India has a higher tuberculosis (TB) burden than any other country, accounting for an estimated one-fourth of the global burden. Drug-resistant tuberculosis (DR-TB) presents a major public health problem in India. Patients with DR-TB often require profound changes in their drug regimens, which are invariably linked to poor treatment adherence and sub-optimal treatment outcomes compared to drug-sensitive TB. The challenge of addressing DR-TB is critical for India, as India contributes over 27% of global DR-TB cases. In recent decades, India has been proactive in its battle against TB, even implementing a revised National Strategic Plan to eliminate TB by 2025. However, to achieve this ambitious goal, the country will need to take a multifaceted approach with respect to its management of DR-TB. Despite concerted efforts made by the National TB Elimination Program, India faces substantial challenges with regard to DR-TB care, especially in peripheral and resource-limited endemic zones. This article describes some of the major challenges associated with mitigating the growing DR-TB epidemic in India and their implications.

India has a higher tuberculosis (TB) burden than any other country, accounting for an estimated one-fourth of the global burden. Drug-resistant tuberculosis (DR-TB) presents a major public health problem in India. Patients with DR-TB often require profound changes in their drug regimens, which are invariably linked to poor treatment adherence and sub-optimal treatment outcomes compared to drug-sensitive TB. The challenge of addressing DR-TB is critical for India, as India contributes over 27% of global DR-TB cases. In recent decades, India has been proactive in its battle against TB, even implementing a revised National Strategic Plan to eliminate TB by 2025. However, to achieve this ambitious goal, the country will need to take a multifaceted approach with respect to its management of DR-TB. Despite concerted efforts made by the National TB Elimination Program, India faces substantial challenges with regard to DR-TB care, especially in peripheral and resource-limited endemic zones. This article describes some of the major challenges associated with mitigating the growing DR-TB epidemic in India and their implications.

Background: Varicella has been known to be a harmless childhood disease. However, it hasbeen reported that severe complications have taken place following Varicella infection, in bothimmunocompetent, as well as immunocompromised, individuals. Cutaneous complications ofVaricella may manifest as preseptal cellulitis, albeit rarely.Report: We present a case of a 4-year-old boy who presented with symptoms and signs ofpreseptal cellulitis following Varicella infection. He was referred to the otorhinolaryngologyteam for a nasoendoscopy to rule out sinusitis, in view of the fear that a child presentingwith a swollen red eye may be a case of true orbital cellulitis. He was treated successfully withintravenous antibiotics and surgical drainage of the preseptal collection.Conclusion: It is imperative for clinicians to be aware that a simple Varicella infection may leadto cutaneous complications in the pediatric age group, especially in children who are 4 yearsand younger. They may develop preseptal cellulitis, whose presentation might mimic that oforbital cellulitis. Empirical treatment with antibiotics would be advantageous for the patient. Anasoendoscopic examination may also be warranted in these cases to rule out sinusitis as a causeof orbital cellulitis.

PURPOSE: In the present study, the protective immunological markers in serum and peripheral blood mononuclear cells (PBMCs) of bacillus Calmette-Guerin (BCG) vaccinated and unvaccinated children were evaluated after vaccination. Further, PBMCs of children with low protective levels were boosted with BCG, Ag85B, and Ag85B peptides to study their booster effects to increase waning BCG induced immunity. MATERIALS AND METHODS: Fifty children from 1 month to 18 years of age were randomized for the study. Blood samples were collected from 27 participants with/without BCG vaccination. Immunological markers (anti-BCG, interferon gamma [IFN-gamma], and adenosine deaminase activity) were assessed in both serum and PBMCs of children. Children with low levels of protective immunological markers were further recruited and their PBMCs were boosted with BCG, Ag85B, and Ag85B peptides. RESULTS: Children in age group of 4-6 years were associated with significantly (p<0.05) higher BCG-specific IgG and IFN-gamma levels compared to those in age group greater than 10 years. Vaccinated children had greater repertoire of immunological memory which on in vitro stimulation with BCG showed increase in BCG-specific response compared to unvaccinated controls. Assessment of booster effects of BCG, Ag85B, and Ag85B peptides in PBMCs of children revealed greater potential of peptides to boost BCG induced immunity compared to BCG and Ag85B. CONCLUSION: To conclude, children within age 4-6 years are associated with high immunological markers which eventually diminish with age thereby suggesting need for booster dose in later years. Mycobacterium tuberculosis peptides along with BCG may be used as attractive candidates to boost such waning BCG induced immunity in children.
Adenosine Deaminase ; Bacillus ; BCG Vaccine ; Child* ; Humans ; Immunoglobulin G ; Immunologic Memory ; Interferon-gamma ; Interferons ; Mycobacterium bovis* ; Mycobacterium tuberculosis ; Peptides* ; Vaccination

