Sheep Associated-Malignant Catarrhal Fever: Past, present, and future

Members of Artiodactyla can contract the infectious disease Malignant Catarrhal Fever (MCF), which has a wide range of symptoms. Ten known viruses contribute to the disease, the two most significant ones being Ovine gamma herpes virus 2 (OvHV-2) and Alcelaphine gamma herpes virus 1 (AIHV-1). In the African subcontinent, AIHV-1 is seen in most MCF cases. In the Indian scenario, Ovine gamma herpes virus-2 is the main culprit. MCF is reported in certain pockets of India. Its threat to wildlife is not yet completely understood. In AIHV-1, wildebeests serve as the primary MCF reservoir, whereas with OvHV-2, the primary MCF reservoir is sheep. In India, OvHV-2 causes MCF in deer species, bison, and water buffaloe. The life cycle and properties of this virus are not yet wholly deciphered. To understand the impact of the disease and the threat it may pose in the future, we need to have diagnostic techniques in place. Currently, PCR is the most commonly used diagnostic technique. Work should be done on field-oriented tests like ELISA and LFA, which are helpful in areas without sophisticated lab facilities. Treatment protocols must be in place, as culling bovines is not an accepted policy in India. Probable plans for overcoming all these problems are discussed in this article

QUASISPECIES FEATURE IN SARS-CoV-2

Since the identification of the SARS-CoV-2, genus Beta- Coronavirus, in January 2020, the virus quickly spread in less than 3 months to all continents with a susceptible human population of about a 7.9billion, and still in active circulation. In the process, it has accumulated mutations leading to genetic diversity. Regular emergence of variants of concern/significance in different ecology shows genetic heterogeneity in the base population of SARS-CoV-2 that is continuously expanding with the passage of the virus in the vast susceptible human population. Natural selection of mutant occurs frequently in a positive sense (+) single-stranded (ss) RNA virus upon replication in the host.  The Pressure of sub-optimal levels of virus-neutralizing antibodies and also innate immunity influence the process of genetic/ antigenic selection. The fittest of the mutants, that could be more than one, propagate and emerge as variants. The existence of different lineages, clades, and strains, as well as genetic heterogeneity of plaque purified virus population, justifies SARS-CoV-2 as ‘Quasispecies’ that refers to swarms of mutant sequences generated during replication of the viral genome, and all mutant sequences may not lead to virion. Viruses having a quasispecies nature may end up with progressive antigenic changes leading to antigenic plurality that is driven by ecology, and this phenomenon challenges vaccination-based control programs

Unravelling key genes associated with ovine Brucellosis by differential gene expression analysis: A holistic bioinformatics study

Ovine Brucellosis, caused by Brucella ovis bacteria, is a pathognomonic reproductive infectious disease of sheep that causes epididymitis in rams (male sheep) and placental inflammation in ewes (female sheep) leading to reduced fertility. The specific molecular process that causes alterations in genome of sheep during brucellosis is not yet fully understood. This study aimed to identify key host genes associated with the pathogenesis of ovine brucellosis caused by B. ovis. The GSE35614 dataset containing six healthy and six Brucella ovis infected sample of rams in the chronic phase 2 was obtained from the NCBI GEO database to examine and detect any differences in gene expression (DEGs). Functional and pathway enrichment analyse of the DEGs were performed along with the construction of protein-protein interaction network. Next, functional modules and hub genes were clustered and identified respectively, using the MCODE plugin. As a result, a total of 316 differentially expresses genes were filtered according to the provided cut-off criteria. The enriched DEGs were related to extracellular matrix interaction, cell adhesion mediated by integrin, angiogenesis, and inflammatory response. Furthermore, the hub gene analysis resulted in five hub genes namely, FN1, FBN1, CDH1, CD44, and SPP1, were up-regulated during the infection which could lead to reproductive disorders in sheep. In conclusion, the DEGs, functional and pathways terms, along with hub genes identified in the current study can provide prospective targets for the early diagnosis and treatment of brucellosis and provide insight into the molecular mechanism underlying the alterations that occur during brucellosis in sheep

