M H Rezvi Sheriff

Publications of M H Rezvi Sheriff

• Patterns and correlates of adult height in Sri Lanka.

  Authors: Priyanga Ranasinghe, M A Naveen A A D Jayawardana, Godwin R Constantine, M H Rezvi Sheriff, David R Matthews, Prasad Katulanda

  Economics and human biology. 01/2011; 9(1):23-9.

  The present study examines patterns and socioeconomic and demographic correlates of adult height among Sri Lankan adults. Data were available for height and socio-demographic factors from aThe present study examines patterns and socioeconomic and demographic correlates of adult height among Sri Lankan adults. Data were available for height and socio-demographic factors from a nationally representative cross-sectional sample of 4477 subjects above 18 years. Recruitment was between 2005 and 2006. Mean age of all subjects was 46.1±15.1 years. Mean height of males and females were 163.6±6.9cm and 151.4±6.4cm respectively. Mean height showed a significant negative correlation with age (p<0.001, r=-0.207). Highest mean height in females 154.0±5.9cm and males 165.6±6.9cm were observed in those born after 1977. Rural females (151.4±6.2cm) were significantly taller than the urban (151.3±7.2cm). However, this was not observed in males. In multivariate analysis, year of birth, level of education and household income were significantly associated with height. Height demonstrated a significant negative correlation with systolic blood pressure (r=-0.032), presence of diabetes (r=-0.069), total cholesterol (r=-0.106), HDL cholesterol (r=-0.142) and LDL cholesterol (r=-0.104). Height was associated with household income and level of education in Sri Lanka and demonstrated a distinct increasing trend over successive generations.

• Distinctive Epidemiologic and Clinical Features of Common Krait (Bungarus caeruleus) Bites in Sri Lanka.

  Authors: Christeine A Ariaratnam, M H Rezvi Sheriff, R David G Theakston, David A Warrell

  The American journal of tropical medicine and hygiene. 10/2008; 79(3):458-62.

  A prospective study was designed to define epidemiologic and clinical features of krait bites to improve diagnosis, management, and prevention. Among 762 cases of venomous snake bites admitted to 10A prospective study was designed to define epidemiologic and clinical features of krait bites to improve diagnosis, management, and prevention. Among 762 cases of venomous snake bites admitted to 10 Sri Lankan hospitals in which the snake responsible was brought and identified, 88 (11.5%) were caused by common kraits (Bungarus caeruleus). Bites were: most frequent in September through November. Distinctive features of B. caeruleus bites (compared with bites by other species in parentheses) were bitten while sleeping on the ground, 100% (1%); indoors, 100% (49%); between 2300 and 0500 hours, 100% (3%). Only 13% of krait victims were bitten on their lower limbs (82%), only 9% had local swelling (in all cases mild) at the site of the bite (93%), 64% developed respiratory paralysis (2%), and 91% experienced (often severe) abdominal pain (10%). Case fatality was 6% (3%). This distinctive pattern of epidemiology and symptoms will aid clinical recognition (syndromic diagnosis) and prevention of krait bite envenoming.

• The importance of poisoning vs. road traffic injuries as a cause of death in rural Sri Lanka.

  Authors: Michael Eddleston, Nilantha Udayakumara, Sriyantha Adhikari, Dhamika de Silva, M H Rezvi Sheriff, Dhananjaya L Waidyaratne

  PLoS ONE. 02/2007; 2(7):e599.

  BACKGROUND: Road traffic crashes are considered by the WHO to be the most important global cause of death from injury. However, this may not be true for large areas of rural Asia where road vehiclesBACKGROUND: Road traffic crashes are considered by the WHO to be the most important global cause of death from injury. However, this may not be true for large areas of rural Asia where road vehicles are uncommon. The issue is important, since emphasising the importance of road traffic crashes risks switching resources to urban areas, away from already underfunded rural regions. In this study, we compared the importance of road traffic crashes with other forms of injury in a poor rural region of South Asia. METHODOLOGY/PRINCIPAL FINDINGS: We collected data on all deaths from injury in the North Central Province of Sri Lanka (NCP; population 1,105,198 at 2001 census) over 18 months using coronial, hospital, and police data. We calculated the incidence of death from all forms of intentional and unintentional injury in the province. The annual incidence of death from injury in the province was high: 84.2 per 100,000 population. Half of the deaths were from self-harm (41.3/100,000). Poisoning (35.7/100,000)-in particular, pesticide self-poisoning (23.7/100,000)-was the most common cause of death, being 3.9-fold more common than road traffic crashes (9.1/100,000). CONCLUSIONS/SIGNIFICANCE: In poor rural regions of South Asia, fatal self-harm and pesticide self-poisoning in particular are significantly more important than road traffic injuries as a cause of death. It is possible that the data used by the WHO to calculate global injury estimates are biased towards urban areas with better data collection but little pesticide poisoning. More studies are required to inform a debate about the importance of different forms of injury and how avoidable deaths from any cause can be prevented. In the meantime, marked improvements in the effectiveness of therapy for pesticide poisoning, safer storage, reduced pesticide use, or reductions in pesticide toxicity are required urgently to reduce the number of deaths from self-poisoning in rural Asia.

