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.

Whole genome sequencing data of Leptospira weilii and Leptospira kirschneri isolated from human subjects of Sri Lanka.

Leptospirosis is a re-emerging zoonotic disease. This article reports the complete genome sequences of three novel strains of Genus Leptospira: two from the species Leptospira weilii (FMAS_RT1, FMAS_PD2) and one from Leptospira kirschneri (FMAS_PN5). These isolates were recovered from the blood samples of acute febrile patients in different geographical and climatic zones of Sri Lanka. High-quality genomic DNA was extracted from the three isolates in mid-log phase cultures. Whole genome sequencing was conducted using the PacBio Single Molecule Real-Time (SMRT) platform to identify the species, genome features, and novelty of the strains. The annotation was conducted using RAST (Rapid Annotation Using Subsystem Technology version 2.0) and the NCBI Prokaryotic Genome Annotation Pipeline. The genome sequences of three isolates have been deposited in the Mendeley data repository and the National Center for Biotechnology Information (NCBI) repository. This data will be useful for future researchers when conducting comparative genomic analysis, revealing the exact mechanism of pathogenesis of leptospirosis and developing molecular diagnostic tools for early detection.

Knowledge and attitudes on attention deficit hyperactivity disorder (ADHD) among school teachers in Anuradhapura district, Sri Lanka: a descriptive cross-sectional study.

OBJECTIVE: This study aimed to assess the knowledge and attitude of school teachers from a rural district in a developing country towards children with attention deficit hyperactivity disorder (ADHD). DESIGN: A population-based descriptive cross-sectional study was conducted using probability proportionate to size cluster sampling. SETTING: This study was conducted in 21 government schools in Anuradhapura district, Sri Lanka. PARTICIPANTS: The study sample consisted of 458 teachers with a mean age of 41 completed years ranging from 24 to 59 years. MAIN OUTCOME MEASUREMENTS: We assessed knowledge, attitudes and sources of information on ADHD using the self-administered, validated Knowledge of Attention Deficit Disorder Scale (KADD), Teacher Attitudes Towards Inclusion Scale (TAIS) and the Perceived and Actual Sources of Information questionnaires. RESULTS: The median KADD score was 11 (IQR 8-14) and 45.5% (n=208) of participants lacked sufficient knowledge. Percentages of the correct answers, misconceptions and 'don't know' responses were 28.2%, 24.5% and 45.5%, respectively. The majority of teachers believed that the children with ADHD generally experience more problems in novel situations than in familiar situations (63.5%), a diagnosis of ADHD by itself makes a child eligible for placement in special education (61.1%), and children with ADHD do not often have difficulties organising tasks and activities (61.1%). Some participants (12%) stated that punishment would improve the outcome of the children with ADHD. The attitudes were positive with TAIS 1 and 2 median scores of 46 (IQR 36-58) and 49 (IQR 40-59). The majority of participants relied on informal knowledge gained through their personal experience in the classroom on ADHD (n=337, 76%). The majority of teachers (n=300, 67.7%) preferred to be educated through seminars. CONCLUSIONS: School teachers possess a positive attitude. However, they have poor knowledge and significant misconceptions regarding ADHD which may affect the identification and management.

Incorporating early pregnancy mental health screening and management into routine maternal care: experience from the Rajarata Pregnancy Cohort (RaPCo), Sri Lanka.

