Levels of Cytokines in Leptospirosis Patients with Different Serovars and rfb Locus.

Leptospirosis has a wide spectrum of clinical manifestations ranging from mild to severe disease. The cytokine response is considered one of the key drivers for this varying manifestation. The different cytokine response observed in patients with leptospirosis could be due to the variation of infecting serovars. Since the rfb locus codes for the lipopolysaccharide synthesis of the bacterial cell wall, which also determines the serovar, this locus may play a role in driving a specific cytokine response in the host. We investigated 12 commonly used cytokine profiles in serum samples of culture, microscopic agglutination test (MAT), or polymerase chain reaction (PCR)-positive patients with leptospirosis. The sequences of the rfb locus in culture-positive samples were generated from whole genome sequencing and serovar status was drawn from original data published. Isolated cultures were subjected to whole genome sequencing using the PacBio RS II system, and the resulting data were used to determine the species. The recovered genomic data were annotated with the Rapid Annotation using Subsystem Technology (RAST) subsystem, and the rfb locus was extracted. The cytokine analysis was carried out using the Qiagen human ELISA kit. Eighteen samples were found to be positive by culture, while the other 7 samples were positive by PCR or MAT. Infections from Leptospira interrogans serovar Autumnalis (5), Pyrogens (3), Icterohaemorrhagiae (1) Leptospira borgpetersenii (all 7 samples clustered in same clonal group with serovar status not determined), Leptospira weilii (1 with serovar status not determined), and Leptospira kirschneri serovar Grippotyphosa (1) were included in the analysis. Three patients [infected with Leptospira interrogansserovar Autumnalis (2) and Pyrogens (1)] and 2 MAT-positive patients (highest titer against serovar Bratislava of L.interrognas) were reported to have severe clinical manifestations, while the rest had mild to moderate symptoms. Although the serum cytokine concentration of patients with severe clinical manifestation was comparatively higher, a statistically significant difference was observed only for interleukin (IL)-1ß (P < 0.05). IL-10/tumor necrosis factor-alpha (TNF-α) ratio was high in patients with severe complications. In general, patients infected with L. interrogans showed higher concentration of cytokines compared to L. borgpetersenii.

Differences in the characteristics of people who purchase pesticides from shops for self-harm versus those who use pesticides available in the domestic environment in Sri Lanka.

OBJECTIVE: Data from South Asia indicate that for 15%-20% of suicide attempts, pesticides are purchased from shops; otherwise, pesticides are obtained from an individual's house or nearby environment. We aimed to investigate the difference between individuals who directly purchase pesticides from shops for suicide attempts and suicide deaths versus those related to accessing the pesticides from an individual's house or nearby environment. METHODS: We conducted two comparative studies in rural Sri Lanka: (1) non-fatal shop cases (n = 50) were survivors of self-poisoning with pesticides who ingested the pesticides after purchasing them from a shop; non-fatal domestic cases (n = 192) were survivors who accessed pesticides from their house or nearby environment. (2) fatal shop cases (n = 50) were individuals who died after ingesting pesticides they purchased for the act; fatal domestic cases (n = 102) were patients who died after ingesting pesticides they accessed at house or nearby environment. Logistic regression analysis was used to assess the characteristics which distinguished between the shop and domestic cases. RESULTS: Data indicate that 20.7% and 32.9% of individuals who used pesticides for suicide attempts and suicide deaths had purchased them from shops, respectively. Being a non-farmer was the main distinguishing characteristic of shop cases: adjusted odds ratios (AOR) 8.9, 95% confidence intervals (CI) 3.2-24.4 for non-fatal shop cases, and AOR 4.0, 95% CI 1.5-10.6 for fatal shop cases. Non-fatal shop cases also had higher suicide intent (AOR 3.0, CI 1.0-8.9), and ingesting an insecticide (AOR 4.8, CI 1.8-1.0-8.9) than non-fatal domestic cases. CONCLUSION: A high suicide intent of individuals who purchase pesticides for the event explains the high proportion of such fatal cases. Such high suicide intent makes the prevention implications difficult to spell out for those individuals who purchase pesticides for self-poisoning. However, our findings are valuable for clinicians to assess pesticide poisoning cases in hospitals.

