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Mahmoud Teaima,1 Magdi M. Abdel Hamid,2 Nabil A. Shoman,2 Bhaskara R. Jasti,3 Mohamed A. El-Nabarawi1 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt; 3Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy & Health Sciences, University of the Pacific, Stockton, California, USACorrespondence: Mahmoud TeaimaDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, EgyptEmail mahmoud.teaima@pharma.cu.edu.egPurpose: Bupropion is an antidepressant drug that facilitates weight loss. It is a highly water-soluble drug that needs multiple dosing, so it is considered a potential candidate for oral controlled-release dosage form. The aim of this research was to formulate and evaluate satiety-inducing swellable floating bupropion tablets by direct compression targeting depression associated with eating disorders. Various combinations of natural and semi-synthetic hydrogels were selected to achieve maximum swelling and remaining buoyant in the stomach. This synergistically enhances weight loss by increasing satiety.Methods: An I-optimal mixture design was conducted to establish the optimal quantitative composition of tablets. Friability, floating lag time, swelling index after 4 and 8 hours, along with the percent of bupropion released at 1 and 8 hours were selected as dependent variables. The optimized formulation was characterized by physicochemical properties, thermal stability, and chemical interaction. In vivo radiographic evaluation of gastric residence besides, the oral bioavailability relative to marketed Wellbutrin® sustained-release tablets were investigated using human volunteers.Results: The optimized formulation (73.3 mg xanthan, 120 mg glucomannan, 8.4 mg tamarind kernel powder, 78.3 mg HPMC K15M) was achieved with the overall desirability equals 0.782. In vivo radiographic study showed that formulation was retained for > 8 hours in the stomach. Compared with the marketed BUP tablets, the Cmax was almost the same with a significant increase (p =0.004) for Tmax.Conclusion: Using combinations of these hydrogels would be promising gastroretentive delivery systems in the control of bupropion rate release with enhanced floating and swelling features.Keywords: gastroretentive drug delivery, natural hydrogels, HPMC, depression, eating disorder

Background: The population structure of the malaria parasite Plasmodium falciparum can reveal underlying adaptive evolutionary processes. Selective pressures to maintain complex genetic backgrounds can encourage inbreeding, producing distinct parasite clusters identifiable by population structure analyses., Methods: We analysed population structure in 3783 P falciparum genomes from 21 countries across Africa, provided by the MalariaGEN Pf7 dataset. We used Principal Coordinate Analysis to cluster parasites, identity by descent (IBD) methods to identify genomic regions shared by cluster members, and linkage analyses to establish their co-inheritance patterns. Structural variants were reconstructed by de novo assembly and verified by long-read sequencing., Findings: We identified a strongly differentiated cluster of parasites, named AF1, comprising 47 (1·2%) of 3783 samples analysed, distributed over 13 countries across Africa, at locations over 7000 km apart. Members of this cluster share a complex genetic background, consisting of up to 23 loci harbouring many highly differentiated variants, rarely observed outside the cluster. IBD analyses revealed common ancestry at these loci, irrespective of sampling location. Outside the shared loci, however, AF1 members appear to outbreed with sympatric parasites. The AF1 differentiated variants comprise structural variations, including a gene conversion involving the dblmsp and dblmsp2 genes, and numerous single nucleotide polymorphisms. Several of the genes harbouring these mutations are functionally related, often involved in interactions with red blood cells including invasion, egress, and erythrocyte antigen export., Interpretation: We propose that AF1 parasites have adapted to some unidentified evolutionary niche, probably involving interactions with host erythrocytes. This adaptation involves a complex compendium of interacting variants that are rarely observed in Africa, which remains mostly intact despite recombination events. The term cryptotype was used to describe a common background interspersed with genomic regions of local origin., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Plasmodium vivax, traditionally overlooked has experienced a notable increase in cases in East Africa. This study investigated the geographical origin and genetic diversity of P. vivax in Sudan using 14 microsatellite markers. A total of 113 clinical P. vivax samples were collected from two different ecogeographical zones, New Halfa and Khartoum, in Sudan. Additionally, 841 geographical samples from the database were incorporated for a global genetic analysis to discern genetic relationships among P. vivax isolates on regional and worldwide scales. On the regional scale, our findings revealed 91 unique and 8 shared haplotypes among the Sudan samples, showcasing a remarkable genetic diversity compared to other geographical isolates and supporting the hypothesis that P. vivax originated from Africa. On a global scale, distinct genetic clustering of P. vivax isolates from Africa, South America, and Asia (including Papua New Guinea and Solomon Island) was observed, with limited admixture among the three clusters. Principal component analysis emphasized the substantial contribution of African isolates to the observed global genetic variation. The Sudanese populations displayed extensive genetic diversity, marked by significant multi-locus linkage disequilibrium, suggesting an ancestral source of P. vivax variation globally and frequent recombination among the isolates. Notably, the East African P. vivax exhibited similarity with some Asian isolates, indicating potential recent introductions. Overall, our results underscore the effectiveness of utilizing microsatellite markers for implementing robust control measures, given their ability to capture extensive genetic diversity and linkage disequilibrium patterns., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Plasmodium vivax Duffy Binding Protein (PvDBP) is essential for interacting with Duffy antigen receptor for chemokines (DARC) on the surface of red blood cells to allow invasion. Earlier whole genome sequence analyses provided evidence for the duplications of PvDBP. It is unclear whether PvDBP duplications play a role in recent increase of P. vivax in Sudan and in Duffy-negative individuals. In this study, the prevalence and type of PvDBP duplications, and its relationship to demographic and clinical features were investigated. A total of 200 malaria-suspected blood samples were collected from health facilities in Khartoum, River Nile, and Al-Obied. Among them, 145 were confirmed to be P. vivax, and 43 (29.7%) had more than one PvDBP copies with up to four copies being detected. Both the Malagasy and Cambodian types of PvDBP duplication were detected. No significant difference was observed between the two types of duplications between Duffy groups. Parasitemia was significantly higher in samples with the Malagasy-type than those without duplications. No significant difference was observed in PvDBP duplication prevalence and copy number among study sites. The functional significance of PvDBP duplications, especially those Malagasy-type that associated with higher parasitemia, merit further investigations., Competing Interests: Authors declare that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Patients who develop severe illness due to COVID-19 are more likely to be admitted to hospital and acquire bacterial co-infections, therefore the WHO recommends empiric treatment with antibiotics. Few reports have addressed the impact of COVID-19 management on emergence of nosocomial antimicrobial resistance (AMR) in resource constrained settings. This study aimed to ascertain whether being admitted to a COVID-19 ward (with COVID-19 infection) compared to a non-COVID-19 ward (as a COVID-19 negative patient) was associated with a change in the prevalence of bacterial hospital acquired infection (HAI) species or resistance patterns, and whether there were differences in antimicrobial stewardship (AMS) and infection prevention and control (IPC) guidelines between COVID-19 and non-COVID-19 wards. The study was conducted in Sudan and Zambia, two resource constrained settings with differing country-wide responses to COVID-19., Methods: Patients suspected of having hospital acquired infections were recruited from COVID-19 wards and non-COVID-19 wards. Bacteria were isolated from clinical samples using culture and molecular methods and species identified. Phenotypic and genotypic resistance patterns were determined by antibiotic disc diffusion and whole genome sequencing. Infection prevention and control guidelines were analysed for COVID-19 and non-COVID-19 wards to identify potential differences., Results: 109 and 66 isolates were collected from Sudan and Zambia respectively. Phenotypic testing revealed significantly more multi-drug resistant isolates on COVID-19 wards in both countries (Sudan p = 0.0087, Zambia p = 0.0154). The total number of patients with hospital acquired infections (both susceptible and resistant) increased significantly on COVID-19 wards in Sudan, but the opposite was observed in Zambia (both p = ≤ 0.0001). Genotypic analysis showed significantly more β-lactam genes per isolate on COVID-19 wards (Sudan p = 0.0192, Zambia p = ≤ 0.0001)., Conclusions: Changes in hospital acquired infections and AMR patterns were seen in COVID-19 patients on COVID-19 wards compared to COVID-19 negative patients on non-COVID-19 wards in Sudan and Zambia. These are likely due to a potentially complex combination of causes, including patient factors, but differing emphases on infection prevention and control, and antimicrobial stewardship policies on COVID-19 wards were highlighted., (© 2023. The Author(s).)

