TB prevalence among patients with diabetes in Bangladesh.

OBJECTIVE: 1) To assess the prevalence of TB among patients with diabetes mellitus (DM) attending diabetic care centres in Bangladesh, and 2) to compare TB- and DM-related sociodemographic and other factors in diabetic patients who had TB and those who did not.METHODS: This cross-sectional study was conducted from 1 June 2019 to 31 March 2020 in 108 centres of the Diabetic Association of Bangladesh (BADAS), with a sample size of 3,649 patients with DM. Data were collected by face-to-face interview using semi-structured questionnaire from each patient/guardian. Other ethical issues were also maintained.RESULTS: Out of 3,649 patients with DM, 676 presumptive TB cases were identified and tested; from them, 85 patients were detected as TB cases. Another 39 patients were already diagnosed and on anti-TB medication. Prevalence of TB among patients with DM attending diabetic care centres was 3.4%. Prevalence was higher in female than male (4.0% vs 2.6%). Underweight (9.0%) patients and patients having diabetes for more than 10 years (7.1%) had a higher prevalence of TB.CONCLUSION: TB prevalence was over 3% among study population with DM. Periodic screening and active case finding among DM patients should be strengthened to reduce the risk of TB infection among DM patients.

Mucosal correlates of isolated HIV semen shedding during effective antiretroviral therapy.

Effective antiretroviral therapy (ART) suppresses the blood HIV RNA viral load (VL) below the level of detection. However, some individuals intermittently shed HIV RNA in semen despite suppression of viremia, a phenomenon termed "isolated HIV semen shedding (IHS)". In a previously reported clinical study, we collected blood and semen samples from HIV-infected men for 6 months after ART initiation, and documented IHS at ≥1 visit in almost half of the participants, independent of ART regimen or semen drug levels. We now report the mucosal immune associations of IHS in these men. Blood and semen plasma cytokine levels were assayed by multiplex enzyme-linked immunosorbent assay, T-cell populations were evaluated by flow cytometry in freshly isolated blood and semen mononuclear cells, and semen cytomegalovirus (CMV) DNA levels were measured by PCR. Although IHS was not associated with altered blood or semen cytokine levels, the phenomenon was associated with a transient, dramatic increase in CD4+ and CD8+ T-cell activation that was restricted to the semen compartment. All participants were CMV infected, and although semen CMV reactivation was common despite ART, this was not associated with T-cell activation or IHS. Further elucidation of the causes of compartmentalized mucosal T-cell activation and IHS may have important public health implications.

Immune reconstitution in the sigmoid colon after long-term HIV therapy.

Early and profound CD4+ T-cell depletion in gut-associated lymphoid tissue (GALT) may drive Human Immunodeficiency Virus (HIV) immunopathogenesis, and GALT immune reconstitution on highly active antiretroviral therapy (HAART) may be suboptimal. Blood and sigmoid colon biopsies were collected from HAART-treated individuals with undetectable blood HIV RNA for > or =4 years and from uninfected controls. HIV proviral levels and T-cell phenotype/function were examined in both compartments. CD4+ T-cell reconstitution in the sigmoid, including CD4+ T cells expressing CCR5, exceeded that in blood and did not differ from uninfected controls. Sigmoid HIV proviral load was not correlated with CD4+ reconsitution, but was correlated with the degree of mucosal CD8+ T-cell immune activation. Colonic Gag-specific T-cell responses were common, but were not associated with proviral load or immune activation. In this select study population, long-term HAART was associated with complete CD4+ T-cell reconstitution in sigmoid colon. However, colonic immune activation may drive ongoing HIV replication.

Cellular localization of interleukin 13 receptor alpha2 in human primary bronchial epithelial cells and fibroblasts.

