Visceral leishmaniasis (VL) or kala-azar is a chronic protozoan infection in humans associated with significant global morbidity and mortality. The causative agent is a haemoflagellate protozoan Leishmania donovani, an obligate intracellular parasite that resides and multiplies within macrophages of the reticulo-endothelial system. Most of the existing anti-leishmanial drugs have serious side effects that limit their clinical application. As an alternate strategy, vaccination is also under experimental and clinical trials. The in vitro evaluation designed to facilitate rapid testing of a large number of drugs has been focussed on the promastigotes milt little attention on the clinically relevant parasite stage, amastigotes. Screening designed to closely reflect the situation in vivo is currently time consuming, laborious, and expensive, since it requires intracellular amastigotes and animal model. The ability to select transgenic Leishmania expressing reporter proteins, such as the green fluorescent proteins (GFP) or the luciferase opened up new possibilities for the development of drug screening models. Many experimental animal models like rodents, dogs and monkeys have been developed, each with specific features, but none accurately reproduces what happens in humans. Available in vitro and in vivo methodologies for antileishmanial drug screening and their respective advantages and disadvantages are reviewed.

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Ischaemic stroke is a disorder involving multiple mechanisms of injury progression including activation of glutamate receptors, release of proinflammatory cytokines, nitric oxide (NO), free oxygen radicals and proteases. Presently, recombinant tissue plasminogen activator (rtPA) is the only drug approved for the management of acute ischaemic stroke. This drug, however, is associated with limitations like narrow therapeutic window and increased risk of intracranial haemorrhage. A large number of therapeutic agents have been tested including N-methly-D-aspartate (NMDA) receptor antagonist, calcium channel blockers and antioxidants for management of stroke, but none has provided significant neuroprotection in clinical trials. Therefore, searching for other potentially effective drugs for ischaemic stroke management becomes important. Immunosuppressive agents with their wide array of mechanisms have potential as neuroprotectants. Corticosteroids, immunophilin ligands, mycophenolate mofetil and minocycline have shown protective effect on neurons by their direct actions or attenuating toxic effects of mediators of inflammation. This review focuses on the current status of corticosteroids, cyclosporine A, FK506, rapamycin, mycophenolate mofetil and minocycline in the experimental models of cerebral ischaemia.

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Background & objectives : Quality of care is an important determinant for utilizing health services. In India, the quality of care in most health services is poor. The government recognizes this and has been working on both supply and demand aspects. In particular, it is promoting community health insurance (CHI) schemes, so that patients can access quality services. This observational study was undertaken to measure the level of satisfaction among insured and uninsured patients in two CHI schemes in India. Methods: Patient satisfaction was measured, which is an outcome of good quality care. Two CHI schemes, Action for Community Organisation, Rehabilitation and Development (ACCORD) and Kadamalai Kalanjiam Vattara Sangam (KKVS), were chosen. Randomly selected, insured and uninsured households were interviewed. The household where a patient was admitted to a hospital was interviewed in depth about the health seeking behaviour, the cost of treatment and the satisfaction levels. Results: It was found that at both ACCORD and KKVS, there was no significant difference in the levels of satisfaction between the insured and uninsured patients. The main reasons for satisfaction were the availability of doctors and medicines and the recovery by the patient. Interpretation & conclusions : Our study showed that insured hospitalized patients did not have significantly higher levels of satisfaction compared to uninsured hospitalized patients. If CHI schemes want to improve the quality of care for their clients, so that they adhere to the scheme, the scheme managers need to negotiate actively for better quality of care with empanelled providers.

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Background & objectives : Despite years of salt iodization, goitre continues to be a major public health problem worldwide. We examined the prevalence of goitre in the post-iodization phase and the relationship of goitre with micronutrient status and thyroid autoimmunity in school children of Chandigarh, north India. Methods: Two phase study; in the first phase, 2148 children of 6 to 16 yr were screened for goitre by two independent observers as per the WHO grading system. In the second phase, a case-control study, 191 children with goitre and 165 children without goitre were compared with respect to urinary iodine, iodine content of salt, serum levels of T ₃ , T ₄ , TSH, anti-TPO (thyroid peroxidase) antibody, haemoglobin, ferritin and selenium. Results: Prevalence of goitre in the studied subjects was 15.1 per cent (13.9% in 6 to 12 yr and 17.7% in 13 to 16 yr age group, P= 0.03). Median urinary iodine excretion in both the groups was sufficient and comparable (137 and 130 μg/l). 3.2 per cent children with goitre and 2.4 per cent without goitre had hypothyroidism (subclinical and clinical) and only one child with goitre had subclinical hyperthyroidism. Nine (4.9%) children in the goitre group and 3 (1.9%) in control group had anti-TPO antibody positivity. The median serum selenium levels were not different in both the groups (181.9 and 193.5 μg/l). Seventy one (37.4%) of the goitrous children had anaemia (haemoglobin <12 g/dl) as compared to 41 (24.8%) of the control group ( P <0.01). More number of goitrous children (39, 20.6%) were depleted of tissue iron stores (serum ferritin <12 μg/l) as compared to controls (11, 6.4%; P<0.001). Serum ferritin level negatively correlated with the presence of goitre (r = - 0.22, P =0.008) and had an OR of 2.8 (CI 1.20 - 6.37, P =0.017). Interpretation & conclusions : There was a high prevalence of goitre in young children despite iodine repletion and low thyroid autoimmunity. The concurrent iron deficiency correlated with the presence of goiter. However, the cause and effect relationship between iron deficiency state and goitre requires further elucidation.

