiocarb. Although new control techniques may eventually involve non-insecticidal approaches, for the moment treatments of nets in such a way that the resistance is minimised may extend the useful life of nets. One such method is to incorporate a synergist along with the insecticide. Piperonyl butoxide (PBO) is a chemical that acts by inhibiting enzymes involved in the natural defence mechanisms of insects, which results in the pyrethroid not being detoxified in the insect and the net remaining potent against mosquitoes despite resistance. Alternative strategies include combining LLINs with IRS using different classes of insecticides.
Rationale and technique of malaria control
Published in David A Warrell, Herbert M Gilles, Essential Malariology, 2017
David A Warrell, Herbert M Gilles
Pyrethrins are nerve poisons, acting through the insect cuticle, which is permeable to them. When sprayed, the droplets come into contact with the insect and their toxic action is fast. The addition of certain synergists increases the toxicity of pyrethrins to insects. Among these synergists, piperonyl butoxide is most commonly used.
The development and hepatotoxicity of acetaminophen: reviewing over a century of progress
Published in Drug Metabolism Reviews, 2020
Mitchell R. McGill, Jack A. Hinson
The first manuscript described the toxicity and showed the importance of drug metabolism (Mitchell et al. 1973). Importantly, the group found that mice are more susceptible to APAP hepatotoxicity than rats. Whereas a dose of 300 mg/kg was toxic to the mouse, a dose 8–10 times higher was required to produce a similar hepatotoxic effect in the rat. Moreover, they observed frequent lethality at these very high doses in the rat. They demonstrated the role of drug metabolism by pre-treating mice with inducers and inhibitors of drug metabolizing enzymes and then histologically evaluating the incidence of hepatic necrosis at 24 hours. Thus, following a dose of 375 mg/kg of APAP, saline pretreated mice had a 46% incidence of hepatic necrosis, whereas pretreatment of mice with the cytochrome P450 inducer phenobarbital increased the incidence of hepatic necrosis to 90%. In contrast, pretreatment with piperonyl butoxide or cobaltous chloride, two inhibitors of drug metabolizing enzymes, decreased the incidence of hepatic necrosis to 0%. These results pointed to a cytochrome P450-dependent mechanism of hepatotoxicity.
Intensity of pyrethroid resistance in Anopheles culicifacies s.l. (Diptera: Culicidae) in Odisha State, India
Published in Pathogens and Global Health, 2020
Sudhansu Sekhar Sahu, Sonia Thankachy, Smrutidhara Dash, Gunasekaran Kasinathan, Ashwani Kumar
In view of increasing resistance in malaria vectors to SPs, many industries have started developing innovative products such as long-lasting non-pyrethroid for IRS with single insecticide or as mixtures and bi-treated nets [22]. However, implementing these newer tools depends on resistance strength in different vectors in different settings of the country which needs to be evaluated. Further, it is proven that piperonyl butoxide (PBO) is an effective synergist for natural pyrethrins and SPs [27]. Earlier, a study conducted in five southern districts of Odisha State showed that the deltamethrin susceptibility could be restored in phenotypic pyrethroid resistant An. culicifacies s.l., when exposed to PBO [5]. The involvement of mono-oxygenase as a major pyrethroid resistance mechanism in An. culicifacies s.l. was also observed as supported by other synergist bioassay study conducted recently in Chhattisgarh State [23].
Clinical presentation of type 1 and type 2 pyrethroid poisoning in humans
Published in Clinical Toxicology, 2022
Manna Sera Jacob, Ramya Iyyadurai, Arun Jose, Jude Joseph Fleming, Grace Rebekah, Anand Zachariah, Samuel George Hansdak, Reginald Alex, Vignesh Kumar Chandiraseharan, Audrin Lenin, John Victor Peter
The clear toxidromic demarcation between type 1 and type 2 pyrethroid poisoning in animals was not as evident in human poisoning although some manifestations were predominant in type 2 poisoning. Nausea and vomiting, which were the most frequent symptom in both groups, is generally attributed to the solvent (piperonyl butoxide) rather than due to the direct effect of pyrethroid compound [7]. Although fine tremors are typically described in type 1 pyrethroid exposure in animals, and coarse tremors with type 2 poisoning in animals [3], in our study, fine tremors were equally observed with type 1 and 2 poisoning; only 3 patients (5.1%) had coarse tremors (Table 2). Choreoathetosis, described in animals with type 2 exposure, was not seen in our cohort.