Showing papers in "Indian Journal of Medical Research in 2013"

Assessment of BCG Vaccination in India. Third Report.

Abstract: The protective effect of BCG vaccination in man has been evaluated in a number of controlled trials. In these trials, the protection observed varied from none to 80 per cent. In view of these conflicting results, a large scale BCG trial was planned in India and the protective effect of BCG vaccinatiou evaluated in a controlled, double-blind, community trial near Madras in south India in a population of about 360,000 persons, In this trial, all individuals aged 1 yr and above were tested with 3 IU of PPD-S and 10 units of PPD-B, and simultaneously, BCG vaccines and placebo were allocated randomly to all those aged 1 mo and above. All individuals aged 10 yr and above were X-rayed, and from such persons whose photoftuorograllls were interpreted as abnormal two specimens of sputum were collected and bacteriologically examined. Intensive efforts were made, by means of regular follow-up surveys every 21/2 yr and more frequently, by selective case-finding among suspects and further by maintaining permauent diagnostic services for symptomatics, to identify all new cases of tuberculosis occurring in the community. Mutually exclusive random samples of the population were retested with tuberculin at 21/2 mo, 21/2; and 4 yr after the intake in order to evaluate the tuberculin sensitivity over time in the study population. The study population was charaterised by a high prevalence of tuberculous infection nd disease as also by a very high prevalence of uonspecific sensitivity. This report presents findings of the first 71/2 yr of follow-up. The, tuberculin sensitivity induced by BCG vaccination was highly satisfactory at 21/2 mo but waned considerably between 21/2 mo and 21/2 yr with no further waning in sensitivity thereafter. Incidence of infection was high in the study population. However, incidence of bacillary disease was more frequent among iuitial tuberculin reactors, especially among the older persons, than among uon-reactors of whom the majority were in the younger age groups. The distribution of new cases of pulmonary tuberculosis among those not infected at intake did not show any evidence of a protective effect of BCG. Certain hypotheses that may explain the findings have been discussed.

Methicillin resistant Staphylococcus aureus (MRSA) in India: Prevalence & susceptibility pattern

Abstract: Staphylococcus aureus continues to be a dangerous pathogen for both community-acquired as well as hospital-associated infections. S. aureus resistant to methicillin were reported soon after its introduction in October 19601. Methicillin resistant S. aureus (MRSA) is now endemic in India. The incidence of MRSA varies from 25 per cent in western part of India2 to 50 per cent in South India3. Community acquired MRSA (CA-MRSA) has been increasingly reported from India4. A network of microbiology laboratories (Indian Network for Surveillance of Antimicrobial Resistance - INSAR) at premier medical colleges and hospitals in India was formed with support from the World Health Organization (Figure). The network aims to monitor antimicrobial resistance and to review the magnitude of its problem in India. Initially, a few organisms of public health importance have been chosen for monitoring their prevalence and antimicrobial resistance patterns, with S. aureus being chosen among the Gram-positive organisms. All participating laboratories shared their antimicrobial susceptibility data and provided technical support to other members. The present study provides a national level initiative to understand emerging trends of antimicrobial resistance among clinical isolates of S. aureus and provides a platform to initiate epidemiological studies for staphylococcal infections. Fig Places marked with red dots are INSAR members whose data one oncluded in teh study. Places marked *are INSAR members whose data are not included in the study.

Novel adjuvants & delivery vehicles for vaccines development: A road ahead

Abstract: The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

Genital Chlamydia trachomatis: an update.

Abstract: Chlamydia trachomatis is the most common cause of curable bacterial sexually transmitted infection (STI) worldwide. It manifests primarily as urethritis in males and endocervicitis in females. Untreated chlamydial infection in man can cause epididymitis and proctitis. Though most women with Chlamydia infection are asymptomatic or have minimal symptoms, some develop salpingitis, endometritis, pelvic inflammatory disease (PID), ectopic pregnancy and tubal factor infertility. It is associated with an increased risk for the transmission or acquisition of HIV and is also attributed to be a risk factor for the development of cervical carcinoma. Early diagnosis and treatment of infected individuals is required to prevent the spread of the disease and severe sequelae. Traditionally, tissue culture was considered the gold standard for the diagnosis. However, with the availability of newer diagnostic techniques particularly molecular methods which are not only highly sensitive and specific but are cost-effective also, the diagnosis has became fast and easy. The purpose of this review is to study the various aspects of genital C. trachomatis infection. Also the advances related to the clinical picture, various diagnostic modalities, prevention, treatment, drug resistance and control measures will be dealt with.

Rheumatic fever & rheumatic heart disease: the last 50 years.

Abstract: Rheumatic fever (RF) and rheumatic heart disease (RHD) continue to be a major health hazard in most developing countries as well as sporadically in developed economies. Despite reservations about the utility, echocardiographic and Doppler (E&D) studies have identified a massive burden of RHD suggesting the inadequacy of the Jones' criteria updated by the American Heart Association in 1992. Subclinical carditis has been recognized by E&D in patients with acute RF without clinical carditis as well as by follow up of RHD patients presenting as isolated chorea or those without clinical evidence of carditis. Over the years, the medical management of RF has not changed. Paediatric and juvenile mitral stenosis (MS), upto the age of 12 and 20 yr respectively, severe enough to require operative treatement was documented. These negate the belief that patients of RHD become symptomatic ≥20 years after RF as well as the fact that congestive cardiac failure in childhood indicates active carditis and RF. Non-surgical balloon mitral valvotomy for MS has been initiated. Mitral and/or aortic valve replacement during active RF in patients not responding to medical treatment has been found to be life saving as well as confirming that congestive heart failure in acute RF is due to an acute haemodynamic overload. Pathogenesis as well as susceptibility to RF continue to be elusive. Prevention of RF morbidity depends on secondary prophylaxis which cannot reduce the burden of diseases. Primary prophylaxis is not feasible in the absence of a suitable vaccine. Attempts to design an antistreptococcal vaccine utilizing the M-protein has not succeeded in the last 40 years. Besides pathogenesis many other questions remain unanswered.

