Epidemiology, impact and control of rabies in Nepal : a systematic review

Background: Rabies is a vaccine-preventable viral zoonosis belonging to the group of neglected tropical diseases. Exposure to a rabid animal may result in a fatal acute encephalitis if effective post-exposure prophylaxis is not provided. Rabies occurs worldwide, but its burden is disproportionately high in developing countries, including Nepal. We aimed to summarize current knowledge on the epidemiology, impact and control of rabies in Nepal. Methods: We performed a systematic review of international and national scientific literature and searched grey literature through the World Health Organization Digital Library and the library of the National Zoonoses and Food Hygiene Research Centre, Nepal, and through searching Google and Google Scholar. Further data on animal and human rabies were obtained from the relevant Nepalese government agencies. Finally, we surveyed the archives of a Nepalese daily to obtain qualitative information on rabies in Nepal. Findings: So far, only little original research has been conducted on the epidemiology and impact of rabies in Nepal. Per year, rabies is reported to kill about 100 livestock and 10–100 humans, while about 1,000 livestock and 35,000 humans are reported to receive rabies post-exposure prophylaxis. However, these estimates are very likely to be serious underestimations of the true rabies burden. Significant progress has been made in the production of cell culture-based anti-rabies vaccine and rabies immunoglobulin, but availability and supply remain a matter of concern, especially in remote areas. Different state and non-state actors have initiated rabies control activities over the years, but efforts typically remained focalized, of short duration and not harmonized. Communication and coordination between veterinary and human health authorities is limited at present, further complicating rabies control in Nepal. Important research gaps include the reporting biases for both human and animal rabies, the ecology of stray dog populations and the true contribution of the sylvatic cycle. Interpretation: Better data are needed to unravel the true burden of animal and human rabies. More collaboration, both within the country and within the region, is needed to control rabies. To achieve these goals, high level political commitment is essential. We therefore propose to make rabies the model zoonosis for successful control in Nepal

Perception and Challenges of Preventive Measures of COVID-19 Among Nepalese Frontline Health Professionals: An Unexplored Realism.

BACKGROUND: A new coronavirus causes COVID-19, a developing respiratory illness. Unfortunately, there is little information assessing healthcare workers' understanding of technology and preventative strategies during the Nepalese epidemic. Researchers from other subspecialties uncovered some mythical thoughts. As a result, we decided to put it to the test with healthcare personnel on the front lines. The research also looked at the problems experienced by frontline health care personnel (HCP) because of the COVID-19 strategic shift in work policy. METHODS: Nepalese healthcare workers participated in web-based cross-sectional research. A pre-tested, structured questionnaire utilizing a Google form was used to get self-informed, digitally typed consent, and examine critical perspectives and problems with current technology and COVID-19 prevention efforts. RESULTS: In total, 243 participants with mean age of 29.66 ± 7.61 years agreed to participate and were doctors (n = 27), health assistants (n = 2), medical intern doctors (n = 1), paramedical (n = 139), pharmacy (n = 1), and paramedical interns (n = 73) in this study. The calculated mean percentage score of knowledge on instruments and tools was 73.64 (SD ± 10.43) %, and perception on COVID-19 transmission and control was 70.06 (SD ± 18.30) %. At various levels, frontline health workers faced significant challenges, including the adoption of digital health technology. CONCLUSION: Frontline HCPs are anticipated to have updated knowledge from what the study has outlined. It is recommended to follow national guidelines. Policies should be put in place so that every frontline worker can demonstrate high standards in prevention, control, and equipment use that do not create misinformation among HCPs. Throughout, support for digital health materials and disease control methods for HCPs is essential

