Investigation of an acute neurological outbreak in Eluru, India, 2020.

On 4th December 2020, a sudden outbreak, with neurological symptoms like seizures, loss of consciousness etc., was reported in a town from south India. By 3rd day about 400 people were involved. A multi disciplinary team from our institute visited the site to investigate the outbreak. Based on the case history and clinical examination of the patients, the team suspected a probable diagnosis of an acute pesticide, heavy metal and/or mycotoxin exposure for which, biological samples (blood, urine) were collected from those who reported the symptoms as well as from a few who did not report symptoms (controls). To identify the source, water and food samples were collected. The samples were subjected to ICP-MS for heavy metal analysis, LC-MS/MS for pesticide analysis, microbiological analysis and ELISA-Kit method for aflatoxins if any. Clinical and dietary details were collected from a total of 112 participants, of which, 103 cases (77 active cases at Hospital and 26 recovered cases from community) and 9 were controls. A total of 109 biological samples, 36 water samples and food samples were collected. The mean age of the study participants was 29.2 years. Among cases, Seizures were seen in 84%, loss of consciousness in 66%, mental confusion in 35%, pinpoint pupil in 11%. Triazophos (organophosphate) pesticide was present in 74% of Blood samples and its metabolites were present in 98% of the urine samples collected from the cases. All the ten heavy metals investigated including lead, mercury and nickel were found to be within permissible limits except for a few samples. No presence of mycotoxins was observed in Food samples. Water samples which included Head pump and reservoir were free from pesticides; however, all water samples from households of cases had triazophos pesticide with a mean concentration of 1.00 ug/L. Thus, it was concluded that, the probable cause of outbreak was Triazophos (Organophosphate) pesticide contamination in water at the Household level. Regular surveillance for the presence of residual pesticides in soil, water and food with heightened vigour is recommended to prevent future outbreaks.

A case of Fanconi syndrome due to a deferasirox overdose and a trial of plasmapheresis.

WHAT IS KNOWN AND OBJECTIVE: Deferasirox has nephrotoxic effects in the context of chronic therapy. This case report illustrates proximal tubular dysfunction (Fanconi syndrome) due to an acute deferasirox overdose. CASE DESCRIPTION: In response, we trialled plasmapheresis to eliminate the drug. Deferasirox levels were obtained in the context of three rounds of plasmapheresis. Given the half-life model of decay, we concluded that plasmapheresis may not have been successful. The patient ultimately recovered normal tubular function after 2 months. WHAT IS NEW AND CONCLUSION: This report is the first to describe acute deferasirox-induced nephrotoxicity, and the application of plasmapheresis that, ultimately, did not change the typical time to recovery.

Chorea as unusual complication of fungicide poisoning.

Chorea is a rare manifestation of poisoning. We report an index case of a young woman who developed generalized chorea following propiconazole toxin ingestion. As large series on neurological complications of toxic compounds are difficult to be compiled, it is of interest to report our experience. This report adds one more compound to the increasing list of toxic chorea.

Is the emergence of fungal resistance to medical triazoles related to their use in the agroecosystems? A mini review

Abstract Triazole fungicides are used broadly for the control of infectious diseases of both humans and plants. The surge in resistance to triazoles among pathogenic populations is an emergent issue both in agriculture and medicine. The non-rational use of fungicides with site-specific modes of action, such as the triazoles, may increase the risk of antifungal resistance development. In the medical field, the surge of resistant fungal isolates has been related to the intensive and recurrent therapeutic use of a limited number of triazoles for the treatment and prophylaxis of many mycoses. Similarities in the mode of action of triazole fungicides used in these two fields may lead to cross-resistance, thus expanding the spectrum of resistance to multiple fungicides and contributing to the perpetuation of resistant strains in the environment. The emergence of fungicide-resistant isolates of human pathogens has been related to the exposure to fungicides used in agroecosystems. Examples include species of cosmopolitan occurrence, such as Fusarium and Aspergillus, which cause diseases in both plants and humans. This review summarizes the information about the most important triazole fungicides that are largely used in human clinical therapy and agriculture. We aim to discuss the issues related to fungicide resistance and the recommended strategies for preventing the emergence of triazole-resistant fungal populations capable of spreading across environments.

