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   Table of Contents - Current issue
March 2019
Volume 149 | Issue 3
Page Nos. 309-432

Online since Monday, June 24, 2019

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What is new in the WHO consolidated guidelines on drug-resistant tuberculosis treatment? Highly accessed article p. 309
Surendra K Sharma, Keertan Dheda
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Health of tribal populations in India: How long can we afford to neglect? p. 313
Jai Prakash Narain
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Centrality of telomerase in cellular life p. 317
Deepak Kumar Mishra, Pramod K Yadava
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Understanding racial diversities in Kaposi's sarcoma p. 319
Sheela Godbole, Manisha Ghate, Sanjay Mehendale
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Medical implications of protein moonlighting p. 322
MN Gupta, Saurabh Pandey, Nasreen Z Ehtesham, Seyed E Hasnain
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Patient-driven initiatives for prioritizing drug discovery for rare diseases Highly accessed article p. 326
Alok Bhattacharya, Sudha Bhattacharya
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Implementation framework for One Health approach p. 329
Rajesh Bhatia
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Nutrition communication - Rhetoric & reality p. 333
SubbaRao M Gavaravarapu
Given the context that undernutrition in India co-exists with the problems of overweight/obesity and associated non-communicable diseases as well as micronutrient deficiencies, integrating nutritional concerns in developmental policies and governance is gaining significance. There are many schemes implemented to tackle malnutrition in India, but creating synergy and linking these schemes with each other to achieve a common goal are lacking. Nutrition communication can be an important component to create the synergy required to change malnourished India to malnutrition-free India. Although nutrition education/communication is recognized as a necessary component in various national nutrition programmes, there is not much evidence of distinct evaluation of these components. Only a minor proportion of community nutrition research has been devoted to nutrition education and communication. Although there are scattered efforts in experimenting with newer communication approaches and media for promoting nutrition, there is a dearth of published literature. In this review an attempt was made to critically examine the nutrition education and communication research and practice with special focus on India. This review provides a historical perspective of evolution of nutrition education and communication with an overview of communication approaches, media, methods and technologies used in various research studies and programmes as well as the lessons learnt.
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Knockdown of human telomerase reverse transcriptase induces apoptosis in cervical cancer cell line p. 345
Anantha Lakshmi Nagapoosanam, Nithya Ganesan, Devan Umapathy, Rajesh Kannan Moorthy, Antony Joseph Velanganni Arockiam
Background & objectives: Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase enzyme that maintains telomere ends by the addition of telomeric repeats to the ends of chromosomal DNA, and that may generate immortal cancer cells. Hence, the activity of telomerase is raised in cancer cells including cervical cancer. The present study aimed to validate the unique siRNA loaded chitosan coated poly-lactic-co-glycolic acid (PLGA) nanoparticle targeting hTERT mRNA to knock down the expression of hTERT in HeLa cells. Methods: The siRNA loaded chitosan coated polylactic-co-glycolic acid (PLGA) nanoparticles were synthesized by double emulsion solvent diffusion method. The characterization of nano-formulation was done to determine efficient siRNA delivery. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot were performed to evaluate silencing efficiency of nano-formulation. Results: Size, zeta potential and encapsulation efficiency of nanoparticles were 249.2 nm, 12.4 mV and 80.5 per cent, respectively. Sustained release of siRNA from prepared nanoparticle was studied for 72 h by ultraviolet method. Staining assays were performed to confirm senescence and apoptosis. Silencing of hTERT mRNA and protein expression were analyzed in HeLa cells by RT-PCR and Western blot. Interpretation & conclusions: The findings showed that biodegradable chitosan coated PLGA nanoparticles possessed an ability for efficient and successful siRNA delivery. The siRNA-loaded PLGA nanoparticles induced apoptosis in HeLa cells. Further studies need to be done with animal model.
