Poisoning by paraquat herbicide is a major medical problem in parts of Asia while sporadic cases occur elsewhere. The very high case fatality of paraquat is due to inherent toxicity and lack of effective treatments. We conducted a systematic search for human studies that report toxicokinetics, mechanisms, clinical features, prognosis and treatment. Paraquat is rapidly but incompletely absorbed and then largely eliminated unchanged in urine within 12-24 h. Clinical features are largely due to intracellular effects. Paraquat generates reactive oxygen species which cause cellular damage via lipid peroxidation, activation of NF-kB, mitochondrial damage and apoptosis in many organs. Kinetics of distribution into these target tissues can be described by a two-compartment model. Paraquat is actively taken up against a concentration gradient into lung tissue leading to pneumonitis and lung fibrosis. Paraquat also causes renal and liver injury. Plasma paraquat concentrations, urine and plasma dithionite tests and clinical features provide a good guide to prognosis. Activated charcoal and Fuller's earth are routinely given to minimize further absorption. Gastric lavage should not be performed. Elimination methods such as haemodialysis and haemoperfusion are unlikely to change the clinical course. Immunosuppression with dexamethasone, cyclophosphamide and methylprednisolone is widely practised, but evidence for efficacy is very weak. Antioxidants such as acetylcysteine and salicylate might be beneficial through free radical scavenging, anti-inflammatory and NF-kB inhibitory actions. However, there are no published human trials. The case fatality is very high in all centres despite large variations in treatment.

In a prospective cohort study of patients presenting with pesticide self-poisoning, Andrew Dawson and colleagues investigate the relative human toxicity of agricultural pesticides and contrast it with WHO toxicity classifications, which are based on toxicity in rats.

BackgroundDeliberate self-poisoning with older pesticides such as organophosphorus compounds are commonly fatal and a serious public health problem in the developing world. The clinical consequences of self-poisoning with newer pesticides are not well described. Such information may help to improve clinical management and inform pesticide regulators of their relative toxicity. This study reports the clinical outcomes and toxicokinetics of the neonicotinoid insecticide imidacloprid following acute self-poisoning in humans.Methodology/Principal FindingsDemographic and clinical data were prospectively recorded in patients with imidacloprid exposure in three hospitals in Sri Lanka. Blood samples were collected when possible for quantification of imidacloprid concentration. There were 68 patients (61 self-ingestions and 7 dermal exposures) with exposure to imidacloprid. Of the self-poisoning patients, the median time to presentation was 4 hours (IQR 2.3–6.0) and median amount ingested was 15 mL (IQR 10–50 mL). Most patients only developed mild symptoms such as nausea, vomiting, headache and diarrhoea. One patient developed respiratory failure needing mechanical ventilation while another was admitted to intensive care due to prolonged sedation. There were no deaths. Median admission imidacloprid concentration was 10.58 ng/L; IQR: 3.84–15.58 ng/L, Range: 0.02–51.25 ng/L. Changes in the concentration of imidacloprid in serial blood samples were consistent with prolonged absorption and/or saturable elimination.ConclusionsImidacloprid generally demonstrates low human lethality even in large ingestions. Respiratory failure and reduced level of consciousness were the most serious complications, but these were uncommon. Substitution of imidacloprid for organophosphorus compounds in areas where the incidence of self-poisoning is high may help reduce deaths from self-poisoning.

SummaryBackgroundAgricultural pesticide self-poisoning is a major public health problem in rural Asia. The use of safer household pesticide storage has been promoted to prevent deaths, but there is no evidence of effectiveness. We aimed to test the effectiveness of lockable household containers for prevention of pesticide self-poisoning.MethodsWe did a community-based, cluster-randomised controlled trial in a rural area of North Central Province, Sri Lanka. Clusters of households were randomly assigned (1:1), with a sequence computer-generated by a minimisation process, to intervention or usual practice (control) groups. Intervention households that had farmed or had used or stored pesticide in the preceding agricultural season were given a lockable storage container. Further promotion of use of the containers was restricted to community posters and 6-monthly reminders during routine community meetings. The primary outcome was incidence of pesticide self-poisoning in people aged 14 years or older during 3 years of follow-up. Identification of outcome events was done by staff who were unaware of group allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT1146496.FindingsBetween Dec 31, 2010, and Feb 2, 2013, we randomly assigned 90 rural villages to the intervention group and 90 to the control group. 27 091 households (114 168 individuals) in the intervention group and 26 291 households (109 693 individuals) in the control group consented to participate. 20 457 household pesticide storage containers were distributed. In individuals aged 14 years or older, 611 cases of pesticide self-poisoning had occurred by 3 years in the intervention group compared with 641 cases in the control group; incidence of pesticide self-poisoning did not differ between groups (293·3 per 100 000 person-years of follow-up in the intervention group vs 318·0 per 100 000 in the control group; rate ratio [RR] 0·93, 95% CI 0·80–1·08; p=0·33). We found no evidence of switching from pesticide self-poisoning to other forms of self-harm, with no significant difference in the number of fatal (82 in the intervention group vs 67 in the control group; RR 1·22, 0·88–1·68]) or non-fatal (1135 vs 1153; RR 0·97, 0·86–1·08) self-harm events involving all methods.InterpretationWe found no evidence that means reduction through improved household pesticide storage reduces pesticide self-poisoning. Other approaches, particularly removal of highly hazardous pesticides from agricultural practice, are likely to be more effective for suicide prevention in rural Asia.FundingWellcome Trust, with additional support from the American Foundation for Suicide Prevention, Lister Institute of Preventive Medicine, Chief Scientist Office of Scotland, University of Copenhagen, and NHMRC Australia.

