Public attitudes towards community pharmacy in Arabic speaking Middle Eastern countries: A systematic review

BackgroundOver the last few years, pharmacy practice in the Arab regions of the Middle East has started to change and develop. There have been small but promising steps to recognize the importance of extending community pharmacists’ roles to meet the expanding public healthcare demands. ObjectivesThis systematic review aims to identify, synthesize and assess the quality of the literature in the Middle East concerning public attitudes on community pharmacist role and services and in relation to public perceptions on strategies to improve pharmacy services and the image of community pharmacist. MethodsA systematic search of 11 electronic databases was conducted to identify all published relevant studies from inception till January 2020. Data was extracted using a designed and tested tool. Studies were assessed for quality using Crowe Critical Appraisal Tool. ResultsThe final study results included 36 studies of which 31 adopted a cross-sectional-survey-based design. Included studies were published between 2004 and 2019. Most studies were done in Saudi Arabia (n = 11) or the United Arab Emirates (UAE) (n = 10). We identified four overarching themes across included studies 1) Use of Community Pharmacies; 2) Attitudes towards Community Pharmacist role; 3) Attitudes towards Current Community Pharmacy Services and 4) Strategies to Improve Community Pharmacy Practice. The most common reason for visiting a community pharmacy was to purchase a prescription or over-the counter-medication. The most common factors that affected patients’ choice of a particular pharmacy included convenient pharmacy location, availability of a good range of products or medicines, friendliness of the pharmacy staff and convenient pharmacy opening hours. There was a general public perception of community pharmacist as a business oriented person. Expectations of pharmacist duties included treatment of minor health ailments, consultation on over-the-counter medications and parapharmaceutical products, and accuracy checking of dispensed medications. Overall satisfaction with community pharmacy varied between the studies and ranged from 33% to 67.1%. Most commonly reported recommendations to improve pharmacy practice were provision of diagnostic, screening and monitoring services, keeping patient records in the pharmacy, advice on minor illness and provision of a private area for consultation. Seven articles were considered of low quality and 13 articles were considered of high quality. ConclusionsWhile the public in the Middle East has a good understanding of the basic duties of a community pharmacist, there is lack of awareness of advanced pharmaceutical services. Decision makers in Middle Eastern countries should set strategies to improve community pharmacist professional image and competence beyond medication dispensing.This work was funded by Qatar University, Qatar Student Grant (QUST-1-CPH-2019-4)

Expanded genome-wide comparisons give novel insights into population structure and genetic heterogeneity of Leishmania tropica complex

Leishmania tropica is one of the main causative agents of cutaneous leishmaniasis (CL). Population structures of L. tropica appear to be genetically highly diverse. However, the relationship between L. tropica strains genomic diversity, protein coding gene evolution and biogeography are still poorly understood. In this study, we sequenced the genomes of three new clinical L. tropica isolates, two derived from a recent outbreak of CL in camps hosting Syrian refugees in Lebanon and one historical isolate from Azerbaijan to further refine comparative genome analyses. In silico multilocus microsatellite typing (MLMT) was performed to integrate the current diversity of genome sequence data in the wider available MLMT genetic population framework. Single nucleotide polymorphism (SNPs), gene copy number variations (CNVs) and chromosome ploidy were investigated across the available 18 L. tropica genomes with a main focus on protein coding genes. MLMT divided the strains in three populations that broadly correlated with their geographical distribution but not populations defined by SNPs. Unique SNPs profiles divided the 18 strains into five populations based on principal component analysis. Gene ontology enrichment analysis of the protein coding genes with population specific SNPs profiles revealed various biological processes, including iron acquisition, sterols synthesis and drug resistance. This study further highlights the complex links between L. tropica important genomic heterogeneity and the parasite broad geographic distribution. Unique sequence features in protein coding genes identified in distinct populations reveal potential novel markers that could be exploited for the development of more accurate typing schemes to further improve our knowledge of the evolution and epidemiology of the parasite as well as highlighting protein variants of potential functional importance underlying L. tropica specific biology