BACKGROUND: Interleukin (IL) 13 is a key cytokine in asthma, regulating fibrosis, airway remodeling, induction of immunoglobulin E synthesis by B cells, bronchial hyperresponsiveness, and mucus production. IL-13 signals through the type II IL-4 receptor (IL-4R), which is composed of the IL-4Ralpha and the IL-13Ralpha1 chains. Another IL-13 binding chain, IL-13Ralpha2, binds IL-13 with high affinity but has no known signaling capability and is thought to serve as a decoy receptor providing tight regulation of IL-13 responses. METHODS: In this study, we investigated the cellular localization of IL-13Ralpha2 in human primary bronchial epithelial cells and fibroblasts using flow cytometry and confocal microscopy, as well as the in vivo expression of IL-13Ralpha2 in the human bronchial mucosa by means of immunohistochemistry. RESULTS: IL-13Ralpha2 is predominantly an intracellular rather than a membrane-bound molecule in both human primary bronchial epithelial cells and fibroblasts and displays a diffuse granular cytoplasmic distribution in both cell types. IL-13Ralpha2 protein is expressed in vivo in the human bronchial mucosa with its expression being higher in bronchial epithelial cells than bronchial fibroblasts both in vivo and in vitro. CONCLUSIONS: IL-13Ralpha2 is expressed by both human primary bronchial epithelial cells and fibroblasts as an intracellular protein with a diffuse cytoplasmic distribution. In vivo, IL-13Ralpha2 is expressed in the human airway mucosa mainly by bronchial epithelial cells.

The genital tract immune milieu: an important determinant of HIV susceptibility and secondary transmission.

HIV is generally sexually acquired across the genital or rectal mucosa after exposure to the genital secretions of an HIV-infected partner. Most exposures to HIV do not result in infection, likely due to protection afforded by an intact mucosal epithelium, as well as by innate and adaptive mucosal immune factors present in the genital tract. Another important mucosal determinant of transmission may be the number and activation status of potential HIV target cells, including CCR5/CD4+ T cells and DC-SIGN+ dendritic cells. The simultaneous presence of other genital infections, including classical sexually transmitted infections (STIs), can enhance HIV susceptibility either by breaching the epithelial barrier, recruiting HIV target cells to the genital tract, or by generating a pro-inflammatory local immune milieu. In HIV-infected individuals, genital co-infections increase HIV levels in the genital secretions, thereby increasing secondary sexual transmission. Co-infections that act as important HIV cofactors include human cytomegalovirus (CMV), Herpes simplex virus type 2 (HSV2), Neisseria gonorrhoeae and many others. Strategies focused on genital co-infections, such as vaccines, microbicides and suppressive therapy, are feasible in the short term and have the potential to curb the pandemic.

Lipopolysaccharide disrupts tight junctions in cholangiocyte monolayers by a c-Src-, TLR4-, and LBP-dependent mechanism.

Bile duct epithelium forms a barrier to the backflow of bile into the liver parenchyma. However, the structure and regulation of the tight junctions in bile duct epithelium is not well understood. In the present study, we evaluated the effect of lipopolysaccharide on tight junction integrity and barrier function in normal rat cholangiocyte monolayers. Lipopolysaccharide disrupts barrier function and increases paracellular permeability in a time- and dose-dependent manner. Lipopolysaccharide induced a redistribution of tight junction proteins, occludin, claudin-1, claudin-4, and zonula occludens (ZO)-1 from the intercellular junctions and reduced the level of ZO-1. Tyrosine kinase inhibitors (genistein and PP2) prevented lipopolysaccharide-induced increase in permeability and subcellular redistribution of ZO-1. Reduced expression of c-Src, TLR4, or LBP by specific small interfering RNA attenuated lipopolysaccharide-induced permeability and redistribution of ZO-1. ML-7, a myosin light chain kinase inhibitor, attenuated LPS-induced permeability. Lipopolysaccharide treatment rapidly increased the phosphorylation of occludin and ZO-1 on tyrosine residues, which was prevented by genistein and PP2. Occludin and ZO-1 were found to be highly phosphorylated on threonine residues in intact cell monolayers. Threonine-phosphorylation of occludin was rapidly reduced by lipopolysaccharide administration. Lipopolysaccharide-induced dephosphorylation of occludin on Thr residues was prevented by genistein and PP2. In conclusion, lipopolysaccharide disrupts the tight junction of a bile duct epithelial monolayer by a c-Src-, TLR4-, LBP-, and myosin light chain kinase-dependent mechanism.

Virtual slope control of a forward dynamic bipedal walker.

Active joint torques are the primary source of power and control in dynamic walking motion. However the amplitude, rate, timing and phasic behavior of the joint torques necessary to achieve a natural and stable performance are difficult to establish. The goal of this study was to demonstrate the feasibility and stable behavior of an actively controlled bipedal walking simulation wherein the natural system dynamics were preserved by an active, nonlinear, state-feedback controller patterned after passive downhill walking. A two degree-of-freedom, forward-dynamic simulation was implemented with active joint torques applied at the hip joints and stance leg ankle. Kinematic trajectories produced by the active walker were similar to passive dynamic walking with active joint torques influenced by prescribed walking velocity. The control resulted in stable steady-state gait patterns, i.e. eigenvalue magnitudes of the stride function were less than one. The controller coefficient analogous to the virtual slope was modified to successfully control average walking velocity. Furture developments are necessary to expand the range of walking velocities.

