Knowledge, attitudes and practices related to neglected tropical diseases (schistosomiasis and fascioliasis) of public health importance: A cross-sectional study.

Background: Snails play an important role as an intermediate host in various parasitic diseases, which are referred to as snail-borne parasitic diseases (SBPDs). The prevalence of the SBPDs, schistosomiasis and fascioliasis is low in Pakistan compared to other countries. The present study investigated knowledge, attitudes, and practices related to these two SPBDs and risk factors associated with them among the humans living in close contact with livestock and pets from three regions of Pakistan: Punjab, Islamabad and Azad Jammu and Kashmir (AJK). Methods: A cross-sectional survey was conducted using a structured questionnaire to assess participants' knowledge, attitude and practices related to schistosomiasis and fascioliasis during 2021-2022. Results: The majority of the 507 participants who were interviewed had good knowledge of schistosomiasis and fascioliasis: 43% were aware of schistosomiasis and 57% were aware of fascioliasis, but only 25% knew about snails as an intermediate host. Most respondents had a positive attitude toward treatment, prevention and control of the diseases but they did not have any healthcare facilities. Conclusion: This study highlights the importance of the public's awareness for the need to control SBPDs. It also draws attention to the need for health education for risk reduction and the prevention of SBPDs in endemic areas.

An Inventory of Anthelmintic Plants across the Globe.

A wide range of novelties and significant developments in the field of veterinary science to treat helminth parasites by using natural plant products have been assessed in recent years. To the best of our knowledge, to date, there has not been such a comprehensive review of 19 years of articles on the anthelmintic potential of plants against various types of helminths in different parts of the world. Therefore, the present study reviews the available information on a large number of medicinal plants and their pharmacological effects, which may facilitate the development of an effective management strategy against helminth parasites. An electronic search in four major databases (PubMed, Scopus, Web of Science, and Google Scholar) was performed for articles published between January 2003 and April 2022. Information about plant species, local name, family, distribution, plant tissue used, and target parasite species was tabulated. All relevant studies meeting the inclusion criteria were assessed, and 118 research articles were included. In total, 259 plant species were reviewed as a potential source of anthelmintic drugs. These plants can be used as a source of natural drugs to treat helminth infections in animals, and their use would potentially reduce economic losses and improve livestock production.

Enzymatic hydrolysis of low temperature alkali pretreated wheat straw using immobilized ß-xylanase nanoparticles.

A low temperature alkali (LTA) pretreatment method was used to treat wheat straw. In order to obtain good results, different factors like temperature, incubation time, NaOH concentration and solid to liquid ratio for the pretreatment process were optimized. Wheat straw is a potential biomass for the production of monomeric sugars. The objective of the current study was to observe the saccharification (%) of wheat straw with immobilized magnetic nanoparticles (MNPs). For this purpose, immobilized MNPs of purified ß-xylanase enzyme was used for hydrolysis of pretreated wheat straw. Wheat straw was pretreated using the LTA method and analyzed by SEM analysis. After completion of the saccharification process, saccharification% was calculated by using a DNS method. Scanning electron micrographs revealed that the hemicellulose, cellulose and lignin were partially removed and changes in the cell wall structure of the wheat straw had caused it to become deformed, increasing the specific surface area, so more fibers of the wheat straw were exposed to the immobilized ß-xylanase enzyme after alkali pretreatment. The maximum saccharification potential of wheat straw was about 20.61% obtained after pretreatment with optimized conditions of 6% NaOH, 1/10 S/L, 30 °C and 72 hours. Our results indicate the reusability of the ß-xylanase enzyme immobilized magnetic nanoparticles and showed a 15% residual activity after the 11th cycle. HPLC analysis of the enzyme-hydrolyzed filtrate also revealed the presence of sugars like xylose, arabinose, xylobiose, xylotriose and xylotetrose. The time duration of the pretreatment has an important effect on thermal energy consumption for the low-temperature alkali method.

TULP3 NLS inhibition: an in silico study to hamper cargo transport to nucleus.

TULP3 is involved in cell regulation pathways including transcription and signal transduction. In some pathological states like in cancers, increased level of TULP3 has been observed so it can serve as a potential target to hamper the activation of those pathways. We propose a novel idea of inhibiting nuclear localization signal (NLS) to interrupt nuclear translocation of TULP3 so that the downstream activations of pathways are blocked. In current in silico study, 3D structure of TULP3 was modeled using 8 different tools including I-TASSER, CABS-FOLD, Phyre2, PSIPRED, RaptorX, Robetta, Rosetta and Prime by Schrödinger. Best structure was selected after quality evaluation by SAVES and implied for the investigation of NLS sequence. Mapped NLS sequence was further used to dock with natural ligand importin-α as control docking to validate the NLS sequence as binding site. After docking and molecular dynamics (MD) simulation validation, these residues were used as binding side for subsequent docking studies. 70 alkaloids were selected after intensive literature survey and were virtually docked with NLS sequence where natural ligand importin-α is supposed to be bound. This study demonstrates the virtual inhibition of NLS sequence so that it paves a way for future in-vivo studies to use NLS as a new drug target for cancer therapeutics.Communicated by Ramaswamy H. Sarma.