A Nexus Approach for the MENA Region—From Concept to Knowledge to Action

There is wide agreement that a nexus or integrated approach to managing and governing natural resources such as land, water, and energy can improve environmental, climate, human, and political security. However, few if any countries in the MENA region have made progress in implementing such an approach. There appear to be several constraints inhibiting the development and adoption of nexus approaches. These constraints include strong sectoral silos, insufficient incentives for integrated planning and policy making at all levels, and limited vision, knowledge, and practical experience to guide successful implementation. In turn, the limited implementation and hence lack of empirical evidence of a nexus approach, which could demonstrate its benefits, does little to strengthen political will for the development of adequate incentives, structures, and procedures. Against this backdrop, this paper presents five case studies which take an integrated approach, in three MENA countries, namely Jordan, Lebanon, and Morocco. Based on an analytical framework developed here, the paper analyses and compares the success factors for nexus implementation, and also for transfer and upscaling. The analysis emphasizes the need for appropriate framework conditions, targeted investments and pioneering actors, to make integrated approaches across sectors and levels work. With the evidence presented, the paper aims to set in motion a positive or virtuous cycle of generating more nexus evidence, improved framework conditions, further nexus implementation on the ground, and from that even more nexus evidence. Finally, the paper contributes to overcoming the repeated requests for better definition and conceptualization of the nexus, which often has slowed down adoption of the concept

Evaluation of an intensive education program on the treatment of tobacco-use disorder for pharmacists: A study protocol for a randomized controlled trial

Background: Tobacco use is presently responsible for the death of over seven million people across the world. In Qatar, it is one of the main causes of premature deaths and preventable diseases. To reduce tobacco use, Qatar has ratified the World Health Organization (WHO)'s Framework Convention on Tobacco Control (FCTC) and has implemented many tobacco-control initiatives. In spite of these measures, tobacco use is still considered a public health threat in Qatar. Pharmacists practicing in retail/community pharmacy settings are often the first port of call for individuals requiring general health advice. Evidence has proven that they have a pivotal role in health promotion and disease prevention including tobacco cessation. However, pharmacists in Qatar are not actively involved in tobacco control and many have not received any education or training about smoking cessation counseling in the past. In an effort to build the capacity of pharmacists towards tobacco control in Qatar, the aim of the proposed study is to design, implement, and evaluate an intensive education program on tobacco dependence treatment for pharmacists in Qatar. Methods/design: The study will be a prospective randomized controlled trial comparing an intensive tobacco-related education program versus non-tobacco-related training on pharmacists' tobacco-use-related knowledge, attitudes, self-efficacy, and skills. Community pharmacists practicing in Qatar will be eligible for participation in the study. A random sample of pharmacists will be selected for participation. Consenting participants will be randomly allocated to intervention or control groups. Participants in the intervention group will receive an intensive education program delivered by a multi-disciplinary group of educators, researchers, and clinicians with expertise in tobacco cessation. A short didactic session on a non-tobacco-related topic will be delivered to pharmacists in the control group. The study has two primary outcomes: post-intervention tobacco-related knowledge and post-intervention skills for tobacco cessation assessed using a multiple-choice-based evaluation instrument and an Objective Structured Clinical Examination (OSCE), respectively. The secondary study outcomes are post-intervention attitudes towards tobacco cessation and self-efficacy in tobacco-cessation interventions assessed using a survey instrument. An additional secondary study outcome is the post-intervention performance difference in relation to tobacco-cessation skills in the practice setting assessed using the simulated client approach. Discussion: If demonstrated to be effective, this education program will be considered as a model that Qatar and the Middle East region can apply to overcome the burden of tobacco-use disorder. Trial registration: ClinicalTrials.gov, ID: NCT03518476. Registered on 8 May 2018. Version 1/22 June 2018. 2019 The Author(s).ASHP: American Society of Health-System Pharmacists; ATTUD: Association for the Treatment of Tobacco use and Dependence; CE: Continuous education; CPG: Clinical practice guidelines; FCTC: Framework Convention on Tobacco Control; FIP: International Pharmaceutical Federation; GATS: Global Adult Tobacco Survey; GYTS: Global Youth Tobacco Survey; HMC: Hamad Medical Corporation; MCQ: Multiple choice question; ME: Middle East; NRT: Nicotine replacement therapy; OSCE: Objective Structured Clinical Examination; PBL: Problem-based learning; QCHP: Qatar Council for Healthcare Practitioners; QU: Qatar University; SPIRIT: Standard Protocol Items: Recommendations for Interventional Trials; SPSS: Statistical Package of Social Sciences; TTM: Transtheoretical model; WHO: World Health OrganizationScopu