Hump-nosed pit vipers of Genus Hypnale are the commonest cause of snake bite in Sri Lanka. Although there are many reports of local effects, coagulopathy and acute kidney injury, it remains unclear how frequent these clinical effects are and therefore the medical importance of this snake genus. The genus has been recently revised to include Hypnale hypnale from Sri Lanka and Western Ghats of Southern India, and the two endemic species to Sri Lanka, Hypnale zara and Hypnale nepa. This was a prospective hospital-based clinical study of definite Hypnale spp. bites from July 2008 to July 2010 in six Sri Lankan hospitals. There were 114 patients included and all snakes were correctly identified by hospital staff as Hypnale spp. Of these, 93 snakes were identified as H. hypnale by an expert, 16 as H. zara and five as H. nepa. Most bites occurred on the lower limbs in the daytime. There was no difference in the clinical effects between the three species. Pain and fang marks were present in all patients, 101 had local swelling and only 16 (14%) developed extensive local swelling that spread proximally and involved more than half of the bitten limb. Systemic symptoms occurred in 18 patients; four patients had an abnormal 20 min whole blood clotting test and one patient developed an acute kidney injury that required haemodialysis. All patients were discharged alive with a median length of stay of 2 days. This study confirms that hump-nosed viper bites cause only minor effects in most cases. Future studies need to undertake formal coagulation studies and identify important early indicators of renal impairment.

Summaryobjectives To identify different rickettsial infections using a specific immunofluorescent technique in patients clinically diagnosed as 'typhus fever' in the Central Province of Sri Lanka, and to define the clinical picture, assess the severity of infection and to determine the pattern of geographical distribution of the infections of the hospital-based patients.methods A specific indirect immunofluorescent antibody technique was used on the sera of two groups of patients in laboratories in Japan and Thailand.results We serodiagnosed infections with Orientia tsutsugamushi, Rickettsia typhi and spotted fever group in 56 of 118 clinically investigated patients. There were eight infections with O. tsutsugamushi, two with R. typhi and 10 spotted fever group patients with IgM antibodies suggestive of acute infection. Nineteen patients had antibodies against these three rickettsial species, suggestive of past exposure, co-infection or cross-reactivity of antigens. Discrete, erythematous maculopapular rash was common to all three types of infection except for five patients who had no rash. Five patients positive for spotted fever antibodies developed fern-leaf type skin necrosis with severe illness. Duration of the febrile period ranged from 4 to 23 days with defervescence occurring after specific antibiotic treatment.conclusions The study has shown the presence of different types of rickettsial infections in the Central Province of Sri Lanka. The characterization of the clinical picture and the severity of infection provide useful information for the proper management of the patients in the future.

BackgroundAntimicrobial resistance (AMR) is a major challenge for global health care. Pharmacists play a key role in the health care setting to help support the quality use of medicines. The education, training, and experiences of pharmacy students have the potential to impact on patterns of antibiotic use in community and hospital settings. The aim of this study was to investigate antibiotic use, knowledge of antibiotics and AMR among undergraduate pharmacy students at Sri Lankan universities and to compare this between junior and senior pharmacy student groups.MethodsA cross-sectional study was conducted at the six universities in Sri Lanka that offer pharmacy undergraduate programmes. All pharmacy students in each university were invited to participate in this study using a self-administered questionnaire with ethics approval. The study instrument comprised five major sections: demographic information, self-reported antibiotic use, knowledge of antibiotic uses in human health, knowledge of AMR and antibiotic use in agriculture. Descriptive data analyses were conducted and Chi-squared analysis was used to explore associations between different variables and level of pharmacy education.ResultsFour hundred sixty-six pharmacy students completed the questionnaire. A majority of participants (76%) reported antibiotic use in the past year. More than half (57%) of the junior pharmacy students incorrectly indicated that antibiotic use is appropriate for the management of cold and flu conditions. Senior pharmacy students (n = 206) reported significantly better antibiotic knowledge than junior students (n = 260), p < 0.05. Overall pharmacy students showed good understanding of AMR and their knowledge level increased as the year of pharmacy study increased.ConclusionsThis study found that pharmacy students commonly report using antibiotics. Junior students report some misconceptions about antimicrobials. A comparison between junior and senior pharmacy students suggests that pharmacy education is associated with improved understanding of appropriate antibiotic use and AMR among undergraduate pharmacy students in Sri Lanka.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3107-8) contains supplementary material, which is available to authorized users.

HIET used to treat CCB-induced cardiovascular toxicity is a safe intervention when administered in a critical care setting. Maximal HIET efficacy may be obtained when HIET is administered in conjunction with conventional therapy relatively early in the course of severe CCB poisoning when insulin resistance is high.