A case–control study to assess the association of obesity and insulin resistance in hypertension at a tertiary care hospital in North Kerala

Background: Non-communicable diseases (NCDs) kill 41 million people each year, equivalent to 71% of all deaths globally. Cardiovascular diseases account for most of the NCD deaths, followed by cancers, respiratory diseases, and diabetes. Detection, screening, and treatment of NCDs are the key components of response to NCDs. Aim and Objective: The objective of this work is to study the association of body mass index (BMI), abdominal obesity, and insulin resistance with hypertension and those with both diabetes and hypertension. Materials and Methods: A case–control study was done among 30–70 years old people who came to Government Medical College, Kozhikode between August 2014 and July 2015. They were divided into two study groups and one control group. Complete history, physical, and laboratory examination was done among them and the data were entered in a pro format. Results: The mean ages in each group were 57.73, 58.5, and 48.71, respectively, in each group. The male: female ratio was 1.37:1, 1.06:1, and 1:1 in each group. BMI, waist circumference, waist hip ratio, and waist-to-height ratio (WHtR) were increased progressively in patients with hypertension and those with both hypertension and diabetes mellitus, respectively. Insulin resistance was highest in patients with both hypertension and diabetes mellitus. Conclusion: Obesity is an important contributor to the development of Type 2 diabetes and hypertension. Among the parameters to measure obesity, WHtR is considered the supreme. Insulin resistance is found in hypertensives and those with diabetes and hypertension.

Homeostasis and dysbiosis of the gut microbiome in health and disease

The human gastrointestinal tract (GIT) harbors taxonomically and functionally complex microbial ecosystem. The composition of the microbial species in the GIT ecosystem varies among individuals and throughout development. Bothenvironmental factors as well as host genetics influence the composition and homeostasis of GIT microbiome. Intrinsic GITmicrobiome can be characterized in terms of diversity, richness, dynamics and resilience. In healthy individual, microbialcommunities maintain homeostatic equilibrium and are resistant against perturbations. The resilience and resistance toperturbations of the GIT microbial ecosystem are robust but not absolute. Several factors can affect the homeostaticequilibrium of GIT microbiome and lead to dysbiotic microbiome configuration. Taxonomic and/or functional dysbiosis inthe GIT microbiome is associated with numerous health disorders like inflammatory bowel disease (IBD), malnutrition,metabolic disorders, asthma and neurodegenerative diseases. In this review, we discuss our current understanding ofhomeostasis and dysbiosis of the microbial ecology in the human gut and health disorders that are associated with themicrobiome dysbiosis.

A 36-year-old man with vomiting, pain abdomen, significant weight loss, hyponatremia, and hypoglycemia.

Diagnosis of Strongyloides stercoralis hyperinfection can be a challenge. The key to a timely diagnosis is to have a high index of suspicion. We present a rare case of a 36-year-old human immunodeficiency virus negative male patient, who was on multidrug therapy for lepromatous leprosy and was treated for type 2 lepra reactions with steroids in the past. The patient presented with vomiting and pain abdomen, persistent hyponatremia, and terminal hypoglycemia. He had features of malnutrition and had a rapid downhill course following admission. A diagnosis of S. stercoralis hyperinfection with sepsis and multiorgan failure, adrenal hemorrhage, and syndrome of inappropriate antidiuretic hormone secretion was established on a postmortem examination.

Probiotic foods: Can their increasing use in India ameliorate the burden of chronic lifestyle disorders.

Probiotics are defined as live microorganisms which, when ingested in adequate amounts, confer health benefits on the host. Chronic diseases such as diabetes, non-alcoholic fatty liver disease, coronary artery disease, a variety of chronic inflammatory disorders with an immune basis, and some forms of cancer are increasing in incidence around the world and in India, and may be attributable in part to rapid changes in our lifestyle. There is considerable public interest in India in the consumption of probiotic foods. This brief review summarizes the background of the gut microbiota, the immunological reactions induced by these, the evidence linking the microbiota to health outcomes, and the evidence linking the use of probiotics for amelioration of chronic lifestyle diseases.

