Peptiduria: a potential early predictor of diabetic kidney disease.

BACKGROUND: To protect the kidney effectively with medication in type 2 diabetics, it is crucial to identify such at-risk patients early for treatment. We investigated whether peptiduria precedes proteinuria (the earliest urinary marker in our model), and thereby serve as an early predictor of diabetic nephropathy. METHODS: A longitudinal study was performed in a rat model of diabetic nephropathy. Peptides, defined as degradation products of proteins of < 13 kD size, were quantified by a previously validated method using a combination of Lowry and Biorad protein assays. Peptides in urine were also confirmed by chromatographically separating low molecular weight fractions from urine and quantifying albumin fragments in these fractions by enzyme immunoassay. Also, the mechanism of peptiduria was addressed by measuring acid phosphatase, a marker of lysosomal activity, in urine and on kidney sections (histochemically). RESULTS: In rats with diabetic nephropathy, proteinuria occurred after 12 weeks of diabetes, while peptiduria occurred as early as 2 weeks after diabetes. Peptiduria was confirmed by showing that the chromatographically separated low molecular weight fractions of urine containing albumin fragments is in proportion to the level of peptiduria. The time course of peptiduria paralleled the increase in urinary acid phosphatase suggesting that the mechanism of early peptiduria could be due to upregulation of lysosomal enzyme activity in the tubules. CONCLUSIONS: Our results showing that peptiduria precedes proteinuria in diabetic nephropathy provide a compelling rationale to perform a prospective human clinical trial to investigate whether peptiduria can serve as an early predictor of diabetic nephropathy.

Urine exosomal ceruloplasmin: a potential early biomarker of underlying kidney disease.

BACKGROUND: Previously we found that kidney tissue and urinary exosomes from patients of diabetic kidney disease showed high levels of ceruloplasmin (CP). Because CP is an acute-phase protein of kidney origin, it could be an early marker of many other kidney diseases. To investigate this hypothesis, we first measured urine exosomal and kidney expression of CP in non-diabetic chronic kidney disease (CKD) patients (membranous nephropathy, focal segmental glomerulosclerosis, lupus nephritis and IgA nephropathy) followed by a longitudinal study in rat passive Heymann nephritis (PHN), a model of human membranous nephropathy. METHODS: Urinary exosomes were isolated from urine of patients (and rats) by differential centrifugation. The exosomal extracts were used for measuring CP using ELISA. Kidney expression of CP was evaluated by immune-staining biopsy tissues. Similar techniques were applied in rat PHN model (produced by injection of anti-gp600 antiserum) to analyze urine exosomal and kidney CP. RESULTS: Urine exosomal CP levels were 10-20 times higher in CKD patients than in controls; consistent with this we found high immune-reactive CP localized in tubules and collecting ducts of biopsies of CKD patients. In the PHN model urinary exosomal CP level was significantly higher prior to the onset of proteinuria. Early rise of urine exosomal CP, which preceded proteinuria, correlated with high immunoreactive CP found in rat kidneys at this time. CONCLUSION: We propose that urine exosomal CP, observed to increase prior to proteinuria, makes it a potential urinary biomarker to diagnose early kidney disease.

Bitter Melon Extract Promotes Granulation Tissue Growth and Angiogenesis in the Diabetic Wound.

OBJECTIVE: Bitter melon is a plant fruit that has been shown to exert a hypoglycemic effect when used systemically in patients with diabetes. This study was designed to investigate the topical effect of bitter melon on diabetic wounds using the wound chamber model in rats. DESIGN: Two bilateral wound chambers were implanted subcutaneously in the thoracic-lumbar region of male Sprague-Dawley rats. Diabetes was induced with streptozotocin 7 days after implantation of wound chambers. After 24 hours of induction of diabetes, aqueous extract of bitter melon was injected into 1 wound chamber, and saline (0.9% sodium chloride solution) was injected into the contralateral chamber once daily for 3 days. Wound fluid was collected on day 4 for analysis, following which rats were euthanized. The granulation tissue encapsulating the wound chamber was removed and processed for histology. Controls included diabetic rats with wound chambers injected with saline (instead of bitter melon) and nondiabetic rats with wound chambers injected with bitter melon. RESULTS: In rats with diabetes, wound granulation tissue treated with bitter melon was well formed, with distinct cellular layers, whereas the saline-treated granulation tissue showed a severe loss of tissue organization and blood vessels. Moreover, the bitter melon treatment increased angiogenesis in the diabetic granulation tissue, marked by abundant microvessels and large blood vessels. In nondiabetic rats, no differences in wound granulation tissues were observed between saline- and bitter melon-treated groups. Bitter melon treatment had no effect on systemic blood glucose levels or insulin receptor substrate 1, suggesting that its stimulatory effect on diabetic granulation tissue was not due to alteration of systemic blood glucose levels. CONCLUSIONS: When applied locally to diabetic wounds, bitter melon extract prevents regression of granulation tissue and blood vessels, thus accelerating and improving wound healing.