The apparent failure of global health security to prevent or prepare for the COVID-19 pandemic has highlighted the need for closer cooperation between human, animal (domestic and wildlife), and environmental health sectors. However, the many institutions, processes, regulatory frameworks, and legal instruments with direct and indirect roles in the global governance of One Health have led to a fragmented, global, multilateral health security architecture. We explore four challenges: first, the sectoral, professional, and institutional silos and tensions existing between human, animal, and environmental health; second, the challenge that the international legal system, state sovereignty, and existing legal instruments pose for the governance of One Health; third, the power dynamics and asymmetry in power between countries represented in multilateral institutions and their impact on priority setting; and finally, the current financing mechanisms that predominantly focus on response to crises, and the chronic underinvestment for epidemic and emergency prevention, mitigation, and preparedness activities. We illustrate the global and regional dimensions to these four challenges and how they relate to national needs and priorities through three case studies on compulsory licensing, the governance of water resources in the Lake Chad Basin, and the desert locust infestation in east Africa. Finally, we propose 12 recommendations for the global community to address these challenges. Despite its broad and holistic agenda, One Health continues to be dominated by human and domestic animal health experts. Substantial efforts should be made to address the social-ecological drivers of health emergencies including outbreaks of emerging, re-emerging, and endemic infectious diseases. These drivers include climate change, biodiversity loss, and land-use change, and therefore require effective and enforceable legislation, investment, capacity building, and integration of other sectors and professionals beyond health., Competing Interests: Declaration of Interests We declare no competing interests. The views and opinions expressed in this paper are those of the authors and not of their institutions., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Platelet-derived lyophilized growth factors (L-GFs) use a standardized number of allogenic pathogen-free platelets instead of autologous platelets used in PRP as a source of growth factors. This study aimed to evaluate the efficacy of L-GF injection versus placebo in subacromial impingement (SIS) treatment., Methods: The current randomized double-blind placebo-controlled study included sixty patients (40 females and 20 males, aged between 24 and 75 years) diagnosed with SIS (both clinically and sonographically). Patients were randomly assigned to two equal groups. Under ultrasound guidance, group 1 received subacromial saline injection, and group 2 received L-GF injection. Clinical examination, pain visual analogue scale (VAS), shoulder pain and disability index (SPADI) and shoulder ultrasound were performed before and at the 8th week after injection., Results: Follow-up assessment showed statistically significant improvement in the L-GF group regarding active flexion, active and passive internal rotation and extension, SPADI-disability scale, VAS and thickness of the supraspinatus tendon by US. Regression analysis showed that group 1 was approximately 30 times more likely than the L-GF group to experience painful arc at follow-up. Both groups showed statistically significant improvement in SPADI-pain scale and SPADI-total, flexion and abduction (still the mean value of abduction was significantly higher in the L-GF group)., Conclusions: L-GF injection resulted in clinically significant reductions in pain and functional disability outcomes in patients with SIS. An objective significant reduction in the thickness of the supraspinatus tendon, measured by ultrasound, in the L-GF group hopefully encourages proper healing and functioning in SIS., Trial Registration: The identification number is NCT04330027, date of first registration (01/04/2020). Unique on 21/11/2019, Protocol ID: 0106178., (© 2023. The Author(s).)