Ecological drivers of gut microbiome and antimicrobial resistance in swine

Doctor of PhilosophyDepartment of Diagnostic Medicine/PathobiologyTiruvoor G. NagarajaVictoriya VolkovaThe pig gastrointestinal tract hosts a large and diverse microbial community, representing a complex and dynamic ecosystem. The microbial communities are not uniformly distributed and differ across the locations of the gastrointestinal tract. The microbial community composition influences the prevalence and distribution of antimicrobial resistance (AMR) in the gut. The microbial taxonomic composition, richness, and diversity are influenced by age of the pig, dietary composition, and antimicrobial drug use. The association between antimicrobial use and AMR development is of interest because of public health implications. Several studies in swine and cattle have reported a decrease in AMR in fecal bacteria with animal age; however, exact dynamics and contributing factors are largely unknown. Investigations on the AMR dynamics in gut microbiome during the production phase of food animals could aid in the design of a framework to address the problem of AMR in the food chain in a sustainable manner. The primary hypothesis of our study was that the dynamics of gut microbiome and AMR in swine are largely a function of age and dietary composition. Therefore, the objectives of the studies were: 1. Perform a scoping review of the literature on the age-dependence of AMR of fecal bacteria in food animals. 2. Conduct longitudinal studies to evaluate the dynamics of fecal bacteriome and mycobiome taxonomic compositions and AMR prevalence between cohorts of production pigs (n=12) from birth to harvest and breeding sows (two cohorts, n=6 and n=12) from 3 weeks through first farrowing and weaning, to test the hypothesis that the dynamics are a function of age, rather than the production system. 3. Investigate interactions between the age-related dynamics and effects of diet (levels and sources of fiber) and antimicrobial treatments (injectable ceftiofur or penicillin G) in influencing the fecal microbiome taxonomic composition and AMR in finisher pigs. 4. Conduct a study to describe bacterial community composition associated with luminal contents and mucosal epithelium from different segments of the gut of piglets. Culture-based and metagenomic analyses coupled with statistical modeling were utilized to monitor microbiome changes and estimate and infer AMR occurrence in gut bacterial communities in relation to age and diet. The scoping review of published data suggested that the animal-level prevalence and within-animal abundance of AMR in enteric or fecal bacteria decreased with age during the production life-span in pigs, in beef and dairy cattle. The age-dependent dynamics of fecal bacteriome and mycobiome taxonomic compositions and associated animal-level prevalence and within-animal abundance of AMR were similar in a cohort of production pigs and two cohorts of breeding sows. The highest AMR prevalence and abundance occurred at the youngest age-points and decreased with age and stabilized around 5 to 6 months of age. The data suggested a strong age-dependence and additional independent diet effects on the fecal microbiome composition and AMR. Data also showed that the concentrations of ceftiofur metabolites in swine feces were lower on day 3 compared to day 1 of the 3-day ceftiofur treatment, irrespective of the animal diet or gender. In a study conducted in piglets (6-7 weeks old: n=3), luminal contents and mucosa were collected from the stomach, duodenum, ileum (at two locations), cecum, spiral colon, and the rectum. The bacterial community composition and AMR genes were determined, and the study showed that the bacterial taxonomic composition and AMR gene repertoire changed throughout the gastrointestinal tract of piglets. Genes encoding bacterial resistance or reduced susceptibility to tetracyclines, β-lactams, aminoglycosides, and glycopeptides were most abundant AMR genes in the samples. In summary, age and diet, in addition to the use of antimicrobials, play an important role in the establishment and maintenance of gut microbial diversity and AMR in pigs

Why has COVID-19 not hit the countries like Nepal yet?