Genetic variants and cell-free hemoglobin processing in sickle cell nephropathy.

Intravascular hemolysis and hemoglobinuria are associated with sickle cell nephropathy. ApoL1 is involved in cell-free hemoglobin scavenging through association with haptoglobin-related protein. APOL1 G1/G2 variants are the strongest genetic predictors of kidney disease in the general African-American population. A single report associated APOL1 G1/G2 with sickle cell nephropathy. In 221 patients with sickle cell disease at the University of Illinois at Chicago, we replicated the finding of an association of APOL1 G1/G2 with proteinuria, specifically with urine albumin concentration (ß=1.1, P=0.003), observed an even stronger association with hemoglobinuria (OR=2.5, P=4.3×10(-6)), and also replicated the finding of an association with hemoglobinuria in 487 patients from the Walk-Treatment of Pulmonary Hypertension and Sickle cell Disease with Sildenafil Therapy study (OR=2.6, P=0.003). In 25 University of Illinois sickle cell disease patients, concentrations of urine kidney injury molecule-1 correlated with urine cell-free hemoglobin concentrations (r=0.59, P=0.002). Exposing human proximal tubular cells to increasing cell-free hemoglobin led to increasing concentrations of supernatant kidney injury molecule-1 (P=0.01), reduced viability (P=0.01) and induction of HMOX1 and SOD2. HMOX1 rs743811 associated with chronic kidney disease stage (OR=3.0, P=0.0001) in the University of Illinois cohort and end-stage renal disease (OR=10.0, P=0.0003) in the Walk-Treatment of Pulmonary Hypertension and Sickle cell Disease with Sildenafil Therapy cohort. Longer HMOX1 GT-tandem repeats (>25) were associated with lower estimated glomerular filtration rate in the University of Illinois cohort (P=0.01). Our findings point to an association of APOL1 G1/G2 with kidney disease in sickle cell disease, possibly through increased risk of hemoglobinuria, and associations of HMOX1 variants with kidney disease, possibly through reduced protection of the kidney from hemoglobin-mediated toxicity.

In Diabetic Kidney Disease Urinary Exosomes Better Represent Kidney Specific Protein Alterations Than Whole Urine.

BACKGROUND: Predicting or diagnosing underlying kidney disease by analyzing whole urine remains the mainstay of nephrology practice. However, whole urine is a poor compartment to assess many structural changes in the kidney because whole urine contains only a few proteins derived from the kidney itself. Urinary exosomes, on the other hand, which are derived from the kidney, contain proteins secreted by the kidney. We experimentally tested the hypothesis that 'urinary exosomes more faithfully represent changes in the kidney tissue than whole urine'. A direct comparison between whole urine and urine exosomal levels of two chosen kidney disease markers, gelatinase and ceruloplasmin, was carried out on diabetic kidney disease patients. METHODS: Urinary exosomes were separated from whole urine by sequential centrifugation including ultra-centrifugation. Gelatinase activity was measured using fluorosceinated gelatin as the substrate, and ceruloplasmin was measured by sandwich ELISA. A few kidney specimens from patients biopsied for atypical features were histochemically stained for validation of the biochemical results. RESULTS: We found that changes in both, gelatinase (decreased activity) and ceruloplasmin (increased levels), in the urinary exosomes of diabetic kidney patients were in agreement with the alterations of these two proteins in the kidney tissue. In contrast, the levels of these two proteins in whole urine were highly variable and did not correlate with levels in the diabetic kidney tissue. CONCLUSION: In conclusion, these results confirmed our hypothesis that protein markers in urinary exosomes better reflected the underlying protein changes in the kidney than in whole urine samples.

Activated omentum slows progression of CKD.