New approaches & technologies of venomics to meet the challenge of human envenoming by snakebites in India.

Abstract: The direct estimate of 46,000 snakebite deaths in India in 2005 (1 for every 2 HIV/AIDS deaths), based on verbal autopsies, renders unrealistic the total of only 47,000 snakebite deaths in the whole world in 2010, obtained indirectly as part of the "Global Burden of Disease 2010" study. Persistent underestimation of its true morbidity and mortality has made snakebite the most neglected of all the WHO's "neglected tropical diseases", downgrading its public health importance. Strategies to address this neglect should include the improvement of antivenom, the only specific antidote to envenoming. To accommodate increased understanding of geographical intraspecific variation in venom composition and the range of snake species that are medically important in India, the design of antivenoms (choice of venom sources and species coverage) should be reconsidered. Methods of preclinical and clinical testing should be improved. The relatively new science of venomics involves techniques and strategies for assessing the toxin composition of snake venoms directly through proteomics-centred approaches or indirectly via high-throughput venom gland transcriptomics and bioinformatic analysis. Antivenomics is translational venomics: a proteomics-based protocol to quantify the extent of cross-reactivity of antivenoms against homologous and heterologous venoms. These approaches could revolutionize the preclinical assessment of antivenom efficacy, leading to a new generation of antivenoms that are clinically more effective.

Prevalence of gestational diabetes mellitus & associated risk factors at a tertiary care hospital in Haryana

Abstract: Background & objectives: Prevalence of gestational diabetes mellitus (GDM) is known to vary widely depending on the region of the country, dietary habits, and socio-economic status. This study was undertaken to determine the prevalence of GDM and risk factors associated with it, in women attending an antenatal care (ANC) clinic at a tertiary care hospital in Haryana. Methods: This study enrolled women, with their estimated gestational age between 24 th and 28 th week, attending antenatal care (ANC) clinic at a tertiary care hospital in Rohtak. After informing, women who consented to participate were given a standardized 2-h 75 g oral glucose tolerance test (OGTT). A proforma containing general information on demographic characteristics, socio-economic status, education level, parity, family history of diabetes and/or hypertension and past history of GDM was filled up. American Diabetes Association (ADA) criteria for 75 g 2-h OGTT was used for diagnosing GDM. Results: A total of 607 women participated in the study and GDM was diagnosed in 43 (7.1%) women. A single abnormal value was observed in additional 66 (10.87%) women. On bivariate analysis risk factors found to be significantly associated with GDM were age, educational level, socio-economic status, pre-pregnancy weight and BMI, weight gain, acanthosis nigricans, family history of diabetes or hypertension and past history of GDM but on multivariate analysis only upper middle class and presence of acanthosis nigricans were found to be significantly associated with GDM. Interpretation & conclusions: The prevalence of GDM was found to be 7.1 per cent in a tertiary care hospital in Haryana. Appropriate interventions are required for control and risk factor modifications.

"Doctor population ratio for India - the reality".

Abstract: India plans to establish some 200 new medical colleges in the next 10 years to meet the projected huge shortage of 600,000 doctors. The projections are based on recommendations that have several caveats and therefore somewhat arbitrary1. As compared to their pre-independence levels, all health parameters have shown remarkable progressive improvement even in rural India2. Shortage of doctors for primary health care has been hyped. In fact, States like Maharashtra are now producing surplus MBBS doctors. The Government of Maharashtra has, therefore, decided to scrap the service bond to serve rural sector given by all students in government medical colleges3. On the other hand, India is already facing gross shortages of medical teachers4. The proposed massive expansion, which would reduce the medical colleges to pathshalas (primary schools), is ill advised. It will not solve India's woes of poor health services, but only downgrade country's standing in the medical world. More attention should now be paid to quality of medical education to facilitate establishment of hubs of excellence in medical services, education and research. Rural health services are today actually in dire need of well trained specialists and super-specialists. The basis for arriving at this huge projected shortage is the recommendation about minimum doctor population ratio of 1:1000 made by ‘High Level Expert Group (HLEG) for Universal Health Coverage’ constituted by the Planning Commission5. The concept was originally developed by the Joint Learning Initiative (JLI)1 and subsequently more or less adopted by the WHO5. The two parameters used by the JLI to arrive at the concept were magnitude of coverage of measles immunization and births conducted by skilled attendant. Both of these are low level medical skills that could be easily done by paramedics. However, the issue is more complex as there are several caveats to the recommendations. Several nations and Indian States have achieved health indices of global standards with much lower doctor population ratio1,5.

Iodine deficiency disorders (IDD) control in India.

