Browsing by Author "Alfaresi, Mubarak"

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Application of Artificial Intelligence in Combating High Antimicrobial Resistance Rates
(2022) Alfaresi, Mubarak
Abstract: Artificial intelligence (AI) is a branch of science and engineering that focuses on the computational understanding of intelligent behavior. Many human professions, including clinical diagnosis and prognosis, are greatly useful from AI. Antimicrobial resistance (AMR) is among the most critical challenges facing Pakistan and the rest of the world. The rising incidence of AMR has become a significant issue, and authorities must take measures to combat the overuse and incorrect use of antibiotics in order to combat rising resistance rates. The widespread use of antibiotics in clinical practice has not only resulted in drug resistance but has also increased the threat of superresistant bacteria emergence. As AMR rises, clinicians find it more difficult to treat many bacterial infections in a timely manner, and therapy becomes prohibitively costly for patients. To combat the rise in AMR rates, it is critical to implement an institutional antibiotic stewardship program that monitors correct antibiotic use, controls antibiotics, and generates antibiograms. Furthermore, these types of tools may aid in the treatment of patients in the event of a medical emergency in which a physician is unable to wait for bacterial culture results. AI’s applications in healthcare might be unlimited, reducing the time it takes to discover new antimicrobial drugs, improving diagnostic and treatment accuracy, and lowering expenses at the same time. The majority of suggested AI solutions for AMR are meant to supplement rather than replace a doctor’s prescription or opinion, but rather to serve as a valuable tool for making their work easier. When it comes to infectious diseases, AI has the potential to be a game-changer in the battle against antibiotic resistance. Finally, when selecting antibiotic therapy for infections, data from local antibiotic stewardship programs are critical to ensuring that these bacteria are treated quickly and effectively. Furthermore, organizations such as the World Health Organization (WHO) have underlined the necessity of selecting the appropriate antibiotic and treating for the shortest time feasible to minimize the spread of resistant and invasive resistant bacterial strains.
Application of CRISPR-Cas System to Mitigate Superbug Infections
(2023) Alfaresi, Mubarak
Abstract: Multidrug resistance in bacterial strains known as superbugs is estimated to cause fatal infections worldwide. Migration and urbanization have resulted in overcrowding and inadequate sanitation, contributing to a high risk of superbug infections within and between different communities. The CRISPR-Cas system, mainly type II, has been projected as a robust tool to precisely edit drug-resistant bacterial genomes to combat antibiotic-resistant bacterial strains effectively. To entirely opt for its potential, advanced development in the CRISPR-Cas system is needed to reduce toxicity and promote efficacy in gene-editing applications. This might involve base-editing techniques used to produce point mutations. These methods employ designed Cas9 variations, such as the adenine base editor (ABE) and the cytidine base editor (CBE), to directly edit single base pairs without causing DSBs. The CBE and ABE could change a target base pair into a different one (for example, G-C to A-T or C-G to A-T). In this review, we addressed the limitations of the CRISPR/Cas system and explored strategies for circumventing these limitations by applying diverse base-editing techniques. Furthermore, we also discussed recent research showcasing the ability of base editors to eliminate drug-resistant microbes.
Association of Cardiovascular Disease with Severe Dengue: A Systematic Review and Meta-Analysis
(2023-12) Alfaresi, Mubarak
Abstract: Background: Cardiovascular disease (CVD) and dengue are both significant global health concerns, and their intersection presents a growing clinical challenge. Emerging evidence suggests that individuals with pre-existing CVD may face an elevated risk of severe dengue outcomes. The present study aims to perform a systematic review to assess the relationship between CVD and the severity of dengue. Methods: We conducted a literature search across multiple databases from inception to November 25, 2023. Primary studies reporting the number of dengue patients with CVD in severe dengue and non-severe dengue groups were included. Quality assessment was performed using the Newcastle-Ottawa Scale, and a meta-analysis was conducted using R software version 4.2 to determine the pooled Relative Risk (RR). The study protocol has been registered in PROSPERO. Results: Based on data from 5 studies involving 274,576 dengue patients, our meta-analysis revealed a significant association between CVD and an increased risk of severe dengue, with a calculated RR of 2.71 (95 % CI: 1.03 to 7.10). However, substantial heterogeneity was observed among the included studies (I2 = 79 %). Conclusion: The current evidence suggests an association between CVD and severe dengue, emphasizing the importance of closely monitoring individuals with pre-existing cardiovascular disease and providing them with targeted interventions upon dengue diagnosis to mitigate the risk of severe outcomes.
