Trimester-specific thyroid hormone reference data in Sri Lankan women.

Introduction: Regional differences in thyroid hormones are noted, especially during pregnancy. Objectives: Establish reference values for thyroid function tests for Sri Lankan pregnant women and to determine their comparability with regional data; and determine the prevalence of 2. Thyroid Peroxidase (TPO) antibody positivity and 3. Iodine deficiency among pregnant women with uncomplicated clinical history. Methods: A cross-sectional study conducted in antenatal clinics of a tertiary care maternity center recruited a minimum of 56 women in each trimester in a multistep approach to derive an "ideal-reference population"; Participants with clinically manifested thyroid disease, followed by subjects with sonographically abnormal thyroids and finally those at high risk for thyroid disease as shown by positive TPO levels and urine iodine deficiency were excluded in sequence. Thyroid hormones were measured by chemiluminescence in the ideal reference population. Reference ranges were derived using median and 5th and 95th centiles. Results: Final sample included 369 women. TSH reference ranges of the first (n=64), second (n=188) and third (n=117) trimesters were 0.014-2.77mIU/L, 0.31-3.2 mIU/L and 0.34-3.4 mIU/L, respectively. TPO antibody level showed a weak but significant correlation with TSH (r=0.10,p 0.021) in the final sample. No significant association was found between urine iodine and thyroid function tests. Conclusions: TSH reference ranges observed in this study are concordant with the Caucasian reference values more than the regional values. Discrepancies in study methodology, defining and selection of reference population and methods employed in measuring thyroid hormones in different studies may have accounted for these differences.

Thyroid Autoimmunity and Dysfunction in Sri Lankan Children and Adolescents After 22 Years of Sustained Universal Salt Iodization.

Background: Sri Lanka introduced universal salt iodization (USI) in 1995 after which we demonstrated a high thyroglobulin antibody (TgAb) prevalence in 1998. However, it is unclear whether thyroid autoimmunity persists in the long term in populations exposed to sustained USI and whether such populations have an excess of thyroid dysfunction. We evaluated the prevalence of thyroid autoantibodies and dysfunction in Sri Lankan children and adolescents after more than two decades of sustained USI. Methods: We selected 10- to 18-year-old subjects of both sexes (randomized cluster sampling) from all 9 provinces of Sri Lanka in this cross-sectional study. Blood, urine, and anthropometric data were collected and thyroid ultrasound scans were performed. Validated statistical methods were used to derive local population-specific reference ranges for all thyroid parameters. We also measured urine iodine concentration (UIC), salt, and water iodine concentrations. Results: Blood and urine samples from 2507 and 2473 subjects respectively, and ultrasound scans from 882 subjects were analyzed. Population-derived upper limits for thyroid peroxidase antibody (TPOAb) and TgAb, and reference ranges for triiodothyronine, thyroxine, and thyrotropin (total and age-year-related groups) were significantly different from manufacturer's reference ranges. Using these derived ranges, the prevalence of TPOAb was 10.3% and TgAb was 6.4%. Of the TPOAb-positive subjects, TPOAb were of low concentration in 66.2% (1-3 times the upper limit of the reference range [ULRR]) and showed the strongest association with subclinical hypothyroidism (SCH) at the highest concentrations (>4 ULRR). The prevalence of SCH was 3%. Median UIC (interquartile range) was 138.5 µg/L (79.4-219.0) with regional variability, and median thyroglobulin was 8.3 ng/mL (4.1-13.5). Goiter prevalence was 0.6% and 1.93% (thyroid volume compared to age and body surface area, respectively). Salt and water iodine concentrations were satisfactory. Conclusions: Sri Lanka has safely and effectively implemented USI with good sources of iodine, leading to sustained iodine sufficiency over more than two decades. The early postiodization TgAb surge (42.1%) has settled (6.4%), and despite a persistently high TPOAb prevalence (10.3%), SCH prevalence remains low (3%). Further studies should be undertaken to monitor thyroid autoimmune dysfunction in Sri Lankan children, using age-specific, population-derived reference ranges.

First Serological Study Revealing High Humoral Response and Evidence for Antigenic Heterogeneity in Leishmania donovani Induced CL in Sri Lanka.

Posing a threat to the ongoing leishmaniasis elimination efforts in the Indian subcontinent, L. donovani-induced cutaneous leishmaniasis (CL) has been recently reported in many countries. Sri Lanka reports a large focus of human cutaneous leishmaniasis (CL) caused by Leishmania donovani, a usually visceralizing parasite. Enhanced case detection, early treatment, and in-depth understanding of sequalae are required to contain the spread of disease. Visceralizing potential of dermotropic strains has not been fully ruled out. Sri Lankan strains have shown a poor response to established serological assays. The present concern was to develop an in-house serological assay and to determine the seroprevalence of CL for identifying visceralizing potential and its usefulness in enhancing case detection. Crude cell lysate of dermotropic L. donovani promastigotes-based indirect enzyme-linked immunosorbent assay (ELISA) was previously optimized. Assay was evaluated using sera from 200 CL patients, 50 endemic and 50 nonendemic healthy controls, 50 patients with other skin diseases, and 50 patients with other systemic diseases. Seroprevalence and clinicoepidemiological associations were analyzed. Assay was compared with light microscopy (LM) and in vitro culturing (IVC). Cost comparison was carried out. Seroprevalence of CL was 82.0%. The assay had 99.5% specificity, and all healthy controls were negative at 0.189 cut-off. Positive and negative predictive values were 99.4% and 84.7%, respectively. Positivity obtained in ELISA was comparable to LM and higher than that of IVC. Cost per patient was 3.0 USD for both ELISA and LM and 6.0 USD for IVC. Infections occurring in all age groups and both genders demonstrated >75.0% of seropositivity. Patients had lesions with different durations/types/sizes showed >70.0% of seropositivity. Study identified a high seroprevalence of L. donovani-induced CL for the first time, indicating potential for visceralization or transient serological response. This can be used as a second line test in LM-negative CL cases to enhance clinical case detection. Further studies are warranted to examine in-depth correlations, antigen profiles, comparison with other established serological tools, and usefulness in the detection of asymptomatic cases. (National patent LK/P/1/19697).

Evidence for Seroprevalence in Human Localized Cutaneous Leishmaniasis Caused by Leishmania donovani in Sri Lanka.

Visceral leishmaniasis (VL) is considered as a major health threat in the Indian subcontinent. Leishmania donovani, a usually visceralizing species, causes cutaneous leishmaniasis (CL) in Sri Lanka. However, visceralizing potential of the local L. donovani is not yet fully understood. This project studied the seroprevalence of local CL by using an in-house ELISA. An IgG-based ELISA using crude Leishmania antigen (Ag) was developed and validated. A total of 50 laboratory confirmed cases of locally acquired CL were examined using the newly developed ELISA. According to the optimized ELISA, seroprevalence of anti-Leishmania IgG antibodies in the study group was 34.0% (n = 17/50). Majority of seropositive individuals were males (n = 13/17), representing 76%. Nearly half of the seropositive individuals were young adults (20-40 years, n = 9/17, 53%). Higher proportions of single lesions, large lesions, and nodular lesions were associated with a seroconversion. A proportion of local L. donovani infections leading to CL have the ability to raise an antibody response in the host. This may indicate early systemic involvement as one possibility. Study of a large number of patients with adequate follow-up would be useful.