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Human poisoning by pesticides has long been seen as a severe public health problem. As early as 1990, a task force of the World Health Organization (WHO) estimated that about one million unintentional pesticide poisonings occur annually, leading to approximately 20,000 deaths. Thirty years on there is no up-to-date picture of global pesticide poisoning despite an increase in global pesticide use. Our aim was to systematically review the prevalence of unintentional, acute pesticide poisoning (UAPP), and to estimate the annual global number of UAPP. We carried out a systematic review of the scientific literature published between 2006 and 2018, supplemented by mortality data from WHO. We extracted data from 157 publications and the WHO cause-of-death database, then performed country-wise synopses, and arrived at annual numbers of national UAPP. World-wide UAPP was estimated based on national figures and population data for regions defined by the Food and Agriculture Organization (FAO). In total 141 countries were covered, including 58 by the 157 articles and an additional 83 by data from the WHO Mortality Database. Approximately 740,000 annual cases of UAPP were reported by the extracted publications resulting from 7446 fatalities and 733,921 non-fatal cases. On this basis, we estimate that about 385 million cases of UAPP occur annually world-wide including around 11,000 fatalities. Based on a worldwide farming population of approximately 860 million this means that about 44% of farmers are poisoned by pesticides every year. The greatest estimated number of UAPP cases is in southern Asia, followed by south-eastern Asia and east Africa with regards to non-fatal UAPP. Our study updates outdated figures on world-wide UAPP. Along with other estimates, robust evidence is presented that acute pesticide poisoning is an ongoing major global public health challenge. There is a need to recognize the high burden of non-fatal UAPP, particularly on farmers and farmworkers, and that the current focus solely on fatalities hampers international efforts in risk assessment and prevention of poisoning. Implementation of the international recommendations to phase out highly hazardous pesticides by the FAO Council could significantly reduce the burden of UAPP.

There is a developing drug epidemic in the United States. Jalal et al. analyzed nearly 600,000 unintentional drug overdoses over a 38-year period. Although the overall mortality rate closely followed an exponential growth curve, the pattern itself is a composite of several underlying subepidemics of different drugs. Geographic hotspots have developed over time, as well as drug-specific demographic differences. Science , this issue p. eaau1184 The drug overdose epidemic in the United States is a composite of drug-specific subepidemics. Better understanding of the dynamics of the current U.S. overdose epidemic may aid in the development of more effective prevention and control strategies. We analyzed records of 599,255 deaths from 1979 through 2016 from the National Vital Statistics System in which accidental drug poisoning was identified as the main cause of death. By examining all available data on accidental poisoning deaths back to 1979 and showing that the overall 38-year curve is exponential, we provide evidence that the current wave of opioid overdose deaths (due to prescription opioids, heroin, and fentanyl) may just be the latest manifestation of a more fundamental longer-term process. The 38+ year smooth exponential curve of total U.S. annual accidental drug poisoning deaths is a composite of multiple distinctive subepidemics of different drugs (primarily prescription opioids, heroin, methadone, synthetic opioids, cocaine, and methamphetamine), each with its own specific demographic and geographic characteristics.

As the most favoured animal companion of humans, dogs occupy a unique place in society. Understanding the senses of the dog can bring benefits to both the dogs themselves and their owners. In the case of bitter taste, research may provide useful information on sensitivity to, and acceptance of, diets containing bitter tasting materials. It may also help to protect dogs from the accidental ingestion of toxic substances, as in some instances bitter tasting additives are used as deterrents to ingestion. In this study we examined the receptive range of dog bitter taste receptors (Tas2rs). We found that orthologous dog and human receptors do not always share the same receptive ranges using in vitro assays. One bitter chemical often used as a deterrent, denatonium benzoate, is only moderately active against dTas2r4, and is almost completely inactive against other dog Tas2rs, including dTas2r10, a highly sensitive receptor in humans. We substituted amino acids to create chimeric dog-human versions of the Tas2r10 receptor and found the ECL2 region partly determined denatonium sensitivity. We further confirmed the reduced sensitivity of dogs to this compound in vivo. A concentration of 100[mu]M (44.7ppm) denatonium benzoate was effective as a deterrent to dog ingestion in a two-bottle choice test indicating higher concentrations may increase efficacy for dogs. These data can inform the choice and concentration of bitter deterrents added to toxic substances to help reduce the occurrence of accidental dog poisonings.

