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.

One of the most celebrated achievements of immunology and modern medicine is the eradication of the dreaded plague smallpox. From the introduction of smallpox vaccination by Edward Jenner, to its popularization by Louis Pasteur, to the eradication effort led by Donald Henderson, this story has many lessons for us today, including the characteristics of the disease and vaccine that permitted its eradication, and the obviousness of the vaccine as a vector for other intractable Infectious diseases. The disease itself, interpreted in the light of modern molecular immunology, is an obvious immunopathological disease, which occurs after a latent interval of 1-2 weeks, and manifests as a systemic cell-mediated delayed type hypersensitivity (DTH) syndrome. The vaccine that slayed this dragon was given the name vaccinia, and was thought to have evolved from cowpox virus, but is now known to be most closely related to a poxvirus isolated from a horse. Of interest is the fact that of the various isolates of orthopox viruses, only variola, vaccinia and monkeypox viruses can infect humans. In contrast to the systemic disease of variola, vaccinia only replicates locally at the site of inoculation, and causes a localized DTH response that usually peaks after 7-10 days. This difference in the pathogenicity of variola vs. vaccinia is thought to be due to the capacity of variola to circumvent innate immunity, which allows it to disseminate widely before the adaptive immune response occurs. Thus, the fact that vaccinia virus is attenuated compared to variola, but is still replication competent, makes for its remarkable efficacy as a vaccine, as the localized infection activates all of the cells and molecules of both innate and adaptive immunity. Accordingly vaccinia itself, and not modified replication incompetent vaccina, is the hope for use as a vector in the eradication of additional pathogenic microbes from the globe.

Exercise based rehabilitation for patients with pulmonary arterial hypertension (PAH) is a new treatment option for these patients to improve their functional capacity and quality of life. Despite the benefits seen in cardiopulmonary rehabilitation in various other conditions, it has been underutilized for the patients with PAH. A review of currently registered ongoing trials on exercise training for patients with PAH from the World Health Organization International Clinical Trial Registry Platform was done using the key words "rehabilitation", "exercise training", "pulmonary artery hypertension" and "pulmonary hypertension" for a period of 10 years (2002-2012). The search revealed 57 registered trials in various trial registries from which seven met the inclusion criteria. The current studies are being carried out in Germany (n=4), Brazil (n=1), Australia (n=1) and India (n=1). This indicates a shift in focus from the only medical management to the rehabilitation and long term care for patients with PAH.

Background & objectives: Disability-adjusted life years (DALYs) have been accepted as a useful method to estimate the burden of disease, and can be adapted to determine the number of productive years lost due to the disability. DALY has been reported for many studies but not for leprosy. Hence this study was carried out in three States of India. In view of the fact that in this study, productive working years are used, the term is modified as DAWLY. Methods: A representative random sample of 150 leprosy affected persons, 50 from each States of Uttar Pradesh, West Bengal and Chhattisgarh, was chosen, and data were collected on detailed work-life history, occupation, time when leprosy was discovered, reported and treatment started, break of job/loss of income due to leprosy. The loss of wages and durations were used to compute the life-years lost due to leprosy, and summarized over the average total duration of 42 years of productive work-life from 18 to 60 years. The percentage losses were determined and differences tested for statistical significance. Results: The overall mean (± SE) disability adjusted working life years was 28.6 (±0.67), a reduction of 13.4 yr from the ideal productive working life period of 42 yr. The youngest patients with disability had a reduction of 41.4 per cent, as compared to the oldest patients. There was a significant increase in loss based on year for those whose disability started earlier (P=0.0024). Interpretation & conclusions: On an average, 30 per cent of the leprosy affected person's work life is lost due to disability.