In silico identification of potential drug-like molecules against G glycoprotein of Nipah virus by molecular docking, DFT studies, and molecular dynamic simulation.

Nipah virus (NiV) is a novel zoonotic pathogen that belongs to the Paramyxovirus family. The pathogen has infected a number of people in countries like Bangladesh, India, Singapore, and Malaysia with high mortality rates. Although the NiV has been classified as a biosafety level four pathogen (BSL-4), there is no drug approved for treatment against it. In this study, the G glycoprotein of the NiV was chosen as an antiviral target. Based on ADMET criteria, BBB- and BBB + group compounds were screened out of the Gold & platinum Asinex library containing 211620 compounds. After careful evaluation, the selected ligands were then virtually screened to identify the potential inhibitors against the G glycoprotein of the NiV through molecular docking, density functional theory (DFT), and molecular dynamic (MD) simulation studies. In our study we identified 5-(1,3-Benzodioxol-5-yl)-2-[(3-fluorobenzyl)sulfanyl]-5,8-dihydropyrido[2,3-d]pyrimidine-4,7(1H,6H)-dione (from BBB- group) and 7,7-Dimethyl-1-(4-methylphenyl)-3-(4-morpholinylcarbonyl)-7,8-dihydro-2,5(1H,6H)-quinolinedione) (from BBB + group) as potential compounds for the prevention and treatment of NiV related diseases.Communicated by Ramaswamy H. Sarma.

Assessment of risk, landscape epidemiology and management strategies to combat alveolar echinococcosis in the rural communities of Hunza, Pakistan.

Background: Human alveolar echinococcosis (AE) is a neglected zoonotic disease. Prevalence of AE in humans is reported in Pakistan as a result of poor economic and sanitary conditions, close proximity to wildlife and limited knowledge of AE. Studies on the prevalence and transmission of AE have been limited, especially for rural Pakistan. The study objectives were to identify knowledge, attitudes and practices relating to AE, to determine awareness of the disease, and to identify knowledge about possible risk factors of infections involving the landscape epidemiological attributes of rural villages in Hunza, one of the districts of Gilgit-Baltistan, a region of Pakistan that borders China. Methods: A community-based cross-sectional study was conducted among the general population of Hunza to establish the level of awareness, knowledge, attitudes, practices, landscape epidemiology, and disease management and control relating to AE in rural areas of Hunza. Data were collected by questionnaire. Results: A total of 387 questionnaires was received. Statistical analysis showed that the population's knowledge about the disease was poor. The attitudes and practices of the participants indicated that their risk of infection was low. Knowledge of landscape epidemiology of the disease was poor but knowledge about AE disease management was good. The attitudes of residents toward disease treatment and control strategies were positive, although the overall knowledge of participants about prevention of infection was poor. Conclusion: Knowledge of AE is poor among the residents of Hunza, Pakistan. Our study demands continued and strengthened awareness of the changes to lifestyle and practices associated with AE, not only in the study locality but throughout other areas of Pakistan.

Prevalence of Fascioliasis in Livestock and Humans in Pakistan: A Systematic Review and Meta-Analysis.

Fascioliasis is a parasitic infection that affects both livestock and humans. Understanding the distribution of Fasciola spp. can help the development of preventive measures to control fascioliasis. This systematic review and meta-analysis aimed to estimate the status of fascioliasis among livestock and humans in Pakistan between 2000 and 2020. Based on the selection criteria, 25 articles were selected from Google Scholar, PubMed, and Scopus. This review included 76,099 animals, including 13,738 that were positive for fascioliasis. The overall prevalence was 18.1%; it was 0.3% in humans and 20.1% in livestock. Among animal hosts, the prevalence was highest in sheep (53.5%), followed by the goats (44.9%), cows (21.3%), buffaloes (16.8%), cattle (12.7%), and humans (0.3%). Sindh had the highest prevalence at 42.7%, followed by Baluchistan (25.2%), Punjab (17.7%), Khyber Pakhtunkhwa (10.7%), and Islamabad capital territory (1.5%). In the Punjab province, sheep had the highest prevalence (65.7%); in Khyber Pakhtunkhwa, it was buffalo (15.9%); and in Baluchistan, it was cows (28.5%). The prevalence of Fasciola spp. was higher in Sindh and Baluchistan than in the other provinces. The presented results are essential for developing preventive approaches for the management of human health and minimizing economic loss in the livestock industry in Pakistan. Preventive-curative treatments two times a year followed by a prophylactic treatment at the end of the dry season are crucial throughout the areas of Pakistan that serve as hotspots for infection by Fasciola sp. For humans, regular, prioritized surveys must be performed for high-risk populations so that the real situation can be assessed and addressed in a timely manner.

