A.R. Wickremasinghe

Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study.

BACKGROUND Indian Asians, who make up a quarter of the worlds population, are at high risk of developing type 2 diabetes. We investigated whether DNA methylation is associated with future type 2 diabetes incidence in Indian Asians and whether differences in methylation patterns between Indian Asians and Europeans are associated with, and could be used to predict, differences in the magnitude of risk of developing type 2 diabetes. METHODS We did a nested case-control study of DNA methylation in Indian Asians and Europeans with incident type 2 diabetes who were identified from the 8-year follow-up of 25 372 participants in the London Life Sciences Prospective Population (LOLIPOP) study. Patients were recruited between May 1, 2002, and Sept 12, 2008. We did epigenome-wide association analysis using samples from Indian Asians with incident type 2 diabetes and age-matched and sex-matched Indian Asian controls, followed by replication testing of top-ranking signals in Europeans. For both discovery and replication, DNA methylation was measured in the baseline blood sample, which was collected before the onset of type 2 diabetes. Epigenome-wide significance was set at p<1 × 10(-7). We compared methylation levels between Indian Asian and European controls without type 2 diabetes at baseline to estimate the potential contribution of DNA methylation to increased risk of future type 2 diabetes incidence among Indian Asians. FINDINGS 1608 (11·9%) of 13 535 Indian Asians and 306 (4·3%) of 7066 Europeans developed type 2 diabetes over a mean of 8·5 years (SD 1·8) of follow-up. The age-adjusted and sex-adjusted incidence of type 2 diabetes was 3·1 times (95% CI 2·8-3·6; p<0·0001) higher among Indian Asians than among Europeans, and remained 2·5 times (2·1-2·9; p<0·0001) higher after adjustment for adiposity, physical activity, family history of type 2 diabetes, and baseline glycaemic measures. The mean absolute difference in methylation level between type 2 diabetes cases and controls ranged from 0·5% (SD 0·1) to 1·1% (0·2). Methylation markers at five loci were associated with future type 2 diabetes incidence; the relative risk per 1% increase in methylation was 1·09 (95% CI 1·07-1·11; p=1·3 × 10(-17)) for ABCG1, 0·94 (0·92-0·95; p=4·2 × 10(-11)) for PHOSPHO1, 0·94 (0·92-0·96; p=1·4 × 10(-9)) for SOCS3, 1·07 (1·04-1·09; p=2·1 × 10(-10)) for SREBF1, and 0·92 (0·90-0·94; p=1·2 × 10(-17)) for TXNIP. A methylation score combining results for the five loci was associated with future type 2 diabetes incidence (relative risk quartile 4 vs quartile 1 3·51, 95% CI 2·79-4·42; p=1·3 × 10(-26)), and was independent of established risk factors. Methylation score was higher among Indian Asians than Europeans (p=1 × 10(-34)). INTERPRETATION DNA methylation might provide new insights into the pathways underlying type 2 diabetes and offer new opportunities for risk stratification and prevention of type 2 diabetes among Indian Asians. FUNDING The European Union, the UK National Institute for Health Research, the Wellcome Trust, the UK Medical Research Council, Action on Hearing Loss, the UK Biotechnology and Biological Sciences Research Council, the Oak Foundation, the Economic and Social Research Council, Helmholtz Zentrum Munchen, the German Research Center for Environmental Health, the German Federal Ministry of Education and Research, the German Center for Diabetes Research, the Munich Center for Health Sciences, the Ministry of Science and Research of the State of North Rhine-Westphalia, and the German Federal Ministry of Health.

Physical disability and psychosocial impact due to chronic filarial lymphoedema in Sri Lanka

Background Information on the physical and psychosocial disability of lymphatic filariasis in Sri Lanka is scarce. Therefore this study was carried out to describe the physical disability and psychosocial impact associated with chronic lymphoedema in patients attending filariasis clinics in the Colombo district, Sri Lanka. Methods Four hundred and thirteen patients with lymphoedema of limbs attending filariasis clinics in Werahera and Dehiwala in the Colombo district were enrolled in the study after obtaining informed written consent. Data were collected using a pre-tested, interviewer-administered questionnaire and analyzed using SPSS. Results Majority (95%) of patients had lower limbs affected and there was a significant association with difficulty in walking (p = 0.023). The swollen limb affected the work of 87 (52 %) of employed patients and 26 persons reported loss of job. Approximately 25 % and 6 % reported having problems interacting with the community and family, respectively and 8.7 % felt that they were rejected by society. The swollen limb was perceived as a major problem by 36.8 % of patients. Of the married persons, 5.7 % and 6.2 % reported sexual and marital problems respectively, due to their swollen limb/s. Of those who had marital problems, 77.3% reported sexual problems as well (p < 0.001). Conclusion Lymphoedema significantly affects physical, psychological and social functioning in affected individuals. Morbidity control, in addition to control of physical disability, should target the psychosocial consequences.

