Background
Higher rates of hepatitis C virus (HCV) reinfection after viral clearance have been well described among HIV‐positive men who have sex with men (MSM) in Europe. The epidemiology of HCV ...reinfection, however, has rarely been investigated among HIV‐positive patients in Asia‐Pacific region.
Methods
We retrospectively identified HIV‐positive patients with recent HCV infection who had cleared their primary infection, either spontaneously or via treatment, between January 2011 and May 2018. All included patients were observed until 31 March 2019. HCV reinfection was defined as recurrent HCV viraemia after achieving viral clearance with anti‐HCV treatment or after spontaneous clearance.
Results
During the study period, 219 HIV‐positive patients (90.4% MSM) were diagnosed with recent HCV infection. Viral clearance with successful treatment was achieved in 108 patients (49.3%) and spontaneous clearance occurred in 20 (9.1%); of them, 18 (14.1%) acquired HCV reinfections, resulting in an incidence rate of 8.2 per 100 person‐years of follow‐up (95% CI 5.2‐13.1). With the adjusted Cox proportional hazards model, we found a higher reinfection risk in patients with syphilis (adjusted hazard ratio 10.3, 95% CI 1.4‐77.8, P = .023) compared to those without syphilis. HCV RNA testing, if performed only following syphilis and elevated aminotransferases, might miss 44.4% and 33.3% of HCV reinfections, respectively.
Conclusions
Similar to the findings in Europe, we observed a high incidence of HCV reinfection among HIV‐positive Taiwanese with recent HCV infection, which was significantly associated with syphilis. To identify HCV reinfections, annual HCV RNA testing should be instituted instead of testing driven by symptoms, syphilis or elevated aminotransferases.
Hepatitis A virus (HAV) and hepatitis E virus (HEV) share the similar fecal‐oral transmission route. During an outbreak of sexually transmitted acute hepatitis A among men who have sex with men (MSM) ...worldwide between 2015 and 2017, we investigated the possibility of sexual transmission and related morbidity of HEV infection among human immunodeficiency virus (HIV)‐positive patients. From March 1, 2015 to August 31, 2017, anti‐HEV immunoglobulin G was retrospectively determined among 3,293 HIV‐positive patients, who were mainly MSM (87.6%) with a median CD4 count of 575 cells/μL. Prevalence and incidence of HEV infection were 3.7% (123 of 3,293) and 4.35 per 1,000 person‐years of follow‐up (PYFU), respectively, which were significantly lower compared with those of HAV infection (31.1% 996 of 3,204 and 12.61 per 1,000 PYFU, respectively). The number of patients with HEV infection did not increase with the hepatitis A epidemic. The factor associated with prevalent HEV infection was older age (per 1‐year increase, adjusted odds ratio, 1.07; 95% confidence interval, 1.05‐1.09), but neither sexual orientation nor acquisition of sexually transmitted infections was related to prevalent or incident HEV infection. Among 23 patients with incident HEV infection, 22 patients had viremia caused by HEV genotype 4. No patients had prolonged HEV viremia or clinical symptoms, and only a mild elevation of serum aminotransferase, ranging from 34 to 77 IU/L, was noted. Although 4 patients had hepatitis for a prolonged duration of between 8 and 17 months, no abdominal imaging revealed liver fibrosis or cirrhosis. Conclusion: HEV endemicity remained low among HIV‐positive patients in Taiwan during the outbreak of acute hepatitis A. Our data suggest that sexual transmission of HEV with significant morbidity of HEV infection, if any, is rare in this population.
Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLPro) reportedly inhibits the production of type I interferons (IFNs) and pro-inflammatory cytokines in Toll-like ...receptor 3 (TLR3) and retinoic acid-inducible gene 1 (RIG-I) pathways. The study investigated the inhibitory effect and its antagonistic mechanism of SARS-CoV PLPro on TLR7-mediated cytokine production. TLR7 agonist (imiquimod (IMQ)) concentration-dependently induced activation of ISRE-, NF-κB- and AP-1-luciferase reporters, as well as the production of IFN-α, IFN-β, TNF-α, IL-6 and IL-8 in human promonocyte cells. However, SARS-CoV PLPro significantly inhibited IMQ-induced cytokine production through suppressing the activation of transcription factors IRF-3, NF-κB and AP-1. Western blot analysis with anti-Lys48 and anti-Lys63 ubiquitin antibodies indicated the SARS-CoV PLPro removed Lys63-linked ubiquitin chains of TRAF3 and TRAF6, but not Lys48-linked ubiquitin chains in un-treated and treated cells. The decrease in the activated state of TRAF3 and TRAF6 correlated with the inactivation of TBK1 in response to IMQ by PLPro. The results revealed that the antagonism of SARS-CoV PLPro on TLR7-mediated innate immunity was associated with the negative regulation of TRAF3/6-TBK1-IRF3/NF-κB/AP1 signals.
Giardia lamblia becomes dormant by differentiation into a water-resistant cyst that can infect a new host. Synthesis of three cyst wall proteins (CWPs) is the fundamental feature of this ...differentiation. Myeloid leukemia factor (MLF) proteins are involved in cell differentiation, and tumorigenesis in mammals, but little is known about its role in protozoan parasites. We developed a CRISPR/Cas9 system to understand the role of MLF in Giardia. Due to the tetraploid genome in two nuclei of Giardia, it could be hard to disrupt a gene completely in Giardia. We only generated knockdown but not knockout mutants. We found that knockdown of the mlf gene resulted in a significant decrease of cwp gene expression and cyst formation, suggesting a positive role of MLF in encystation. We further used mlf as a model gene to improve the system. The addition of an inhibitor for NHEJ, Scr7, or combining all cassettes for gRNA and Cas9 expression into one plasmid resulted in improved gene disruption efficiencies and a significant decrease in cwp gene expression. Our results provide insights into a positive role of MLF in inducing Giardia differentiation and a useful tool for studies in Giardia.
To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress ...of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21% (95% CI, 5.39-7.12%) in 2018 to 2.09% (95% CI, 1.60-2.77%) in 2021 (decline by 66.4% 95% CI, 55.4-74.7%); the incidence has declined from 25.94 per 1000 PYFU (95% CI, 20.44-32.47) in 2019 to 12.15% per 1000 PYFU (95% CI, 8.14-17.44) (decline by 53.2% 95% CI, 27.3-70.6%). However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination.
We present 12 new transit light curves of the hot-Jupiter TrES-3b observed during 2012−2018 to probe the transit timing variation (TTV). By combining the midtransit times determined from these 12 ...transit data with those reestimated through uniform procedure from 71 transit data available in the literature, we derive new linear ephemeris and obtain the timing residuals that suggest the possibility of TTV in the TrES-3 system. However, the frequency analysis shows that the possible TTV is unlikely to be periodic, indicating the absence of an additional body in this system. To explore the other possible origins of TTV, the orbital decay and apsidal precession ephemeris models are fitted to the transit time data. We find the decay rate of TrES-3b to be ms yr−1, and the corresponding estimated modified stellar tidal quality factor of is consistent with the theoretically predicted values for the stars hosting the hot-Jupiters. The shift in the transit arrival time of TrES-3b after 11 years is expected to be Tshift ∼ 69.55 s, which is consistent with the rms of the timing residuals. Besides, we find that the apsidal precession ephemeris model is statistically less probable than the other considered ephemeris models. It is also discussed that despite the fact that the linear ephemeris model appears to be the most plausible model to represent the transit time data, the possibility of the orbital decay cannot be completely ruled out in the TrES-3 system. To confirm this, further high-precision and high-cadence follow-up observation of transits of TrES-3b would be important.
