Typhoid fever is a systemic disease caused by the human specific Gram-negative pathogen Salmonella enterica serovar Typhi (S. Typhi). The extra-intestinal infections caused by Salmonella are very fatal. The incidence of typhoid fever remains very high in impoverished areas and the emergence of multidrug resistance has made the situation worse. To combat and to reduce the morbidity and mortality caused by typhoid fever, many preventive measures and strategies have been employed, the most important being vaccination. In recent years, many Salmonella vaccines have been developed including live attenuated as well as DNA vaccines and their clinical trials have shown encouraging results. But with the increasing antibiotic resistance, the development of potent vaccine candidate for typhoid fever is a need of the hour. This review discusses the latest trends in the typhoid vaccine development and the clinical trials which are underway.

Background & objectives: There is a need to develop an affordable and reliable tool for hearing screening of neonates in resource constrained, medically underserved areas of developing nations. This study valuates a strategy of health worker based screening of neonates using a low cost mechanical calibrated noisemaker followed up with parental monitoring of age appropriate auditory milestones for detecting severe-profound hearing impairment in infants by 6 months of age. Methods: A trained health worker under the supervision of a qualified audiologist screened 425 neonates of whom 20 had confirmed severe-profound hearing impairment. Mechanical calibrated noisemakers of 50, 60, 70 and 80 dB (A) were used to elicit the behavioural responses. The parents of screened neonates were instructed to monitor the normal language and auditory milestones till 6 months of age. This strategy was validated against the reference standard consisting of a battery of tests - namely, auditory brain stem response (ABR), otoacoustic emissions (OAE) and behavioural assessment at 2 years of age. Bayesian prevalence weighted measures of screening were calculated. Results: The sensitivity and specificity was high with least false positive referrals for 70 and 80 dB (A) noisemakers. All the noisemakers had 100 per cent negative predictive value. 70 and 80 dB (A) noisemakers had high positive likelihood ratios of 19 and 34, respectively. The probability differences for pre- and post- test positive was 43 and 58 for 70 and 80 dB (A) noisemakers, respectively. Interpretation & conclusions: In a controlled setting, health workers with primary education can be trained to use a mechanical calibrated noisemaker made of locally available material to reliably screen for severe-profound hearing loss in neonates. The monitoring of auditory responses could be done by informed parents. Multi-centre field trials of this strategy need to be carried out to examine the feasibility of community health care workers using it in resource constrained settings of developing nations to implement an effective national neonatal hearing screening programme.

Background & objectives: Detection of prodromal symptoms among patients with mania by their immediate relatives has been seldom examined. We carried out this study to examine the ability to detect and report prodromol symptoms of manic relapses by patients themselves and their relatives. Methods: The ability of patients and their relatives to detect prodromal symptoms was examined among 60 remitted patients, 30 each with DSM-IV diagnoses of bipolar disorder and recurrent depressive disorder, with recent manic/depressive relapses, and their 60 immediate relatives, using an instrument composed of items from common symptom-scales, as well as by unstructured interview. Results: Seventy per cent of patients with mania reported prodromes prior to relapse. This was significantly (P<0.01) less than the proportion of their relatives (97%), as well as the proportion of patients with unipolar depression (93%), reporting prodromal symptoms (P<0.05) among patients. Mean duration of the prodromal period reported by patients with mania was about 20 days (median-10 days); relatives reported durations which were longer by about 5 days. Prodromes of unipolar depression (mean 42.7 days; median- 21 days), were significantly longer than of mania, when reported by patients, but not by their relatives. Differences in reporting of prodromes, between relatives and patients seen in mania, were not observed in unipolar depression. The number and type of prodromal symptoms of mania reported was similar among patients and relatives. Interpretation & conclusions: Our findings showed that relatives of patients with mania were better at detecting prodromes of relapse; thus, input from relatives can improve the early detection of prodromal symptoms to prevent relapses of bipolar disorder.