Smoking has been positively associated with hearing loss in human. However, its effect on the cochlea has not been previously evaluated. Aim of work is to investigate the effect of nicotine, which is the primary pharmacological component of tobacco, on the structure of the cochlea of adult male guinea pigs. Fifteen male guinea pigs were classified into two groups: group I (control) and group II (nicotine treated group). Group II was further subdivided into two subgroups; IIA and IIB according to the dose of nicotine (3 mg/kg and 6 mg/kg, respectively). The cochlea was harvested and processed for light microscopy, transmission electron microscopy and scanning electron microscopy. Nicotine administration induced damage of outer hair cells which were distorted in shape with vacuolated cytoplasm and heterochromatic nuclei. Topography revealed damage of the stereocilia which included disorganization, bent and limp or complete loss and expansion of the surrounding supporting cells. These changes were more pronounced in the basal turn of the cochlea and mainly involved the outer hair cells. High dose induced more damage and resulted in protrusion of the apical poles of hair cells (blebing), particularly the outer two rows. Nicotine is proved to be harmful to the cells of the cochlea, particularly the outer hair cells of the basal turn. High doses induce blebing of hair cells.
Adult ; Animals ; Cochlea* ; Cytoplasm ; Guinea Pigs* ; Hair ; Hearing Loss ; Humans ; Male ; Microscopy ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Nicotine* ; Smoke ; Smoking ; Stereocilia ; Tobacco

OBJECTIVEToxic metal ions have been implicated in the generation of reactive oxygen species (ROS) and nitric oxide (NO). Metallothionines (MT) and plant flavonoids have been reported in the intervention against oxidative damage. We investigated the effect of zinc induced MT and green tea polyphenol (GTP) in reducing the oxidative responses induced by nickel and platinum.

METHODSZinc (10 mg/kg b. wt, sc) was administered to rats twice at a gap of 24 hrs and GTP (10 mg/100 mL in drinking water) was fed ad libitum for 8 days. Nickel chloride (150 umol/kgb.wt, ip) and cisplatin (50 mumol/kg b.wt, sc) was administered to rats 24 h after Zn or GTP pre-treatment. Animals of all the groups were sacrificed 16 hrs after treatment and biochemical markers for toxicity were monitored.

RESULTSZinc or GTP pre-treatment caused significant protection against nickel or cisplatin enhanced mortality in rats, and reduction in lipid peroxidation and NO.

CONCLUSIONIt is proposed that inhibition of ROS and NO by GTP and zinc may prove useful as a selective pharmacological agent in the amelioration of metal toxicity.

