Opportunistic screening using point-of-care testing leads to successful linkage to care of HBV-infected migrant populations in a low endemic country.

Background and aims: In low endemic countries, screening for hepatitis B surface antigen (HBsAg) in migrants is cost-effective in reducing the disease burden of hepatitis B virus (HBV) infections, but linkage to care (LTC) remains a challenge. This study aims to guide future screening initiatives, with 3 objectives: 1. to compare LTC between different ethnic groups screened for HBsAg with point-of-care testing (POCT) in an outreach setting; 2. to estimate the proportion of HBsAg seropositivity for ethnic minorities; and 3. to investigate the association between seropositivity and HBV risk factors. Methods: Opportunistic outreach screenings using finger prick HBsAg tests were performed at civic integration programmes between 11/2017 and 09/2022. If an individual tested positive, an appointment was given immediately at the outpatient hepatology clinic for follow-up and confirmation of HBsAg positivity in blood. Dedicated personnel contacted these individuals to motivate them for further LTC, which was defined as being assessed by a hepatologist, a blood test and an abdominal ultrasound. Results: A total of 677 people from different ethnicities (Asian, Middle Eastern and African) were serologically screened using POCT. The observed positivity for HBsAg was 3.4 % (95% CI 2.17-5.05, 23/677). Apart from ethnicity and male sex, none of the surveyed HBV risk factors were associated with HBsAg seropositivity. All HBsAg positive individuals were linked to care and assessed by a hepatologist, despite the COVID-19 pandemic increase in time to follow-up of 82 days (95% CI 51-112 days) vs. 24 days (95% CI 5-43 days, p = 0.008)).Among HBV-infected patients, 31.8% (7/22), 100 % (22/22) and 26.1% (6/23) met the criteria for treatment indication, intrafamilial transmission risk and need for hepatocellular carcinoma surveillance, respectively. Conclusion: The proportion of HBsAg seropositivity in ethnic minorities was 3.4%. POCT and commitment of dedicated personnel can overcome previously identified barriers resulting in a 100% LTC.

Temporal patterns of functional anti-dengue antibodies in dengue infected individuals with different disease outcome or infection history.

Heterotypic secondary dengue virus (DENV) infection is a risk factor for the development of severe disease. To assess the contribution of the developing polyclonal humoral immune response to the course of acute infection, we have determined anti-DENV IgG titers, neutralizing antibodies, percentages of antibodies binding to DENV-infected cells and antibody­dependent enhancement (ADE) to the infecting serotype in DENV-infected Cambodian children (n = 58), ranging from asymptomatic dengue to severe disease. The results showed that ADE titers are highest against the infecting serotype during heterotypic secondary DENV-2 infection. Moreover, IgG titers, neutralizing antibodies and ADE titers against the infecting serotype peak at D10 and are maintained until D60 after laboratory-confirmed secondary DENV infection. Anti-DENV IgG titers and the magnitude of the functional antibody response were higher in secondary DENV-infected patients compared to primary infected patients. No differences in antibody titers, neutralizing or enhancing antibodies could be observed between asymptomatic or hospitalized patients between 6 and 8 days after laboratory-confirmed DENV-1 infection. However, at this time point, the level of IgG bound to DENV-infected cells was associated with disease severity in hospitalized patients. Taken together, our data offer insights for more comprehensive interpretation of antibody response profile to natural infection and its correlation to disease outcome.

Decreased Type I Interferon Production by Plasmacytoid Dendritic Cells Contributes to Severe Dengue.

The clinical presentation of dengue virus (DENV) infection is variable. Severe complications mainly result from exacerbated immune responses. Type I interferons (IFN-I) are important in antiviral responses and form a crucial link between innate and adaptive immunity. Their contribution to host defense during DENV infection remains under-studied, as direct quantification of IFN-I is challenging. We combined ultra-sensitive single-molecule array (Simoa) digital ELISA with IFN-I gene expression to elucidate the role of IFN-I in a well-characterized cohort of hospitalized Cambodian children undergoing acute DENV infection. Higher concentrations of type I IFN proteins were observed in blood of DENV patients, compared to healthy donors, and correlated with viral load. Stratifying patients for disease severity, we found a decreased expression of IFN-I in patients with a more severe clinical outcome, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). This was seen in parallel to a correlation between low IFNα protein concentrations and decreased platelet counts. Type I IFNs concentrations were correlated to frequencies of plasmacytoid DCs, not DENV-infected myloid DCs and correlated inversely with neutralizing anti-DENV antibody titers. Hence, type I IFN produced in the acute phase of infection is associated with less severe outcome of dengue disease.