Search Results (75)

Rabies, a viral encephalitis caused by rabies virus (RABV), is 100% fatal upon the onset of symptoms. Effective post-exposure prophylaxis (PEP) measures are available, but they are often difficult to access in low-income countries. WHO estimates about 59,000 deaths due to rabies globally, and the majority are contributed by developing countries. Hence, developing drugs for the treatment of post-symptomatic rabies is an urgent and unmet demand. It is worth noting that previous efforts regarding antiviral strategies, such as small-interfering RNA, antibodies and small-molecule inhibitors, against the rabies virus have failed to show efficacy in pre-clinical studies, especially when the virus has reached the central nervous system (CNS). Therefore, drug repurposing seems to be an alternative tool for the development of new anti-rabies drugs. We validated and used a high-throughput, FITC-conjugated antibody-based flow cytometry assay to expedite the identification of repurposable new drug candidates against the RABV. The assay was validated using ribavirin and salinomycin as reference compounds, which showed EC50 values of 10.08 µM and 0.07 µM, respectively. We screened a SelleckChem library comprising 3035 FDA-approved compounds against RABV (CVS-11) at 10 µM concentration. Five compounds (clofazimine, tiamulin, difloxacin, harringtonine and homoharringtonine) were active against RABV, with greater than 90% inhibition. Homoharringtonine (HHT) identified in the present study is active against laboratory-adapted RABV (CVS-11) and clinical isolates of RABV, with an average EC50 of 0.3 µM in both BHK-21 and Neuro-2a cell lines and exhibits post-entry inhibition. Full article

This experiment evaluated the effects of a nose flap (NF) device and bovine-appeasing substance (BAS) administration on the growth, temperament, immune response, and pasture behavior of calves during weaning. A total of 24 Nellore calves were used in a 2 × 2 factorial arrangement. The factors were the use of an NF or not (NoNF) for 14 d before weaning and the administration of BASs or not (NoBAS) at weaning (d 0). NF vs. NoNF reduced (p ≤ 0.01) the average daily gain (ADG; d −7 to 84; −0.289 vs. 0.378 ± 0.13 kg/d) and the time ruminating but increased (p ≤ 0.05) the exit score from the chute (d 14 and 28) and the time grazing. BAS vs. NoBAS administration increased (p ≤ 0.02) the ADG (d 14 to 84; 0.487 vs. −0.08 ± 0.10 kg/d) and the time grazing, reduced (p < 0.01) the time ruminating, and tended to decrease (p ≤ 0.10) the exit score (d 7, 14 and 28) and the time vocalizing. Treatments did not affect (p ≥ 0.35) serum rabies titer concentration. Thus, the use of NFs reduced growth and increased stress after weaning, while BAS administration increased growth and decreased stress after weaning, altering behavior but not the immune system. According to the results of this experiment, the use of BASs but not NFs is recommended to alleviate weaning stress in beef calves. Full article

Background/Objectives: Rabies is almost invariably fatal once clinical symptoms manifest. Timely and accurate diagnosis is essential for effective treatment and prevention. Dogs are the principal reservoirs of the virus, particularly in developing nations, highlighting the importance of precise diagnostic and control measures to prevent human cases. This systematic review and meta-analysis assessed the accuracy of laboratory tests for diagnosing rabies in humans and dogs. Methods: The PubMed database was searched for published studies on rabies diagnosis between 1990 and 2024. Following PRISMA statement recommendations, we included 60 studies that met the selection criteria. Results: The results demonstrated the effectiveness of immunological tests like the Enzyme-Linked Immunosorbent Assay (ELISA) and molecular tests such as Reverse Transcription Polymerase Chain Reaction (RT-PCR) for both humans and dogs. In this study, the Direct Fluorescent Antibody Test (DFAT) exhibited lower diagnostic performance, with an area under the curve for false positive rates (AUC_FPR = 0.887). In contrast, ELISA (AUC_FPR = 0.909) and RT-PCR (AUC_FPR = 0.905) provided more consistent results. Notably, the Rapid Immunochromatographic Test (RIT) showed the best performance (AUC_FPR = 0.949), highlighting its superior diagnostic capabilities compared to DFAT. Conclusions: These findings underscore the need to modernize rabies diagnostic protocols by incorporating advanced methodologies to improve diagnostic accuracy, reduce transmission, and decrease mortality rates. Full article