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.  We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent.  We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines.  Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 MalariaGEN et al.)

Plasmodium vivax is the most widespread cause of human malaria. Recent reports of drug resistant vivax malaria and the challenge of eradicating the dormant liver forms increase the importance of vaccine development against this relapsing disease. P. vivax reticulocyte binding protein 1a (PvRBP1a) is a potential vaccine candidate, which is involved in red cell tropism, a crucial step in the merozoite invasion of host reticulocytes. As part of the initial evaluation of the PvRBP1a vaccine candidate, we investigated its genetic diversity and antigenicity using geographically diverse clinical isolates. We analysed pvrbp1a genetic polymorphisms using 202 vivax clinical isolates from six countries. Pvrbp1a was separated into six regions based on specific domain features, sequence conserved/polymorphic regions, and the reticulocyte binding like (RBL) domains. In the fragmented gene sequence analysis, PvRBP1a region II (RII) and RIII (head and tail structure homolog, 152-625 aa.) showed extensive polymorphism caused by random point mutations. The haplotype network of these polymorphic regions was classified into three clusters that converged to independent populations. Antigenicity screening was performed using recombinant proteins PvRBP1a-N (157-560 aa.) and PvRBP1a-C (606-962 aa.), which contained head and tail structure region and sequence conserved region, respectively. Sensitivity against PvRBP1a-N (46.7%) was higher than PvRBP1a-C (17.8%). PvRBP1a-N was reported as a reticulocyte binding domain and this study identified a linear epitope with moderate antigenicity, thus an attractive domain for merozoite invasion-blocking vaccine development. However, our study highlights that a global PvRBP1a-based vaccine design needs to overcome several difficulties due to three distinct genotypes and low antigenicity levels., Competing Interests: The authors have declared that no competing interests exist.

Anopheles stephensi mosquitoes are urban malaria vectors in Asia that have recently invaded the Horn of Africa. We detected emergence of An. stephensi mosquitoes in 2 noncontiguous states of eastern Sudan. Results of mitochondrial DNA sequencing suggest the possibility of distinct invasions, potentially from a neighboring country.

Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common enzymopathy globally, and deficient individuals may experience severe hemolysis following treatment with 8-aminoquinolines. With increasing evidence of Plasmodium vivax infections throughout sub-Saharan Africa, there is a pressing need for population-level data at on the prevalence of G6PDd. Such evidence-based data will guide the expansion of primaquine and potentially tafenoquine for radical cure of P. vivax infections. This study aimed to quantify G6PDd prevalence in two geographically distinct areas in Sudan, and evaluating the performance of a qualitative CareStart rapid diagnostic test as a point-of-care test. Blood samples were analyzed from 491 unrelated healthy persons in two malaria-endemic sites in eastern and central Sudan. A pre-structured questionnaire was used which included demographic data, risk factors and treatment history. G6PD levels were measured using spectrophotometry (SPINREACT) and first-generation qualitative CareStart rapid tests. G6PD variants (202 G>A; 376 A>G) were determined by PCR/RFLP, with a subset confirmed by Sanger sequencing. The prevalence of G6PDd by spectrophotometry was 5.5% (27/491; at 30% of adjusted male median, AMM); 27.3% (134/491; at 70% of AMM); and 13.1% (64/490) by qualitative CareStart rapid diagnostic test. The first-generation CareStart rapid diagnostic test had an overall sensitivity of 81.5% (95%CI: 61.9 to 93.7) and negative predictive value of 98.8% (97.3 to 99.6). All persons genotyped across both study sites were wild type for the G6PD G202 variant. For G6PD A376G all participants in New Halfa had wild type AA (100%), while in Khartoum the AA polymorphism was found in 90.7%; AG in 2.5%; and GG in 6.8%. Phenotypic G6PD B was detected in 100% of tested participants in New Halfa while in Khartoum, the phenotypes observed were B (96.2%), A (2.8%), and AB (1%). The African A- phenotype was not detected in this study population. Overall, G6PDd prevalence in Sudan is low-to-moderate but highly heterogeneous. Point-of-care testing with the qualitative CareStart rapid diagnostic test demonstrated moderate performance with moderate sensitivity and specificity but high negative predicative value. The two sites harbored primarily the African B phenotype. A country-wide survey is recommended to understand GP6PD deficiencies more comprehensively in Sudan., Competing Interests: The authors have declared that no competing interests exist.