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Background & objectives : Athletes in Malaysia need to perform in a hot and humid environment due to the climatic nature of the country. c0 hronic supplementation of Panax ginseng (PG) (a deciduous perennial plant belonging to the Araliaceae family) enhances physical performance. As the ergogenic effect of acute supplementation of PG on endurance performance has not been explored in the Malaysian population especially in a hot and humid condition this study was taken up. Methods: Nine heat adapted recreational runners (age : 25.4 ± 6.9 yr, body mass : 57.6 ± 8.4 kg; body height : 168.3 ± 7.6 cm) were recruited in this placebo-controlled double-blind randomized study. Subjects ingested 200 mg of PG one hour before the exercise test on treadmill at 70 per cent of their VO _2max in a laboratory environment of 31 ^o C and 70 per cent relative humidity. They drank 3 ml/kg body weight of cool water every 20 min during the exercise to prevent adverse effects of dehydration. Blood samples were drawn every 20 min for the analysis of glucose, lactate, insulin and free fatty acids. Oxygen uptake was determined every 20 min while heart rate, body and skin temperatures, and ratings of perceived exertion (RPE) were recorded every 10 min during the trials. Results: Endurance running time to exhaustion did not differ between PG and placebo trials. Heart rate, skin temperature, core body temperature, oxygen uptake, RPE, plasma insulin, glucose, free fatty acid and lactate levels during the endurance exercise did not show any significant differences between the trials. Interpretation & conclusions : We conclude that acute supplementation of 200 mg of PG did not affect the endurance running performance of the heat-adapted male recreational runners in the heat.

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Background & objectives : Bacillus cereus is one of the pathogens responsible for human diarrhoea, mainly due to consumption of contaminated food. The present study was undertaken to determine the occurrence of B. cereus among diarrhoeal patients and its phenotypic and genetic characteristics that determine the virulence and clonal features. Methods: Stool specimens were collected for two years from acute diarrhoeal patients attending the two referral hospitals in Kolkata. Presence of virulence genes in B. cereus was determined by PCR. Clonality was assessed by pulsed-field gel analysis (PFGE) by restriction digestion with SmaI and NotI enzymes. Enterotoxins were detected by haemolysin assay and using BCET-RPLA kit. Invasion assay was done on Hep-2 cell line. Antimicrobial susceptibility was tested by disc diffusion method. Results: B. cereus was identified in 54 (3.5%) of the 1536 diarrhoeal cases studied. Majority of the isolates were susceptible to many antibiotics but showed resistant to amoxyclav and cephalosporins. Six genes covering the two different enterotoxic complexes determining the pathogenicity of B. cereus have been characterized by PCR. The nhe genes were detected in a higher proportion than hbl. Except in two, clonal diversity was noticed among 21 B. cereus isolates. Haemolytic enterotoxin was detected in 76 per cent of the isolates. Majority of the isolates (67%) produced in vitro enterotoxin (BCET) confirming its involvement in the infection. Interpretation & conclusions : Though the presence of B. cereus was not high in patients with diarrhoea, several virulence factors confirm their association with diarrhoea. Distinct clonality was identified in majority of the isolates indicating their origin from different sources.

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Background & objectives : Cardiovascular disease (CVD) and diabetes have become a leading threat to public health in India. This study examines socio-economic differences in self-reported morbidity due to CVD and diabetes, where people having these conditions seek care, how much households pay for and how they finance hospital treatment for these conditions. Methods : Data for this study are taken from the National Sample Survey Organization (NSSO) 60 ^th round on 'Morbidity and Health Care' conducted between January and June 2004. Information from 2,129 and 438 individuals hospitalized for CVD and diabetes was analyzed. Results : The self-reported prevalence among adults was 12 per cent for CVD, 4 per cent (7% urban and 3% rural) for heart disease and 6 per cent (10% in urban and 4% in rural) for diabetes. Both self-reported CVD and diabetes appeared to afflict the wealthier more. The private sector was the main provider of outpatient and inpatient care for CVD and diabetes treatment, though the poor depended more on the public sector. Out-of-pocket payments (OOPS) for hospital treatment claimed a large share of annual household expenditures; 30 per cent for CVD and 17 per cent for diabetes. The OOPS share for diabetes treatment declined with increasing income. The majority of OOPS for hospital treatment paid by the poor was financed through borrowings. Interpretation & conclusions : The considerable financial strain which households, particularly the poor, face in treating CVD and diabetes is alarming. As the burden due to CVD and diabetes increases in India, more households will be subject to these financial strains and unfortunately, the economically vulnerable among them will be the worst affected. While primary prevention of these conditions need more emphasis, in addition, insurance schemes targeted at the poor like the RSBY have an important role to play in financially protecting vulnerable households.