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Racial disparities in incidence & survival of Kaposi's sarcoma in the United States p. 354
Vivek Kumar, Parita Soni, Mohit Garg, Arsalan Talib Hashmi, Abhinav Binod Chandra
Background & objectives: In the United States (US), Kaposi's sarcoma (KS) is usually seen in the patients affected by human immunodeficiency virus (HIV). The racial differences in the incidence rates and survival of patients with KS have been reported in the US. We undertook this study to analyse the disparities in the race-specific incidence rate and survival of KS patients of two different races in the US based on SEER (Surveillance, Epidemiology and End Results) database. Methods: Data on KS patients of African-American (AA) and non-Hispanic White (NHW) races who were diagnosed during 1973-2013 were extracted from SEER database to estimate the incidence rates and survival of KS patients. Results: A total of 18,388 NHWs and 3,455 AAs were diagnosed with KS. The age-adjusted incidence rate (AAIR) of KS in patients aged 20-44 yr was 3.8 times higher in AAs than in NHWs. The decline in AAIR of KS among NHWs started during 1989-1994 and preceded decline in the AAIR of AAs. After introduction of highly active antiretroviral therapy (HAART), the incidence continued to decline, but the decrease in the AAIR in AAs [annual percentage change (APC): −6.2; 95% confidence interval (CI): −8.8 to −3.5] was slower than that in NHWs (APC: −10.9; 95% CI: −12.6 to −9.1). The hazard ratio for all-cause mortality in KS patients of the AA race increased from 1.1 (95% CI: 1-1.2) in 1981-1995 to 1.55 (95% CI: 1.4-1.7) in 1996-2013 as compared to those of the NHW race. Interpretation & conclusions: Several significant racial disparities that emerged after HAART introduction in the incidence and survival of KS patients continued to persist, despite improvement in care of patients with HIV. Further studies need to be done to find out the underlying factors leading to these disparities.
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Oestrogen receptor Rsa I gene polymorphism in osteoporosis periodontitis patients with or without dental fluorosis p. 364
Dalvi Priyanka, Kharidi Laxman Vandana
Background & objectives: There is a paucity of information on association between dental fluorosis, osteoporosis and periodontitis. The aim of this pilot study was to evaluate oestrogen receptor (ER) Rsa 1 gene polymorphism in osteoporosis periodontitis patients with and without dental fluorosis. Methods: Twenty one primary osteoporotic patients suffering from periodontitis with dental fluorosis and 20 primary osteoporotic patients suffering from periodontitis without dental fluorosis participated in this study. Periodontitis was diagnosed based on age, gender T-scores using clinical parameters such as plaque scores, gingival bleeding scores and probing pocket depth, clinical attachment level (CAL) and severity of dental fluorosis. DNA was genotyped at the RsaI RFLP (in exon 5) inside the ER gene to study ER Rsa I gene polymorphism in osteoporosis periodontitis patients with and without dental fluorosis. Results: Patients with dental fluorosis had higher degree of osteoporosis than those without fluorosis. CAL was significantly higher (P <0.05) in those with dental fluorosis compared with those without. Rr heterozygote (21.95%) was observed in patients without fluorosis whereas RR mutant homozygote was absent in both the groups. Rr wild homozygote type was seen more in the patients with fluorosis (51.21%). Significant differences were found in distribution of these genotypes between patients with and without dental fluorosis. Interpretation & conclusions: This preliminary study showed the presence of ER I gene polymorphism in osteoporosis periodontitis patients without dental fluorosis. Further studies with large sample size are needed to confirm the association shown in this preliminary study.
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Expanding healthcare coverage: An experience from Rashtriya Swasthya Bima Yojna p. 369
Sonalini Khetrapal, Arnab Acharya
Background & objective: Given that Ayushman Bharat Yojna was launched in 2018 in India, analysis of Rashtriya Swasthya Bima Yojna (RSBY) become relevant. The objective of this study was to examine the scheme design and the incentive structure under RSBY. Methods: The study was conducted in the districts of Patiala and Yamunanagar in the States of Punjab and Haryana, respectively (2011-2013). The mixed method study involved review of key documents; 20 in-depth interviews of key stakeholders; 399 exit interviews of RSBY and non-RSBY beneficiaries in Patiala and 353 in Yamunanagar from 12 selected RSBY empanelled hospitals; and analysis of secondary databases from State nodal agencies and district medical officers. Results: Insurance companies had considerable implementation responsibilities which led to conflict of interest in enrolment and empanelment. Enrolment was 15 per cent in Patiala and 42 per cent in Yamunanagar. Empanelment of health facilities was 17 (15%) in Patiala and 37 (30%) in Yamunanagar. Private-empanelled facilities were geographically clustered in the urban parts of the sub-districts. Monitoring was weak and led to breach of contracts. RSBY beneficiaries incurred out-of-pocket (OOP) expenditures (₹5748); however, it was lower than that for non-RSBY (₹10667). The scheme had in-built incentives for Centre, State, insurance companies and health providers (both public and private). There were no incentives for health staff for additional RSBY activities. Interpretation & conclusions: RSBY has in-built incentives for all stakeholders. Some of the gaps identified in the scheme design pertained to poor enrolment practices, distribution of roles and responsibilities, fixed package rates, weak monitoring and supervision, and incurring OOP expenditure.