Background: This study was conducted to determine the seroprevalence and risk factors of chikungunya (CHIKV), dengue (DENV), and Zika (ZIKV) viruses in Tanzania., Methods: The study covered the districts of Buhigwe, Kalambo, Kilindi, Kinondoni, Kondoa, Kyela, Mvomero, and Ukerewe in Tanzania. Blood samples were collected from individuals recruited from households and healthcare facilities. An ELISA was used to screen for immunoglobulin G antibodies against CHIKV, DENV, and ZIKV., Results: A total of 1818 participants (median age 34 years) were recruited. The overall CHIKV, DENV, and ZIKV seroprevalence rates were 28.0%, 16.1%, and 6.8%, respectively. CHIKV prevalence was highest in Buhigwe (46.8%), DENV in Kinondoni (43.8%), and ZIKV in Ukerewe (10.6%) and Mvomero (10.6%). Increasing age and frequent mosquito bites were significantly associated with CHIKV and DENV seropositivity (P < 0.05). Having piped water or the presence of stagnant water around the home (P < 0.01) were associated with higher odds of DENV seropositivity. Fever was significantly associated with increased odds of CHIKV seropositivity (P < 0.001). Visiting mines had higher odds of ZIKV seropositivity (P < 0.05)., Conclusions: These findings indicate that DENV, CHIKV, and ZIKV are circulating in diverse ecological zones of Tanzania. There is a need to strengthen the control of mosquito-borne viral diseases in Tanzania., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the prevalence of key endodontic pathogens and their association with the clinical features and the cause of apical periodontitis., Methods: The study population included patients referred to Khartoum Dental teaching Hospital, Sudan for endodontic treatment. Samples were collected from single-rooted teeth carious or traumatised teeth with clinical and radiographic evidence of apical periodontitis. The endodontic pathogens Porphyromonas endodontalis, Fusobacterium nucleatum and Treponema denticola were quantified by real time polymerase chain reaction (qPCR). The prevalence of each species was identified at both a low detection threshold (>50 bacteria) and a high detection threshold (>1000 bacteria)., Results: 75 patients (mean age 30.1 yrs SD 10.1) were included in the analysis. The most prevalent bacterium at both the low and high threshold was F. nucleatum followed by T. denticola at the low threshold and P. endodontalis at the high threshold. There was no association with symptoms at the low detection threshold, but at high threshold P. endodontalis was associated with swelling, adjusted odds ratio (OR), 9.32 95%CI 1.11- 78.66, P=0.04. All species were more prevalent in apical periodontitis due to caries only at the low detection threshold, OR=5.01 (P=0.006) for T. denticola; 4.84 (P=0.01) for F. nucleatum; and 3.62 (P=0.03) for P. endodontalis., Conclusion: There was a high prevalence of the F. nucleatum, T. denticola and P. endodontalis in apical periodontitis associated with caries. None of these bacterial were associated with pain but the presence of P. endodontalis at high levels was associated with swelling.

Background: In spite of the global effort to eliminate malaria, it remains the most significant vector-borne disease of humans. Plasmodium falciparum is the dominant malaria parasite in sub-Saharan Africa. However, Plasmodium vivax is becoming widely spread throughout Africa. The overuse of vector control methods has resulted in a remarkable change in the behaviour of mosquito that feeds on human as well as on vector composition. The aim of this study was to identify Anopheles mosquito species in vivax malaria endemic regions and to investigate their role in P. vivax circumsporozoite protein (Pvcsp) allele diversity., Methods: Mosquito samples were collected from Central Sudan (Rural Khartoum and Sennar) and Eastern Sudan (New Halfa, Kassala state) using pyrethrum spray catch (PSC) and CDC light traps. Mosquitoes were identified using appropriate morphological identification keys and Anopheles gambiae complex were confirmed to species level using molecular analysis. A subset of blood-fed anopheline mosquitoes were dissected to determine the presence of natural infection of malaria parasites. In addition, the rest of the samples were investigated for the presence of Pvcsp gene using nested-PCR., Results: A total of 1037 adult anopheline mosquitoes were collected from New Halfa (N = 467), Rural Khartoum (N = 132), and Sennar (N = 438). Morphological and molecular identification of the collected mosquitoes revealed the presence of Anopheles arabiensis (94.2%), Anopheles funestus (0.5%), and Anopheles pharoensis (5.4%). None of the dissected mosquitoes (N = 108) showed to be infected with malaria parasite. Overall P. vivax infectivity rate was 6.1% (63/1037) by Pvcsp nested PCR. Co-dominance of An. arabiensis and An. pharoensis is reported in Sennar state both being infected with P. vivax., Conclusion: This study reported P. vivax infection among wild-caught anopheline mosquitoes in Central and Eastern Sudan. While An. arabiensis is the most abundant vector observed in all study areas, An. funestus was recorded for the first time in New Halfa, Eastern Sudan. The documented Anopheles species are implicated in Pvcsp allele diversity. Large-scale surveys are needed to identify the incriminated vectors of P. vivax malaria and determine their contribution in disease transmission dynamics.

Antimicrobial resistance is of concern to global health security worldwide. We aimed to identify the prevalence, resistance patterns, and risk factors associated with Escherichia coli ( E. coli ) resistance from poultry farms in Kelantan, Terengganu, and Pahang states of east coast peninsular Malaysia. Between 8 February 2019 and 23 February 2020, a total of 371 samples (cloacal swabs = 259; faecal = 84; Sewage = 14, Tap water = 14) were collected. Characteristics of the sampled farms including management type, biosecurity, and history of disease were obtained using semi-structured questionnaire. Presumptive E. coli isolates were identified based on colony morphology with subsequent biochemical and PCR confirmation. Susceptibility of isolates was tested against a panel of 12 antimicrobials and interpreted alongside risk factor data obtained from the surveys. We isolated 717 E. coli samples from poultry and environmental samples. Our findings revealed that cloacal (17.8%, 46/259), faecal (22.6%, 19/84), sewage (14.3%, 2/14) and tap water (7.1%, 1/14) were significantly ( p < 0.003) resistant to at least three classes of antimicrobials. Resistance to tetracycline class were predominantly observed in faecal samples (69%, 58/84), followed by cloacal (64.1%, 166/259), sewage (35.7%, 5/14), and tap water (7.1%, 1/84), respectively. Sewage water (OR = 7.22, 95% CI = 0.95-151.21) had significant association with antimicrobial resistance (AMR) acquisition. Multivariate regression analysis identified that the risk factors including sewage samples (OR = 7.43, 95% CI = 0.96-156.87) and farm size are leading drivers of E. coli antimicrobial resistance in the participating states of east coast peninsular Malaysia. We observed that the resistance patterns of E. coli isolates against 12 panel antimicrobials are generally similar in all selected states of east coast peninsular Malaysia. The highest prevalence of resistance was recorded in tetracycline (91.2%), oxytetracycline (89.1%), sulfamethoxazole/trimethoprim (73.1%), doxycycline (63%), and sulfamethoxazole (63%). A close association between different risk factors and the high prevalence of antimicrobial-resistant E. coli strains reflects increased exposure to resistant bacteria and suggests a concern over rising misuse of veterinary antimicrobials that may contribute to the future threat of emergence of multidrug-resistant pathogen isolates. Public health interventions to limit antimicrobial resistance need to be tailored to local poultry farm practices that affect bacterial transmission.