Acetaldehyde disrupts tight junctions and adherens junctions in human colonic mucosa: protection by EGF and L-glutamine.

Acetaldehyde, a toxic metabolite of ethanol oxidation, is suggested to play a role in the increased risk for gastrointestinal cancers in alcoholics. In the present study, the effect of acetaldehyde on tyrosine phosphorylation, immunofluorescence localization, and detergent-insoluble fractions of the tight junction and the adherens junction proteins was determined in the human colonic mucosa. The role of EGF and L-glutamine in prevention of acetaldehyde-induced effects was also evaluated. Acetaldehyde reduced the protein tyrosine phosphatase activity, thereby increasing the tyrosine phosphorylation of occludin, E-cadherin, and beta-catenin. The levels of occludin, zonula occludens-1, E-cadherin, and beta-catenin in detergent-insoluble fractions were reduced by acetaldehyde, while it increased their levels in detergent-soluble fractions. Pretreatment with EGF or L-glutamine prevented acetaldehyde-induced protein tyrosine phosphorylation, redistribution from intercellular junctions, and reduction in the levels of detergent-insoluble fractions of occludin, zonula occludens-1, E-cadherin, and beta-catenin. These results demonstrate that acetaldehyde induces tyrosine phosphorylation and disrupts tight junction and adherens junction in human colonic mucosa, which can be prevented by EGF and glutamine.

L-Glutamine ameliorates acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer.

Role of L-glutamine in the protection of intestinal epithelium from acetaldehyde-induced disruption of barrier function was evaluated in Caco-2 cell monolayer. L-Glutamine reduced the acetaldehyde-induced decrease in transepithelilal electrical resistance and increase in permeability to inulin and lipopolysaccharide in a time- and dose-dependent manner; d-glutamine, L-aspargine, L-arginine, L-lysine, or L-alanine produced no significant protection. The glutaminase inhibitor 6-diazo-5-oxo-L-norleucine failed to affect the L-glutamine-mediated protection of barrier function. L-Glutamine reduced the acetaldehyde-induced redistribution of occludin, zonula occludens-1 (ZO-1), E-cadherin, and beta-catenin from the intercellular junctions. Acetaldehyde dissociates occludin, ZO-1, E-cadherin, and beta-catenin from the actin cytoskeleton, and this effect was reduced by L-glutamine. L-Glutamine induced a rapid increase in the tyrosine phosphorylation of EGF receptor, and the protective effect of L-glutamine was prevented by AG1478, the EGF-receptor tyrosine kinase inhibitor. These results indicate that L-glutamine prevents acetaldehyde-induced disruption of the tight junction and increase in the paracellular permeability in Caco-2 cell monolayer by an EGF receptor-dependent mechanism.

Recent Advances in Alcoholic Liver Disease I. Role of intestinal permeability and endotoxemia in alcoholic liver disease.

A significant body of evidence indicates that endotoxemia and endotoxin-mediated hepatocellular damage play a crucial role in the pathogenesis of alcoholic liver disease. A close correlation between endotoxemia and the severity of alcohol-induced liver injury is supported by a number of clinical and experimental studies. Elevated intestinal permeability appears to be the major factor involved in the mechanism of alcoholic endotoxemia and the pathogenesis of alcoholic liver disease. Ethanol and its metabolic derivatives, acetaldehyde in particular, alter intracellular signal-transduction pathways leading to the disruption of epithelial tight junctions and an increase in paracellular permeability to macromolecules. Studies addressing the mechanisms of such epithelial disruption and the protective factors that prevent ethanol and acetaldehyde-mediated disruption of epithelial tight junctions are critically important in the investigations toward the search of preventive and therapeutic strategies for alcoholic liver disease.

Epidermal growth factor prevents acetaldehyde-induced paracellular permeability in Caco-2 cell monolayer.