Factors associated with early pregnancy anemia in rural Sri Lanka: Does being 'under care' iron out socioeconomic disparities?

Globally, more than a third of pregnant women are anemic, and progress in its prevention and control is slow. Sri Lanka is a lower-middle-income country with a unique public health infrastructure that provides multiple interventions across the lifecycle for anemia prevention, despite which anemia in pregnancy remains a challenge. Studying the factors associated with maternal anemia in this context would provide unique information on challenges and opportunities encountered as low-and-middle-income countries attempt to control anemia by improving health care coverage. All first-trimester pregnant women registered for antenatal care in the Anuradhapura district between July 2019 to September 2019 were invited to participate in the baseline of a cohort study. Interviewer-administered and self-completed questionnaires were used. Anemia was defined using a full blood count. A hierarchical logistic regression model was built to identify factors associated with anemia. Out of 3127 participants, 451 (14.4%) were anemic. According to the regression model (Chi-square = 139.3, p<0.001, n = 2692), the odds of being anemic increased with the Period of gestation (PoG) (OR = 1.07, 95% CI = 1.01-1.13). While controlling for PoG, age and parity, history of anemia (OR = 3.22, 95%CI = 2.51-4.13), being underweight (OR = 1.64, 95%CI = 1.24-2.18), having the last pregnancy five or more years back (OR = 1.57,95%CI = 1.15-2.15) and having used intrauterine devices for one year or more (OR = 1.63, 95%CI = 1.16-2.30) increased the odds of anemia. Breast feeding during the last year (OR = 0.66, 95%CI = 0.49-0.90) and having used contraceptive injections for one year or more (OR = 0.61,95%CI = 0.45-0.83) reduced the risk of anemia. Proxy indicators of being in frequent contact with the national family health program have a protective effect over the socioeconomic disparities in preventing early pregnancy anemia. Maintaining the continuum of care through the lifecycle, especially through optimizing pre and inter-pregnancy care provision should be the way forward for anemia control.

Epidemiology of wheeze among preschool children: a population-based cross-sectional study from rural Sri Lanka.

OBJECTIVES: To assess the prevalence of wheeze and factors associated with its severity among 3-6 years old children. METHODOLOGY: DESIGN: A population-based, cross-sectional study using the WHO 30 cluster methodology with probability proportionate to size sampling. SETTING: 36 preschools registered at the divisional secretariat offices of Anuradhapura district, Sri Lanka. PARTICIPANTS: We recruited 1060 preschool children from 36 preschools aged 3-6 years. MAIN OUTCOME MEASUREMENTS: We used the International Study of Asthma and Allergy in Childhood questionnaire to assess the prevalence, symptomatology and associated factors of wheeze. RESULTS: The study sample consisted of 548 (51.70%) male and 512 (48.30%) female children with a mean age of 4.41 (±0.66) years. At least one wheezing episode ever was reported in 323 (30.47%; 95% CI 27.71% to 33.34%) children and 247 (23.30%; 95% CI 20.79% to 25.97%) children had a wheezing attack in the preceding year. Severe episodes of wheezing were reported in 76 (7.17%; 95% CI 5.69% to 8.89%) participants. However, only 27 (35.53%; 95% CI 24.88% to 47.34%) children with severe wheezing had been diagnosed as asthmatics by a clinician. The identified independent risk factors for severe wheeze were allergic rhinitis (OR 6.90; 95% CI 3.84 to 12.40), domestic dog(s) (OR 2.34; 95% CI 1.01 to 5.40), frequent consumption of skipjack tuna (OR 1.94; 95% CI 1.11 to 3.39) and passive smoking (OR 1.70; 95% CI 0.93 to 3.11) while living in a house with a cement floor is a protective factor (OR 0.41; 95% CI 0.21 to 0.80). CONCLUSION: Wheezing commonly affects one-fourth of preschool children in rural Sri Lanka. Severe wheezing is often not diagnosed as asthma despite frequent symptoms, probably due to hesitancy in labelling preschool children as asthmatics. Allergic rhinitis, domestic dogs, frequent consumption of Skipjack tuna fish and exposure to passive smoking were independent risk factors for severe wheeze.