Background & objectives: Tissue stiffness in liver is related to tissue composition, which is changed by cirrhosis, hepatocellular carcinoma or metastases. Shear wave ultrasonographic elastography is a new imaging technique by which the elasticity of soft tissue can be measured quantitatively. The aim of this study was to measure the elasticity values of liver segments in healthy volunteers. Methods: One hundred twenty seven healthy volunteers (89 women, 38 men; mean age 37, 72 ± 9.11 yr, range 17-63 yr) were examined on shear wave elastography and ultrasonography by using convex probe with a frequency of 3 MHz. Individuals with liver hepatosteatosis, cirrhosis, chronic liver disease, or focal liver lesions were excluded from the study. Results: The mean elasticity values of right posterior, right anterior, left medial and left lateral segments of the liver was determined as 4 (±2.2), 3.3 (±2.1), 3.8 (±2.1), and 3.7 (±1.9) kPa for each segments, respectively. There was no significant difference in liver elasticity values between men and women. Interpretation & conclusions: In this preliminary study the elasticity values of liver segments were measured by shear wave ultrasonographic elastography in normal healthy volunteers. Further studies, comparing elasticity values of normal and pathologic tissues are needed to detect the diagnostic role of this new technique.

Background & objectives: Regular practice of slow breathing has been shown to improve cardiovascular and respiratory functions and to decrease the effects of stress. This pilot study was planned to evaluate the short term effects of pranayama on cardiovascular functions, pulmonary functions and galvanic skin resistance (GSR) which mirrors sympathetic tone, and to evaluate the changes that appear within a short span of one week following slow breathing techniques. Methods: Eleven normal healthy volunteers were randomized into Pranayama group (n=6) and a non-Pranayama control group (n=5); the pranayama volunteers were trained in pranayama, the technique being Anuloma-Viloma pranayama with Kumbhak. All the 11 volunteers were made to sit in similar environment for two sessions of 20 min each for seven days, while the pranayama volunteers performed slow breathing under supervision, the control group relaxed without conscious control on breathing. Pulse, GSR, blood pressure (BP) and pulmonary function tests (PFT) were measured before and after the 7-day programme in all the volunteers. Results: While no significant changes were observed in BP and PFT, an overall reduction in pulse rate was observed in all the eleven volunteers; this reduction might have resulted from the relaxation and the environment. Statistically significant changes were observed in the Pranayama group volunteers in the GSR values during standing phases indicating that regular practice of Pranayama causes a reduction in the sympathetic tone within a period as short as 7 days. Interpretation & conclusions: Beneficial effects of pranayama started appearing within a week of regular practice, and the first change appeared to be a reduction in sympathetic tone.

Background & objectives: There are only a few studies on aetiology of portal hypertension among adults presenting to tertiary care centres in India; hence we conducted this study to assess the aetiological reasons for portal hypertension in adult patients attending a tertiary care centre in southern India. Methods: Causes of portal hypertension were studied in consecutive new adult patients with portal hypertension attending department of Hepatatology at a tertiary care centre in south India during July 2009 to July 2010. Results: A total of 583 adult patients (>18 yr old) were enrolled in the study. After non-invasive testing, commonest causes of portal hypertension were cryptogenic chronic liver disease (35%), chronic liver disease due to alcohol (29%), hepatitis B (17%) or hepatitis C (9%). Of the 203 patients with cryptogenic chronic liver disease, 39 had liver biopsy - amongst the latter, idiopathic non cirrhotic intrahepatic portal hypertension (NCIPH) was seen in 16 patients (41%), while five patients had cirrhosis due to non alcoholic fatty liver disease. Fifty six (10%) adult patients with portal hypertension had vascular liver disorders. Predominant causes of portal hypertension in elderly (>60 yrs; n=83) were cryptogenic chronic liver disease (54%) and alcohol related chronic liver disease (16%). Interpretation & conclusions: Cryptogenic chronic liver disease was the commonest cause of portal hypertension in adults, followed by alcohol or hepatitis B related chronic liver disease. Of patients with cryptogenic chronic liver disease who had liver biopsy, NCIPH was the commonest cause identified. Vascular liver disorders caused portal hypertension in 10 per cent of adult patients. Cryptogenic chronic liver disease was also the commonest cause in elderly patients.