• Plasma alkalinization for acute organophosphorus poisoning--is it a reality in the developing world?

  Authors: Darren M Roberts, Andrew H Dawson, Ariyasena Hittarage, K Jeganathan, M H Rezvi Sheriff, Nick A Buckley

  Clinical toxicology (Philadelphia, Pa.). 02/2007; 45(1):90-1; author reply 92-3.

• Compliance for single and multiple dose regimens of superactivated charcoal: a prospective study of patients in a clinical trial.

  Authors: Fahim Mohamed, M Roshini Sooriyarachchi, Lalith Senarathna, Shifa Azhar, M H Rezvi Sheriff, Nick A Buckley, Michael Eddleston

  Clinical toxicology (Philadelphia, Pa.). 02/2007; 45(2):132-5.

  BACKGROUND: Although activated charcoal is widely used for the treatment of self-poisoning, its effectiveness is unknown. An important consideration is patient compliance since poor compliance willBACKGROUND: Although activated charcoal is widely used for the treatment of self-poisoning, its effectiveness is unknown. An important consideration is patient compliance since poor compliance will limit effectiveness. We aimed to describe compliance in a randomized controlled trial (RCT) performed in Sri Lanka, presuming that this would set the upper limits for compliance in routine clinical use. METHOD: 1,103 patients randomized to single or multiple (six doses q4h) 50 g doses of superactivated charcoal were prospectively observed. Charcoal was given by study doctors who recorded the amount ingested and the amount of persuasion required for the patients to drink the charcoal. RESULTS: 559 patients were randomized to receive one dose and 544 to receive six doses. Data was available for 1,071 (97%) patients. Eighty-eight were unable to complete their course; 98 required a NG tube, leaving 885 patients that received the first dose by mouth. The mean estimated amount of the prescribed dose of charcoal taken orally as a single or first dose was 83% (95% C.I. 82-84%). For patients receiving multiple doses, this amount fell over the next five doses to 66% (63-69%). While only 3.2% of patients refused the first dose, 12.3% refused the sixth. Relatively less persuasion was required for patients ingesting the first or single dose; 38% of patients required intense persuasion by the sixth dose. CONCLUSION: Compliance for a single dose of superactivated charcoal among trial patients was good. However, even in the ideal circumstances of a RCT, compliance decreased thereafter for patients taking more than one dose.

• The hazards of gastric lavage for intentional self-poisoning in a resource poor location.

  Authors: Michael Eddleston, Sapumal Haggalla, K Reginald, K Sudarshan, M Senthilkumaran, Lakshman Karalliedde, Ariaranee Ariaratnam, M H Rezvi Sheriff, David A Warrell, Nick A Buckley

  Clinical toxicology (Philadelphia, Pa.). 02/2007; 45(2):136-43.

  OBJECTIVE: The 10-20% case fatality found with self-poisoning in the developing world differs markedly from the 0.5% found in the West. This may explain in part why the recent movement away from theOBJECTIVE: The 10-20% case fatality found with self-poisoning in the developing world differs markedly from the 0.5% found in the West. This may explain in part why the recent movement away from the use of gastric lavage in the West has not been followed in the developing world. After noting probable harm from gastric lavage in Sri Lanka, we performed an observational study to determine how lavage is routinely performed and the frequency of complications. CASE SERIES: Fourteen consecutive gastric lavages were observed in four hospitals. Lavage was given to patients unable or unwilling to undergo forced emesis, regardless of whether they gave consent or the time elapsed since ingestion. It was also given to patients who had taken non-lethal ingestions. The airway was rarely protected in patients with reduced consciousness, large volumes of fluid were given for each cycle (200 to more than 1000 ml), and monitoring was not used. Serious complications likely to be due to the lavage were observed, including cardiac arrest and probable aspiration of fluid. Health care workers perceived lavage as being highly effective and often life-saving; there was peer and relative pressure to perform lavage in self-poisoned patients. CONCLUSIONS: Gastric lavage as performed for highly toxic poisons in a resource-poor location is hazardous. In the absence of evidence for patient benefit from lavage, (and in agreement with some local guidelines), we believe that lavage should be considered for few patients - in those who have recently taken a potentially fatal dose of a poison, and who either give their verbal consent for the procedure or are sedated and intubated. Ideally, a randomized controlled trial should be performed to determine the balance of risks and benefits of safely performed gastric lavage in this patient population.

