The burden of HEV-related acute liver failure in Bangladesh, China and India: a systematic review and meta-analysis.

BACKGROUND: Hepatitis E can potentially progress to HEV-related acute liver failure (HEV-ALF). East and South Asia bear a substantial burden of HEV infection, with Bangladesh, China, and India facing the most severe threat in this region. Therefore, we conducted a systematic review and meta-analysis to evaluate the burden of HEV-ALF in these three high-risk countries. METHODS: A systematic literature search was performed utilizing PubMed, the Cochrane Library, Medline, Embase, and Web of Science databases. Studies in English or Chinese that reported data on the burden of HEV-ALF in Bangladesh, China and India were included. Outcomes were pooled with meta-analysis utilizing R software. Estimates were calculated with random-effects models, and subgroup analysis and sensitivity analysis were conducted to address heterogeneity. Egger's test and Begg's test were performed to assess publication bias. RESULTS: A total of 20 eligible studies were included in this study. The pooled HEV-attributable proportion of viral-related acute liver failure was estimated to be 40.0% (95% CI: 0.28-0.52), 30.0% (95% CI: 0.18-0.44), and 61.0% (95% CI: 0.49-0.72) among non-pregnant individuals in India, China and Bangladesh, while in Indian pregnant females, it was 71.0% (95% CI: 0.62-0.79). The combined prevalence among non-pregnant HEV-infected participants was 28.0% (95% CI: 0.20-0.37) and 10.0% (95% CI: 0.01-0.28) in India and China, and it was 34.0% (95% CI: 0.27-0.42) in Indian pregnant females with HEV infection. The overall mortality of HEV-ALF was estimated to be 32.0% (95% CI: 0.23-0.42) and 64.0% (95% CI: 0.50-0.77) among the non-pregnant and the pregnant participants in India, and it was 23.0% (95% CI: 0.14-0.34) in Chinese non-pregnant participants. CONCLUSIONS: The burden of HEV-ALF in Bangladesh, China, and India is non-negligible despite geographic and population heterogeneity. The prevention of HEV infection and early recognition of HEV-ALF are of great significance, especially in high-risk countries and populations. REGISTRATION: PROSPERO registration ID is CRD42022382101.

Tiratricol inhibits yellow fever virus replication through targeting viral RNA-dependent RNA polymerase of NS5.

Yellow fever virus (YFV) infection is a major public concern that threatens a large population in South America and Africa. No specific antiviral drugs are available for treating yellow fever. Here, we report that tiratricol (triiodothyroacetic acid, TRIAC), a clinically approved drug used to treat thyroid hormone resistance syndrome (THRS), is a potent YFV inhibitor both in host cells and in animal models.An in vitro study demonstrates that TRIAC remarkably suppresses viral RNA synthesis and protein expression in a dose-dependent manner in human hepatoma cell lines (Huh-7) with an EC50 value of 2.07 µM and a CC50 value of 385.77 µM respectively. The surface plasmon resonance assay and molecular docking analysis indicate that TRIAC hinders viral replication by binding to the RNA-dependent RNA polymerase (RdRp) domain of viral nonstructural protein NS5, probably through interacting with the active sites of RdRp.The inhibitory effect of TRIAC in vivo is also confirmed in 3-week old C57BL/6 mice challenged with YFV infection, from which the survival of the mice as well as lesions and infection in their tissues and serum issignificantly promoted following oral administration of TRIAC (0.2 mg/kg/day). Additionally, TRIAC shows a broad-spectrum antiviral activity against multiple flaviviruses such as TBEV, WNV,ZIKV, andJEV in vitro. Our data demonstrate that the TH analogue TRIAC is an effective anti-YFV compound and may act as a potential therapeutic candidate for the treatment of YFV infection if its clinical importance is determined in patients in future.

Evaluation of the efficacy, safety and influencing factors of concomitant and sequential administration of viral respiratory infectious disease vaccines: a systematic review and meta-analysis.

