Phage Therapy an Effective Remedy Against Drug-Resistant Bugs and Hard to Treat Bacterial Infections-A Review

The injudicious use of antibiotics not only in medicine but also to promote the growth of farm animals has led to the development of antibiotic resistance against many bacterial diseases. One of the remedy against such drug resistant bacterial infections is the application of phage (Bacteriophage) therapy. Phage therapy involves using phages or their products as bioagents for the treatment or prophylaxis of bacterial infections. There are two types of phages based on their type of life cycle: the lytic and the lysogenic phages. Only the lytic phages are used in phage therapy, because of the disadvantages of lysogenic pahges (Superinfection immunity, lysogenic conversion, specialized transduction). Apart from live phages the phage byproducts like phage lysins can also be used specifically against certain bacterial infections. The reports indicate that appropriate administration of living phages can be used to treat lethal infectious diseases caused by bacteria, like Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella spp. and Staphylococcus aureus etc. In the coming time the phage therapy will compensate for unavoidable complications of antimicrobial therapy, particularly the appearance of multidrug resistance bacteria (super bugs)

Virulence gene profile and antimicrobial resistance of Staphylococcus aureus isolated from bovine mastitis in Kashmir, India

The Staphylococcus aureusis often responsible for a number of diseases in humans and animals, and it is considered as a main etiological agent of bovine mastitis. The pathogenicity of S. aureus is due to both its ability to resist antibiotics, and the production of toxins. This study investigated virulence genes, prevalence and antibiogram profile of S. aureus isolated from dairy cows suffering from mastitis in the Kashmir. A total of 70 S. aureus isolates were obtained from 250 mastitic milk samples collected from both organized (47/150) and unorganized (23/100) dairy farms. Five pathogenic factors including clfA, hld, seo, lukM, and coa and one resistance gene mecAgene were checked through PCR. Clumping factor gene (clfA) was found in most of the isolates with a percentage of 81.42 % whereas,hld, seo, lukM, and coa were present in 61.2, 54.28, 70, and 71 percent of isolates, respectively. However, amplification of coagene yielded DNA bands of two different sizes. A high percentage of antimicrobial resistance rates were observed, wherein, Ampicillin showed highest resistance with 85.7 %, followed by Kanamycin, Cefotaxime, Sulphadizine and Streptomicin showing 71.42 %, 54.28 %, 51.48 % and 42 %, respectively. A high frequency of Methicillin resistant S. aureus (MRSA 28.57 %) was observed in these isolates and all methicillin resistant isolates were found to be positive for mecA gene via PCR amplification. These results revealed that mastitis-associated S. aureus among bovines of Kashmir is able to accumulate different virulence factors and resistance to antimicrobials, making the treatment of infections difficult

Isolation, virulence gene profiling with molecular cloning of ibeA gene and antibiogram of Escherichia coli from respiratory tract infections of broiler chicken in Kashmir, India

he present study has determined prevalence, serological diversity, virulence gene profileand in vitro antibiogram of Escherichia coli (E. coli) isolates from respiratory tract of broiler chicken in Kashmir valley along with molecular cloning of ibeA gene, an important zoonotic among invasion-associated genes responsible for neonatal meningitis in humans. A total of 224 broilerchickens with a history of respiratory tract infections, in a flock size of 2692 birds from organised and unorganised poultry farms of Kashmir valley, were screened for E. coli isolation. The prevalence of E. coli in birds with respiratory tract infection was found to be 6.38 per cent. Serogrouping revealed that the E. coli isolates were typeable into 10 serogroups with prevalence rate of 8.8% for serogroup O2, along with few isolates rough or untypeable. The screening of E. coli isolates for virulence gene profile revealed the presence of iss in (89.53%), iucDin (85.46 %), tsh in (51.74 %), cva/cvi in (33.14 %), irp2in (55.23 %), papCin (33.72 %), vat in (31.39 %), astAin (38.95 %), fimCin (93.60 %) and ibeAin (1.16 %) isolates. The antibiogram screening of E. coli isolates revealed majority of isolates to be resistant to tetracycline (94.71%), ampicillin (92.67%) and cephalaxin (79.67%).However, most of the isolates were sensitive to amikacin (74.41%) followed by amoxacillin-sulbactam (68.60%) and gentamicin (67.44%). The study thus, suggests that the E. coli isolates from respiratory tract infection of poultry harbour differential virulence genes along with the genes of zoonotic interest and variable antimicrobial resistance, thus, opening the areas for devising dynamic, emergent and effective treatment line

Attitudes of Canadian psychiatry residents if mentally ill: awareness, barriers to disclosure, and help-seeking preferences