• Study protocol: a randomised controlled trial of multiple and single dose activated charcoal for acute self-poisoning.

  Authors: Michael Eddleston, Edmund Juszczak, Nick A Buckley, Lalith Senarathna, Fahim Mohammed, Stuart Allen, Wasantha Dissanayake, Ariyasena Hittarage, Shifa Azher, K Jeganathan, Shaluka Jayamanne, M H Rezvi Sheriff, David A Warrell

  BMC emergency medicine. 01/2007; 7:2.

  BACKGROUND: The case fatality for intentional self-poisoning in rural Asia is 10-30 times higher than in the West, mostly due to the use of highly toxic poisons. Activated charcoal is a widelyBACKGROUND: The case fatality for intentional self-poisoning in rural Asia is 10-30 times higher than in the West, mostly due to the use of highly toxic poisons. Activated charcoal is a widely available intervention that may - if given early - bind to poisons in the stomach and prevent their absorption. Current guidelines recommend giving a single dose of charcoal (SDAC) if patients arrive within an hour of ingestion. Multiple doses (MDAC) may increase poison elimination at a later time by interrupting any enterohepatic or enterovascular circulations. The effectiveness of SDAC or MDAC is unknown. Since most patients present to hospital after one hour, we considered MDAC to have a higher likelihood of clinical benefit and set up a study to compare MDAC with no charcoal. A third arm of SDAC was added to help determine whether any benefit noted from MDAC resulted from the first dose or all doses. METHODS/DESIGN: We set up a randomised controlled trial assessing the effectiveness of superactivated charcoal in unselected adult self-poisoning patients admitted to the adult medical wards of three Sri Lankan secondary hospitals. Patients were randomised to standard treatment or standard treatment plus either a single 50 g dose of superactivated charcoal dissolved in 300 ml of water or six doses every four hours. All patients with a history of poison ingestion were approached concerning the study and written informed consent taken from each patient, or their relative (for unconscious patients or those <16 yrs), recruited to the study. The exclusion criteria were: age under 14 yrs; prior treatment with activated charcoal during this poisoning episode; pregnancy; ingestion of a corrosive or hydrocarbon; requirement for oral medication; inability of the medical staff to intubate the patient with a Glasgow Coma Score <13; presentation >72 hrs post-ingestion, and previous recruitment. The primary outcome was in-hospital mortality; secondary outcomes included the occurrence of serious complications (need for intubation, time requiring assisted ventilation, fits, cardiac dysrhythmias). Analysis will be on an intention-to-treat basis; the effects of reported time to treatment after poisoning and status on admission will also be assessed. DISCUSSION: This trial will provide important information on the effectiveness of both single and multiple dose activated charcoal in the forms of poisoning commonly seen in rural Asia. If charcoal is found to be effective, it should be possible to make it widely available across rural Asia in an affordable formulation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02920054.

• Physical vulnerability and fatal self-harm in the elderly.

  Authors: Michael Eddleston, Mathisha Dissanayake, M H Rezvi Sheriff, David A Warrell, David Gunnell

  The British journal of psychiatry : the journal of mental science. 10/2006; 189:278-9.

  Although the high rate of suicide in elderly people is conventionally explained as being due to greater intent to die, we have noted elderly Sri Lankans dying after relatively mild poisoning. UsingAlthough the high rate of suicide in elderly people is conventionally explained as being due to greater intent to die, we have noted elderly Sri Lankans dying after relatively mild poisoning. Using data from cases of yellow oleander poisoning, we investigated the effect of age on outcome in 1697 patients, controlling for gender and amount ingested. In fully adjusted models, people over 64 years old were 13.8 (95% CI 3.6-53.0) times more likely to die than those less than 25 years old. The high number of suicides in elderly people globally is likely to be due, in part, to the difficulty they face in surviving the effects of both the poisoning and its treatment.

