A. Pathmeswaran

The Global Burden of Snakebite: A Literature Analysis and Modelling Based on Regional Estimates of Envenoming and Deaths

Background Envenoming resulting from snakebites is an important public health problem in many tropical and subtropical countries. Few attempts have been made to quantify the burden, and recent estimates all suffer from the lack of an objective and reproducible methodology. In an attempt to provide an accurate, up-to-date estimate of the scale of the global problem, we developed a new method to estimate the disease burden due to snakebites. Methods and Findings The global estimates were based on regional estimates that were, in turn, derived from data available for countries within a defined region. Three main strategies were used to obtain primary data: electronic searching for publications on snakebite, extraction of relevant country-specific mortality data from databases maintained by United Nations organizations, and identification of grey literature by discussion with key informants. Countries were grouped into 21 distinct geographic regions that are as epidemiologically homogenous as possible, in line with the Global Burden of Disease 2005 study (Global Burden Project of the World Bank). Incidence rates for envenoming were extracted from publications and used to estimate the number of envenomings for individual countries; if no data were available for a particular country, the lowest incidence rate within a neighbouring country was used. Where death registration data were reliable, reported deaths from snakebite were used; in other countries, deaths were estimated on the basis of observed mortality rates and the at-risk population. We estimate that, globally, at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite. These figures may be as high as 1,841,000 envenomings and 94,000 deaths. Based on the fact that envenoming occurs in about one in every four snakebites, between 1.2 million and 5.5 million snakebites could occur annually. Conclusions Snakebites cause considerable morbidity and mortality worldwide. The highest burden exists in South Asia, Southeast Asia, and sub-Saharan Africa.

Low-Dose Adrenaline, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom following Snakebite: A Randomised, Double-Blind, Placebo-Controlled Trial

In a factorial randomized trial conducted in Sri Lanka, de Silva and colleagues evaluate the safety and efficacy of pretreatments intended to reduce the risk of serious reactions to antivenom following snakebite.

Multiple-dose activated charcoal for treatment of yellow oleander poisoning: a single-blind, randomised, placebo-controlled trial

BACKGROUND Deliberate self-poisoning with yellow oleander seeds is common in Sri Lanka and is associated with severe cardiac toxicity and a mortality rate of about 10%. Specialised treatment with antidigoxin Fab fragments and temporary cardiac pacing is expensive and not widely available. Multiple-dose activated charcoal binds cardiac glycosides in the gut lumen and promotes their elimination. We aimed to assess the efficacy of multiple-dose activated charcoal in the treatment of patients with yellow-oleander poisoning. METHODS On admission, participants received one dose of activated charcoal and were then randomly assigned either 50 g of activated charcoal every 6 h for 3 days or sterile water as placebo. A standard treatment protocol was used in all patients. We monitored cardiac rhythm and did 12-lead electocardiographs as needed. Death was the primary endpoint, and secondary endpoints were life-threatening cardiac arrhythmias, dose of atropine used, need for cardiac pacing, admission to intensive care, and number of days in hospital. Analysis was by intention to treat. FINDINGS 201 patients received multiple-dose activated charcoal and 200 placebo. There were fewer deaths in the treatment group (five [2.5%] vs 16 [8%]; percentage difference 5.5%; 95% CI 0.6-10.3; p=0.025), and we noted difference in favour of the treatment group for all secondary endpoints, apart from number of days in hospital. The drug was safe and well tolerated. INTERPRETATION Multiple-dose activated charcoal is effective in reducing deaths and life-threatening cardiac arrhythmias after yellow oleander poisoning and should be considered in all patients. Use of activated charcoal could reduce the cost of treatment.

Soil-transmitted helminth infections among plantation sector schoolchildren in Sri Lanka: prevalence after ten years of preventive chemotherapy.