Background & objectives: High prevalence and poor control of asthma make its management a major public health issue worldwide, especially in developing countries. Optimum review of asthma management in the community is essential to improve asthma control. This study was conducted to investigate the quality of asthma management, knowledge about asthma and quality of life of asthma patients referred to a public tertiary care chest hospital in Delhi. Methods: Diagnosis of asthma was confirmed by symptoms and reversible spirometry in 50 referred patients on their first visit. Patients were interviewed using three questionnaires on quality of asthma management before visiting referral hospital, asthma knowledge and asthma quality of life (AQLQ). Correlation amongst quality of treatment, asthma quality of life, and asthma knowledge was also determined. Results: Findings revealed that only 60 per cent of patients were informed about their disease, and 10 per cent had undergone lung function tests previously. Only 44 per cent of patients were prescribed inhalers. None were provided with any educational material. Patients had poor knowledge of aetiology, pathophysiology, medication and how to assess the severity of their asthma. The mean scores in AQLQ indicated a moderate degree of impairment in quality of life. Interpretations & conclusions: This study provides evidence of unsatisfactory asthma management and patient-doctor interaction as patients had limited knowledge of asthma disease, its management and had poor quality of life as measured by a standardized questionnaire. Thus, there is need to implement suitable interventions to improve asthma management according to standard treatment guidelines in the community.

Background & objectives: A large numbers of subjects were exposed to the aerosol of methyl isocyanate (MIC) during Bhopal gas disaster and lung was one of the most commonly affected organs. The aim of the present study was to analyze retrospectively the lung function abnormalities among the surviving MIC exposed population (gas victims) and to compare it with the non-MIC exposed (non gas exposed) population. Methods: The spirometry data of both gas victims and non gas exposed population who attended the Bhopal Memorial Hospital & Research Centre for evaluation of their respiratory complaints from August 2001 to December 2009, were retrospectively evaluated and compared. Results: A total 4782 gas victims and 1190 non gas exposed individuals performed spirometry during the study period. Among the gas victims, obstructive pattern was the commonest (50.8%) spirometric abnormality followed by restrictive pattern (13.3%). The increased relative risk of developing restrictive abnormality among gas victims was observed in 20-29 yr age group only (adjusted relative risk: 2.94, P<0.001). Male gas victims were more affected by severe airflow obstruction than females and the overall increased relative risk (1.33 to 1.45, P<0.001) of developing obstructive pattern among gas victims was observed. Interpretation & conclusions: The present study showed that the relative risk for pulmonary function abnormalities in gas victims was significantly more among those who were young at the time of disaster. Increased smoking habit among gas victims might have played an additive effect on predominance of obstructive pattern in spirometry.

Background & objectives: Electroconvulsive therapy (ECT) is used frequently in developing countries, but investigations of patients' awareness and perception of ECT are rare. The present study thus attempted a comprehensive examination of knowledge, experience and attitudes concerning ECT among patients treated with brief-pulse, bilateral, modified ECT, and their relatives. Methods: Of the 153 recipients of ECT, 77 patients and relatives were eventually assessed using questionnaires designed to evaluate their awareness and views about ECT. Results: Patients were middle-aged, poorly-educated, often unemployed, with chronic, severe, and predominantly psychotic illnesses. Relatives were mainly parents, older, better-educated and usually employed. Apart from the very rudimentary aspects, patients were largely unaware of the procedure. Though most did not find the experience of ECT upsetting, sizeable proportions expressed dissatisfaction with aspects such as informed consent, fear of treatment and memory impairment. Although patients were mostly positive about ECT, ambivalent attitudes were also common, but clearly negative views were rare. Relatives were significantly likely to be more aware, more satisfied with the experience and have more favourable attitudes towards ECT, than patients. Interpretation & conclusions: The results endorse the notion that recipients of ECT are generally well-disposed towards the treatment, but also indicate areas where practice of ECT needs to be improved to enhance satisfaction among patients and relatives.

