Provenance and peer review Not commissioned; externally peer reviewed.Data availability statement There are no data in this work.

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.

Metabolic syndrome (MetS) in pregnancy shows epigenetic associations with intergenerational inheritance of metabolic diseases. The presence of different diagnostic criteria influences MetS prevalence estimates. We evaluated MetS and metabolic derangements to determine the utility of its assessment in early pregnancy. A cross-sectional analysis of metabolic derangements in pregnant women with period of gestation (POG) ≤ 12 weeks was done among Rajarata Pregnancy Cohort participants in Sri Lanka. 2682 women with mean age 27.9 year (SD-5.5) and median POG 8.0wk (IQR-3) were analyzed. Mean levels of triglycerides (TG), total cholesterol (TC), high-density-lipoprotein (HDL), low-density-lipoprotein (LDL), fasting plasma glucose, and 2 h oral glucose tolerance test were 87.71 (SD 38.7), 172.2 (SD 34.7), 49.6 (SD 11.5), 122.6 (SD 32.3), 82.2 (SD 12.8) and 120.3 (SD 11.5) respectively. All serum lipids except LDL increase significantly from 6 to 12 weeks, with TG by 23 and TC by 8 units. High MetS prevalence was observed with AHA/NHLBI (n = 150, 5.6%, 95% CI 4.8–6.5) followed by IDF (n = 144, 5.4%, 95% CI 4.6–6.3), NCEP-ATP III (n = 112, 4.2%, 95% CI 3.4–5.0) and WHO (n = 81, 3.0%, 95% CI 2.4–3.7) definitions respectively. Significant difference in prevalence was noted among different sociodemographic characteristics (p < 0.001). Regardless of the criterion used, the change of metabolic parameters in early pregnancy leads to significant differences in prevalence estimates of MetS. The best MetS definition concerning pregnancy outcomes needs to be determined with prospective studies.

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.

No abstract

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.

Renal functions in pregnancy undergo rapid changes, and the thresholds for normal values is a major research gap and are still debatable. We used a prospective cohort design with 2,259 first trimester pregnant women from Anuradhapura, Sri Lanka to estimate the gestational age-specific serum creatinine levels and 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 a 97.5th percentile of 89.0 μmol/L. The mean (SD) sCr was 55.1, 52.7, 51.0, 47.2, and 49.3, while the 97.5th percentile for sCr was 72.4, 69.2, 69.3, 63.9, and 66.0 μmol/L, respectively, in the sample of pregnant women. In the first and second trimesters, the average sCr value was 84.7% and 76.4% of that of the nonpregnant group, respectively. The mean eGFR increased up to 129.4 mL/min/1.73 m2 in the 24th week of gestation. The analysis of cohort data clearly confirmed a significant reduction in sCr with advancing pregnancy (p<0 .001). This study confirms the previously reported secondary-data-based thresholds, and the clinical validation of the upper limits proposed needs to be evaluated with pregnancy and new-born outcomes.

Proteinuria is an important prognostic marker in the diagnosis and management of kidney diseases. Sulfosalicylic acid method (SSA) is a simple, low cost, qualitative test, widely used to assess proteinuria. The aim of this study was to optimize SSA test as a quantitative screening tool to assess proteinuria at lower excretory levels which would facilitate the screening and early diagnosis of renal impairment using protein-to-creatinine ratio (PCR). The study was conducted in two phases. In phase I, optimum SSA percentage to detect low-grade proteinuria was selected by comparing the performance of 3%, 6%, and 25% SSA methods in manual spectrophotometric analysis. In phase II, clinical applicability of the optimized method was evaluated using retained urine samples of patients with chronic kidney disease (CKD) assessed for urine protein by the pyrogallol red (PGR) method in a tertiary care hospital in Sri Lanka. Optimized 25% SSA protein-to-creatinine ratio (PCR) was compared with PGR PCR and albumin-to-creatinine ratio (ACR). Sensitivity, specificity, degree of agreement, correlation, and diagnostic accuracy were evaluated. Turbidimetric analysis using 25% SSA was linear in the range 3–50 mg/dL giving the highest analytical sensitivity. The test yielded a sensitivity of 86.5% and specificity of 96.5% and a degree of agreement of 5 mg/dL with the PGR method. Optimal cut-off for 25% SSA PCR in receiver operating characteristic analysis was 166 mg/g. Spearman’s correlation coefficient for 25% SSA PCR versus ACR was r = 0.823, p < 0.0001 , and for 25% SSA PCR versus PGR PCR was r = 0.913, p < 0.0001 . The 25% SSA PCR has a sensitivity of 92% against ACR, the current prognostic marker for proteinuria in patients with CKD. The 25% SSA test is a simple method, and it performs satisfactorily as a screening test with a cut-off for PCR optimized at 166 mg/g. The test merits further evaluation due to its low cost.