Stem cells show promise in the treatment of AKI but do not survive long term after injection. However, organ repair has been achieved by extending and attaching the omentum, a fatty tissue lying above the stomach containing stem cells, to various organs. To examine whether fusing the omentum to a subtotally nephrectomized kidney could slow the progression of CKD, we used two groups of rats: an experimental group undergoing 5/6 nephrectomy only and a control group undergoing 5/6 nephrectomy and complete omentectomy. Polydextran gel particles were administered intraperitoneally before suture only in the experimental group to facilitate the fusion of the omentum to the injured kidney. After 12 weeks, experimental rats exhibited omentum fused to the remnant kidney and had lower plasma creatinine and urea nitrogen levels; less glomerulosclerosis, tubulointerstitial injury, and extracellular matrix; and reduced thickening of basement membranes compared with controls. A fusion zone formed between the injured kidney and the omentum contained abundant stem cells expressing stem cell antigen-1, Wilms' tumor 1 (WT-1), and CD34, suggesting active, healing tissue. Furthermore, kidney extracts from experimental rats showed increases in expression levels of growth factors involved in renal repair, the number of proliferating cells, especially at the injured edge, the number of WT-1-positive cells in the glomeruli, and WT-1 gene expression. These results suggest that contact between the omentum and injured kidney slows the progression of CKD in the remnant organ, and this effect appears to be mediated by the presence of omental stem cells and their secretory products.

Stem cells from foreign body granulation tissue accelerate recovery from acute kidney injury.

BACKGROUND: In previous studies, we obtained mesenchymal stem cells called granulation tissue stem cells (GTSC) from a regenerating granulation tissue created by placing a foreign body in the subcutaneous tissue of rats. Here, we used GTSC to ameliorate ischemia/reperfusion-induced acute kidney injury (AKI) in rats. METHODS: In two groups of Fischer rats, we induced ischemia/reperfusion injury. Group 1 (treated rats) received one intravenous injection of GTSC 3 h after injury; Group 2 (control rats) received vehicle. Both groups were subsequently studied by renal function tests, kidney histology and immunohistochemistry. RESULTS: At 24 and 48 h after injury, plasma creatinine and blood urea nitrogen were significantly lower in the treated rats as compared to control rats. The levels remained low and declined to near baseline levels by Day 4 in the treated group. At the cortico-medullary region, the treated rats showed significantly higher renal tubular cell proliferation and less tubular cell apoptosis. Histological analysis of the kidney for tubular dilatation, necrosis, congestion and casts was not significantly different in the two groups. To understand the mechanism of the GTSC effect, messenger RNA levels of several growth and immune modulatory factors were quantified in cultured GTSC and compared with those in cultured glomerular epithelial cell (GEC; a non-stem cell line). GTSC had 2- to 8-fold higher expression of FGF2, HGF, IGF-1, vascular endothelial growth factor (growth factors) and IL-4, IL-6 (anti-inflammatory factors) than GEC. CONCLUSIONS: Administration of GTSC accelerates recovery in rats with ischemia/reperfusion-induced AKI. This effect may be mediated by the paracrine action of growth and immune-suppressive factors secreted by these cells.

Human parainfluenza virus type 3 infections in a haemato-oncology unit: social distancing measures needed in outpatient clinics.

BACKGROUND: Human parainfluenza virus type 3 (HPIV3) infections are associated with high mortality in immunocompromised settings, especially in bone marrow transplant recipients. Asymptomatic infection and lack of effective antiviral treatment makes HPIV3 prevention and treatment a real challenge. AIM: To retrospectively investigate the epidemiological characteristics, clinical characteristics and outcomes of 51 haematology patients with confirmed HPIV3 infections, detected between February and May 2019 in the haematology unit at King's College Hospital, London. METHODS: Between February and May 2019, HPIV3 RNA was detected in combined nose and throat swab samples collected from 51 symptomatic haematology patients, 41 of whom attended the haematology outpatient unit. Clinical data were reviewed retrospectively and a timeline of patients' appointments drawn up to investigate transmission. Sequencing analysis was performed on 14 stored samples. FINDINGS: Fifty-one patients were identified with HPIV3 infection. Mean age was 54 years (SD: 12; range: 19-72) and 60% (31/51) were male. There were 41 (80%) bone marrow transplant recipients, 24 had an allograft, and 17 an autograft. Thirty-day and 3-month mortality post HPIV3 was 6% and 14%, respectively. Lower respiratory tract infection and inpatient acquisition were associated with higher mortality (6/7 vs 1/7, P = 0.010; and 5/7 vs 2/7, P = 0.031). Onset of HPIV3 infection in patients within 6 days of attending the clinic was associated with the clusters identified in phylogenetic analysis (64% (9/14) vs 21% (8/37); odds ratio: 6.5 (confidence interval: 95% 1.7-25); P = 0.006). CONCLUSION: Timelines suggested community transmission, but also possible transmission patterns within the outpatients and subsequent nosocomial transmission within the same ward. Early recognition of HPIV3 infection and the use of polymerase chain reaction and sequence analysis is fundamental in identifying respiratory virus outbreaks and person-to-person transmission. Careful planning of outpatient clinic attendance is required to minimize contact and prevent respiratory virus transmission in immunosuppressed patients.