Abstract: Iodine deficiency disorders (IDD) constitute the single largest cause of preventable brain damage worldwide. Majority of consequences of IDD are invisible and irreversible but at the same time these are preventable. In India, the entire population is prone to IDD due to deficiency of iodine in the soil of the subcontinent and consequently the food derived from it. To combat the risk of IDD, salt is fortified with iodine. However, an estimated 350 million people do not consume adequately iodized salt and, therefore, are at risk for IDD. Of the 325 districts surveyed in India so far, 263 are IDD-endemic. The current household level iodized salt coverage in India is 91 per cent with 71 per cent households consuming adequately iodized salt. The IDD control goal in India was to reduce the prevalence of IDD below 10 per cent in the entire country by 2012. What is required is a "mission approach" with greater coordination amongst all stakeholders of IDD control efforts in India. Mainstreaming of IDD control in policy making, devising State specific action plans to control IDD, strict implementation of Food Safety and Standards (FSS) Act, 2006, addressing inequities in iodized salt coverage (rural-urban, socio-economic), providing iodized salt in Public Distribution System, strengthening monitoring and evaluation of IDD programme and ensuring sustainability of IDD control activities are essential to achieve sustainable elimination of IDD in India.

Sputum smear microscopy in tuberculosis: is it still relevant?

Abstract: Tuberculosis (TB) is a leading cause of morbidity and death worldwide, with approximately two billion people infected and approximately two million annual deaths attributable to it. In 2010, there were an estimated 8.8 million incident cases of TB (range, 8.5-9.2 million) globally, equivalent to 128 cases per 100 000 population, and an estimated 12.0 million prevalent cases (range, 11.0-14.0 million) of TB. This is equivalent to 178 cases per 100,000 population. Thus, approximately 1.4 million people (range, 1.2-1.5 million) died of TB in 20101. The current guidelines of the World Health Organization1 and the International Union Against Tuberculosis and Lung Disease (The Union)2 specify that the essential step in the investigation of patients who are suspected of having pulmonary tuberculosis should be the microscopic examination of their sputum samples. Standard 2 of the International Standards for Tuberculosis Care categorically states that all patients (adults, adolescents, and children who are capable of producing sputum) suspected of having pulmonary tuberculosis should have at least two, and preferably three, sputum specimens obtained for microscopic examination3. However, in the current era of molecular diagnostics, where does sputum smear microscopy stand? It is important to consider the role of smear microscopy, particularly in view of the recent WHO endorsement of the new rapid, automated nucleic acid amplification test, Xpert MTB/RIF2. Sputum smear microscopy has been the primary method for diagnosis of pulmonary tuberculosis in low and middle income countries3, which is where nearly 95 per cent of TB cases and 98 per cent of deaths due to TB occur. It is a simple, rapid and inexpensive technique which is highly specific in areas with a very high prevalence of tuberculosis3. It also identifies the most infectious patients and is widely applicable in various populations with different socio-economic levels3,4,5. Hence, it has been an integral part of the global strategy for TB control. However, sputum smear microscopy has significant limitations in its performance. The sensitivity is grossly compromised when the bacterial load is less than 10,000 organisms/ml sputum sample. It also has a poor track record in extra-pulmonary tuberculosis, paediatric tuberculosis and in patients co-infected with HIV and tuberculosis6,7. Due to the requirement of serial sputum examinations, some patients who do not come back for repeated sputum examinations become “diagnostic defaulters”8. Some do not come back for results, and are lost to treatment and follow up. A personal observation showed that limited resources, large numbers of samples, all combined together often reduce the observation time per slide to less than 60 seconds, and this also contributes to reduction in the sensitivity of the test. Therefore, techniques for optimization of smear microscopy are under active investigation. There has been an attempt to reduce diagnostic defaulting by assessing the feasibility of diagnosing pulmonary tuberculosis by collecting two sputum samples on a single day (1-day protocol), and comparing this protocol with the national policy of collecting samples on consecutive days (2-day protocol). It was felt that since the 2-day protocol did not show a statistically significant difference in diagnostic performance compared with the 1-day protocol, the latter may be adopted as an alternative protocol, particularly for patients who are more likely to default9. Fluorescence microscopy was introduced in the 1930s, in an attempt to improve outcomes of smear microscopy. Fluorochrome dyes are used to stain the smear. A halogen or high-pressure mercury vapour lamp is traditionally used to excite the dye, and make it flouresce. A meta analysis of studies comparing fluorescent and conventional microscopy found that the sensitivity of fluorescent microscopy was 10 per cent higher than that of conventional microscopy, and that it remains high even after concentration of the samples3. Sensitivity was found to be higher particularly in low grade smear positive sputum. Specificity estimates, however, were similar to conventional microscopy, though turnaround times were shorter. This meta analysis concluded that the successful and widespread implementation of fluorescence microscopy might be expected to improve case finding through an expected increase in sensitivity and decrease in time spent on microscopic examination. Although fluorescence microscopy increases the sensitivity of sputum smear microscopy, additional data on specificity and on the clinical consequences associated with false-positive results are needed to guide implementation of this technology in high HIV prevalence settings10. Cost constraints are major issues with fluorescent microscopy. This may be circumvented by the use of light-emitting diodes (LEDs) which cost less than 10 per cent of a mercury vapour lamp. With a life >50,000 h, it can run on batteries and thus has been used in peripheral areas with definite operational advantages11. Rapid culture based methods for diagnosis of tuberculosis include rapid automated liquid culture, where results may be available in a few weeks12; thin layer agar culture, which has an average turnaround time of 11.5 days13, and Microscopic Observation Drug-Susceptibility Assay (MODS), which can provide results in an average of 9.2 days13. Phage based assays give results in 2 days14. While performance indicators of these techniques might be better than that of smear microscopy, turnaround times are longer. There are also requirements in terms of investment in infrastructure and equipment, leading to higher costs per test. Nucleic acid amplification tests (NAATs) attempt to provide accurate and rapid diagnosis of TB using a technology that provides improved sensitivity and specificity functions as compared to sputum smear microscopy. Unfortunately, NAATs have infrastructure and investment requirements that are often beyond the scope of most diagnostic facilities that offer TB diagnostics to communities, particularly in developing countries. While most NAATs are unable to match the accessibility of sputum smear microscopy, Loop-mediated Isothermal Amplification (LAMP) is one NAAT, which has the potential to be accessible and cost-effective. LAMP is being evaluated as a point of care test for the diagnosis of pulmonary tuberculosis. The overall performance characteristics of LAMP and fluorescence smear microscopy appear to be broadly similar. However, the performance of LAMP in smear negative samples was not found to be completely acceptable15. In addition, culture and drug sensitivity testing will still be required to monitor progress of the disease. As ground realities go, it will take a fair amount of time before the new NAAT on the block, Xpert MTB/RIF, can be decentralized sufficiently to replace smear microscopy as a diagnostic test. This is particularly true in geographical areas with high prevalence of multi-drug-resistant TB or HIV/TB co-infections, because most of these areas are in poorly developed zones of low income group countries, with irregular availability of electricity and water, as well as a poorly developed infrastructure for uninterrupted supply of consumables and their storage. Ironically, these are the areas where Xpert has the potential to make the maximum impact. Therefore, it must also be kept in mind that Xpert MTB/RIF technology does not eliminate the need for conventional microscopy, culture and drug sensitivity testing, which are required to monitor treatment progress and to detect resistance to drugs other than rifampicin. In addition, cost considerations tilt in favour of smear microscopy as the initial diagnostic and screening tool for tuberculosis. Talking hypothetically, a rapid and universally accessible test that is not affected by HIV status, with a sensitivity of 85 per cent, and a specificity of 97 per cent, has the potential to save 392,000 adjusted lives annually, or 22 per cent of the global TB deaths16. Ideally, in order to be able to efficiently diagnose tuberculosis, a test should be available for use in peripheral centres where there are limited resources. This test should require no electricity, refrigeration, or access to clean water. It should be widely available, user friendly, with a requirement of minimal, or even no training. The results should be available within an hour, and it should have high sensitivity, specificity and positive and negative predictive values. The technology should be robust and stand the test of time. The diagnostic test should face up to the challenge of making effective TB diagnosis available to populations that need it most, but can afford the least. Currently, such a diagnostic test does not exist. However, as of now, the closest we have to this is sputum smear microscopy. Till such an effective, point of care diagnostic test is available; perhaps, sputum smear microscopy is here to stay.18