Comparison of human health risks resulting from exposure to fungicides and mycotoxins via food.

The interest in holistic considerations in the area of food safety is increasing. Risk managers may face the problem that reducing the risk of one compound may increase the risk of another compound. An example is the potential increase in mycotoxin levels due to a reduced use of fungicides in crop production. The Integrated Probabilistic Risk Assessment (IPRA) model was used to compare the estimated health impacts on humans caused by crops contaminated with the fungicides spiroxamine (SPI) and tebuconazole (TEB) or with the mycotoxins deoxynivalenol (DON) and zearalenone (ZEA). The IPRA model integrates a distribution characterising the exposure of individuals with a distribution characterising the susceptibility of individuals towards toxic effects. Its outcome, a distribution of Individual Margins of Exposure (IMoE), served as basis to perform comparisons of compounds, effects, countries, and population groups. Based on the available data and the assumptions made, none of the four compounds was found to have impact on human health in the addressed scenarios. The IMoE distributions were located as follows: DON

Human poisoning with hexastar: a hexaconazole-containing agrochemical fungicide.

We report a patient who ingested 500 ml of Hexastar 5.5% EC, a hexaconazole-containing product. Clinical toxicity consisted primarily of central nervous system depression and generalized trembling. The patient recovered without sequelae with supportive therapy.

Comparative toxicity of citalopram and the newer antidepressants after overdose.

OBJECTIVE: To compare the toxicity of citalopram, venlafaxine, mirtazapine, and nefazadone after overdose. METHODS: Two-year retrospective review of consecutive patients admitted to the toxicology unit of Edinburgh Royal Infirmary. Outcome measure included physiological variables, ECG recordings, peak creatine kinase, development of arrhythmias, seizure, tremor or agitation, and the need for admission to a critical care facility. RESULTS: A total of 225 patients were studied. Venlafaxine was associated with a significantly higher pulse rate (p < 0.0001) and tremor (p = 0.007) than other antidepressants. Citalopram was associated with a significantly longer QT interval on ECG recording (p < 0.0001) but mean QTc durations were not significantly different between all drugs studied. No arrhythmias were recorded. Only venlafaxine and citalopram caused seizures and were associated with the need for admission to Intensive Care, but there was no significant difference between them. CONCLUSIONS: Mirtazapine and nefazadone appear safe in overdose and were associated with minimal features of neurological or cardiovascular toxicity. Citalopram is more likely to cause QT prolongation but other features of cardiovascular toxicity were uncommon. Both citalopram and venlafaxine are proconvulsants. Venlafaxine also causes more frequent features of the serotonin syndrome.

Nefazodone poisoning: toxicokinetics and toxicodynamics using continuous data collection.

Nefazodone overdose has been reported infrequently. The commonest effects reported are drowsiness, nausea, dizziness, and vomiting, less commonly hypotension and bradycardia. We report a case of single-agent nefazodone poisoning. Serial drug concentrations were taken for quantification of parent drug and metabolites. Clinical findings were documented every 1 to 2 hours. We modeled both the toxicokinetics of nefazodone and correlated this with clinical effects and electrocardiograph (ECG) abnormalities. A 16-year-old female took 2.4 g of nefazodone. She had significant drowsiness in the first 6 hours, associated with hypotension (systolic BP < 90 mmHg; lowest BP 70/30 mmHg) for 18 hours, and mild bradycardia (slowest rate of 56 bpm). She had a prolonged QT/QTc which normalized over 24 hours. She was given charcoal and intravenous fluids and was observed carefully, recovering with no problems. The terminal elimination half-life for nefazodone was 8.3 hours, and its metabolite hydroxy(OH)-nefazodone was 14.6 hours. BP-time curves demonstrated an 18-hour period of hypotension. There was a significant correlation between systolic BPand OH-nefazodone (R2 = 0.602). HR remained between 56 and 66 bpm for 30 hours despite hypotension. QT was significantly correlated with nefazodone (R2 = 0.911) and OH-nefazodone (R2 = 0.797), but no significant relationship between QTc and drug concentrations. The case demonstrates that nefazodone may potentially cause cardiac toxicity, which appears to be concentration-dependent. Although QT was concentration-dependent, this would need confirmation with other cases. Bradycardia, hypotension, and drowsiness are the most significant effects and are maximal in the first 12 hours when parent and metabolite concentrations are high.