Dengue is a rapidly growing public health threat in Kassala state, eastern Sudan. The objective of this study was to determine the seroprevalence, entomological transmission indices, and socioeconomic risk factors associated with dengue in this region. A cross-sectional community-based study was conducted in four dengue-endemic sites; Khatmia, West Gash, Thoriba, and Shokriya between March 2016 to March 2017. Enzyme-linked immunosorbent assay (ELISA) of immunoglobulin G (IgG) was used to determine the prevalence of dengue virus among the study participants. An entomological survey was conducted using pyrethrum spray catch and dipping for the collection of adults and aquatic stages of Aedes aegypti, respectively. Ribonucleic acid was extracted from the buffy coat of participants as well as from adult female Ae. aegypti to assess the possible circulation of dengue virus using Reverse Transcription Polymerase Chain Reaction (RT-PCR). Multiple logistic regression model was used to estimate the association between potential risk factors and dengue seropositivity. A total of 409 persons were recruited to the study: 45.5% were in the 20-39 years' age category; 57.9% were living in houses with 6-10 persons; and 29.1% had at most secondary school education. In the majority (65.8%) of the households, the socioeconomic status was low (P<0.001). Long-lasting insecticide-treated bed nets were used in 56.5% of the households. Over three-quarters (77.8%) claimed not to have experienced febrile illness in the last three months. Routine entomological survey across Kassala state identified a total of 3,304 larvae and 390 pupae Ae. aegypti, respectively. The overall house index was 32.8% and Breteau Index was 35.96% (146/406). The overall pupal demographic index was 13.31%, and the pupal children index was 97.26%. Antibodies against IgG were detected from 66 (42.04%) out of a total of 157 sera. Twenty-two positive sera (75.9%) were collected from Khatmia. A total of 329 adults Ae. aegypti were identified but only one (0.3%) was positive for DENV in Khatmia. Finally, four independent risk factors were identified to derive dengue circulation in Kassala: elder age (> 60 years) (OR 6.31, CI 1.09-36.36); type of bathroom (OR 3.52, CI 1.35-9.20); using water-based air conditioner (OR 6.90, CI 1.78-26.85) and previous infection of any household member with dengue (OR 28.73, CI 3.31-249.63). Our findings suggest that Kassala state is facing an increasing occurrence of dengue and emphasizes the need for developing appropriate interventions to address the identified risk factors, and place control programs into actions. Establishment of routine dengue epidemiological and entomological surveillance, and climate warning systems will contribute to early warning and timely detection and response to emerging outbreaks., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study was to formulate, evaluate, and compare satiety-enhancing floating raft system (FRS) of bupropion as gastroretentive drug delivery systems (GRDDS) using in-situ gelling pectin and alginate. Bupropion was considered as a good candidate for such systems due to high water solubility that requires frequent dosing. Pectin and alginate could prolong satiety sensation augmenting weight loss of bupropion. A 2 4 full factorial design was tailored to inspect the effect of the response variables (gel-forming polymer type, calcium carbonate percentage, glyceride lipid type and percentage). Gelation lag time, floating lag time, as well as drug released percent after 1 and 8 h were selected as dependent variables. The optimal system was investigated for compatibility and bioavailability study in healthy human volunteers relative to marketed Wellbutrin® sustained release tablets. The optimal FRS (3% alginate, 2% precirol®, and 2% CaCO 3 ) was selected. This system had an optimum viscosity that will allow a rapid sol-gel transformation in the stomach, excellent floating behavior, and controlled release profile with a comparable bioavailability. The optimal FRS would be a novel liquid GRDDS in controlling bupropion rate release especially for depression associated with eating disorders or dysphagia improving patient compliance and drug efficacy., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Antimicrobial resistance (AMR) is of growing concern globally and AMR status in sub-Saharan Africa (SSA) is undefined due to a lack of real-time data recording, surveillance and regulation. World Health Organization (WHO) Joint External Evaluation (JEE) reports are voluntary, collaborative processes to assess country capacities and preparedness to prevent, detect and rapidly respond to public health risks, including AMR. The data from SSA JEE reports were analysed to gain an overview of how SSA is working towards AMR preparedness and where strengths and weaknesses lie., Methods: SSA country JEE AMR preparedness scores were analysed. A cumulative mean of all the SSA country AMR preparedness scores was calculated and compared to the overall mean SSA JEE score. AMR preparedness indicators were analysed, and data were weighted by region., Findings: The mean SSA AMR preparedness score was 53% less than the overall mean SSA JEE score. East Africa had the highest percentage of countries reporting having AMR National Action Plans in place, as well as human and animal pathogen AMR surveillance programmes. Southern Africa reported the highest percentage of countries with training programmes and antimicrobial stewardship., Conclusions: The low mean AMR preparedness score compared to overall JEE score, along with the majority of countries lacking implemented National Action Plans, suggests that until now AMR has not been a priority for most SSA countries. By identifying regional and One Health strengths, AMR preparedness can be fortified across SSA with a multisectoral approach.