T cell ageing: effects of age on development, survival & function.

Abstract: Age associated decline of the immune system continues to be a major health concern. All components of innate and adaptive immunity are adversely affected to lesser or greater extent by ageing resulting in an overall decline of immunocompetence. As a result in the aged population, there is increased susceptibility to infection, poor responses to vaccination, and increased incidence of autoreactivity. There is an increasing focus on the role of T cells during ageing because of their impact on the overall immune responses. A steady decline in the production of fresh naive T cells, more restricted T cell receptor (TCR) repertoire and weak activation of T cells are some of the effects of ageing. In this review we summarize our present understanding of the effects of ageing on naive CD4 T cells and potential approaches for therapeutic interventions to restore protective immunity in the aged population.

Chronic obstructive pulmonary disease.

Abstract: The global prevalence of physiologically defined chronic obstructive pulmonary disease (COPD) in adults aged >40 yr is approximately 9-10 per cent. Recently, the Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis in Adults had shown that the overall prevalence of chronic bronchitis in adults >35 yr is 3.49 per cent. The development of COPD is multifactorial and the risk factors of COPD include genetic and environmental factors. Pathological changes in COPD are observed in central airways, small airways and alveolar space. The proposed pathogenesis of COPD includes proteinase-antiproteinase hypothesis, immunological mechanisms, oxidant-antioxidant balance, systemic inflammation, apoptosis and ineffective repair. Airflow limitation in COPD is defined as a postbronchodilator FEV1 (forced expiratory volume in 1 sec) to FVC (forced vital capacity) ratio <0.70. COPD is characterized by an accelerated decline in FEV1. Co morbidities associated with COPD are cardiovascular disorders (coronary artery disease and chronic heart failure), hypertension, metabolic diseases (diabetes mellitus, metabolic syndrome and obesity), bone disease (osteoporosis and osteopenia), stroke, lung cancer, cachexia, skeletal muscle weakness, anaemia, depression and cognitive decline. The assessment of COPD is required to determine the severity of the disease, its impact on the health status and the risk of future events (e.g., exacerbations, hospital admissions or death) and this is essential to guide therapy. COPD is treated with inhaled bronchodilators, inhaled corticosteroids, oral theophylline and oral phosphodiesterase-4 inhibitor. Non pharmacological treatment of COPD includes smoking cessation, pulmonary rehabilitation and nutritional support. Lung volume reduction surgery and lung transplantation are advised in selected severe patients. Global strategy for the diagnosis, management and prevention of Chronic Obstructive Pulmonary Disease guidelines recommend influenza and pneumococcal vaccinations.