Background and objectives: Tribal men's reluctance in sharing responsibilities as supportive partners in reproductive and sexual health matters debar women from their sexual rights coupled with their negligence in health care and lesser utilization of reproductive health facilities. As a matter of fact a large proportion of ill health particularly related to sexually transmitted infections (STIs) suffered not only by men but also by their spouses. The present study was planned among one of the primitive tribes of Madhya Pradesh to understand the knowledge of males about reproductive tract infection (RTI)/STI/HIV/AIDS, RTI symptoms suffered, perception on sexual health, utilization of health services and to improve the knowledge by intervention of need based IEC (information, education, communication) strategy. Method: The study was conducted among 400 currently married men in the age group of 15-40 yr in one of the primitive tribes, Baigas of Dindori district of Madhya Pradesh. Eighteen villages were explored in the study. The IEC intervention was made by using quasi-experimental before and after with control design. Result: The baseline data generated indicated that Baigas male were poorly informed about RTI (18%), STI (21.5%) and HIV/AIDS (10%). Further, men also projected misconception on different aspects of sexuality. Women's views recorded also suggested a disturbing trend regarding male involvement in reproductive health particularly related to STIs. Interpretation & conclusions: After intervention of IEC targeting male population in age group 15 - 40 yr by adopting a before and after with controls design the awareness was improved significantly. The utilization of the health services was also improved significantly. The study recommends replication of the IEC strategy designed in other Baiga villages for improving the reproductive health of the tribe.

Background & objectives: Essential hypertension is a multifactorial disorder with a complex phenotype. Here we report a susceptibility locus for the hypertension mapped by a genome-wide microsatellite scanning in an affected Chinese family, in which 11 members had hypertension before the age of 40. Methods: A total of 22 individuals from a single family from Shanghai, PR China, were genotyped on more than 400 microsatellite markers with a spacing gap of less than 10 cm for nearly the entire scanned genome. Results: Linkage analysis suggested that an affected disorder is linked to a locus in the chromosome interval 12q23.1 to 12q23.3; two-point parametric analysis showed a logarithm of odds (LOD) score of 2.97 for the marker D12S346 (12q23.1) and 1.40 for the marker D12S78 (12q23.3). Fine mapping and haplotype analysis subsequently confirmed that eight continuous markers (D12Sac023161, D12S1706, D12S346, D12S1588, D12S1607, D12Sac010202, D12S78, D12Sac084356) had positive LOD with a maximum two-point LOD score of 3.34 for the marker D12S1706 and a maximum multi-point LOD score was 2.4002 for D12Sac010202, their NPL scores were 10.9091 for D12S1706 and 10.9114 for D12Sac010202. Interpretation & conclusions: A novel locus for essential hypertension was identified on chromosome 12q23.1 - q23.3. This finding implies that the region 12q23.1 to 12q23.3 might encompass a susceptible gene that caused hypertension in this Chinese family.

Background & objectives: The treatment outcomes under national antiretroviral therapy (ART) programme are being evaluated in some ART centres in the country. We carried out this study to analyze the impact of first line antiretroviral therapy in HIV infected patients attending a free ART roll out national programme clinic in Pune, India. Methods: Antiretroviral naive HIV infected patients attending the clinic between December 2005 and April 2008 and followed up till March 31, 2011 were included in the analysis. The enrolment and follow up of these patients were done as per the national guidelines. Viral load estimations were done in a subset of patients. Results: One hundred and forty two patients with median CD4 count of 109 cells/μl (IQR: 60-160) were initiated on treatment. The median follow up was 44 months (IQR: 37-53.3 months). Survival analysis showed that the probability of being alive at the end of 5 years was 85 per cent. Overall increase in the median CD4 count was statistically significant (P<0.001). It was significant in patients with >95 per cent adherence (P<0.001). In 14 per cent patients, the absolute CD4 count did not increase by 100 or more cells/μl at the end of 12 months. Viral load estimation in a subset of 68 patients showed undetectable levels in 61 (89.7%) patients after a median duration of 46 months (IQR: 38.3-54.8). Interpretation & conclusions: The first line treatment was effective in patients attending the programme clinic. The adherence level influenced immunological and virological outcomes of patients.