Early identification of mental health problems in pregnancy in low-income and middle-income countries is scarcely reported. We present the experience of a programme assimilating screening and management of antenatal anxiety and depression in conjunction with the Rajarata Pregnancy Cohort, in Sri Lanka. We adopted a two-stage screening approach to identify the symptoms and the reasons for anxiety and depression. Pregnant women (n=3074), less than 13 weeks of period of gestation underwent screening with the Edinburgh Postnatal Depression Scale (EPDS). Scores were positive among 23% and 14% of women in the first and second trimesters, respectively. Clinical (telephone) interviews (n=78, response 56.9%) were held for women having high EPDS scores to screen for clinical depression using the 'mental health GAP' tool. Targeted interventions including counselling, financial and social support and health education were employed. The procedure was repeated in the second trimester with in-person clinical interviews and inquiry into intentional self-harm. Our findings indicated that (1) the majority of mental health problems in early pregnancy were anxiety related to early pregnancy-associated conditions manageable at the primary healthcare level, (2) coupling mental health screening using psychometric tools with clinical interviews facilitates targeted patient-centred care, (3) the majority of intentional self-harm during pregnancy is not in the routine health surveillance system and (4) promoting women to attend the psychiatry clinic in tertiary care hospital has been difficult. Following the experience, we propose a model for mental health service provision in routine pregnancy care programme starting from early pregnancy.

Complete genome sequences of twelve strains of Leptospira interrogans isolated from humans in Sri Lanka.

Leptospirosis, a major zoonotic disease caused by pathogenic Leptospira spp. is recognized globally as an emerging zoonotic disease. Whole-genome sequencing reveals hidden messages about Leptospira's pathogenesis. We used Single Molecule Real-Time (SMRT) sequencing to obtain complete genome sequences of twelve L. interrogans isolates from febrile patients from Sri Lanka for a comparative whole genome sequencing study. The sequence data generated 12 genomes with a coverage greater than X600 with sizes ranging from 4.62 Mb to 5.16 Mb, and a G + C content ranging from 35.00% to 35.42%. The total number of coding sequences predicted by the NCBI (National Center for Biotechnology Information) genome assembly platform ranged from 3845 to 4621 for the twelve strains. Leptospira serogroup with similar-sized LPS biosynthetic loci that belonged to the same clade had a close relationship in the phylogenetic analysis. Nonetheless, variations in the genes encoding sugar biosynthesis were found in the serovar determinant region (rfb locus). Type I and Type III CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) systems were found in all of the strains. Genome BLAST Distance Phylogeny of these sequences allowed for detailed genomic strain typing. These findings may help us better understand the pathogenesis, develop a tools for early diagnosis, comparative genomic analysis and evolution of Leptospira.

Serum creatinine and estimated glomerular filtration rate (eGFR) in early pregnancy and changes during the pregnancy.

Renal functions in pregnancy undergo rapid changes, and the thresholds for normal values are a major research gap and are still debatable. The lack of prospective population-based studies with early pregnancy recruitment hampered the decision-making process on the best thresholds to be used in clinical practice. We present the serum creatinine (sCr) and sCr-based estimated glomerular filtration rates (eGFR) in early pregnancy with changes over the gestational period in a large prospective, community-based cohort, the Rajarata Pregnancy Cohort (RaPCo). We carried out a community-based prospective cohort study with 2,259 healthy pregnant women with a gestation period of less than 13 weeks and without pre-existing medical conditions. Gestational period-specific sCr and sCr-based eGFR were calculated for different age strata, and the participants were followed up until the second trimester. Renal functions of pregnant women were compared with 2.012 nonpregnant women from the same geographical area. The mean (SD) sCr of the 2,012 nonpregnant women was 62.8(12.4) µmol/L, with the 97.5th percentile of 89.0 µmol/L. Among the pregnant women, mean (SD) sCr was 55.1(8.3), 52.7(8.1), 51.1(9.1), 47.1(7.2), and 49.3 (9.9), while the 97.5th percentile for sCr was 72.4, 69.1, 70.0, 63.6, and 66.0 µmol/L respectively during the 4-7, 8-9, 10-12, 24-27 and 28-30 weeks of gestation. The average sCr value was 84.7% and 76.4% of the nonpregnant group, respectively, in the first and second trimesters. The mean eGFR was 123.4 (10.7) mL/min/1.73 m2 in the first trimester and increased up to 129.5 mL/min/1.73 m2 in the 24th week of gestation. The analysis of cohort data confirmed a significant reduction in sCr with advancing pregnancy (p<0 .001). This study provides thresholds for renal functions in pregnancy to be used in clinical practice. Clinical validation of the proposed thresholds needs to be evaluated with pregnancy and newborn outcomes.