• Patterns of hospital transfer for self-poisoned patients in rural Sri Lanka: implications for estimating the incidence of self-poisoning in the developing world.

  Authors: Michael Eddleston, K Sudarshan, M Senthilkumaran, K Reginald, Lakshman Karalliedde, Lalith Senarathna, Dhammika de Silva, M H Rezvi Sheriff, Nick A Buckley, David Gunnell

  Bulletin of the World Health Organization. 05/2006; 84(4):276-82.

  OBJECTIVES: Most data on self-poisoning in rural Asia have come from secondary hospitals. We aimed to: assess how transfers from primary to secondary hospitals affected estimates of case-fatalityOBJECTIVES: Most data on self-poisoning in rural Asia have come from secondary hospitals. We aimed to: assess how transfers from primary to secondary hospitals affected estimates of case-fatality ratio (CFR); determine whether there was referral bias according to gender or poison; and estimate the annual incidence of all self-poisoning, and of fatal self-poisoning, in a rural developing-world setting. METHODS: Self-poisoning patients admitted to Anuradhapura General Hospital, Sri Lanka, were reviewed on admission from 1 July to 31 December 2002. We audited medical notes of self-poisoning patients admitted to 17 of the 34 surrounding peripheral hospitals for the same period. FINDINGS: A total of 742 patients were admitted with self-poisoning to the secondary hospital; 81 died (CFR 10.9%). 483 patients were admitted to 17 surrounding peripheral hospitals. Six patients (1.2%) died in peripheral hospitals, 249 were discharged home, and 228 were transferred to the secondary hospital. There was no effect of gender or age on likelihood of transfer; however, patients who had ingested oleander or paraquat were more likely to be transferred than were patients who had taken organophosphorus pesticides or other poisons. Estimated annual incidences of self-poisoning and fatal self-poisoning were 363 and 27 per 100,000 population, respectively, with an overall CFR of 7.4% (95% confidence interval 6.0-9.0). CONCLUSION: Fifty per cent of patients admitted to peripheral hospitals were discharged home, showing that CFRs based on secondary hospital data are inflated. However, while incidence of self-poisoning is similar to that in England, fatal self-poisoning is three times more common in Sri Lanka than fatal self-harm by all methods in England. Population based data are essential for making international comparisons of case fatality and incidence, and for assessing public health interventions.

• Choice of poison for intentional self-poisoning in rural Sri Lanka.

  Authors: Michael Eddleston, Ayanthi Karunaratne, Manjula Weerakoon, Subashini Kumarasinghe, Manjula Rajapakshe, M H Rezvi Sheriff, Nick A Buckley, David Gunnell

  Clinical toxicology (Philadelphia, Pa.). 02/2006; 44(3):283-6.

  BACKGROUND: Although intentional self-poisoning is a major public health problem in rural parts of the Asia-Pacific region, relatively little is known of its epidemiology. We aimed to determine whyBACKGROUND: Although intentional self-poisoning is a major public health problem in rural parts of the Asia-Pacific region, relatively little is known of its epidemiology. We aimed to determine why Sri Lankan self-poisoning patients choose particular poisons, and whether acts of self-harm with highly dangerous poisons were associated with more premeditation and effort. METHODS: We interviewed 268 self-poisoning patients presenting to two district general hospitals in rural Sri Lanka. RESULTS: Eighty-five percent of patients cited easy availability as the basis for their choice of poison. There was little premeditation: more than 50% ingested the poison less than 30 minutes after deciding to self-harm. Patients had little knowledge about treatment options or lethality of the poison chosen. We found no difference in reasons for choice of poison between people ingesting different poisons, despite marked differences in toxicity, and between people who died and those who survived. CONCLUSIONS: Poisons were chosen on the basis of availability, often at short notice. There was no evidence that people using highly toxic poisons made a more serious or premeditated attempt. Restrictions on availability of highly toxic poisons in rural communities must be considered in strategies to reduce the number of intentional self-poisoning deaths in the Asia Pacific region.

• Epidemiology of intentional self-poisoning in rural Sri Lanka.