Food production & availability - Essential prerequisites for sustainable food security

Abstract: Food and nutrition security are intimately interconnected, since only a food based approach can help in overcoming malnutrition in an economically and socially sustainable manner. Food production provides the base for food security as it is a key determinant of food availability. This paper deals with different aspects of ensuring high productivity and production without associated ecological harm for ensuring adequate food availability. By mainstreaming ecological considerations in technology development and dissemination, we can enter an era of evergreen revolution and sustainable food and nutrition security. Public policy support is crucial for enabling this.

Emerging & re-emerging infections in India: An overview

Abstract: The incidence of emerging infectious diseases in humans has increased within the recent past or threatens to increase in the near future. Over 30 new infectious agents have been detected worldwide in the last three decades; 60 per cent of these are of zoonotic origin. Developing countries such as India suffer disproportionately from the burden of infectious diseases given the confluence of existing environmental, socio-economic, and demographic factors. In the recent past, India has seen outbreaks of eight organisms of emerging and re-emerging diseases in various parts of the country, six of these are of zoonotic origin. Prevention and control of emerging infectious diseases will increasingly require the application of sophisticated epidemiologic and molecular biologic technologies, changes in human behaviour, a national policy on early detection of and rapid response to emerging infections and a plan of action. WHO has made several recommendations for national response mechanisms. Many of these are in various stages of implementation in India. However, for a country of size and population of India, the emerging infections remain a real and present danger. A meaningful response must approach the problem at the systems level. A comprehensive national strategy on infectious diseases cutting across all relevant sectors with emphasis on strengthened surveillance, rapid response, partnership building and research to guide public policy is needed.

Prevalence of Rh, Duffy, Kell, Kidd & MNSs blood group antigens in the Indian blood donor population

Abstract: Background & objectives: Little data are available regarding the frequencies of the blood group antigens other than ABO and RhD in the Indian population. Knowledge of the antigen frequencies is important to assess risk of antibody formation and to guide the probability of finding antigen-negative donor blood, which is especially useful when blood is required for a patient who has multiple red cell alloantibodies. This study was carried out to determine the frequencies of the D, C, c, E, e, K, k, Fy a , Fy b , Jk a , Jk b , M, N, S and s antigens in over 3,000 blood donors. Methods: Samples from randomly selected blood donors from Delhi and nearby areas (both voluntary and replacement) were collected for extended antigen typing during the period January 2009 to January 2010. Antigens were typed via automated testing on the Galileo instrument using commercial antisera. Results: A total of 3073 blood samples from donors were phenotyped. The prevalence of these antigens was found to be as follows in %: D: 93.6, C: 87, c: 58, E: 20, e: 98, K: 3.5, k: 99.97, Fy a : 87.4, Fy b : 57.6, Jk a : 81.5, Jk b : 67.4, M: 88.7, N: 65.4, S: 54.8 and s: 88.7. Interpretation & conclusions: This study found the prevalence of the typed antigens among Indian blood donors to be statistically different to those in the Caucasian, Black and Chinese populations, but more similar to Caucasians than to the other racial groups.

Serum vitamin-D predicts insulin resistance in individuals with prediabetes.

Abstract: Background & objectives: Patients with diabetes and vitamin-D insufficiency have increased insulin resistance. Similar observations among individuals with prediabetes are not well documented. The aim of this study was to find the occurrence of vitamin-D insufficiency/deficiency among individuals with prediabetes and to evaluate the relationship between vitamin-D status and insulin resistance. Methods: One hundred fifty seven individuals with prediabetes who fulfilled all the inclusion and exclusion criteria underwent clinical examination, anthropometric measurements (waist circumference, waist-hip ratio, waist-height ratio) and blood sampling after overnight fast for estimation of fasting blood glucose, fasting insulin, 25(OH)vitamin-D, intact parathyroid hormone (iPTH) and lipid profile. One hour post 75 g glucose (1hPG) blood glucose during oral glucose tolerance test was measured. Results: Vitamin-D deficiency/insufficiency was found in 115 (73.25%) individuals with prediabetes. Severe vitamin-D deficiency ( 155 mg/dl had significantly higher BMI and worse insulin resistance, and 1hPG correlated well with 2 hour post glucose blood glucose (r=0.57; P Interpretations & conclusions: Vitamin-D deficiency/insufficiency may have some role in the development/worsening of insulin resistance in individuals with prediabetes in our country who have a high cardiovascular risk. Prospective studies on a large group of individuals need to be done to confirm the findings.

Tuberculosis: From an incurable scourge to a curable disease - journey over a millennium

Abstract: Globally, tuberculosis (TB) still remains a major public health problem. India is a high TB burden country contributing to 26 per cent of global TB burden. During 1944-1980, TB became treatable and short-course chemotherapy emerged as the standard of care. When TB elimination seemed possible in the early 1980s, global human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) pandemic resulted in a resurgence of TB. Widespread occurrence of multidrug-resistant and extensively drug-resistant TB (M/XDR-TB) is threatening to destabilize TB control globally. Atypical clinical presentation still poses a challenge. Disseminated, miliary and cryptic TB are being increasingly recognized. Availability of newer imaging modalities has allowed more efficient localization of lesions and use of image guided procedures has facilitated definitive diagnosis of extrapulmonary TB. Introduction of liquid culture, rapid drug-susceptibility testing (DST), molecular diagnostic methods has helped in rapid detection, speciation and DST profiling of Mycobacterium tuberculosis isolates. While treatment of TB and HIV-TB co-infection has become simpler, efforts are on to shorten the treatment duration. However, drug toxicities and drug-drug interactions still constitute a significant challenge. Recently, there has been better understanding of anti-TB drug-induced hepatotoxicity and its frequent confounding by viral hepatitis, especially, in resource-constrained settings; and immune reconstitution inflammatory syndrome (IRIS) in HIV-TB. Quest for newer biomarkers for predicting a durable cure, relapse, discovery/repurposing of newer anti-TB drugs, development of newer vaccines continues to achieve the goal of eliminating TB altogether by 2050.