Emerging pesticides responsible for suicide in rural Sri Lanka following the 2008-2014 pesticide bans.

BACKGROUND: Sri Lanka has reduced its overall suicide rate by 70% over the last two decades through means restriction, through a series of government regulations and bans removing highly hazardous pesticides from agriculture. We aimed to identify the key pesticide(s) now responsible for suicides in rural Sri Lanka to provide data for further pesticide regulation. METHODS: We performed a secondary analysis of data collected prospectively during a cluster randomized controlled trial in the Anuradhapura district of Sri Lanka from 2011 to 16. The identity of pesticides responsible for suicides were sought from medical or judicial medical notes, coroners' records, and the person's family. Trend analysis was done using a regression analysis with curve estimation to identify relative importance of key pesticides. RESULTS: We identified 337 suicidal deaths. Among them, the majority 193 (57.3%) were due to ingestion of pesticides while 82 (24.3%) were due to hanging. A specific pesticide was identified in 105 (54.4%) of the pesticide suicides. Ingestion of carbosulfan or profenofos was responsible for 59 (56.2%) of the suicides with a known pesticide and 17.5% of all suicides. The increasing trend of suicides due to carbosulfan and profenofos over time was statistically significant (R square 0.846, F 16.541, p 0.027). CONCLUSION: Ingestion of pesticides remains the most important means of suicides in rural Sri Lanka. The pesticides that were once responsible for most pesticide suicides have now been replaced by carbosulfan and profenofos. Their regulation and replacement in agriculture with less hazardous pesticides will further reduce the incidence of both pesticide and overall suicides in rural Sri Lanka.

Cytokine response in human leptospirosis with different clinical outcomes: a systematic review.

BACKGROUND: Leptospirosis is a neglected zoonotic disease which is a major challenge for clinicians and public health professionals in tropical countries. The cytokine storm during the second (immune) phase is thought to be a major contributory factor for the leptospirosis disease severity. We aim to summarize evidence for cytokine response in leptospirosis at different clinical outcomes. METHODS: A systematic review was carried out to examine the cytokine response in leptospirosis patients using relevant scientific databases. Reference lists of the selected articles were also screened. Quality of the selected studies was assessed by using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS: Of the 239 articles retrieved in the initial search, 18 studies fulfilled the selection criteria. India and Thailand have produced the highest number of studies (17% each, n = 3). The majority were comparative cross-sectional studies (72%, n = 13). Overall the quality of the selected studies was fair regardless of few drawbacks such as reporting of sample size and the lack of adjustment for confounders. Microscopic agglutination test (67% - 12/18) and enzyme-linked immunosorbent assay (50% - 9/18) were commonly used for the confirmation of leptospirosis and the measurement of cytokines respectively. IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10 and TNF-α levels were found to be significantly higher in severe than in mild leptospirosis. There were equivocal findings on the association between IL-1ß, TNF-α and IL-10/TNF-α ratio and disease severity. CONCLUSIONS: Leptospirosis had a wide-range of elevated cytokines. However, prospective studies in-relation to the onset of the symptom are required to better understand the pathophysiology of cytokine response in leptospirosis.

In vivo, ex vivo and in vitro evidence for atropine-mediated attenuation of glucagon-like peptide-1 secretion: findings from a systematic review.