Hepatitis C virus (HCV) reinfections after successful treatment with direct-acting antivirals (DAAs) pose a significant challenge to HCV elimination, especially among high-risk people living with HIV ...(PLWH). In this study, PLWH who had achieved HCV viral clearance with DAAs were included between January 2018 and June 2021. PLWH having acquired HCV infections after 2017 were classified as "recent-infection group," and those before 2017 as "remote-infection group," and the incidences of HCV reinfection were compared between two groups. Clinical and behavioural characteristics were evaluated to identify associated factors with HCV reinfection. A total of 284 PLWH were included: 179 in the recent-infection group and 105 in the remote-infection group. After a median follow-up of 2.32 years (interquartile range IQR, 0.13-3.94), the overall incidence of HCV reinfection was 5.8 per 100 person-years of follow-up (PYFU). The incidence in the recent-infection group was significantly higher than that in the remote-infection group (9.8 vs. 0.4 per 100 PYFU, p < 0.001). The leading HCV genotypes before DAA treatment were genotypes 2 (31.0%), 1b (26.8%), and 6 (21.8%); however, genotype 6 (58.8%) became predominant upon reinfection. Younger age (adjusted odds ratio aOR per 1-year increase, 0.95; 95% CI, 0.90-0.99), condomless receptive anal sex (aOR, 14.5; 95% CI, 2.37-88.8), rimming (aOR, 3.87; 95% CI, 1.14-13.1), and recent syphilis (aOR, 2.73; 95% CI, 1.26-5.91) were linked to HCV reinfections. In conclusion, PLWH acquiring HCV after 2017 had a significantly higher risk for sexually-transmitted HCV reinfections. The predominance of HCV genotype 6 reinfections suggests possible on-going clustered HCV infections among at-risk PLWH.
Background
Acute hepatitis C virus (HCV) infections have been increasingly reported among human immunodeficiency virus (HIV)‐positive men who have sex with men (MSM) in the Asia‐Pacific region. It ...remains unknown whether international network of HCV transmission has occurred in this region.
Methods
HIV‐positive patients with acute HCV infection, defined as HCV seroconversion within a year or documented acute hepatitis with seroconversion, diagnosed in Hong Kong, Taipei and Tokyo during 2010‐2016 were included in this molecular epidemiology study. The NS5B region of the HCV genome (365 bp) was amplified using nested polymerase chain reaction and sequenced.
Results
Of 234 HIV‐positive patients with acute HCV infection, all were male with 94% being MSM. At the diagnosis of acute HCV infection, 73.5% had concurrent sexually transmitted diseases and 88.0% were receiving combination antiretroviral therapy. The most prevalent HCV genotype was 3a, 2a and 1b in Hong Kong, Taipei and Tokyo respectively. Nine independent clusters belonging to five genotypes (1b, 2a, 2c, 3a and 6a) were identified, each of which occurred in one city without overlapping except for one 3a sequence from Taipei that was closely related genetically to the Hong Kong cluster.
Conclusions
No international network of HCV transmission was identified among HIV–positive patients in the three Asia‐Pacific cities. The transmission dynamics of sexually acquired HCV differed by city, but the risk of intercity clustering should not be ignored.
Abstract
We perform transit timing variation (TTV) and transmission spectroscopy analyses of the planet HAT-P-37b, which is a hot Jupiter orbiting a G-type star. Nine new transit light curves are ...obtained and analyzed together with 21 published light curves from the literature. The updated physical parameters of HAT-P-37b are presented. The TTV analyses show a possibility that the system has an additional planet that induced the TTVs amplitude signal of 1.74 ± 0.17 minutes. If the body is located near the 1:2 mean-motion resonance orbit, the sinusoidal TTV signal could be caused by the gravitational interaction of a sub-Earth-mass planet with mass of 0.06
M
⊕
. From the analysis of an upper-mass limit for the second planet, a Saturn-mass planet with orbital period less than 6 days is excluded. The broadband transmission spectra of HAT-P-37b favors a cloudy atmospheric model with an outlier spectrum in the
B
filter.
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