Asymptomatic bacteriuria & obstetric outcome following treatment in early versus late pregnancy in north Indian women.

Abstract: Background & objectives: Asymptomatic bacteriuria during pregnancy if left untreated, may lead to acute pyelonephritis, preterm labour, low birth weight foetus, etc. Adequate and early treatment reduces the incidence of these obstetric complications. The present study was done to determine presence of asymptomatic bacteriuria (ASB) and obstetric outcome following treatment in early versus late pregnancy. Methods: A prospective cohort study was conducted at a tertiary care teaching hospital of north India. Pregnant women till 20 wk (n=371) and between 32 to 34 wk gestation (n=274) having no urinary complaints were included. Their mid stream urine sample was sent for culture and sensitivity. Women having > 10 [5] colony forming units/ml of single organism were diagnosed positive for ASB and treated. They were followed till delivery for obstetric outcome. Relative risk with 95% confidence interval was used to describe association between ASB and outcome of interest. Results: ASB was found in 17 per cent pregnant women till 20 wk and in 16 per cent between 32 to 34 wk gestation. Increased incidence of preeclamptic toxaemia (PET) [RR 3.79, 95% CI 1.80-7.97], preterm premature rupture of membrane (PPROM)[RR 3.63, 45% CI 1.63-8.07], preterm labour (PTL) [RR 3.27, 95% CI 1.38-7.72], intrauterine growth restriction (IUGR)[RR 3.79, 95% CI 1.80-79], low birth weight (LBW) [RR1.37, 95% CI 0.71-2.61] was seen in late detected women (32-34 wk) as compared to ASB negative women, whereas no significant difference was seen in early detected women (till 20 wk) as compared to ASB negative women. Interpretation & conclusions: Early detection and treatment of ASB during pregnancy prevents complications like PET, IUGR, PTL, PPROM and LBW. Therefore, screening and treatment of ASB may be incorporated as routine antenatal care for safe motherhood and healthy newborn.

Effect of exercise training on functional capacity & quality of life in head & neck cancer patients receiving chemoradiotherapy

Abstract: Background & objectives: Patients with head and neck cancer (HNC) undergoing chemoradiotherapy (CRT) suffer from fatigue causing a decrease in functional capacity and quality of life (QoL). Limited research in the field of exercise training among these patients demanded the need for this study to assess the effects of exercise training on functional capacity and quality of life. Methods: A randomized controlled trial was conducted on 48 patients with HNC undergoing CRT. The exercise group received an individually tailored, supervised, exercise programme for six weeks, while the control group did not receive any form of exercise. Functional capacity and QoL were assessed at baseline and at the end of the intervention using the six minute walk distance (6MWD) and medical outcomes survey short form 36 (SF 36). Results: The mean age of patients was 52 yr with 42 males. After six weeks, the 6MWD improved by 42 metres ( P P P =0.064 and -17.3; P P Interpretation & conclusions: Our results showed that the functional capacity and QoL decreased among those not receiving a supervised exercise program, while exercise training improved functional capacity and QoL in HNC patients undergoing CRT.

Family burden with substance dependence: a study from India.

Abstract: Background & objectives: A substance dependent person in the family affects almost all aspects of family life. This leads to problems, difficulties or adverse events which impact the lives of family members and causes enormous burden on family caregivers. The present study aimed to assess the pattern of burden borne by the family caregivers of men with alcohol and opioid dependence. Methods: A cross-sectional study was conducted with ICD-10 diagnosed substance dependence subjects and their family caregivers attending a de-addiction centre at a multispecialty teaching hospital in north India. Family Burden Interview Schedule was used to assess the pattern of burden borne by the family caregivers of 120 men with alcohol and/or opioid dependence. Results: Compared to opioid and alcohol+opioid dependence groups, more often the alcohol dependence group was older, married, currently working, having a higher income and with the wife as a caregiver. Family burden was moderate or severe in 95-100 per cent cases in all three groups and more for 'disruption of family routine', 'financial burden', 'disruption of family interactions' and 'disruption of family leisure'. Family burden was associated with low income and rural location. It was associated neither with age, education or duration of dependence of the patients, nor with family size, type of caregiver or caregiver's education and occupation. Interpretation & conclusions: Almost all (95-100%) caregivers reported a moderate or severe burden, which indicates the gravity of the situation and the need for further work in this area.

Tricalcium phosphate/hydroxyapatite (TCP-HA) bone scaffold as potential candidate for the formation of tissue engineered bone.

Abstract: Background & objectives: Various materials have been used as scaffolds to suit different demands in tissue engineering. One of the most important criteria is that the scaffold must be biocompatible. This study was carried out to investigate the potential of HA or TCP/HA scaffold seeded with osteogenic induced sheep marrow cells (SMCs) for bone tissue engineering. Methods: HA-SMC and TCP/HA-SMC constructs were induced in the osteogenic medium for three weeks prior to implantation in nude mice. The HA-SMC and TCP/HA-SMC constructs were implanted subcutaneously on the dorsum of nude mice on each side of the midline. These constructs were harvested after 8 wk of implantation. Constructs before and after implantation were analyzed through histological staining, scanning electron microscope (SEM) and gene expression analysis. Results: The HA-SMC constructs demonstrated minimal bone formation. TCP/HA-SMC construct showed bone formation eight weeks after implantation. The bone formation started on the surface of the ceramic and proceeded to the centre of the pores. H&E and Alizarin Red staining demonstrated new bone tissue. Gene expression of collagen type 1 increased significantly for both constructs, but more superior for TCP/HA-SMC. SEM results showed the formation of thick collagen fibers encapsulating TCP/HA-SMC more than HA-SMC. Cells attached to both constructs surface proliferated and secreted collagen fibers. Interpretation & conclusions: The findings suggest that TCP/HA-SMC constructs with better osteogenic potential compared to HA-SMC constructs can be a potential candidate for the formation of tissue engineered bone.