Epidemiology of Toxoplasmosis among the Pakistani Population: A Systematic Review and Meta-Analysis.

Toxoplasma gondii is an intracellular obligate parasite that causes toxoplasmosis, a zoonotic infection that affects warm-blooded animals and humans worldwide. To comprehensively characterize the disease condition in Pakistan for future reference, we ascertained the prevalence of Toxoplasma infection and predisposing factors in the Pakistani population over a 20-year period. We systematically reviewed research articles published in English (2000−2020) from PubMed and Google Scholar. The search results 26 publications involving 10,924 people and 2611 seropositive cases. The toxoplasmosis seropositivity rate was higher in women (25.44%) as compared to men (21.48%) and were statistically significant (p < 0.001). Furthermore, seropositivity was high among people with direct contact with cats, who consumed uncooked meat and raw vegetables, had poor education, and lived in rural areas. The 35−65-year age group had the highest prevalence rate of T. gondii infection. Toxoplasma infection was significantly more prevalent in Khyber Pakhtunkhwa province (25.87%) than in Punjab (20.42%) (p < 0.001). This is the first comprehensive analysis of T. gondii infection epidemiology in Pakistan. It reveals a high frequency of infection among women. We strongly encourage further research to aid patient care and the development of more efficient diagnostic tests and preventative techniques.

Effective utilization of magnetic nano-coupled cloned ß-xylanase in saccharification process.

The ß-xylanase gene (DCE06_04615) with 1041 bp cloned from Thermotoga naphthophila was expressed into E. coli BL21 DE3. The cloned ß-xylanase was covalently bound to iron oxide magnetic nanoparticles coated with silica utilizing carbodiimide. The size of the immobilized MNPs (50 nm) and their binding with ß-xylanase were characterized by Fourier-transform electron microscopy (FTIR) (a change in shift particularly from C-O to C-N) and transmission electron microscopy (TEM) (spherical in shape and 50 nm in diameter). The results showed that enzyme activity (4.5 ± 0.23 U per mL), thermo-stability (90 °C after 4 hours, residual activity of enzyme calculated as 29.89% ± 0.72), pH stability (91% ± 1.91 at pH 7), metal ion stability (57% ± 1.08 increase with Ca2+), reusability (13 times) and storage stability (96 days storage at 4 °C) of the immobilized ß-xylanase was effective and superior. The immobilized ß-xylanase exhibited maximal enzyme activity at pH 7 and 90 °C. Repeated enzyme assay and saccharification of pretreated rice straw showed that the MNP-enzyme complex exhibited 56% ± 0.76 and 11% ± 0.56 residual activity after 8 times and 13 times repeated usage. The MNP-enzyme complex showed 17.32% and 15.52% saccharification percentage after 1st and 8th time usage respectively. Immobilized ß-xylanase exhibited 96% residual activity on 96 days' storage at 4 °C that showed excellent stability.

Epidemiology, Distribution and Identification of Ticks on Livestock in Pakistan.

