Novel genetic variants of Hepatitis B Virus in fulminant hepatitis

Fulminant hepatitis (FH) is a life-threatening liver disease characterised by intense immune attack and massive liver cell death. The common precore stop codon mutation of hepatitis B virus (HBV), A1896, is frequently associated with FH, but lacks specificity. This study attempts to uncover all possible viral nucleotides that are specifically associated with FH through a compiled sequence analysis of FH and non-FH cases from acute infection. We retrieved 67 FH and 280 acute non-FH cases of hepatitis B from GenBank and applied support vector machine (SVM) model to seek candidate nucleotides highly predictive of FH. Six best candidates with top predictive accuracy, 92.5%, were used to build a SVM model; they are C2129 (85.3%), T720 (83.0%), Y2131 (82.4%), T2013 (82.1%),K2048 (82.1%), and A2512 (82.1%). This model gave a high specificity (99.3%), positive predictive value (95.6%), and negative predictive value (92.1%), but only moderate sensitivity (64.2%).We successfully built a SVM model comprising six variants that are highly predictive and specific for FH: four in the core region and one each in the polymerase and the surface regions. These variants indicate that intracellular virion/core retention could play an important role in the progression to FH

The oxidative stress of hyperglycemia and the inflammatory process in endothelial cells

Hyperglycemia and insulin resistance are common in many critically ill patients. Hyperglycemia increases the production of reactive oxygen species in cells, stimulates the production of the potent proinflammatory cytokines IL-8 and TNF-alpha, and enhances the expression of haem oxygenase-1, an inducible stress protein. It has been shown that administration of insulin and the semi-essential amino acid glutamine have been beneficial to the septic patient. The aim of our study is to test whether these two molecules, glutamine and insulin used in combination attenuate the proinflammatory responses in endothelial cells which have been triggered by hyperglycaemia. Our results demonstrate that a combination of insulin and glutamine are significantly more effective in reducing the expression of IL-8, TNF-alpha and HO-1 than insulin or glutamine alone

Viral load and sequence analysis reveal the symptom severity, diversity, and transmission clusters of Rhinovirus infections

Background:Rhinovirus (RV) is one of the main viral etiologic agents of acute respiratory illnesses. Despite the heightened disease burden caused by RV, the viral factors that increase the severity of RV infection, the transmission pattern, and seasonality of RV infections remain unclear. Methods: An observational study was conducted among 3935 patients presenting with acute upper respiratory illnesses in the ambulatory settings between 2012 and 2014. Results: The VP4/VP2 gene was genotyped from all 976 RV-positive specimens, where the predominance of RV-A (49%) was observed, followed by RV-C (38%) and RV-B (13%). A significant regression in median nasopharyngeal viral load (VL) (P < .001) was observed, from 883 viral copies/µL at 1-2 days after symptom onset to 312 viral copies/µL at 3-4 days and 158 viral copies/µL at 5-7 days, before declining to 35 viral copies/µL at ≥8 days. In comparison with RV-A (median VL, 217 copies/µL) and RV-B (median VL, 275 copies/µL), RV-C-infected subjects produced higher VL (505 copies/µL; P < .001). Importantly, higher RV VL (median, 348 copies/µL) was associated with more severe respiratory symptoms (Total Symptom Severity Score ≥17, P = .017). A total of 83 phylogenetic-based transmission clusters were identified in the population. It was observed that the relative humidity was the strongest environmental predictor of RV seasonality in the tropical climate. Conclusions: Our findings underline the role of VL in increasing disease severity attributed to RV-C infection, and unravel the factors that fuel the population transmission dynamics of R

Influence of viral and host characteristics on clinical outcome of hepatitis B / Chook Jack Bee

Hepatitis B is a global health problem, affecting >2 billion people worldwide. Chronicity develops in >90% of neonates infected by hepatitis B virus (HBV). After several decades of the infection, about a-quarter-to-half may progress to liver cirrhosis and hepatocellular carcinoma (HCC). In contrast, more than 90% of people infected during adulthood may clear the infection, resulting in acute self-limiting hepatitis. Both virus and host may influence clinical outcome of the infection. Basal core promoter (BCP; A1762T/G1764A) and precore stop codon (G1896A) mutations have been commonly associated with cirrhosis and HCC, whereas wild-types of these mutations with acute hepatitis. These associations have been inconsistent; the disease progression may have been affected by other non-viral factors. Host iron status could be one of the important factors; iron overload increases risk of cirrhosis and HCC. It has rarely been considered in chronic hepatitis B studies. The present study is divided into two sections. The aim of the first section is to investigate the influence of viral genomic variations and host iron markers (serum iron and serum ferritin) on progression to cirrhosis and HCC, whereas the second section to identify potential viral genomic variations associated with chronicity based on in silico observation. Overlapping polymerase chain reaction (PCR) was applied to amplify viral genomic fragments. The fragments were then sequenced and assembled. Sera were also sent to clinical laboratory for testing of the iron markers. To search for candidate nucleotides associated with cirrhosis, comparative sequence analysis was performed in 20 cirrhotic cases and 20 controls, whereas for HCC, the analysis was done in 21 HCC cases and 24 controls. The most potential viral marker was then applied in larger chronic hepatitis B populations, including 216 controls, 78 cirrhosis and 39 HCC cases. Binary logistic regression analysis showed that older age, cigarette smoking, family history of cirrhosis/HCC, HBV precore wild-type, serum iron and serum ferritin were associated independently iv with HCC, whereas older age, male gender, Malay ethnicity, precore wild-type, serum iron and serum alanine aminotransferase (ALT) with cirrhosis. To search for candidate nucleotides associated with chronicity, comparative sequence analysis was conducted in 177 acute cases and 1,149 chronic cases. Binary logistic regression coupled with Bonferroni-correction identified four novel viral variants (G1171, T1785, A1786 and T3112) independently associated with acute hepatitis. These variants are located in enhancer-I-X-promoter and S promoter regions, mutations in which result in reduced viral replication and release. In conclusions, older age, precore wild-type and serum iron markers may increase the risk of progression to cirrhosis and HCC, but not to NAFLD. Cigarette smoking, male gender, Malay ethnicity and high serum ALT should also be considered. The present study has also identified novel variants (G1171, T1785, A1786 and T3112) highly specific for acute self-limited infection. These putatively replicationdefective variants may be responsible for lower rate of chronicity in some cases of HBV infection. Further in vitro and in vivo investigations are required to confirm this hypothesis