Background & objectives: People travelling to high altitude for occupational, recreational or religious purposes are mostly healthy and fit but sometimes they use drugs for common ailments like influenza, acute mountain sickness or chronic disease like diabetes. Limitation of oxygen at high altitude may compromise metabolism of drugs. Hence, we undertook this study to assess the effect of hypobaric hypoxia on some commonly used drugs in rats and rabbits. Methods: Effect of intermittent hypobaric hypoxia on phenotypic expression of anesthetic drugs pentabarbitone, thiopentone and zoxazolamine (sleeping time) was assessed in rats exposed to 282.4 mm Hg equivalent to 25000 feet in a decompression chamber. Plasma clearance of some commonly used drugs was investigated in rabbits exposed to 429 mm Hg equivalent to 15000 feet. Pharmacokinetic parameters were computed by plotting drug concentration versus time curve on semi log scale. Results: A significant delay in regaining rightening reflex was observed in rats exposed to intermittent hypobaric hypoxia in response to zoxazolamine, pentobarbitone and thiopentone sodium. Pharmacokinetics of acetyl salicylic acid, gentamicin, phenobarbitone and acetazolamide showed increase in plasma half life (t _1/2 ), decrease in elimination rate constant (k _el ) and hence prolonged residence of these drugs in hypoxic animals. Interpretation & conclusions: This experimental study showed that hypoxia altered therapeutic effectiveness and clearance of several drugs, in rats and rabbits exposed to intermittent hypobaric hypoxia. s0 uch studies need to be done in human volunteers to see the effect of hypoxia on pharmacokinetics of some common drugs.

Background & objectives: Concentric lamellar calcifications known as psammoma bodies (PB) are found in benign and malignant tumours. Whether or not the inorganic element concentrations in psammomas are similar to serous adenocarcinoma of the ovary and thyroid papillary cancer tissues has not yet been ascertained. We undertook this retrospective study to establish if there is any difference in the concentrations of inorganic ions found in psammomas in serous adenocarcinoma of the ovary, and those found in thyroid papillary cancer tissue. Methods: PB samples from patients with adenocarcinoma of the ovary (n = 10) and with thyroid papillary cancer (n = 10) were analyzed through inductively-coupled plasma spectroscopy (ICP). Results: There were no significant differences in the concentrations of inorganic elements in PB from thyroid papillary cancer than in those PB from ovarian cancer. Interpretation & conclusions: Differences in the concentrations of inorganic elements may be due to the variation in environmental pollution. Our study had limitation of small sample size. Our results suggest that some inorganic elements can participate in the origin of psammoma bodies.

Background & objectives: Considerable efforts are being made to develop new, more effective drugs for osteoporosis, including novel forms of bisphosphonates. The present study was carried out to compare the effect of a novel agent glucosamine alendronate (GA) alone and is combination with dihydroquercetin (DHQ) against the effect of a known drug alendronate (ALN) in the senescence-accelerated OXYS rats as model of osteoporosis. Methods: Male OXYS and Wistar (control) rats were randomized across four experimental groups (n=15), which received 1.26 mg GA, 0.84 mg ALN, or 1.26 mg GA + 5.06 mg DHQ per kg of body weight. Untreated rats were used as control groups. At the end of treatment, the bone mineral density (BMD), bone biomechanical properties, and the levels of serum osteocalcin, αC-terminal crosslinked telopeptides of type I collagen (α-CTx) and calcium were measured. Results: All treatments increased BMD in rats of both strains, but the improvement was more pronounced in OXYS rats: GA+DHQ increased both the strength of the femur by 20 per cent (P<0.01) and BMD by 7.6 per cent (P<0.023). GA+DHQ and ALN reduced serum α-CTx in OXYS rats. Only GA increased the level of osteocalcin in OXYS rats (P<0.05). ALN increased the cross-sectional area of the femur by 9 per cent (P<0.04) in OXYS and by 12 per cent (P<0.05) in Wistar rats. Interpretation & conclusions: The combined treatment with GA+DHQ appears to be more effective at maintaining strength of the femur and BMD in OXYS rats, when compared to the individual drugs GA and ALN.