Background & objectives: HIV/AIDS patients may have renal involvement also, however, Indian data are sparse. The present study was done to find the spectrum of renal diseases in HIV/AIDS patients in north India. Methods: In this prospective pilot study, HIV positive patients aged >18 yr were screened for renal involvement [serum creatinine >1.5 mg% and/or significant proteinuria (>500 mg /day)]. Patients who were positive on screening were followed up prospectively and underwent kidney biopsy if indicated. Results: A total of 526 patients were screened, of these, 91 (17.3%) were found to have renal involvement. Group A (Treatment naοve) comprised 392 patients who were not on antiretroviral treatment (ART) and group B (patients on ART) comprised 134 patients. More patients (74/392, 18.9%) in group A had renal involvement as compared to patients in group B (17/134, 12.7%). Of the 91 patients with renal involvement, 26 were followed up and underwent kidney biopsy. Thirteen patients had only proteinuria and another 13 had renal dysfunction with or without proteinuria. Most common histological diagnosis was mesangioproliferative glomerulonephritis (mes PGN) (10/26). Two patients had collapsing FSGS (focal segmental glomerulosclerosis) and three patients had immune complex glomerulonephritis. Seven patients had acute kidney injury, whom six totally recovered from their renal function. All patients with mesPGN tolerated angiotensin converting enzyme (ACE) inhibitors well. There was mixed response of collapsing FSGS to steroids. Both patients with MPGN (membranoproliferative glomerulonephritis) did well on low dose of steroid and ART. Interpretation & conclusions: Renal involvement was found to be common in HIV positive patients (17.3%). A low occurrence of renal involvement found in patients already on ART suggests some renoprotective effect of ART. Our preliminary results showed that collapsing FSGS was not rare in Indian HIV positive population, but classical HIV associated nephropathy was not seen. Longitudinal studies with robust study design and large sample size need to be done to confirm the findings.

Background & objectives: In India enteric fever is a major public health problem and Salmonella Typhi is the most common aetiologic agent. Any control strategy for such infections depends to a large extent on the understanding of the disease and relatedness of strains across the world. Multi locus sequence typing (MLST) is one such method of genotyping of bacteria based upon housekeeping genes of known function and chromosome position. MLST data of pathogens are important to determine the molecular evolution by a stable and reproducible method. This study was undertaken to determine the sequence types of representatives S. Typhi isolates obtained from enteric fever patients in a tertiary care centre in north India, over a period of 20 years (1990-2010). Methods: A total of 30 representative isolates of S. Typhi identified by biochemical and serological tests were subjected to multi locus sequence typing (MLST). Seven housekeeping genes of known function and chromosome position were used for the typing by MLST. Sequencing was carried out by using an automated DNA sequencer and results were analyzed to generate phylogenetic tree. Results: MLST pattern grouped S. Typhi into two sequence types- ST1 and ST2. ST1 was predominantly present followed by ST2. Interpretation & conclusions: By MLST the presence of both sequence types, ST1 and ST2, was found in S. Typhi isolates in our region. Predominately ST1 was present followed by ST2. These preliminary results corroborate the global distribution of both sequence types of S. Typhi and also emphasize for the continuous screening of S. Typhi.

Background & objectives: Subinhibitory concentrations (sub-MICs) of antibiotics, although not able to kill bacteria, but influence bacterial virulence significantly. Fluoroquinolones (FQs) which are used against other bacterial pathogens creates resistance in non-targeted Streptococcus pyogenes. This study was undertaken to characterize the effect of sub-MICs of FQs on S. pyogenes biofilm formation. Methods: Biofilm forming six M serotypes M56, st38, M89, M65, M100 and M74 of S. pyogenes clinical isolates were challenged against four FQs namely, ciprofloxacin, ofloxacin, levofloxacin and norfloxacin. The antibiofilm potential of these FQs was analysed at their subinhibitory concentrations (1/2 to 1/64 MIC) using biofilm assay, XTT reduction assay, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Results: Among the four FQs tested, ofloxacin and levofloxacin at 1/2 MIC showed the maximum inhibition (92%) of biofilm formation against M56 and M74 serotypes. FQs effectively interfered in the microcolony formation of S. pyogenes isolates at 1/2 to 1/8 sub-MICs. Inhibition of biofilm formation was greatly reduced beyond 1/16 MICs and allowed biofilm formation. XTT reduction assay revealed the increase in metabolic activity of S. pyogenes biofilm against the decrease in FQs concentration. SEM and CLSM validated the potential of sub-MICs of FQs against the six S. pyogenes. Interpretation & conclusions: Our results showed that the inhibitory effect all four FQs on S. pyogenes biofilm formation was concentration dependent. FQs at proper dosage can be effective against S. pyogenes and lower concentrations may allow the bacteria to form barriers against the antibiotic in the form of biofilm.