Increased Coffee Intake Reduces Circulating HBV DNA and HBsAg Levels in HBeAg-Negative Infection: A Cohort Study

Coffee is hepatoprotective and potentially antiviral; however, its anti-hepatitis B virus (anti-HBV) property is not known in humans. This study investigated the influence of coffee drinking behaviour as well as clinical and biochemical profiles of hepatitis B e antigen (HBeAg) negative participants on circulating HBV DNA and hepatitis B surface antigen (HBsAg) levels at a 24-week interval. Exactly 114 chronically HBV-infected adult participants were enrolled from the University of Malaya Medical Centre (UMMC), Malaysia. A significant reduction of HBV DNA level was observed in those drinking three or more cups of coffee per day, with a median reduction of 523 IU/mL (P = 0.003). Reduction of HBsAg level was observed in those drinking two cups per day, with a median reduction of 37 IU/mL (P &lt; 0.001). Multivariate analysis showed that increased coffee intake (P = 0.015) and lower ALT level (P = 0.033) were the significant predictors for a lower HBV DNA level, whereas increased coffee intake (P = 0.002) and having a family history of HBV infection (P = 0.021) were the significant predictors for a lower HBsAg level. These data suggest that drinking three cups or more coffee per day reduces circulating HBV DNA and HBsAg levels

Genetic diversity of Coxsackievirus A21 associated with sporadic cases of acute respiratory infections in Malaysia

10.1186/s12879-021-06148-xBMC Infectious Diseases21144

State-level differentials in COVID-19 fatality: exploring age and sex disparities in Malaysia’s pandemic experience

Abstract Issue COVID-19 has resulted in mortality worldwide and exposed vulnerabilities in public health systems. Although countries have since transitioned to the endemic phase, it is nonetheless important to identify inequities within populations to improve public health strategies in light of another health crisis. Purpose This study aims to offer deeper insights into the sex and age differentials in COVID-19 fatality across different states in Malaysia, from the pandemic’s start to the country’s transition to the endemic phase. Methodology Analyses utilized data on the number of COVID-19 cases and deaths in Malaysia from January 2020 until April 2022. Case fatality rate (CFR) was computed for each state based on sex and age groups, for four periods (January–December 2020, January–June 2021, July–December 2021, and January–April 2022). Principal component analysis (PCA) uncovered patterns in the data and produced a multivariate visualization of the COVID-19 fatality within Malaysia. Findings Findings revealed heterogeneity in fatality and identified several vulnerable states, notably in the northern region (Kelantan, Perlis) and on the East Coast (Sabah, Sarawak). A sex disparity was apparent in Kelantan as the CFR among older females was higher than their male counterparts. Sabah exhibited relatively higher CFR among the child population from 2020 to 2021. Implication The findings deepened our understanding of COVID-19 fatality complexity, providing recommendations for Malaysia’s government in preparing for future health crises. Malaysia’s case study offers lessons on the need to address regional disparities and implement targeted strategies to protect vulnerable subgroups

Application of a VP4/VP2-inferred transmission clusters in estimating the impact of interventions on rhinovirus transmission

Despite the clinical burden attributable to rhinovirus (RV) infections, the RV transmission dynamics and the impact of interventions on viral transmission remain elusive. Methods A total of 3,935 nasopharyngeal specimens were examined, from which the VP4/VP2 gene was sequenced and genotyped. RV transmission clusters were reconstructed using the genetic threshold of 0.005 substitutions/site, estimated from the global VP4/VP2 sequences. A transmission cluster is characterized by the presence of at least two individuals (represent by nodes), whose viral sequences are genetically linked (represent by undirected edges) at the estimated genetic distance threshold supported by bootstrap value of ≥ 90%. To assess the impact of facemask, pleconaril and social distancing on RV transmission clusters, trials were simulated for interventions with varying efficacy and were evaluated based on the reduction in the number of infected patients (nodes) and the reduction in the number of nodes-connecting edges. The putative impact of intervention strategies on RV transmission clusters was evaluated through 10,000 simulations