BACKGROUND: Intestinal permeability and endotoxemia play a crucial role in the pathogenesis of alcoholic liver disease. Previous studies showed that acetaldehyde disrupts intestinal epithelial barrier function and increases paracellular permeability by a tyrosine kinase-dependent mechanism. In the present study, the role of epidermal growth factor (EGF) in protection of epithelial barrier function from acetaldehyde was evaluated in Caco-2 intestinal epithelial cell monolayer. METHODS: Caco-2 cells on Transwell inserts were exposed to acetaldehyde in the absence or presence of EGF, and the paracellular permeability was evaluated by measuring transepithelial electrical resistance and unidirectional flux of inulin. Integrity of epithelial tight junctions and adherens junctions was analyzed by confocal immunofluorescence microscopy and immunoblot analysis of occludin, zonula occludens (ZO)-1, E-cadherin, and beta-catenin in the actin cytoskeleton. Reorganization of actin cytoskeletal architecture was examined by confocal microscopy. RESULTS: Acetaldehyde increased paracellular permeability to inulin and lipopolysaccharide, and EGF significantly reduced these effects of acetaldehyde in a time- and dose-dependent manner. EGF prevented acetaldehyde-induced reorganization of occludin, ZO-1, E-cadherin, and beta-catenin from the cellular junctions to the intracellular compartments. Acetaldehyde treatment induced a reorganization of actin cytoskeletal network and reduced the levels of occludin, ZO-1, E-cadherin, and beta-catenin associated with the actin cytoskeleton. EGF effectively prevented acetaldehyde-induced reorganization of actin cytoskeleton and the interaction of occludin, ZO-1, E-cadherin, and beta-catenin with the actin cytoskeleton. CONCLUSION: These results indicate that EGF attenuates acetaldehyde-induced disruption of tight junctions and adherens junctions and prevents acetaldehyde-induced reorganization of actin cytoskeleton and its interaction with occludin, ZO-1, E-cadherin, and beta-catenin.

Novel treatment of chronic severe hand dermatitis with bexarotene gel.

BACKGROUND: Hand dermatitis is an eczematous inflammation of the hands that is related to occupation or to routine activities. It often becomes chronic, and in some patients may become severe and disabling. Topical corticosteroids are effective treatment, particularly for milder forms, but they often lose effectiveness with time and can produce skin atrophy. OBJECTIVES: To evaluate bexarotene gel topical therapy for safety, tolerability and efficacy in patients with chronic hand dermatitis. METHODS: A phase I-II open-label randomized clinical study of bexarotene gel, alone and in combination with a low- and a mid-potency steroid, was conducted in 55 patients with chronic severe hand dermatitis at two academic clinics. RESULTS: Patients using bexarotene gel monotherapy reached a 79% response rate for > or = 50% clinical improvement and a 39% response rate for > or = 90% clearance of hands. Adverse events possibly related to treatment in all patients were stinging or burning (15%), flare of dermatitis (16%) and irritation (29%). Thirteen patients (24%) withdrew early, including two for related adverse events and five for inadequate response. CONCLUSIONS: Bexarotene gel appears to be safe, tolerated by most patients, with useful therapeutic activity in chronic severe hand dermatitis.

Passive derivation of basic walker-assisted gait characteristics from measured forces and moments.

This work describes a method that passively assesses basic walker-assisted gait characteristic, including heel strikes, toe-off events, as well as stride time, double support and right & left single support phases using only force-moment measurements from the walker's handles. The passively derived gait characteristics were validated against motion capture gait analysis and showed good correlations. This research is part of an effort that aims to identify user intent, from measuring forces and moments exerted on the handles of the walker as well as from perceiving the environment, and to incorporate identified intent into a passive shared steering control system for the walker. The primary focus of the work leading to This work is to identify the double support phase, and to engage the steering control at the beginning of this phase to maximize the user's stability. However, the application of the method presented and the instrumented walker can be extended to longitudinal outside the lab Gait assessment.

Tyrosine phosphorylation of occludin attenuates its interactions with ZO-1, ZO-2, and ZO-3.