Genetic Variants and Protective Immunity against SARS-CoV-2
(2022-11) Alfaresi, Mubarak
Abstract: The novel coronavirus-19 (SARS-CoV-2), has infected numerous individuals worldwide, resulting in millions of fatalities. The pandemic spread with high mortality rates in multiple waves, leaving others with moderate to severe symptoms. Co-morbidity variables, including hypertension, diabetes, and immunosuppression, have exacerbated the severity of COVID-19. In addition, numerous efforts have been made to comprehend the pathogenic and host variables that contribute to COVID-19 susceptibility and pathogenesis. One of these endeavours is understanding the host genetic factors predisposing an individual to COVID-19. Genome-Wide Association Studies (GWAS) have demonstrated the host predisposition factors in different populations. These factors are involved in the appropriate immune response, their imbalance influences susceptibility or resistance to viral infection. This review investigated the host genetic components implicated at the various stages of viral pathogenesis, including viral entry, pathophysiological alterations, and immunological responses. In addition, the recent and most updated genetic variations associated with multiple host factors affecting COVID-19 pathogenesis are described in the study.
Global Prevalence and Potential Influencing Factors of COVID-19 Vaccination Hesitancy: A Meta-Analysis
(2022-08) Alfaresi, Mubarak
Abstract: Countries worldwide have deployed mass COVID-19 vaccination drives, but there are people who are hesitant to receive the vaccine. Studies assessing the factors associated with COVID-19 vaccination hesitancy are inconclusive. This study aimed to assess the global prevalence of COVID-19 vaccination hesitancy and determine the potential factors associated with such hesitancy. We performed an organized search for relevant articles in PubMed, Scopus, and Web of Science. Extraction of the required information was performed for each study. A single-arm meta-analysis was performed to determine the global prevalence of COVID-19 vaccination hesitancy; the potential factors related to vaccine hesitancy were analyzed using a Z-test. A total of 56 articles were included in our analysis. We found that the global prevalence of COVID-19 vaccination hesitancy was 25%. Being a woman, being a 50-year-old or younger, being single, being unemployed, living in a household with five or more individuals, having an educational attainment lower than an undergraduate degree, having a non-healthcare-related job and considering COVID-19 vaccines to be unsafe were associated with a higher risk of vaccination hesitancy. In contrast, living with children at home, maintaining physical distancing norms, having ever tested for COVID-19, and having a history of influenza vaccination in the past few years were associated with a lower risk of hesitancy to COVID-19 vaccination. Our study provides valuable information on COVID-19 vaccination hesitancy, and we recommend special interventions in the sub-populations with increased risk to reduce COVID-19 vaccine hesitancy.
Investigation of potential ascorbate peroxidase inhibitors for anti-leishmaniasis therapy
(2024-08) Alfaresi, Mubarak
Abstract L eishmaniasis is a prevalent disease that impacts 98 countries and territories, mainly in Africa, Asia, and South America. It can cause substantial illness and death, particularly in its visceral manifestation that can be specifically targeted in the development of medications to combat leishmaniasis. This study has found natural compounds with possible inhibitory activity against APX using a reliable and accurate QSAR model. Despite the severe side effects of current treatments and the absence of an effective vaccination, these compounds show promise as a potential treatment for the disease. Nine hit compounds were found, and subsequent molecular docking was performed. Estradiol cypionate showed the lowest binding energy (- 10.5 kcal/mol), thus showing the strongest binding, and also had the strongest binding affinity, with a ΔGTotal of - 26.31 ± 3.01 kcal/mol, second only to the control molecule. Additionally, three hits viz. cloxacillin-sodium (- 16.57 ± 2.89 kcal/mol), cinchonidine (- 16.04 ± 3.27 kcal/mol), and quinine hydrochloride dihydrate (13.38 ± 1.06 kcal/mol) also showed significant binding affinity. Multiple interactions between drugs and active site residues demonstrated a substantial binding affinity with the target protein. The identified compounds exhibited drug-like effects and were orally bioavailable based on their ADME-toxicology features. Overall, estradiol cypionate, cloxacillin sodium, cinchonidine, and quinine hydrochloride dihydrate all exhibited inhibitory effects on the APX enzyme of Leishmania donovani. These results suggest that further investigation is needed to explore the potential of developing novel anti-leishmaniasis drugs using these compounds.
Monkeypox and Its Possible Sexual Transmission: Where Are We Now with Its Evidence?