Background: The medical culture is defined by mental illness stigma, non-disclosure, and avoidance of professional treatment. Little research has explored attitudes and help-seeking behaviors of psychiatry trainees if they were to become mentally ill.Method: Psychiatry residents (n = 106) from training centres across Ontario, Canada completed a postal survey on their attitudes, barriers to disclosure, and help-seeking preferences in the context of hypothetically becoming mentally ill.Results: Thirty-three percent of respondents reported personal history of mental illness and the frequency of mental illness by year of training did not significantly differ. The most popular first contact for disclosure of mental illness was family and friends (n = 61, 57.5%). Frequent barriers to disclosure included career implications (n = 39, 36.8%), stigma (n = 11, 10.4%), and professional standing (n = 15, 14.2%). Personal history of mental illness was the only factor associated with in-patient treatment choice, with those with history opting for more formal advice versus informal advice.Conclusions: At the level of residency training, psychiatrists are reporting barriers to disclosure and help-seeking if they were to experience mental illness. A majority of psychiatry residents would only disclose to informal supports. Those with a history of mental illness would prefer formal treatment services over informal services

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Detection and sequencing of plasmid encoded tetracycline resistance determinants (tetA and tetB) from food–borne Bacillus cereus isolates

AbstractObjectiveTo investigate the detection and sequencing of plasmid encoded tetracycline resistance genes (tetA and tetB) from food-borne and standard strains of Bacillus cereus (B. cereus).MethodsA PCR was carried out to detect the tetracycline resistance genes (tetA and tetB) in food-borne B. cereus strains and the amplified products were sequenced.ResultsThe phenotypic resistance against tetracycline was observed in 39 of the 118 food-borne isolates and two reference strains (MTCC 430 and MTCC 1307) of B. cereus. Among the phenotypically resistant isolates, tetA was detected in 36 food-borne isolates and two reference strains (MTCC 430 and MTCC 1307), whereas, tetB was detected in 12 food-borne isolates and MTCC 1307 strain.ConclusionsA close association was therefore found between phenotypic resistance against tetracycline and presence of tetracycline resistance genes. The tetA and tetB gene fragments were amplified, purified and sequenced. The gene sequences of the isolates studied herein were found similar to tetA and tetB gene sequences of other bacteria available in NCBI. The occurrence of tetA and tetB genes in B. cereus indicate the horizontal transfer of antibiotic resistance determinants from other bacteria into B. cereus. The transfer of these resistant determinants to other potentially pathogenic bacteria may be a matter of great concern

Black Quarter in crossbred dairy cattle- A Case Report

Aim: A sporadic incident of Clostridial disease that affected Holstein Friesian (HF) cross bred cows (n=8) at an organized dairy farm was investigated. Materials and Methods: Detailed clinical investigations and treatment were carried out on all the affected animals. Complete blood count (CBC) and plasma biochemistry were performed on survived animals (n=6). The needle biopsy samples were subjected to culture and identification of the organism by Gram staining. Results: Two cows were died before instituting the treatment in this clinical incident. The carcasses were seen with typical bloated appearance immediately after death, laying one side with affected leg stuck out. Post-mortem of the carcasses were not been carried out. Pertinent findings of the CBC were a relative neutrophilia whilst a normal total leucocyte count and lowered Hb. Plasma biochemical parameters revealed significant increase in the mean activity of aspartate aminotransferase while alanine aminotransferase levels were within limits. Gram's staining of the inoculated culture revealed the presence of small gram-positive rods with sub terminal spores. Clinical treatment of the cases was performed with administration of heavy dose of crystalline penicillin and non-steroidal anti-inflammatory drugs (NSAIDS). Clinical recoveries of the cases were good and cessation of spread within the herd confining itself as a sporadic clinical incident. Conclusion: Sporadic Clostridiosis (BQ) of eight cross bred dairy cows was dealt in the present case study by including the details of its alterations in hematological parameters, Plasma biochemical parameters, observation of characteristic clinical signs of the disease and employment of empirical treatment with Penicillin. [Vet World 2012; 5(12.000): 767-770

Virulence gene profile and antimicrobial resistance of Staphylococcus aureus isolated from bovine mastitis in Kashmir, India

The Staphylococcus aureusis often responsible for a number of diseases in humans and animals, and it is considered as a main etiological agent of bovine mastitis. The pathogenicity of S. aureus is due to both its ability to resist antibiotics, and the production of toxins. This study investigated virulence genes, prevalence and antibiogram profile of S. aureus isolated from dairy cows suffering from mastitis in the Kashmir. A total of 70 S. aureus isolates were obtained from 250 mastitic milk samples collected from both organized (47/150) and unorganized (23/100) dairy farms. Five pathogenic factors including clfA, hld, seo, lukM, and coa and one resistance gene mecAgene were checked through PCR. Clumping factor gene (clfA) was found in most of the isolates with a percentage of 81.42 % whereas,hld, seo, lukM, and coa were present in 61.2, 54.28, 70, and 71 percent of isolates, respectively. However, amplification of coagene yielded DNA bands of two different sizes. A high percentage of antimicrobial resistance rates were observed, wherein, Ampicillin showed highest resistance with 85.7 %, followed by Kanamycin, Cefotaxime, Sulphadizine and Streptomicin showing 71.42 %, 54.28 %, 51.48 % and 42 %, respectively. A high frequency of Methicillin resistant S. aureus (MRSA 28.57 %) was observed in these isolates and all methicillin resistant isolates were found to be positive for mecA gene via PCR amplification. These results revealed that mastitis-associated S. aureus among bovines of Kashmir is able to accumulate different virulence factors and resistance to antimicrobials, making the treatment of infections difficult