SARIMA and ARDL models for predicting leptospirosis in Anuradhapura district Sri Lanka.

Leptospirosis is considered a neglected tropical disease despite its considerable mortality and morbidity. Lack of prediction remains a major reason for underestimating the disease. Although many models have been developed, most of them focused on the districts situated in the wet zone due to higher case numbers in that region. However, leptospirosis remains a major disease even in the dry zone of Sri Lanka. The objective of this study is to develop a time series model to predict leptospirosis in the Anuradhapura district situated in the dry zone of Sri Lanka. Time series data on monthly leptospirosis incidences from January 2008 to December 2018 and monthly rainfall, rainy days, temperature, and relative humidity were considered in model fitting. The first 72 months (55%) were used to fit the model, and the subsequent 60 months(45%) were used to validate the model. The log-transformed dependent variable was employed for fitting the Univariate seasonal ARIMA model. Based on the stationarity of the mean of the five variables, the ARDL model was selected as the multivariate time series technique. Residuals analysis was performed on normality, heteroskedasticity, and serial correlation to validate the model. The lowest AIC and MAPE were used to select the best model. Univariate models could not be fitted without adjusting the outliers. Adjusting seasonal outliers yielded better results than the models without adjustments. Best fitted Univariate model was ARIMA(1,0,0)(0,1,1)12,(AIC-1.08, MAPE-19.8). Best fitted ARDL model was ARDL(1, 3, 2, 1, 0),(AIC-2.04,MAPE-30.4). The number of patients reported in the previous month, rainfall, rainy days, and temperature showed a positive association, while relative humidity was negatively associated with leptospirosis. Multivariate models fitted better than univariate models for the original data. Best-fitted models indicate the necessity of including other explanatory variables such as patient, host, and epidemiological factors to yield better results.

Asthma in a prospective cohort of rural pregnant women from Sri Lanka: Need for better care during the pre-conceptional and antenatal period.

OBJECTIVES: To describe the epidemiology and the effect of asthma on pregnancy outcomes in pregnant women from a rural geography. METHODS: We conducted a prospective cohort study in Anuradhapura district, Sri Lanka enrolling all eligible pregnant women registered in the maternal care program. An interviewer-administered questionnaire-based symptom analysis and clinical assessment was conducted in the first and second trimesters. RESULTS: We recruited 3374 pregnant women aged 15-48 years at conception. Self-reported physician-diagnosed asthma prevalence was 6.6% (n = 223) with only 41.7% (n = 93) on regular medical follow-up for asthma. The prevalence of wheeze reduced from pre-pregnancy (67.0%) to the first (46.4%) and second trimesters (47.7%; p<0.01). Of the 73 asthmatic women who did not have wheeze in the last 3 months preceding pregnancy, new-onset wheeze was reported by 6(8.2%) and 12(16.4%) in the first and second trimester, respectively. Pregnant women who sought medical care for asthma in the private sector had a lower likelihood of developing new-onset wheeze in the first trimester (p = 0.03; unadjusted OR = 0.94;95%CI 0.89-0.99). Thirty-four (33.3%) pregnant women had at least one hospital admission due to exacerbation of wheeze during the first and second trimester. The prevalence of low birth weight (16.0%) was higher among pregnant asthmatic women. CONCLUSION: This study reports the high prevalence of asthma and asthma-associated pregnancy outcomes in women from a rural geography signifying the importance of targeted management.

Fatty Liver Index is a valid predictor of non-alcoholic fatty liver disease (NAFLD) in pregnancy.