Occludin, the transmembrane integral protein of the tight junction, plays a crucial role in the molecular organization and function of tight junction. While the homotypic interaction of extracellular loops of occludin appears to determine the barrier function of tight junction, the intracellular C-terminal tail, C-occludin, interacts with other tight junction proteins such as ZO-1, ZO-2, and ZO-3 and with the actin filaments of cytoskeleton. In the present study we phosphorylated GST-fused C-occludin on tyrosine residues, in TKX1 Epicurian coli or by active c-Src in vitro. c-Src binds to occludin and phosphorylates it on tyrosine residues. The effect of tyrosine phosphorylation of C-occludin on its ability to bind ZO-1, ZO-2, ZO-3, and F-actin was evaluated. Results show that the amounts of ZO-1, ZO-2, and ZO-3 bound to tyrosine phosphorylated C-occludin were several fold less than the amounts bound to non-phosphorylated C-occludin. However, the amount of tyrosine phosphorylated C-occludin bound to F-actin was not significantly different from the amount of non-phosphorylated C-occludin bound to F-actin. These results demonstrate that tyrosine phosphorylation of occludin reduces its ability to bind ZO-1, ZO-2, and ZO-3, but not F-actin. Results also suggest that c-Src-mediated disruption of tight junction may involve tyrosine phosphorylation of occludin.

Platelets from patients with the Quebec platelet disorder contain and secrete abnormal amounts of urokinase-type plasminogen activator.

The Quebec platelet disorder (QPD) is an autosomal dominant platelet disorder associated with delayed bleeding and alpha-granule protein degradation. The degradation of alpha-granule, but not plasma, fibrinogen in patients with the QPD led to the investigation of their platelets for a protease defect. Unlike normal platelets, QPD platelets contained large amounts of fibrinolytic serine proteases that had properties of plasminogen activators. Western blot analysis, zymography, and immunodepletion experiments indicated this was because QPD platelets contained large amounts of urokinase-type plasminogen activator (u-PA) within a secretory compartment. u-PA antigen was not increased in all QPD plasmas, whereas it was increased more than 100-fold in QPD platelets (P <.00009), which contained increased u-PA messenger RNA. Although QPD platelets contained 2-fold more plasminogen activator inhibitor 1 (PAI-1) (P <.0008) and 100-fold greater u-PA-PAI-1 complexes (P <.0002) than normal platelets, they contained excess u-PA activity, predominantly in the form of two chain (tcu-PA), which required additional PAI-1 for full inhibition. There was associated proteolysis of plasminogen in QPD platelets, to forms that comigrated with plasmin. When similar amounts of tcu-PA were incubated with normal platelet secretory proteins, many alpha-granule proteins were proteolyzed to forms that resembled degraded QPD platelet proteins. These data implicate u-PA in the pathogenesis of alpha-granule protein degradation in the QPD. Although patients with the QPD have normal to increased u-PA levels in their plasma, without evidence of systemic fibrinogenolysis, their increased platelet u-PA could contribute to bleeding by accelerating fibrinolysis within the hemostatic plug. QPD is the only inherited bleeding disorder in humans known to be associated with increased u-PA.

'VIT1', a novel gene associated with vitiligo.

To define genes associated with the pigmentary disorder vitiligo, gene expression was compared in non-lesional melanocytes cultured from three vitiligo patients and from three control melanocyte cultures by differential display. A basic local alignment search tool search did not reveal homology of six differentially expressed cDNA fragments to previously identified expressed sequence tags; thus, one was used to screen a melanocyte cDNA library. The underlying VIT1 gene maps to chromosome 2p16. The 3' portion of the VIT1 message is complementary to the 3' end of hMSH6 mRNA, enabling the formation of RNA-RNA hybrids, which may interfere with G/T mismatch repair function. Moreover, the aligned cDNA sequence revealed an open reading frame identical to a hypothetical protein expressed in brain, with a similarity to Drosophila calmodulin, and containing a zinc-finger motif partially identical to N-recognin. Expression of ORF mRNA was confirmed for multiple skin cell types, suggesting its importance for skin physiology.

PIG3V, an immortalized human vitiligo melanocyte cell line, expresses dilated endoplasmic reticulum.