Engineered viral vectors designed to deliver genetic material to specific targets offer significant potential for disease treatment, safer vaccine development, and the creation of novel biochemical research tools. Viral tropism, the specificity of a virus for infecting a particular host, is often modified in recombinant viruses to achieve precise delivery, minimize off-target effects, enhance transduction efficiency, and improve safety. Key factors influencing tropism include surface protein interactions between the virus and host-cell, the availability of host-cell machinery for viral replication, and the host immune response. This review explores current strategies for modifying the tropism of recombinant viruses by altering their surface proteins. We provide an overview of recent advancements in targeting non-enveloped viruses (adenovirus and adeno-associated virus) and enveloped viruses (retro/lentivirus, Rabies, Vesicular Stomatitis Virus, and Herpesvirus) to specific cell types. Additionally, we discuss approaches, such as rational design, directed evolution, and in silico and machine learning-based methods, for generating novel AAV variants with the desired tropism and the use of chimeric envelope proteins for pseudotyping enveloped viruses. Finally, we highlight the applications of these advancements and discuss the challenges and future directions in engineering viral tropism. Full article

Information on the long-term effects of the addition of organics and fertilizers to wheat under the pearl millet–wheat cropping system with semi-arid conditions in north-western India is still lacking. The present research was conducted in an ongoing field experiment initiated during Rabi 1995 at the Research Farm of Chaudhary Charan Singh at Haryana Agricultural University, Hisar. After 25 years, the impacts of nutrient management practices on soil fertility and wheat productivity were evaluated. The experiment comprised a total of eight treatment combinations viz. half and full doses of recommended fertilizers (N and P), organic manures (FYM: farmyard manure, POM: poultry manure, and PRM: press mud) alone and in combination with NP fertilizers. The conjoint application of organic manure and chemical fertilizers resulted in a positive influx of nutrients via increasing total organic carbon (TOC), available N, P, K, and S, which ranged from 0.46 to 1.42%, 122.70 to 194.70, 15.66 to 74.92, 340.5 to 761.2, and 15.26 to 54.63 kg ha⁻¹ in surface soil (0–15 cm), respectively. Carbon fractions and crop yield were significantly improved by adopting integrated nutrient management (INM). The TOC showed a positive and significant correlation with C fractions (r > 0.92) and with soil-available N, P, K, and S (r > 0.77) content. The data also revealed a strong relationship between TOC and soil-available (0–15 cm) nutrients i.e., available N (R²= 0.769), available P (R² = 0.881), available K (R² = 0.758), and available S (R² = 0.914), respectively. Thus, practices that increased TOC were also beneficial in enhancing the availability of the nutrients in the soil. A positive and highly significant correlation was also found among wheat yield, nutrient (NPKS) content, and uptake. A polynomial relationship between grain yield and grain N (R² = 0.962), P (R² = 0.946), and K (R² = 0.967) content, and between straw yield and straw N (R² = 0.830), P (R² = 0.541) and K (R² = 0.976) content was obtained. Integrated use of PRM_7.5 followed by FYM₁₅ and POM₅ coupled with NP fertilizers proved best, which could be beneficial for obtaining nutritious and highest wheat yield (grain: 6.01 t ha⁻¹ and straw: 7.70 t ha⁻¹) coupled with improved fertility within a sustained manner under the pearl millet–wheat sequence in prevailing semi-arid conditions of the North Indian state of Haryana. Full article