Background The plantation sector in Sri Lanka lags behind the rest of the country in terms of living conditions and health. In 1992, a sector-wide survey of children aged 3–12 years and women of reproductive age showed >90% prevalence of soil-transmitted helminth infections. Biannual mass de-worming targeting children aged 3–18 years started in 1994 and was continued until 2005. The present study was carried out to assess the status of infection four years after cessation of mass de-worming. Methods/Findings A school-based cross-sectional survey was carried out. Faecal samples from approximately 20 children from each of 114 schools in five districts were examined using the modified Kato-Katz technique. Data regarding the school, the childs family and household sanitation were recorded after inspection of schools and households. Multivariate analysis was carried out using logistic regression, to identify risk factors for infection. Faecal samples were obtained from 1890 children. In 4/5 districts, >20% were infected with one or more helminth species. Overall combined prevalence was 29.0%; 11.6% had infections of moderate-heavy intensity. The commonest infection was Ascaris lumbricoides, present in all five districts, as was Trichuris trichiura. Hookworm was not detected in two districts. Multivariate analysis identified low altitude and maternal under-education as risk factors for all three infections. Poor household sanitation was identified as a risk factor for A. lumbricoides and hookworm, but not T. trichiura infections. Conclusions/Significance The results indicate that regular mass de-worming of plantation sector children should be resumed along with more emphasis on better sanitation and health education. They show that even after 10 years of mass chemotherapy, prevalence can bounce back after cessation of preventive chemotherapy, if the initial force of transmission is strong and other long-term control measures are not concomitantly implemented.

Liv.52 in alcoholic liver disease: a prospective, controlled trial

Liv.52, a hepatoprotective agent of herbal origin, is used empirically for the treatment of alcoholic liver disease in Sri Lanka. We conducted a controlled trial to assess the efficacy of Liv.52 in patients with alcoholic liver disease. Patients with evidence of alcoholic liver disease attending outpatient clinics were included in a prospective, double blind, randomized, placebo controlled trial. During the trial period, 80 patients who fulfilled inclusion criteria were randomly assigned Liv.52 (cases; n = 40) or placebo (controls) the recommended dose of three capsules twice daily for 6 months. All patients underwent clinical examination (for which a clinical score was computed), and laboratory investigations for routine blood chemistry and liver function before commencement of therapy (baseline). Thereafter, clinical assessments were done monthly for 6 months, while laboratory investigations were done after 1 and 6 months of therapy. There was no significant difference in the age composition, alcohol intake and baseline liver function between the two groups. The two-sample t-test was used to analyze data obtained after 1 and 6 months of therapy against baseline values. There was no significant difference in clinical outcome and liver chemistry between the two groups at any time point. There were no reports of adverse effects attributable to the drug. Our results suggest that Liv.52 may not be useful in the management of patients with alcohol induced liver disease.

Fetal effects of environmental exposure of pregnant women to organophosphorus compounds in a rural farming community in Sri Lanka

Background. The possible deleterious effects of low-grade, chronic environmental and occupational exposure to organophosphorus compounds (OPCs) are not well documented. Objective. To investigate the possible effects of low-level, chronic exposure of pregnant mothers to OPCs on the fetus by measuring OPC levels, and using markers of OPC exposure, oxidative stress and oxidative tissue damage. Methods. Toxicity was assessed by measuring (i) OPC levels in breast milk and plasma from maternal and cord blood using gas chromatography, (ii) maternal and fetal butyrylcholinesterase (BChE) activity using inhibition assays, (iii) antioxidant status of the fetus using superoxide dismutase activity assays, (iv) oxidative stress in the fetus by determining malondialdehyde (MDA) concentrations, and (v) examining for fetal DNA fragmentation using electrophoresis. Samples were obtained from consenting mothers living in a farming community in southern Sri Lanka at the end of the pesticide spray season (study group) and just before the commencement of the spray season (in-between spray season; control group). Results. Organophosphate residues were detected in only two subjects (chlorpyrifos in maternal and cord blood of one during the spray season and dimethoate in breast milk of another during the in between spray season), but the test employed was capable of only detecting concentrations above 0.05mg/l. However, cord blood obtained during the spray season showed significant inhibition of BChE activity, increased oxidative stress and more DNA fragmentation when compared with cord blood obtained during the in-between spray season. Conclusions. Inhibition of cord blood BChE activity indicates fetal exposure to organophosphorus compounds during times when there is a high probability of environmental drift. This provides a plausible explanation for the increased oxidative stress and high DNA fragmentation in the fetus. Long-term outcomes of such exposures are unknown.