A review of tracking progress towards elimination of iodine deficiency disorders in Tamil Nadu, India.

BACKGROUND: Iodine deficiency disorders (IDD) are significant health problem in India. But there is dearth of regional/state level information for the same. OBJECTIVE: This study was designed to study the current status of IDD in Tamil Nadu. MATERIALS AND METHODS: A cross-sectional community-based survey was conducted in the state of Tamil Nadu. The study population was children in the age group of 6-12 years and the probability proportional to size 30 cluster methodology was used for sample selection. The parameters studied were prevalence of goiter, urinary iodine excretion, and iodine content in salt at the household level. RESULTS: A total of 1230 children aged between 6 and 12 years were studied. The total goiter rate was 13.5% (95% CI: 11.1-14.9). The median urinary iodine excretion was found to be 89.5 µg/L (range, 10.2-378 µg/L). The 56% of the urinary iodine excretion values were <100 µg/L. The proportion of households consuming adequately iodized salt (iodine content ≥ 15 parts per million) was 18.2% (95% CI: 16.1-20.5). CONCLUSION: The total goiter rate of 13.5% and median urinary iodine excretion of 89.5 µg/L is indicative of iodine deficiency in Tamil Nadu.

Plasma CRP levels in premenopausal women with major depression: a 12-month controlled study.

C-reactive protein (CRP), an inflammatory marker of cardiovascular risk, is often elevated in major depressive disorder (MDD). The magnitude and consistency of this elevation have not been previously characterized in premenopausal women with MDD. The aim of the study was to prospectively assess plasma CRP levels, body composition, endocrine and metabolic parameters, and depressive status in premenopausal women with MDD (n=77) and controls (n=41), aged 21 to 45. Women were enrolled in a 12-month, controlled study of bone turnover, the P.O.W.E.R. ( Premenopausal, Osteoporosis, Women, Al Endronate, Dep Ression) Study. Blood samples were taken at Baseline, Month 6, and Month 12. Most subjects with MDD were in clinical remission. These women tended to have consistently higher CRP levels than controls over 12 months (p=0.077). BMI was positively related to log[CRP] in women with MDD only. Nine women with MDD had CRP levels greater than 10 mg/l, a value associated with a very high cardiovascular risk. This subset was obese and had significantly higher triglycerides, total cholesterol, LDL-cholesterol, fasting insulin, and HOMA-IR than the rest of women with MDD. The variations in CRP levels over time were high (intra- and inter-individual coefficients of variations of approximately 30-50% and approximately 70-140%, respectively). No control had CRP levels greater than 10 mg/l. Depression was associated with increased plasma CRP in women with MDD. The clinical significance of abnormal plasma CRP for cardiovascular risk needs to be assessed in large prospective studies of women with depression.

International open trial of uniform multi-drug therapy regimen for 6 months for all types of leprosy patients: rationale, design and preliminary results.