The goal of this study is to identify the optimum NPK fertilization to maximize yield and productivity under local environmental constraints. To address this concern, a field experiment was conducted at Agronomy Research Farm, The University of Agriculture, Peshawar, during the rabi seasons of 2019–2020 and 2020–2021 in a randomized complete block design (RCBD) with three replications. Treatments consisted of five Chinese wheat hybrids (18A-1, JM-1215, JM-1683, JM-1216, H-1) and one Australian hybrid (WS-1) with two local checks (Wadan-17 and Pirsabak-15) and two NPK levels, i.e., basal dose (120-90-60 NPK kg ha⁻¹) and 25% higher than basal dose (150-112-75 NPK kg ha⁻¹). The results of the two years’ experimentation exhibited that wheat hybrid WS-1 produced higher tillers (444 and 423 m⁻²), leaf area (32.7 and 30.7 cm²), leaf area index (5.0 and 5.4), plant height (105.3 and 103.1 cm), spike length (21.9 and 21.5 cm), spikes (329 and 322 m⁻²), grains spike⁻¹ (59 and 58), thousand grain weight (62.2 and 62.2 g) and biological yield (9769 and 9906 kg ha⁻¹) as compared to local check varieties. Wheat hybrids WS-1, JM-1683, H-1 and 18A1 produced 31%, 27%, 26% and 26% higher grain yield than local check Pirsabak-15, respectively, while a higher harvest index (61 and 59%) was noted for JM-1683 in both years. Application of NPK at the rate of 150-112-75 kg ha⁻¹ increased emergence (87 m⁻²), tillers (421 and 407 m⁻²), leaf area (23 and 20.5 cm²), leaf area index (3.3), plant height (98.2 and 96.9 cm), spike length (15.9 and 16.3 cm), spikes (317 and 314 m⁻²), grains spike⁻¹ (43), thousand grain weight (56.5 and 56.3 g), biological yield (9057 and 9163 kg ha⁻¹) and grain yield (3702 and 3778 kg ha⁻¹) compared to the lower level of NPK (120-90-60 kg ha⁻¹). It is concluded that Chinese wheat hybrid JM-1683 and Australian hybrid WS-1 responded better to the higher level of NPK (150-112-75 kg ha⁻¹) in terms of grain yield and its components and are therefore recommended for the agro-climatic condition of the Peshawar valley. Full article

The measurement of rabies-neutralizing antibody is important for monitoring the response to rabies vaccination. For all the purposes of measurement, such as routine monitoring of vaccine response in humans and animals, serosurveys, and biologics qualification, accurate and precise results are necessary. The risks associated with sample handling variation, which may impact the test results, can be overlooked within a laboratory. To determine the robustness of rabies-neutralizing antibodies in human and animal serum, samples were treated to mimic various possible deviations in the sample handling protocols. Potential deviations were designed to investigate common client inquiries and possible sample conditions experienced during shipping, storage, and laboratory processes. The treatments included the duration that sera were kept at a temperature greater than that of a refrigerator (room temperature, zero hours to two weeks), the number and duration of heat inactivation treatments (i.e., heat inactivation directly from freezer storage, etc.), the number of freeze–thaw cycles (zero, four, or six cycles), and the storage duration of sample dilutions in chamber slides before the addition of virus (zero hours to overnight). The results provided evidence for the robustness of rabies antibodies and the antibodies’ neutralizing function in uncontaminated, clear human and animal serum. In addition, prolonged heat exposure was identified as exerting the greatest impact on the measurement of rabies antibodies. Full article

The objective of this study was to evaluate the bait preference of three selected bait types by local dogs and the induced immunogenicity of the oral rabies vaccine strain SPBN GASGAS in Morocco. The vaccine strain, combined with different bait types, has been tested in many different settings, but not yet in northern Africa. Overall, bait consumption and preference were similar in other studies using the same materials (bait type and sachet). The intestine bait had the highest acceptance rate (97.6%, 95%CI: 87.4–99.9), followed by the egg bait (83.0%, 95%CI: 69.2–92.4). Only 52% (95%CI: 37.4–66.3) of the dogs showed an interest in the fish meal bait. However, considering the successful release of the contents of the sachet (blue-dyed water) into the oral cavity, the egg bait (65.7%, 95%CI: 47.8–80.9) scored better than the intestine bait (51.7%, 95%CI: 32.5–70.6). The dogs selected for the immunogenicity study were offered the egg bait containing a sachet filled with SPBN GASGAS (3.0 mL, 10^7.5 FFU/mL) or were given the same dose by direct oral administration (d.o.a.). In addition, several dogs were vaccinated by the parenteral route (s.c.) using a commercially available inactivated rabies vaccine. Unfortunately, due to the COVID-19 pandemic and subsequent travel restrictions, it was not possible to collect blood samples directly after vaccination. The blood samples were collected pre-vaccination and on five occasions between 450 and 1088 days post vaccination. The seroconversion rate, as determined for rabies-virus-neutralizing antibodies by the FAVN test, was significantly lower than that found for binding antibodies, as determined by ELISA, for all blood samples collected post vaccination. No treatment effect (bait, d.o.a., s.c.) could be seen in the seroconversion rate. At 15 months post vaccination, 84.2% of the dogs offered vaccine bait still tested sero-positive in ELISA. Only after 3 years was a clear drop in the seroconversion rate observed in all three treatment groups. This study confirms the long-term immunogenicity of the oral rabies vaccine SPBN GASGAS in dogs under field conditions. Full article