BACKGROUND: Despite the evidence for adverse pregnancy outcomes, non-alcoholic fatty liver disease (NAFLD) is not routinely addressed in early pregnancy. The Fatty Liver Index (FLI) has been proposed as a screening tool for NAFLD in the general population. We aim to develop mathematical models for predicting NAFLD in pregnancy and validate the FLI for first-trimester pregnant women. METHODS: Biochemical and biophysical parameters were analysed in pregnant women with period of gestation <12 weeks was done among Rajarata Pregnancy Cohort, Sri Lanka. Fatty liver was graded as (FLG) 0, I or II by ultrasound scan. Binary logistic regression models were employed to identify the factors predicting FLG-II. Six FLIs were developed to predict FLG-II. Validity of the FLIs was compared using the receiver operating characteristic curves. RESULTS: The study sample consisted of 632 pregnant women with a mean age of 28.8 years (SD: 5.8 years). Age (OR: 1.6, 95% CI 1.1 to 2.3), body mass index (OR: 1.7, 95% CI 1.1 to 2.5) and gamma-glutamyl transferase levels (OR: 2.1, 95% CI 1.5 to 3.0) were the independent predictors of FLG-II. While the model with liver enzymes provided the best prediction of NAFLD (both FLG I and II) (area under the curve [(AUC]): -0.734), the highest AUC (0.84) for predicting FLG-II was observed with the full model (model with all parameters). The proposed budget model (AUC >0.81) is the best model for screening fatty liver in community health setup. CONCLUSION: FLIs could be used as screening tools for NAFLD based on resource availability in different settings. External validation of the FLI and further investigation of the proposed FLI as a predictor of adverse pregnancy outcomes are recommended.

Demographic, exposure, clinical, biochemical and diagnostic data of febrile patients recruited for the largest field study on leptospirosis in Sri Lanka.

This dataset includes data from febrile patients recruited for a large hospital-based study in Sri Lanka from 2016 to 2019. The variables include primary socio-demographic data, exposure data, clinical data, biochemical and investigation data. Some of these data are available as serial data from admission to discharge daily. Microscopic agglutination test, quantitative PCR of whole blood, urine and serum and culture isolation was performed to diagnose the patients with leptospirosis.

Diagnostic method-based underestimation of leptospirosis in clinical and research settings; an experience from a large prospective study in a high endemic setting.

BACKGROUND: Leptospirosis has globally significant human mortality and morbidity, yet estimating the clinical and public health burden of leptospirosis is challenging because timely diagnosis remains limited. The goal of the present study was to evaluate leptospirosis undercounting by current standard methods in both clinical and epidemiological study settings. METHODOLOGY/PRINCIPAL FINDINGS: A prospective hospital-based study was conducted in multiple hospitals in Sri Lanka from 2016 to 2019. Culture, whole blood, and urine samples were collected from clinically suspected leptospirosis cases and patients with undifferentiated fever. Analysis of biological samples from 1,734 subjects confirmed 591 (34.1%) cases as leptospirosis and 297 (17.1%) were classified as "probable" leptospirosis cases. Whole blood quantitative PCR (qPCR) did identify the most cases (322/540(60%)) but missed 40%. Cases missed by each method include; urine qPCR, 70% (153/220); acute sample microscopic agglutination test (MAT), 80% (409/510); paired serum sample MAT, 58% (98/170); and surveillance clinical case definition, 53% (265/496). qPCR of negative culture samples after six months of observation was of diagnostic value retrospectively with but missed 58% of positives (109/353). CONCLUSION: Leptospirosis disease burden estimates should consider the limitations of standard diagnostic tests. qPCR of multiple sample types should be used as a leading standard test for diagnosing acute leptospirosis.

Non-alcoholic fatty liver disease (NAFLD): a significant predictor of gestational diabetes mellitus (GDM) and early pregnancy miscarriages-prospective study in Rajarata Pregnancy Cohort (RaPCo).