OBJECTIVE: To describe the rationale, design and preliminary results of an open trial of 6 months uniform multi-drug therapy (U-MDT) for all types of leprosy patients assuming a cumulative relapse rate not exceeding 5% over 5 years of follow-up. METHODS: We intended to recruit 2500 patients each in multi-bacillary (MB) and pauci-bacillary (PB) groups from India (five centres) and China (two centres). Standardized clinical criteria were used to assess skin lesions in the field. RESULTS: A total of 2912 patients enrolled from November 2003 to May 2007 (India, 2746; China, 166). MB patients constituted 39% and 3% had grade 2 disability. During follow-up, 27 patients (0.9%) developed new lesions. Of these, 78% were on account of reactions. Six patients had clinically confirmed relapse. Clofazimine-related skin pigmentation was short-lived and was acceptable to patients. We analysed data for clinical status of skin lesions. About 2.9% of patients were lost to follow-up; 85.9% completed treatment, of whom 19% had inactive skin lesions. PB patients responded better than MB patients (27%vs. 6%; P < 0.001). At the end of the first (n = 2013) and second year (n = 807) of follow-up post-U-MDT, in 49% and 46% patients, lesions were inactive, respectively (59% and 57% in PB, 37% and 28% in MB; P < 0.001). CONCLUSION: U-MDT appears to be promising with respect to clinical status of skin lesions.

Author Correction: A method to generate small-scale, high-resolution sedimentary bedform architecture models representing realistic geologic facies.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Progressive glomerular and tubular damage in sickle cell trait and sickle cell anemia mouse models.

Homozygosity for the hemoglobin (Hb) S mutation (HbSS, sickle cell anemia) results in hemoglobin polymerization under hypoxic conditions leading to vaso-occlusion and hemolysis. Sickle cell anemia affects 1:500 African Americans and is a strong risk factor for kidney disease, although the mechanisms are not well understood. Heterozygous inheritance (HbAS; sickle cell trait) affects 1:10 African Americans and is associated with an increased risk for kidney disease in some reports. Using transgenic sickle mice, we investigated the histopathologic, ultrastructural, and gene expression differences with the HbS mutation. Consistent with progressive glomerular damage, we observed progressively greater urine protein concentrations (P = 0.03), glomerular hypertrophy (P = 0.002), and glomerular cellularity (P = 0.01) in HbAA, HbAS, and HbSS mice, respectively. Ultrastructural studies demonstrated progressive podocyte foot process effacement, glomerular basement membrane thickening with reduplication, and tubular villous atrophy with the HbS mutation. Gene expression studies highlighted the differential expression of several genes involved in prostaglandin metabolism (AKR1C18), heme and iron metabolism (HbA-A2, HMOX1, SCL25A37), electrolyte balance (SLC4A1, AQP6), immunity (RSAD2, C3, UBE2O), fatty acid metabolism (FASN), hypoxia hall-mark genes (GCK, SDC3, VEGFA, ETS1, CP, BCL2), as well as genes implicated in other forms of kidney disease (PODXL, ELMO1, FRMD3, MYH9, APOA1). Pathway analysis highlighted increased gene enrichment in focal adhesion, extracellular matrix-receptor interaction, and axon guidance pathways. In summary, using transgenic sickle mice, we observed that inheritance of the HbS mutation is associated with glomerular and tubular damage and identified several candidate genes and pathways for future investigation in sickle cell trait and sickle cell anemia-related kidney disease.

Sustainable leprosy related disability care within integrated general health services: findings from Salem District, India.

The main focus of leprosy control has been case detection and treatment delivery with relative neglect of prevention of disability. Absence of reliable data and lack of research have added to the problem. This raised concerns about the capacity of the general health system to address the needs of people living with leprosy-related disabilities. In this prospective study appropriate services for people living with leprosy-related disabilities were introduced in the form of self-care training, guidance and monitoring by the general health staff facilitated by a non-governmental organisation leprosy centre in a district in south India with a population of 3.1 million (estimated in 2005). The staff identified 1232 people with leprosy-related disabilities and trained them in self-care. Follow-up assessments indicated that 86% were found to be practising self-care regularly and all the 239 general health workers were found to be actively involved. The most heartening outcome was the healing of plantar ulcers in 70% of people at the 1-year follow up. This intervention is sustainable because of the simplicity of the procedures and the involvement of all health staff including supervisors.

A method to generate small-scale, high-resolution sedimentary bedform architecture models representing realistic geologic facies.

Small-scale (mm to m) sedimentary structures (e.g. ripple lamination, cross-bedding) have received a great deal of attention in sedimentary geology. The influence of depositional heterogeneity on subsurface fluid flow is now widely recognized, but incorporating these features in physically-rational bedform models at various scales remains problematic. The current investigation expands the capability of an existing set of open-source codes, allowing generation of high-resolution 3D bedform architecture models. The implemented modifications enable the generation of 3D digital models consisting of laminae and matrix (binary field) with characteristic depositional architecture. The binary model is then populated with petrophysical properties using a textural approach for additional analysis such as statistical characterization, property upscaling, and single and multiphase fluid flow simulation. One example binary model with corresponding threshold capillary pressure field and the scripts used to generate them are provided, but the approach can be used to generate dozens of previously documented common facies models and a variety of property assignments. An application using the example model is presented simulating buoyant fluid (CO2) migration and resulting saturation distribution.