Background: There is no clear conclusion on the immunogenicity and adverse events of concomitant administration the viral respiratory infectious disease vaccines. We aimed to evaluate the impact of concomitant administering viral respiratory infectious disease vaccines on efficiencies, safety and influencing factors. Methods: This meta-analysis included studies from PubMed, Embase, Cochrane Central Register of Clinical Trials, Web of Science, WHO COVID-19 Research, and ClinicalTrials.gov databases. Randomized controlled trials of the adult participants concomitant administered with viral respiratory infectious disease vaccine and other vaccines were included. The main outcomes were the seroconversion rate and seroprotection rate of each vaccine. Used the Mantel-Haenszel fixed effects method as the main analysis to estimate the pooled RRs and the corresponding 95% confidence intervals. The risk of bias for each trial was assessed using the Cochrane Handbook for Systematic Reviews of Interventions, while evidence certainty was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Results: A total of 21 studies comprising 14060 participants with two types of vaccines were retained for the meta-analysis. Concomitant immunization reduced the geometric mean titer (RR: 0.858, 95% CI: (0.785 to 0.939)) and the geometric mean fold rise (0.754 (0.629 to 0.902)) in the SARS-COV-2 vaccine group but increased the seroconversion rate (1.033 (1.0002 to 1.067)) in the seasonal influenza vaccine group. Concomitant administration were influenced by the type of vaccine, adjuvant content, booster immunization, and age and gender of the recipient. Conclusion: This meta-analysis suggested that the short-term protection and safety of concomitant administered were effective. Appropriate adjuvants, health promotion and counselling and booster vaccines could improve the efficiency and safety of Concomitant vaccination. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022343709.

Evaluation of the Therapeutic Effect of Antibiotics on Scrub Typhus: A Systematic Review and Network Meta-Analysis.

Background: To explore the efficacy and safety of drugs in patients with scrub typhus. Methods: For this systematic review and network meta-analysis, we searched PubMed, Embase, Web of Science, Cochrane Central Register of Clinical Trials, China National Knowledge Infrastructure (CNKI), and Wanfang data (WF) up to December 2021. All randomized controlled trials (RCTs) of antibiotics used to treat scrub typhus were included without language or date restrictions. The overall effectiveness was evaluated from 4 perspectives: cure rate (CR), defervescence time (DT), gastrointestinal symptoms-adverse events (GS-AD), and abnormal blood count-adverse events (ABC-AD). The quality of evidence was evaluated using the Cochrane Risk of Bias tool and GRADE system. Results: Sixteen studies involving 1,582 patients were included to evaluate 7 drugs, namely, azithromycin, doxycycline, chloramphenicol, tetracycline, rifampin, moxifloxacin, and telithromycin. In this network meta-analysis, rifampicin (82%) and chloramphenicol (65%) were more effective in terms of CR, and moxifloxacin (3%) from the quinolone family was the worst. Azithromycin caused the fewest events in terms of ABC-AD. No differences were found in this network meta-analysis (NMA) in terms of DT and GS-AD. Conclusions: Rifampicin was associated with the highest CR benefit and the lowest risk of DT when used to treat patients with scrub typhus, except in areas where tuberculosis (TB) was endemic. Azithromycin was found to be better in CR and was associated with a lower probability of GS-AD and ABC-AD; therefore, it may be considered to treat pregnant women and children. Moxifloxacin had a much lower CR than other drugs and is, therefore, not recommended for the management of scrub typhus. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021287837.

Meta-analysis of the effects of ambient temperature and relative humidity on the risk of mumps.