  Authors: Michael Eddleston, David Gunnell, Ayanthi Karunaratne, Dhammika de Silva, M H Rezvi Sheriff, Nick A Buckley

  The British journal of psychiatry : the journal of mental science. 01/2006; 187:583-4.

  We investigated the epidemiology of intentional self-poisoning in rural Sri Lanka by prospectively recording 2189 admissions to two secondary hospitals. Many patients were young (median age 25We investigated the epidemiology of intentional self-poisoning in rural Sri Lanka by prospectively recording 2189 admissions to two secondary hospitals. Many patients were young (median age 25 years), male (57%) and used pesticides (49%). Of the 198 who died,156 were men (case fatality 12.4%) and 42 were women (4.5%). Over half of female deaths were in those under 25 years old; male deaths were spread more evenly across age groups. Oleander and paraquat caused 74% of deaths in people under 25 years old; thereafter organophosphorous pesticides caused many deaths. Although the age pattern of self-poisoning was similar to that of industrialised countries, case fatality was more than 15 times higher and the pattern of fatal self-poisoning different.

• Refractory status epilepticus following self-poisoning with the organochlorine pesticide endosulfan.

  Authors: Darren M Roberts, Wasantha Dissanayake, M H Rezvi Sheriff, Michael Eddleston

  Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 10/2004; 11(7):760-2.

  We describe a case of refractory status epilepticus presenting to a rural general hospital in Sri Lanka. This patient's condition was precipitated by intentional self-poisoning with theWe describe a case of refractory status epilepticus presenting to a rural general hospital in Sri Lanka. This patient's condition was precipitated by intentional self-poisoning with the organochlorine insecticide endosulfan. Although rarely seen in developed countries, pesticide poisoning particularly with endosulfan is an important cause of difficult-to-manage seizures in Asian countries. In this case report, we discuss the management of status epilepticus and refractory status epilepticus. Further, we specifically discuss the clinical pharmacology and toxicology of endosulfan.

• Speed of initial atropinisation in significant organophosphorus pesticide poisoning--a systematic comparison of recommended regimens.

  Authors: Michael Eddleston, Nick A Buckley, Helaina Checketts, Lalith Senarathna, Fahim Mohamed, M H Rezvi Sheriff, Andrew Dawson

  Journal of toxicology. Clinical toxicology. 02/2004; 42(6):865-75.

  OBJECTIVE: Early deaths from organophosphorus (OP) pesticide self-poisoning result from respiratory failure and cardiovascular collapse. Therapy requires the urgent use of atropine to reverseOBJECTIVE: Early deaths from organophosphorus (OP) pesticide self-poisoning result from respiratory failure and cardiovascular collapse. Therapy requires the urgent use of atropine to reverse cholinergic excess, thereby improving respiratory function, heart rate, and blood pressure. We aimed to assess variation in textbook recommendations for early atropinisation and to see whether this variation affected time to stabilisation using model data from 22 severely poisoned patients seen in a Sri Lankan clinical trial. METHODS: We extracted prospectively recorded data on atropine requirements for 22 OP poisoned patients who required intubation but survived to discharge. We did a systematic search for textbook recommendations for initial atropinisation regimens. These regimens were then applied to data from the Sri Lankan patients. RESULTS: The patients required a mean of 23.4 mg (standard deviation 22.0, range 1-75 mg) atropine to clear the lungs, raise the pulse above 80 bpm, and restore systolic blood pressure to more than 80 mmHg. Textbook recommendations varied markedly--atropinisation of an average patient, requiring the mean dose of 23.4 mg, would have taken 8 to 1380 mins; atropinisation of a very ill patient, requiring 75 mg, would have taken 25 to 4440 mins. Atropinisation was attained most rapidly with a regimen of increasing bolus doses after failure to respond to the previous bolus. CONCLUSIONS: There is great variation in recommendations for atropinisation, with some regimens taking hours and even days to stabilise a patient. The guidelines are very flexible--possibly appropriate for experienced emergency physicians or clinical toxicologists, but completely inappropriate for the inexperienced junior doctors who see most cases worldwide. We recommend that a consensus guideline be developed by appropriate organisations to bring order to this important part of OP therapy, while acknowledging the paucity of data to drive the guidelines.

• Acute human self-poisoning with the N-phenylpyrazole insecticide fipronil--a GABAA-gated chloride channel blocker.

