Exotic viral hepatitis: A review on epidemiology, pathogenesis, and treatment.

Certain "exotic" viruses are known to cause clinical diseases with potential liver involvement. These include viruses, beyond regular hepatotropic viruses (hepatitis A, -B(D), -C, -E, cytomegalovirus, Epstein-Barr virus), that can be found in (sub)tropical areas and can cause "exotic viral hepatitis". Transmission routes typically involve arthropods (Crimean Congo haemorrhagic fever, dengue, Rift Valley fever, yellow fever). However, some of these viruses are transmitted by the aerosolised excreta of rodents (Hantavirus, Lassa fever), or via direct contact or contact with bodily fluids (Ebola). Although some exotic viruses are associated with high fatality rates, such as Ebola for example, the clinical presentation of most exotic viruses can range from mild flu-like symptoms, in most cases, right through to being potentially fatal. A smaller percentage of people develop severe disease with haemorrhagic fever, possibly with (fulminant) hepatitis. Liver involvement is often caused by direct tropism for hepatocytes and Kupffer cells, resulting in virus-mediated and/or immune-mediated necrosis. In all exotic hepatitis viruses, PCR is the most sensitive diagnostic method. The determination of IgM/IgG antibodies is a reasonable alternative, but cross-reactivity can be a problem in the case of flaviviruses. Licenced vaccines are available for yellow fever and Ebola, and they are currently under development for dengue. Therapy for exotic viral hepatitis is predominantly supportive. To ensure that preventive measures can be introduced to control possible outbreaks, the timely detection of these viruses is very important.

The Exchange of Informational Support in Online Health Communities at the Onset of the COVID-19 Pandemic: Content Analysis.

BACKGROUND: Online health communities (OHCs) provide social support for ongoing health-related problems. COVID-19, the disease caused by SARS-CoV-2, has been an acute and substantial stressor worldwide. The disease and its impact, especially in the beginning phases, left many people with questions about the nature, treatment, and prevention of COVID-19. Unlike typical chronic ailments discussed on OHCs, which are more established, COVID-19, at least at the onset of the pandemic, is distinct in that it lacks a consensus of clinical diagnosis and an existing community foundation. OBJECTIVE: The study aims to investigate a newly formed OHC for COVID-19 to determine the topics and types of information exchange as well as the sources of information this community referenced during the early phases of the COVID-19 pandemic in the United States. METHODS: A total of 357 posts from a COVID-19 OHC on the MedHelp platform were annotated according to an open-coding process. Participants' engagement patterns, topics of posts, and sources of information were quantified. RESULTS: Participants who offered informational support had a significantly higher percentage of responding more than once than those seeking information (P<.001). Among the information-seeking topics, symptoms and public health practice and psychological impacts were the most frequently discussed, with 26% (17/65) and 15% (10/65) of posts, respectively. Most informational support was expressed through feedback/opinion (181/220, 82.3%). Additionally, the most frequently referenced source of information was news outlets/websites, at 55% (11/20). Governmental websites were referenced less frequently. CONCLUSIONS: The trends of this community could be useful in prioritizing public health responses to address the most common questions asked by the public during crisis communication and in identifying which venue of communication is most effective in reaching a public audience during such times.

Evaluation of the Hepatitis B Vaccination Programme in Medical Students in a Dutch University Hospital.

Healthcare workers (HCW) are at increased risk of contracting hepatitis B virus (HBV) and are, therefore, vaccinated pre-exposure. In this study, the HBV vaccination programme for medical students in a university hospital in the Netherlands was evaluated. In the first part, the effectiveness of the programme, which consisted of a vaccination with Engerix-B® at 0, 1, and 6 months, was retrospectively evaluated over 7 years (2012-2019). In the second part of this study, we followed students (the 2019 cohort) who had previously been vaccinated against HBV vaccination (4-262 months prior to primary presentation) in order to investigate the most efficient strategy to obtain an adequate anti hepatitis B surface antigen titre. In the latter, titre determination was performed directly during primary presentation instead of giving previously vaccinated students a booster vaccination first. The vaccination programme, as evaluated in the retrospective first part of the study, was effective (surpassed the protection limit of 10 IU/L) in 98.8 percent of the students (95% CI (98.4-99.2)). In the second part of our study, we found that 80 percent (95% CI (70-87)) of the students who had previously been vaccinated against HBV were still sufficiently protected and did not require a booster vaccination. With this strategy, the previously vaccinated students needed an average of 1.4 appointments instead of the 2 appointments needed with the former strategy. This knowledge is important and can save time and resources in the process of occupational HBV vaccination of HCW.

Point-of-care thrombocyte function testing using multiple-electrode aggregometry in dengue patients: an explorative study.