Histopathology reporting in colorectal cancer: a proforma improves quality.

Aim  The histopathology report is vital to determine the need for adjuvant therapy and prognosis in colorectal cancer (CRC). Completeness of those in text format is inadequate. This study evaluated the improvement of quality of histopathology reports following the introduction of a template proforma, based on standards set by the Royal College of Pathologists (RCP), UK.

Mapping the Risk of Snakebite in Sri Lanka - A National Survey with Geospatial Analysis.

Background There is a paucity of robust epidemiological data on snakebite, and data available from hospitals and localized or time-limited surveys have major limitations. No study has investigated the incidence of snakebite across a whole country. We undertook a community-based national survey and model based geostatistics to determine incidence, envenoming, mortality and geographical pattern of snakebite in Sri Lanka. Methodology/Principal Findings The survey was designed to sample a population distributed equally among the nine provinces of the country. The number of data collection clusters was divided among districts in proportion to their population. Within districts clusters were randomly selected. Population based incidence of snakebite and significant envenoming were estimated. Model-based geostatistics was used to develop snakebite risk maps for Sri Lanka. 1118 of the total of 14022 GN divisions with a population of 165665 (0.8%of the country’s population) were surveyed. The crude overall community incidence of snakebite, envenoming and mortality were 398 (95% CI: 356–441), 151 (130–173) and 2.3 (0.2–4.4) per 100000 population, respectively. Risk maps showed wide variation in incidence within the country, and snakebite hotspots and cold spots were determined by considering the probability of exceeding the national incidence. Conclusions/Significance This study provides community based incidence rates of snakebite and envenoming for Sri Lanka. The within-country spatial variation of bites can inform healthcare decision making and highlights the limitations associated with estimates of incidence from hospital data or localized surveys. Our methods are replicable, and these models can be adapted to other geographic regions after re-estimating spatial covariance parameters for the particular region.

Impact of mass chemotherapy for the control of filariasis on geohelminth infections in Sri Lanka

The aims of the World Health Organizations Global Programme to Eliminate Lymphatic Filariasis are to stop the spread of Wuchereria and Brugia infection and alleviate the suffering of individuals affected by lymphatic filariasis. Control of transmission is based on mass drug administrations (MDA). In the MDA entire populations at risk of filarial infection will be given four to six annual treatments with a combination of albendazole and a microfilaricide - either diethylcarbamazine citrate (DEC) or ivermectin. Inclusion of albendazole in this two-drug treatment regimen is expected to result in a public-health impact beyond lymphatic filariasis (LF) alone largely because of this drugs effectiveness against geohelminth infections. The anticipated health benefits of albendazole use include nutritional benefits (such as height and weight gains and reduction of anaemia) greater cognitive development among children and greater productivity in the adult population (Ottesen et al. 1999). (excerpt)

Effects of pollution on health of residents in an industrial area in Sri Lanka.

Abstract The authors conducted a cross-sectional comparative prevalence study to evaluate the effect of pollution on individuals who lived in an industrial zone in Sri Lanka. In this study, 81 male and female children who were 1-12 yr of age and 158 adults (51 males, 107 females) in the industrial zone were matched with 73 children (32 males, 41 females) and 146 adults (58 males, 88 females), respectively, who lived in a nonindustrialized area and whose ages were similar to those of the exposed individuals. The authors used a pretested questionnaire and a detailed clinical examination, including peak expiratory flow rate measurements, to assess the prevalence of illness. Children in the industrial area were 2.3 times more likely to have unexplained episodic cough (95% confidence interval [Cl] = 0.98, 10.3) and 2.8 times more likely to have rhinitis (95% Cl = 1.1, 7.1). The adult population was 2.1 times more likely to have unexplained episodic cough (95% Cl = 1.13, 7.09), 3.7 times more likely to have unexplained headaches (95% Cl = 2.2, 6.3), and adults had a significantly greater reduction in expiratory flow (peak expiratory flow rate = 446 - 92x [industrial area] + 91 x [male] - 0.8x [years lived in the area]).