Toxicities and outcomes associated with nefazodone poisoning: an analysis of 1,338 exposures.

Toxicities and medical outcomes associated with nefazodone poisoning were characterized using national poisoning data from the American Association of Poison Control Centers and through prospective collection of additional data elements. Nefazodone exposures involving concomitant agents were excluded. There were 1,338 human exposures included in the final data analysis. Seventy-five percent of exposures were acute and 20% involved children < 13 years. Twenty-five percent of patients remained asymptomatic. There were no deaths. No dose response relationship was evident in the 45 cases where estimated doses were available. The most common manifestations were drowsiness (17.3% of all patients), nausea (9.7%), and dizziness (9.5%). The most common serious clinical effect was hypotension (1.6%). The median onset time for symptoms was 1.75 hours. Manifestations resolved within 8 to 24 hours. Most patients were treated with only gastrointestinal decontamination. No patients required intubation, mechanical ventilation, or vasopressors. Nefazodone appears to be of low toxicity during poisonings.

How the variability issue was uncovered: the history of the UK residue variability findings.

As a result of routine monitoring data on carrots generated in the 1990s indicating MRL exceedances, further studies showed that residues of organophosphorus compounds in individual roots could vary up to 25 times the levels found in composite samples. Additional work found that this phenomenon also extended to other crops including apples, peaches and celery. Variability (defined as the highest residue level found in any one crop item divided by the level found in a composite sample from the same batch) of up to 34 times mean values was found in one batch of plums. Conventional deterministic methods used in consumer assessments were likely to give gross overestimates of short-term exposure because of the assumptions employed. This led to the development of probabilistic models which made the best use of all available information and was capable of indicating percentages of consumers that could exceed relevant toxicological end points. This indicated that there was unlikely to be serious health effects as a result of ingesting these residues and has subsequently proved to be a useful aid to regulatory decision making.

Akinetopsia from nefazodone toxicity.

PURPOSE: To investigate two cases of selective impairment of motion perception (akinetopsia) induced by toxicity from the antidepressant nefazodone, a new drug that blocks serotonin reuptake and antagonizes 5-HT2 receptors. METHODS: Case reports. RESULTS: A 47-year-old man receiving nefazodone (Serzone; Bristol-Meyers Squibb, New York, N.Y.) (100 mg twice daily), reported a bizarre derangement of motion perception. Moving objects were followed by a trail of multiple "freeze-frame" images, which dissipated promptly when motion ceased. A 48-year-old woman receiving nefazodone (400 mg daily at bedtime) reported a similar phenomenon, with visual trails following moving objects. In both patients, vision returned to normal after the dosage of nefazodone was reduced or eliminated. CONCLUSIONS: Nefazodone toxicity can result in akinetopsia, characterized by the inability to perceive motion in a normal, smooth fashion; persistence of multiple, strobelike images; and visual trails behind moving objects. In this rare syndrome, stationary elements are perceived normally, indicating that nefazodone causes selective impairment of pathways involved in motion processing in the visual system.

Nefazadone-induced acute dystonic reaction.

A 53-y-o patient presented approximately 2 h after taking her first dose of nefazadone. Chief complaint was lip smacking with hand and arm gesturing. The patient also took 25 mg meclizine which she had used before with no adverse effects. Diphenhydramine followed by benztropine led to resolution of symptoms within 1 h. Patient subsequently used meclizine with no untoward reactions. Nefazadone should be added to the list of agents that cause acute dystonic reactions.

Nefazodone overdose: a case report.

Nefazodone (Serzone) is one of the newer medications developed to treat major depression. It is a phenylpiperazine derivative that inhibits the reuptake of both norepinephrine and serotonin and antagonizes the 5HT2 and alpha-one adrenergic receptors. It is well tolerated by patients, and is felt to have a much wider margin of safety than older antidepressants. We report the case of a woman who attempted suicide by ingesting a large amount of nefazodone and a smaller amount of verapamil. We review the literature regarding nefazodone side effects and previous cases of overdose, discuss the clinical complications of such an overdose and discuss treatment recommendation.