A national sample survey of leprosy was undertaken in partnership with Indian Council of Medical Research (ICMR) institutions, National Leprosy Eradication Programme (NLEP), Panchayati Raj members, and treated leprosy patients to detect new cases of leprosy in India. The objectives of the survey were to estimate the new leprosy case load; record both Grade 1 and Grade 2 disabilities in the new cases; and to assess the magnitude of stigma and discrimination prevalent in the society. A cluster based, cross-sectional survey involving all States was used for the door-to-door survey using inverse sampling methodology. Rural and urban clusters were sampled separately. The population screened for detecting 28 new cases in rural and 30 in urban clusters was enumerated, recorded and analyzed. Data capture and analysis in different schedules were the main tools used. For quality control three tiers of experts were utilized for the confirmation of cases and disabilities. Self-stigma was assessed in more than half of the total new patients detected with disabilities by the approved questionnaire. A different questionnaire was used to assess the stigma in the community. A population of 14,725,525 (10,302,443 rural; 4,423,082 urban) was screened and 2161 new cases - 1300 paucibacillary (PB) and 861 multibacillary (MB) were detected. New case estimates for leprosy was 330,346 (95% Confidence limits, 287,445-380,851). Disabilities observed in these cases were 2.05/100,000 population and 13.9 per cent (302/2161) in new cases. Self-stigma in patients with disabilities was reduced, and the patients were well accepted by the spouse, neighbour, at workplace and in social functions.

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Breast cancer is a heterogeneous disease and may present with different clinical and biological characteristics. At present, breast cancer is divided into molecular subgroups besides its histopathological classification. Decision for adjuvant chemotherapy is made based on not only histopathological characteristics but also molecular and genomic characteristics using indices, guidelines and calculators in early-stage breast cancer. Making a treatment plan through all these prognostic and predictive methods according to risk categories aims at preventing unnecessary or useless treatments. In this review, an attempt to make a general assessment of prognostic and predictive methods is made which may be used for planning individualized therapy and also the comments of the guidelines used by the oncologists worldwide on these methods.

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With confirmation of Zika virus (ZIKV) presence in India, screening of a large number of febrile illness samples yielded only four positive cases. In this review, we address the current concern with context to India. The possible reasons for low level of Zika prevalence in India have been discussed, by extracting some probable explanations from previous experience of chikungunya virus-vector model/studies. In the current context, it is hypothesized that Indian mosquito strains have lower susceptibility gradient/threshold for ZIKV. The very low positivity in the humans also indicates low levels of mosquito-human-mosquito transmission cycle. There is also a need to look for the existence of any such animal cycle/sylvatic involvement in India. The recently detected four cases in India show local transmission of ZIKV suggesting that ZIKV might have been present in India since long time. The earlier vector-virus relationship studies with chikungunya suggested that in due course of time, ZIKV might become a major public health concern in the future.

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Background & objectives: Transfusion-transmitted infections (TTIs) are the major problem associated with blood transfusion. Accurate estimates of risk of TTIs are essential for monitoring the safety of blood supply. The present study was undertaken to determine the percentage of voluntary donors (VDs) and replacement donors (RDs) and also, to estimate and compare the seroprevalence and changing trends of TTIs amongst VDs and RDs in a regional blood transfusion centre in north India. Methods: This retrospective study was based on the records of all voluntary and replacement donations which were collected from January 2008 to December 2014 in a Regional Blood Transfusion Centre placed in a tertiary care hospital in Delhi, India. Results: Of the total 220,482 donations, 163,540 (74.17%) were voluntary and 56,942 (25.83%) were replacement donation. The overall seroprevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis and malaria were 0.32, 1.61, 0.73, 1.62 and 0.06 per cent, respectively. Furthermore, the TTIs were more frequently encountered in RDs in comparison to VDs. Interpretation & conclusions: The increase in public awareness regarding voluntary blood donation, meticulous donor screening, counselling and use of highly sensitive tests can help in reducing the risk of TTIs.