Assessment of well water quality in Tsunami affected regions of south-west coast of Kerala, India.

The quality of well waters, based on 23 parameters of water, at 12 stations of south-west coast of Kerala, India, was assessed during monsoon, 2009 and summer, 2010, to determine their suitability for drinking and other domestic purposes. The stations selected were grouped into four regions viz. least, slightly, moderately and severely affected ones based on the severity of 2004 Asian Tsunami at each station. The depths of wells showed variations depending on the seasons and on their distance from the seacoast. The average water temperatures during monsoon and summer seasons were 28.5oC and 30.2oC respectively. The pH of well waters were below 6.5 in least and slightly affected regions and above this value in moderately and severely affected regions. In all the four regions, the well water parameters of electrical conductivity, hardness, fluoride, free chlorine, copper, zinc, calcium and nickel were below, and phosphorus, lead, iron cadmium and manganese were above the standard permissible levels set for them in drinking water. The values of salinity, sodium and potassium in the well waters of moderately and severely affected regions, and the values of nitrate-nitrogen, nitrate and magnesium in the well waters of severely affected regions were above the permissible limits set for them in drinking water. Water quality index calculated on the basis of drinking water standards revealed that the well waters of least and slightly affected regions were moderately polluted in both monsoon and summer seasons and the same of moderately affected region were excessively polluted during monsoon and severely polluted during summer seasons, whereas the well waters of severely affected regions were severely polluted in both seasons. Suitable recommendations were made to improve the quality of well waters of least and slightly affected regions.

Development and Validation of Language Evaluation Scale Trivandrum for Children Aged 0-3 years - LEST (0-3).

Objective: To develop and validate a simple screening tool which can be used in the Community to identify delay in language development among children of 0-3 years of age. Methods: The normal range for the 33-items of “Language Evaluation Scale Trivandrum for 0-3years-LEST(0-3)” were carefully selected from various existing language development charts and scales, by experts keeping in mind the face validity and content validity. The criterion validity was assessed using a community sample of 643 children of 0 to 3 years of age, including 340 (52.9%) boys. LEST (0-3) was validated against Receptive Expressive Energent Language Scale, for screening delay in language development among children of 0-3 years. Results: When one item delay was taken as ‘LEST delay’ (test positive), the sensitivity and specificity of LEST(0-3), was found to be 95.85% and 77.5%, respectively with a negative predictive value of 99.8% and LR (negative) of 0.05.When two item delay was taken as ‘LEST delay’ (test positive), the sensitivity and specificity of LEST(0-3), was found to be 66.7% and 94.8% respectively with a negative predictive value of 98.7% and LR (negative) of 0.35. The test-retest and inter-rater reliability were good and acceptable (Inter-class correlation of 0.69 for testretest and 0.94 for inter-rater). Conclusion: LEST (0-3) is a simple, reliable and valid screening tool for use in the community to identify children between 0-3 years with delay in language development, enabling early intervention practices.

Epidemiology and Prospects for Prevention of Rotavirus Disease in India.

Context: With rotavirus vaccines now available globally, it will be useful to assemble the available evidence on the epidemiology and burden of rotavirus gastroenteritis in India, in order to weigh the urgency of introducing a vaccine to help control rotavirus disease. Evidence Acquisition: We reviewed published studies on rotavirus infection and genotype distribution in India, as well as safety and immunogenicity studies of currently available vaccines. PubMed was searched for papers published after 1990, and several authors who are experts in the field recommended papers of known significance. Results: Rotavirus accounts for close to 40% of hospitalizations for diarrhea in India, with more recent studies showing an increased proportion compared with older studies. There is substantial serotype diversity in India, although there is less intra-country variation than previously thought. Two genotypes, G1P[8] and G2P[4], account for roughly 50% of symptomatic infections in non-neonates. Currently licensed vaccines are safe, and although the efficacy appears lower in developing countries, given the extremely high incidence of diarrhea these could still be cost-effective interventions. Conclusions: The epidemiology and burden of rotavirus diarrhea is fairly well characterized in India. Introducing rotavirus vaccine into the UIP, along with adequate surveillance, should be an important part of efforts to reduce diarrhea mortality, the third leading cause of death among Indian children, and achieve the country’s MDG goals.