Air pollution and health in Sri Lanka: a review of epidemiologic studies

BackgroundAir pollution is increasingly documented as a threat to public health in most developing countries. Evaluation of current air quality levels, regulatory standards and scientific literature on outdoor and indoor air pollution, and health effects are important to identify the burden, develop and implement interventions and to fill knowledge gaps in Sri Lanka.MethodsPUBMED and Medline databases, local journals and conference proceedings were searched for epidemiologic studies pertaining to air pollution and health effects in Sri Lanka. All the studies pertaining to air pollution and health effects were considered.ResultsSixteen studies investigated the association between exposure to ambient or indoor air pollution (IAP) and various health outcomes ranging from respiratory symptoms, low birth weight and lung cancers. Of the sixteen, three used a case control design. Half of the studies collected exposure data only through questionnaires. There were positive associations between air pollution and adverse health effects in all studies. Methodological limitations in most of the studies resulted in poor quantification of risk estimates.ConclusionA limited number of epidemiological studies in Sri Lanka have investigated the health effects of air pollution. Based on findings of studies and reported air quality levels, air pollution may be considered a neglected public health problem in Sri Lanka.

A Comparison between Revised NCEP ATP III and IDF Definitions in Diagnosing Metabolic Syndrome in an Urban Sri Lankan Population: The Ragama Health Study

Background. The prevalence of metabolic syndrome (MetS) within individual cohorts varies with the definition used. The aim of this study was to compare the prevalence of MetS between IDF and revised NCEP ATP III criteria in an urban Sri Lankan population and to investigate the characteristics of discrepant cases. Methods. 2985 individuals, aged 35–65 years, were recruited to the study. Anthropometric and blood pressure measurements and laboratory investigations were carried out following standard protocols. Results. Age and sex-adjusted prevalences of MetS were 46.1% and 38.9% by revised NCEP and IDF definitions, respectively. IDF criteria failed to identify 21% of men and 7% of women identified by the revised NCEP criteria. The discrepant group had more adverse metabolic profiles despite having a lower waist circumference than those diagnosed by both criteria. Conclusion. MetS is common in this urban Sri Lankan cohort regardless of the definition used. The revised NCEP definition was more appropriate in identifying the metabolically abnormal but nonobese individuals, especially among the males predisposed to type 2 diabetes or cardiovascular disease. Further research is needed to determine the suitability of the currently accepted Asian-specific cut-offs for waist circumference in Sri Lankan adults.

Effects of occupational exposure to organophosphate pesticides on nerve and neuromuscular function.

This study aimed to investigate whether occupational exposure to organophosphate (OP) pesticides caused neurophysiological abnormalities. Thirty farmers who regularly spray OP pesticides and 30 fishermen (controls), living close by but not involved in pesticide spraying, were evaluated during and be

Larvivorous Potential of Fish Species Found in River Bed Pools Below the Major Dams in Sri Lanka

Abstract Malaria in Sri Lanka is closely associated with the river systems in the country. Construction of major dams across rivers has resulted in year-round pooling and anopheline mosquito breeding in river beds below the dams. This study was carried out to determine the larvivorous activity of fish found in river bed pools below the dams to identify the potential fish species for anopheline larval control in these areas. Fish species in five river beds below the dams, namely, Laxapana, Kotmale, Nilambe, Victoria, and Rantembe, were identified in June 2000. The larvivorous potential of the 12 fish species collected was determined in the laboratory based on the number of larvae consumed per fish within 10 min and an hour. Danio malabaricus Jerdon, Oreochromis mossambicus Peters, Oreochromis niloticus L., and Poecilia reticulata Peters consumed nine or more larvae per fish within 10 min. Aplocheilus dayi Steindachner and Rasbora daniconius Hamilton consumed nine and eight larvae, respectively, within 1 h. O. mossambicus, O. niloticus, and P. reticulata consumed 10 larvae per fish within 10 min. Despite some species having a high larvivorous potential in the laboratory, field studies are required to determine the feasibility of using these fish for anopheline mosquito control in the river bed pools below the dams.

The health and nutritional status of school children in two rural communities in Sri Lanka.