EVOLUTIONARY ANALYSIS AND DETECTION OF POSITIVE SELECTION OF HEMAGGLUTININ AND NEURAMINIDASE GENES OF H5N1 AVIAN INFLUENZA FROM CHICKEN, DUCK AND GOOSE ACROSS ASIA

Outbreaks of very high pathogenic avian influenza (H5N1) viruses are being reported in poultry in almost all countries including Asia. It has been reported that the spread is very fast and found that this virus is spreading in avian species for several years. In this study, the evidence of positive selection prominent to mutations were analyzed for the Hemagglutinin (HA) and Neuraminidase (NA) nucleotide sequences of H5N1 avian influenza from chicken, duck, and goose across Asia. H5N1 avian influenza viruses are being a severe risk to public health. Detection of positive selection sites in Hemagglutinin (HA) and Neuraminidase (NA) genes will help to trace the evolutionary path of these viruses from different poultry hosts. The positive/ diversifying selection (dN/dS (ω) >1) was found to be showing significant signals in the mutation of HA and NA genes and is evolving rapidly. The cumulative dN/dS (ω) ratio was found ranging from 0.21 to 0.23 in the HA gene and 0.16 to 0.25 in the NA gene of Avian Influenza Virus from chicken, duck, and goose. Furthermore, statistical Bayesian model methods were applied to interpret the genetic diversity of H5N1 strain, the evolutionary rates were ranging from 2.36x10-3 to 5.19x10-3 in the HA gene and 2.28x10-3 to 6.25x10-3 in the NA gene from chicken, duck, and goose respectively, which revealed a rapid evolution in these viruses with respect to their genetic ancestor. Substitution rates and selection pressure in these three different hosts indicate that their dynamics of mutation and replication remain similar among the species studied and are important for evolution

Progression-free survival estimation of docetaxel-based second-line treatment for advanced non-small cell lung cancer: a pooled analysis from 18 randomized control trials

BackgroundLung cancer is the foremost cause of cancer-related death globally, with non-small cell lung cancer (NSCLC) accounting for 85–90% of cases. Targeted therapy is the most essential therapeutic option for NSCLC, other common treatments include radiation therapy, surgery, chemotherapy, and immunotherapy.ObjectiveOur study objective was to estimate whether progression-free survival (PFS) is an outcome of NSCLC extracted from 18 randomized control trials (RCTs) with docetaxel as experimental group and antineoplastic agent, kinase inhibitor, and monoclonal antibodies as a control group.MethodsWe selected relevant studies published between 2011 and 2022 using Google Scholar, PubMed, Scopus, Science Direct, and Cochrane Library. Advanced NSCLC, chemotherapy, RCT, docetaxel, and second-line treatment were the terms included in the search. A total of 9738 patients were evaluated from the 18 identified studies. We used the meta package of R Studio to perform the meta-analysis. Graphical funnel plots were used to evaluate publication bias visually.ResultsPatients who underwent docetaxel-based therapy had a considerably longer PFS than those who got antineoplastic agents, kinase inhibitors, or monoclonal antibodies-based treatment. Patients in the standard treatment arm had a slightly longer PFS than those in the experimental therapy arm in the overall meta-analysis.ConclusionDocetaxel outperformed monoclonal antibodies, antineoplastic agents, and kinase inhibitors in the second-line therapy of advanced NSCLC since PFS was extensively utilized

The first study on analysis of the codon usage bias and evolutionary analysis of the glycoprotein envelope E2 gene of seven Pestiviruses