Storing Drinking-water in Copper pots Kills Contaminating Diarrhoeagenic Bacteria.

Microbially-unsafe water is still a major concern in most developing countries. Although many water-purification methods exist, these are expensive and beyond the reach of many people, especially in rural areas. Ayurveda recommends the use of copper for storing drinking-water. Therefore, the objective of this study was to evaluate the effect of copper pot on microbially-contaminated drinking-water. The antibacterial effect of copper pot against important diarrhoeagenic bacteria, including Vibrio cholerae O1, Shigella flexneri 2a, enterotoxigenic Escherichia coli, enteropathogenic E. coli, Salmonella enterica Typhi, and Salmonella Paratyphi is reported. When drinking-water (pH 7.83±0.4; source: ground) was contaminated with 500 CFU/mL of the above bacteria and stored in copper pots for 16 hours at room temperature, no bacteria could be recovered on the culture medium. Recovery failed even after resuscitation in enrichment broth, followed by plating on selective media, indicating loss of culturability. This is the first report on the effect of copper on S. flexneri 2a, enteropathogenic E. coli, and Salmonella Paratyphi. After 16 hours, there was a slight increase in the pH of water from 7.83 to 7.93 in the copper pots while the other physicochemical parameters remained unchanged. Copper content (177±16 ppb) in water stored in copper pots was well within the permissible limits of the World Health Organization. Copper holds promise as a point-of-use solution for microbial purification of drinking-water, especially in developing countries.

QRDR mutations, efflux system & antimicrobial resistance genes in enterotoxigenic Escherichia coli isolated from an outbreak of diarrhoea in Ahmedabad, India.

Background & objectives: Diverse mechanisms have been identified in enteric bacteria for their adaptation and survival against multiple classes of antimicrobial agents. Resistance of bacteria to the most effective fluoroquinolones have increasingly been reported in many countries. We have identified that most of the enterotoxigenic Escherichia coli (ETEC) were resistant to several antimicrobials in a diarrhoea outbreak at Ahmedabad during 2000. The present study was done to identify several genes responsible for antimicrobial resistance and mobile genetic elements in the ETEC strains. Methods: Seventeen ETEC strains isolated from diarrhoeal patients were included in this study. The antimicrobial resistance was confirmed by conventional disc diffusion method. PCR and DNA sequencing were performed for the identification of mutation in the quinolone resistance-determining regions (QRDRs). Efflux pump was tested by inhibiting the proton-motive force. DNA hybridization assay was made for the detection of integrase genes and the resistance gene cassettes were identified by direct sequencing of the PCR amplicons. Results: Majority of the ETEC had GyrA mutations at codons 83 and 87 and in ParC at codon 80. Six strains had an additional mutation in ParC at codon 108 and two had at position 84. Plasmid-borne qnr gene alleles that encode quinolone resistance were not detected but the newly described aac(6’)-Ib-cr gene encoding a fluoroquinolne-modifying enzyme was detected in 64.7 per cent of the ETEC. Class 1 (intI1) and class 2 (intI2) integrons were detected in six (35.3%) and three (17.6%) strains, respectively. Four strains (23.5%) had both the classes of integrons. Sequence analysis revealed presence of dfrA17, aadA1, aadA5 in class 1, and dfrA1, sat1, aadA1 in class 2 integrons. In addition, the other resistance genes such as tet gene alleles (94.1%), catAI (70.6%), strA (58.8%), blaTEM-1(35.2%), and aphA1-Ia (29.4%) were detected in most of the strains. Interpretation & conclusions: Innate gene mutations and acquisition of multidrug resistance genes through mobile genetic elements might have contributed to the emergence of multidrug resistance (MDR) in ETEC. This study reinforces the necessity of utilizing molecular techniques in the epidemiological studies to understand the nature of resistance responsible for antimicrobial resistance in different species of pathogenic bacteria.