Repeated sputum microscopy is not essential for monitoring tuberculosis treatment response.

SETTING: This study was conducted in two districts in India where DOTS has been implemented. There are 39 microscopy centres in Anantpur district and 34 in Nellore district (one per 100,000 population), each with a trained microscopist. Periodic follow-up sputum microscopy is performed for all tuberculosis (TB) patients on treatment, with two sputum specimens examined on each follow-up. Results are recorded in a laboratory register. OBJECTIVE: To determine whether examining two sputum specimens for follow-up is useful for assessing treatment outcome. DESIGN: A retrospective study using data from laboratory registers of all microscopy centres for 2002 in Anantpur and 2003 (January-June) in Nellore. RESULTS: Of 5086 follow-up examinations done in Anantpur and 1028 in Nellore, 8% were acid-fast bacilli positive. One additional positive result was obtained on examination of a second sputum specimen. This result did not significantly add to the assessment of treatment outcome. CONCLUSION: The yield of a second on-the-spot sputum specimen is negligible, provided that the first smear is from an overnight specimen. From the data available, it is evident that repeated follow-up smears are not essential for documenting treatment outcome.

Trends in new case-detection leprosy in Bihar, India.

Multi-drug therapy (MDT) has been successfully implemented in all leprosy endemic countries. Prevalence of leprosy has declined remarkably after the introduction of MDT. Detection of new cases did not show expected decline in many endemic and low endemic situations. Bihar in India started implementing MDT in 1993. The Damien Foundation India Trust (DFIT) supported the leprosy control programme in Bihar by providing a district technical support team (DTST) for each district assigned to DFIT. Effective coverage was achieved in 1996-98. Data for the period 1996-2004 from 10 districts are presented in this paper. The total population in these districts was 29.4 million. Deformity among newly detected leprosy patients declined to 1% indicating effective early case-detection. Intensive new case-detection activities were in vogue contributing to high new case-detection rate (NCDR). The NCDR remained high during the 9-year period reported here and did not show any declining trend.

Community prevalence of hepatitis B infection and modes of transmission in Tamil Nadu, India.

BACKGROUND AND OBJECTIVE: There have been very few community based studies on prevalence of hepatitis B virus (HBV) infection in India. We undertook this study to determine the prevalence of HBV infection in a southern State of India, Tamil Nadu and to describe the important factors related to transmission of the virus in the community. METHODS: Analysis of stored blood samples from a representative population of Tamil Nadu from an earlier community cluster survey on sexually transmitted diseases (STD) prevalence using proportionate to population size (PPS) technique was done. Serum markers of HBV viz., hapatitis B surface antigen (HBsAg), hepatitis B e antigen (HBe Ag) and antibody to surface antigen (anti-HBs) were performed. RESULTS: 1981 subjects were screened in the study. HBsAg prevalence was 5.7 per cent (CI 4.6- 6.8) with 23.5 per cent (25/106) of these having positive HBe-antigen. Community seroprevalence (HbsAg + anti-HBs) of hepatitis B infection was 27.4 per cent (CI: 25.3-29.5) with the highest prevalence of 32.7 per cent (CI: 30.2-35.2) noted in the 15-20 yr age group. Significant independent association (OR 1.4; P=0.006) was detected with family history of exposure to HBV infection by logistic modeling. Other risk factors noted to have significant association were use of disposable needles during injection (OR 0.5; P=0.02) in men, smoking (OR 3; P=0.04) and use of condom (OR 0.6; P=0.08) in women. INTERPRETATION AND CONCLUSION: This community based study shows a high prevalence of hepatitis B infection in the state of Tamil Nadu with the highest prevalence being in the younger (15-20 yr) age group. High prevalence rate in childhood with e-antigenemia seen in 23.5 per cent of HBsAg positive subjects suggest childhood transmission. Poor injection practices and high-risk sexual behavior were found to be additional risk factors for transmission of the disease in the community.