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is increasing globally with a mounting body of evidence on various adverse effects on pregnancy. Yet, prospective studies, especially from low-income and middle-income countries, are lacking in examining the impact of NAFLD in pregnancy. In this study, we explored the effect of NAFLD on the development of gestational diabetes mellitus (GDM) and early pregnancy miscarriages. METHODS: A population-based prospective cohort study was conducted among first-trimester pregnant women who registered in the national pregnancy care programme during July-September 2019 in Anuradhapura district, Sri Lanka. Baseline clinical-biochemical parameters and ultrasound scan (USS) of the liver were done to assess fatty liver. Those who were normoglycaemic based on WHO criteria were followed up, and a repeat oral glucose tolerance test was performed between 24 and 28 weeks of gestation. RESULTS: Of the 632 pregnant women studied, 90 (14%) and 234 (37%) were diagnosed as having fatty liver grade (FLG) II and I, respectively. The cumulative incidence of GDM in FLG 0, I, and II were 11, 44, and 162 per 1000 pregnancies, respectively. After adjusting for age and other known risk factors, women with FLG II had a relative risk (RR) of 12.5 (95% CI 2.2 to 66.4) for developing GDM compared with FLG 0. In addition, women with FLG I (RR 2.1, 95% CI 1.01 to 4.64) and FLG II (RR 4.5, 95% CI 2.1 to 9.9) were significant risk factors for early pregnancy miscarriages, and FLG II remained as the only independent predictor of miscarriages after adjusting for age, parity, body mass index, blood sugar, blood pressure, and haemoglobin level (adjusted OR 4.2 (95% CI 1.9 to 9.1)). CONCLUSION: In this rural south Asian community, NAFLD is shown to be a major risk factor for GDM and early pregnancy miscarriages. Therefore, routine identification of NAFLD through a simple USS may help in the early identification of high-risk mothers.

Temporal Variation and Factors Associated with Allergic Rhinitis in a Cohort of Rural Preschool Children from Sri Lanka.

BACKGROUND: Allergic rhinitis is a common chronic childhood disease with a low diagnosis rate, causing poor quality of life, absenteeism, decreased school performance and significant healthcare cost. However, data on the prevalence of allergic rhinitis is sparse in preschoolers of rural geography, especially in developing countries. AIM: To describe the epidemiology of allergic rhinitis in preschoolers from a rural geography of a developing country. METHODS: A population-based cross-sectional study was conducted in Anuradhapura district, Sri Lanka using the WHO-30 cluster methodology with probability proportionate to size sampling. The International Study of Asthma and Allergy in Childhood questionnaire was used to assess symptomatology. RESULTS: The response rate was 91.8%, with 548 (51.7%) male and 512 (48.3%) female participants. The mean age was 4.4 (± 0.7) years. Allergic rhinitis was reported in 123 (11.6%; 95% CI 9.7-13.5), and eye symptoms were reported in 41 (3.9%; 95% CI 2.8-5.2) children. Activities of daily living were disturbed due to nasal symptoms in 113 (10.7%; 95% CI 8.8-12.5). Allergic rhinitis was independently associated with severe asthma (OR 6.26; 95% CI 3.54-11.06), sleeping on the floor (OR 4.79; 95% CI 1.33-17.25) and having cats in the households (OR 1.86; 95% CI 1.18-2.91). Nasal symptoms were more common in January and August to October months. The standardized local highest monthly temperature, lowest monthly temperature, highest monthly humidity and dew point strongly predicted allergic rhinitis symptom exacerbation (F=4.8, p=0.036, adjusted R square=57.8%, VIF≤2.259, DW=2.1). CONCLUSIONS: Allergic rhinitis affects 1 in 10 preschool children of rural Sri Lanka. The factors associated and environmental factor model developed to predict symptom exacerbation could be used to prevent allergic rhinitis exacerbations.