A 4-month-old male Himalayan cat presented with clinical signs of acute lethargy and motor incoordination after being treated with amitraz for parasite control. On clinical examination, the patient was lethargic and ataxic with severe pulicosis, hypothermia, pale mucous membranes, bradycardia, weak femoral pulses, hyperglycemia, and bilateral mydriasis. Blood tests revealed non-regenerative hypochromic microcytic anemia. Serum alanine levels were elevated tenfold. The patient received supportive treatment with atipamezole (an [alpha]2-adrenergic antagonist) at a dose of 0.1 mg/kg intramuscularly. After 24 h of hospitalization and constant monitoring, the patient recovered and was discharged. The published literature showed that the active ingredient amitraz is effective in the treatment of some parasitic diseases in cats, such as scabies and demodicosis; therefore, it is still used for this purpose. Given the small therapeutic margin of this insecticide, veterinarians should caution owners about its potential toxicity. This report emphasized the significance of amitraz intoxication in feline species and the success of the treatment, which should be initiated in the first hour after intoxication. Key words: intoxication, insecticide, formamidine, felines, atipamezole, amitraz. Um gato da raça Himalaia, macho, com quatro meses de idade, apresentou sinais clínicos de letargia aguda e incoordenação motora após ser medicado com amitraz para controle de parasitas. No exame clínico, o paciente se apresentava letárgico e atáxico, com pulicose grave, hipotermia, mucosaspálidas, bradicardia, pulso femoral fraco, hiperglicemia e midríase bilateral. O exame de sangue revelou anemia microcítica hipocrômica não regenerativa. Os níveis séricos de ALT estavam 10x elevados. O paciente recebeu tratamento de suporte e administração de atipamezol (antagonista [alpha]2-adrenérgico) na dose de 0,1 mg/kg por via intramuscular. Após 24 horas de internação e acompanhamento constante, o paciente se recuperou e recebeu alta. Dados publicados na literatura demonstram que o princípio ativo amitraz é eficaz no tratamento de algumas doenças parasitárias em gatos como sarna e demodicose e, portanto, ainda é utilizado para esta finalidade. Dada a pequena margem terapêutica deste inseticida, os veterinários devem informar os proprietários sobre o seu potencial de toxicidade. O objetivo deste relato é enfatizar a importância da intoxicação por amitraz na espécie felina e o sucesso do tratamento, que deve ocorrer nas primeiras horas após a intoxicação. Palavras-chave: intoxicação, inseticida, formamidina, felinos, atipamezole, amitraz.

[This corrects the article DOI: 10.1371/journal.pone.0151655.].

Suicide attempts by self-poisoning have become a critical health problem. This study aimed to investigate the trend, incidence, and the associated risk factors of suicide attempts by self-poisoning. A total of 7398 Egyptian patients were analyzed. The trend of suicide attempts by self-poisoning was analyzed using 6745 patients over four registry years from January 1, 2016, to January 1, 2020. Then, the associated risk factors behind attempted suicide by self-poisoning from January 1, 2019, to January 1, 2020, were assessed using 2523 suicide attempters by self-poisoning, 201 fatalities by self-poisoning, and another 653 survivors of accidental poisoning. Results showed a rising trend of suicide attempts by self-poisoning over the studied years. The incidence of suicide attempts through deliberate self-poisoning represented 26.63/1,000 (CI95%: 25.63–27.86) to the admitted patients and 26.10/100,000 (CI95%: 25.10–27.14) to the regional population. The death rate due to suicide attempts by self-poisoning was 2.08/100,000 (1.90–2.49). The case fatality rate and the proportionate mortality rate for suicide by self-poisoning were 7.38% (CI95%: 6.45–8.42) and 14.11% (CI95%: 12.4–16.0) respectively. Multivariate analysis revealed that attempted suicide by self-poisoning was predicted among patients aged <25 or 25–40 years old (OR = 27.49, CI95%: 15.28–49.64 and OR = 59.42, CI95%: 32.76–107.77 respectively), those of low or moderate socioeconomic status (OR = 35.03, CI95%: 21.32–57.56 and OR = 14.11, CI95%: 10.86–18.43 respectively), students (OR = 2.91, CI95%: 1.57–5.43) and those living in rural residency (OR = 4.12, CI95%: 3.27–5.19). Suicide attempts by self-poisoning exhibited an incremental rise across time which raises a serious concern. Efforts should be directed to overcome the mentioned risk factors triggering suicide attempts by self-poisoning.