ICMR-DBT Guidelines for Evaluation of Probiotics in Food.

There has been an increased influx of probiotic products in the Indian market during the last decade. However, there has been no systematic approach for evaluation of probiotics in food to ensure their safety and efficacy. An initiative was, therefore, taken by the Indian Council of Medical Research (ICMR) along with the Department of Biotechnology (DBT) to formulate guidelines for regulation of probiotic products in the country. These guidelines define a set of parameters required for a product/strain to be termed as ‘probiotic’. These include identification of the strain, in vitro screening for probiotic characteristics, animal studies to establish safety and in vivo animal and human studies to establish efficacy. The guidelines also include requirements for labeling of the probiotic products with strain specification, viable numbers at the end of shelf life, storage conditions, etc., which would be helpful to the consumers to safeguard their own interest.

Rapid situation & response assessment of diarrhoea outbreak in a coastal district following tropical cyclone AILA in India.

Background & objectives: Cyclone AILA hit Indian States on eastern coast on May 25, 2009. An investigation was conducted to examine if AILA was responsible for increased reporting of diarrhoea cases from the district of East-Medinipur in West Bengal. Identifying causative organisms for diarrhoea and assessing their antibiotic susceptibility profile were other objectives. Methods: Rapid situation and response assessment technique was employed to triangulate primary and secondary data collected through field visits. Prescription audit was also conducted. Results: Significantly increased occurrence of diarrhoea was observed in June 2009 in two subdivisions namely Haldia and Egra (OR 1.6 and 1.3 respectively; 95% CI 1.52-1.65 and 1.21-1.32 P<0.001) considering 2007 as baseline. Vibrio cholerae grew from 54 per cent of the stool samples (21/39; 17 V. cholerae O1-Ogawa and 4 non-O1-non-O139), confirming a community outbreak of cholera. Shigella flexneri 3a was isolated from 5 per cent stool specimens. Increased rate of admission in treatment centres due to diarrhoea in the whole district coincided with the formation of cyclone and showed over two-fold rise compared to the admission recorded 6 days ago. Haldia subdivision had the highest attack rate of 9 per 1000 in the month of June, 2009 whereas for the whole district it was 5 per 1000 in the same month. All the isolates of V. cholerae were resistant to ampicillin and furazolidone and sensitive to norfloxacin and azithromycin. Interpretation & conclusions: Pre-AILA changes in the environment, AILA and seasonality of diarrhoea in the study district interplayed towards increased occurrence of diarrhoea. Continuous tracking of ‘seasonality of diarrhoea in the community with vulnerability assessment of potential hosts’, ‘antibiotic sensitivity profile of the causative microorganisms’, and ‘prescription practice of physicians’ would help appropriate disaster management.

Hybrid & El Tor variant biotypes of Vibrio cholerae O1 in Thailand.

Background & objectives: El Tor Vibrio cholerae O1 carrying ctxBC trait, so-called El Tor variant that causes more severe symptoms than the prototype El Tor strain, first detected in Bangladesh was later shown to have emerged in India in 1992. Subsequently, similar V. cholerae strains were isolated in other countries in Asia and Africa. Thus, it was of interest to investigate the characteristics of V. cholerae O1 strains isolated chronologically (from 1986 to 2009) in Thailand. Methods: A total of 330 V. cholerae O1 Thailand strains from hospitalized patients with cholera isolated during 1986 to 2009 were subjected to conventional biotyping i.e., susceptibility to polymyxin B, chicken erythrocyte agglutination (CCA) and Voges-Proskauer (VP) test. The presence of ctxA, ctxB, zot, ace, toxR, tcpAC, tcpAE, hlyAC and hlyAE were examined by PCR. Mismatch amplification mutation assay (MAMA) - and conventional- PCRs were used for differentiating ctxB and rstR alleles. Results: All 330 strains carried the El Tor virulence gene signature. Among these, 266 strains were typical El Tor (resistant to 50 units of polymyxin B and positive for CCA and VP test) while 64 had mixed classical and El Tor phenotypes (hybrid biotype). Combined MAMA-PCR and the conventional biotyping methods revealed that 36 strains of 1986-1992 were either typical El Tor, hybrid, El Tor variant or unclassified biotype. The hybrid strains were present during 1986-2004. El Tor variant strains were found in 1992, the same year when the typical El Tor strains disappeared. All 294 strains of 1993-2009 carried ctxBC ; 237 were El Tor variant and 57 were hybrid. Interpretation & conclusions: In Thailand, hybrid V. cholerae O1 (mixed biotypes), was found since 1986. Circulating strains, however, are predominantly El Tor variant (El Tor biotype with ctxBC).