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Background & objectives: Age at first drink has its influence on later life drinking patterns. The association between age at first drink and adult alcohol consumption has not been studied in clinical population. This study was aimed to determine the age at first drink and its correlation with adult life drinking patterns in alcohol-dependent patients. Methods: Adult participants with alcohol dependence were included from the inpatient and outpatient wards of a tertiary care de-addiction facility in India. Questionnaires administered were National Institute on Alcohol Abuse and Alcoholism-Quantity Frequency for alcohol and the Fagerstrom Test for Nicotine Dependence for tobacco. Results: Of the 99 participants (92% males) with mean age 37±8.36 yr, mean age at first drink was 21.14±5.33 yr. After controlling for age, satisfaction with life scores and smoking, age at first drink showed a significant negative correlation with drinking days per week (r=-0.259, P=0.012), typical drink per day (r=-0.218, P=0.035) and maximum drinks in the previous month/year (r=-0.233, -0.223 and P=0.024, 0.031, respectively). Interpretation & conclusions: Our study suggested that earlier age of first drink correlated with chronic heavy drinking patterns in later adult life in alcohol-dependent patients. This may have implications for alcohol control policies determining the age for legal consumption.

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Background & objectives: In India, health expenditure accounts for less than 5 per cent of the Gross Domestic Product and the level of out-of-pocket (OOP) spending is 69.5 per cent of total health expenditures. OOP expenditure exacerbates poverty and has a negative impact on equity and can increase the risk of vulnerable groups slipping into poverty. This study was conducted to estimate the OOP expenditure on health and catastrophic health expenditure and their socio-demographic determinants in a rural area of Maharashtra, India. Methods: This was a prospective observational study involving monthly follow up visits, done in 180 households of three villages under a primary health centre in Wardha district, India. Results: Of the 180 families, 18.9 per cent had catastrophic health expenditure over a period of one year. The median total out-of-pocket health expenditure was '1105.00 with median medical expenditure being '863.85 and median non-medical health expenditure being '100.00. A total of 151 (83.9%) had enough money, 27 (15%) borrowed money and two (1.1%) of them sold assets. The significant correlates for the ratio of out-of-pocket health expenditure to total annual income of the family were the occupation of head of family, caste category and type of village. The significant correlate for catastrophic health expenditure was type of village. Interpretation & conclusions: Around one-fifth of the households had catastrophic health expenditure. People with no healthcare facility located in their village had higher odds of having catastrophic health expenditure. Private providers were preferred for the treatment of acute illnesses and medical college hospitals for hospitalization.

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Background & objectives: Development of antibacterial resistance and its association with antibiotic overuse makes it necessary to identify a specific and sensitive biomarker for the diagnosis of bacterial infection and guiding antibiotic therapy. Procalcitonin (PCT), as a sepsis biomarker, may play a role in guiding antibiotics treatment in hospital settings. The aim of the current meta-analysis was to analyze the utility of PCT on various outcomes of interest in inpatients. Methods: Different databases were searched for randomized controlled trials comparing PCT-guided therapy with standard therapy in admitted patients with bacterial infections. Twenty six articles were found suitable for full text search and of these, 16 studies were considered finally for data extraction. Results: There were no significant differences found in total mortality [pooled odds ratio (OR) 1.04, 95% confidence interval (CI) 0.89-1.22, P=0.63], 28-day mortality (pooled OR 0.97, 95% CI 0.80-1.19, P=0.79), need of Intensive Care Unit admission (OR=0.80, 95% CI 0.59-1.09, P=0.16) and duration of stay in hospital (pooled mean difference −0.01, 95% CI −0.50-0.49, P=0.98) between treatment and control groups. PCT-guided treatment significantly decreased the duration of antibiotic treatment (pooled mean difference −2.79, 95% CI −3.52-−2.06, P<0.00001). Interpretation & conclusions: PCT-guided therapy significantly decreased antibiotics exposure and thus treatment cost. However, the hard endpoints did not demonstrate any significant benefits, possibly due to low power to detect differences and/or the presence of comorbidities.

