Susceptible and Protective HLA Class 1 Alleles against Dengue Fever and Dengue Hemorrhagic Fever Patients in a Malaysian Population

BACKGROUND: The human leukocyte antigen alleles have been implicated as probable genetic markers in predicting the susceptibility and/or protection to severe manifestations of dengue virus (DENV) infection. In this present study, we aimed to investigate for the first time, the genotype variants of HLA Class 1(-A and -B) of DENV infected patients against healthy individuals in Malaysia. METHODOLOGY/PRINCIPAL FINDINGS: This study was carried out with 92 dengue disease patients and 95 healthy controls from three different ethnic groups (Malay, Chinese and Indian) in Malaysia. All patients with clinical and laboratory confirmation of DENV infection were typed for the HLA-A and B loci, using polymerase chain reaction-sequence specific primer techniques. In our total population, a significant increase for HLA-B*53 (P = 0.042, Pc = 1.008) allele and a significant decrease for A*03 (P = 0.015, Pc = 0.18, OR = 5.23, 95% CI = 1.19-23.02) and B*18 (P = 0.017, Pc = 0.408) alleles were noted in DHF patients as compared to healthy donors. We also observed that in the Malay DHF patients, allele B*13 (P = 0.049, Pc = 1.176, OR = 0.18, 95% CI = 0.03-0.90) was present at a significantly higher frequency in this population while allele HLA-B*18 (P = 0.024, Pc = 0.576) was seen to be negatively associated with DHF. CONCLUSIONS/SIGNIFICANCE: These are the first findings on genetic polymorphisms in our population and we conclude that: (1) In our total population, HLA-B*53 probably involve in disease susceptibility, while the HLA-A*03 and HLA-B*18 may confer protection from progression to severe disease; (2) In the Malay population, HLA-B*13 and B*18 are probably associated in disease susceptibility and protection, respectively. These results could furnish as a valuable predictive tool to identify ethnically different individuals at risk and/or protection from severe forms of DENV infection and would provide valuable informations for the design of future dengue vaccine

Benzotiazoles sustituidos y sus aplicaciones terapéuticas para el tratamiento de enfermedades humanas

La presente invención se refiere a una familia de benzotialoles diferentemente sustituidos que presentan actividad inhibitoria de la enzima caseína quinasa 1 (CK-1), por lo que son útiles para el tratamiento o prevención de enfermedades mediadas por esta enzima, especialmente, enfermedades relacionadas con el ritmo circadiano, enfermedades inflamatorias, autoinmunes, psiquiátricas, neurodegenerativas, neurológicas, oftalmológicas, así como para inducir regeneración celularPeer reviewedConsejo Superior de Investigaciones CientíficasB1 Patente sin examen previ

Cancers in the TREAT Asia HIV Observational Database (TAHOD): a retrospective analysis of risk factors

<p>Abstract</p> <p>Background</p> <p>This retrospective survey describes types of cancers diagnosed in HIV-infected subjects in Asia, and assesses risk factors for cancer in HIV-infected subjects using contemporaneous HIV-infected controls without cancer.</p> <p>Methods</p> <p>TREAT Asia HIV Observational Database (TAHOD) sites retrospectively reviewed clinic medical records to determine cancer diagnoses since 2000. For each diagnosis, the following data were recorded: date, type, stage, method of diagnosis, demographic data, medical history, and HIV-related information. For risk factor analyses, two HIV-infected control subjects without cancer diagnoses were also selected. Cancers were grouped as AIDS-defining cancers (ADCs), and non-ADCs. Non-ADCs were further categorized as being infection related (NADC-IR) and unrelated (NADC-IUR).</p> <p>Results</p> <p>A total of 617 patients were included in this study: 215 cancer cases and 402 controls from 13 sites. The majority of cancer cases were male (71%). The mean age (SD) for cases was 39 (10.6), 46 (11.5) and 44 (13.7) for ADCs, NADC-IURs and NADCs-IR, respectively. The majority (66%) of cancers were ADCs (16% Kaposi sarcoma, 40% non-Hodgkin's lymphoma, and 9% cervical cancer). The most common NADCs were lung (6%), breast (5%) and hepatocellular carcinoma and Hodgkin's lymphoma (2% each). There were also three (1.4%) cases of leiomyosarcoma reported in this study. In multivariate analyses, individuals with CD4 counts above 200 cells/mm³were approximately 80% less likely to be diagnosed with an ADC (p < 0.001). Older age (OR: 1.39, p = 0.001) and currently not receiving antiretroviral treatment (OR: 0.29, p = 0.006) were independent predictors of NADCs overall, and similarly for NADCs-IUR. Lower CD4 cell count and higher CDC stage (p = 0.041) were the only independent predictors of NADCs-IR.</p> <p>Conclusions</p> <p>The spectrum of cancer diagnoses in the Asia region currently does not appear dissimilar to that observed in non-Asian HIV populations. One interesting finding was the cases of leiomyosarcoma, a smooth-muscle tumour, usually seen in children and young adults with AIDS, yet overall quite rare. Further detailed studies are required to better describe the range of cancers in this region, and to help guide the development of screening programmes.</p

