Seok Mui Wang

The dynamics and protectiveness of the hybrid immune responses, especially in individuals who have experienced severe COVID-19, remain to be fully understood. This study aims to identify the prevalence and persistence of neutralising antibodies throughout time, and to investigate the longitudinal profile of anti-SARS-CoV-2 IgG antibodies targeting the receptor binding domain (RBD) in patients recovering from severe COVID-19. A total of 42 hospitalised COVID-19 survivors were enrolled from three medical centres in Malaysia. Serial blood samples were collected at four time points post-discharge (approximately 90, 180, 270 and 360 days). IgG titres were quantified using ELISA and neutralising antibodies (NAbs). Statistical analyses were performed to explore antibody dynamics and correlations. Among 42 participants, 24 completed all four visits. Mean antibody titre showed an initial decline after the first visit, followed by a gradual increase over time, with the highest being at Visit 4 (360-390 days post-discharge). The highest titre (266.7 ± 30.9 BAU/mL) was observed in a recipient, 10 days after receiving the fourth vaccination. All participants except one demonstrated protective NAbs at the final visit. Higher BMI was significantly associated with disease severity (P = 0.006), while IgG titres were higher in individuals with more severe initial infections (Category 5). This study highlights the persistence of antibody response with hybrid immunity, with the booster vaccinations contributing to increased antibody titres. RBD-specific IgG titres provide useful insights into their trends, while the concurrent NAbs assessment is important for a comprehensive understanding of the protective efficacy following hybrid immunity.

Backgrounds: Intestinal protozoan infections (IPI), including Entamoeba spp., Giardia lamblia and Cryptosporidium spp., are common in diarrhoea patients in Malaysia. These parasites are primarily transmitted through contaminated food and water sources and pose a significant public health concern. Entamoeba spp., causes amoebiasis, which is characterised by severe diarrhoea with bloody stools, while Giardia spp., causes giardiasis, which is characterised by watery diarrhoea, abdominal pain and flatulence. Cryptosporidium spp. causes cryptosporidiosis, which is particularly severe in immunocompromised individuals. Despite efforts to improve water quality, sanitation, hygiene, and surveillance, limited epidemiological data prevent a clear understanding of the prevalence of intestinal protozoa and response to treatment. This systematic review and meta-analysis aimed to estimate prevalence, identify risk factors, and evaluate detection methods. Methods: A comprehensive literature search was carried out in the following databases: Scopus, Google Scholar, Web of Science, PubMed and Cochrane Library. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidance. Based on the random effects model, results were reported as proportions with 95% confidence intervals (CI). Subgroup analyses were performed based on detection methods, target populations and regions. Results: A total of 103 articles were found on the prevalence and risk factors of IPI in Malaysia. After removing duplicates and screening for eligibility, 49 studies were included in this meta-analysis. The overall pooled prevalence of IPI in Malaysia was 24% (95% CI: 0.17.0, 0.29). with I² = 98.94%, (P < 0.001). Among the identified protozoa, Entamoeba spp. had the highest prevalence at 18% (95% CI: 0.12, 0.24), followed by G. lamblia at 11% (95% CI: 0.08, 0.14) and Cryptosporidium spp. at 9% (95% CI: 0.03, 0.14). A subgroup analysis revealed that Kelantan and Perak state have the highest prevalence of 39% and 29% while Selangor and Kuala Lumpur reported the lowest (13.6%). The highest prevalence was observed in the indigenous communities (27%), followed by the local communities that mainly comes from rural area (23%). According to a meta-analysis of ten risk factors, the pooled prevalence of protozoal intestinal infections was significantly higher (between 38% and 52%) in children under 15 years of age, in males, in those with low income or no formal education, and in those exposed to untreated water, poor sanitation or unhygienic practises. A high level of heterogeneity was observed (I² > 98%), reflecting substantial variability across the included studies. Conclusion: This review provides valuable insights into the epidemiology of protozoal intestinal infections in Malaysia. The high pooled prevalence of 24% underscores a substantial and ongoing burden of intestinal protozoal infections in Malaysia. The pooled prevalence should be interpreted with caution due to high heterogeneity, as the findings may not be generalizable to all settings. These findings support the development of evidence-based interventions to reduce the impact of these infections. Targeted screening, improved diagnostics, better access to clean water and sanitation, and health education for vulnerable groups are essential to reduce the burden of intestinal protozoa and strengthen national control measures.