Animals ; Antioxidants ; pharmacology ; Biomarkers ; Cisplatin ; administration & dosage ; toxicity ; Flavonoids ; administration & dosage ; pharmacology ; Free Radical Scavengers ; pharmacology ; Lipid Peroxidation ; drug effects ; Metallothionein ; metabolism ; Mortality ; Nickel ; administration & dosage ; toxicity ; Nitric Oxide ; metabolism ; Phenols ; administration & dosage ; pharmacology ; Polyphenols ; Rats ; Tea ; chemistry ; Time Factors ; Zinc ; administration & dosage ; pharmacology

PURPOSE: In the present study booster efficacies of Ag85 B, Bacillus Calmette-Guerin (BCG), and Ag85B peptides were evaluated using prime boost regimes in BALB/c mice. MATERIALS AND METHODS: Mice were primed with BCG vaccine and subsequently boosted with Ag85B, BCG and cocktail of Ag85B peptides. RESULTS: Based on analysis of immune response it was observed mice boosted with Ag85B peptides showed significant (p < 0.001) cytokines levels (interferon gamma, interleukin 12) and BCG specific antibodies (anti-BCG and anti-purified protein derivative titre) compared to booster dose of BCG, Ag85B and BCG alone. CONCLUSION: Our pilot results suggest that prime boost regimes with Ag85B peptides can boost waning BCG induced immunity and may improve immunogenicity of BCG vaccine. However, lot of work is further needed using experimental model of tuberculosis infection to justify the result.
Animals ; Antibodies ; Bacillus ; BCG Vaccine ; Cytokines ; Interleukins ; Mice* ; Models, Theoretical ; Mycobacterium bovis* ; Peptides* ; Pilot Projects* ; Tuberculosis ; Vaccines*

OBJECTIVETo investigate the effect of Lead (Pb) acetate exposure on Semliki forest virus (SFV) pathogenesis in mice.

METHODSDifferent doses (62.5, 125, 250 and 500 mg/Kg body weight) of Pb dissolved in normal saline were given to mice by oral intubation in a sub-acute (28 days) and sub-chronic (90 days) regimen followed by SFV infection. Morbidity, mortality, clinical symptoms, mean survival time (MST), changes in body and organ weight, accumulation of lead in soft tissues, virus titre in brain and histopathological alterations were compared between lead exposed and infected groups.

RESULTSEarly appearance of virus symptoms, increased mortality, decreased MST, enhanced SFV titre and greater tissue damage were observed in lead exposed-SFV-infected mice.

CONCLUSIONPre-exposure to lead increases the susceptibility of mice towards SFV infection. Further studies are suggested in view of the persistence of lead in the environment and the possibility of infection by microbial pathogens.

Alphavirus Infections ; etiology ; veterinary ; Animals ; Brain ; pathology ; Dose-Response Relationship, Drug ; Kidney ; pathology ; Lead ; administration & dosage ; toxicity ; Liver ; pathology ; Mice ; Semliki forest virus ; pathogenicity

Evaluation and screening of vaccines against tuberculosis depends on development of proper cost effective disease models along with identification of different immune markers that can be used as surrogate endpoints of protection in preclinical and clinical studies. The objective of the present study was therefore evaluation of subcutaneous model of M.tuberculosis infection along with investigation of different immune biomarkers of tuberculosis infection in BALB/c mice. Groups of mice were infected subcutaneously with two different doses : high (2x10(6) CFU) and low doses (2x10(2) CFU) of M.tuberculosis and immune markers including humoral and cellular markers were evaluated 30 days post M.tuberculosis infections. Based on results, we found that high dose of subcutaneous infection produced chronic disease with significant (p<0.001) production of immune markers of infection like IFNgamma, heat shock antigens (65, 71) and antibody titres against panel of M.tuberculosis antigens (ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of which correlated with high bacterial burden in lungs and spleen. To conclude high dose of subcutaneous infection produces chronic TB infection in mice and can be used as convenient alternative to aerosol models in resource limited settings. Moreover assessment of immune markers namely mycobacterial antigens and antibodies can provide us valuable insights on modulation of immune response post infection. However further investigations along with optimization of study protocols are needed to justify the outcome of present study and establish such markers as surrogate endpoints of vaccine protection in preclinical and clinical studies in future.
Animals ; Antibodies ; Biomarkers* ; Chronic Disease ; Hot Temperature ; Lung ; Mass Screening ; Mice* ; Shock ; Spleen ; Tuberculosis* ; Vaccines