Seroprevalence of lyssaviruses in certain bat species has been proven in the Republic of Croatia, but there have been no confirmed positive bat brain isolates or human fatalities associated with bat injuries/bites. The study included a retrospective analysis of bat injuries/bites, post-exposure prophylaxis (PEP) and geographic distribution of bat injuries in persons examined at the Zagreb Antirabies Clinic, the Croatian Reference Centre for Rabies. In the period 1995–2020, we examined a total of 21,910 patients due to animal injuries, of which 71 cases were bat-related (0.32%). Of the above number of patients, 4574 received rabies PEP (20.87%). However, for bat injuries, the proportion of patients receiving PEP was significantly higher: 66 out of 71 patients (92.95%). Of these, 33 received only the rabies vaccine, while the other 33 patients received the vaccine with human rabies immunoglobulin (HRIG). In five cases, PEP was not administered, as there was no indication for treatment. Thirty-five of the injured patients were biologists or biology students (49.29%). The bat species was confirmed in only one of the exposure cases. This was a serotine bat (Eptesicus serotinus), a known carrier of Lyssavirus hamburg. The results showed that the bat bites were rather sporadic compared to other human injuries caused by animal bites. All bat injuries should be treated as if they were caused by a rabid animal, and according to WHO recommendations. People who come into contact with bats should be strongly advised to be vaccinated against rabies. Entering bat habitats should be done with caution and in accordance with current recommendations, and nationwide surveillance should be carried out by competent institutions and in close collaboration between bat experts, epidemiologists and rabies experts. Full article

Animal bites are a common reason for children to visit primary care and emergency departments. Dog bites are the most prevalent, followed by cat bites at 20–30%. Other animals such as bats, monkeys, snakes, and rats collectively contribute less than 1% of cases. Hospitalization is necessary in only 4% of animal bite incidents. The main aim of this narrative review is to summarize the main protocols currently followed in pediatrics in cases involving the most common bites from different animal species. Analysis of the literature showed that the management of common animal bites in children presents a multifaceted challenge requiring a comprehensive understanding of the epidemiology, clinical presentation, and treatment modalities associated with each specific species. Effective wound management is paramount in reducing the risk of infection and promoting optimal healing outcomes. Additionally, tetanus vaccination status should be assessed and updated as necessary, and prophylactic antibiotics may be indicated in certain cases to prevent secondary infections. Furthermore, the role of rabies prophylaxis cannot be overstated, particularly in regions where rabies is endemic or following bites from high-risk animals. In addition to medical management, psychosocial support for both the child and their caregivers is integral to the overall care continuum. Future studies exploring the efficacy of novel treatment modalities, such as topical antimicrobial agents or advanced wound dressings, may offer new insights into optimizing wound healing and reducing the risk of complications. Full article

The importance of selecting an appropriate berseem variety and implementing effective nutrient management practices is crucial for maximizing both the production and economic potential of forage crops. This was clearly demonstrated in a field experiment conducted during the rabi seasons of 2019–2020 and 2020–2021. The experimental setup was a factorial randomized block design incorporating five berseem varieties (Mescavi, HB-1, HB-2, BL-10, and BL-42) and five integrated nutrient management practices: 100% recommended dose of fertilizers (RDF) or NM-1, 75% RDF + plant growth-promoting rhizobacteria (PGPR) or NM-2, 75% RDF + municipal solid waste compost (MSWC) or NM-3, 75% RDF + farmyard manure (FYM) + PGPR or NM-4, and 50% RDF + MSWC + PGPR or NM-5. The objective of the experiment was to evaluate the physio-morphological responses, biomass yield, and economic efficiencies of different berseem varieties under various nutrient management practices. The experimental results highlighted the superior performance of the BL-42 variety in terms of growth and yield attributes compared to the other tested berseem varieties. Specifically, BL-42 showed an enhancement in total green fodder yield by 17.10%, 26.60%, 37.75%, and 28.04% over the varieties BL-10, HB-2, HB-1, and Mescavi, respectively. Moreover, the application of the 75% RDF + FYM + PGPR treatment (NM-4) significantly boosted the total green fodder yield by 13.08%, 14.29%, 34.48%, and 39.02% over the 75% RDF + MSWC, 100% RDF, 75% RDF + PGPR, and 50% RDF + MSWC + PGPR treatments, respectively. In terms of economic returns, BL-42 achieved a significantly higher gross return (GR) and net return (NR) of 194,989 ₹/ha and 145,142 ₹/ha, respectively, compared to the GR and NR of BL-10 (166,512 and 116,665 ₹/ha, respectively). Similarly, the nutrient management practice of 75% RDF + FYM + PGPR recorded the highest GR and NR (191,638 and 137,346 ₹/ha, respectively) compared to the 100% RDF treatment (167,593 and 120,716 ₹/ha, respectively). These findings underscore the critical role of variety selection and tailored nutrient management in optimizing both the yield and economic gains in forage crop cultivation. The significant differences in production and returns highlight the potential of targeted agronomic strategies to enhance the profitability and sustainability of forage farming. Full article