Glucagon-like peptide-1 (GLP-1) is involved in postprandial glucose homeostasis. Secretion of which involves a cholinergic pathway. Anticholinergic agent like atropine could act as a competitive antagonist of acetylcholine at muscarinic receptors. This review explores studies that assess the role of atropine in GLP-1 secretion. We selected published original articles from PubMed, Science Direct, The Cochrane Library, Trip, Google and the reference lists of the selected articles. Reporting was done according to the PRISMA statement. Relevant standard and previously published tools were used to assess the risk of bias of the selected articles. Twelve articles out of 185 search results fulfilled the review criteria. Eight were in vivo studies (six animal and two human studies), three were ex vivo studies and one was an in vitro study. Animal studies had rats, mice, pigs and monkeys as the subjects. Human studies involved healthy men and women. Majority of the studies reported an atropine-mediated attenuation of GLP-1 secretion and postprandial secretion of GLP-1 was mainly affected. However, atropine failed to significantly affect GLP-1 secretion when dipeptidyl peptidase-4 (DPP-4) enzyme was inhibited.

The status of dermatoglyphics as a biomarker of Tel Hashomer camptodactyly syndrome: a review of the literature.

INTRODUCTION: Tel Hashomer camptodactyly syndrome is a rare disease and only a few cases have been reported. Dermatoglyphics potentially provide relevant phenotypic biomarkers that were initially noted as a vital clinical feature of this disease. Dermatoglyphics possibly can indicate growth disturbances that took place during early fetal development at the time when epidermal ridges were being formed into discernable patterns. Consequently, these intrauterine effects might well have occurred in association with the expression of the Tel Hashomer camptodactyly syndrome. Therefore, this review was undertaken to provide, as far as we know, the first attempt to broadly assess dermatoglyphic features that are connected with the Tel Hashomer camptodactyly syndrome. If a developmental association between dermatoglyphics and Tel Hashomer camptodactyly can be firmly established, this would probably document that Tel Hashomer camptodactyly disease has its origins during the early fetal period. METHODS: A systematic literature search was conducted using articles from PubMed (Medline), POPLINE, Trip Database, Cochrane Library, and gray literature up to 31 March 2015. The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: Fourteen relevant publications were included in the review. There were 23 cases of patients with Tel Hashomer camptodactyly syndrome that were described in these published articles. We reviewed the dermatoglyphics of 21 available cases out of all of the published and electronically available cases of Tel Hashomer camptodactyly. Eight cases reported whorls to be the most common digital pattern with an expected rise of ridge count. Two cases show significantly high frequencies of arch patterns. Further, there were increased numbers of palmar creases, along with abnormal flexion creases or other palmar dermatoglyphic abnormalities reported in all cases. CONCLUSION: This review highlighted the desirability of thoroughly observing and recording dermatoglyphic features when reporting on future patients with Tel Hashomer camptodactyly syndrome, in conjunction with carrying out modern molecular methods.

Dermatoglyphics in kidney diseases: a review.

Kidney diseases are becoming a major cause of global burden with high mortality and morbidity. The origins of most kidney diseases are known, but for some the exact aetiology is not yet understood. Dermatoglyphics is the scientific study of epidermal ridge patterns and it has been used as a non-invasive diagnostic tool to detect or predict different medical conditions that have foetal origin. However, there have been a limited number of studies that have evaluated a dermatoglyphic relationship in different kidney diseases. The aim of this review was to systematically identify, review and appraise available literature that evaluated an association of different dermatoglyphic variables with kidney diseases. This review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. The PubMed(®) (Medline), POPLINE, Cochrane Library and Trip Database and grey literature sources such as OpenGrey, Google Scholar, and Google were searched to earliest date to 17 April 2014. Of the 36 relevant publications, 15 were included in the review. Of these studies, there are five case reports, seven case series and three comparative studies. Possible association of dermatoglyphics with Wilms tumor (WT) had been evaluated in two comparative studies and one case series that found fewer whorls and a lower mean total ridge count (TRC). Another study evaluated adult polycystic kidney disease (APCD) type III that revealed lower TRC means in all cases. All other case series and case reports describe dermatoglyphics in various kidney disease such as acro-renal-ocular syndrome, potter syndrome, kabuki makeup syndrome, neurofaciodigitorenal syndrome, syndactyly type V, ring chromosome 13 syndrome, trisomy 13 syndrome and sirenomelia. It is evident that whorl pattern frequency and TRC have been used widely to investigate the uncertainty related to the origin of several kidney diseases such as WT and APCD type III. However, small sample sizes, possibly methodological issues, and discrepancy in the make up between cases and control groups limits interpretation of any significant findings. Future studies with proper protocol, adequate cases, and control groups may provide stronger evidence to resolve uncertainty related to the aetiology of kidney diseases.