BACKGROUND: Dengue virus (DENV) causes the hospitalisation of an estimated 500,000 people every year. Outbreaks can severely stress healthcare systems, especially in rural settings. It is difficult to discriminate patients who need to be hospitalized from those that do not. Earlier work identified thrombocyte count and subsequent function as a promising prognostic marker of DENV severity. Herein, we investigated the potential of quantitative thrombocyte function tests in those admitted in the very early phase of acute DENV infections, using Multiplate™ multiple-electrode aggregometry to explore its potential in triage. METHODS: In this prospective cohort study all patients aged ≥13 admitted to Universitas Airlangga Hospital in Surabaya, Indonesia with a fever (≥38 °C) between 25 January and 1 August 2018 and with a clinical suspicion of DENV, were eligible for inclusion. Exclusion criteria were a thrombocyte count below 100 × 109/L and the use of any medication with a known anticoagulant effect, nonsteroidal anti-inflammatory drugs and acetyl salicylic acid. Clinical data was collected and blood was taken on admission, day 1 and day 7. Samples were tested for acute DENV, using Panbio NS1 ELISA. Platelet aggregation using ADP-, TRAP- and COL-test were presented as Area Under the aggregation Curve (AUC). Significance was tested between DENV+, probably DENV, fever of another origin, and healthy controls (HC). RESULTS: A total of 59 patients (DENV+ n = 10, DENV probable n = 25, fever other origin n = 24) and 20 HC were included. We found a significantly lower thrombocyte aggregation in the DENV+ group, compared with both HCs and the fever of another origin group (p < .001). Low ADP AUC values on baseline correlated to a longer hospital stay in DENV+ and probable DENV cases. CONCLUSION: Thrombocyte aggregation induced by Adenosine diphosphate, Collagen and Thrombin receptor activating peptide-6 is impaired in human DENV cases, compared with healthy controls and other causes of fever. This explorative study provides insights to thrombocyte function in DENV patients and could potentially serve as a future marker in DENV disease.

Therapeutic Vaccine in Chronically HIV-1-Infected Patients: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Trial with HTI-TriMix.

Therapeutic vaccinations aim to re-educate human immunodeficiency virus (HIV)-1-specific immune responses to achieve durable control of HIV-1 replication in virally suppressed infected individuals after antiretroviral therapy (ART) is interrupted. In a double blinded, placebo-controlled phase IIa multicenter study, we investigated the safety and immunogenicity of intranodal administration of the HIVACAT T cell Immunogen (HTI)-TriMix vaccine. It consists of naked mRNA based on cytotoxic T lymphocyte (CTL) targets of subdominant and conserved HIV-1 regions (HTI), in combination with mRNAs encoding constitutively active TLR4, the ligand for CD40 and CD70 as adjuvants (TriMix). We recruited HIV-1-infected individuals under stable ART. Study-arms HTI-TriMix, TriMix or Water for Injection were assigned in an 8:3:3 ratio. Participants received three vaccinations at weeks 0, 2, and 4 in an inguinal lymph node. Two weeks after the last vaccination, immunogenicity was evaluated using ELISpot assay. ART was interrupted at week 6 to study the effect of the vaccine on viral rebound. The vaccine was considered safe and well tolerated. Eighteen percent (n = 37) of the AEs were considered definitely related to the study product (grade 1 or 2). Three SAEs occurred: two were unrelated to the study product, and one was possibly related to ART interruption (ATI). ELISpot assays to detect T cell responses using peptides covering the HTI sequence showed no significant differences in immunogenicity between groups. There were no significant differences in viral load rebound dynamics after ATI between groups. The vaccine was safe and well tolerated. We were not able to demonstrate immunogenic effects of the vaccine.

Correction to: iHIVARNA phase IIa, a randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy.

Following publication of the original article [1], we have been notified that end note would need to be adjusted.

iHIVARNA phase IIa, a randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy.

BACKGROUND: HIV therapeutic vaccination aims to improve the immune responses against HIV in order to control viral replication without the need for combined antiretroviral therapy (cART). iHIVARNA-01 is a novel vaccine combining mRNA delivery and T-cell immunogen (HTI) based on conserved targets of effective antiviral T-cell responses. In addition, it holds adequate stimuli required for activating antigen presenting cells (APC)s and co-activating specific T-cells (TriMix), including human CD40L, constitutively active TLR4 (caTLR4) and CD70. We propose that in-vivo targeting of dendritic cells (DCs) by direct administration of a HIV mRNA encoding these immune modulating proteins might be an attractive alternative to target DCs in vitro. METHODS/DESIGN: This is a phase-IIa, randomized, double-blinded, placebo-controlled, multicenter study in chronically HIV-1 infected patients under stable cART. One of the three study arms is randomly allocated to subjects. Three vaccinations with either HIVACAT T-cell immunogen (HTI)-TriMix (iHIVARNA-01), TriMix or water for injection (WFI) (weeks 0, 2 and 4) are administered by intranodal injection in the inguinal region. Two weeks after the last immunization (week 6) cART is stopped for 12 weeks. The two primary endpoints are: (1) safety and tolerability of intranodal iHIVARNA-01 vaccination compared with TriMix or WFI and (2) induced immunogenicity, i.e., increase in the frequency of HIV-specific T-cell responses between baseline, week 6 and 12 weeks after treatment interruption in iHIVARNA-01-treated patients as compared to the control groups, immunized with TriMix-mRNA or WFI measured by an IFNγ ELISPOT assay. Secondary endpoints include the evaluation of time to viral rebound, plasma viral load (pVL) at w18, the proportion of patients with control of viral load, induction of T-cell responses to new HIV epitopes, polyfunctionality of HIV-specific T-cells, CD8+ T-cell in-vitro HIV suppressive capacity, the effect on viral reservoir (measured by proviral DNA and cell-associated RNA), assessment of viral immune escape by mutation and mRNA expression profiles of host immune genes. DISCUSSION: This trial aims to direct target DC in situ with mRNA encoding HTI and TriMix for co-stimulation. Intranodal injection circumvents laborious DC isolation and handling in the laboratory. The trial extends on the safety results of a phase-I dose-escalating trial. This candidate vaccine could complement or even replace cART for chronic HIV infection and could be applicable to improve the care and cost of HIV infection. TRIAL REGISTRATION: EudraCT 2016-002724-83 (22 September 2016); ClinicalTrials.gov, ID: NCT02888756 . Registered on 23 August 2016.