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Digital pressure in haemodialysis patients with brachial arteriovenous fistula p. 376
Alexandru Oprea, Adrian Molnar, Traian Scridon, Petru Adrian Mircea
Background & objectives: The pathophysiological mechanisms involved in distal pressure changes following arteriovenous fistula (AVF) creation in patients with end-stage renal disease (ESRD) are not completely understood. This study was aimed to assess digital pressure changes post-AVF creation and to identify the factors that might influence these changes in ESRD patients. Methods: In this prospective study, 41 patients with ESRD underwent AVF creation. Basal digital pressure (BDP), digital brachial index (DBI), calcium, phosphorus and blood urea levels were assessed preoperatively. BDP, DBI, vein and artery diameters, and AVF blood flow were also evaluated at one and two month(s) post-AVF creation. Results: Mean BDP significantly decreased from 131.64±25.86 mmHg (baseline) to 93.15±32.14 and 94.53±32.90 mmHg at one and two months post-AVF creation, respectively (P <0.001). Mean DBI significantly decreased one month post-AVF creation versus baseline (0.70±0.18 vs. 0.89±0.17 mm, P <0.001) and remained similar at two versus one month(s) postoperatively (0.70±0.23 vs. 0.70±0.18 mm). At both postoperative timepoints, no correlation between DBI decrease and increased artery and vein diameters or fistula blood flow was observed. Mean DBI difference between patients with previous ipsilateral access versus those without was not significant from pre to one month postoperatively. No correlation was observed between baseline phosphorus, calcium and blood urea nitrogen and DBI changes. Interpretation & conclusions: Our findings suggest that decrease in distal pressure following AVF creation may not be influenced by the arterial remodelling degree, vein diameter or fistula flow. In uraemic patients, those with low calcium and/or increased phosphorus, no association between these parameters and DBI changes could be observed.
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Impact of tuberculosis on glycaemic status: A neglected association p. 384
Darshan Krishnappa, Surendra K Sharma, Achintya Dinesh Singh, Sanjeev Sinha, AC Ammini, Manish Soneja
Background & objectives: Diabetes mellitus (DM) is an important risk factor for tuberculosis and has received increasing emphasis. However, the reverse association of tuberculosis impacting blood sugar levels has not been well studied. The present study was conducted to evaluate the prevalence of hyperglycemia in patients with tuberculosis and assess its resolution following successful treatment of tuberculosis. Methods: In this prospective study, a total of 582 patients with tuberculosis were evaluated for hyperglycaemia [DM or impaired glucose tolerance (IGT)] with random blood sugar (RBS) and all patients with RBS >100 mg/dl were subjected to a 75 g oral glucose tolerance test (OGTT). All patients received thrice weekly intermittent Directly Observed Treatment Short Course (DOTS) for tuberculosis. Patients with hyperglycaemia were re-evaluated at the end of anti-tuberculosis treatment with an OGTT and glycated hemoglobin (HbA1c) levels to assess for glycaemic status. Results: In the present study, 41 of the 582 patients were found to have DM [7%, 95% confidence interval (CI) (5.2, 9.4)] while 26 patients were found to have IGT [4.5%, 95% CI (3, 6.5)]. Three patients were lost to follow up. Of the 26 patients with IGT, 17 [65.4%, 95% CI (46.1, 80.7)] reverted to euglycaemic status following successful treatment of tuberculosis, while the blood sugar levels improved in all patients with DM following treatment of tuberculosis. Interpretation & conclusions: Our study results show that tuberculosis adversely impacts glycaemic status with improvement in blood sugar levels at the end of successful treatment of tuberculosis. Longitudinal studies with large sample size are required to confirm these findings.