An experimental study of phage mediated bactericidal selection & emergence of the El Tor Vibrio cholerae.

Background & objectives: Factor causing the elimination of the classical biotype of Vibrio cholerae O1, and its replacement by the El Tor biotype causing the 7th cholera pandemic are unclear. Possible ability of the El Tor strains to adapt better than the classical strains to undefined environmental forces have been largely implicated for the change. Here we describe an environmental bacteriophage designated JSF9 which might have contributed to the range of factors. Methods: Competition assays were conducted in the infant mice model and in microcosms between representative El Tor and classical biotype strains in the absence or in the presence of JSF9 phage. Results: The JSF9 phage was found to kill classical strains and favour enrichment of El Tor strains, when mixtures containing strains of the two biotypes and JSF9 phage were subjected to alternate passage in infant mice and in samples of environmental water. Spontaneous derivatives of the classical biotype strains, as well as transposon mutants which developed resistance to JSF9 phage were found to be defective in colonization in the infant mouse model. Interpretation & conclusions: These results suggest that in addition to other factors, the inherent ability of El Tor biotype strains to evade predation by JSF9 or similar phages which kill classical biotype strains, might have enhanced the emergence of El Tor strains as the predominant pandemic biotype.

Risk assessment of the amnesic shellfish poison, domoic acid, on animals and humans.

Risk assessment of the amnesic shellfish poison, domoic acid, a potent neurotoxin, is evaluated based on its current knowledge and its harmful effects, and is presented under four headings, viz., (1) hazard identification, (2) dose response assessment, (3) exposure assessment and (4) risk characterization. Domoic acid binds the glutamate receptor site of the central nervous system (CNS) of humans and causes depolarization of neurons and an increase in cellular calcium. In nature, domoic acid is produced by the algae, Pseudonitzschia spp. and they enter into the body of shellfish through their consumption. This toxin is reported to cause gastroenteritis, renal insufficiency, confusion and memory loss in humans, since it affects the hippocampus of the brain. In rats, intraperitonial and oral administration of domoic acid result in scratching, tremor and convulsions, and in monkeys, the toxic symptoms like mastication, salivation, projectile vomiting, weakness, teeth grinding and lethargy are apparent. The no-observed-adverse-effect-level (NOAEL) in animals reveals that pure toxin is more effective than those isolated from shellfish. Based on LD50 values, it is found that intraperitonial administration of this toxin in animals is 31 fold more effective than oral administration. Low levels of domoic acid (0.20 – 0.75 ppm) show no toxic symptoms in non-human primates, but clinical effects are apparent in them and in humans, at a concentration of 1.0 ppm. The tolerable daily intake (TDI) of domoic acid for humans is calculated as 0.075 ppm, whereas for razor clams and crabs, the TDI are 19.4 and 31.5 ppm respectively. The hazard quotient (HQ) is found to be 2. Being an irreversible neurotoxin, domoic acid has severe public health implications. Death occurs in those above 68 years old. In order to ensure adequate protection to public health, the concentration of domoic acid in shellfish and shellfish parts at point of sale shall not exceed the current permissible limit of 20 μg g-1 tissue. While processing shellfish, it may be advisable to pay attention to factors such as environmental conditions, inter-organ variability in concentrations of domoic acid and cross contaminations.