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Background & objectives: Dermatophytes are keratinophilic fungi that infect keratinized tissues of human and animal origin. Trichophyton mentagrophytes is considered to be a species complex composed of several strains, which include both anthropophiles and zoophiles. Accurate discrimination is critical for comprehensive understanding of the clinical and epidemiological implications of the genetic heterogeneity of this complex. Molecular strain typing renders an effective way to discriminate each strain. The objective of the study was to characterize T. mentagrophytes clinical isolates to sub-species level using molecular techniques and non-transcribed spacer (NTS) region as marker. Methods: Sixty four T. mentagrophytes clinical isolates were identified by phenotypic methods. These were subjected to polymerase chain reaction targeting three sub-repeat elements (SREs), TmiS0, TmiS1 and TmiS2 of the NTS region. Sequence analysis of internal transcribed spacer (ITS) region of different types was also done. Results: Strain-specific polymorphism was observed in all three loci. Totally, 13 different PCR types were obtained on combining all the three SREs loci. No variation was observed in the ITS region. Interpretation & conclusions: The study described the usefulness of molecular strain typing technique for the discrimination of the T. mentagrophytes isolates. This will help for the future explorations into the epidemiology of T. mentagrophytes and its complex.

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Background & objectives: The in vitro assays for susceptibility of Plasmodium falciparum to antimalarial drugs are important tools for monitoring drug resistance. During the present study, efforts were made to establish long-term continuous in vitro culture of Indian field isolates of P. falciparum and to determine their sensitivity to standard antimalarial drugs and antibiotics. Methods: Four (MZR-I, -II, -III and -IV) P. falciparum isolates were obtained from four patients who showed artemisinin-based combination therapy (ACT) from Mizoram, a north-eastern State of India, and characterized for their in vitro susceptibility to chloroquine diphosphate (CQ), quinine hydrochloride dehydrate, mefloquine, piperaquine, artemether, arteether, dihydro-artemisinin (DHA), lumefantrine and atovaquone and antibiotics, azithromycin and doxycycline. These patients showed ACT treatment failure. Two-fold serial dilutions of each drug were tested and the effect was evaluated using the malaria SYBR Green I fluorescence assay. K1 (chloroquine-resistant) and 3D7 (chloroquine-sensitive) reference strains were used as controls. Results: Growth profile of all field isolates was identical to that of reference parasites. The IC50 values of all the drugs were also similar against field isolates and reference parasite strains, except K1, exhibited high IC50 value (275±12.5 nM) of CQ for which it was resistant. All field isolates exhibited higher IC50 values of CQ, quinine hydrochloride dihydrate and DHA compared to reference strains. The resistance index of field isolates with respect to 3D7 ranged between 260.55 and 403.78 to CQ, 39.83 and 46.42 to quinine, and 2.98 and 4.16 to DHA, and with respect to K1 strain ranged between 6.51 and 10.08, 39.26 and 45.75, and 2.65 and 3.71. MZR-I isolate exhibited highest resistance index. Interpretation & conclusions: As the increase in IC50 and IC90 values of DHA against field isolates of P. falciparum was not significant, the tolerance to DHA-piperaquine (PPQ) combination might be because of PPQ only. Further study is required on more number of such isolates to generate data for a meaningful conclusion.