Dengue virus (DENV) poses a significant global health burden, with current treatments being limited and primarily supportive. Aptamers are an emerging class of molecular recognition elements that are cheaper, less immunogenic and have no batch-to-batch variation as compared to antibodies. In light of their advantages, aptamers can potentially offer a novel approach to counteract DENV by targeting viral proteins or host factors essential for viral replication and pathogenesis. This review gleans the recent advancements in the development of aptamer-based therapeutic agents targeting dengue virus infection. The latest advancement on aptamers targeting specific dengue virus components such as capsid protein (C), envelope domain III (E3), and nonstructural proteins (NS); and their roles in inhibiting viral replication are highlighted. Although the development of aptamers as potential therapeutics for dengue infections is still in its early stages, based on their therapeutic potentiality, they hold immense potential for dengue viral treatment.

Background: Intestinal protozoal infections caused by Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum are prevalent in Malaysia. They cause severe diarrheal diseases with symptoms such as bloody stools, abdominal pain, stomach discomfort, and bloating. These infection outbreaks have been reported in diverse socioeconomic backgrounds and geographical regions usually during the rainy season or in areas with poor sanitation. Despite the importance of these infections, data on its overall prevalence, risk factors, and diagnostic methods remain limited. Objective: The aim of this study is to systematically review and synthesize evidence on the risk factors, prevalence, and detection methods for intestinal protozoal infections in Malaysia, offering insights that are applicable to other tropical and low-income regions. Methods: Studies on intestinal protozoal infections among Malaysian patients published after January 2010 up to November 2024 will be eligible for inclusion. The eligibility criteria include studies investigating infections caused by E. histolytica, G. lamblia, and C. parvum using validated diagnostic methods such as microscopy, molecular techniques, or immunoassays. Case reports, reviews, and studies without original data will be excluded. Comprehensive database searches will be conducted in PubMed/MEDLINE, Scopus, ProQuest, Web of Science, Google Scholar, and the Cochrane Library. The reference lists of selected papers are also checked. A standardized data extraction form will be used to record study characteristics, outcomes, and associated variables. Risk of bias will be assessed using the Joanna Briggs Institute tools and Newcastle-Ottawa Scale approach. Data synthesis will utilize a random effects model to estimate pooled prevalence and identify risk factors associated with these infections. Subgroup analyses will examine variations by geographic region and diagnostic method. Statistical heterogeneity will be assessed using I2 statistic and meta-regression. Publication bias will be assessed using Egger and Begg funnel plot test. The results are reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results: This systematic review was funded in June 2024. Database searches were started in July 2024, and we identified 1652 papers as of December 2024 for screening. Completion of study screening is anticipated by May 2025, with data extraction and analysis expected to conclude by December 2025. Conclusions: Our study will address critical knowledge gaps in the epidemiology and risk factors of intestinal protozoal infections in Malaysia. Study limitations include potential bias in study selection, heterogeneity in diagnostic methods, and differences in the reporting quality of the included studies. Our findings will provide valuable insights into the prevalence of these infections, the associated risk factors, and the diagnostic techniques employed, which should strengthen public health measures, improve diagnostic procedures, and guide future research to reduce the prevalence of intestinal protozoal infections in Malaysia. Trial Registration: PROSPERO (International Prospective Registry of Systematic Reviews) registration CRD42023456199; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023456199 International Registered Report Identifier (IRRID): DERR1-10.2196/66350