Background: Ticks are ectoparasites that transmit a variety of pathogens that cause many diseases in livestock which can result in skin damage, weight loss, anemia, reduced production of meat and milk, and mortality. Aim: The aim of this study was to identify tick species and the distribution on livestock hosts (sheep, goat, dairy cattle, and buffalo) of Punjab, Khyber Pakhtunkhwa Province and Islamabad from October 2019 to November 2020. Materials and Methods: Surveillance was performed to calculate the prevalence of ticks on livestock. Tick prevalence data (area, host, breed, gender, age, and seasonal infestation rate) was recorded and analyzed. Results: A total of 2080 animals were examined from selected farms, and, of these, 1129 animals were tick-infested. A total of 1010 male tick samples were identified to species using published keys. Haemaphysalis punctata, Haemaphysalis sulcata, Hyalomma anatolicum, Hyalomma detritum, Hyalomma dromedarii, Hyalomma excavatum, Hyalomma marginatum, Hyalomma rufipes, Rhipicephalus decoloratus Rhipicephalus microplus, and Rhipicephalus sanguineus were collected from goats, sheep, buffalo, and cattle. The overall rates of tick infestation on livestock were 34.83% (buffalo), 57.11% (cattle), 51.97% (sheep) and 46.94% (goats). Within each species, different breeds demonstrated different proportions of infestation. For cattle breeds, infestation proportions were as follows: Dhanni (98.73%), Jersey (70.84%) and the Australian breed of cattle (81.81%). The Neeli Ravi breed (40%) of buffalo and the Beetal breed (57.35%) of goats were the most highly infested for these species. Seasonally, the highest prevalence of infestation (76.78%) was observed in summer followed by 70.76% in spring, 45.29% in autumn, and 20% in winter. The prevalence of tick infestation in animals also varied by animal age. In goats, animals aged 4-6 years showed the highest prevalence (90%), but in cattle, the prevalence of ticks was highest (68.75%) in 6 months-1-year-old animals. 1-3 years old buffalo (41.07%) and 6 months-1 year sheep (65.78%) had the highest prevalence rate. Females had significantly higher infestation rates (61.12%, 55.56% and 49.26%, respectively) in cattle, sheep, and goats. In buffalo, males showed a higher prevalence (38.46%) rate. Conclusions: This study showed tick diversity, infestation rate, and numerous factors (season, age, and gender of host) influencing tick infestation rate in different breeds of cattle, sheep, goats, and buffalo in Punjab Province, Khyber Pakhtunkhwa Province, and Islamabad, Pakistan. Higher tick burdens and rates of tick-borne disease reduce production and productivity in animals. Understanding tick species' prevalence and distribution will help to develop informed control measures.

A Retrospective Cohort Study on Human Cystic Echinococcosis in Khyber Pakhtunkhwa Province (Pakistan) Based on 16 Years of Hospital Discharge Records.

Human cystic echinococcosis (CE) is a worldwide-distributed parasitic zoonotic disease, which represents a threat for both human and animals. The current study aimed at estimating the prevalence of human CE in Khyber Pakhtunkhwa (KPK) province of Pakistan. Clinical records from four major hospitals in this region were reviewed for CE human cases during the period of 2006-2021. Out of 251 (0.00071%) CE patients identified during the considered period, 142 (56.6%) were females, and 109 (43.4%) were males. The highest number of CE cases was recorded in the 21-30 (27.9%) age group, followed by 31-40 (23.1%) and 41-50 (16.3%). Most of the CE patients in KPK province were members of the Afghani ethnic group (17.1%); secondarily, they were Pakistani (6.4%), while for 76.5% ethnicity data were not available. The liver (41%) and the lungs (4.8%) were the most infected organs identified among CE patients in KPK province. The present study identified CE as a significant public health problem in KPK province, and the current findings demonstrated a constant endemicity of CE during the last 15 years. Further filed studies on the active search of CE carriers by means of ultrasound population-based surveys are needed to fill knowledge gaps on clinical and molecular epidemiology of human CE in Pakistan.

A computer aided drug discovery based discovery of lead-like compounds against KDM5A for cancers using pharmacophore modeling and high-throughput virtual screening.

KDM5A over-expression mediates cancer cell proliferation and promotes resistance toward chemotherapy through epigenetic modifications. As its complete mechanism of action is still unknown, there is no KDM5A specific drug available at clinical level. In the current study, lead compounds for KDM5A were determined through pharmacophore modeling and high-throughput virtual screening from Asinex libraries containing 0.5 million compounds. These virtual hits were further evaluated and filtered for ADMET properties. Finally, 726 compounds were used for docking analysis against KDM5A. On the basis of docking score, 10 top-ranked compounds were selected and further evaluated for non-central nervous system (CNS) and CNS drug-like properties. Among these compounds, N-{[(7-Methyl-4-oxo-1,2,3,4-tetrahydrocyclopenta [c] chromen-9-yl) oxy]acetyl}-l-phenylalanine (G-score: -11.363 kcal/mol) was estimated to exhibit non-CNS properties while 2-(3,4-Dimethoxy-phenyl)-7-methoxy-chromen-4-one (G-score: -7.977 kcal/mol) was evaluated as CNS compound. Docked complexes of both compounds were finally selected for molecular dynamic simulation to examine the stability. This study concluded that both these compounds can serve as lead compounds in the quest of finding therapeutic agents against KDM5A associated cancers.

Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Prevalence of different tick species on livestock and associated equines and canine from different agro-ecological zones of Pakistan.