Noble CORONA Virus (COVID-19) is an infectious disease similar form of pneumonia/ SARS-CoV-2- impacting globally. The fear of coronavirus looks pandemic, but its severity is uncertain. Nepal was one of the first nine countries outside of China to report a COVID-19 case. Also, its unpredictability of mode or range of surface, the lifespan of the virus, objects of transmission (a distance of air/air currents, living duration in air, humidity, duration on objects, surface). The first case was found in Wuhan in December 2019 in China. The purpose is to summarize the current information about COVID-19 and to explore in terms of why Nepal is not hitting severely, while other countries are on death toll? We summarized the published articles form the web sources and news, Academic Journals, Ministry of health and population Nepal, WHO/CDC update reports/guidelines, Google search engine. Thematic analysis is made to explore the situation. Although, Nepal has a lack of health services, testing kits, advance lab and protecting equipment (PPE), why COVID-19 does not hit Nepal than China, Europe and North America, it still tremendous uncertainty. Is lockdown, isolation, social distance and quarantine the best ways of prevention? The hypothesis is floating globally – do BCG vaccinated countries are safer than non-user OR due to not having enough kits to screen populations at risk for the virus – while lack of testing a big cause for missing case OR Nepalese have better immune systems? It has attracted global attention. We believe that the COVID-19 is still evolving and it is too early to predict of an outbreak in Nepal. The government needs to increase funding for local health departments, begin planning for future epidemics and be prepared to bolster the economy by supporting consumer spending the midst of a serious outbreak. COVID-19 is a serious health challenge for Nepal, but so far the number of death has been lower than was foretell. It is, therefore essential to carry out more scientific evidence to explore results. Nepalese health services need to maintain up than today and follow lockdown, isolation, social distance and an advance screening test kit through the country

Why has COVID-19 not hit the countries like Nepal yet?

Noble CORONA Virus (COVID-19) is an infectious disease similar form of pneumonia/SARS-CoV-2-impacting globally. The fear of coronavirus looks pandemic, but its severity is uncertain. Nepal was one of the first nine countries outside of China to report a COVID-19 case. Also, its unpredictability of mode or range of surface, the lifespan of the virus, objects of transmission (a distance of air/air currents, living duration in air, humidity, duration on objects, surface). The first case was found in Wuhan in December 2019 in China. The purpose is to summarize the current information about COVID-19 and to explore in terms of why Nepal is not hitting severely, while other countries are on death toll? We summarized the published articles form the web sources and news, Academic Journals, Ministry of health and population Nepal, WHO/CDC update reports/guidelines, Google search engine. Thematic analysis is made to explore the situation. Although, Nepal has a lack of health services, testing kits, advance lab and protecting equipment (PPE), why COVID-19 does not hit Nepal than China, Europe and North America, it still tremendous uncertainty. Is lockdown, isolation, social distance and quarantine the best ways of prevention? The hypothesis is floating globally – do BCG vaccinated countries are safer than non-user OR due to not having enough kits to screen populations at risk for the virus – while lack of testing a big cause for missing case OR Nepalese have better immune systems? It has attracted global attention. We believe that the COVID-19 is still evolving and it is too early to predict of an outbreak in Nepal. The government needs to increase funding for local health departments, begin planning for future epidemics and be prepared to bolster the economy by supporting consumer spending the midst of a serious outbreak. COVID-19 is a serious health challenge for Nepal, but so far the number of death has been lower than was foretell. It is, therefore essential to carry out more scientific evidence to explore results. Nepalese health services need to maintain up than today and follow lockdown, isolation, social distance and an advance screening test kit through the country

Variation in fluoroquinolone pharmacodynamic parameter values among isolates of two bacterial pathogens of bovine respiratory disease

To design an antimicrobial treatment regimen for a bacterial disease, data on the drug pharmacodynamics (PD) against selected drug-susceptible strains of the pathogen are used. The regimen is applied across such strains in the field, assuming the PD parameter values remain the same. We used time-kill experiments and PD modeling to investigate the fluoroquinolone enrofloxacin PD against different isolates of two bovine respiratory disease pathogens: four Mannheimia haemolytica and three Pasteurella multocida isolates. The models were fitted as mixed-effects non-linear regression; the fixed-effects PD parameter values were estimated after accounting for random variation among experimental replicates. There was both inter- and intra- bacterial species variability in the PD parameters Hill-coefficient and Emax (maximal decline of bacterial growth rate), with more variable PD responses among M. haemolytica than among P. multocida isolates. Moreover, the Hill-coefficient was correlated to the isolate's maximal population growth rate in the absence of antimicrobial exposure (a.k.a. specific growth rate; Spearman's ρ = 0.98, p-value = 0.003, n = 6 isolates excluding one outlier). Thus, the strain's properties such as growth potential may impact its PD responses. This variability can have clinical implications. Modifying the treatment regimen depending on phenotypic properties of the pathogen strain causing disease may be a precision medicine approach