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Nucleic acid amplification test: Bridging the gap in blood safety & re-evaluation of blood screening for cryptic transfusion-transmitted infection among Indian donors p. 389
Sanghamitra Datta, Kamini Khillan, Vivek Ranjan, Chand Wattal
Background & objectives: Nucleic acid amplification test (NAT) in blood donor screening not only detects window period (WP) donors but also those with chronic occult infections which are negative by routine serological screening. This study was conducted to determine the time trend of NAT positivity and seroprevalence of transfusion-transmitted infections (TTIs) through a period of six years and evaluate the strength of NAT as a supplementary test in identifying the cryptic carriers in blood donor population. Methods: A total of 1,01,411 blood donations were screened between January 2011 and December 2016 by the ELISA and individual donor (ID) NAT Procleix Ultrio Plus Assay. Additional molecular and serological assays were done on the NAT yield samples to differentiate the type of cryptic carriers. Results: NAT yields comprised 0.05 per cent (50/101411) of the total samples tested with a yield rate of 1/2028. Hepatitis B virus (HBV) contributed to 80 per cent of the total NAT yields and the rest 20 per cent due to hepatitis C virus (HCV). Majority of HBV NAT yields (75%) were from chronic occult donors and 25 per cent were WP donors. Both HBV and HCV NAT yields had a wide range of viral count. There was no HIV NAT yield. A significant decline in the prevalence rate of TTIs through the study period of six years was observed. Interpretation & conclusions: The cryptic infections found in blood donors increase the risk of TTIs. Blood screening by both serology and NAT can reduce this threat.
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Seroprevalence of measles, mumps & rubella antibodies among 5-10 years old children in north India p. 396
Madhu Gupta, Jaya Prasad Tripathy, Madhur Verma, Mini P Singh, Ramanpreet Kaur, RK Ratho, Rajesh Kumar
Background & objectives: Globally, there is an effort to eliminate the measles and control rubella as these diseases lead to considerable morbidity and mortality especially among under-five children and are important public health problems. This study was aimed to estimate the seroprevalence of measles, mumps and rubella (MMR) antibodies among children of age 5-10 yr in Chandigarh, north India, to provide evidence on prevalent immunity levels. Methods: This cross-sectional study was conducted in Chandigarh, among 196 randomly selected healthy children (5-10 yr), who received either one or two doses of measles or MMR combination vaccine. Socio-economic background and immunization history were recorded. Blood sample (2 ml) was collected to estimate the MMR IgG antibody titres by using ELISA kits. Results: Protective seroprevalence of MMR antibodies was 40.8, 75.5 and 86.2 per cent, respectively. The geometric mean titres of MMR IgG antibodies in the study children were 11.3, 50.6 and 54.3 international units (IU)/ ml, respectively. The proportion of seroprotected children for measles was significantly higher among those who had received two or more doses (46.4%) of measles vaccine compared to those who had received single dose (35.6%) ( P <0.001). About 16 per cent of children had received single dose of MMR vaccine. Among these, 71.4 and 100 per cent were seroprotected against mumps and rubella, respectively. Interpretation & conclusions: A large proportion of children aged 5-10 yr lacked protective immunity against measles (60%); about one-fourth (15-25%) were susceptible to infection with mumps and rubella virus. Mumps vaccination may be considered to be included in National Immunization Schedule for children with periodic serosurveillance.