Background: Current malaria control and elimination strategies rely mainly on efficacious antimalarial drugs. However, drug resistance is a major threat facing malaria control programs. Determination of drug resistance molecular markers is useful in the monitoring and surveillance of malaria drug efficacy. This study aimed to determine the mutations and haplotypes frequencies of different genes linked with antimalarial drug resistance in certain areas in Sudan., Methods: A total of 226 dried blood spots (DBS) of microscopically diagnosed P. falciparum isolates were collected from Khartoum and three other areas in Sudan during 2015-2017. Plasmodium falciparum confirmation and multiplicity of infection was assessed using the Sanger's 101 SNPs-barcode and speciation was confirmed using regions of the parasite mitochondria. Molecular genotyping of drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, exonuclease, Pfk13, parasite genetic background (PGB) (Pfarps10, ferredoxin, Pfcrt, Pfmdr2)) was also performed. All genotypes were generated by selective regions amplicon sequencing of the parasite genome using the Illumina MiSeq platform at the Wellcome Sanger Institute, UK then genotypes were translated into drug resistance haplotypes and species determination., Findings: In total 225 samples were confirmed to be P. falciparum. A higher proportion of multiplicity of infection was observed in Gezira (P<0.001) based on the Sanger 101 SNPs -barcode. The overall frequency of mutant haplotype Pfcrt 72-76 CVIET was 71.8%. For Pfmdr1, N86Y was detected in 53.6%, Y184F was observed in 88.1% and D1246Y was detected in 1.5% of the samples. The most frequently observed haplotype was YFD 47.4%. For Pfdhfr (codons 51, 59,108,164), the ICNI haplotype was the most frequent (80.7%) while for Pfdhps (codons 436, 437, 540, 581, 613) the (SGEAA) was most frequent haplotype (41%). The Quadruple mutation (dhfr N51I, S108N + dhps A437G, K540E) was the highest frequent combined mutation (33.9%). In Pfkelch13 gene, 18 non-synonymous mutations were detected, 7 of them were detected in other African countries. The most frequent Pfk13 mutation was E433D detected in four samples. All of the Pfk13 mutant alleles have not been reported to belong to mutations associated with delayed parasite clearance in Southeast Asia. PGB mutations were detected only in Pfcrt N326S\I (46.3%) and Pfcrt I356T (8.2%). The exonuclease mutation was not detected. There was no significant variation in mutant haplotypes between study areas., Conclusions: There was high frequency of mutations in Pfcrt, Pfdhfr and Pfdhps in this study. These mutations are associated with chloroquine and sulfadoxine-pyrimethamine (SP) resistance. Many SNPs in Pfk13 not linked with delayed parasite clearance were observed. The exonuclease E415G mutation which is linked with piperaquine resistance was not reported., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Understanding the feeding behavior and host choice of sand flies provides valuable information on vector-host relationships and elucidates the epidemiological patterns of leishmaniasis transmission. Blood meal analysis studies are essential for estimating the efficiency of pathogen transmission, assessing the relative human disease risk, and assist in identifying the other potential hosts of leishmaniasis. In Sudan and most of East Africa, there are large remaining gaps in knowledge regarding the feeding habits of phlebotomine vectors. The study aimed to identify the blood meal sources and, therefore, the host preferences of the principal vectors Phlebotomus orientalis and Ph. papatasi in leishmaniasis endemic areas of eastern and central Sudan., Materials and Methods: Sand flies were collected from two endemic villages in eastern and central Sudan using CDC light traps and sticky traps. The phlebotomine sand flies were morphologically and then molecularly identified. The source of blood meal of the engorged females was determined using a multiplex PCR methodology and specific primers of cytochrome b gene of mitochondrial DNA for human, goat, cow, and dog. The detection of the Leishmania parasite was done using PCR., Results: The total number of collected female phlebotomine sand flies was 180. Morphological identification revealed the abundance of Ph. orientalis 103 (57.2%), Ph. papatasi 42 (23.3%), Ph. bergeroti 31 (17.2%), Ph. rodhaini 2 (1.1%) and Ph. duboscqi 2 (1.1%) in the study sites. Out of the 180 collected, 31 (17%) were blood-fed flies. Three species were blood-fed and molecularly identified: Ph. papatasi (N = 7, 22.6%), Ph. bergeroti (N = 9, 26%), and Ph. orientalis (N = 15, 48.4%). Blood meal analysis revealed human DNA in two Ph. orientalis (6.4%), hence, the anthropophilic index was 13.3%., Conclusions: Multiplex PCR protocol described here allowed the identification of blood meal sources of many vertebrate species simultaneously. The results indicate that wild-caught Ph. orientalis are anthropophilic in the study areas. Further studies on larger blood-fed sample size are required to validate the potential applications of this technique in designing, monitoring and evaluating control programs, particularly in investigating the potential non-human hosts of leishmaniasis., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Infection with the causative agent of visceral leishmaniasis (VL) may be either symptomatic or asymptomatic. In this study we aimed at investigating the prevalence of asymptomatic infections of leishmania in non-endemic villages in Gedaref state, Sudan. A descriptive cross-sectional study conducted during September and October 2014. Blood samples were collected for serological and molecular analysis. Sticky-traps, knockdown spray and CDC-miniature light traps were used for the collection of sandflies., Results: Ninety-Five participants were included; 52 from Abukishma, 15 Algadamblia Tirfa, 25 Abualnaja and 3 were from Algadamblia Aljabal. Females constituted 56 (58.9%) of the study participants while males were 39 (41.1%). The most frequent age group was > 40-years (54.7%). Balanites/Acacia trees were the most planted tree inside the houses; 78 (82.1%). Also, 85 (89.5%) of the participants breed animals inside the house. DAT test revealed 5 positive participants (5.2%). 4/5 DAT positive were past VL infection. PCR detected 35 (36.8%) positive participants. A total of 31/35 was considered asymptomatic infections based on PCR. Households planted Balanites/Acacia trees or breed domestic animals were found in high percentages with L. donovani PCR positive participants (60.1%, 91.4%). No statistically significant was found for VL associated risk factors and VL asymptomatic participants.