Background and Aim: Pestivirus, a genus of the Flaviviridae family, comprises viruses that affect bovines, sheep, and pigs. Symptoms, including hemorrhagic syndromes, abortion, respiratory complications, and deadly mucosal diseases, are produced in infected animals, which cause huge economic losses to the farmers. Bovine viral diarrhea virus-1, bovine viral diarrhea virus-2, classical swine fever virus, border disease virus, Bungowannah, Hobi-like, and atypical porcine pestivirus belonging to the Pestivirus genus were selected for the study. This study aimed to estimate the codon usage bias and the rate of evolution using the glycoprotein E2 gene. Furthermore, codon usage bias analysis was performed using publicly available nucleotide sequences of the E2 gene of all seven Pestiviruses. These nucleotide sequences might elucidate the disease epidemiology and facilitate the development of designing better vaccines. Materials and Methods: Coding sequences of the E2 gene of Pestiviruses A (n = 89), B (n = 60), C (n = 75), D (n = 10), F (n = 07), H (n = 52), and K (n = 85) were included in this study. They were analyzed using different methods to estimate the codon usage bias and evolution. In addition, the maximum likelihood and Bayesian methodologies were employed to analyze a molecular dataset of seven Pestiviruses using a complete E2 gene region. Results: The combined analysis of codon usage bias and evolutionary rate analysis revealed that the Pestiviruses A, B, C, D, F, H, and K have a codon usage bias in which mutation and natural selection have played vital roles. Furthermore, while the effective number of codons values revealed a moderate bias, neutrality plots indicated the natural selection in A, B, F, and H Pestiviruses and mutational pressure in C, D, and K Pestiviruses. The correspondence analysis revealed that axis-1 significantly contributes to the synonymous codon usage pattern. In this study, the evolutionary rate of Pestiviruses B, H, and K was very high. The most recent common ancestors of all Pestivirus lineages are 1997, 1975, 1946, 1990, 2004, 1990, and 1990 for Pestiviruses A, B, C, D, F, H, and K, respectively. This study confirms that both mutational pressure and natural selection have played a significant role in codon usage bias and evolutionary studies. Conclusion: This study provides insight into the codon usage bias and evolutionary lineages of pestiviruses. It is arguably the first report of such kind. The information provided by the study can be further used to elucidate the respective host adaptation strategies of the viruses. In turn, this information helps study the epidemiology and control methods of pestiviruses

A comparative clinical study of efficacy of microimmuno assay with WIDAL-test in enteric fever in children

The diagnosis of typhoid fever in young children is also a dilemma because of its manifestations and typical presentation may not be seen in all cases. Antibodies to Salmonella typhi antigen are developed in the human body, which can be detected as a diagnostic test for the enteric fever. Objective: This study was undertaken to compare the efficacy of WIDAL-test with micro-immunoassay (dot enzyme immunosorbent assay). Method: 40 cases of clinically suspected enteric fever cases were included in this study. Result: In the present study, nearly 92% were positive for micro immunoassay (dot-enzyme immunosorbent assay) by Enterocheck-WB kit, 80% were positive for WIDAL and only 15% were culture positive. Immunoassay positive, but WIDAL negative cases were 20%, whereas WIDAL positive and immunoassay negative cases were only 7.5%. The positive predictivity of micro-immunoassay in diagnosing enteric fever is better than WIDAL both in 1st and 2nd week of illness. Micro-immunoassay done in the study was rapid in diagnosing the case. Conclusion: It is concluded from the present study that the micro-immunoassay (Enterocheck-WB) is better than WIDAL-test in the diagnosis of enteric fever in children