  Authors: Fahim Mohamed, Lalith Senarathna, Adrian Percy, Manel Abeyewardene, Geoffrey Eaglesham, Ron Cheng, Shifa Azher, Ariyasena Hittarage, Wasantha Dissanayake, M H Rezvi Sheriff, Willie Davies, Nick A Buckley, Michael Eddleston

  Journal of toxicology. Clinical toxicology. 01/2004; 42(7):955-63.

  OBJECTIVE: Fipronil, a broad spectrum N-phenylpyrazole insecticide that inhibits GABAA-gated chloride channels, has been in use since the mid-1990s. A high affinity for insect compared to mammalianOBJECTIVE: Fipronil, a broad spectrum N-phenylpyrazole insecticide that inhibits GABAA-gated chloride channels, has been in use since the mid-1990s. A high affinity for insect compared to mammalian GABA receptors results in lower animal toxicity than other insecticides blocking this channel. To date, only two accidental cases of fipronil poisoning in humans have been published. CASE SERIES: We report seven patients with fipronil self-poisoning seen prospectively in Sri Lanka together with pharmacokinetics for four patients. Non-sustained generalized tonic-clonic seizures were seen in two patients (peak measured plasma fipronil concentrations 1600 and 3744 microg/L); both were managed with diazepam without complications. A patient with a peak measured plasma concentration of 1040 microg/L was asymptomatic throughout his stay. Plasma concentration was still high at discharge 3-4 days post-ingestion when the patients were well. Retrospective review of >1000 pesticide poisoning deaths since 1995 found only one death from fipronil-based products. In contrast to the good outcome of the above cases, this patient required intubation and ventilation and had continuous fits despite therapy with barbiturates and benzodiazepines. CONCLUSIONS: Our experience with prospectively observed patients suggests that fipronil poisoning is characterized by vomiting, agitation, and seizures, and normally has a favorable outcome. Management should concentrate on supportive care and early treatment of seizures. However, further experience is needed to determine whether increased susceptibility to fipronil or larger doses can produce status epilepticus.

• Deaths due to absence of an affordable antitoxin for plant poisoning.

  Authors: Michael Eddleston, Lalith Senarathna, Fahim Mohamed, Nick Buckley, Edmund Juszczak, M H Rezvi Sheriff, Ariaranee Ariaratnam, Senaka Rajapakse, David Warrell, K Rajakanthan

  Lancet. 10/2003; 362(9389):1041-4.

  There is a severe shortage of affordable antivenoms and antitoxins in the developing world. An anti-digoxin antitoxin for oleander poisoning was introduced in Sri Lanka in July, 2001, but because ofThere is a severe shortage of affordable antivenoms and antitoxins in the developing world. An anti-digoxin antitoxin for oleander poisoning was introduced in Sri Lanka in July, 2001, but because of its cost, stocks ran out in July, 2002. We looked at the effect of its introduction and withdrawal on case fatality, and determined its cost-effectiveness. The antitoxin strikingly reduced the case fatality; its absence resulted in a three-fold rise in deaths. At the present price of US2650 dollars per course, every life saved cost 10209 dollars and every life year cost 248 dollars. Reduction of the antitoxin's price to 400 dollars would reduce costs to 1137 dollars per life gained; a further reduction to 103 dollars would save money for every life gained. Treatments for poisoning and envenoming should be included in the present campaign to increase availability of affordable treatments in the developing world.

• Influence of pesticide regulation on acute poisoning deaths in Sri Lanka.

  Authors: Darren M Roberts, Ayanthi Karunarathna, Nick A Buckley, Gamini Manuweera, M H Rezvi Sheriff, Michael Eddleston

  Bulletin of the World Health Organization. 02/2003; 81(11):789-98.