Background: The emergence of resistant parasites to artemisinin poses a threat to malaria treatment. The study aimed to investigate K13 gene mutations in Plasmodium falciparum artesunate (AS)/sulfadoxine-pyrimethamine (SP) efficacy study in Sudan., Methods: A total of 31 (14 failures and 17 adequate clinical and parasitological response [ACPR]) pretreatment dried blood samples from patients with uncomplicated P. falciparum malaria treated with AS/SP were examined. Nested polymerase chain reaction (PCR) and DNA sequencing of the K13 gene was performed., Results: PCR products were obtained from 30 (96.8%) samples and sequencing was successful in 28 (90.3%). No mutation of the K13 gene was recorded in the treatment failure group. A single mutation (C>T; A621V) in one ACPR patient sample was detected., Conclusion: There is no evidence of K13 mutation among AS/SP treatment failure patients. A single mutation of the K13 gene not linked to treatment failure has been detected., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The commonest surgical procedure for women is cesarean delivery. Postpartum hemorrhage and intra-operative blood during cesarean delivery is a major concern to all obstetricians. This study was conducted to assess the efficacy of the adjuvant use of misoprostol and oxytocin in decreasing intra-operative blood loss in cesarean delivery., Methods: This was a double-blinded randomized clinical trial including 636 term pregnant woman scheduled for cesarean section at Ain Shams University Maternity Hospital, Cairo, Egypt, between February 2013 and February 2014. Participants received either 400-μg misoprostol rectally or sublingually or placebo before cesarean section together with 5-IU oxytocin IV. The main outcome measure was intra-operative blood loss. Difference between the three groups was analyzed using one-way ANOVA test (for numeric variables) and Chi-square test (for categorical variables). P < 0.05 was considered statistically significant., Results: Intra-operative blood loss was higher in patients who did not receive misoprostol (Placebo Group) (295-1075 ml, 641.7 ± 135.7) than those who received it, regardless the route of administration, rectal (135-830 ml, 457.5 ± 140.7; P < 0.001), and sublingual (135-680 ml, 357.8 ± 129.7; P < 0.001). In addition, sublingual route was associated with significantly lower estimated intra-operative blood loss compared to rectal administration (P < 0.001)., Conclusions: Misoprostol with oxytocin is an effective drug-combination for decreasing intra-operative blood loss during cesarian section with clinical superiority to sublingual over rectal route.

Background:  Malaria continues to present a global health threat; the World Health Organization (WHO) reported 214 million cases of malaria by the year 2015 with a death rate of 438000. Sudan is endemic to malaria with over 95% of malaria cases due to Plasmodium falciparum . Chloroquine is a well-established drug in the treatment of P. falciparum malaria although its use has declined since its introduction as the drug of choice in treatment of malaria in Sudan. The mechanism of resistance has been attributed to mutations in P. falciparum Chloroquine resistance transporter gene coding for a key food vacuole proteins. In current study we aimed at verifying the genetic cause of resistance to Chloroquine in field isolates of P. falciparum . Methods: Twenty P. falciparum cases were diagnosed from East Nile hospital in Khartoum and recruited in the investigation. Nested PCR was conducted to isolate mutation region in the PfCRT gene and the amplicons were sequenced using Sanger sequencing technique (Macrogen, Soule Korea). Results: 16/20 (80%) of the field isolates contained base pair mutation of codon 76 in the pfcrt gene thus being resistant to chloroquine treatment and only 4/20 (20%) did not contain such mutation. Conclusions: High treatment failures associated with Chloroquine treatment is evident of the high prevalence of mutant strains of P. falciparum field isolates thus suggesting the reduced relevance of Chloroquine as a treatment choice in the management of P. falciparum malaria., Competing Interests: No competing interests were disclosed.

Background: Artemisinin-based combination therapy (ACT), together with other control measures, have reduced the burden of falciparum malaria in sub-Saharan countries, including Sudan. Sudan adopted ACT in 2004 with a remarkable reduction in mortality due to falciparum malaria. However, emergence of resistance to the first-line treatment artesunate and sulfadoxine/pyrimethamine (AS/SP) has created new challenges to the control of malaria in Sudan. A search for an alternative drug of choice for treating uncomplicated malaria has become inevitable. The objective of this study was to evaluate the therapeutic efficacies of dihydroartemisinin/piperaquine (DHA-PPQ) and AS/SP in an area of unstable transmission in Blue Nile State, Sudan in 2015-16., Methods: A total of 148 patients with uncomplicated malaria were recruited in the study from November 2015 to end of January 2016. Seventy-five patients received DHA-PPQ while 73 received AS/SP. Patients were monitored for clinical and parasitological outcomes following the standard WHO protocol for a period of 42 days for DHA-PPQ and 28 days for AS/SP; nested PCR (nPCR) was performed to confirm parasite re-appearance from day 7 onwards., Results: Fifty-five patients completed the DHA-PPQ arm protocol with success cure rate of 98.2% (95% CI 90.3-100%) and one late clinical failure 1.8% (95% CI 0.0-9.7%). The AS/SP showed adequate clinical and parasitological response (ACPR) of 83.6% (95% CI 71.9-91.8%), early treatment failure was 1.6% (95% CI 0.0-8.8%) and late parasitological failure (LPF) was 14.8% (95% CI 7-26.2%). The respective PCR uncorrected LPF was 20%., Conclusion: DHA-PPQ is an efficacious ACT and candidate for replacement of first-line treatment in Sudan while AS/SP showed high treatment failure rate and must be replaced.

Cardiovascular disease is stabilizing in high-income countries and has continued to rise in low-to-middle-income countries. Association of lipid profile with lipoprotein lipase gene was studied in case and control subject. The family history, hypertension, diabetes mellitus, smoking and alcohol consumption were the most risk factors for early-onset of coronary heart disease (CHD). Sudanese patients had significantly (P<0.05) lower TC and LDL-C levels compared to controls. Allele frequency of LPL D9N, N291S and S447X carrier genotype was 4.2%, 30.7% and 7.1%, respectively. We conclude that lipoprotein lipase polymorphism was not associated with the incidence of CHD in Sudan., (Copyright © 2015 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.)