Background: Encephalitis is the most common infectious disease of the central nervous system and is associated with high morbidity, mortality, and disability. Therefore, rapid and accurate diagnosis is crucial to provide patients with timely and appropriate therapeutic intervention. In this study, a comprehensive systematic review with meta-analysis will be conducted to summarize the available data and evaluate the diagnostic accuracy of multiplex real-time polymerase chain reaction (PCR) in the detection of viral encephalitis. Methods: We will search PubMed, MEDLINE, EMBASE, Web of Science (WoS), Scopus and Cochrane Library databases for studies evaluating the diagnostic accuracy of multiplex PCR for the diagnosis of encephalitis caused by viruses from January 2014 to December 2024. Observational study designs with full text will be exported and included. Risk of bias will be assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Analyses will be performed using the “mada” package of R software (R Foundation for Statistical Computing, Vienna, Austria), and the Summary Receiver Operating Characteristic (SROC) will be calculated using the “midas” package of STATA version 15.0 (Stata Corp., College Station, TX, USA). Certainty of evidence will be performed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) software. Results: The results will provide clinical evidence for the diagnostic accuracy of the multiplex PCR assay for the detection of viruses that cause encephalitis, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-). Finally, we intent to submit this systematic review and meta-analysis to a peer-reviewed journal for publication. Conclusion: This systematic review aims to provide current evidence for multiplex PCR assay for the diagnosis of viruses causing encephalitis. Importantly, this study focuses on the use of multiplex PCR for viral diagnosis and helps clinicians and patients to better understand its role in the diagnosis of CNS diseases. Systematic review registration: PROSPERO registration number: CRD42023485942

BACKGROUND Intestinal protozoal infections caused by Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum are prevalent in Malaysia. They cause severe diarrheal diseases with symptoms such as bloody stools, abdominal pain, stomach discomfort, and bloating. These infection outbreaks have been reported in diverse socioeconomic backgrounds and geographical regions usually during the rainy season or in areas with poor sanitation. Despite the importance of these infections, data on its overall prevalence, risk factors, and diagnostic methods remain limited. OBJECTIVE The aim of this study is to systematically review and synthesize evidence on the risk factors, prevalence, and detection methods for intestinal protozoal infections in Malaysia, offering insights that are applicable to other tropical and low-income regions. METHODS Studies on intestinal protozoal infections among Malaysian patients published after January 2010 up to November 2024 will be eligible for inclusion. The eligibility criteria include studies investigating infections caused by E. histolytica, G. lamblia, and C. parvum using validated diagnostic methods such as microscopy, molecular techniques, or immunoassays. Case reports, reviews, and studies without original data will be excluded. Comprehensive database searches will be conducted in PubMed/MEDLINE, Scopus, ProQuest, Web of Science, Google Scholar, and the Cochrane Library. The reference lists of selected papers are also checked. A standardized data extraction form will be used to record study characteristics, outcomes, and associated variables. Risk of bias will be assessed using the Joanna Briggs Institute tools and Newcastle-Ottawa Scale approach. Data synthesis will utilize a random effects model to estimate pooled prevalence and identify risk factors associated with these infections. Subgroup analyses will examine variations by geographic region and diagnostic method. Statistical heterogeneity will be assessed using I2 statistic and meta-regression. Publication bias will be assessed using Egger and Begg funnel plot test. The results are reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS This systematic review was funded in June 2024. Database searches were started in July 2024, and we identified 1652 papers as of December 2024 for screening. Completion of study screening is anticipated by May 2025, with data extraction and analysis expected to conclude by December 2025. CONCLUSIONS Our study will address critical knowledge gaps in the epidemiology and risk factors of intestinal protozoal infections in Malaysia. Study limitations include potential bias in study selection, heterogeneity in diagnostic methods, and differences in the reporting quality of the included studies. Our findings will provide valuable insights into the prevalence of these infections, the associated risk factors, and the diagnostic techniques employed, which should strengthen public health measures, improve diagnostic procedures, and guide future research to reduce the prevalence of intestinal protozoal infections in Malaysia. CLINICALTRIAL PROSPERO (International Prospective Registry of Systematic Reviews) registration CRD42023456199; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023456199 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/66350

A myrid of aptamers were isolated thus far against SARS-CoV-2 by using in silico selection.