Ticks are ectoparasites that act as vectors for transmission of various pathogens to wild and domesticated animals and pose a serious threat to human health. Because of the hot and humid conditions in different agro-ecological zones of Pakistan, ticks are abundant and parasitize a variety of animals. The aim of this study was to identify different tick species and distribution on different hosts especially livestock, such as sheep, goat, cattle, buffalo, and camel, and livestock associated canines and equines, such as horse, donkey, and dog, across different agro-ecological zones of Pakistan. The ticks samples were collected and morphologically identified at genus and species level using morphological keys under stereomicroscope. A total of 2,846 animals were examined for the tick infestation, and 408 animals were tick-infested. Eleven tick species belonging to 4 genera were identified: Hyalomma anatolicum, Hyalomma scupense, Hyalomma dromedarii, Hyalomma isaaci, Rhipicephalus microplus, Rhipicephalus haemaphysaloides, Rhipicephalus turanicus, Haemaphysalis cornupunctata, Haemaphysalis montgomeryi, Haemaphysalis bispinosa, and Ixodes kashmiricus. The overall tick prevalence was 14.3%; host-wise infestation rate was 12.2% in sheep; 12.6%, goat; 11.7%, buffalo; 11.7%, cattle; 19.6%, camel; 27.4%, donkey; 23.5%, horse; and 24.3%, dog. Tick infestation of different animals differed on the basis of the zones. Camels showed the highest tick infestation rate in zones 1 and 2 (21.4 and 26.7%, respectively), whereas donkeys showed the highest infestation rate in zones 3, 4, 6, and 7 (25, 39.3, 3.3, and 21.4%, respectively). The infestation rates of Hyalomma and Rhipicephalus were the highest in zone 2 (71.4 and 52.9%, respectively). The infestation rate of Hyalomma was the highest (47.4%) in sheep; Haemaphysalis (46.9%), goat; Rhipicephalus (69.7%), buffalo; Rhipicephalus (62.3%), cattle; Hyalomma (70%), camel; Ixodes (60.9%), donkey; Ixodes (75%), horse; and Rhipicephalus (61.1%), dog. This study showed the diversity and infestation rate of different ticks with respect to their hosts and agro-ecological zones of Pakistan. High tick burdens and infestation rates are responsible for the spread of different tick-borne infections, resulting in loss of animal productivity and posing a threat to animal and human health. Understanding different tick species and their distribution across different zones will be helpful for developing efficient control strategies against different tick born infections.

Demographic Attributes of Knowledge, Attitude, Practices, and One Health Perspective Regarding Diarrhea in Pakistan.

Background: Loose bowels is a clinical sign of gastrointestinal transport channel proteins, channels, and physical and chemical boundaries being harmed, prompting issues of water and electrolyte transport in the intestinal system. It is still considered as a major reason for emergency visits to hospitals in low-middle income countries. Zinc is a suitable treatment along with ORS for diarrhea. KAP surveys are usually conducted to collect information about general or specific topics of a particular population. The objective of this study was to investigate the knowledge, attitude, practices (KAP), and one health perspective regarding diarrhea among the participants from urban and rural populations of Rawalpindi and Islamabad, Pakistan. Methods: Data was collected by conducting a survey among residents of twin cities over a period of 6 months (from July 2020 to December 2020). The questionnaire compromised socio-demographic features and the degree of KAP with respect to diarrhea management and control. One way ANOVA tests were applied to observe the demographic relationship and various factors influencing knowledge, attitude, practices, and one health perspective about diarrhea. Results: A total of 338 subjects participated in the study. Female subjects were in the majority with 63% while the rest were male. A majority of the participants were between 15-25 years of age and 79.6% participants were un-married. The leading ethnic group was Punjabi with 52.7%; the lowest ethnic group were of Sindhi ethnicity with 8.6%. Age has a significant association with respect to knowledge and attitude. Religion has a significant association with respect to knowledge, practices, and one health, while education/qualification has an association with knowledge. The rest of the variables found no association with each other. Conclusion: It is concluded from the recent study that most residents of the twin cities of Pakistan knew about diarrhea and had a good attitude and practices toward it. Age, religion, and education have different roles regarding different diseases in the population of Pakistan. The current study has its limitations as well. Parts of the study were conducted in the capital of Pakistan which is more developed as compared to other areas of Pakistan. It would be better to explore the remote areas of Pakistan where basic amenities of life such as education, wealth, and unemployment are not available. It is important to create more awareness among community members. They should be aware how dangerous these viruses and bacteria can be. Other parts of Pakistan should also be explored for better understanding that will help in making a nationwide health policy.