We analysed deaths certified as due to poisoning in England & Wales, 1968–2000, in children aged <10 years by age, sex, circumstances of death, intent, and agents involved. The number of deaths fell from 165 (20.6 per million children) in 1968 to 30 (4.6 per million) in 2000, a decrease of approximately 80%. The age-specific death rates were similar in boys and girls. The rate was initially much higher, and fell more, in those aged <5 years. Most deaths ( n = 1923) occurred in fires, and had been attributed to inhaling combustion products. A small number ( n = 104) occurred in fires resulting from motor vehicle and other transport accidents. From 1979 (use of ICD-9) the coding of some of these deaths changed from poisoning with carbon monoxide to poisoning with ‘other gases, fumes or vapours’. These ‘fire deaths’ do not appear as poisonings in mortality statistics based on a single underlying cause of death, and cannot be tabulated as poisoning in many countries. Fire deaths and deaths coded to accidental, deliberate, or undetermined poisoning ( n = 702) decreased substantially with time, and by 2000 numbered 14 and 10, respectively. Accidental deaths declined from 151 in 1968 to 23 in 2000, but homicides and open verdicts varied from 5 to 20 per year, with no clear trend. Deaths attributed to carbon monoxide and to ‘other gases, fumes or vapours’ (mostly fire-related) totalled 2431 (84% of all poisoning deaths). Overall, 10% of these deaths were either certified as homicides or open verdicts. However, homicide or open verdict was recorded in half of the 47 fatal opiate poisonings. Opioids have now superseded antidepressants as the commonest agents encountered in fatal poisoning with drugs in children.

abstract Life expectancy in the US increased 3.3 years between 1990 and 2015, but the drivers of this increase are not well understood. We used vital statistics data and cause-deletion analysis to identify the conditions most responsible for changing life expectancy and quantified how public health, pharmaceuticals, other (nonpharmaceutical) medical care, and other/unknown factors contributed to the improvement. We found that twelve conditions most responsible for changing life expectancy explained 2.9 years of net improvement (85 percent of the total). Ischemic heart disease was the largest positive contributor to life expectancy, and accidental poisoning or drug overdose was the largest negative contributor. Forty-four percent of improved life expectancy was attributable to public health, 35 percent was attributable to pharmaceuticals, 13 percent was attributable to other medical care, and -7 percent was attributable to other/unknown factors. Our findings emphasize the crucial role of public health advances, as well as pharmaceutical innovation, in explaining improving life expectancy.

This study aimed to synthesize and analyze toxicological characteristics from reported cases of human anticoagulant rodenticide poisoning, providing reference data for clinical diagnosis and forensic practices. We systematically identified English-language case reports (published since 2000) of human anticoagulant rodenticide poisoning via PubMed and Web of Science. A retrospective analysis was performed on various characteristics, including year, age, gender, manner of poisoning, latency period, clinical symptoms and examination results, primary treatment methods, pathological changes in fatal cases, types and concentrations of rodenticides, and toxicological analysis methods. A total of 88 poisoning cases were identified, comprising 52 cases of accidental poisoning, 31 cases of suicidal poisoning, 3 cases of unknown poisoning and 2 cases of homicide. The median latency period was 4 days (range: 1 ∼ 30). Multi-organ hemorrhage was the predominant clinical manifestation, with hematuria being the most frequently reported symptom (n = 39). Coagulation function tests revealed average values of aPTT, PT, and INR of aPTT: 110 (3.71 ∼ 212) s, PT: 100 (11.6 ∼ 300) s and INR: 9 (0.98 ∼ 38.2), respectively, all significantly exceeding normal ranges. Vitamin K1 administration (intravenous or oral) was the primary treatment. Six fatalities occurred and autopsy findings in three cases primarily indicated multi-organ hemorrhage and necrosis. About the types of rodenticides, a total of 38 cases reported 7 distinct types, with brodifacoum and bromadiolone being the most common, presenting median concentrations of 0.15 μg/mL (0.05 ∼ 10) and 0.1215 μg/mL (0.00032 ∼ 1.665), respectively, which may be significant for clinical diagnosis and forensic identification. In Conclusion, this retrospective analysis characterized key features of 88 cases of anticoagulant rodenticide poisoning and may provide valuable reference to support clinical management and forensic investigation in suspected poisoning events. [Display omitted] •88 cases of poisoning by anticoagulant rodenticides were retrieved and analyzed.•The epidemiological and clinical characteristics of these cases were summarized.•The common types and concentrations of anticoagulant rodenticides were listed.•These data can be used as references and applied in forensic practice.