Phytochemicals are widely used as biocontrol agent against vector mosquitoes. The present study was undertaken to isolate and evaluate the mosquitocidal activity of various extracts of berries of S. nigrum against Culex quinquefasciatus. Crude and chloroform: methanol (1:1, v/v) extracts of fresh, mature, green berries of S. nigrum were tested against Cx. quinquefasciatus. The lethal concentration was determined and the chemical nature of the active substance was evaluated. A qualitative phytochemical analysis of chloroform: methanol (1:1, v/v) extract was performed in search of the active ingredient. The appropriate lethal concentrations at 24 h for chloroform: methanol (1:1, v/v) extract was also studied on non-target organisms. In a 72 h bioassay experiment with crude extract, the highest mortality was recorded in 3 per cent extract. In the chloroform: methanol (1:1, v/v) solvent extract, the maximum mortality was recorded at a concentration of 120 μg/ml. The log probit analysis (95% confidence level) recorded lowest LC ₅₀ value at 72 h of exposure. Both crude and chloroform: methanol (1:1, v/v) extracts showed good larvicidal activity against Cx. quinquefasciatus. The isolated active ingredient may be tested as a potential larvicide after determination of its structure.

Background & objectives: Galantamine, a centrally-acting cholinesterase inhibitor, has been used in the treatment of mild-to-moderate dementia of Alzheimer disease. Increased mortality, mainly due to cardiovascular events, was observed in placebo-controlled trials of galantamine. Several studies have evaluated the efficacy of galantamine in dementia, it is not clear whether it has an effect on platelet function. It is important to clarify this effect, because it may be related to thrombotic tendency or bleeding diathesis. This study was aimed to investigate the effect of galantamine on platelet aggregation in whole blood from healthy, elderly subjects. Methods: Fifteen healthy (mean age 76.8 ± 7.2 yr) volunteers were included in the study. Three concentrations of galantamine solution (20, 40 and 80 ng/μl) were prepared. Each concentration of galantamine solution and control diluent without galantamine were incubated with whole blood. After incubation, aggregation responses were evaluated with ADP (5 μM) and collagen (2 μg/ml) in platelet-rich plasma. Results: Compared to control, pre-incubation with all dilutions of galantamine had no detectable effect on platelet aggregation response induced by ADP and collagen. Galantamine also had no detectable effect on platelet aggregation in a dose-dependent manner. Interpretation & conclusions: This in vitro study suggested that galantamine administration had no effect on platelet aggregation in the clinically relevant doses.

Background & objectives: Enterococci are the leading cause of nosocomial infections, and are thus a persisting clinical problem globally. We undertook this study to determine the virulence factors and the antibiotic resistance in Enterococcus clinical isolates. Methods: One hundred and fifty Enterococcus isolates obtained from various clinical specimens were speciated biochemically and subjected to antibiotic susceptibility testing using Kirby-Bauer disk diffusion method. Resistance to vancomycin was determined by using agar screen method. Haemolysin and gelatinase productions were detected using 5 per cent sheep blood agar and 12 per cent gelatin agar, respectively. Results: Among the 150 Enterococcus isolates, 84 (56%) were E. faecalis. 51(34%) E. faecium, and 15 (10%) were other Enterococcus spp. Haemolysin production was seen among 123 (82%) isolates while 61 (40.6%) isolates produced gelatinase. Nearly 50 per cent of the isolates showed high level aminoglycoside resistance (HLAR). A total of 13 (8.6%) isolates showed vancomycin resistance, of which 11(7.3%) had an MIC >8 ΅g/ml. Interpretation & conclusions: Presence of VRE was found to be low among the isolates studied. However, occurrence of VRE along with HLAR calls for regular detection of vancomycin resistance promptly and accurately to recognize VRE colonization and infection. Early detection of VRE and HLAR along with their virulence trait will help in preventing the establishment and spread of multidrug resistant Enterococcus species.