Analysis of codon usage bias of classical swine fever virus

Background and Aim: Classical swine fever (CSF), caused by CSF virus (CSFV), is a highly contagious disease in pigs causing 100% mortality in susceptible adult pigs and piglets. High mortality rate in pigs causes huge economic loss to pig farmers. CSFV has a positive-sense RNA genome of 12.3 kb in length flanked by untranslated regions at 5' and 3' end. The genome codes for a large polyprotein of 3900 amino acids coding for 11 viral proteins. The 1300 codons in the polyprotein are coded by different combinations of three nucleotides which help the infectious agent to evolve itself and adapt to the host environment. This study performed and employed various methods/techniques to estimate the changes occurring in the process of CSFV evolution by analyzing the codon usage pattern. Materials and Methods: The evolution of viruses is widely studied by analyzing their nucleotides and coding regions/ codons using various methods. A total of 115 complete coding regions of CSFVs including one complete genome from our laboratory (MH734359) were included in this study and analysis was carried out using various methods in estimating codon usage bias and evolution. This study elaborates on the factors that influence the codon usage pattern. Results: The effective number of codons (ENC) and relative synonymous codon usage showed the presence of codon usage bias. The mononucleotide (A) has a higher frequency compared to the other mononucleotides (G, C, and T). The dinucleotides CG and CC are underrepresented and overrepresented. The codons CGT was underrepresented and AGG was overrepresented. The codon adaptation index value of 0.71 was obtained indicating that there is a similarity in the codon usage bias. The principal component analysis, ENC-plot, Neutrality plot, and Parity Rule 2 plot produced in this article indicate that the CSFV is influenced by the codon usage bias. The mutational pressure and natural selection are the important factors that influence the codon usage bias. Conclusion: The study provides useful information on the codon usage analysis of CSFV and may be utilized to understand the host adaptation to virus environment and its evolution. Further, such findings help in new gene discovery, design of primers/probes, design of transgenes, determination of the origin of species, prediction of gene expression level, and gene function of CSFV. To the best of our knowledge, this is the first study on codon usage bias involving such a large number of complete CSFVs including one sequence of CSFV from India

African swine fever: A permanent threat to Indian pigs

India has 9 million pigs, of which 45% are in the North eastern (NE) states of India. Viral diseases affecting pigs are a major concern of mortality causing huge loss to the pig farmers. One such disease is African swine fever (ASF) that has already knocked the porous borders of NE states of India. ASF is a highly contagious devastating disease of pigs and wild boars causing 100% mortality. The causative agent African swine fever virus (ASFV) belongs to the genus Asfivirus, family Asfarviridae. Pig is the only species affected by this virus. Soft ticks (Ornithodoros genus) are shown to be reservoir and transmission vectors of ASFV. Transmission is very rapid and quickly engulfs the entire pig population. It is very difficult to differentiate classical swine fever from ASF since clinical symptoms overlap. Infected and in contact pigs should be culled immediately and buried deep, and sheds and premises be disinfected to control the disease. There is no vaccine available commercially. Since its first report in Kenya in 1921, the disease has been reported from the countries in Europe, Russian federation, China, and Myanmar. The disease is a threat to Indian pigs. OIE published the first report of ASF in India on May 21, 2020, wherein, a total of 3701 pigs died from 11 outbreaks (Morbidity - 38.45% and mortality - 33.89%) in Assam and Arunachal Pradesh states of India. ASF is non-zoonotic

An Estimate of Global Anthrax Prevalence in Livestock: A Meta-analysis

Background and Aim: Anthrax, caused by the soil-borne spore-forming bacteria called Bacillus anthracis, is a zoonotic disease that persists worldwide in livestock and wildlife and infects humans. It is a great hazard to livestock; henceforth, evaluating the global concerns about the disease occurrence in livestock is essential. This study was conducted to estimate the global prevalence of anthrax and predict high-risk regions, which could be an input to veterinarians to take necessary steps to control and avoid the disease. Materials and Methods: A literature review was performed using online databases, namely, PubMed, Google Scholar, Scopus, Biomed Central, and Science Direct, to extract relevant publications worldwide between 1992 and 2020. Initially, 174 articles were selected, and after scrutinizing, 24 articles reporting the prevalence of anthrax were found to be adequate for the final meta-analysis. The statistical study was accompanied by employing fixed effects and random effects models using R. Results: The pooled prevalence of anthrax globally was 28% (95% confidence interval, 26-30%) from 2452 samples through the fixed effects model. Continent-wise subgroup analysis through the random effects model revealed that the pooled prevalence of anthrax was highest in Africa (29%) and least in North America (21%). Conclusion: In these publications, anthrax causes economic loss to farmers and, thus, to the world. Hence, controlling anthrax infections in high-risk regions are essential by implementing appropriate control measures to decrease the effect of the disease, thereby reducing economic loss