Rabies encephalitis has plagued humankind for thousands of years. In developed countries, access to preventive care, both pre-exposure and post-exposure, has significantly reduced the burden of suffering and disease. However, around the world, rabies remains a neglected tropical disease, largely due to uncontrolled dog rabies, and tens of thousands perish each year. Currently, the standard of care for management of rabies encephalitis is palliation. Heroic attempts to treat human rabies patients over the last few decades have yielded glimpses into our understanding of pathophysiology, opening the door to the development of new antiviral therapies and modalities of treatment. Researchers continue to investigate new compounds and approaches to therapy, yet there remain real challenges given the complexity of the disease. We explore and review some of the promising therapies on the horizon in pursuit of a salvage treatment for rabies. Full article

Rabies is a highly fatal zoonotic disease that causes an estimated 60,000 human deaths each year, many of which occur in Africa and Asia where the disease is likely underreported. Uncontrolled transmission of rabies presents a major threat to public health in countries such as Mongolia, where 26% of the population lives a pastoralist lifestyle characterized by increased interaction with livestock animals. Here, we report a case of rabies exposure in a six-year-old male after being bitten by a horse in both the head region and the leg. At the suspicion of rabies, post-exposure prophylaxis (PEP) was initiated, with the patient receiving four doses of PEP vaccine as well as a single treatment of rabies immunoglobulin. The horse was later confirmed to be rabies-positive through rapid antigen testing and RT-PCR. Human rabies exposure from horses is unusual within Mongolia, given that historically over 70% of human rabies cases within the country are attributed to dogs, wolves, or foxes. This case further emphasizes the need for more routine vaccination of domestic animals within Mongolia. Additionally, animal bites, even from animals not frequently associated with rabies, should be treated as possible rabies exposure events. Full article

A comprehensive study spanning three kharif and rabi seasons (2018–2019, 2020–2021, and 2021–2022) was conducted to investigate the intricate interactions among different cropping sequences and their impacts on cumin yield, financial outcomes, and soil microbial dynamics. The experiment was designed using a randomized block design, comprising eight distinct treatment combinations, each replicated three times. The results revealed compelling insights into the potential of specific cropping sequences to enhance multiple aspects of agricultural sustainability. The results revealed that the highest cumin yield (averaging 592 kg ha⁻¹ over the three years) was achieved when cumin was cultivated subsequent to pearl millet, showcasing significant increases of 14.28% and 23.07% over the cumin–fallow and cumin–cotton cropping systems, respectively. When it came to cumin equivalent yield, the cumin–cotton cropping sequence (985 kg ha⁻¹) emerged as the most favorable, closely followed by cumin–groundnut (968 kg ha⁻¹). Furthermore, analyzing net realizations and benefit–cost ratios demonstrated that the cumin–pearl millet cropping sequence stood out with the maximum values (₹88,235 ha⁻¹ and 2.7, respectively), followed by the cumin–mung bean cropping system (₹84,164 ha⁻¹ and 2.47, respectively). Among the various cropping sequences studied, cumin–mung bean, cumin–cluster bean, cumin–pearl millet and cumin–groundnut were recorded as statistically similar in terms of soil microbial enzymatic activities viz. fluorescein diacetate (FDA), alkaline phosphatase (ALP), dehydrogenase activity (DHA), and microbial biomass carbon and were at par over the cumin–sorghum, cumin–sesame, cumin–cotton and cumin–fallow cropping systems. These findings emphasize the significance of strategic crop sequencing for sustainable agriculture practices that simultaneously optimize productivity and maintain soil health. Full article