SummaryThere is growing evidence of considerable burden of morbidity and mortality due to infectious diseases and undernutrition in school children. This study describes the nutritional status and parasitic infections of school children in two areas of rural Sri Lanka. All children in four primary schools in the Moneragala district of Sri Lanka were included in the study. The height and weight of children were measured and anthropometric indices calculated. Stool and blood samples were examined for evidence of intestinal helminthiasis, malaria and anaemia. A greater proportion of boys than girls were underweight, wasted and stunted. Over 80% of the children were anaemic but did not apparently have iron deficiency anaemia according to their blood picture. The prevalence of parasitic infections such as hookworm and Plasmodium spp that may contribute to anaemia was low.

Respiratory health status of children from two different air pollution exposure settings of Sri Lanka: a cross-sectional study

BACKGROUND Health effects due to air pollution is becoming a major public health problem with growing traffic congestion and establishment of small- to medium-scale industries with poor emission controls in urban cities of Sri Lanka. METHODS Respiratory health status of 7- to 10-year-old children in two settings (urban and semi-urban) was assessed using standard questionnaires. Information on socio-demographic characteristics and potential determinants of both outdoor and indoor air pollutants exposure levels were also obtained. The respiratory health status of children in the two settings was compared. RESULTS We found that children from the urban setting had a significantly higher prevalence of wheezing within the last 12 months as compared to children from the semi-urban setting (adjusted OR = 2.02; 95% CI = 1.13-3.59). Indoor cooking with unclean fuels was a risk factor for wheezing independent of the area of residence (adjusted OR = 1.57; 95% CI = 1.01-2.46). CONCLUSIONS Poor indoor air quality was a major determinant of wheezing for the overall study group. Children from urban areas of Sri Lanka have poorer respiratory health status as compared to children from semi-urban areas. Besides poor outdoor air quality, this difference may also be due to other unexplored factors which may differ between urban and semi-urban areas in Sri Lanka.

Efficacy of a limb-care regime in preventing acute adenolymphangitis in patients with lymphoedema caused by bancroftian filariasis, in Colombo, Sri Lanka

Abstract The efficacy of a programme of community home-based care (CHBC) for lymphoedematous limbs was evaluated among 163 lymphoedema patients attending two filariasis clinics in Colombo. Each patient was interviewed and examined and his or her lymphoedema was graded during a baseline assessment, before the CHBC programme, and again, during a post-intervention assessment, after the patient had been in the programme for 1 year. The number of patients having entry lesions was 24% lower at the post-intervention assessment than at the baseline (P<0.001), with a reduction in the frequency of each type of entry lesion investigated. In the year the patients were in the CHBC programme, 30% fewer of them experienced at least one attack of adenolymphangitis (ADL; P<0.001), the mean number of ADL attacks/patient was lower (P<0.001), and the mean duration of each ADL attack suffered was slightly shorter (5.70 v. 5.84 days; P>0.05) than in the year before the baseline assessment. The reduction in the incidence of ADL attacks was greatest in the patients with the higher grades of lymphoedema. Approximately 66% of the patients perceived an improvement in their swollen limb post-intervention. Eleven patients had grade-II lymphoedema at baseline but only grade-I lymphoedema after being on the CHBC programme for a year (P=0.012). The programme appeared to increase the frequencies with which patients followed each of the limb-care measures considered and most of the measures for the home management of ADL attacks that were investigated. It is recommended that the CHBC programme be implemented as a national programme in Sri Lanka.

Costs and effectiveness of application of Poecilia reticulata (guppy) and temephos in anopheline mosquito control in river basins below the major dams of Sri Lanka.

In this study we examined the costs and effectiveness of using larvivorous fish, Poecilia reticulata, and a chemical larvicide, temephos, in anopheline mosquito control in the riverbeds below the major dams in Sri Lanka. Five riverbeds below the dams, namely Laxapana, Kotmale 1, Kotmale 2, Nilambe, Rantembe and Victoria, were selected. Riverbed pools in Laxapana and Kotmale 1 were treated with P. reticulata; Rantembe and Victoria were treated with temephos; and Kotmale 2 and Nilambe were kept as controls. In each area, the anopheline larval density, before and after application of fish/temephos, was estimated. The cost of application of fish/temephos was estimated by activities involved for each treatment. After intervention, there was a significant reduction in anopheline larval density in the fish-treated areas compared with the temephos-treated and control areas. Application of P. reticulata was 2.67 times less costly than that of temephos. The cost of fish application can be further reduced if the community is involved in the application.