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Background & objectives: Immune complexes (ICs) play a crucial role which can either be beneficial or pathological to the host. Involvement of circulating immune complexes (CICs) has been shown in tuberculosis (TB) cases (adults and neonates form), but its immunomodulatory effect has not been studied in vivo. Hence, this study was carried out to understand and explore the prognostic therapeutic potential of CICs on the host immune system in guinea pigs animal TB model. Methods: In this study, the guinea pigs (group I) were immunized with in vitro synthesized antigen excess IC (AgX-IC), group II with antibody excess IC (AbX-IC) and group III with phosphate-buffered saline. All these animals were sensitized with Mycobacterium tuberculosis H37Rv before immunization and subsequently infected with M. tuberculosis H37Rv strain post-immunization with IC. Results: Mortality was observed in animals belonging of groups II and III, while all animals in group I survived. A steady increase in the body weight of animals immunized with AgX-IC was observed when compared to the other groups. The infection load in the spleen and lungs was less in animals from group I when compared to the other groups. The CICs were found to be in higher concentration in serum of IC-immunized guinea pigs when compared to ICs non-immunized animals. Interpretation & conclusions: Based on our findings, it can be speculated that the ICs may have a protective immunomodulatory role pertaining to disease progression and development of pathology. As a new perspective, with further insight into the underlying mechanism of action and correlation with clinical data, ICs may also be used as a potential tool for assessing the immune status of the infected individuals, especially the close contacts of TB patients.

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Background & objectives: Polyethylene terephthalate (PET) graft, designed and developed at our institute for vascular reconstruction, is porous to promote optimal incorporation and neointima formation, requiring pre-clotting or biomodification by sealing the pores before implantation. The objective of this study was to characterize, test and perform preclinical evaluation of hydrogel (alginate dialdehyde cross-linked gelatin) sealed fluoropassivated PET vascular prosthesis in pig model, so as to avoid pre-clotting, for its safety and efficacy before employing the indigenous and less expensive graft for clinical use. Methods: Hydrogel sealed, fluoropassivated PET vascular prosthesis were tested for haemocompatibility and toxicity followed by small animal toxicology tests and in vivo experiments in pigs receiving implantation at thoracic aorta. All 33 animals received test as well as control grafts with a plan for phased explantation at 2, 12 and 26 weeks. All animals underwent completion angiogram at the end of procedure as well as before graft explantation. Results: Haemocompatibility tests for haemolysis and toxicity tests showed no adverse events in tested mice and rabbits. Completion angiogram showed intact anastamosis and patent graft in each animal in post-operative period and at explantation. Gross and histopathological examination showed well-encapsulated grafts, clean glistening neointima and no evidence of thrombus in both test and control grafts. Interpretation & conclusions: Hydrogel sealed, fluoropassivated PET vascular prosthesis was found non-toxic, haemocompatible and remained patent in in vivo studies at planned intervals.

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Background & objectives: Uncertainty often arises in differentiating seasonal variation from outbreaks of malaria. The present study was aimed to generalize the theoretical structure of sine curve for detecting an outbreak so that a tool for early warning of malaria may be developed. Methods: A 'case/mean-ratio scale' system was devised for labelling the outbreak in respect of two diverse districts of Assam and Rajasthan. A curve-based method of analysis was developed for determining outbreak and using the properties of sine curve. It could be used as an early warning tool for Plasmodium falciparum malaria outbreaks. Result: In the present method of analysis, the critical C_max(peak value of sine curve) value of seasonally adjusted curve for P. falciparum malaria outbreak was 2.3 for Karbi Anglong and 2.2 for Jaisalmer districts. On case/mean-ratio scale, the C_max value of malaria curve between C_maxand 3.5, the outbreak could be labelled as minor while >3.5 may be labelled as major. In epidemic years, with mean of case/mean ratio of ≥1.00 and root mean square (RMS) ≥1.504 of case/mean ratio, outbreaks can be predicted 1-2 months in advance. Interpretation & conclusions: The present study showed that in P. falciparum cases in Karbi Anglong (Assam) and Jaisalmer (Rajasthan) districts, the rise in C_maxvalue of curve was always followed by rise in average/RMS or both and hence could be used as an early warning tool. The present method provides better detection of outbreaks than the conventional method of mean plus two standard deviation (mean+2 SD). The identified tools are simple and may be adopted for preparedness of malaria outbreaks.

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