  OBJECTIVES: To assess in a developing Asian country the impact of pesticide regulation on the number of deaths from poisoning. These regulations, which were implemented in Sri Lanka from the 1970s,OBJECTIVES: To assess in a developing Asian country the impact of pesticide regulation on the number of deaths from poisoning. These regulations, which were implemented in Sri Lanka from the 1970s, aimed to reduce the number of deaths - the majority from self-poisoning - by limiting the availability and use of highly toxic pesticides. METHODS: Information on legislative changes was obtained from the Ministry of Agriculture, national and district hospital admission data were obtained from the Sri Lanka Health Statistics Unit, and individual details of deaths by pesticide poisoning were obtained from a manual review of patients' notes and intensive care unit records in Anuradhapura. FINDINGS: Between 1986 and 2000, the total national number of admissions due to poisoning doubled, and admissions due to pesticide poisoning increased by more than 50%. At the same time, the case fatality proportion (CFP) fell for total poisonings and for poisonings due to pesticides. In 1991_92, 72% of pesticide-induced deaths in Anuradhapura were caused by organophosphorus (OP) and carbamate pesticides - in particular, the WHO class I OPs monocrotophos and methamidophos. From 1991, the import of these pesticides was reduced gradually until they were banned for routine use in January 1995, with a corresponding fall in deaths. Unfortunately, their place in agricultural practice was taken by the WHO class II organochlorine endosulfan, which led to a rise in deaths from status epilepticus - from one in 1994 to 50 in 1998. Endosulfan was banned in 1998, and over the following three years the number of endosulfan deaths fell to three. However, at the end of the decade, the number of deaths from pesticides was at a similar level to that of 1991, with WHO class II OPs causing the most deaths. Although these drugs are less toxic than class I OPs, the management of class II OPs remains difficult because they are, nevertheless, still highly toxic, and their toxicity is exacerbated by the paucity of available facilities. CONCLUSION: The fall in CFP amidst a rising incidence of self-poisoning suggests that Sri Lanka's programmes of pesticide regulation were beneficial. However, a closer inspection of pesticide-induced deaths in one hospital revealed switching to other highly toxic pesticides, as one was banned and replaced in agricultural practice by another. Future regulation must predict this switching and bear in mind the ease of treatment of replacement pesticides. Furthermore, such regulations must be implemented alongside other strategies, such as integrated pest management, to reduce the overall pesticide availability for self-harm.

• Severe propanil [N-(3,4-dichlorophenyl) propanamide] pesticide self-poisoning.

  Authors: Michael Eddleston, Manjula Rajapakshe, Darren Roberts, K Reginald, M H Rezvi Sheriff, Wasantha Dissanayake, Nick Buckley

  Journal of toxicology. Clinical toxicology. 02/2002; 40(7):847-54.

  BACKGROUND: Propanil pesticide poisoning can produce methemoglobinemia, tissue hypoxia, and depression of central nervous system and respiratory system. It has been recorded only rarely worldwide andBACKGROUND: Propanil pesticide poisoning can produce methemoglobinemia, tissue hypoxia, and depression of central nervous system and respiratory system. It has been recorded only rarely worldwide and most current poison texts consider propanil to be of low toxicity. However, propanil self-poisoning is a significant clinical problem in parts of Sri Lanka and an occasional cause of death. AIM OF STUDY: To report the clinical features and management of severe propanil poisoning. PATIENTS AND METHODS: We report a retrospective case series of patients who were treated in the intensive care unit of and/or died in Anuradhapura General Hospital between 1998 and early 2002. RESULTS: Sixteen patients were identified. Common manifestations of toxicity included confusion, reduced conscious level, cyanosis, and respiratory depression. Marked hemolysis was noted in several patients. Nine deaths occurred due to respiratory depression and cardiorespiratory arrest. Management was difficult given the lack of i.v. methylene blue, inability to measure methemoglobin levels, and paucity of intensive care unit beds. CONCLUSIONS: This series indicates that propanil poisoning can be a severe form of self-poisoning, particularly in resource-poor settings. We have now initiated the establishment of a prospective series of propanil poisoned patients to further describe its clinical features, responsiveness to therapy, and case fatality rate.

• Refractory status epilepticus following self-poisoning with the organochlorine pesticide endosulfan

  Authors: Darren M. Roberts, Wasantha Dissanayake, M.H. Rezvi Sheriff, Michael Eddleston

  Journal of Clinical Neuroscience.

  We describe a case of refractory status epilepticus presenting to a rural general hospital in Sri Lanka. This patient's condition was precipitated by intentional self-poisoning with theWe describe a case of refractory status epilepticus presenting to a rural general hospital in Sri Lanka. This patient's condition was precipitated by intentional self-poisoning with the organochlorine insecticide endosulfan. Although rarely seen in developed countries, pesticide poisoning particularly with endosulfan is an important cause of difficult-to-manage seizures in Asian countries. In this case report, we discuss the management of status epilepticus and refractory status epilepticus. Further, we specifically discuss the clinical pharmacology and toxicology of endosulfan.

• Efficacy of single dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis.