Endemic and emerging acute virus infections in Indonesia: an overview of the past decade and implications for the future.

Being the largest archipelago country in the world, with a tropical climate and a unique flora and fauna, Indonesia habitats one of the most diverse biome in the world. These characteristics make Indonesia a popular travel destination, with tourism numbers increasing yearly. These characteristics also facilitate the transmission of zoonosis and provide ideal living and breading circumstances for arthropods, known vectors for viral diseases. A review of the past 10 years of literature, reports of the Ministry of Health, Republic of Indonesia and ProMED-mail shows a significant increase in dengue infection incidence. Furthermore, chikungunya, Japanese encephalitis and rabies are proven to be endemic in Indonesia. The combination of cohort studies, governmental data and ProMED-mail reveals an integrated overview for those working in travel medicine and public health, focusing on both endemic and emerging acute virus infections. This review summarizes the epidemiology of acute virus infections in Indonesia, including outbreak reports, as well as public health response measurements and their potential or efficacy. Knowledge about human behaviour, animal reservoirs, climate factors, environment and their role in emerging virus infection are discussed. We aim to support public health authorities and health care policy makers in a One Health approach.

Persistent annual permanent pacemaker implantation rate after surgical aortic valve replacement in patients with severe aortic stenosis.

BACKGROUND: Degenerative aortic valve stenosis (AS) is associated with conduction abnormalities. Pacemaker implantation is encountered after surgical aortic valve replacement (SAVR). Not much is known about the pacemaker implantation rate during midterm follow-up after SAVR. Our objectives were to determine the incidence of permanent pacemaker implantation (PPI) in the midterm after SAVR in a tertiary care facility. METHODS: We reviewed procedural data of 734 consecutive patients (56% men; mean age, 68.9±9.5 years) with degenerative severe AS who underwent SAVR between January 1, 2003, and December 31, 2008. Perioperative electrocardiograms were assessed for occurrence of conduction abnormalities, and we sought to determine the incidence and indication for PPI with a median follow-up of 3.76 years (interquartile range, 2.44 to 5.59 years). Univariate and multivariate logistic regression models were applied to identify predictors for early (≤30 days) and late (>30 days) PPI. RESULTS: Isolated SAVR was performed in 56%, SAVR with coronary artery bypass grafting in 35%, and SAVR with any other valve therapy in 5.8%. Complete bundle branch block (BBB) was present in 7% and first-degree atrioventricular block in 11%. New BBBs were detected in 63 patients (8.6%). Fifteen patients (2.0%) required a PPI within 30 days after SAVR, and 28 (4.0%) underwent PPI more than 30 days after SAVR. The linearized rate of PPI after SAVR was 1.01%±0.37% per patient-year. Patients with BBB at baseline had a higher PPI incidence after SAVR than patients without BBB, both within 30 days (8% vs 1.5%, p=0.001) and after 30 days (10% vs 2.9%, p=0.006). PPI incidence after 30 days was also significantly higher in patients with a new BBB after SAVR (7.8% vs 2.9%, p=0.038). By multivariate logistic regression analysis, BBB and the combination of AS and regurgitation predicted PPI within 30 days after SAVR (hazard ratio [HR], 470; 95% confidence interval [CI], 1.55 to 14.27; and HR, 1.33; 95% CI, 0.03 to 1.73, respectively). BBB (HR, 3.26; 95% CI, 1.41 to 7.54), previous cardiac operation (HR, 3.40; 95% CI, 1.16 to 9.94), and severe left ventricular dysfunction (HR, 9.82; 95% CI, 2.90 to 33.26) were predictors for PPI after 30 days post-SAVR. CONCLUSIONS: Patients with severe AS who underwent SAVR have a persistent 1% annual risk for PPI. Postoperative presence of BBB predicted the need for PPI both within 30 days and after 30 days after SAVR.