Drinking well water and occupational exposure to Herbicides is associated with chronic kidney disease, in Padavi-Sripura, Sri Lanka.

BACKGROUND: The chronic kidney disease of unknown etiology (CKDu) among paddy farmers in was first reported in 1994 and has now become most important public health issue in dry zone of Sri Lanka. The objective was to identify risk factors associated with the epidemic in an area with high prevalence. METHODS: A case control study was carried out in Padavi-Sripura hospital in Trincomalee district. CKDu patients were defined using health ministry criteria. All confirmed cases (N = 125) fulfilling the entry criteria were recruited to the study. Control selection (N = 180) was done from people visiting the hospital for CKDu screening. Socio-demographic and data related to usage of applying pesticides and fertilizers were studied. Drinking water was also analyzed using ICP-MS and ELISA to determine the levels of metals and glyphosate. RESULTS: Majority of patients were farmers (N = 107, 85.6%) and were educated up to 'Ordinary Level' (N = 92, 73.6%). We specifically analyzed for the effect modification of, farming by sex, which showed a significantly higher risk for male farmers with OR 4.69 (95% CI 1.06-20.69) in comparison to their female counterparts. In the multivariable analysis the highest risk for CKDu was observed among participants who drank well water (OR 2.52, 95% CI 1.12-5.70) and had history of drinking water from an abandoned well (OR 5.43, 95% CI 2.88-10.26) and spray glyphosate (OR 5.12, 95% CI 2.33-11.26) as a pesticide. Water analysis showed significantly higher amount of hardness, electrical conductivity and glyphosate levels in abandoned wells. In addition Ca, Mg, Ba, Sr, Fe, Ti, V and Sr were high in abandoned wells. Surface water from reservoirs in the endemic area also showed contamination with glyphosate but at a much lower level. Glyphosate was not seen in water samples in the Colombo district. CONCLUSION: The current study strongly favors the hypothesis that CKDu epidemic among farmers in dry zone of Sri Lanka is associated with, history of drinking water from a well that was abandoned. In addition, it is associated with spraying glyphosate and other pesticides in paddy fields. Farmers do not use personnel protective equipments and wears scanty clothing due to heat when spraying pesticides.

The role of private pesticide vendors in preventing access to pesticides for self-poisoning in rural Sri Lanka.

In 15% to 20% of self-poisoning cases, the pesticides used are purchased from shops just prior to ingestion. We explored how pesticide vendors interacted with customers at risk of self-poisoning to identify interventions to prevent such poisonings. Two strategies were specifically discussed: selling pesticides only to farmers bearing identity cards or customers bearing pesticide 'prescriptions'. Vendors reported refusing to sell pesticides to people thought to be at risk of self-poisoning, but acknowledged the difficulty of distinguishing them from legitimate customers; vendors also stated they did want to help to improve identification of such customers. The community did not blame vendors when pesticides used for self-poison were purchased from their shops. Vendors have already taken steps to restrict access, including selling low toxic products, counselling and asking customer to return the next day. However, there was little support for the proposed interventions of 'identity cards' and 'prescriptions'. Novel public health approaches are required to complement this approach.