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Efficacité d’un analogue d’Imiqualines, l’EAPB0503 : Un nouveau traitement prometteur contre la Leishmaniose Cutanée

Cutaneous Leishmaniasis (CL) is a parasitic infection classified by the WHO as one of the most uncontrolled spreading neglected diseases. In the Middle East Region, CL is mostly endemic in Syria where it is mainly caused by Leishmania tropica and Leishmania major. CL has been lately introduced to under endemic countries, following the large-scale displacement of refugees from Syria fleeing the crisis. Therapeutic interventions against CL include local, systemic and physical treatments. However, the high risk for selection and spread of drug-resistant parasites is high; consequently new therapeutic approaches are still needed. Imiquimod is an FDA approved immunomodulatory compound with a tested efficacy against some leishmania species. In this study, our interest was to investigate the efficacy of an Imiquimod analog, EAPB0503 in comparison to the original compound, against promastigote and amastigote stages of L.tropica and L.major.We showed that Imiquimod affects the motility of promastigotes of both strains. EAPB0503 affected L. major promastigotes’ motility and impaired the invasion of L.tropica promastigotes into macrophages. Both drugs reduced amastigote replication, with a higher potency of EAPB0503. This activity is due to the upregulation of Toll-Like Receptor-7 (TLR7), mainly by Imiquimod, and to a lesser extent by EAPB0503. Importantly, both drugs activated the NF-κB canonical pathway leading to production of pro-inflammatory cytokines and upregulation of i-NOS levels. A decrease of anti-inflammatory cytokines secretion was obtained, explaining the leishmanicidal activity of both drugs. Importantly, EAPB0503 led to a prominent increase in TLR8 and TLR9 transcripts, presumably conferring protection against the infection.Collectively, our findings show the effect of Imiquimod against both strains especially, the aggressive L. tropica strain. We also show that EAPB0503 displays a more potent in vitro leishmanicidal activity than Imiquimod. These drugs seemingly activate different TLRs, but both activate the canonical NF-κB pathway and its subsequent mediated immune response. These results highlight the promising effect of immunomodulatory drugs against CL and warrant an in depth in vivo preclinical then clinical studies of these compounds.La leishmaniose cutanée (LC) est une infection parasitaire classifiée par l’Organisation de Santé Mondiale (WHO) comme étant une des maladies tropicales négligées non-contrôlées. Dans la région du Moyen Orient, la LC est généralement endémique en Syrie et elle est causée principalement par Leishmania tropica et Leishmania major. La LC a été récemment introduite à des pays non endémiques, suite au déplacement intense des réfugiés Syriens échappant à la crise. Les interventions thérapeutiques contre la LC incluent des traitements locaux, systémiques et physiques. En revanche, le risque élevé de sélection et de résistance des parasites aux traitements actuels suscitent une quête sérieuse, pour trouver de nouvelles approches thérapeutiques. L’Imiquimod est un composé immunomodulateur approuvé pour utilisation clinique, et présente une efficacité vis-à-vis de certaines espèces de Leishmania. Dans cette étude, notre intérêt s’est focalisé sur l’efficacité d’un analogue de l’Imiquimod, l’EAPB0503, contre les stades promastigotes et amastigotes de L.tropica et L.major.Nos résultats montrent que l’Imiquimod et particulièrement l’EAPB0503 affectent les deux espèces. L’Imiquimod affecte majoritairement la motilité des promastigotes des deux espèces, alors que l’EAPB0503 affecte la motilité des promastigotes de L. major mais surtout l’invasion des promastigotes de L. tropica dans les macrophages. Les deux composés réduisent la réplication des amastigotes, avec un effet plus prominent de l’EAPB0503. Cet effet est médié par l’augmentation de l’expression du récepteur toll-Like-7 (TLR7), particulièrement pour l’Imiquimod et d’une manière moins importante pour l’EAPB0503. Les deux composés induisent l’activation de la voie de signalisation canonique de NF-κB. Ceci conduit à une production des cytokines pro-inflammatoires, et une diminution des cytokines anti-inflammatoires expliquant l’activité leishmanicide des deux composés. L’EAPB0503 semble agir via un autre TLR que l’imiquimod, comme il induit une expression plus élevée des transcrits TLR8 et TLR9, conférant une protection contre l’infection.Collectivement, nos résultats montrent l’effet de l’Imiquimod contre l’espèce la plus aggressive, L. tropica, et souligne l’activité plus puissante de l’EAPB0503 contre les deux espèces. De plus, cette étude montre le mécanisme d’action de ces deux composés, qui vraisemblablement activent des TLRs différents, mais finissent par induire la voie NF-κB et la réponse immunitaire correspondante. Ces résultats soulignent l’importance des drogues immuno-modulatrices contre la LC et ouvrent des perspectives sur des études précliniques puis cliniques de ces composés