Many studies have shown that the relationship between ambient temperature, relative humidity and mumps has been highlighted. However, these studies showed inconsistent results. Therefore, the goal of our study is to conduct a meta-analysis to clarify this relationship and to quantify the size of these effects as well as the potential factors. Systematic literature researches on PubMed, Embase.com, Web of Science Core Collection, Cochrane library, Chinese BioMedical Literature Database (CBM) and China National Knowledge Infrastructure (CNKI) were performed up to February 7, 2022 for articles analyzing the relationships between ambient temperature, relative humidity and incidence of mumps. Eligibility assessment and data extraction were conducted independently by two researchers, and meta-analysis was performed to synthesize these data. We also assessed sources of heterogeneity by study region, regional climate, study population. Finally, a total of 14 studies were screened out from 1154 records and identified to estimate the relationship between ambient temperature, relative humidity and incidence of mumps. It was found that per 1 °C increase and decrease in the ambient temperature were significantly associated with increased incidence of mumps with RR of 1.0191 (95% CI: 1.0129-1.0252, I2 = 92.0%, Egger's test P = 0.001, N = 13) for per 1 °C increase and 1.0244 (95% CI: 1.0130-1.0359, I2 = 86.6%, Egger's test P = 0.077, N = 9) for per 1 °C decrease. As to relative humidity, only high effect of relative humidity was slightly significant (for per 1 unit increase with RR of 1.0088 (95% CI: 1.0027-1.0150), I2 = 72.6%, Egger's test P = 0.159, N = 9). Subgroup analysis showed that regional climate with temperate areas may have a higher risk of incidence of mumps than areas with subtropical climate in cold effect of ambient temperature and low effect of relative humidity. In addition, meta-regression analysis showed that regional climate may affect the association between incidence of mumps and cold effect of ambient temperature. Our results suggest ambient temperature could affect the incidence of mumps significantly, of which both hot and cold effect of ambient temperature may increase the incidence of mumps. Further studies are still needed to clarify the relationship between the incidence of mumps and ambient temperature outside of east Asia, and many other meteorological factors. These results of ambient temperature are important for establishing preventive measures on mumps, especially in temperate areas. The policy-makers should pay more attention to ambient temperature changes and take protective measures in advance.

Rifapentine is an entry and replication inhibitor against yellow fever virus both in vitro and in vivo.

Yellow fever virus (YFV) infection is a major public concern that threatens a large population in South America and Africa. No specific anti-YFV drugs are available till now. Here, we report that rifapentine is a potent YFV inhibitor in various cell lines by high-throughput drugs screening, acting at both cell entry and replication steps. Kinetic test and binding assay suggest that rifapentine interferes the viral attachment to the target cells. The application of YFV replicon and surface plasmon resonance assay indicates that rifapentine suppresses viral replication by binding to the RNA-dependent RNA polymerase (RdRp) domain of viral nonstructural protein NS5. Further molecular docking suggests that it might interact with the active centre of RdRp. Rifapentine significantly improves the survival rate, alleviates clinical signs, and reduces virus load and injury in targeted organs both in YFV-infected type I interferon receptor knockout A129-/- and wild-type C57 mice. The antiviral effect in vivo is robust during both prophylactic intervention and therapeutic treatment, and the activity is superior to sofosbuvir, a previously reported YFV inhibitor in mice. Our data show that rifapentine may serve as an effective anti-YFV agent, providing promising prospects in the development of YFV pharmacotherapy.

A cross-sectional serum investigation of a clustering hepatitis C virus infection in Southwest China.

Serum samples were collected in a village with a clustering hepatitis C virus (HCV) infection. HCV antibody, HCV RNA loads, liver function indexes, HCV envelope antibody, and neutralizing activity were assessed. Among 851 adult sera, 342 samples were positive for anti-HCV. Of these positive samples, 254 (74.3%) were HCV RNA positive (≥800 copies/mL). None of the 69 children's sera were positive for HCV antibody or RNA. Among the HCV antibody positive sera, alanine aminotransferase, and aspartate aminotransferase levels increased with the higher virus loads, but decreased when virus loads were higher than 1 × 10 6 copies/mL. HCV envelope antibody and neutralizing antibody levels increased with viral load.