Introduction: One of the key instruments used to assess attention-deficit/hyperactivity disorder (ADHD) in children and adolescents is the ADHD Rating Scale-5. This study aimed to test the psychometric characteristics of the ADHD Rating Scale-5 teacher version (ADHD-T) in Dari among school-aged children in Kabul City. Methods: Face and content validity, explanatory factor analysis (EFA), confirmatory factor analysis (CFA) and reliability of the questionnaire were conducted. The structure, validity, and reliability of the scales were evaluated using the translated versions of the ADHD-T questionnaires for the assessment of ADHD in children. Teachers completed the ADHD-T-Dari on behalf of three hundred and fifty-eight public primary school students. Results: Face validity, content quality, and internal consistency of the ADHD-T-Dari were excellent. Significant collinearity was found between the items of the inattention and/or hyperactivity-impulsivity domains of the ADHD-T-Dari. The Kaiser-Meyer-Olkin index was 0.913 and was satisfactory. The two-factor model of the scale showed a better fit with an RMSEA of 0.065, a CMIN/ df of 20.501, and a CFI of 905 compared to the one- and three-factor models of ADHD-T-Dari. The Cronbach’s alpha for the total ADHD-T-Dari scale with 18 items was 0.898, while it was 0.851 and 0.847 for the inattention and/or hyperactivity-impulsivity subscales with 9 items each. Conclusion: The exploratory and CFA showed that the psychometric qualities have strong concept validity and very good psychometric properties with good reliability. Therefore, the ADHD-T-Dari is valid, reliable, and suitable for the assessment of ADHD symptoms in Afghan school children and adolescents.

Diseases caused by Rickettsiales are often overlooked, although they pose important public health concerns. The Rickettsiales family comprises a broad range of intracellular bacteria with distinct evolutionary adaptations, making the development of treatment measures to combat infections, such as vaccines or antibiotics, a challenge. Interestingly, the outer membrane protein A (OmpA) was found to exist in the cell surface of most human pathogenic bacteria in the order Rickettsiales. However, knowledge about OmpA in each species and strain is scattered and ambiguous. In this study, we systematically compiled the existing information on OmpA and its relationship with human pathogenic rickettsiae to serve as a reference for future research. A comprehensive literature search was conducted using specific keywords across five databases. According to the literature, OmpA of spotted fever group rickettsia plays a crucial role as an adhesin and invasin that directly interacts with the surface of mammalian host cells to mediate bacterial localization in host cells. The presence of a premature stop codon in the amino acid sequence resulted in the secretion of non-functional OmpA, which is one of the main reasons for rickettsial strains or species to become avirulent. Similarly, OmpA also functions as an important adhesin in the Anaplasma family when it interacts with the sLex and sLex-like glycan of myeloid and endothelial cells, respectively. However, the OmpA of Anaplasma must be co-functional with the other two adhesins to promote bacterial internalization. Interestingly, certain sites in the amino acid residues of Ehrlichia and Orientia OmpA are predicted to be homologous to the binding domain region of Anaplasma OmpA. It is therefore suggested that OmpA is an important adhesin for bacteria to bind to their specific mammalian host cells.

Despite reports on the efficacy of proprotein convertase subtilisin-Kexin type 9 (PCSK9) inhibitors as a potent lipid-lowering agent in various large-scale clinical trials, the anti-atherogenic properties of PCSK9 inhibitors in reducing PCSK9 and atherogenesis biomarkers via the NF-ĸB and eNOS pathway has yet to be established. This study aimed to investigate the effects of PCSK9 inhibitors on PCSK9, targeted early atherogenesis biomarkers, and monocyte binding in stimulated human coronary artery endothelial cells (HCAEC). HCAEC were stimulated with lipopolysaccharides (LPS) and incubated with evolocumab and alirocumab. The protein and gene expression of PCSK9, interleukin-6 (IL-6), E-selectin, intercellular adhesion molecule 1 (ICAM-1), nuclear factor kappa B (NF-ĸB) p65, and endothelial nitric oxide synthase (eNOS) were measured using ELISA and QuantiGene plex, respectively. The binding of U937 monocytes to endothelial cell capacity was measured by the Rose Bengal method. The anti-atherogenic effects of evolocumab and alirocumab were contributed to by the downregulation of PCSK9, early atherogenesis biomarkers, and the significant inhibition of monocyte adhesion to the endothelial cells via the NF-ĸB and eNOS pathways. These suggest the beyond cholesterol-lowering beneficial effects of PCSK9 inhibitors in impeding atherogenesis during the initial phase of atherosclerotic plaque development, hence their potential role in preventing atherosclerosis-related complications.