Efficacy of the Imiqualine analog EAPB0503 against Cutaneous Leishmaniasis : A promising new treatment paradigm

La leishmaniose cutanée (LC) est une infection parasitaire classifiée par l’Organisation de Santé Mondiale (WHO) comme étant une des maladies tropicales négligées non-contrôlées. Dans la région du Moyen Orient, la LC est généralement endémique en Syrie et elle est causée principalement par Leishmania tropica et Leishmania major. La LC a été récemment introduite à des pays non endémiques, suite au déplacement intense des réfugiés Syriens échappant à la crise. Les interventions thérapeutiques contre la LC incluent des traitements locaux, systémiques et physiques. En revanche, le risque élevé de sélection et de résistance des parasites aux traitements actuels suscitent une quête sérieuse, pour trouver de nouvelles approches thérapeutiques. L’Imiquimod est un composé immunomodulateur approuvé pour utilisation clinique, et présente une efficacité vis-à-vis de certaines espèces de Leishmania. Dans cette étude, notre intérêt s’est focalisé sur l’efficacité d’un analogue de l’Imiquimod, l’EAPB0503, contre les stades promastigotes et amastigotes de L.tropica et L.major.Nos résultats montrent que l’Imiquimod et particulièrement l’EAPB0503 affectent les deux espèces. L’Imiquimod affecte majoritairement la motilité des promastigotes des deux espèces, alors que l’EAPB0503 affecte la motilité des promastigotes de L. major mais surtout l’invasion des promastigotes de L. tropica dans les macrophages. Les deux composés réduisent la réplication des amastigotes, avec un effet plus prominent de l’EAPB0503. Cet effet est médié par l’augmentation de l’expression du récepteur toll-Like-7 (TLR7), particulièrement pour l’Imiquimod et d’une manière moins importante pour l’EAPB0503. Les deux composés induisent l’activation de la voie de signalisation canonique de NF-κB. Ceci conduit à une production des cytokines pro-inflammatoires, et une diminution des cytokines anti-inflammatoires expliquant l’activité leishmanicide des deux composés. L’EAPB0503 semble agir via un autre TLR que l’imiquimod, comme il induit une expression plus élevée des transcrits TLR8 et TLR9, conférant une protection contre l’infection.Collectivement, nos résultats montrent l’effet de l’Imiquimod contre l’espèce la plus aggressive, L. tropica, et souligne l’activité plus puissante de l’EAPB0503 contre les deux espèces. De plus, cette étude montre le mécanisme d’action de ces deux composés, qui vraisemblablement activent des TLRs différents, mais finissent par induire la voie NF-κB et la réponse immunitaire correspondante. Ces résultats soulignent l’importance des drogues immuno-modulatrices contre la LC et ouvrent des perspectives sur des études précliniques puis cliniques de ces composés.Cutaneous Leishmaniasis (CL) is a parasitic infection classified by the WHO as one of the most uncontrolled spreading neglected diseases. In the Middle East Region, CL is mostly endemic in Syria where it is mainly caused by Leishmania tropica and Leishmania major. CL has been lately introduced to under endemic countries, following the large-scale displacement of refugees from Syria fleeing the crisis. Therapeutic interventions against CL include local, systemic and physical treatments. However, the