  Authors: M M Ismail, R L Jayakody, G J Weil, N Nirmalan, K S Jayasinghe, W Abeyewickrema, M H Rezvi Sheriff, H N Rajaratnam, N Amarasekera, D C de Silva, M L Michalski, A S Dissanaike

  Transactions of the Royal Society of Tropical Medicine and Hygiene. 92(1):94-7.

  In a 'blind' trial on 50 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of a single dose of albendazole (alb) 600 mgIn a 'blind' trial on 50 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of a single dose of albendazole (alb) 600 mg alone or in combination with ivermectin (iver) 400 micrograms/kg or diethylcarbamazine citrate (DEC) 6 mg/kg was compared with a single dose of the combination DEC 6 mg/kg and iver 400 micrograms/kg over a period of 15 months after treatment. All but one subject, with 67 microfilariae (mf)/mL, had pre-treatment counts > 100 mf/mL. All 4 treatments significantly reduced mf counts, but alb/iver was the most effective regimen for clearing mf from night blood: 9 of 13 subjects (69%) were amicrofilaraemic by membrane filtration 15 months after treatment compared to one of 12 (8%), 3 of 11 (27%), and 3 of 10 (30%) in the groups treated with alb, alb/DEC, and DEC/iver, respectively. Filarial antigen tests suggested that all 4 treatments had significant activity against adult W. bancrofti; alb/DEC had the greatest activity according to this test, with antigen levels decreasing by 77% 15 months after therapy. All 4 regimens were well tolerated and clinically safe, although mild, self-limited systemic reactions were observed in all treatment groups. These results suggest that alb/iver is a safe and effective single dose regimen for suppression of microfilaraemia in bancroftian filariasis that could be considered for control programmes. Additional benefits of this combination are its potent, broad spectrum activity against intestinal helminths and potential relative safety in areas of Africa where DEC cannot be used for filariasis control because of co-endemicity with onchocerciasis or loiasis.

• Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study.

  Authors: Michael Eddleston, Peter Eyer, Franz Worek, Fahim Mohamed, Lalith Senarathna, Ludwig von Meyer, Edmund Juszczak, Ariyasena Hittarage, Shifa Azhar, Wasantha Dissanayake, M H Rezvi Sheriff, Ladislaus Szinicz, Andrew H Dawson, Nick A Buckley

  Lancet. 366(9495):1452-9.

  BACKGROUND: Although more than 100 organophosphorus insecticides exist, organophosphorus poisoning is usually regarded as a single entity, distinguished only by the compound's lethal dose in animals.BACKGROUND: Although more than 100 organophosphorus insecticides exist, organophosphorus poisoning is usually regarded as a single entity, distinguished only by the compound's lethal dose in animals. We aimed to determine whether the three most common organophosphorus insecticides used for self-poisoning in Sri Lanka differ in the clinical features and severity of poisoning they cause. METHODS: We prospectively studied 802 patients with chlorpyrifos, dimethoate, or fenthion self-poisoning admitted to three hospitals. Blood cholinesterase activity and insecticide concentration were measured to determine the compound and the patients' response to insecticide and therapy. We recorded clinical outcomes for each patient. FINDINGS: Compared with chlorpyrifos (35 of 439, 8.0%), the proportion dying was significantly higher with dimethoate (61 of 264, 23.1%, odds ratio [OR] 3.5, 95% CI 2.2-5.4) or fenthion (16 of 99, 16.2%, OR 2.2, 1.2-4.2), as was the proportion requiring endotracheal intubation (66 of 439 for chlorpyrifos, 15.0%; 93 of 264 for dimethoate, 35.2%, OR 3.1, 2.1-4.4; 31 of 99 for fenthion, 31.3%, 2.6, 1.6-4.2). Dimethoate-poisoned patients died sooner than those ingesting other pesticides and often from hypotensive shock. Fenthion poisoning initially caused few symptoms but many patients subsequently required intubation. Acetylcholinesterase inhibited by fenthion or dimethoate responded poorly to pralidoxime treatment compared with chlorpyrifos-inhibited acetylcholinesterase. INTERPRETATION: Organophosphorus insecticide poisoning is not a single entity, with substantial variability in clinical course, response to oximes, and outcome. Animal toxicity does not predict human toxicity since, although chlorpyrifos is generally the most toxic in rats, it is least toxic in people. Each organophosphorus insecticide should be considered as an individual poison and, consequently, patients might benefit from management protocols developed for particular organophosphorus insecticides.