Allergic rhinitis is a common childhood disease where children suffer nasal symptoms­sneezing, runny nose or blocked nose when the child does not have a cold or the flu­and itchy-watery eyes. We assessed 1060 preschool children from a rural district in Sri Lanka. We report that more than 1 in 10 preschool children from rural Sri Lanka had symptoms of allergic rhinitis. Children with severe asthma symptoms (a medical condition where the airways through which air flows in and out of the lungs become excessively narrow under certain conditions) or those sleeping on the floor or exposed to domestic cats had a higher likelihood of developing allergic rhinitis. These nasal symptoms were more common in January and August to October. We assessed the role of environmental weather factors on increased nasal symptoms during different weather conditions. The standardized highest monthly temperature, lowest monthly temperature, and highest monthly humidity and dew point were predictive of the number of children developing nasal symptoms in a given month in this rural geography.

The variable presence of Leptospira in the environment; an epidemiological explanation based on serial analysis of water samples.

Human leptospirosis involves the classic epidemiological triad (agent, host and environment); hence the investigations should include the knowledge on Leptospira within the animals and the environment. The objectives of this study are to explore the abundance of Leptospira in different climate zones of Sri Lanka and to describe the presence of Leptospira in the same water source at serial time points. First, water and soil samples were collected from different parts of Sri Lanka (Component-1); second, water sampling continued only in the dry zone (Component-2). Finally, serial water sampling from ten open wells was performed at five different time points (Component-3). Quantitative PCR of water and metagenomic sequencing of soil were performed to detect Leptospira. Three replicates for each sample were used for PCR testing, and positive result of two or more replicates was defined as 'strongly positive,' and one positive replicate was defined as positive. In the water and soil sample analysis in the whole country (Component-1), two out of 12 water sites were positive, and both were situated in the wet zone. Very small quantities of the genus Leptospira were detected by 16 amplicon analysis of soil in all 11 sites. In the dry zone water sample analysis (Component-2), only samples from 6 out of 26 sites were positive, of which one site was strongly positive. In the serial sample analysis (Component-3), Six, five, four, five, and six wells were positive in serial measurements. All wells were positive for at least one time point, while only one well was positive for all five time points. Proximity to the tank and greater distances from the main road were associated with strong positive results for Leptospira (P<0.05). The presence of Leptospira was not consistent, indicating the variable abundance of Leptospira in the natural environment. This intermittent nature of positivity could be explained by the repetitive contamination by animal urine.

Neglecting the neglected during the COVID-19 pandemic: the case of leptospirosis in Sri Lanka.

The coronavirus disease 2019 (COVID-19) pandemic has disrupted global health systems and affected the transmission dynamics as well as the surveillance of other infectious diseases. This study described the probable effect of the COVID-19 pandemic on the surveillance and control of leptospirosis in Sri Lanka. With 8,579 reported cases and more than 800 estimated deaths, the Sri Lankan public health surveillance system documented the largest outbreak of leptospirosis in Sri Lankan history in 2020. This was the worst infectious disease outbreak Sri Lanka experienced in 2020, but it was neglected, primarily due to the COVID-19 pandemic.

Clinical spectrum of endemic leptospirosis in relation to cytokine response.