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Azithromycin resistance mechanisms in typhoidal salmonellae in India: A 25 years analysis p. 404
Priyanka Sharma, Bhavana Kumari, Sushila Dahiya, Umay Kulsum, Sambuddha Kumar, Neelam Manral, Sangeeta Pandey, Punit Kaur, Seema Sood, Bimal Kumar Das, Arti Kapil
Background & objectives: Azithromycin has been in use as an alternate treatment option for enteric fever even when the guidelines on the susceptibility testing were not available. There is lack of data on susceptibility and mechanisms of resistance of azithromycin in Salmonella Typhi and S. Paratyphi A. The aim of the present study was to determine the azithromycin susceptibility and resistance mechanisms in typhoidal salmonellae isolates archived in a tertiary care centre in north India for a period of 25 years. Methods: Azithromycin susceptibility was determined in 602 isolates of S. Typhi (469) and S. Paratyphi A (133) available as archived collection isolated during 1993 to 2016, by disc diffusion and E-test method.PCR was done for ereA, ermA, ermB, ermC, mefA, mphA and msrA genes from plasmid and genomic DNA and sequencing was done to detect mutations in acrR, rplD and rplV genes. Results: Azithromycin susceptibility was seen in 437/469 [93.2%; 95% confidence interval (CI), 90.5 to 95.1%] isolates of S. Typhi. Amongst 133 isolates of S. Paratyphi A studied, minimum inhibitory concentration (MIC) of ≤16 mg/l was found in 102 (76.7%; 95% CI, 68.8 to 83.0). MIC value ranged between 1.5 and 32 mg/l with an increasing trend in MIC50and MIC90with time. Mutations were found in acrR in one and rplV in two isolates of S. Typhi. No acquired mechanism for macrolide resistance was found. Interpretation & conclusions: Azithromycin could be considered as a promising agent against typhoid fever on the basis of MIC distribution in India. However, due to emergence of resistance in some parts, there is a need for continuous surveillance of antimicrobial susceptibility and resistance mechanisms. There is also a need to determine the breakpoints for S. Paratyphi A.
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Immunological detection assays for recombinant Shiga toxin & Shigella dysenteriae p. 412
Pallavi Gupta, Ram Kumar Dhaked
Background & objectives: Shiga toxin (Stx) is produced by Shigella dysenteriae, a Gram-negative, facultative anaerobic bacillus that causes shigellosis, haemolytic uraemic syndrome (HUS) and Reiter's syndrome. The detection methods for shiga toxin needs to be rapid, accurate, reliable and must be extensively evaluated under field conditions. The aim of this study was to develop rapid, sensitive and specific detection method for Stx. Methods: Mice and rabbits were immunized with purified recombinant Shiga toxin B (rStxB). Using these antibodies dot ELISA, sandwich ELISA and flow through assay were developed. Results: The high-titre antibodies specifically reacted with purified rStxB. Dot-ELISA, sandwich ELISA and flow-through assay were developed and standardized that could detect StxB with limit of detection (LOD) of 9.75, 9.7 ng/ml and 0.46 μg/cassette, respectively. Interpretation & conclusions: The rStxB was used to produce antibodies to avoid handling of pathogen. The Flow through assay 'developed was specific, rapid and field amenable.
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Retrospective analysis of colistin-resistant bacteria in a tertiary care centre in India p. 418
Sharmili Sinha, Suneeta Sahu, Jyotirmaya Pati, Banambar Ray, Saroj Kumar Pattnaik
The incidence of carbapenem-resistant Enterobacteriaceae has been steadily rising. The morbidity, mortality and financial implications of such patients are significant. We did a retrospective analysis of the case records of 11 patients who had culture report positive for pan drug-resistant (PDR) organisms. There were total 15 isolates of PDR organisms in 11 patients. These were associated with catheter-associated urinary tract infections (7), tracheitis (4), bacteraemia (2), meningitis (1) and soft-tissue infection (1). Average APACHE II score was 23.72 (range 7-36) indicating patients with multiple co-morbidities and organ dysfunction. The average length of hospital stay was 60.72 (25-123) days. The overall mortality rate was 81.81 per cent, while PDR infection-related mortality was 18.18 per cent. Strict implementation of antibiotic stewardship programme is essential to limit use and prevent abuse of colistin.
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Urticaria in patients with diabetes: Adverse drug reaction or relapse of underlying autoimmune urticaria? p. 423
Sujoy Khan
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A rare case of carcinosarcoma of the temporal bone p. 426
Jian-Hui Wu, Jia Li
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Palpable crepitus as a rare clinical presentation of emphysematous pyelonephritis p. 428
Amit Jain, Ramanitharan Manikandan
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Medical biostatistics, fourth edition p. 430
Sundaram Ramaiyer Karimassery
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Erratum: Antimicrobial susceptibility profile & resistance mechanisms of Global Antimicrobial Resistance Surveillance System (GLASS) priority pathogens from India p. 432

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