Changing predominant SARS-CoV-2 lineages drives successive COVID-19 waves in Malaysia, February 2020 to March 2021

Malaysia has experienced three waves of coronavirus disease 2019 (COVID-19) as of March 31, 2021. We studied the associated molecular epidemiology and SARS-CoV-2 seroprevalence during the third wave. We obtained 60 whole-genome SARS-CoV-2 sequences between October 2020 and January 2021 in Kuala Lumpur/Selangor and analyzed 989 available Malaysian sequences. We tested 653 residual serum samples collected between December 2020 to April 2021 for anti-SARS-CoV-2 total antibodies, as a proxy for population immunity. The first wave (January 2020) comprised sporadic imported cases from China of early Pango lineages A and B. The second wave (March–June 2020) was associated with lineage B.6. The ongoing third wave (from September 2020) was propagated by a state election in Sabah. It is due to lineage B.1.524 viruses containing spike mutations D614G and A701V. Lineages B.1.459, B.1.470, and B.1.466.2 were likely imported from the region and confined to Sarawak state. Direct age-standardized seroprevalence in Kuala Lumpur/Selangor was 3.0%. The second and third waves were driven by super-spreading events and different circulating lineages. Malaysia is highly susceptible to further waves, especially as alpha (B.1.1.7) and beta (B.1.351) variants of concern were first detected in December 2020/January 2021. Increased genomic surveillance is critical

Changing predominant SARS-CoV-2 lineages drives successive COVID-19 waves in Malaysia, February 2020 to March 2021

Malaysia has experienced three waves of coronavirus disease 2019 (COVID-19) as of March 31, 2021. We studied the associated molecular epidemiology and SARS-CoV-2 seroprevalence during the third wave. We obtained 60 whole-genome SARS-CoV-2 sequences between October 2020 and January 2021 in Kuala Lumpur/Selangor and analyzed 989 available Malaysian sequences. We tested 653 residual serum samples collected between December 2020 to April 2021 for anti-SARS-CoV-2 total antibodies, as a proxy for population immunity. The first wave (January 2020) comprised sporadic imported cases from China of early Pango lineages A and B. The second wave (March–June 2020) was associated with lineage B.6. The ongoing third wave (from September 2020) was propagated by a state election in Sabah. It is due to lineage B.1.524 viruses containing spike mutations D614G and A701V. Lineages B.1.459, B.1.470, and B.1.466.2 were likely imported from the region and confined to Sarawak state. Direct age-standardized seroprevalence in Kuala Lumpur/Selangor was 3.0%. The second and third waves were driven by super-spreading events and different circulating lineages. Malaysia is highly susceptible to further waves, especially as alpha (B.1.1.7) and beta (B.1.351) variants of concern were first detected in December 2020/January 2021. Increased genomic surveillance is critical

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ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network) II: protocol for case based antimicrobial resistance surveillance

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia: Correlations between clinical, phenotypic, genotypic characteristics and mortality in a tertiary teaching hospital in Malaysia

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a serious infection that can result in significant morbidity and mortality. A retrospective cohort study was conducted to determine the predictors of mortality in patient with MRSA bacteremia correlating with clinical, phenotypic and genotypic characteristics of the relevant strains. Most of the bacteremia cases were healthcare-associated (P < 0.0001). Older age (P < 0.0001) and comorbidities (diabetes mellitus, hypertension and chronic kidney disease) were identified as the risk factors for MRSA bacteremia. All the strains were sensitive to vancomycin. Most MRSA strains causing bacteremia belonged to SCCmec type III-ST239 and exhibited pulsotype H. According to the multivariate analysis, age ≥ 60 years old (P = 0.022), female gender (P = 0.0003), pneumonia (P = 0.011) as source of infection as well as high APACHE II, Charlson comorbidity Index and Pitt's bacteremia scores were significantly associated with patient's mortality. There were emergence of MRSA clones such as SCCmec type I-ST152, SCCmec type V-ST45 and SCCmec type V-ST951 that was discovered for the first time in Malaysia. To our knowledge, this is the first study correlating the clinical, phenotypic and genotypic characteristics of patients with MRSA bacteremia as well as determining the risk factors for mortality in Malaysian hospital