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Background & objectives : Chronic hepatitis B is an important cause of morbidity and mortality. We conducted a study comparing the efficacy of adefovir and lamivudine with respect to their impact on serum and hepatic viral DNA clearance, and improvement in hepatic necro-inflammatory score, in naive patients of chronic hepatitis B. Methods: This prospective randomized pilot study was conducted in Lok Nayak Hospital, New Delhi, involving 30 patients of chronic hepatitis B (both e antigen positive and negative); 15 were randomly selected to receive either adefovir or lamivudine for a period of 6 months. Quantification of serum and hepatic HBV DNA levels was done by real time PCR and liver biopsy was done at the beginning and end of 6 months. Results: Serum ALT was elevated to 2 or more times normalized in both the groups. In the adefovir group, two patients became HBeAg negative. In the lamivudine group, one patient became HBeAg negative. After therapy HBV DNA was negative in 26.7 per cent patients from adefovir group and 13.3 per cent patients from lamivudine group. Serum HBV DNA levels were correlated with the hepatic levels before therapy (r=0.843; P<0.001) and after therapy (r=0.713, P<0.001) showing strong correlation. There was a median reduction of 1.92 and 2.06 log copies per ml in serum HBV DNA load after adefovir and lamivudine therapy, respectively. The mean reduction in the histotogy activity index (HAI) score was 2 and 1.53, fibrosis score was 2.33 and 3.06 after adefovir and lamivudine therapy respectively. Interpretation & conclusions : Adefovir and lamivudine treatment caused biochemical and serological improvement when administered for about 6 months with significant reduction in HBV DNA, serum and hepatic viral load without completely clearing the virus from either serum or liver. It also helped in reduction of the necro-inflammatory and fibrosis score of patients with chronic hepatitis B. Our study also showed significant correlation between serum and hepatic HBV DNA levels both before and after therapy. There was not enough evidence to show therapeutic advantage of one drug over the other in any of the parameters measured.

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Background & objectives: Group A streptococcal (GAS) pharyngitis, especially among children, leads to high prevalence of rheumatic fever (RF)/rheumatic heart disease (RHD) in India, as compared to the western world where invasive diseases are common. GAS encodes numerous virulence factors that cause diseases by exhibiting extraordinary biological diversity. Hence, we studied the virulence factors genes of GAS isolated from the throat of children with pharyngitis and also asymptomatic carriers. Methods: Fifty GAS isolates cultured from throats of north Indian children aged 5-15 yr with mild pharyngitis (20), severe pharyngitis (24) and asymptomatic pharyngeal carriers (6), during 2000-2003 along with reference M1 strain were emm typed and characterized for virulence factors genes by PCR. The presence of virulence factors was also checked for their association with emm type in pharyngitis. Results: Twenty emm types, six sequence types, and one non-typeable strain were found circulating in north India. The five most prevalent types were emm 74 (12%), 11 & StI129 (8% each) and emm 68 and NS292 (6% each). The spe B gene was found to be significantly higher (P=0.0007) in opacity factor (OF) negative isolates. emm 3, 11, 77, 86, 87, 109 and StI129 showed maximum virulence factors genes. Interpretation & conclusions: GAS isolates collected from throats of children from north India possess highly virulent antigens. This study also supports concept of isolate-associated virulence rather than type relatedness.

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Background & objectives : Due to tsunami in 2004 a large proportion of population in Nicobar group of Islands become homeless, and in 2006 large scale labour migration took place to construct the houses. In 2008, a significant increase in malaria incidence was observed in this area. Therefore, in March 2008, the situation of malaria was assessed in Nancowry Islands in Nicobar District to study the reasons for the observed upsurge in the number of cases, and to suggest public health measures to control the infection. Methods: The methods included a retrospective analysis of long term trend in the behaviour of malaria over the years from 2001 to 2008, analysis of the acute malaria situation, and rapid fever and malaria parasitemia survey along with environmental component. Mass radical therapy (MRT) and post-intervention parasitemia survey were carried out. The malaria situation in the aftermath of MRT was analysed. Results: During the post tsunami year (2005) there was a large increase in the incidence of malaria and this trend continued till 2008. The percentage of Plasmodium falciparum increased from 23 to 53 per cent from 2006 to 2007 that coincides with the labour influx from mainland. The study showed that Nancowry was highly endemic, with high transmission setting, and high risk area for malaria. Though, more number of migrant labourers suffered fever (75 vs 20%) and sought malaria treatment over past month but parasitemia survey showed higher point prevalence of malaria among native tribes (7.4 vs 6.5%). Post-MRT, there was a decline in the occurrence of malaria, though it did not last long. Interpretation & conclusions : The study findings suggest that the migrant workers hailing from non-endemic or moderately endemic settings became victims of malaria in epidemic proportion in high endemic and high transmission setting. To find out the reasons for deterioration of malaria situation at Nancowry in the aftermath of tsunami requires further research.