high risk for selection and spread of drug-resistant parasites is high; consequently new therapeutic approaches are still needed. Imiquimod is an FDA approved immunomodulatory compound with a tested efficacy against some leishmania species. In this study, our interest was to investigate the efficacy of an Imiquimod analog, EAPB0503 in comparison to the original compound, against promastigote and amastigote stages of L.tropica and L.major.We showed that Imiquimod affects the motility of promastigotes of both strains. EAPB0503 affected L. major promastigotes’ motility and impaired the invasion of L.tropica promastigotes into macrophages. Both drugs reduced amastigote replication, with a higher potency of EAPB0503. This activity is due to the upregulation of Toll-Like Receptor-7 (TLR7), mainly by Imiquimod, and to a lesser extent by EAPB0503. Importantly, both drugs activated the NF-κB canonical pathway leading to production of pro-inflammatory cytokines and upregulation of i-NOS levels. A decrease of anti-inflammatory cytokines secretion was obtained, explaining the leishmanicidal activity of both drugs. Importantly, EAPB0503 led to a prominent increase in TLR8 and TLR9 transcripts, presumably conferring protection against the infection.Collectively, our findings show the effect of Imiquimod against both strains especially, the aggressive L. tropica strain. We also show that EAPB0503 displays a more potent in vitro leishmanicidal activity than Imiquimod. These drugs seemingly activate different TLRs, but both activate the canonical NF-κB pathway and its subsequent mediated immune response. These results highlight the promising effect of immunomodulatory drugs against CL and warrant an in depth in vivo preclinical then clinical studies of these compounds

Toxoplasmosis: Current and Emerging Parasite Druggable Targets

Toxoplasmosis is a prevalent disease affecting a wide range of hosts including approximately one-third of the human population. It is caused by the sporozoan parasite Toxoplasma gondii (T. gondii), which instigates a range of symptoms, manifesting as acute and chronic forms and varying from ocular to deleterious congenital or neuro-toxoplasmosis. Toxoplasmosis may cause serious health problems in fetuses, newborns, and immunocompromised patients. Recently, associations between toxoplasmosis and various neuropathies and different types of cancer were documented. In the veterinary sector, toxoplasmosis results in recurring abortions, leading to significant economic losses. Treatment of toxoplasmosis remains intricate and encompasses general antiparasitic and antibacterial drugs. The efficacy of these drugs is hindered by intolerance, side effects, and emergence of parasite resistance. Furthermore, all currently used drugs in the clinic target acute toxoplasmosis, with no or little effect on the chronic form. In this review, we will provide a comprehensive overview on the currently used and emergent drugs and their respective parasitic targets to combat toxoplasmosis. We will also abridge the repurposing of certain drugs, their targets, and highlight future druggable targets to enhance the therapeutic efficacy against toxoplasmosis, hence lessening its burden and potentially alleviating the complications of its associated diseases