Vitiligo is an enigmatic pigmentary disorder of the skin. Factors potentially involved in the progressive loss of melanocytes from the basal layer of the epidermis include genetically determined aberrancies of the vitiligo melanocyte. It follows that analysis of melanocytes cultured from vitiligo donors can contribute to a further understanding of the etiopathomechanism. A setback for vitiligo research has been the limited availability of vitiligo-derived melanocytes. To overcome this limitation, we have generated a vitiligo melanocyte cell line according to a protocol established previously for the immortalization of normal human melanocytes. Vitiligo melanocytes Ma9308P4 were transfected with HPV16 E6 and E7 genes using the retroviral construct LXSN16E6E7. Successful transformants were selected using geneticin and subsequently cloned to ensure genetic homogeneity. The resulting cell line PIG3V has undergone more than 100 cell population doublings since its establishment as a confluent primary culture, whereas untransfected melanocytes derived from adult skin senesce after a maximum of 50 population doublings. Cells immortalized by this transfection procedure retain lineage-specific characteristics and proliferate significantly faster than parental cells. In this study, the phenotype of PIG3V resembled melanocytes rather than melanoma cells in culture. Tyrosinase was processed properly and melanosomes remained pigmented. Importantly, ultrastructural characterization of PIG3V cells revealed dilated endoplasmic reticulum profiles characteristic of vitiligo melanocytes. An explanation for this dilation may be found in the retention of proteins with molecular weight of 37.5. 47.5, and 56.5 kDa, as determined by gel electrophoresis of microsomal proteins isolated from radiolabeled cells.

Osteoporosis and exercise: a review.

BACKGROUND: Osteoporosis is a widespread bone disorder which primarily effects postmenopausal women, with annual costs of six billion dollars. Several studies have looked at the potential value of exercise as an inexpensive and widely available treatment. METHODS: Using Medline, English-language articles published after 1989 in major medical journals and containing the key words 'exercise' and 'osteoporosis' were obtained. Selected prospective studies which included twenty or more subjects were reviewed with special attention to the exercise portion of the protocol. Studies felt to be historically important were also reviewed. RESULTS: Quality of studies, design types and exercise intervention varied greatly. Detailed exercise protocols, high compliance rates and low drop-out rates appeared to favorably effect results. CONCLUSION: As a whole, the literature suggests that exercise induced improvement in bone mineral density in select individuals. Based on the review the author suggests an ideal program.

Seroprevalence of hepatitis A virus in Mumbai, and immunogenicity and safety of hepatitis A vaccine.

OBJECTIVES: Since epidemiologic trends of hepatitis A are changing worldwide, we studied its seroprevalence in Mumbai, which is thought to be a high-endemicity area. The immunogenicity and safety of a hepatitis A vaccine were also studied. METHODS: Six hundred and seventy subjects (456 men; age range 6 mo-60 y) answered a questionnaire on social and medical history. Qualitative analysis of total anti-HAV was performed in all subjects by ELISA. One hundred and seven of 147 anti-HAV negative subjects received hepatitis A vaccine at months 0, 1 and 6. Subjects were followed up (months 1, 2, 6, 7) to look for side-effects and seroconversion. RESULTS: The seroprevalence of HAV was 523/670 (78%); 38% of children < 5 years were anti-HAV negative. Seroprevalence rates of 80% were reached by 15 years. Prevalence was lower in the higher socio-economic group (151/234; 64.5%) compared with the lower socio-economic group (372/436; 85%) (p < 0.001). One month after doses 1, 2 and 3 of the hepatitis A vaccine, seropositivity was 92%, 99% and 100%, respectively. Minor self-limited side-effects occurred in 19.5% of subjects; there were no major side-effects. CONCLUSIONS: The seroprevalence of anti-HAV is high in Mumbai. Seroprevalence is lower in the higher socio-economic groups. The hepatitis A vaccine is safe and immunogenic.

PIP: Prevention of hepatitis A virus (HAV) can be achieved through improved hygiene and living conditions, access to clean drinking water, and passive and active immunization. The present study assessed the age-related seroprevalence of HAV in Mumbai, India, in 1995-96 and the immunogenicity and safety of a newly developed inactivated HAV vaccine. 670 children and adults were recruited from 2 sites: a private hospital serving a predominantly middle- and upper-class population and a public hospital with low-income patients. Overall, 523 subjects (78%) were positive for anti-HAV. This rate was higher among low-income patients (85.3%) than those of higher socioeconomic status (64.5%). 38% of children under 5 years of age and 80% of those 11-15 years old were seropositive. 107 patients seronegative for anti-HAV were offered the vaccine. Anti-HAV antibody appeared 1 month after the first injection in 92.4% of vaccine recipients and 1 month after the second injection in 99%. Side effects were mild and self-limited. These findings confirm both the safety and the immunogenicity of the inactivated hepatitis A vaccine in high endemicity areas. However, universal immunization remains too costly in India. Further epidemiologic studies are needed to identify specific risk groups and regions that should be targeted for hepatitis A vaccine.