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Background & objectives : An association between over-expression of proto-oncogene Her-2/neu and resistance to tamoxifen in estrogen receptor (ER) positive, primary and metastatic breast cancer has been suggested. HR+/Her-2/neu+ patients have a poor response to endocrine therapy, making this group a matter of debate. The present study was carried out to examin whether Her-2/neu expression in breast cancer patients predicted tamoxifen effectiveness. Methods : An enzyme-linked immunosorbent assay (ELISA) specific for the extracellular domain of the Her-2/neuoncoprotein product was used to detect serum Her-2/neu levels in 207 patients with histological confirmed breast cancer. Tissue Her-2 /neu expression was studied in 100 breast cancer patients by immunohistochemistry (IHC) and compared with serum Her-2/neu levels by ELISA. Results : Among 207 histologically confirmed breast cancer patients, 53 were serum Her-2/neu positive. Patients who were treated with surgery, chemotherapy, and radiotherapy showed significantly (P<0.05) reduced serum Her-2/neu levels, showing good response to treatment. Patients who were treated with tamoxifen in addition to the above regimen did not show any significant reduction in serum Her-2/neu levels showing resistance to treatment. Interpretation & conclusions : The present findings study support the hypothesis that Her-2/neu overexpression contributes to tamoxifen resistance. Trastuzumab or other growth factor inhibitors should be used in combination with tamoxifen, since monotherapy is not likely to be optimal in HR+/Her-2/neu+ tumours.

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Background & objectives : Measuring maternal mortality in developing countries poses a major challenge. In Nepal, vital registration is extremely deficient. Currently available methods to measure maternal mortality, such as the sisterhood method, pose problems with respect to validity, precision, cost and time. We conducted this field study to test a community-based method (the motherhood method), to measure maternal and child mortality in a developing country setting. Methods : Motherhood method was field tested to derive measures of maternal and child mortality at the district and sub-regional levels in Bara district, Nepal. Information on birth, death, risk factors and health outcomes was collected within a geographic area as in an unbiased census, but without visiting every household. The sources of information were a vaccination registry, focus group discussions with local health workers, and most importantly, interview in group setting with women who share social bonds formed by motherhood and aided by their peer memory. Such groups included all women who have given birth, including those whose babies died during the measurement period. Results : A total of 15161 births were elicited in the study period of two years. In the same period 49 maternal deaths, 713 infant deaths, 493 neonatal deaths and 679 perinatal deaths were also recorded. The maternal mortality ratio was 329 (95%CI:243-434)/100000 live birth, infant mortality rate was 48(44-51)/1000LB, neonatal mortality rate was 33(30-36)/1000LB, and perinatal mortality rate was 45(42-48)/1000 total birth. Interpretation & conclusions : The motherhood method estimated maternal, perinatal, neonatal and infant mortality rates and ratios. It has been field tested and validated against census data, and found to be efficient in terms of time and cost. Motherhood method can be applied in a time and cost-efficient manner to measure and monitor the progress in the reduction of maternal and child deaths. It can give current estimates of mortalities as well as averages over the past few years. It appears to be particularly well-suited to measuring and monitoring programmes in community and districts levels.

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Background & objectives : Acanthamoeba keratitis (AK) is a painful and vision-threatening ocular infection. The differentiation of Acanthamoeba at the species and subspecies level is complicated. Nearly all the AK isolates have been shown to belong to T4 genotype when analysed by ribosomal RNA gene sequences and there is no universally acceptable method for differentiation of different subtypes of T4. The purpose of this study was to attempt further discrimination of T4 genotypes. Methods : In the present investigation, 15 Acanthamoeba isolates obtained from cornea of keratitis patients were subjected to fluorescence amplified fragment length polymorphism (FAFLP) genotyping to differentiate T4 subtypes. Results : FAFLP profiles showed five distinct clusters (I to V) within T4 clonal complex which clearly depicted genetic differences among the isolates of T4 sequence type of Acanthamoeba. Interpretation & conclusions : Our study demonstrated the usefulness of FAFLP for reliable differentiation of T4 clonal complex of Acanthamoeba.

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