Background: Hymenolepis nana is among the most common intestinal parasitic infections causing a public health threat in poor communities in Sub-Saharan Africa. The present study was conducted to determine the prevalence of H. nana infections and associated risk factors among preschool children of displacement communities in Khartoum state, Sudan., Methods: A cross-sectional survey was conducted in May 2013 in displacement camps, Khartoum state, Sudan. A simple random sample of preschool children from the displacement camps, aged between 1 and 5 years, were included. Information was collected by presenting a questionnaire and taking 500 fresh stool specimens which were examined microscopically for the presence of eggs, using direct saline and formal-ether concentration techniques., Results: The prevalence of H. nana was determined to be 32.6% (163/500), 95% CI (28.5%-36.9%). Infections of H. nana were more prevalent among males than females, and this association was statistically significant (P < 0.001, OR = 2.125, 95% CI = 1.452-3.108). H. nana infections were significantly prevalent among the older age group (2.6-5.0 years) (P < 0.001, OR = 2.909, 95% CI = 1.914-4.420). Approximately 76.7% of infected preschool children had diarrhea and it was significantly associated with H. nana infection (P < 0.001, OR = 9.45, 95% CI = 6.10-14.64). None of the preschool children had access to a clean water supply. No significant association was found between use of latrines and infections of H. nana (P = 0.56, OR = 0.880, 95% CI = 0.73-1.763)., Conclusions: There was a high prevalence rate of H. nana infection among preschool children of displacement camps in Khartoum state, Sudan. Being male, aged between 2.6 and 5.0 years, and having diarrhea were identified as important risk factors for H. nana infection. Measures including health education, environmental hygiene, water supply and treatment should be taken into account to reduce the high prevalence of H. nana., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Context: Content uniformity (CU) testing was developed and improved to control the effectiveness and safety of dosage units. Many modifications of compendial CU test have been introduced and several alternatives have been suggested., Objectives: This study aims to evaluate the degree of suitability of current USP CU test for low dose tablets and to compare the performance of the current test with that of the former USP27-NF22 and other alternatives for different sample sizes., Methods: All locally marketed risperidone (RSP) tablets were analyzed using newly developed and validated isocratic UPLC method. The CU results were statistically analyzed in groups with sample sizes comparable to the USP sampling plans., Results: Seven out of eleven products failed the different requirements of the former and current USP <905>chapters as well as of several alternative CU tests with several substantial deviations., Conclusion: The current USP <905> chapter was found to have some deficiencies that allowed such failed products to exist in the market. The dependence of compendial CU test on two-staged sampling plan and the use of arithmetic mean to calculate the reference and acceptance values were obvious shortcomings.

Valence stabilization of polyvalent ions in gamma irradiated aqueous solutions is sometimes necessary in some chemical operations. In previous publications, valence stabilization of some polyvalent ions in solution upon gamma irradiation was achieved by using inorganic additives capable of interacting with the oxidizing or reducing species formed during water radiolysis. The results showed that the nature and duration of valence stabilization of Fe(II) depend on the concentration of the inorganic additives used. In the present work, a series of some organic additives has been used to investigate their capability in inducing valence stabilization of polyvalent iron ions, taken as an indicator, in aqueous acidic solutions when subjected to extended gamma irradiation. The results showed that the efficiency of valence stabilization depends on the amount and chemical structure of the organic additive used.

Open wedge high tibial osteotomy has become the trend for correction of varus knee deformities. The drawbacks were the need of autogenous bone graft with its associated morbidity, and later the use of bone substitutes with their cost and delayed healing. In this study, a total of 58 consecutive patients underwent high tibial osteotomy with internal fixation by wedge (toothed) plate and screws without bone graft, from 2004 to 2008. Age of the patients ranged from 24 to 65 years. There were 37 women and 21 men. The osteotomy opening size ranged from 8 to 14 mm. The mean follow-up was 38 months. The osteotomy united in all patients. Average time to union was 12.4 weeks (range 8-16 weeks). Partial loss of correction occurred in one osteotomy. There was significant difference between the healing time and the size of the osteotomy opening. The results at the final follow-up using the HSS score were excellent in 51 knees (88%) and good in seven knees (12%). Despite the routine addition of bone graft as a part of the high tibial osteotomy procedure, this study supports medial opening-wedge high tibial osteotomy up to 14 mm without bone graft or bone substitutes, which shortens the operative time and avoids unnecessary morbidity.

Cutaneous leishmaniasis in Sudan is caused by Leishmania major zymodeme LON1. Self-healing usually occurs within 1 year but occasionally its duration is prolonged and treatment is required. The clinical forms are ulcers, nodules and noduloulcerative lesions. Here we describe seven patients with uncommon lesions that were difficult to recognize as Leishmania infections. These included mycetoma-like lesions, lesions that resembled L. tropica infection and others. One HIV/AIDS patient had Kaposi's sarcoma with Leishmania parasites in the Kaposi lesions. Most of these uncommon clinical forms were difficult to treat. The diagnosis depended on a high degree of suspicion and the demonstration of parasites in smears or culture. PCR was used to characterize parasites from the patients described here. Leishmania major was found by kDNA PCR in all patients, except one, who had a leishmanioma due to L. donovani. In three patients, including one with a L. tropica like-lesion, the parasites were confirmed as L. major by gp63 PCR-RFLP.

A new antibiotic, NRC-501, was isolated and purified from the fermentation broth of Streptomyces species NRC-501. Physical, chemical, and biological characteristics of the antibiotic NRC-501 were revealed.