Background & objectives: Studies on cardiovascular diseases (CVD) in India have shown about 10-20 per cent of cases with no obvious risk factors, raising a suspicion of infections as a cause. There is a paucity of data on this possible role of infections. This study was, therefore, undertaken to find out the association between infection due to Chlamydia pneumoniae and other organisms and coronary artery disease (CAD). Methods: Patients with CAD were selected in group I (acute myocardial infarction, AMI) and group III (patients undergoing coronary artery bypass graft (CABG) surgery), and normal controls in group II. Routine biochemical, haematological and inflammatory tests [C-reactive protein (CRP), total leucocyte count (TLC), fibrinogen, ESR], serodiagnostic tests for IgA and IgG antibodies to C. pneumoniae, Helicobacter pylori, cytomegalovirus (CMV), Mycoplasma pneumoniae and Parvovirus B-19 by ELISA kits, C. pneumoniae antigen by microimmunofluorescence and PCR from endothelial tissue obtained at CABG were carried out. Aortic punch biopsies were done in patients who underwent CABG. Results: Acute MI patients had a significantly higher association with accepted cardiac risk factors, lipid profile, inflammatory and thrombogenic tests. IgG and IgA antibodies levels against C. pneumoniae were not significantly different in the controls as against the AMI group. However, C. pneumoniae antigen seropositive group had significant association with HDL cholesterol, lipid tetrad index (P<0.001) and with triglycerides. Parvovirus B antigen was detected in 8.3 per cent of tissue specimens by PCR and of 44 patients with AMI (6.8%) were also positive for parvovirus B-19 IgG antibodies. Interpretation & conclusions: There was no direct evidence of the involvement of C. pneumoniae and other infective agents and viruses in CAD. It is possible that such infections produce an indirect adverse effect on the lipid profile.

Background & objectives: Heat stress related hyperthermia may cause damage to various organ systems. There are very few studies on the effects of hyperthermia on the endocrine system. We therefore, investigated effects of exogenously induced hyperthermia on adrenal, testicular and thyroid functions and behavioural alterations in pre-pubertal male Sprague-Dawley rats. Methods: Three groups of 30-day old rats (n=7 per group) were used. Body temperature was increased to 39°C (Group I) and 41°C (Group II) in a hyperthermia induction chamber for 30 min. The rats in the Group III served as control (36 °C). All animals received saline and were decapitated 48 h after the experiments. Serum free triiodothyronin (fT3), free thyroxine (fT4), total testosterone and dehydroepiandrosterone sulphate (DHEA-S) levels were determined by chemiluminescence assay, and corticosterone by enzyme immunoassay. Testes, pituitary and adrenal glands were dissected out and processed for histopathological examination. To assess activity and anxiety of the animals, the open field test and elevated-0-maze test, respectively, were used in all groups 24 h before (day 29) and after (day 31) hyperthermia induction. Results: Serum corticosterone levels (3.22±1.3) were significantly reduced in the 39°C (1.3±0.9) and 41°C (1.09±0.7) hyperthermia groups (P<0.01) compared to controls. Serum levels of thyroid hormones did not significantly differ among the groups. DHEA-S and testosterone values were below the limit of detection in all groups. Histopathological examination revealed that there was mild hydropic degeneration in the pituitary and adrenal glands. Apoptotic germ cells were seen in the seminiferous tubules of pre-pubertal male rats exposed to hyperthermia (41°C). Progression time in the open field test was significantly decreased and anxiety test scores increased in animals exposed to 39°C compared to the control group (P<0.01). These parameters were more pronounced in the 41°C hyperthermia group. Interpretation & conclusions: Our results show that heat exposure-induced stress may cause delayed reduction in serum corticosterone levels which may be associated with behavioural deficits in pre-pubertal male rats.

Background & objectives: Coriandrum sativum (CS), has been widely used in traditional systems of medicine for treatment of rheumatoid arthritis. However, the mechanism of action for its antiarthritic effects is not clearly known. Therefore, the present study was carried out to evaluate the antiarthritic activity of CS in rats in two experimental models. Methods: The antiarthritic activity of CS seed hydroalcoholic extract (CSHE) was evaluated in adult Wistar rats by using two experimental models, viz. formaldehyde and Complete Freund's adjuvant (CFA) induced arthritis. The expression of pro-inflammatory cytokines (predominantly contributed by macrophages) was also evaluated. TNF- α level was estimated in serum by ELISA method. TNF-R1, IL-1 β and IL-6 expression in the synovium was analysed by immunohistochemistry. Results: CSHE produced a dose dependent inhibition of joint swelling as compared to control animals in both, formaldehyde and CFA induced arthritis. Although there was a dose dependent increase in serum TNF-α levels in the CSHE treated groups as compared to control, the synovial expression of macrophage derived pro-inflammatory cytokines/cytokine receptor was found to be lower in the CSHE treated groups as compared to control. Interpretation & conclusions: Our results demonstrate that the antiarthritic activity of CSHE may be attributed to the modulation of pro-inflammatory cytokines in the synovium. In further studies CSHE could be explored to be developed as a disease modifying agent in the treatment of RA.