Detection of coronaviruses in insectivorous bats of Fore-Caucasus, 2021.

Coronaviruses (CoVs) pose a huge threat to public health as emerging viruses. Bat-borne CoVs are especially unpredictable in their evolution due to some unique features of bat physiology boosting the rate of mutations in CoVs, which is already high by itself compared to other viruses. Among bats, a meta-analysis of overall CoVs epizootiology identified a nucleic acid observed prevalence of 9.8% (95% CI 8.7-10.9%). The main objectives of our study were to conduct a qPCR screening of CoVs' prevalence in the insectivorous bat population of Fore-Caucasus and perform their characterization based on the metagenomic NGS of samples with detected CoV RNA. According to the qPCR screening, CoV RNA was detected in 5 samples, resulting in a 3.33% (95% CI 1.1-7.6%) prevalence of CoVs in bats from these studied locations. BetaCoVs reads were identified in raw metagenomic NGS data, however, detailed characterization was not possible due to relatively low RNA concentration in samples. Our results correspond to other studies, although a lower prevalence in qPCR studies was observed compared to other regions and countries. Further studies should require deeper metagenomic NGS investigation, as a supplementary method, which will allow detailed CoV characterization.

Gut microbiota of bats: pro-mutagenic properties and possible frontiers in preventing emerging disease.

Bats are potential natural reservoirs for emerging viruses, causing deadly human diseases, such as COVID-19, MERS, SARS, Nipah, Hendra, and Ebola infections. The fundamental mechanisms by which bats are considered "living bioreactors" for emerging viruses are not fully understood. Some studies suggest that tolerance to viruses is linked to suppressing antiviral immune and inflammatory responses due to DNA damage by energy generated to fly. Our study reveals that bats' gut bacteria could also be involved in the host and its microbiota's DNA damage. We performed screening of lactic acid bacteria and bacilli isolated from bats' feces for mutagenic and oxidative activity by lux-biosensors. The pro-mutagenic activity was determined when expression of recA increased with the appearance of double-strand breaks in the cell DNA, while an increase of katG expression in the presence of hydroxyl radicals indicated antioxidant activity. We identified that most of the isolated bacteria have pro-mutagenic and antioxidant properties at the same time. This study reveals new insights into bat gut microbiota's potential involvement in antiviral response and opens new frontiers in preventing emerging diseases originating from bats.

High sustained virological response rates using imported generic direct acting antiviral treatment for hepatitis C.

BACKGROUND: High prices of direct acting antivirals (DAAs) for hepatitis C virus (HCV) can lead to restrictions on access to treatment in high- and middle-income countries. An increasing number of people in these countries are treating their HCV infection with generic drugs produced in India, China, Bangladesh or Egypt. This analysis assessed the efficacy of generic imported DAAs. METHODS: Patients sourced generic versions of sofosbuvir (SOF), ledipasvir (LDV) and daclatasvir (DCV) from suppliers in India, Bangladesh, China and Egypt via three buyers' clubs. The choice of DAAs and the length of treatment were determined on baseline RNA levels, HCV genotype and stage of fibrosis. Patient HCV RNA levels were evaluated pre-treatment, during treatment, at end of treatment (EOT) and then for sustained virological response (SVR) at 4, 12, and 24 weeks, normally by a treating clinician. RESULTS: Overall 616 patients submitted results: 199 from an Australian buyers' club, 205 from a South-east Asian buyers' clubs, and 212 from an Eastern European buyers' club. Of the 616 patients treated, 276 received SOF/LDV (35 with ribavirin [RBV]) and 340 received SOF/DCV (61 with RBV). At baseline, 61% were male, 52% had HCV genotype 1 and 11% had liver cirrhosis. The mean age was 44.3 years and the mean baseline HCV RNA was 6.9 log10 IU/mL. A rapid virological response (RVR) was observed in 314/375 (84%) of the patients treated. Based on currently available data, the percentage of patients with HCV RNA below the lower limit of quantification (LLoQ) was 99% (234/237) at EOT, 99% (299/303) at SVR4 and 99% (247/250) at SVR12. CONCLUSIONS: In this analysis, treatment with imported generic DAAs achieved high rates of HCV RNA undetectability at the end of treatment, and SVR12 in 99% of patients evaluated to date. Mass treatment with generic DAAs is a feasible and economical alternative route of accessing curative DAAs, where the high prices for branded alternatives prevent access to treatment.

Access to hepatitis C treatment for people who inject drugs in low and middle income settings: Evidence from 5 countries in Eastern Europe and Asia.

BACKGROUND: People who inject drugs (PWID) are disproportionately affected by the hepatitis C (HCV) epidemic. Of the estimated 16 million PWID worldwide, approximately 8 million live with chronic HCV, and around 26% and 23% of the global HCV infections among PWID occur in East/Southeast Asia and Eastern Europe respectively. Globally, few PWID have access to treatment for HCV. METHODS: We conducted a systematic literature review and internet survey in 2014 to document the burden of disease, access to diagnosis and treatment and the existence of national policy and treatment guidelines for HCV. We included Georgia, Russia, Ukraine, Myanmar and Indonesia as countries with injection drug use epidemics. FINDINGS: HCV antibody prevalence among the general population ranged from 0.80% in Indonesia to 5% in Georgia, and among PWID from 48.1% in Myanmar to 92% in Georgia. PWID carried a significant burden of disease, ranging from 2.7% in Indonesia to 40.4% in Russia. Yearly treatment uptake was under 1% for the general population and PWID in all countries. Diagnostic tools and disease staging investigations as well as pegylated interferon/ribavirin treatment were available at a range of prices. Despite policy and treatment protocols for HCV in the majority of countries, strategies focusing on PWID were largely absent. CONCLUSION: PWID are a priority group for treatment, and access to treatment should be based on sound national policy, accessible public treatment programmes and functional surveillance systems.