(2022-08) Alfaresi, Mubarak
Abstract: Monkeypox is a rare disease but is increasing in incidence in different countries since the first case was diagnosed in the UK by the United Kingdom (UK) Health Security Agency on 6 May 2022. As of 9 August, almost 32,000 cases have been identified in 89 countries. In endemic areas, the monkeypox virus (MPXV) is commonly transmitted through zoonosis, while in non-endemic regions, it is spread through human-to-human transmission. Symptoms can include flu-like symptoms, rash, or sores on the hands, feet, genitalia, or anus. In addition, people who did not take the smallpox vaccine were more likely to be infected than others. The exact pathogenesis and mechanisms are still unclear; however, most identified cases are reported in men who have sex with other men (MSM). According to the CDC, transmission can happen with any sexual or non-sexual contact with the infected person. However, a recent pooled meta-analysis reported that sexual contact is involved in more than 91% of cases. Moreover, it is the first time that semen analysis for many patients has shown positive monkeypox virus DNA. Therefore, in this review, we will describe transmission methods for MPXV while focusing mainly on potential sexual transmission and associated sexually transmitted infections. We will also highlight the preventive measures that can limit the spread of the diseases in this regard.
Pooled rates and demographics of POTS following SARS-CoV-2 infection versus COVID-19 vaccination: Systematic review and meta-analysis
(2023) Alfaresi, Mubarak
Purpose: To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination. Methods: We searched PubMed, Web of Science, and Scopus as of 1st June 2023. We performed a systematic review and meta-analysis of pooled POTS rate in SARS-CoV-2-infected and COVID-19 vaccinated groups from epidemiological studies, followed by subgroup analyses by characteristic. Meta-analysis of risk ratio was conducted to compare POTS rate in infected versus uninfected groups. Meta-analysis of demographics was also performed to compare cases of post-infection and post-vaccination POTS from case reports and series. Results: We estimated the pooled POTS rate of 107.75 (95 % CI: 9.73 to 273.52) and 3.94 (95 % CI: 0 to 16.39) cases per 10,000 (i.e., 1.08 % and 0.039 %) in infected and vaccinated individuals based on 5 and 2 studies, respectively. Meta-regression revealed age as a significant variable influencing 86.2 % variance of the pooled POTS rate in infected population (P < 0.05). Moreover, POTS was 2.12-fold more likely to occur in infected than uninfected individuals (RR = 2.12, 95 % CI: 1.71 to 2.62, P < 0.001). Meta-analyzed demographics for cases of post-infection (n = 43) and post-vaccination (n = 17) POTS found no significant differences in several variables between groups, except that the time from exposure to symptom onset was shorter for cases of post-vaccination POTS (P < 0.05). Conclusion: Although evidence is limited for post-vaccination POTS, our study showed that POTS occur more frequently following SARS-CoV-2 infection than COVID-19 vaccination.
Potential Strategies to Control the Risk of Antifungal Resistance in Humans: A Comprehensive Review
(2023) Alfaresi, Mubarak
Abstract: Fungal infections are becoming one of the main causes of morbidity and mortality in people with weakened immune systems. Mycoses are becoming more common, despite greater knowledge and better treatment methods, due to the regular emergence of resistance to the antifungal medications used in clinical settings. Antifungal therapy is the mainstay of patient management for acute and chronic mycoses. However, the limited availability of antifungal drug classes limits the range of available treatments. Additionally, several drawbacks to treating mycoses include unfavourable side effects, a limited activity spectrum, a paucity of targets, and fungal resistance, all of which continue to be significant issues in developing antifungal drugs. The emergence of antifungal drug resistance has eliminated accessible drug classes as treatment choices, which significantly compromises the clinical management of fungal illnesses. In some situations, the emergence of strains resistant to many antifungal medications is a major concern. Although new medications have been developed to address this issue, antifungal drug resistance has grown more pronounced, particularly in patients who need long-term care or are undergoing antifungal prophylaxis. Moreover, the mechanisms that cause resistance must be well understood, including modifications in drug target affinities and abundances, along with biofilms and efflux pumps that diminish intracellular drug levels, to find novel antifungal drugs and drug targets. In this review, different classes of antifungal agents, and their resistance mechanisms, have been discussed. The latter part of the review focuses on the strategies by which we can overcome this serious issue of antifungal resistance in humans.