Temporal dynamics of the fecal microbiome in female pigs from early life through estrus, parturition, and weaning of the first litter of piglets

Abstract Background Age-associated changes in the gastrointestinal microbiome of young pigs have been robustly described; however, the temporal dynamics of the fecal microbiome of the female pig from early life to first parity are not well understood. Our objective was to describe microbiome and antimicrobial resistance dynamics of the fecal microbiome of breeding sows from early life through estrus, parturition and weaning of the first litter of piglets (i.e., from 3 to 53 weeks of age). Results Our analysis revealed that fecal bacterial populations in developing gilts undergo changes consistent with major maturation milestones. As the pigs progressed towards first estrus, the fecal bacteriome shifted from Rikenellaceae RC9 gut group- and UCG-002-dominated enterotypes to Treponema- and Clostridium sensu stricto 1-dominated enterotypes. After first estrus, the fecal bacteriome stabilized, with minimal changes in enterotype transition and associated microbial diversity from estrus to parturition and subsequent weaning of first litter piglets. Unlike bacterial communities, fecal fungal communities exhibited low diversity with high inter- and intra-pig variability and an increased relative abundance of certain taxa at parturition, including Candida spp. Counts of resistant fecal bacteria also fluctuated over time, and were highest in early life and subsequently abated as the pigs progressed to adulthood. Conclusions This study provides insights into how the fecal microbial community and antimicrobial resistance in female pigs change from three weeks of age throughout their first breeding lifetime. The fecal bacteriome enterotypes and diversity are found to be age-driven and established by the time of first estrus, with minimal changes observed during subsequent physiological stages, such as parturition and lactation, when compared to the earlier age-related shifts. The use of pigs as a model for humans is well-established, however, further studies are needed to understand how our results compare to the human microbiome dynamics. Our findings suggest that the fecal microbiome exhibited consistent changes across individual pigs and became more diverse with age, which is a beneficial characteristic for an animal model system

Age influences the temporal dynamics of microbiome and antimicrobial resistance genes among fecal bacteria in a cohort of production pigs

Abstract Background The pig gastrointestinal tract hosts a diverse microbiome, which can serve to select and maintain a reservoir of antimicrobial resistance genes (ARG). Studies suggest that the types and quantities of antimicrobial resistance (AMR) in fecal bacteria change as the animal host ages, yet the temporal dynamics of AMR within communities of bacteria in pigs during a full production cycle remains largely unstudied. Results A longitudinal study was performed to evaluate the dynamics of fecal microbiome and AMR in a cohort of pigs during a production cycle; from birth to market age. Our data showed that piglet fecal microbial communities assemble rapidly after birth and become more diverse with age. Individual piglet fecal microbiomes progressed along similar trajectories with age-specific community types/enterotypes and showed a clear shift from E. coli/Shigella-, Fusobacteria-, Bacteroides-dominant enterotypes to Prevotella-, Megaspheara-, and Lactobacillus-dominated enterotypes with aging. Even when the fecal microbiome was the least diverse, the richness of ARGs, quantities of AMR gene copies, and counts of AMR fecal bacteria were highest in piglets at 2 days of age; subsequently, these declined over time, likely due to age-related competitive changes in the underlying microbiome. ARGs conferring resistance to metals and multi-compound/biocides were detected predominately at the earliest sampled ages. Conclusions The fecal microbiome and resistome—along with evaluated descriptors of phenotypic antimicrobial susceptibility of fecal bacteria—among a cohort of pigs, demonstrated opposing trajectories in diversity primarily driven by the aging of pigs

Number of rabies outbreaks reported during 2005–2014 to the Veterinary Epidemiology Center of the Directorate of Animal Health, Department of Livestock Services, Ministry of Agricultural Development.

<p>See <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004461#pntd.0004461.s004" target="_blank">S4 File</a> for raw data and abbreviations.</p