Distribution, seasonal variation & dengue transmission prediction in Sisaket, Thailand

Abstract: Background & objectives : Environmental factors including weather variables may play a significant role in the transmission of dengue. This study investigated the effect of seasonal variation on the abundance of Aedes aegypti and Ae. albopictus larvae and explored the impact of weather variability on dengue transmission in Sisaket, Thailand. Methods : The monthly mosquito larval surveys were carried out in urban and rural areas in Sisaket, Thailand from January to December 2010. Data on monthly-reported cases of dengue fever over the period 2004-2010 were obtained from the Ministry of Public Health. Weather data over the same period were obtained from the Thai Meteorological Department. Chi-square test was used to find the differences relating to seasonal variability, areas of study, and mosquito species factors using entomological survey data. Time series Poisson regression analysis was performed using data on monthly weather variables and dengue cases. Results : There were more Ae. aegypti larvae per household than Ae. albopictus larvae in the winter and rainy seasons. More Aedes larvae per household were found in the rainy season than in the winter and summer seasons. Relative humidity at a lag of one month and rainy days in the current month were significant predictors of dengue incidence in Sisaket. Interpretation & conclusions : Increased rain during the current month and less humidity during the previous month might trigger a higher incidence of dengue epidemic in Sisaket. The present findings suggest that the dengue incidence corresponds with the number of Aedes larvae. The seasonal patterns of dengue outbreaks coincide with the rainy season.

Phenotypic & genotypic characterization of vancomycin resistant Enterococcus isolates from clinical specimens

Abstract: Background & objectives: Enterococci have emerged as important nosocomial pathogens and emergence of resistance to many of the antimicrobials used for Gram-positive organisms has made the management of infections due to Enterococcus species difficult. Resistance to glycopeptide antibiotics, especially vancomycin is of special concern. This study was undertaken to perform a phenotypic and genotypic characterization of vancomycin resistant Enterococcus (VRE) isolates obtained from clinical samples in a tertiary care hospital in southern India. Methods: Susceptibility testing was performed for Enterococcus isolates collected over a period of one year (November 2008-October 2009). Minimum inhibitory concentrations (MIC) of vancomycin and teicoplanin were determined for the isolates by the agar dilution method. Genotypic characterization of VRE isolates was done by performing multiplex polymerase chain reaction (PCR) for detecting the various vancomycin resistance genes. Results: Of the 367 isolates of Enterococcus species isolated, 32 were found to be resistant to vancomycin after MIC testing. VanA was the commonest phenotype of vancomycin resistance and the commonest genotype was vanA. Among the other important findings of the study was the presence of heterogeneity in isolates of VRE with the vanA gene cluster with regards to resistance to teicoplanin and the coexistence of vanA and vanC1 gene clusters in an isolate of E. gallinarum which conferred high level glycopeptide resistance to the isolate. Interpretation & conclusions: Enterococcus species have emerged as important nosocomial pathogens in our patients with a capacity to cause a variety of infections. The vancomycin resistance among Enterococcus isolates was 8.7 per cent in our study which was high compared to other Indian studies. VanA was the commonest phenotype of glycopeptide resistance and vanA was the commonest vancomycin resistance gene. The study also demonstrates phenotypic as well as genotypic heterogeneity among isolates of VRE from clinical specimens.

Probiotics as efficient immunopotentiators: Translational role in cancer prevention

Abstract: Accumulating evidences indicate that some diseases are triggered by abnormalities of the gut microbiota. Among these, immune-related diseases can be the promising targets for probiotcs. Several studies have proved the efficacy of probiotics for preventing such diseases including cancers, infections, allergies, inflammatory bowel diseases and autoimmune diseases. Lactobacillus casei strain Shirota (LcS) is one of the most popular probiotics, benefits of which in health maintenance and disease control have been supported by several science-based evidences. This review summarizes human clinical trials with this probiotic against cancer development and also discusses the possible immunomodulatory mechanisms by which LcS exerts anti-cancer activity.