Prevalence of Hepatocellular Carcinoma in Hepatitis B Population within Southeast Asia: A Systematic Review and Meta-Analysis of 39,050 Participants
(2023) Alfaresi, Mubarak
Background and aim: Hepatocellular carcinoma (HCC) is a significant complication of hepatitis B and still poses a global public health concern. This systematic review and meta-analysis provide adequate details on the prevalence of HCC in the HBV population within Southeast Asian countries. Method: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria, a thorough search for literature discussing the prevalence of HCC in the HBV population within southeast Asia was performed. Eligible studies were subjected to a meta-analysis utilising a DerSimonian and Laird approach and a random effect model. A protocol was registered with PROSPERO (CRD42023423953). Result: Our study meticulously recovered 41 articles from seven countries in Southeast Asia, namely Cambodia, Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. A total of 39,050 HBV patients and 7479 HCC cases in southeast Asia were analysed. The pooled prevalence of HCC in HBV cases within southeast Asia was 45.8% (95% CI, 34.3–57.8%, I 2 = 99.51%, p < 0.001). Singapore (62.5%, CI: 42.4–79.1) had the highest pooled prevalence of HCC in the HBV population compared to Vietnam, with the lowest estimate (22.4%, CI: 9.9–44.9). There was a drop in the pooled prevalence of HCC in HBV from 2016 until now (37.6%, CI: 19.2–60.5). Conclusion: The findings of this review reveal a high pooled prevalence of HCC in the HBV population and therefore stir the need for routine screening, management, and surveillance.
Promising Antimycobacterial Activities of Flavonoids against Mycobacterium sp. Drug Targets: A Comprehensive Review
(2022-08) Alfaresi, Mubarak
Abstract: Tuberculosis (TB) caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb) remains a threat to mankind, with over a billion of deaths in the last two centuries. Recent advancements in science have contributed to an understanding of Mtb pathogenesis and developed effective control tools, including effective drugs to control the global pandemic. However, the emergence of drug resistant Mtb strains has seriously affected the TB eradication program around the world. There is, therefore, an urgent need to develop new drugs for TB treatment, which has grown researchers’ interest in small molecule-based drug designing and development. The small molecules-based treatments hold significant potential to overcome drug resistance and even provide opportunities for multimodal therapy. In this context, various natural and synthetic flavonoids were reported for the effective treatment of TB. In this review, we have summarized the recent advancement in the understanding of Mtb pathogenesis and the importance of both natural and synthetic flavonoids against Mtb infection studied using in vitro and in silico methods. We have also included flavonoids that are able to inhibit the growth of non-tubercular mycobacterial organisms. Hence, understanding the therapeutic properties of flavonoids can be useful for the future treatment of TB.
Suspected Adenovirus Causing an Emerging HEPATITIS among Children below 10 Years: A Review
(2022) Alfaresi, Mubarak
Abstract: In October 2021, a case of acute hepatic failure without any known cause was identified in the United States of America. Upon further investigation, other children aged 1–6 years were reported to have the same liver failure, and some of them were positive for adenovirus 41 type F. On 21 April 2022, the Centers for Disease Control and Prevention (CDC) released an alert after 74 cases were identified in United Kingdom (UK) between 5 and 8 April in children below 10 years of age, some of whom were also found to be positive for SARS-CoV-2. All the patients showed symptoms such as vomiting, diarrhea, jaundice, and abdominal pain. The patients’ liver enzymes were remarkably increased. A total of 650 cases had been reported from 33 countries as of 27 May 2022, among which 222 cases were reported in the UK alone. No connection with SARS-CoV-2 or its vaccine has been found so far. However, the suspected cause is adenovirus, including its genomic variations, because its pathogenesis and laboratory investigations have been positively linked. Until further evidence emerges, hygiene precautions could be helpful to prevent its spread.
Tools to Alleviate the Drug Resistance in Mycobacterium tuberculosis
(2022) Alfaresi, Mubarak
Abstract: Mycobacterium tuberculosis (Mtb), an acid-fast bacillus that causes Tuberculosis (TB), is a pathogen that caused 1.5 million deaths in 2020. As per WHO estimates, another 4.1 million people are suffering from latent TB, either asymptomatic or not diagnosed, and the frequency of drug resistance is increasing due to intrinsically linked factors from both host and bacterium. For instance, poor access to TB diagnosis and reduced treatment in the era of the COVID-19 pandemic has resulted in more TB deaths and an 18% reduction in newly diagnosed cases of TB. Additionally, the detection of Mtb isolates exhibiting resistance to multiple drugs (MDR, XDR, and TDR) has complicated the scenario in the pathogen’s favour. Moreover, the conventional methods to detect drug resistance may miss mutations, making it challenging to decide on the treatment regimen. However, owing to collaborative initiatives, the last two decades have witnessed several advancements in both the detection methods and drug discovery against drug-resistant isolates. The majority of them belong to nucleic acid detection techniques. In this review, we highlight and summarize the molecular mechanism underlying drug resistance in Mtb, the recent advancements in resistance detection methods, and the newer drugs used against drug-resistant TB.