OBJECTIVES: To describe the clinical spectrum and the cytokine response of leptospirosis patients in an endemic setting of Sri Lanka. METHODS: Patients presenting to the university teaching hospital, Anuradhapura, Sri Lanka with a leptospirosis-compatible illness were recruited over a period of 12 months starting from June 2012. Daily clinical and biochemical parameters of the patients were prospectively assessed with a follow-up of 14 days after discharge. A magnetic bead-based multiplex cytokine kit was used to detect 17 cytokines. RESULTS: Of the 142 clinically suspected leptospirosis patients recruited, 47 were confirmed and, 29 cases were labeled as "probable." Thrombocytopenia and leukocytosis were observed at least once during the hospital stay among 76(54%) and 39(28%) patients, respectively. Acute kidney injury was observed in 31 patients (22%) and it was significantly higher among confirmed and probable cases. Hu TNF-α and IL-1ß were detected only in patients without complications. Hu MIP-1b levels were significantly higher among patients with complications. During the convalescence period, all tested serum cytokine levels were lower compared to the acute sample, except for IL-8. The cytokine response during the acute phase clustered in four different groups. High serum creatinine was associated GM-CSF, high IL-5 and IL-6 level were correlates with lung involvement and saturation drop. The patients with high billirubin (direct)>7 mmol/l had high IL-13 levels. CONCLUSIONS: Results of this study confirms that the knowledge on cytokine response in leptospirosis could be more complex than other similar tropical disease, and biosignatures that provide diagnostic and prognostic information for human leptospirosis remain to be discovered.

The hidden burden of adolescent pregnancies in rural Sri Lanka; findings of the Rajarata Pregnancy Cohort.

BACKGROUND: Adolescent fertility is a main indicator of the Sustainable Developmental Goal (SGD) three. Although Sri Lanka is exemplary in maternal health, the utilization of Sexual and Reproductive Health services (SRH) by adolescents is less documented. We describe the hidden burden, associated biological and psychosocial factors and utilization patterns of pre-conceptional services among pregnant adolescents in rural Sri Lanka. METHODS: The study is based on the baseline assessment of the Rajarata Pregnancy Cohort (RaPCo) in Anuradhapura. Pregnant women newly registered from July to September 2019 were recruited to the study. The period of gestation was confirmed during the second follow-up visit (around 25-28 weeks of gestation) using ultra sound scan data. A history, clinical examination, anthropometric measurements, blood investigations were conducted. Mental health status was assessed using the Edinburgh Postpartum Depression Scale (EPDS). RESULTS: Baseline data on gestation was completed by 3,367 pregnant women. Of them, 254 (7.5%) were adolescent pregnancies. Among the primigravida mothers (n = 1037), 22.4% (n = 233) were adolescent pregnancies. Maternal and paternal low education level, being unmarried, and less time since marriage were statistically significant factors associated with adolescent pregnancies (p < 0.05). Contraceptive usage before pregnancy, utilization of pre-conceptional health care services, planning pregnancy and consuming folic acid was significantly low among adolescents (p < 0.001). They also had low body mass index (p < 0.001) and low hemoglobin levels (p = 0.03). Adolescent mothers were less happy of being pregnant (p = 0.006) and had significantly higher levels of anxiety (p = 0.009). CONCLUSION: One fifth of women in their first pregnancy in this study population are adolescents. Nulli-parous adolescents exert poor social stability and compromised physical and mental health effects. The underutilization and/or unavailability of SRH services is clearly associated with adolescent pregnancies.

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.

Optimizing the microscopic agglutination test (MAT) panel for the diagnosis of Leptospirosis in a low resource, hyper-endemic setting with varied microgeographic variation in reactivity.

The microscopic agglutination test (MAT) is the standard serological reference test for the diagnosis of leptospirosis, despite being a technically demanding and laborious procedure. The use of a locally optimised MAT panel is considered essential for proper performance and interpretation of results. This paper describes the procedure of selecting such an optimised panel for Sri Lanka, a country hyper-endemic for leptospirosis. MAT was performed using 24 strains on 1132 serum samples collected from patients presenting with acute undifferentiated fever. Of 24 strains, 15 were selected as the optimised panel, while only 11% of serum samples showed positivity. A geographical variation in predominantly reactive serovars was observed, whereas reactivity was low with the saprophytic strain Patoc. Testing with paired sera yielded a higher sensitivity but provided only a retrospective diagnosis. Serological tests based on ELISA with complementary molecular diagnosis using PCR are a feasible and robust alternative approach to diagnose leptospirosis in countries having a higher burden of the disease.