Eradicating poliomyelitis: India's journey from hyperendemic to polio-free status

Abstract: India's success in eliminating wild polioviruses (WPVs) has been acclaimed globally. Since the last case on January 13, 2011 success has been sustained for two years. By early 2014 India could be certified free of WPV transmission, if no indigenous transmission occurs, the chances of which is considered zero. Until early 1990s India was hyperendemic for polio, with an average of 500 to 1000 children getting paralysed daily. In spite of introducing trivalent oral poliovirus vaccine (tOPV) in the Expanded Programme on Immunization (EPI) in 1979, the burden of polio did not fall below that of the pre-EPI era for a decade. One of the main reasons was the low vaccine efficacy (VE) of tOPV against WPV types 1 and 3. The VE of tOPV was highest for type 2 and WPV type 2 was eliminated in 1999 itself as the average per-capita vaccine coverage reached 6. The VE against types 1 and 3 was the lowest in Uttar Pradesh and Bihar, where the force of transmission of WPVs was maximum on account of the highest infant-population density. Transmission was finally interrupted with sustained and extraordinary efforts. During the years since 2004 annual pulse polio vaccination campaigns were conducted 10 times each year, virtually every child was tracked and vaccinated - including in all transit points and transport vehicles, monovalent OPV types 1 and 3 were licensed and applied in titrated campaigns according to WPV epidemiology and bivalent OPV (bOPV, with both types 1 and 3) was developed and judiciously deployed. Elimination of WPVs with OPV is only phase 1 of polio eradication. India is poised to progress to phase 2, with introduction of inactivated poliovirus vaccine (IPV), switch from tOPV to bOPV and final elimination of all vaccine-related and vaccine-derived polioviruses. True polio eradication demands zero incidence of poliovirus infection, wild and vaccine.

Serum trace elements in obese women with or without diabetes

Abstract: Background & objectives: Relationship of trace elements with obesity and diabetes is complex, alterations in their metabolism can be induced by the diseases and their complications. To study the role of the trace elements in diabetes and obesity, serum trace elements levels (Cr, Se, Fe, Zn, Cu and Mn) were measured in obese women with or without diabetes as well as healthy women. Further, correlation between serum trace elements levels and glucose, insulin, homeostasis model assessment (HOMA-IR), glycated haemoglobin (HbA 1 c), body mass index (BMI), waist circumferences, waist -to -hip ratio and high-sensitivity C-reactive protein(hsCRP) were also determined in these women. Methods: This study was performed with morbidly obese (BMI >40 kg/m 2 women with diabetes (n=41), without diabetes (n=45) and 50 healthly non obese women. Anthropometric measurements were taken and levels of serum Zn, Cr, Fe Cu and Mn were determined. Biochemical parameters included serum glucose, insulin, lipids, haemoglobin, hsCRP and HbA1C. Results: The levels of Zn (P Interpretation & conclusions: Our findings showed significant association between Zn and Fe deficiencies and obesity. Also, obese women with diabetes may be at a greater risk of developing imbalances and deficiencies of trace elements compared with obese women without diabetes.

Antimicrobial susceptibility of Salmonella enterica serovars in a tertiary care hospital in southern India.

Abstract: Background & objectives: Salmonella enterica serovars Typhi and Paratyphi are predominantly known to cause enteric fever. Multidrug resistance in S. Tphi and S. Paratyphi has emerged as a cause of concern. This study was done to evaluate status in antimicrobial susceptibility patterns of Salmonella enterica serovar Typhi (S. Typhi) and S. Paratyphi obtained from blood culture in a tertiary care hospital in south India. Methods: Blood isolates of Salmonella species over a two year period between May 2009 and June 2011 were studied. A total of 322 isolates of Salmonella species were tested for antimicrobial susceptibility by Kirby-Bauer disc diffusion method. The MIC of ciprofloxacin was obtained by E-test, and azithromycin MIC was confirmed by agar dilution method for a limited number of isolates. Results: Of the total of 322 isolates studied, 186 (57.8%) were S. Typhi, 134 (41.6%) were S. Paratyphi A, and two were S. Paratyphi B. Of these, 44(13.66%) were resistant to ciprofloxacin (MIC Interpretation & conclusions: Nalidixic acid resistance screening is not a reliable surrogate indicator of ciprofloxacin resistance. Ciprofloxacin MIC should to be routinely done. Azithromycin resistance appears to be emerging. However, isolates showed a high degree of susceptibility to ampicillin, co-trimoxazole and chloramphenicol. Thus, antibiotics like ampicillin and co-trimoxazole may once again be useful for the management of enteric fever in southern India.

Modulation of autoimmune diseases by interleukin (IL)-17 producing regulatory T helper (Th17) cells

Abstract: Following the discovery of interleukin (IL)-17 producing T helper (Th17) cells as a distinct lineage of CD4+ T helper cells it became clear that these cells play an important role in the host defense against extracellular fungal and bacterial pathogens and participate in the pathogenesis of multiple inflammatory and autoimmune disorders. Depending on the microenvironment, Th17 cells can alter their differentiation programme ultimately giving rise to either protective or pro-inflammatory pathogenic cells. We found that besides the conventional in vitro protocol for Th17 differentiation by transforming growth factor-beta (TGF-β) plus IL-6 cytokines, a combination of IL-23 plus IL-6 can also induce Th17 cells. The Th17 cells induced by IL-23 plus IL-6 (termed as effector Th17, Teff17 cells) are pathogenic upon adoptive transfer into non-obese diabetic (NOD) mice contributing to the development of type 1 diabetes (T1D) while cells induced by TGF-β plus IL-6 (termed as regulatory T cells, Treg17 cells) are non pathogenic and regulatory, and suppressed the pathogenic T cells in T1D. These cells differentially expressed a number of cytokines where Teff17 cells exhibited an increase in granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-22 whereas Treg17 cells demonstrated increased expression of IL-21 and immunosuppressive cytokine IL-10. Differentiation of Th17 cells is controlled by a transcription factor, RORγT although these cells also express variable levels of T-bet and FoxP3 transcription factors. This points to a dual functional role of Th17 subsets in autoimmune diseases particularly T1D. We suggest that similar to conventional regulatory T cells (Treg), induction of regulatory Treg17 cells could play an important role in modulating and preventing certain autoimmune diseases.